Clinical trial NCT02607930
Conditions: HIV-1 Infection
Keywords: HIV
Sponsor: Gilead Sciences
Start date: 2015-11-13; Completion date: 2021-07-02
Enrollment: 631 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of a fixed dose combination (FDC) containing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus a FDC containing abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral treatment naive-adults.

Detailed description:

Arms: arm 1: B/F/TAF + ABC/DTG/3TC placebo administered without regard to food for at least 144 weeks. arm 2: ABC/DTG/3TC + B/F/TAF placebo administered without regard to food for at least 144 weeks. arm 3: After Week 144, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants will be given the option to receive open-label (OL) B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF is not commercially available will be given the option to continue OL B/F/TAF until the product becomes accessible through an access program or until Gilead elects to discontinue the study in that country, whichever occurs first. arm 4: After Week 144, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants will be given the option to receive OL B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF is not commercially available will be given the option to continue OL B/F/TAF until the product becomes accessible through an access program or until Gilead elects to discontinue the study in that country, whichever occurs first.
Interventions: intervention 1: ABC/DTG/3TC intervention 2: B/F/TAF intervention 3: ABC/DTG/3TC Placebo intervention 4: B/F/TAF Placebo
Intervention descriptions: intervention 1: 600/50/300 milligrams (mg) tablets administered orally, once daily intervention 2: 50/200/25 mg tablets administered orally, once daily, without regard to food intervention 3: Tablets administered orally, once daily intervention 4: Tablets administered orally, once daily

Protocol documents:
SAP_010.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the 
Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir 
Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in 
HIV-1 Infected, Antiretroviral Treatment-Naïve Adults
Name of Test Drug:
Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF; GS-9883/F/TAF)
Study Number:
GS-US-380-1489
Protocol Version (Date):
Amendment 3 (04 April 2019)
Analysis Type:
Final Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
22 September 2021
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
 
PPD


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TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN ...............................................................................................................................1
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................4
1.
INTRODUCTION..................................................................................................................................................8
1.1.
Study Objectives........................................................................................................................................8
1.2.
Study Design .............................................................................................................................................8
1.3.
Sample Size and Power ...........................................................................................................................11
2.
TYPE OF PLANNED ANALYSIS......................................................................................................................12
2.1.
Data Monitoring Committee Analyses....................................................................................................12
2.2.
Interim Analyses......................................................................................................................................12
2.2.1.
Week 48 Analysis..................................................................................................................12
2.2.2.
Week 96 Analysis..................................................................................................................12
2.2.3.
Week 144 Analysis................................................................................................................12
2.2.4.
Open Label Week 48 Analysis..............................................................................................12
2.3.
Final Analysis..........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................13
3.1.
Analysis Sets ...........................................................................................................................................14
3.1.1.
All Randomized Analysis Set................................................................................................14
3.1.2.
All B/F/TAF Analysis Set .....................................................................................................15
3.1.3.
DXA Analysis Set for All B/F/TAF Analysis.......................................................................15
3.2.
Subject Grouping.....................................................................................................................................15
3.3.
Strata and Covariates...............................................................................................................................16
3.4.
Examination of Subject Subgroups .........................................................................................................16
3.4.1.
Subject Subgroups for Safety Analyses ................................................................................16
3.5.
Multiple Comparisons .............................................................................................................................16
3.6.
Missing Data and Outliers.......................................................................................................................16
3.6.1.
Missing Data..........................................................................................................................16
3.6.2.
Outliers ..................................................................................................................................17
3.7.
Data Handling Conventions and Transformations ..................................................................................17
3.8.
Analysis Windows...................................................................................................................................17
3.8.1.
Definition of Study Day ........................................................................................................17
3.8.2.
Analysis Windows.................................................................................................................19
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window .................................................................................................................................24
4.
SUBJECT DISPOSITION ...................................................................................................................................26
4.1.
Subject Enrollment and Disposition........................................................................................................26
4.1.1.
Subject Enrollment ................................................................................................................26
4.1.2.
Subject Disposition................................................................................................................26
4.2.
Extent of Study Drug Exposure and Adherence......................................................................................27
4.2.1.
Duration of Exposure to Study Drug.....................................................................................27
4.2.2.
Adherence to Study Drug Regimen.......................................................................................27
4.3.
Protocol Deviations .................................................................................................................................28
4.4.
Missing Protocol-Specified Information due to COVID-19 ...................................................................29
5.
BASELINE CHARACTERISTICS .....................................................................................................................30
5.1.
Demographics and Baseline Characteristics ...........................................................................................30
5.2.
Baseline Disease Characteristics .............................................................................................................30


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5.3.
Medical History.......................................................................................................................................30
6.
EFFICACY ANALYSES.....................................................................................................................................31
6.1.
Primary Efficacy Endpoint......................................................................................................................31
6.2.
Secondary Efficacy Endpoints ................................................................................................................31
6.2.1.
Definition of the Secondary Efficacy Endpoints...................................................................31
6.3.
Efficacy Endpoints for all B/F/TAF Analysis.........................................................................................32
6.3.1.
Definition of the Efficacy Endpoint for all B/F/TAF Analysis.............................................32
6.3.2.
Analysis of the Efficacy Endpoints for all B/F/TAF Analysis..............................................32
6.4.
Changes From Protocol-Specified Efficacy Analyses ............................................................................33
7.
SAFETY ANALYSES.........................................................................................................................................34
7.1.
Adverse Events and Deaths.....................................................................................................................34
7.1.1.
Adverse Event Dictionary .....................................................................................................34
7.1.2.
Adverse Event Severity .........................................................................................................34
7.1.3.
Relationship of Adverse Events to Study Drug.....................................................................34
7.1.4.
Serious Adverse Events.........................................................................................................34
7.1.5.
Treatment-Emergent Adverse Events....................................................................................34
7.1.6.
Summaries of Adverse Events and Death .............................................................................35
7.1.7.
Additional Analysis of Adverse Events ................................................................................36
7.2.
Laboratory Evaluations ...........................................................................................................................37
7.2.1.
Summaries of Numeric Laboratory Results ..........................................................................37
7.2.2.
Graded Laboratory Values ....................................................................................................38
7.2.3.
Metabolic Laboratory Evaluations ........................................................................................39
7.2.4.
Liver-Related Laboratory Evaluations ..................................................................................40
7.2.5.
Renal-Related Laboratory Evaluations..................................................................................40
7.3.
Bone Safety Analyses..............................................................................................................................41
7.3.1.
Bone Mineral Density............................................................................................................41
7.4.
Body Weight, Height, and Vital Signs ....................................................................................................42
7.5.
Prior and Concomitant Medications........................................................................................................43
7.5.1.
Nonstudy Drug Antiretroviral Medications...........................................................................43
7.5.2.
Concomitant Non-ARV Medications....................................................................................43
7.6.
Electrocardiogram Results.......................................................................................................................44
7.7.
Other Safety Measures ............................................................................................................................44
7.8.
Changes From Protocol-Specified Safety Analyses................................................................................44
8.
PHARMACOKINETIC ANALYSES..................................................................................................................45
9.
SPECIAL POPULATION ANALYSES..............................................................................................................46
9.1.
Analyses for HIV/HBV Coinfected Subjects..........................................................................................46
9.2.
Analyses for HIV/HCV Coinfected Subjects..........................................................................................47
10.
REFERENCES.....................................................................................................................................................48
11.
SOFTWARE.........................................................................................................................................................49
12.
SAP REVISION...................................................................................................................................................50
13.
APPENDICES......................................................................................................................................................51
Appendix 1.
Study Procedures Table...........................................................................................................52
Appendix 2.
Cardiovascular or Cerebrovascular Events..............................................................................58
Appendix 3.
Hepatic Events.........................................................................................................................59
Appendix 4.
Adverse Events of COVID-19.................................................................................................60
Appendix 5.
Determining Missing and Virtual Visits Due to COVID-19...................................................61
Appendix 6.
Programming Specification .....................................................................................................64


