A Phase 3, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Switching to a Fixed Dose Combination (FDC) of GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) From Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) or Atazanavir + Ritonavir + Emtricitabine/Tenofovir Disoproxil Fumarate (ATV+RTV+FTC/TDF) in Virologically Suppressed HIV-1 Infected Women
Phase: PHASE3
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences

(fJ GILEAiJ 
CLINICAL STUDY PROTOCOL 
Study Title: 
A Phase 3, Randomized, Open Label Study to Evaluate the 
Safety and Efficacy of Switching to a Fixed Dose Combination 
(FDC) of GS-9883/Emtricitabine/Tenofovir Alafenamide 
(GS-9883/F IT AF) from Elvitegravir/Cobicistat/Emtricitabine/ 
Tenofovir Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/ 
Emtricitabine/T enofovir Disoproxil Fmnarate (E/C/F /TDF) or 
Atazanavir + Ritonavir + Emti·icitabine/Tenofovir Disoproxil 
Fmnarate (ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV -1 Infected Women 
Sponsor: 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
IND Number: 
125589 
EudraCT Number: 
Not Applicable 
Clinical Trials.gov Identifier: 
Not Available 
Indication: 
HIV -1 Infection 
Protocol ID: 
GS-US-380-1961 
Gilead Clinical Program 
Manager: 
Gilead Medical Monitor: 
Protocol Version/Date: 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Mobile: 
Original: 
PPD 
Huyen Cao, MD 
PD 
PPD 
PPD 
20 November 2015 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this docmnent, particularly m1published data, is the prope1iy or 
under conti·ol 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 info1mation is only to be used 
by you in connection with authorized clinical studies of the investigational dmg described in the 
protocol. You will not disclose any of the info1mation to others without written authorization 
from Gilead Sciences, Inc., except to the extent necessruy to obtain infmm ed consent from those 
persons to whom the dmg may be administered. 

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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....................................................................11
1.
INTRODUCTION ..............................................................................................................................................14
1.1.
Background ............................................................................................................................................14
1.2.
GS-9883 .................................................................................................................................................15
1.2.1.
General Information .............................................................................................................15
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................15
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................17
1.3.
Information About Emtricitabine (Emtriva®, FTC) ...............................................................................26
1.4.
Information About Tenofovir Alafenamide (TAF, GS-7340)................................................................26
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide 
(FTC/TAF)...........................................................................................................................26
1.4.2.
Clinical Trials of FTC/TAF as Part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF).........................................................................................................................28
1.5.
Information About GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) .......................29
1.5.1.
GS-US-141-1233: Relative Bioavailability of GS-9883, FTC, and TAF 
Between GS-9883/F/TAF and GS-9883 + F/TAF ...............................................................30
1.6.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)...................................................................................31
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®) ..................................................31
1.8.
Ritonavir (RTV, /r, Norvir®)..................................................................................................................31
1.9.
Atazanavir (ATV, Reyataz®)..................................................................................................................31
1.10.
Rationale for This Study ........................................................................................................................31
1.11.
Risk/Benefit Assessment for the Study..................................................................................................32
1.12.
Rationale for Dose Selection..................................................................................................................33
1.13.
Compliance ............................................................................................................................................35
2.
OBJECTIVES.....................................................................................................................................................36
3.
STUDY DESIGN................................................................................................................................................37
3.1.
Endpoints ...............................................................................................................................................37
3.2.
Study Design..........................................................................................................................................37
3.3.
Study Treatments ...................................................................................................................................37
3.4.
Duration of Treatment............................................................................................................................38
3.5.
Biomarker Testing..................................................................................................................................38
3.5.1.
Biomarker Samples for Optional Future Research...............................................................38
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................43
5.1.
Randomization .......................................................................................................................................43
5.2.
Description and Handling.......................................................................................................................43

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5.2.1.
Formulation..........................................................................................................................43
5.2.2.
Packaging and Labeling .......................................................................................................45
5.2.3.
Storage and Handling...........................................................................................................46
5.3.
Dosage and Administration of GS-9883/F/TAF, E/C/F/TAF, E/C/F/TDF and 
ATV+RTV+FTC/TDF...........................................................................................................................46
5.4.
Prior and Concomitant Medications.......................................................................................................46
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................48
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................48
6.
STUDY PROCEDURES ....................................................................................................................................49
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................49
6.2.
Pretreatment Assessments......................................................................................................................49
6.2.1.
Screening Visit .....................................................................................................................49
6.2.2.
Day 1 Assessments...............................................................................................................51
6.3.
Randomization .......................................................................................................................................52
6.4.
Treatment Assessments (Weeks 4-48) ...................................................................................................52
6.5.
Treatment Assessments (Post Week 48) ................................................................................................55
6.5.1.
Post Week 48 Assessments ..................................................................................................55
6.6.
Post-Treatment Assessments..................................................................................................................56
6.6.1.
Early Study Drugs Discontinuation (ESDD) Assessments...................................................56
6.6.2.
30 Day Follow Up................................................................................................................58
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................59
6.8.
Other Evaluations...................................................................................................................................59
6.8.1.
Markers of Renal Tubular Function .....................................................................................59
6.9.
Blood and Urine Storage........................................................................................................................60
6.10.
Assessments for Premature Discontinuation from Study.......................................................................60
6.11.
End of Study...........................................................................................................................................60
6.12.
Post Study Care......................................................................................................................................60
6.13.
Virologic Failure....................................................................................................................................60
6.13.1.
Management of Virologic Rebound .....................................................................................60
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation or 
Week 48 ...............................................................................................................................62
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................63
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events....................................63
7.1.1.
Adverse Events.....................................................................................................................63
7.1.2.
Serious Adverse Events........................................................................................................63
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................64
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................64
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................64
7.2.2.
Assessment of Severity ........................................................................................................65
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................65
7.3.1.
Adverse Events.....................................................................................................................65
7.3.2.
Serious Adverse Events........................................................................................................66
7.4.
Gilead Reporting Requirements.............................................................................................................67
7.5.
Toxicity Management ............................................................................................................................67
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................67
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................68
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................68
7.5.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................68
7.5.5.
Management of Hyperbilirubinemia ....................................................................................70

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7.5.6.
On-Treatment Hepatitis C Management...............................................................................71
7.5.7.
Management of Potential Nephrotoxicity.............................................................................71
7.6.
Special Situations Reports......................................................................................................................71
7.6.1.
Definitions of Special Situations..........................................................................................71
7.6.2.
Instructions for Reporting Special Situations.......................................................................72
8.
STATISTICAL CONSIDERATIONS................................................................................................................74
8.1.
Analysis Objectives and Endpoints........................................................................................................74
8.1.1.
Analysis Objectives..............................................................................................................74
8.1.2.
Primary Endpoint .................................................................................................................74
8.1.3.
Secondary Endpoint .............................................................................................................74
8.2.
Analysis Conventions.............................................................................................................................74
8.2.1.
Analysis Sets ........................................................................................................................74
8.3.
Data Handling Conventions ...................................................................................................................75
8.4.
Demographic Data and Baseline Characteristics ...................................................................................76
8.5.
Efficacy Analysis ...................................................................................................................................76
8.5.1.
Primary Analysis..................................................................................................................76
8.5.2.
Secondary Analyses .............................................................................................................77
8.6.
Safety Analysis.......................................................................................................................................78
8.6.1.
Extent of Exposure...............................................................................................................78
8.6.2.
Adverse Events.....................................................................................................................78
8.6.3.
Laboratory Evaluations ........................................................................................................79
8.6.4.
Other Safety Evaluations......................................................................................................79
8.7.
Pharmacokinetic Analysis......................................................................................................................79
8.8.
Sample Size............................................................................................................................................79
8.9.
Independent Data Monitoring Committee..............................................................................................79
9.
RESPONSIBILITIES..........................................................................................................................................81
9.1.
Investigator Responsibilities ..................................................................................................................81
9.1.1.
Good Clinical Practice..........................................................................................................81
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................81
9.1.3.
Informed Consent.................................................................................................................81
9.1.4.
Confidentiality......................................................................................................................82
9.1.5.
Study Files and Retention of Records ..................................................................................82
9.1.6.
Case Report Forms...............................................................................................................83
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................84
9.1.8.
Inspections............................................................................................................................84
9.1.9.
Protocol Compliance............................................................................................................84
9.2.
Sponsor Responsibilities ........................................................................................................................84
9.2.1.
Protocol Modifications.........................................................................................................84
9.2.2.
Study Report and Publications .............................................................................................85
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................85
9.3.1.
Payment Reporting...............................................................................................................85
9.3.2.
Access to Information for Monitoring..................................................................................85
9.3.3.
Access to Information for Auditing or Inspections ..............................................................86
9.3.4.
Study Discontinuation..........................................................................................................86
10.
REFERENCES ...................................................................................................................................................87
11.
APPENDICES ....................................................................................................................................................88
Appendix 1.
Investigator Signature Page....................................................................................................89
Appendix 2.
Study Procedures Table..........................................................................................................90

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Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................93
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............94
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................117
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................119
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) ...........19
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) ...........................................................................................................20
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)....................................................................................................20
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)........................................................................................21
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.................................................................................................33
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)..........................................47
Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens) .........................................................................................48
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).......................................................................................22
Figure 3-1.
Study Schema.........................................................................................................................38
Figure 6-1.
Virologic Rebound Schema....................................................................................................62

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety 
and Efficacy of Switching to a Fixed Dose Combination (FDC) of 
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) 
from Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir
Disoproxil Fumarate (E/C/F/TDF) or Atazanavir + Ritonavir + 
Emtricitabine/Tenofovir Disoproxil Fumarate 
(ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV-1 Infected Women
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
Not Applicable
Not Available
Study Centers Planned:
Approximately 47 centers in North America
Approximately 2 centers in Dominican Republic
Approximately 6 centers in Thailand
Approximately 20 centers in Russia
Approximately 1 center in Uganda
Objectives:
The primary objective of this study is:

To evaluate the efficacy of switching to an FDC of 
GS-9883/F/TAF versus continuing on a regimen consisting of 
E/C/F/TAF, E/C/F/TDF or ATV+RTV+FTC/TDF in 
virologically suppressed HIV-1 infected women as determined 
by the proportion of subjects with virologic failure 
(HIV-1 RNA ≥ 50 copies/mL) at Week 48
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups 
through Week 48

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Study Design:
Randomized, open label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to an FDC of 
GS-9883/F/TAF in HIV-1 infected women who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting 
of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir 
Disoproxil Fumarate (E/C/F/TDF), or ATV+RTV+FTC/TDF for 
≥12 consecutive weeks prior to screening.    
All subjects will be HIV positive women drawn from pre-defined 
Gilead clinical studies and must be virologically suppressed. 
Women in Gilead study GS-US-236-0128 who completed the 
Week 48 open-label extension (OLE) visit or any post Week 48 
OLE visits or women in study GS-US-292-0109 who completed the 
Week 96 visit or any post Week 96 visits may be eligible to enroll. 
Subjects who provide written consent and meet all eligibility 
criteria will be randomized in a 1:1 ratio to receive open label 
medication as follows: 

Treatment Group 1: 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 = 200) 

Treatment Group 2: Stay on baseline regimen (SBR), 
including E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF
administered orally, once daily, with food (n = 200) 
Randomization will be stratified by the prior treatment regimen 
group (ie, E/C/F/TAF, E/C/F/TDF and ATV+RTV+FTC/TDF).
Number of Subjects 
Planned:
Approximately 400 subjects total
Target Population:
HIV-1 infected women who are virologically suppressed 
(HIV-1 RNA < 50 copies/mL) on a stable regimen of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥12 weeks prior to 
screening
Duration of Treatment:
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, 
subjects in a country where GS-9883/F/TAF FDC is not available 
will be given the option to receive GS-9883/F/TAF FDC for an 
additional 48 weeks, or 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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Subjects who complete the study through the Week 48 Visit and 
do not continue participation in the study will be required to return 
to the clinic 30 days after the Week 48 Visit for a 30 Day 
Follow-Up Visit.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected women who meet the following 
criteria:

Currently on a stable antiretroviral regimen consisting of 
E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF continuously 
for ≥12 consecutive weeks preceding the screening visit

Documented plasma HIV-1 RNA levels < 50 copies/mL for 
≥12 weeks preceding the Screening visit. After reaching 
HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by re-suppression to < 50 copies/mL 
is allowed

HIV-1 RNA <50 copies/mL at screening

Estimated glomerular filtration rate (eGFR) ≥50 mL/min 
according to the Cockcroft-Gault (C-G) formula at the 
screening visit
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 
48 weeks. Following the Screening and Day 1 visits, subjects will 
return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
until the Week 48 visit. 
For all eligible subjects, blood and urine will be collected at Day 1, 
Weeks 4, 8, 12, and then every 12 weeks through the Week 48 visit. 
Laboratory analyses (including 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.
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:
Current antiretroviral drug regimen consisting of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF administered orally,
once daily, with food.

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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 with virologic failure (HIV-1 RNA 
≥50 copies/mL at Week 48, as defined by the modified 
United States (US) Food and Drug Administration (FDA) 
snapshot algorithm).
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
Pharmacokinetics:
For all subjects on GS-9883/F/TAF (Treatment Group 1), a single 
anytime pre or post-dose PK blood sample will be collected at 
Weeks 8, 24, and 36. 
For all subjects on GS-9883/F/TAF (Treatment Group 1), 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 PK blood 
sample will be collected between 1 and 4 hours post-dose. 
The concentration of GS-9883 may be summarized using 
descriptive statistics. 
Statistical Methods:
The primary analysis will consist of a non-inferiority test of 
switching to GS-9883/F/TAF FDC versus staying on baseline 
regimen (SBR) with respect to the proportion of subjects with 
virologic failure (HIV-1 RNA ≥ 50 copies/mL) at Week 48 as 
defined by the modified US FDA snapshot algorithm. It will be 
concluded that GS-9883/F/TAF is non-inferior to SBR if the upper 
bound of the 2-sided 95% confidence interval (CI) of the difference 
between treatment groups (GS-9883/F/TAF – SBR) in the virologic 
failure rate is less than 4%; ie, a margin of 4% is applied to 
non-inferiority assessment. The 2-sided 95% CIs will be 
constructed based on the exact method.
The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the FDA snapshot algorithm will also be 
summarized. The 95% CIs will be constructed in the same manner 
as described for the primary efficacy endpoint. 

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The change from baseline in CD4+ cell count at Week 48 will be 
summarized by treatment using descriptive statistics. The 
differences and the associated 95% CIs will be constructed using 
Analysis of Variance (ANOVA) model, including treatment 
(GS-9883/F/TAF vs. SBR) as a fixed effect in the model. 
Adverse events and clinical laboratory assessments will be 
summarized using descriptive statistics.
A total of approximately 400 HIV-1 infected women, randomized 
in a 1:1 ratio to 2 treatment groups (200 subjects per treatment 
group), achieves at least 80% power to detect a non-inferiority 
margin of 4% in Week 48 virologic failure rate (HIV-1 RNA 
≥50 copies/mL) difference between the 2 treatment groups. 
For sample size and power computation, it is assumed that both 
treatment groups have a virologic failure rate of 2% (based on the 
historical Gilead E/C/F/TAF and Stribild® (STB) studies), that a 
non-inferiority margin is 4%, 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
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq®
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir, Reyataz®
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, C, /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
DSPH
Drug Safety and Public Health
DTG
dolutegravir, Tivicay®
EC50
50% effective inhibitory concentration
ECG
electrocardiogram
eCRF
electronic case report form(s)
EVG, E
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

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FSH
follicle-stimulating hormone
FTC, F
emtricitabine, Emtriva®
FTC/TAF 
emtricitabine/tenofovir alafenamide 
FTC/TDF
emtricitabine/tenofovir disoproxil fumarate, Truvada®
GCP
Good Clinical Practice (Guidelines)
GGT
gamma glutamyl transferase
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
IC50
50% maximal inhibitory concentration
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
institutional ethics 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
MT4
human t cell leukemia cell line
nM
nanoMolar
NNRTI
non-nucleoside reverse transcriptase inhibitor
NOAEL
no observed adverse effect level

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NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
OCT2
organic cation transporter 2
PI
protease inhibitor
PK
pharmacokinetic
PT
preferred term 
PT
prothrombin time 
QD
once daily 
RAL
raltegravir
RNA
ribonucleic acid
RTV
ritonavir, Norvir®
SAE
serious adverse event
STB
Stribild®, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide, GS-7340
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

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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 {36201}. 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 
{27881}, {5125}, {8284}.
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 {29705}. 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 {34898}. 
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 {21053}, {29702}.
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.
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 NRTI’s, 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.