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LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, Hematology, 
Chemistry, Urinalysis, and Urine Pregnancy Laboratory Tests, eGFRCG, Vital Signs, 
and Weight for Randomized Phase Analysis ..........................................................................19
Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, Hematology, 
Chemistry, Urinalysis, and Urine Pregnancy Laboratory Tests, eGFRCG, Vital Signs, 
and Weight for all B/F/TAF Analysis .....................................................................................20
Table 3-3.
Analysis Windows for Metabolic Assessments for Randomized Phase Analysis ..................20
Table 3-4.
Analysis Windows for Metabolic Assessments for all B/F/TAF Analysis .............................21
Table 3-5.
Analysis Windows for TSH and Renal Function for Randomized Phase Analysis ................21
Table 3-6.
Analysis Windows for TSH and Renal Function for all B/F/TAF Analysis...........................22
Table 3-7.
Analysis Windows for HBV and HCV Serology, HBV DNA and HCV RNA 
Assessments for Randomized Phase Analysis.........................................................................22
Table 3-8.
Analysis Windows for HBV and HCV Serology, HBV DNA and HCV RNA 
Assessments for all B/F/TAF Analysis ...................................................................................22
Table 3-9.
Analysis Windows for Safety ECG for Randomized Phase Analysis.....................................23
Table 3-10.
Analysis Windows for Safety ECG for all B/F/TAF Analysis................................................23
Table 3-11.
Analysis Windows for DXA BMD for Randomized Phase Analysis .....................................23
Table 3-12.
Analysis Windows for DXA BMD for all B/F/TAF Analysis (For Subjects That 
Were Randomized to B/F/TAF Group Only)..........................................................................24
Table 7-1.
Normal, Osteopenia, and Osteoporosis as Defined by T-score...............................................42


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LIST OF ABBREVIATIONS
3TC
lamivudine
ABC
abacavir
ABC/DTG/3TC
fixed dose combination of abacavir (ABC) 600 mg / dolutegravir (DTG) 50 mg / 
lamivudine (3TC) 300 mg
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARV
antiretroviral
ART
antiretroviral treatment
AST
aspartate aminotransferase
BIC
bictegravir
B/F/TAF
fixed dose combination of bictegravir (BIC; B) 50 mg / emtricitabine (FTC; F) 200 mg / 
tenofovir alafenamide (TAF) 25 mg
BLQ
below limit of quantitation
BMD
bone mineral density
BMI
body mass index
CDER
Center for Drug Evaluation and Research
CG
Cockcroft-Gault
CI
confidence interval
CMH
Cochran-Mantel-Haenszel 
CRF
case report form
CSR
clinical study report 
CV
coefficient of variation
DC
premature study drug discontinuation
DNA
deoxyribonucleic acid
DTG
dolutegravir, tivicay
DXA
dual energy x-ray absorptiometry
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
full Analysis Set
FDA
Food and Drug Administration
FDC
fixed dose combination
F/TAF
fixed dose combination of emtricitabine (FTC; F)/ tenofovir alafenamide (TAF)
FTC, F
emtricitabine
GEN
Genvoya, E/C/F/TAF
GFR
glomerular filtration rate


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GLPS
Global Patient Safety
Gilead
Gilead Sciences, Inc.
GS-9883
bictegravir
HBcAb
hepatitis B core antibody 
HBeAb
hepatitis B e-antibody 
HBeAg
hepatitis B e-antigen
HBsAb
hepatitis B surface antibody 
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb
hepatitis C antibody
HDL
high density lipoprotein
HIV-1
human immunodeficiency virus (Type 1) 
HLGT
high level group term
HLT
high level term
ICH
International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use
ID
identification
IDMC
independent data monitoring committee
IWRS
interactive web response system
LDL
low density lipoprotein
LLT
lowest level term
MedDRA
Medical Dictionary for Regulatory Activities
MH
Mantel-Haenszel 
OL
open label
PEP
post-exposure prophylaxis 
PrEP
pre-exposure prophylaxis
PK
pharmacokinetic
PP
per protocol
PT
preferred term
PVE
Pharmacovigilance and Epidemiology
Q
quartile
Q1
first quartile
Q3
third quartile
QD
once daily
RBP
retinol binding protein
RNA
ribonucleic acid
SAE
serious adverse events
SD
standard deviation
SMQ
Standardised MedDRA Query


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SOC
system organ class
TAF
tenofovir alafenamide 
TFL
tables, figures, and listings
TFV
tenofovir
TSH
thyroid stimulating hormone; thyrotropin
ULN
upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the final analysis clinical study 
report (CSR) for Study GS-US-380-1489. Final analysis will be performed when all subjects 
have completed the study or prematurely discontinued from the study drug. This SAP is based on 
the study protocol amendment 3 dated 04 April 2019 and the electronic case report form (eCRF). 
The SAP will be finalized before database finalization. Any changes made after the finalization 
of the SAP will be documented in the CSR.
1.1.
Study Objectives
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) containing bictegravir 
(GS-9883; BIC; B) /emtricitabine (FTC; F) /tenofovir alafenamide (TAF) versus a FDC 
containing abacavir /dolutegravir /lamivudine (ABC/DTG/3TC) in HIV-1 infected, 
antiretroviral treatment (ART)-naïve adult subjects as determined by the achievement of 
HIV-1 ribonucleic acid (RNA) < 50 copies/mL at Week 48.
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the 2 treatment groups through 
Weeks 48, 96, and 144.