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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 half maximal inhibitory concentration (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 the human T cell leukemia MT4 cell line 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 μM. 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 organic cation transporter 2 (OCT2)
(IC50 = 0.42 μM). As a result, 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.

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GS-9883 does not activate AhR and only weakly activates PXR at concentrations up to 50 μM 
(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 μg•h/mL and 1931 μg•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 μg•h/mL and 1078 μg•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.
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 4.7-fold based on expected human exposure with the once daily dosing of the 
GS-9883/F/TAF (50/200/25 mg) tablet.

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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 (ongoing)

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)

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 (ongoing)

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 (ongoing)

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
GS-US-311-1790, a Phase 1 Randomized, 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 (ongoing)

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 (ongoing)

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.
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.
Increases 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.

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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.
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)
5 mg
(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 geometric least squares mean (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 1 b 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 the table 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) paIQ95
a
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).

GS-9883/F/T AF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Final 
Original 
The mean and 95% Cis of change from baseline in HIV -1 RNA (log10 copieslmL) are presented 
in Figure 1-1. 
Figure 1-1. 
<( 
z 
n:: 
-1 
~ 
J: 
c 
-2 
-~ 
8i 
~ -3 
E 
,g 
~ -4 
~ 
(.) 
GS-9883 5 mg <~ ): 
GS-9883 25 mg (~): 
GS-9883 50 mg (~): 
GS-9883 100 mg (~): 
Placebo(~): 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
e = GS-9883 5 mg 
0 = GS-9883 25 mg 
b. = GS-9883 50 mg 
0 = GS-9883 100 mg 
0 = Placebo 
BL 
2 
3 
4 
3 
3 
3 
3 
4 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
3 
4 
4 
4 
4 
7 
8 
9 
Day 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
------
--
10 
11 
14 
17 
3 
3 
3 
3 
4 
4 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study drug. 
2 
0 
-1 
-2 
-3 
-4 
-5 
Mean viral load change on Day 11 was - 2.08log10 in the 25 mg cohort, - 2.06 log10 in the 50 mg 
cohott, and - 2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVGll) was - 0.92log10 in the 5 mg cohot1~ - 1.33log10 in the 25 mg cohort, 
- 1.37log10 in the 50 mg cohort and - 1.61 log10 in the 100 mg cohmt. Viral suppression 
(HIV-1 RNA < 50 copieslmL) 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. 
Summaty 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 IT AF versus dolutegravir (DTG)+F IT AF in HIV -infected, antiretroviral therapy 
(ART)-naive adult subjects. 
CONFIDENTIAL 
Page22 
20 November 2015 

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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20 November 2015
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. 
1.2.3.4.
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 study treatment, one 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 estimated glomerular 
filtration rate [eGFR] using the Cockcroft-Gault method [eGFRCG]) were similar between the 
2 treatment groups.
Median (Q1, 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.
1.2.3.5.
Efficacy Results
Virologic success at Week 12 and 24 was assessed using the US FDA 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 was considered a virologic failure by US FDA snapshot 
algorithm with HIV-1 RNA of 60 copies/mL.

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Protocol GS-US-380-1961
Final
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Original
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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 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 
(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.
1.2.3.6.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 58.5%, 38 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common TEAEs (occurring in > 1 subject) 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, and 1 other SAE (appendicitis), also in the GS-9883/F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator, resulted in study 
drug discontinuation, or required interruption of study drug, 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 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.
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 

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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 treatment-emergent laboratory abnormalities occurring in at least 
2 subjects in either treatment group were as follows: creatine kinase (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 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.

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.

GS-9883/F/TAF
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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 Food and Drug Administration (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)

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-9883/F/TAF
Protocol GS-US-380-1961
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
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-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)
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). 

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
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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)

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)

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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 Food and Drug 
Administration (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 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.

GS-9883/F/TAF
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1.5.1.
GS-US-141-1233: 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 will evaluate 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 Cohort 1 is complete; preliminary results are summarized below. The 
in-life portion of Cohort 2 is ongoing.
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
Preliminary data of Cohort 2 showed that GS-9883 and Cmax and AUCinf following 
GS-9883/F/TAF FDC (50/200/25 mg) administration under fasted conditions were 
78% and 79%, respectively as the exposures following administration of single-agent GS-9883 
(75 mg) with the F/TAF FDC (200/25 mg). FTC and TAF exposure was similar following 
administration of GS-9883/F/TAF (50/200/25 mg) or single-agent GS-9883 (75 mg) with the 
F/TAF FDC (200/25 mg). 
Food had a small effect on GS-9883 exposure following GS 9883/F/TAF (50/200/25 mg) single 
dose. A high fat meal increased GS-9883 Cmax and AUCinf by 13% and 24%, respectively 
compared to exposure under fasted conditions. Similarly, a moderate fat meal increased GS-9883 
Cmax and AUCinf by 20% and 24%, respectively. 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 exposures following administration of the GS-9883/F/TAF (75/200/25 mg and 
50/200/25 mg) FDC tablets are approximately dose proportional under fasted and fed conditions. 
GS 9883/F/TAF may be taken without regard to food.
1.6.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)
Further information is available in the US Prescribing Information and Investigator’s Brochure 
for E/C/F/TDF.
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®)
Further information is available in the Prescribing Information for Truvada®.
1.8.
Ritonavir (RTV, /r, Norvir®)
Further information is available in the Prescribing Information for Norvir®.
1.9.
Atazanavir (ATV, Reyataz®)
Further information is available in the Prescribing Information for Reyataz®.
1.10.
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.

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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 
an 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.Approximately 50% of the global population of HIV-infected 
persons are women, however they remain under-represented in most clinical HIV studies. In 
general, studies to date have not shown gender differences in virologic responses to antiretroviral 
therapy (ART), but a number of studies have suggested that gender may influence the frequency, 
presentation, and severity of selected ARV-related adverse events. Although data are limited, the
pharmacokinetics for some ARV drugs may differ between men and women, possibly because of 
variations in factors such as body weight, plasma volume, gastric emptying time, plasma protein 
levels, CYP450 activity, drug transporter function, and excretion activity. It is important to 
understand potential gender-specific safety and efficacy issues in women when assessing 
virologic response, tolerability, and adherence. This study will ensure that there is adequate 
safety data in HIV-1-infected women in the Phase 3 program for GS-9883/F/TAF.
The objective of this study is to evaluate the safety and efficacy of an FDC containing 
GS-9883/F/TAF versus continuing on a regimen consisting of E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF in women who are virologically suppressed. Switching to 
GS-9883/F/TAF offers the advantages of a single-tablet FDC containing the unboosted, 
next-generation INSTI, GS-9883, combined with a TAF-based nucleotide backbone.
GS-9883/F/TAF FDC which includes TAF, has the potential to offer an effective and safer 
alternative to standard nucleos(t)ide based regimens, without the need for close monitoring of 
renal or bone toxicities or increase risk of cardiovascular complications as patients age and 
confront non HIV-related comorbidities.
1.11.
Risk/Benefit Assessment for the Study
All patients with HIV-1 infection should receive effective anti-retroviral 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: allergy to any 
components of the tablets. Protease inhibitors may be associated with increased lipid levels and 
gastrointestinal side effects. If patients are currently infected with hepatitis B and discontinue 
their existing or new therapy, there is a risk of severe acute exacerbations of hepatitis B.
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.
The overall benefit-risk assessment for GS-9883/F/TAF is favorable at this time.

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1.12.
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) paIQ95
a
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 interim 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 is being 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 is being 
developed for use in the Phase 3 studies. Comparability of GS-9883 exposures will be 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.  
E/C/F/TAF
EVG/COBI/FTC/TAF (200/25/25 mg) is a fixed dose combination, with only one dose 
combination available; and has been approved by the United States Food and Drug Administration 
(FDA) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and 
pediatric patients 12 years of age and older with no ARV treatment history or to replace the current 
ARV regimen in those who are virologically suppressed on a stable ARV regimen with no history 
of treatment failure and no known substitutions associated with resistance. This FDC contains the 
equivalent doses of EVG, COBI and FTC in the marketed product, Stribild® (STB).

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E/C/F/TDF (STB)
EVG/COBI/FTC/TDF (150/150/200/300 mg) is a fixed dose combination, with only one dose 
combination available; and is approved for use (Stribild®) in the United States by the 
Food and Drug Administration (FDA), for the treatment of HIV-1 infection in treatment-naïve 
adults.
ATV+RTV+FTC/TDF
ATV (300 mg), RTV (100 mg) and FTC/TDF (200/300 mg) represent the current marketed 
doses of these products.
1.13.
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 switching to an FDC of GS-9883/F/TAF versus continuing on a 
regimen consisting of E/C/F/TAF, E/C/F/TDF or ATV+RTV+FTC/TDF in virologically 
suppressed HIV-1 infected women as determined by the proportion of subjects with virologic 
failure (HIV-1 RNA ≥ 50 copies/mL) at Week 48. 
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups through Week 48.  

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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

The proportion of subjects with virologic failure (HIV-1 RNA ≥ 50 copies/mL at Week 48, 
as defined by the modified United States (US) Food and Drug Administration (FDA) 
snapshot algorithm). 
The secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA snapshot algorithm.

The change from baseline in CD4+ cell count at Week 48. 
3.2.
Study Design
This protocol describes a randomized, open label, multicenter, active-controlled study to evaluate 
the safety and efficacy of switching to a GS-9883/F/TAF FDC in HIV-1 infected women who 
are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF), 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF), or 
ATV+RTV+FTC/TDF for ≥ 12 consecutive weeks prior to screening.
3.3.
Study Treatments
Subjects who complete the following criteria will be given the option to participate in this study:

Completion of the Week 48 OLE visit or any post Week 48 OLE visits in study
GS-US-236-0128, or

Completion of the Week 96 visit or any post Week 96 visits in study GS-US-292-0109 
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to receive open label medication:

Treatment Group 1: 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 = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)

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3.4. 
Duration of Treatment 
Final 
Original 
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, subjects in a colliltly where 
GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/TAF FDC 
for an additional48 weeks and attend study visits evety 12 weeks, or lliltil the product becomes 
accessible to subjects through an access program, or lliltil Gilead Sciences elects to discontinue 
the study in that colliltty, whichever occurs first. 
Subjects who complete the study through the Week 48 Visit and do not continue post Week 48 
will be required to retum to the clinic 30 days after the Week 48 Visit for a 30 Day Follow-Up 
Visit. 
Figure 3-1. 
Screening 
~ 30 days pl'iot· 
to Day 1 
Study Schema 
Dayl 
a 
Treatment Group 1: GS-9883/F/TAF FDC 
N=200 
Treatment Group 2: Stay on baseline 
regimen (E/C/F/TAF, EICIFITDF or 
ATV+RTV+FTCITDF) N=200 
b 
Wet>k48 
30 
Day 
Ftu' 
a 
Following the Day 1 visit, subje.cts will be required to return for study visits at Weeks 4, 8, 12 and then every 12 weeks 
tlu·ough Week 48 
b 
Aftet· Week 48, subjects in a cmmtry where GS-9883/F!TAF FDC is not available will be given the option to receive 
GS-9883/F!TAF for an additional48 weeks, or tmtil the product becomes accessible to subjects through an access program, 
or tmtil Gilead Sciences elects to discontinue the study in that cotmtry, whichever occurs fu·st 
c 
Subjects who complete the study tlu·ough Week 48 and do not wish to receive GS-9883/F!TAF FDC will be required to 
rettun to the clinic 30 days after the completion of study dmg for a 30-day follow-up visit 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Future Research 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 400 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) Female, (at birth), Age ≥18 years
3) Currently on a stable antiretroviral regimen of E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF continuously for ≥12 consecutive weeks preceding the screening 
visit
4) Completion of the Week 48 OLE visit or any post Week 48 OLE visits in 
study GS-US-236-0128 or completion of the Week 96 visit or any post Week 96 visits in 
study GS-US-292-0109
5) Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥ 12 weeks preceding the 
Screening Visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by resuppression to < 50 copies/mL are allowed
6)
HIV-1 RNA < 50 copies/mL at screening
7) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) 
8) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min according to the Cockcroft-Gault formula 
{2202}:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg)
72 (serum creatinine in μmol/L)
0.85
0. 6786
CrCL (mL/sec)
9) Hepatic transaminases (AST and ALT) ≤5 × upper limit of normal (ULN).
10) Total bilirubin 1.5 mg/dL (26 μmol/L), or normal direct bilirubin.

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11) 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)).
12) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN).
13) Women 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 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Women 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. 
b) Female subjects who have stopped menstruating for ≥12 months but do not have 
documentation of ovarian hormonal failure must have a serum follicle stimulating 
hormone (FSH) level at screening within the post-menopausal range based on the 
Central Laboratory reference range.
14) Have no documented or suspected resistance to FTC, TFV, ATV or EVG including, but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I
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 5)
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 
subject study compliance  
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

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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 clinical trial other than GS-US-236-0128 or GS-US-292-0109, 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, E/C/F/TAF, E/C/F/TDF, 
ATV, RTV, or FTC/TDF
10) Women who are pregnant (as confirmed by positive serum pregnancy test)
11) Women who are breastfeeding  
12) Subjects receiving ongoing therapy with any of the medications in Table 5-1 or Table 5-2.
Administration of any disallowed agent 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) Active tuberculosis infection

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visit cannot occur until 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. 

Treatment Group 1: 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 = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)
The IWRS will assign study drug bottle numbers of open label FDC of GS-9883/F/TAF, 
open label E/C/F/TAF, open label E/C/F/TDF or open label ATV+RTV+FTC/TDF at each study 
visit for each subject.  
Randomization will be stratified by the prior treatment regimen group (ie, E/C/F/TAF, E/C/F/TDF 
and ATV+RTV+FTC/TDF).
5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) 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.

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5.2.1.2.
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF)
Tablets
E/C/F/TAF tablets are capsule-shaped, film-coated green tablets and are debossed with “GSI” on 
one side of the tablet and “510” on the other side of the tablet. E/C/F/TAF tablets contain 150 mg
of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir 
alafenamide. In addition to the active ingredients, the E/C/F/TAF tablets contain colloidal silicon 
dioxide, croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium 
stearate, microcrystalline cellulose, and sodium lauryl sulfate. The tablet cores are film-coated 
with indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, titanium 
dioxide, and yellow iron oxide.
5.2.1.3.
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate
(E/C/F/TDF, Stribild®) Tablets
E/C/F/TDF tablets are capsule-shaped, film-coated green tablets and are debossed with either 
“GSI” on one side and the number “1” surrounded by a square box on the other side, or 
“GILEAD” on one side and plain-faced on the other side of the tablet. E/C/F/TDF tablets contain 
150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of 
tenofovir disoproxil fumarate. In addition to the active ingredients, the E/C/F/TDF tablets 
contain colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, lactose 
monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The 
tablet cores are film-coated with indigo carmine (FD&C Blue #2) aluminum lake, polyethylene
glycol, polyvinyl alcohol, talc, titanium dioxide, and yellow iron oxide.
5.2.1.4.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®) Tablets
FTC/TDF tablets are capsule shaped film-coated blue and are debossed with “GILEAD” on 
one side of the tablet and the number “701” on the other side. FTC/TDF tablets contain 
200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate. Further information is 
available in the Prescribing Information for Truvada®.
5.2.1.5.
Ritonavir (RTV, Norvir®) Tablets
RTV tablets, 100 mg, are ovaloid shaped film coated white and are debossed with “aNK” on 
one side and plain faced on the other side. Further information is available in the Prescribing 
Information for Norvir®.
5.2.1.6.
Atazanavir (ATV, Reyataz®) Capsules
ATV capsules, 300 mg, have a red and blue body and have “BMS 300 mg” in white characters 
on the cap of the capsule and “3622” in white characters on the body of the capsule. Further 
information is available in the Prescribing Information for Reyataz®. 