To evaluate the bone safety of the 2 treatment groups as determined by the percentage change 
from baseline in hip and spine bone mineral density (BMD) through Weeks 48, 96, and 144.

To evaluate the long term efficacy and safety of FDC B/F/TAF through OL Weeks 48 and 
96.
1.2.
Study Design
Design Configuration and Subject Population
GS-US-380-1489 is a randomized, double-blinded, multicenter, active-controlled study to 
evaluate the safety and efficacy of B/F/TAF FDC versus ABC/DTG/3TC FDC in HIV-1 infected 
ART-naive adult subjects.
Treatment Groups
Subjects who provide written consent and meet all eligibility criteria will be randomized in a 
1:1 ratio to one of the following 2 treatment groups:

Treatment Group 1: FDC of bictegravir 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (B/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard 
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
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of bictegravir 50 mg/ emtricitabine 
200 mg/ tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily, without 
regard to food (n = 300)
Key Eligibility Criteria
Medically stable HIV-1 infected subjects who meet the following criteria:

Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening

ART-naive (≤ 10 days of prior therapy with any antiretroviral [ARV] agent following a 
diagnosis of HIV-1 infection) except the use for pre-exposure prophylaxis (PrEP) or 
post-exposure prophylaxis (PEP), up to 1 month prior to screening.

Screening genotype report must show sensitivity to FTC, tenofovir (TFV), 3TC, and ABC

Negative screening test for HLA-B*5701 allele

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine 
clearance

No chronic Hepatitis B Virus (HBV) infection, as determined by either
Positive HBV surface antigen (HBsAg) and negative HBV surface antibody (HBsAb), 
regardless of HBV core antibody (HBcAb) status, at the screening visit
Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
Study Periods / Phases
Subjects will be treated for at least 144 weeks during the blinded treatment phase. After 
Week 144, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead Sciences Inc. (Gilead) completes the Week 144 analysis, all subjects 
will return to the clinic (preferably within 30 days) for an End of Blinded Treatment Visit. At the 
End of Blinded Treatment Visit, subjects will be given B/F/TAF FDC in an open-label (OL) 
extension phase for 96 weeks. After Week 96 OL, subjects will discontinue the study drug, 
transition onto commercially available treatment and complete a 30-Day Follow-up Visit. In a 
country where B/F/TAF is not available, subjects will be given the option to continue OL 
B/F/TAF until the product becomes accessible to subjects through an access program, or until 
Gilead elects to discontinue the study in that country, whichever occurs first. 
All subjects participating in the OL extension phase, without regard to their blinded treatment 
regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for 96 weeks.


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Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the OL B/F/TAF FDC extension phase will be required to return to the clinic after 
the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
Schedule of Assessments
After screening procedures, eligible subjects will be randomized 1:1 to Treatment Group 1 or 
Treatment Group 2 and treated for 144 weeks. Following the Day 1 visit, subjects will be 
required to return for study visits at Weeks 4, 8, and 12, and then every 12 weeks from Week 12 
through Week 144. After Week 144, all subjects will continue to take their blinded study drugs 
and attend study visits every 12 weeks until the End of Blinded Treatment Visit. All subjects 
participating in the OL extension phase, without regard to their blinded treatment regimen, will 
return for study visits at Week 12 OL and every 12 weeks thereafter for at least 96 weeks.
For all eligible subjects, blood will be collected at Day 1, Weeks 4, 8, 12, and then every 
12 weeks through the End of Blinded Treatment Visit. Blood will also be collected at Week 12 
OL and every 12 weeks thereafter for at least 96 weeks during the OL extension phase. 
Laboratory analyses (hematology, chemistry, and urinalysis), HIV-1 RNA, CD4+ cell count, and 
complete or symptom directed physical examinations will be performed at Screening, Day 1, and 
all subsequent visits. In addition, blood will be collected and stored for possible evaluation of 
markers of inflammation and immune activation, which may include but are not limited to: 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14, and sCD163. Platelet function evaluations may also 
be assessed, including but not limited to soluble glycoprotein VI (sGPVI), P-selectin, and soluble 
CD40 ligand. Urine will be collected for evaluations of renal function including urine albumin, 
urine creatinine, urine protein, retinol binding protein (RBP), and beta-2 microglobulin.
For all subjects on study drug, except subjects located in Germany, dual energy x-ray 
absorptiometry (DXA) scans will be performed prior to or within 24 hours of the Day 1 Visit, 
and then at Weeks 24, 48, 96, 144 and at the End of Blinded Treatment Visit or Early Study 
Drug Discontinuation Visit, if > 12 weeks since last scan. DXA will be performed at Week 48 
OL and Week 96 OL for subjects who were randomized to B/F/TAF, complete the blinded phase 
and enter the OL extension phase, except subjects located in Germany. DXA scan results will be 
provided to study sites when available.
Adverse events (AEs) and concomitant medications will be assessed at each visit.
More details for study procedures can be found in Appendix 1.