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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg
(GS-9883/F/TAF) Tablets
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.
5.2.2.2.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Alafenamide 10 mg (E/C/F/TAF) Tablets
E/C/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.
5.2.2.3.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Disoproxil Fumarate 300 mg (E/C/F/TDF, Stribild®) Tablets
E/C/F/TDF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets and a silica gel desiccant with or without polyester coil fiber. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.4.
Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg 
(FTC/TDF, Truvada®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.5.
Ritonavir (RTV, Norvir®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.6.
Atazanavir (ATV, Reyataz®) Capsules
Refer to commercially available Prescribing Information.
All study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(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 GS-9883/F/TAF FDC, E/C/F/TAF and E/C/F/TDF 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.
Commercial product of Norvir® (RTV), Reyataz® (ATV), and Truvada® (FTC/TDF) will be used 
for the study. Further information regarding storage and handling are available in the 
Prescribing Information for commercial products.
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/F/TAF, E/C/F/TAF, E/C/F/TDF and 
ATV+RTV+FTC/TDF
Study drugs GS-9883/F/TAF FDC, E/C/F/TAF, E/C/F/TDF, and ATV+RTV+FTC/TDF 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) administered orally, once daily, without regard to food (n = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)
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. 
5.4.
Prior and Concomitant Medications
The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following tables 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. 

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Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)
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 2 hours before and 6 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 
1000mg either when starting or at study entry.
*
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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Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens)
Drug Class
Agents Disallowed*
Alpha-1 Adrenoreceptor Antagonist 
Alfuzosin
Antiarrhythmic Agent 
Amiodarone, Dronedarone
Anticonvulsants 
Phenytoin, Carbamazepine and Phenytoin
Antimycobacterials 
Rifampin
Antipsychotics
Lurasidone, Pimozide
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements 
St. John’s Wort
Anticancer drugs
Irinotecana
Ergot Derivatives
Ergotamine, Ergonovine, Dihydroergotamine, Methylergonovine, Ergometrine
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Phosphodiesterase-5 Inhibitors
Sildenafil (for PAH)
Sedatives/Hypnotics 
Midazolam (PO), Triazolam
Calcium Channel Blockers 
Bepridil
Chronic angina 
Ranolazine
a
Applied to ATV regimen only
*
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.
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 the 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 screening visit may coincide with the Week 48 OLE visit or any post-Week 48
OLE visits in study GS-US-236-0128 or the Week 96 visit or any post-Week 96 visits in 
study GS-US-292-0109. 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 (women of childbearing potential only). If the test is positive, the 
subject will not be enrolled
FSH test is required for women who have stopped menstruating for ≥ 12 months but do 
not have documentation of ovarian hormonal failure

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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, 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:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg)
72 (serum creatinine in μmol/L)
0.85
0. 6786
CrCL (mL/sec)
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 (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

Review of adverse events and concomitant medications
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. Subjects must continue to take their 
current study treatment regimen up until their scheduled 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.

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6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
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

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin
Urine pregnancy test (women 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.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, 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

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• 
• 
• 
• 
-
Plasma HIV-1 RNA 
-
CD4+ cell cmmt 
-
Plasma storage samples for safety, virology, or PK testing 
-
Whole blood sample for potential virologic resistance testing and/or HIV DNA 
genotyping 
-
Subjects who meet the definition ofHBV infection at Screening Visit (positive semm 
HBsAg or positive HBcAb with quantifiable HBV DNA), will have plasma HBV DNA 
tested 
PD 
Provide subject dosing diaty to all subjects in Treatment Group 1 
Dispense study dmg 
Subjects in treatment group 1 should be instructed to take study dmgs without regard to food . 
Subjects in treatinent group 2 should be instmcted to take study dmg with food. Subjects are 
required to initiate dosing of study dmgs the day of the Day 1 visit. The subject should be 
counseled regarding the impoliance 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 confinned and prior to or dming 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 perfmmed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedmes have been completed and subject 
eligibility has been confi1med. 
6.4. 
Treatment Assessments (Weeks 4-48) 
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, and 48 unless 
othetwise 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 at Week 24 and Week 36, unless 
othetwise specified. The visit window at Week 48 will be ± 6 weeks of the protocol-specified 
visit date, and these clinical visit windows coincide with the Week 48 statistical analysis window 
for HIV-1 RNA. 
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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 and 48) (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 and 48)

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin (Weeks 24 and 48)
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, subjects on 
GS-9883/F/TAF will be discontinued.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, 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 and 48, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. At Weeks 24 and 48, 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 and 48)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula 
Hematology profile: complete blood count (CBC) with differential and platelet count

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Plasma HIV-1 RNA
CD4+ cell count
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

For subjects who meet the definition of HBV infection, the following will be 
conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) 
and HBeAg (if negative, reflex HBeAb) (Weeks 12, 24 and 48)
HCV RNA for subjects with positive HCVAb at screening. (Weeks 24 and 48)
Plasma storage sample for safety, virology, or PK testing

Pharmacokinetic Blood Collection for all subjects on GS-9883/F/TAF only 
(Treatment Group 1). Details of pharmacokinetic blood sampling procedures and sample 
management will be documented in the study’s laboratory manual.
Single Anytime, Trough and Post-Dose PK Samples: (GS-9883/F/TAF –
Treatment Group 1 only)

Subjects will have a single anytime pre or post-dose PK blood sample at 
Weeks 8, 24 and 36

Observed dosing at the clinic: If possible, subjects will have a trough PK blood 
sample collected between 20-28 hours following the 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. 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 single 
trough PK blood sample collection. In the event a subject routinely takes their study 
drug in the evening, a single anytime 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. A single PK blood sample will be collected between 1 and 4 hours post 
dose.  

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.

Provide subject dosing diary to all subjects in Treatment Group 1 (Weeks 4, 8, 12 and 24)

Document study drug dispensation and accountability for all study drugs dispensed

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
Subjects who meet the criteria for virologic rebound will be managed according to the 
Management of Virologic Rebound Section 6.13.1.

HIV-1 genotype/phenotype testing for subjects with virologic failure (Week 48)
6.5.
Treatment Assessments (Post Week 48)
6.5.1.
Post Week 48 Assessments
At the Week 48 Visit, subjects who completed 48 weeks of study drug treatment and are in a 
country where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for an additional 48 weeks and attend study visits every 12 weeks or until 
the product becomes accessible to subject through an access program, or until Gilead Sciences 
elects to discontinue the study in that country, whichever occurs first. 
Subjects who continue participation in the study and receive GS-9883/F/TAF will return for 
study visits every 12 weeks. Study visits are to be completed within ± 6 days of the 
protocol-specified visit date unless otherwise specified.
Subjects participating in the study post Week 48 will be required to return for study visits 
according to the schedule presented in Appendix 2 Study Procedures Table and described in the 
text below:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination as needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin. (Every 24 weeks)
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, subjects on 
GS-9883/F/TAF will be discontinued
Urine storage sample for possible additional clinical testing 

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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, 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) TSH will 
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
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

For subjects who meet the definition of HBV infection, the following will be 
conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) 
and HBeAg (if negative, reflex HBeAb) (Every 24 Weeks)
HCV RNA for subjects with positive HCVAb at screening. (Every 24 Weeks)
Plasma storage samples for safety, virology, or PK testing

Subjects who meet the criteria for virologic rebound will be managed according to the 
Management of Virologic Rebound Section 6.13.1

Document study drug dispensation and accountability for all study drugs dispensed.
6.6.
Post-Treatment Assessments
6.6.1.
Early Study Drugs Discontinuation (ESDD) Assessments
If the subject discontinues study drug prior to the Week 48 Visit, the subject will be asked to 
return to the clinic within 72 hours of stopping study drug for the Early Study Drugs 
Discontinuation Visit. The subject will be asked to continue attending the scheduled study visits 
through the Week 48 Visit.

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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 to baseline, 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

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, 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
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 samples for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability

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6.6.2.
30 Day Follow Up
Subjects who complete the study through the Week 48 visit and do not continue participation in
the study 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 permanently discontinue study drug and refuse to continue in the study through the 
Week 48 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 permanently discontinue study drug 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 participate post Week 48 will complete a 30-Day Follow-Up Visit 30 days after 
last dose of study drug.   
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

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight 

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women 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, 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

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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 may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator.

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Lack of efficacy 

Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study; refer to Appendix 6

Development of active tuberculosis infection

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.
Other Evaluations
6.8.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include but are not limited to urine albumin, urine creatinine, urine protein, retinol binding 
protein and beta-2-microglobulin at the Day 1 Visit, Weeks 24, 48, and every 24 weeks post 
Week 48. At the conclusion of this study, these samples may be retained in storage by 
Gilead Sciences for a period up to 15 years.

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6.9.
Blood and Urine Storage
A portion of the blood and urine samples drawn at all visits (except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its research partners to help answer questions about the 
study drug, about the disease and its associated conditions and/or to provide additional safety 
data. No human genetic testing will be performed without expressed consent of study subjects. 
At the conclusion of this study, these samples may be retained in storage by Gilead Sciences for 
a period up to 15 years. 
6.10.
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.
6.11.
End of Study
The end of study will be the last patient’s last observation (or visit). 
6.12.
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. 
6.13.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥ 50 copies/mL at study 
drug discontinuation or Week 48.  
6.13.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any post Day 1 visit, a rebound in HIV-1 RNA ≥ 50 copies/mL, which is subsequently
confirmed at the following scheduled or unscheduled visit; 
OR

Any subject with HIV RNA ≥ 50 copies/mL at study drug discontinuation
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 

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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-Day 1 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 genotype and phenotype assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping 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 discuss 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. 
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation or 
Week 48
Subjects with HIV-1 RNA ≥ 50 copies/mL at study drug discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 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 or Week 48
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

Persistent or significant disability/incapacity

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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to IMP interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 7.5.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified 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 4). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
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 case report form (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 (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) 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 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 Study IMP, he/she should promptly document and 
report the event to Gilead DSPH.
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 DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
form and submit within 24 hours to:
Gilead DSPH 
contact information:
Fax:
E-mail:
+1 (650) 522-5477
Safety_FC@gilead.com

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.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

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
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

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.
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 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 3 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 4). 

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 t 
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 should 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 should 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 should be permanently discontinued and the subject 
managed according to local practice. The subject should be followed as clinically indicated 
until the laboratory abnormality returns to baseline or is otherwise explained, whichever 
occurs first. A clinically significant Grade 4 laboratory abnormality that is not confirmed by 
repeat testing should be managed according to the algorithm for the new toxicity grade.

Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant 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
An 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 Hyperbilirubinemia
Most patients taking atazanavir sulfate experience asymptomatic elevations in indirect 
(unconjugated) bilirubin related to inhibition of UDP-glucuronyl transferase (UGT). Hepatic 
transaminase elevations that occur with hyperbilirubinemia should be evaluated for alternative 
etiologies. Dose modification of atazanavir sulfate is not permitted. Subjects who experience 
unacceptable jaundice/scleral icterus can be discontinued from study at the discretion of the 
Investigator.

Subjects with bilirubin levels of 5-10 × ULN, if isolated and not accompanied by 
unacceptable clinical jaundice (scleral icterus or cutaneous jaundice) may continue on study, 
if agreed upon by the subject and the Investigator. All subjects with serum bilirubin levels 
5-10 × ULN must have bilirubin, AST and ALT repeated at least once within 7 days of the 
Investigator being notified of the elevated bilirubin level. Thereafter, serum bilirubin levels 
5-10 × ULN without clinically significant elevation in AST or ALT should be followed 
according to the clinical judgment of the Investigator.

Subjects whose hyperbilirubinemia (5-10 × ULN) is accompanied by ≥ Grade 2 ALT or AST 
elevation or who experience a one Grade worsening in ALT or AST do not qualify as having 
isolated hyperbilirubinemia and will be discontinued.

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
Confirmed hyperbilirubinemia > 10 × ULN will require discontinuation.

Elevation of conjugated (direct) bilirubin > 2 mg/dL in association with Grade 2 ALT or 
AST elevation will require discontinuation.
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.
7.5.7.
Management of Potential Nephrotoxicity
Estimated glomerular filtration rate according to the Cockcroft-Gault formula (eGFRC-G), will be 
followed post-baseline during the study. All subjects with estimated GFR < 50 mL/min 
(0.83 mL/sec) must have serum creatinine and subject’s weight measured again within 
3 calendar days of receipt of results.
If a subject has confirmed eGFRC-G < 50 mL/min, the Medical Monitor should be notified and 
discontinuation of the study drug should be discussed. For subjects with confirmed eGFRC-G
< 50 mL/min who are not discontinued based on toxicity management procedures above and are 
considered to have stable renal function per Principal Investigator and Medical Monitor, it is not 
mandatory to repeat eGFR assessments within 3 days.
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, 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.

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An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject 
in question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in study subjects that are identified after initiation of 
study medication and throughout the study, including the post-study drug follow-up period, to 
the Gilead DSPH using the pregnancy report form within 24 hours of becoming aware of the 
pregnancy. 
Refer to below and the eCRF completion guidelines for full instructions on the mechanism of 
pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE or SAE
term, as applicable.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post study 
must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH 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 DSPH. Gilead DSPH contact information is as follows:
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477.
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.

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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 DSPH 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 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.

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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is to evaluate the efficacy of switching to a GS-9883/F/TAF
FDC versus staying on baseline regimen (SBR) in virologically suppressed HIV-1 infected 
women as determined by the proportion of subjects with virologic failure 
(HIV-1 RNA ≥50 copies/mL) at Week 48.
The secondary objective of this study is to evaluate the safety, and tolerability of the 
two treatment groups through Week 48.
8.1.2.
Primary Endpoint
The primary efficacy endpoint is the proportion of subjects with virologic failure
(HIV-1 RNA ≥50 copies/mL) at Week 48 as defined by the modified FDA snapshot algorithm.
8.1.3.
Secondary Endpoint
Secondary endpoints include:

The proportion of subjects withHIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
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.
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 (2) have received at least 1 dose of 
study drug. Subjects will be grouped according to the treatment to which they were randomized.

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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 (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:

Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing is due to discontinuation of study drug for lack of efficacy. 

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 5 including drugs not to be used with 
GS-9883, FTC, TAF, EVG, COBI, ATV and RTV.

Non adherence 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.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
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 of 
GS-9883/F/TAF, and (3) have at least 1 non missing PK concentration data for GS-9883 under 
evaluation reported by the PK lab. 
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. 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 
(e.g., 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.