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Pharmacokinetics 
Version 1.0 
For all subjects on study chug, a single anytime pre- or post-dose PK blood sample will be 
collected at Weeks 8, 24, and 36. 
For all subjects on study chug, a trnugh PK blood sample will be obtained 20-28 hours following 
the last dose at Weeks 4 and 12. Following an observed dose, one post-dose PK blood sample 
will be collected between 1 and 4 hours post-dose. 
Randomization 
Subjects will be randomized in a 1: 1 ratio to 1 of 2 Treatment Groups (Treatment Group 1: 
Treatment Group 2). Randomization will be stratified by HIV-1 RNA level 
(~ 100,000 copies/mL, > 100,000 to~ 400,000 copies/mL, or > 400,000 copies/mL) at screening, 
CD4+ cell count(< 50 cells/µL, 50 - 199 cells/µL, or ~ 200 cells/µL) at screening, and region 
(US or Ex-US) at randomization. 
Site and/or Stratum Enrollment Limits 
Approximately 150 study sites in No1th America, Europe, and Latin America paiticipated. There 
was no emollment limit for individual sites. 
Study Duration 
The randomized, double-blind phase of this study is at least 144 weeks in duration. The OL 
phase is 96 weeks in duration. 
1.3. 
Sample Size and Power 
A total of approximately 600 HIV-1 infected subjects, randomized in a 1: 1 ratio to 2 treatment 
groups (300 subjects per treatment group), achieves at least 95% power to detect a noninferiority 
margin of 12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as determined by the 
United States [US] Food and Drng Achninistration [FDA]-defined snapshot algorithm) difference 
between the 2 treatment groups. For sample size and power computation, it is assumed that both 
treatment groups have a response rate of 91 % (based on Gilead Genvoya [GEN; E/C/F IT AF] 
Studies GS-US-292-0104 and GS-US-292-0111), that a noninferiority margin is 12%, and that 
the significance level of the test is at a one-sided 0.025 level. Sample size and power calculations 
were made using the statistical softwai·e package nQue1y Advisor (Version 6.0). 
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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee Analyses
The Week 12 Independent Data Monitoring Committee (IDMC) analysis was conducted after 
approximately the first 50% of subjects enrolled completed their Week 12 visit or prematurely 
discontinued the study drug. The Week 24 IDMC analysis was conducted after all subjects 
enrolled completed their Week 24 visit or prematurely discontinued the study drug. The purpose 
of these interim analyses was to provide the IDMC with a statistical report for review. More 
details are documented in the IDMC charter. 
Gilead does not have a prior intent to ask the IDMC to review Week 48 results or to consider 
early termination of the study even if there is early evidence of favorable efficacy for B/F/TAF. 
2.2.
Interim Analyses
2.2.1.
Week 48 Analysis
The Week 48 analysis was conducted after all subjects either completed their Week 48 visit or 
prematurely discontinued from the study drug.
2.2.2.
Week 96 Analysis
The Week 96 analysis was conducted after all subjects either completed their Week 96 visit or 
prematurely discontinued from the study drug.
2.2.3.
Week 144 Analysis
The Week 144 analysis was conducted after all subjects either complete their Week 144 visit or 
prematurely discontinue from the study drug.
2.2.4.
Open Label Week 48 Analysis
The OL label Week 48 analysis was conducted after all subjects either complete their open label 
Week 48 visit or prematurely discontinue from the study drug.
2.3.
Final Analysis
The final statistical analysis will be conducted after all subjects either complete the study or 
prematurely discontinue from the study.
This statistical analysis plan describes the analysis plan for the final analysis.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
The Final Analysis will include two sets of analysis: randomized phase analysis and all B/F/TAF 
analysis. All table summaries in this final analysis will be based on data included in the All 
B/F/TAF analysis (eg, data collected during the study period when participants were on 
B/F/TAF). Randomized phase analysis (eg, including data collected during double-blind phase 
when participants were on the double-blind study drug) and the corresponding analysis window 
defined in Section 3.8, will be used to support applicable listings where data collected from the 
double-blind phase are indicated. The wording of randomized phase or double-blind phase might 
be used interchangeably throughout the SAP and in the TFLs.
Randomized Phase Analysis:

For subjects who are never treated in the extension phase of the study including those who 
prematurely discontinue the randomized study drug or who complete the randomized study 
drug and do not receive any dose of B/F/TAF in the extension phase, all available data will 
be included in the randomized phase analysis.

For subjects who complete the randomized phase and receive at least 1 dose of B/F/TAF in 
the extension phase, the randomized phase analysis will include (1) all available AE, 
concomitant medication, pregnancy, and death data collected prior to the extension phase 
first dose date; (2) all available other data, such as laboratory, vital sign, electrocardiogram 
(ECG), collected on or prior to the extension phase first dose date.
All B/F/TAF Analysis:

For subjects who receive B/F/TAF in the randomized phase, all available data for subjects 
who actually receive B/F/TAF in the randomized phase will be included. 

For subjects who actually receive ABC/DTG/3TC in the randomized phase and receive at 
least 1 dose of B/F/TAF in the extension phase, (1) all available AE, concomitant 
medication, pregnancy, and death data with start date on or after the first dose date of 
B/F/TAF in the extension phase and (2) all available other data, such as laboratory, vital sign, 
and ECG data, collected after the first dose date of B/F/TAF in the extension phase will be 
included. Except that the data collected on or prior to the first dose date of B/F/TAF will be 
used to derive the baseline value for the all B/F/TAF analysis. 
Note that all data for subjects who actually receive ABC/DTG/3TC in the randomized phase and 
do not receive any dose of B/F/TAF in the extension phase will be excluded from all B/F/TAF 
analysis. The actual treatment received will differ from the randomized treatment only when the 
actual treatment received differs from randomized treatment for the entire treatment duration.


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Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
For All B/F/TAF Analysis, no statistical comparison between treatment groups will be 
conducted.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set unless 
otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). Data 
collected on log forms, such as AEs, will be presented in chronological order within a subject. 
The treatment group to which subjects were randomized will be used in the listings. Most listings 
will be provided for all randomized analysis set for data from both phases of the study. Some 
listings for All B/F/TAF analysis set will also be provided.
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. For randomized but never dosed subjects, age on the date of 
randomization will be used. For screen failures, age on the date of the informed consent was 
signed will be used. If only birth year is collected on the eCRF, “01 January” will be used for the 
unknown birth day and month for the purpose of age calculation, similarly, if only birth year and 
month are collected on the eCRF, “01” will be used for the unknown birth day for the purpose of 
age calculation. 
In general, permanent discontinuation of the randomized study drug refers to premature 
discontinuation of the randomized study drug or completion of the randomized study drug. 
Similarly, permanent discontinuation of the extension phase study drug refers to premature 
discontinuation of the extension phase study drug or completion of the extension phase study 
drug. More specifically, for all B/F/TAF analysis, study drug refers to B/F/TAF. 
3.1.
Analysis Sets
Analysis Sets define the subjects to be included in an analysis. Analysis Sets and their definitions 
are provided in this section. Subjects included in each Analysis Set will be determined before the 
study blind is broken for analysis. The Analysis Set will be included as a subtitle of each table, 
figure, and listing. A summary of the number and percentage of subjects in each Analysis Set 
will be provided by treatment group and in total.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set will include all subjects who are randomized into the 
randomized phase of the study. This is the primary analysis set for by-subject listings. 


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3.1.2.
All B/F/TAF Analysis Set
The All B/F/TAF Analysis Set will include all subjects who (1) are randomized into the study 
and (2) have received at least 1 dose of the B/F/TAF in the randomized phase or at least 1 dose 
of the B/F/TAF in the extension phase. This is the primary analysis set for the all B/F/TAF 
efficacy and safety analyses. 
For efficacy analyses, all efficacy data collected for the all B/F/TAF analysis will be included.
For safety analyses, all safety data collected up to 30 days after permanent discontinuation of the 
B/F/TAF (including randomized and open label phases) will be included in the safety summaries, 
unless specified otherwise.
3.1.3.
DXA Analysis Set for All B/F/TAF Analysis
3.1.3.1.
Hip DXA Analysis Set for All B/F/TAF Analysis
The Hip DXA Analysis Set for All B/F/TAF Analysis will include all subjects who (1) are 
randomized into the B/F/TAF group , (2) have received at least 1 dose of study drug, and 
(3) have nonmissing baseline hip BMD values. Subjects will be grouped according to the 
treatment they actually received.
3.1.3.2.
Spine DXA Analysis Set for All B/F/TAF Analysis
The Spine DXA Analysis Set for All B/F/TAF Analysis will include all subjects who (1) are 
randomized into the B/F/TAF group , (2) have received at least 1 dose of study drug, and 
(3) have nonmissing baseline spine BMD values. Subjects will be grouped according to the 
treatment they actually received.
For the hip DXA and spine DXA analysis sets for All B/F/TAF Analysis, all DXA data collected 
including both phases only for subjects that were randomized to B/F/TAF group will be 
included, since during open label phase, hip and spine DXA will only be collected for subjects 
that were randomized to B/F/TAF group during randomized phase. 
3.2.
Subject Grouping
For analysis using the All Randomized Analysis Set, subjects will be grouped by the randomized 
treatment (labeled as B/F/TAF vs. ABC/DTG/3TC).
For all efficacy and safety analyses included in the all B/F/TAF analysis, subjects will be 
grouped into the following 2 groups:

 B/F/TAF group: This group includes all subjects who actually received B/F/TAF in the 
randomized phase of this study, regardless whether subjects receive any B/F/TAF in the 
extension phase or not.


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
 ABC/DTG/3TC to B/F/TAF group: This group includes all subjects who actually received 
ABC/DTG/3TC regimen in the randomized phase of this study and then receive at least 
1 dose of B/F/TAF in the extension phase.
3.3.
Strata and Covariates
Randomization was 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, CD4+ cell count (< 50 cells/μL, 
50 - 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US or Ex-US) at randomization.
3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Safety Analyses 
Selected safety endpoints may be analyzed for the following subject subgroups (see Section 9.1 
for details) for all B/F/TAF analysis set:

Subjects with HIV/HBV coinfection at baseline

Subjects with incident HIV/ HBV coinfection while on study drug (if any)
Selected safety endpoints will be analyzed for the following subject subgroups (see Section 9.2 
for details):

Subjects with HIV/hepatitis C virus (HCV) coinfection at baseline

Subjects with incident HIV/HCV coinfection while on study drug (if any) 
3.5.
Multiple Comparisons
No alpha level adjustment is applied other than for the primary endpoint.
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
A missing datum for a given study analysis window may be due to any of the following reasons:

A visit occurring in the window but data were not collected or were unusable 

A visit not occurring in the window

A subject prematurely discontinuing from the study before reaching the window
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.


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For missing last dosing date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for 
concomitant medications in Section 7.5.2.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety 
outcomes, unless specified otherwise. All data will be included in the analyses. 
3.7.
Data Handling Conventions and Transformations
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 as follows except for urine creatinine:

A value that is 1 unit less than the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “< x” (where x is considered the 
limit of quantitation). For example, if the values are reported as < 50 and < 5.0, values of 
49 and 4.9, respectively, will be used for calculation of summary statistics. An exception to 
this rule is any value reported as < 1 or < 0.1, etc. For values reported as < 1 or < 0.1, a value 
of 0.9 or 0.09, respectively, will be used for calculation of summary statistics.

A value that is 1 unit above the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “> x” (where x is considered the 
limit of quantitation). Values with decimal points will follow the same logic as above.

The limit of quantitation will be used for calculation of descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the limit of quantitation).
For urine creatinine, a value of “< 1” is handled as a missing value in its summary and the 
calculation of related ratios. 
Logarithmic (base 10) transformations will be applied to HIV-1 RNA and HBV DNA data for 
efficacy analyses. 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 purposes. HBV DNA results of 
“<20 IU/mL HBV DNA detected” or “No HBV DNA detected” will be imputed as 19 IU/mL for 
analysis purposes. HCV RNA results of “<15 IU/mL HCV RNA detected” or “No HCV RNA 
detected” will be imputed as 14 IU/mL for analysis purposes. 
3.8.
Analysis Windows
3.8.1.
Definition of Study Day
Study Day 1 for the Randomized Phase analysis is defined as the day when the first dose of 
randomized study drug (ie, B/F/TAF or ABC/DTG/3TC) was taken, as recorded on the 
“Randomized Phase” Study Drug Administration eCRF. 


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Last Dose Date for the Randomized Phase analysis is the latest of the randomized study drug 
(including B/F/TAF or ABC/DTG/3TC) end dates recorded on the Study Drug Administration 
eCRF form.
If the last dose date for the randomized phase analysis is missing (eg, only year of last dose date 
is known or completely missing due to lost to follow-up), the latest of the randomized study drug 
start dates and end dates or the latest clinical and laboratory visit dates prior to the first dose date 
of B/F/TAF in the extension phase (if applicable), excluding the 30-day follow-up visit date, will 
be used to impute the last dose date. For other partial missing last dose date, please see the 
programming specifications for imputation rule details.
Study Day 1 for the all B/F/TAF analysis is defined as 

For subjects who actually received B/F/TAF in the randomized phase of this study 
(ie, B/F/TAF group), Study Day 1 for the all B/F/TAF analysis is defined as the day when the 
first dose of B/F/TAF in the randomized phase was taken, as recorded on the Study Drug 
Administration eCRF form.

For subjects who actually received ABC/DTG/3TC in the randomized phase of this study and 
then receive at least 1 dose of B/F/TAF in the extension phase (ie, ABC/DTG/3TC to 
B/F/TAF group), Study Day 1 for the all B/F/TAF analysis is defined as the day when the 
first dose of B/F/TAF in the extension phase was taken, as recorded on the Study Drug 
Administration eCRF form. 
Last Dose Date for the All B/F/TAF Analysis is the latest of B/F/TAF (including both phases) 
end dates recorded on the Study Drug Administration eCRF form.
If the last dose date for the all B/F/TAF analysis is missing (eg, only year of last dose date is 
known or completely missing due to lost to follow-up), the latest of the B/F/TAF (including both 
phases) start dates and end dates, the latest clinical and laboratory visit dates, excluding the 
30-day follow-up visit date, will be used to impute the last dose date. 
Study Days are calculated relative to Study Day 1 for either the randomized phase analysis or 
the all B/F/TAF analysis, as appropriate. For events that occurred on or after the Study Day 1 
date, study days are calculated as (visit date minus Study Day 1 plus 1). For events that occurred 
prior to Study Day 1, study days are calculated as (visit date minus Study Day 1). 
Last Study Date is the latest of the study drug (including ABC/DTG/3TC, and B/F/TAF in both 
phases) start dates and end dates, the clinic visit dates, and the laboratory visit dates, including 
the 30-day follow-up visit date.
Baseline Value is defined as the last nonmissing value obtained on or prior to Study Day 1 for 
either the randomized phase analysis or the all B/F/TAF analysis, as appropriate. Subjects who 
actually received ABC/DTG/3TC in the randomized phase and received at least 1 dose of 
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3.8.2. Analysis Windows 
Subject visits might not occur on protocol specified days. Therefore, for the purpose of analysis, 
observations will be assigned to two different analysis windows based on the following tables: 
the analysis windows for the randomized phase analysis are derived relative to the Study Day 1 
for the randomized phase analysis, while the analysis windows for the all B/F/TAF analysis are 
derived relative to the Study Day 1 for the all B/F/TAF analysis. 
The analysis windows for HIV-1 RNA, CD4+ cell count, CD4 %, hematology, chemistry, 
urinalysis, urine pregnancy laboratory tests, eGFRCG, vital signs, and weight (if collected) are 
presented in Table 3-1 and Table 3-2 for randomized phase analysis and all B/F/TAF analysis 
separately.
Table 3-1.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, 
Hematology, Chemistry, Urinalysis, and Urine Pregnancy Laboratory 
Tests, eGFRCG, Vital Signs, and Weight for Randomized Phase 
Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 4
28
2
42
Week 8
56
43
70
Week 12
84
71
126
Week 24
168
127
210
Week 36
252
211
294
Week 48
336
295
378
Week 60
420
379
462
Week 72
504
463
546
Week 84
588
547
630
Week 96
672
631
714
Week 108
756
715
798
Week 120
840
799
882
Week 132
924
883
966
Week 144
1008
967
1050
Week K
(K is every 12 weeks after previous visit)
K*7
(K-6)*7+1
(K+6)*7


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Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, 
Hematology, Chemistry, Urinalysis, and Urine Pregnancy Laboratory 
Tests, eGFRCG, Vital Signs, and Weight for all B/F/TAF Analysis
B/F/TAF Group
ABC/DTG/3TC to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 4
28
2
42
NA
NA
NA
Week 8
56
43
70
NA
NA
NA
Week 12
84
71
126
84
2
126
Week 24
168
127
210
168
127
210
Week 36
252
211
294
252
211
294
Week 48
336
295
378
336
295
378
Week 60
420
379
462
420
379
462
Week 72
504
463
546
504
463
546
Week 84
588
547
630
588
547
630
Week 96
672
631
714
672
631
714
Week k
K*7
(K-6)*7+1
(K+6)*7
K*7
(K-6)*7+1
(K+6)*7
NA = Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the ABC/DTG/3TC to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension 
phase. 
Note: Week k is every 12 weeks after previous visit. 
The analysis windows for metabolic assessments (including fasting glucose and lipid panel: total 
cholesterol, high density lipoprotein [HDL], direct low density lipoprotein [LDL], triglycerides, 
and total cholesterol to HDL ratio) are presented in Table 3-3 and Table 3-4 for randomized 
phase analysis and all B/F/TAF analysis separately.
Table 3-3.
Analysis Windows for Metabolic Assessments for Randomized Phase 
Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 12
84
2
126
Week 24
168
127
252
Week 48
336
253
420
Week 72
504
421
588
Week 96
672
589
756
Week 120
840
757
924
Week 144
1008
925
1092
Week K
(K is every 24 weeks after previous visit)
K*7
(K-12)*7+1
(K+12)*7


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Table 3-4.
Analysis Windows for Metabolic Assessments for all B/F/TAF 
Analysis
B/F/TAF Group
ABC/DTG/3TC to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 12
84
2
126
NA
NA
NA
Week 24
168
127
252
168
2
252
Week 48
336
253
420
336
253
420
Week 72
504
421
588
504
421
588
Week 96
672
589
756
672
589
756
Week K
K*7
(K-12)*7+1
(K+12)*7
K*7
(K-12)*7+1
(K+12)*7
NA = Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the ABC/DTG/3TC to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension 
phase. 
Note: Week k is every 24 weeks after previous visit.
The analysis windows for thyroid stimulating hormone (TSH; thyrotropin), and renal function 
(including: urine albumin, urine creatinine, urine protein, urine RBP, and urine beta-2 
microglobulin, and derived ratios) are presented in Table 3-5 and Table 3-6.
Table 3-5.
Analysis Windows for TSH and Renal Function for Randomized 
Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 24
168
2
252
Week 48
336
253
420
Week 72
504
421
588
Week 96
672
589
756
Week 120
840
757
924
Week 144
1008
925
1092
Week K
(K is every 24 weeks after previous visit)
K*7
(K-12)*7+1
(K+12)*7


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Table 3-6.
Analysis Windows for TSH and Renal Function for all B/F/TAF 
Analysis
B/F/TAF Group
ABC/DTG/3TC to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 24
168
2
252
168
2
252
Week 48
336
253
420
336
253
420
Week 72
504
421
588
504
421
588
Week 96
672
589
756
672
589
756
Week k
K*7
(K-12)*7+1
(K+12)*7
K*7
(K-12)*7+1
(K+12)*7
NA = Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the ABC/DTG/3TC to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension 
phase. 
Note: Week k is every 24 weeks after previous visit.
The analysis windows for HBV and HCV Serology (including HBsAb, HBsAg, hepatitis B 
e-antigen [HBeAg], hepatitis B e-antibody [HBeAb], HBcAb, and HCV antibody [HCVAb]), 
HBV DNA and HCV RNA assessments are presented in Table 3-7 and Table 3-8.
Table 3-7.
Analysis Windows for HBV and HCV Serology, HBV DNA and 
HCV RNA Assessments for Randomized Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 48
336
2
504
Week 96
672
505
840
Week 144
1008
841
1176
Week K
(K is every 48 weeks after previous visit)
K*7
(K-24)*7+1
(K+24)*7
Table 3-8.
Analysis Windows for HBV and HCV Serology, HBV DNA and 
HCV RNA Assessments for all B/F/TAF Analysis
B/F/TAF Group
ABC/DTG/3TC to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 48
336
2
504
336
2
504
Week 96
672
505
840
672
505
840
Week k
K*7
(K-24)*7+1
(K+24)*7
K*7
(K-24)*7+1
(K+24)*7
NA = Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the ABC/DTG/3TC to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension 
phase. 
Note: Week k is every 48 weeks after previous visit.


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The analysis windows for safety ECG are presented in Table 3-9 and Table 3-10.
Table 3-9.
Analysis Windows for Safety ECG for Randomized Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 24
168
2
252
Week 48
336
253
504
Week 96
672
505
840
Week 144
1008
841
1176
Week K
(K is every 48 weeks after previous visit)
K*7
(K-24)*7+1
(K+24)*7
Table 3-10.
Analysis Windows for Safety ECG for all B/F/TAF Analysis
B/F/TAF Group
ABC/DTG/3TC to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 24
168
2
252
NA
NA
NA
Week 48
336
253
504
336
2
504
Week 96
672
505
840
672
505
840
Week k
K*7
(K-24)*7+1
(K+24)*7
K*7
(K-24)*7+1
(K+24)*7
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the ABC/DTG/3TC to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension 
phase. 
Note: Week k is every 48 weeks after previous visit.
NA = Not Applicable.
The analysis windows for DXA BMD are presented in Table 3-11 and Table 3-12.
Table 3-11.
Analysis Windows for DXA BMD for Randomized Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
14
Week 24
168
15
252
Week 48
336
253
504
Week 96
672
505
840
Week 144
1008
841
1176
Post Week 144
NA
1177
NA
NA = Not Applicable.
Note: The baseline value of DXA BMD is defined as the last value obtained on or prior to Study Day 14.