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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 race, ethnicity, and age. 
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution 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
The primary efficacy endpoint is the proportion of subjects with virologic failure 
(HIV-1 RNA ≥50 copies/mL) at Week 48 as defined by the modified FDA snapshot algorithm. 
The primary analysis of the efficacy will be based on the FAS.
8.5.1.1.
Modified FDA Snapshot Algorithm
The modified FDA snapshot algorithm appears below.
The analysis window at Week 48 is defined as from Study Day 294 to Study Day 377, inclusive. 
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: 

Virologic Success: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window 

Virologic Failure: this include subjects 
a) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window, or 
b) Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and 
1) Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or 
2) Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than lack of efficacy and have the last available on-treatment 
HIV-1 RNA ≥ 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 reasons 
other than lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL or,
b) Missing data during the window but on study drug 
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects with virologic failure 
(HIV-1 RNA ≥50 copies/mL) at Week 48 in the GS-9883/F/TAF group is at least 4% higher
than the virologic failure rate in the SBR group; the alternative hypothesis is that the virologic 
failure rate in the GS-9883/F/TAF group is less than 4% higher than that in the SBR group.
Non-inferiority will be assessed using the conventional confidence interval (CI) approach. The 
point estimate of treatment difference (GS-9883/F/TAF – SBR) and the associated 2-sided 
95% CI will be constructed based on the exact method.  
It will be concluded that GS-9883/F/TAF is non-inferior to E/C/F/TAF if the upper bound of the 
2-sided 95% CI of the difference between treatment groups (GS-9883/F/TAF – SBR) in the 
virologic failure rate is less than 4% (ie, a margin of 4% is applied to non-inferiority assessment).
If non-inferiority of GS-9883/F/TAF to SBRis established, the upper bound of the 95% CI will 
be compared to 0; if the upper bound of the 95% CI is less than 0, superiority of GS-9883/F/TAF
over SBR will be established.
8.5.2.
Secondary Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the
US FDA snapshot algorithm will also be evaluated. The 95% CIs will be constructed in the same 
manner as for the primary efficacy endpoint. However, non-inferiority will be assessed using a 
margin of 10%. It will be concluded that GS-9883/F/TAF is non- inferior to SBRif the lower 
bound of the 2-sided 95% CI of the difference between treatment groups (GS-9883/F/TAF - SBR) 
in the response rate is greater than −10%.
The changes from baseline in CD4+ cell count at Week 48 will be summarized by treatment 
using descriptive statistics. The differences in changes from baseline in CD4+ cell count between 
the 2 treatment groups and the associated 95% CIs will be constructed using ANOVA models, 
including treatment (GS-9883/F/TAF vs. SBR) as a fixed effect in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.

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8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that 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.
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 Illnesses definition of 
an AIDS-Defining Diagnosis will be listed.  
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.

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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 4.
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.
8.7.
Pharmacokinetic Analysis
For the PK analyses, the pharmacokinetics of GS-9883 may be evaluated using descriptive 
statistics or population approaches.
TAF and FTC concentrations may be analyzed as applicable.  
8.8.
Sample Size
A total of approximately 400 HIV-1 infected subjects, randomized in a 1:1 ratio to 
2 treatment groups (200 subjects per treatment group), achieves at least 80% power to detect a 
non-inferiority margin of 4% in Week 48 virologic failure rate (HIV-1 RNA ≥50 copies/mL) 
difference between the 2 treatment groups. For the sample size and power computation, it is 
assumed that both treatment groups have a virologic failure rate of 2% (based on the historical 
Gilead E/C/F/TAF and STB studies), that the non-inferiority margin is 4%, and that the 
significance level of the test is at a one-sided 0.025 level.
8.9.
Independent 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 all 
subjects enrolled complete Week 24 of the study or prematurely discontinue 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.

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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.
An analysis for the Week 24 IDMC meeting will be conducted after the last subjects enrolled 
completes Week 24 of the study. For each IDMC analysis performed prior to analysis for the 
primary efficacy endpoint, an alpha penalty of 0.00001 will be applied for the primary analysis 
of the primary efficacy endpoint.

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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. 

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The 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. The consent form will inform subjects about pharmacogenomic testing and 
sample retention, and their right to receive clinically relevant pharmacogenomic analysis results.
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, CRF and query forms, 
IRB/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);

Documentation of the reason(s) a consented subject is not enrolled

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
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 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 

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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/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.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.

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

GS-9883/F/TAF
Protocol GS-US-380-1961
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Gilead Sciences, Inc.
Original
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9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
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10.
REFERENCES
2202
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum 
creatinine. Nephron 1976;16:31-41.
5125
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. 
Lancet 1998;352 (9142):1725-30.
8284
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.
13585
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.
21053
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.
27881
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.
29702
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a 
difference? Curr Med Res Opin 2013;30 (1):89-97.
29705
Costagliola D. Demographics of HIV and aging. Curr Opin HIV AIDS 2014;9 
(4):294-301.
34898
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.
36201
The Joint United Nations Programme oHAU. Fact Sheet: 2014 Global Statistics. 
Available at: 
http://www.unaids.org/sites/default/files/media_asset/20150714_FS_MDG6_Rep
ort_en.pdf.  2014.

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

GS-98R31F/T AF 
Protocol GS-US-380-1 961 
Final 
Gilead Sciences, Inc. 
Original 
Appendix l. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Switching to a 
Fixed Dose Combination (FDC) ofGS-9883/Emnicitabine/Tenofovir Alafenamide 
(GS-9883/F/T AF) from Elvitegravir/Cobicistat/Emtricitabineffenofovir Alafenamide 
(6/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabinerrenofovir Disoproxi l Fumarate (E/C/F!T DF) 
or Atazanavir + Ritonavir + Emtricitabineffenofovir Disoproxil Fumarate 
(ATV+RTV+FTCffDF) in Virologically Suppressed HIV-1 infected Women 
GS-US-380-1961, Original, 20 Novembea· 2015 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
ppo--------------
Huyen Cao, MD (Printed) 
Author 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary details 
for me and my staff to conduct this study as described. 1 will conduct this study as outlined herein 
and wil1 make a reasonable eff01t to complete the study within the time designated. 
1 will provide aJl study personnel under my supervision copies of the protocol and access to all 
infonnation provided by Gilead Sciences, Inc. 1 will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 89 
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Gilead Sciences, Inc.
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Appendix 2.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48d,v
30 Day 
Follow-Upe
ESDDf
4
8
12
24
36
48
Every 12 Weeks
Informed Consent
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam 
X
X
X
X
X
Symptom-Directed Physical Exam
X
X
X
X
X
X
12-Lead ECG 
X
X
X
X
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Chemistryh
X
X
X
Xw
Urine Pregnancy Testi
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testi
X
Chemistry Profilej
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentsk
X
X
X
X
Xw
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilel
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAm
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 Planeln
X

GS-9883/F/T AF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Study Procedure 
Plasma HBV DNA
0 
HCVAb" 
HCVRNAP 
HIV -1 Genotype/Phenotype q 
Single PK Draw 
Trough PK Draw• 
PK Sample (post-dose)' 
Observed In-Clinic Dose• 
Provide Dosing Diatyu 
Collect Dosing DiarY' 
Plasma Sample Storage
1 
Urine Sample Storage
1 
Whole Blood Storage Sample
1 
~PD 
n 
I 
Randomization 
Study Drug Dispensation 
Study Drug Accountability 
Sc.reening• 
X 
X 
I 
a 
Evaluations to be completed within 30 days prior to Day 1. 
Day lb 
4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b 
Subjects should initiate dosing of study dmg on the same day as the Day 1 visit. 
8 
X 
X 
X 
X 
X 
X 
X 
End ofWeE'kc 
12 
24 
36 
48 
X 
X 
X 
X 
X 
~ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
xv 
X 
X 
X 
X 
Post Week 48d,v 
Every 12 Weeks 
xw 
xw 
X 
X 
xv 
X 
30Day 
Follow-up• 
Final 
Original 
ESDDr 
X 
xq 
X 
X 
X 
c 
All study visits should be± 2 days of the protocol-specified visit date based on the Day 1 visit through We.ek 12 and completed \.,'ithin ± 6 days at We.ek 24 and Week 36, 
lmless othetwise specified. The visit window at Week 48 will be± 6 weeks of the protocol-specified visit date. 
d 
At the Week 48 Visit, subjects in a cmmtry where GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/T AF FDC for an additional48 weeks, 
or until the product becomes accessible to subjects through an access program, or lmtil Gilead Sciences elects to discontinue the study in that cmmtry, whichever occm-s first. 
Study visits are to be completed every 12 weeks, within± 6 days of the protocol-spe.cified visit date lmless otherwise specified. 
CONFIDENTIAL 
Page 91 
20 November 2015 

GS-9883/F/TAF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Final 
Original 
e 
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30-Day Follow-Up Visit, a± 6 days window may be used. Required for subjects 
who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Subjects who participate 
post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit. 
f 
Early Study Drug Discontinuation visit to occur within 72 hours oflast dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Week 48 Visit even if the subject discontinues study drug. 
g 
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature 
h 
Urine Chemistry includes urine albumin, urine creatinine, urine protein, retinol binding protein, and beta-2 microglobulin 
Women of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test. 
Chemistry profile: alkaline phosphatase, AST, AL T, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, 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 x ULN). At Day 1, 
Weeks 24, and 48 and every 24 weeks during the post Week 48 period, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of the 
chemistry profile. TSH will be collected at Screening, Day 1, Weeks 24, and 48, as well as every 24 weeks post Week 48, and ESDD if applicable. 
k 
Fasting 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. 
CBC with differential and platelet count. 
m 
If the HIV-1 RNA value is 2: 50 copies/mL at Week 48, a retest HIV -1 RNA value must be collected within two to three weeks of the initial test. 
n 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb). 
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 HB V DNA (if positive, reflex HBeAg). If HBeAg is performed and found to be negative, reflex HBeAb. 
o 
For subjects who meet the definition ofHBV infection, the following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) and HBeAg 
(if negative, reflex HBeAb) at Days 1, 12, 24 and then every 24 weeks. 
p 
Subjects who are HCVAb positive will have a HCV RNA test performed at screening and every 24 weeks. 
q 
HIV-1 genotype/phenotype testing for subjects with HIV-1 RNA 2: 200 copies/mL and virologic rebound, at early study drug discontinuation or Week 48. Following 
unconfirmed 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/phenotype (reverse transcriptase, protease and integrase) blood draw. Based on the results of this testing, subjects should be managed 
according to the Virologic Rebound Schema (Section 6.13. 1 ). 
r 
All subjects on GS-9883/FfrAF (Treatment Group 1 only) will have a single anytime PK blood sample collected at Weeks 8, 24 and 36. 
s 
Subjects on GS-9883/FfrAF (Treatment Group 1 only) 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. 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 single trough PK blood sample collection. In the event a subject routinely takes their 
study drug in the evening, a single anytime 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. A post-dose PK blood sample will be collected between 1 and 4 hours post dose following an observed, in-clinic dose. 
Plasma storage samples banked for possible future protocol-related testing (safety, virology, pharmacokinetic analysis). Urine storage samples banked for ossible future 
IJrotocol-related safety testi11g includi11g urine chernist:ry. Whole blood sampl:::::.Jotential virologic resistance testing and/or HIV DNA genotyping . .__P_D _____ ___. 
u 
A dos1ng diary will be dispensed for all Treatment Group 1 sUDJects to complete pnor to each of the PK sample visits. 
v 
Open-label GS-9883/F/T AF FDC will be dispensed to subjects participating in the study post Week 48 starting at the Week 48 Visit. 
w 
Every 24 weeks only. 
x 
Dosing diaries will be collected from subjects for the single anytime PK and trough PK collection (Treatment Group 1 only). 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. 
CONFIDENTIAL 
Page 92 
20November 2015 

GS-9883/F/TAF 
Protocol GS-US-380-1961 
Final 
Gilead Sciences, Inc. 
Original 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
Grade I 
~-----G_r_a_d_e_2----~~ 
~
~ ______ G_r_a_de-3------~~ ~
~ __________ G_m_d_e_4--------~ 
! 
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 con tinned and possibly or probably 
related to investigational medicinal products, discontinue a11 
investigational medicinal products dosing permanently 
Repeat lab to 
confirm toxicity 
grade 
1 
1 
lfc 
elated to 
inve 
dicinal products, 
onfrrmed and unr 
stigationalme 
ng may contin 
he investigator 
dosi 
ue at the discretion 
oft 
If confirmed and 
possibly or probably 
I-+ 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 
CONFIDENTIAL 
Page 93 
20 November 2015 

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 94
20 November 2015
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count  
(ANC)
Adult and Pediatric, 
≥ 7 Months#
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL

GS-9883/F/TAF
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Final
Gilead Sciences, Inc.
Original
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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-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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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

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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 97
20 November 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 98
20 November 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (corrected for 
albumin if appropriate*)
Adult and Pediatric 7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to  <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63  to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
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

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 99
20 November 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 100
20 November 2015
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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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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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-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 102
20 November 2015
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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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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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
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Original
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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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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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20 November 2015
RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced 
to 70% to 80%
FEV1 or peak flow 50% to 
69%
FEV1 or peak flow 25% to 
49% 
Cyanosis OR FEV1 or peak 
flow 25% OR Intubation
Dyspnea or Respiratory Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities 
Dyspnea on exertion causing 
greater than minimal 
interference with usual social 
& functional activities 
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate 
for age
Nasal flaring OR Intercostal 
retractions OR Pulse 
oximetry 90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
OR Pulse oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis 
OR Medical intervention 
indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in 
affected eye(s) 
Visual Changes (from baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing 
greater than minimal 
interference with usual social 
& functional activities
Visual changes causing 
inability to perform usual 
social & functional activities
Disabling visual loss in 
affected eye(s)

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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
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SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by study 
participant or  caregiver (for 
disabled adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or 
morbilliform rash with 
vesicles or limited number of 
bullae OR Superficial 
ulcerations of mucous 
membrane limited to one site
Extensive or generalized 
bullous lesions OR Stevens-
Johnson syndrome OR 
Ulceration of mucous 
membrane involving two or 
more distinct mucosal sites 
OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
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Original
CONFIDENTIAL
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20 November 2015
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

GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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20 November 2015
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
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
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, Dysphagia-
Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal 
bleeding OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 24–
48 hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening 
consequences (eg, 
hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening 
consequences (eg, sepsis, 
circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ Stomatitis 
for Clinical Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities OR 
Medical intervention 
indicated 
Symptoms causing inability 
to perform usual social/ 
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences (eg, 
perforation)
Vomiting
Transient or intermittent 
vomiting with no or minimal 
interference with oral intake
Frequent episodes of 
vomiting with no or mild 
dehydration
Persistent vomiting resulting 
in orthostatic hypotension 
OR Aggressive rehydration 
indicated
Life-threatening 
consequences (eg, 
hypotensive shock)

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

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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Headache 
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities
Symptoms causing inability 
to perform usual social & 
functional activities
Symptoms causing inability 
to perform basic self-care 
functions OR Hospitalization 
indicated (other than ER 
visit) OR Headache with 
significant impairment of 
alertness or other neurologic 
function 
Insomnia
NA
Difficulty sleeping causing 
greater than minimal 
interference with usual 
social/functional activities
Difficulty sleeping causing 
inability to perform usual 
social & functional activities
Disabling insomnia causing 
inability to perform basic 
self-care functions
Neuromuscular Weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength on exam 
OR Minimal muscle 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
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)

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

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

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

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

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

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

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

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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 {13585}

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Appendix 6.
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.  
Females 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, females 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.
2) Contraception Requirements for Women
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 and the latest versions of the 
E/C/F/TAF, E/C/F/TDF, ATV, RTV and FTC/TDF package inserts or investigator’s brochures
for additional information.  
b. Contraception Requirements for Women 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 a 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) 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.
4) 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 immediately. The investigator will counsel the subject regarding 
pregnancy management options. Counseling will be provided regarding alternative anti-HIV 
treatment. Information on the risks and benefits of antiretroviral therapies will be discussed, 
including the risk of ongoing fetal exposure to the study drug versus the new alternative therapy 
and the risk of discontinuing maternal therapy.
If the subject is on GS-9883/F/TAF, they must discontinue study drug immediately. Subjects 
may be allowed to continue on study drug if they are taking E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF and an additional informed consent will be required.
If the subject elects to discontinue study drugs but remain in the study, a new ARV regimen will 
be constructed at the Investigator’s discretion. 
The Investigator should counsel the subject on the need to inform the study site of the outcome 
of the pregnancy. Information collected will include gestational dating, ultrasound report, records 
of maternal, fetal complications and pregnancy outcome. 
Instructions for reporting pregnancy and pregnancy outcome are outlined in Section 7.6.