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Table 3-12.
Analysis Windows for DXA BMD for all B/F/TAF Analysis 
(For Subjects That Were Randomized to B/F/TAF Group Only)
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
14
Week 24
168
15
252
Week 48
336
253
504
Week 96
672
505
840
Week 144
1008
841
1176
Week 192
1344
1177
1512
Week 240
1680
1513
1848
Post Week 240
NA
1849
NA
Note: The baseline value of DXA BMD is defined as the last value obtained on or prior to Study Day 14.
NA = Not Applicable.
Note: In open label phase, hip and spine DXA will only be collected for subjects that were randomized to B/F/TAF group during 
randomized phase.
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Window
Depending on the statistical analysis method, single values are required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time to event analysis would not require one value per analysis window. When a single value is 
needed, the following rule(s) will be used. 
If multiple nonmissing numeric observations exist in a window, then records will be chosen as 
follows:

For baseline, the latest available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, average will be used for the baseline value, except for HIV-1 RNA (see below). 

For postbaseline visits:
For CD4+ cell count, CD4%, and BMD data, the record(s) collected on the latest day in 
the window will be selected for analysis.
For other numeric observations (ie, except HIV-1 RNA, CD4+ cell count, CD4%, and 
BMD data), the record(s) collected on the day closest to the nominal day for that visit 
will be selected. If there are 2 days equidistant from the nominal day, the later day will be 
selected.
For any numeric observations except HIV-RNA, if there are multiple records on the 
selected day, the average will be taken.


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
For baseline and postbaseline HIV-1 RNA, the latest (considering both date and time) 
record(s) in the window will be selected. If both “HIV RNA Taqman 2.0” and “HIV RNA 
Repeat” (ie, the HIV-1 RNA result obtained from an additional aliquot of the original sample) 
are available with the same collection time, the results from the “HIV RNA Repeat” will be 
selected for analysis purposes; otherwise, if there are multiple “HIV RNA Taqman 2.0” 
records with the same collection time, the geometric mean will be taken for analysis purposes.
If multiple valid nonmissing categorical observations exist in a window, records will be chosen 
as follows:

For baseline, the last available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected (eg, normal will be selected over 
abnormal for safety ECG findings).

For postbaseline visits, the most conservative value within the window will be selected 
(eg, abnormal will be selected over normal for safety ECG findings).


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
4.1.1.
Subject Enrollment
All necessary summaries on subject enrollment have been performed as part of the Week 48 
CSR, and will not be repeated for the final analysis.
4.1.2.
Subject Disposition
The summary of subject disposition will be provided by treatment group and overall for all 
Randomized subjects. This summary will include subjects randomized, subjects randomized but 
never treated, subjects in the Safety Analysis Set.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:

Subjects completing study drug in the randomized phase

Subjects prematurely discontinuing study drug in the randomized phase (with summary of 
reasons for discontinuing study drug in the randomized phase)

Subjects completing study in the randomized phase

Subjects prematurely discontinuing from study in the randomized phase (with summary of 
reasons for discontinuing from study in the randomized phase)

Subjects completing study drug in the randomized phase and not entering the OL extension 
phase

Subjects entering the OL extension phase

Subjects treated in the OL extension phase

Subjects completing study drug in the OL extension phase

Prematurely discontinuing study drug in the OL extension phase (with summary of reasons 
for discontinuing study drug in the OL extension phase)

Subjects completing study in the OL extension phase

Prematurely discontinuing from study in the OL extension phase (with summary of reasons 
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The denominator for the percentages of subjects in each category in the randomized phase, 
including “Subjects entering the OL extension phase”, will be the number of subjects 
randomized and treated in the randomized phase. The denominator for the percentages of 
subjects in each category in the OL extension phase will be the number of subjects who were 
treated in OL extension phase.
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided. Reasons for premature study drug/study 
discontinuation due to COVID-19 will also be provided in a separate listing.
4.2.
Extent of Study Drug Exposure and Adherence
4.2.1.
Duration of Exposure to Study Drug
Duration of exposure to study drug will be defined for the all B/F/TAF analysis. For the all 
B/F/TAF analysis, the terms “first dose date” and “last dose date” in the text below refer to the 
first dose date and last dose date defined for the all B/F/TAF phase analysis. Duration of 
exposure to study drug will be defined as (the last dose date – the first dose date + 1), regardless 
of temporary interruptions in study drug administration, and will be expressed in weeks using up 
to 1 decimal place (eg, 4.5 weeks).
Duration of exposure to study drug will be summarized using descriptive statistics (sample size, 
mean, SD, median, Q1, Q3, minimum, and maximum) and as the number and percentage of 
subjects exposed for specified periods, eg, ≥ 4 weeks (28 days), ≥ 8 weeks (56 days), ≥ 12 weeks 
(84 days), ≥ 24 weeks (168 days), ≥ 36 weeks (252 days), ≥ 48 weeks (336 days), ≥ 60 weeks 
(420 days), ≥ 72 weeks (504 days), ≥ 84 weeks (588 days), ≥ 96 weeks (672 days), ≥ 108 weeks 
(756days), ≥ 120 weeks (840 days), ≥ 132 weeks (924 days), ≥ 144 weeks (1008 days), etc. 
Summaries will be provided by treatment group for subjects in All B/F/TAF Analysis Set for the 
all B/F/TAF analysis, respectively. No inferential statistics will be provided. 
Time to premature discontinuation of study drug will be analyzed by treatment group using the 
Kaplan-Meier (KM) method for the all B/F/TAF Analysis Set. No statistical comparisons will be 
made for the all B/F/TAF analysis. A plot of KM estimates for the time to permanent 
discontinuation of study drug by treatment group will be generated for the all B/F/TAF analysis. 
Subjects who completed study drug will be censored at the last dose date of the study. 
4.2.2.
Adherence to Study Drug Regimen
Adherence to study drug regimen will be defined for the all B/F/TAF analysis. For all B/F/TAF 
analysis, study drug adherence (for B/F/TAF) will be computed for both treatment groups as 
defined in Section 3.2. Study drug regimen adherence will be computed based on pill counts. The 
numbers of pills of study drug dispensed and returned are captured on study drug accountability 
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Adherence (%) of study drug regimen will be calculated as follows:






]
2
[
]
1
[
period
dispensing
each 
at 
prescribed
pills
of
No.
period
dispensing
each 
at 
 taken 
pills
of
No.
100
prescribed
pills
of
No.
Total
 taken
pills
of
No.
Total
100
(%)
Adherence
[1]
Number of pills taken at a distinct dispensing period for a study drug is calculated as the minimum of (a) the daily number 
of pills prescribed for the study drug multiplied by the duration of treatment at the dispensing period, and (b) the number of pills 
taken for the study drug (number of pills dispensed minus the number of pills returned). Total number of pills taken is determined 
by summing the number of pills taken from all evaluable dispensing periods.
[2]
Number of pills prescribed at a distinct dispensing period for a study drug is calculated as the daily number of pills 
prescribed for the study drug multiplied by the duration of treatment at the dispensing period. Total number of pills prescribed is 
determined by summing the number of pills prescribed from all evaluable dispensing periods.
The duration of treatment at a dispensing period for a study drug is calculated as the minimum of 
(a) the last returned date of study drug at a dispensing period, (b) date of premature 
discontinuation of the study drug, and (c) next pill dispensing date of the study drug, minus 
dispensing date of the study drug.
The next pill dispensing date is the following dispensing date of the study drug regardless of the 
bottle return date. 
For a record where the number of pills returned was missing (with “Yes” answered for 
“Was Bottle returned?” question), it is assumed the number of pills returned was zero. If the 
number of pills dispensed was missing or any study drug bottle was not returned or the bottle 
return status was unknown, then all records in that dispensing period for that study drug will be 
excluded from both denominator and numerator calculation.
Overall adherence will be calculated for the all B/F/TAF analysis. Overall adherence for the all 
B/F/TAF analysis will use all available data for subjects who actually received B/F/TAF in the 
randomized phase, and data on or after the first dose date of extension B/F/TAF for subjects who 
actually received ABC/DTG/3TC in the randomized phase and received at least 1 dose of 
B/F/TAF in the extension phase.
Descriptive statistics for adherence to study drug regimen (n, mean, SD, median, Q1, Q3, 
minimum, and maximum) along with the number and percentage of subjects belonging to 
adherence categories (eg, < 80%, ≥ 80% to < 90%, ≥ 90% to < 95%, ≥ 95%) will be provided by 
treatment group for subjects who return at least 1 bottle of randomized study drug, and who have 
calculable adherence for the All B/F/TAF Analysis Set. No inferential statistics will be provided.
4.3.
Protocol Deviations
A listing will be provided for all randomized subjects who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met. A listing of subjects who 
received the wrong study drug will also be provided.


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4.4.
Missing Protocol-Specified Information due to COVID-19
An overall summary of the number and percentage of subjects with missed or virtual visits due to 
the COVID-19 pandemic will be provided. The denominator for the percentage calculation will 
be the total number of subjects in the all B/F/TAF analysis set.
A by-subject listing of subjects with missed or virtual visits due to COVID-19 will be provided 
by subject ID number in ascending order. 
The determination of missing or virtual Visits due to COVID-19 was done using Natural 
Language Processing (NLP) to search the CRF comment fields. A detailed explanation of the 
algorithm is given in Appendix 5. 


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, race, and ethnicity) and baseline characteristics 
(eg, body weight, height, and body mass index [BMI]) will be summarized by treatment group 
and overall using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
for continuous data and by the number and percentage of subjects for categorical data. The 
summaries of demographic data and baseline characteristics will be provided by treatment 
groups for subjects in All B/F/TAF Analysis Set (noticing that the baseline for all B/F/TAF 
analysis will be adjusted based on first dose of B/F/TAF), respectively.
No statistical comparisons will be made for the all B/F/TAF analysis.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics for subjects in All B/F/TAF Analysis Set:

HIV-1 RNA (log10 copies/mL)

HIV-1 RNA categories (copies/mL): (a) ≤ 100,000, (b) > 100,000 to ≤ 400,000, and 
(c) > 400,000 

CD4+ cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, 
(d) ≥ 350 to < 500, and (e) ≥ 500 

CD4 percentage (%)

Mode of infection (HIV risk factors)

HIV disease status

eGFRCG (mL/min)

HIV/HBV coinfection status (Yes/No/Missing, see Section 9.1 for definition) 

HIV/HCV coinfection status (Yes/No/Missing, see Section 9.2 for definition) 

Hip BMD and Spine BMD.
No statistical comparisons will be made for the all B/F/TAF analysis.
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will be coded using the current version of Medical Dictionary for Regulatory 
Activities (MedDRA). 


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6.
EFFICACY ANALYSES 
All necessary summaries on the primary efficacy endpoint (at Week 48) and the secondary 
efficacy endpoints at Weeks 48, 96 and 144 have been performed as part of the Week 48 CSR, 
Week 96 CSR, Week 144 CSR, and will not be repeated for the final analysis.
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as determined by the US FDA-defined snapshot algorithm {U. S. Department of Health 
and Human Services 2015}. The proportions are expressed as percentages for presentation 
purposes. 
The statistical analysis methods for the primary efficacy endpoint were described in the Week 48 
SAP and the analysis was performed in the Week 48 analysis 
6.2.
Secondary Efficacy Endpoints
6.2.1.
Definition of the Secondary Efficacy Endpoints
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA  50 copies/mL at Weeks 96 and 144 as 
determined by the US FDA-defined snapshot algorithm

The proportion of subjects with HIV-1 RNA  20 copies/mL at Weeks 48, 96, and 144 as 
determined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, 
and 144

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 OL and 96 
OL as defined by Missing = Excluded and Missing = Failure algorithm

The change from baseline in CD4+ cell count at Weeks 48 OL and 96 OL.
The statistical analysis methods for the secondary efficacy endpoints at Weeks 48, 96, and 144 
(based on data included in the randomized phase analysis) and at Week 48 OL (based on data 
included in the All B/F/TAF analysis) were described in the previous interim analyses SAPs or 
programming specification, and the analyses were performed in the previous interim analyses. In 
this final analysis, the last 2 secondary endpoints will be analyzed for all visits with details 
defined in the next section (Section 6.3).


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6.3.
Efficacy Endpoints for all B/F/TAF Analysis
6.3.1.
Definition of the Efficacy Endpoint for all B/F/TAF Analysis 
The efficacy endpoints for all B/F/TAF analysis include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL by M = E and M=F approach 

The change from baseline in CD4+ Cell Count and CD4 percentage (%)by visit
The analyses for the efficacy endpoints above will be conducted using the All B/F/TAF Analysis 
Set.
6.3.2.
Analysis of the Efficacy Endpoints for all B/F/TAF Analysis 
6.3.2.1.
Analysis of the Proportion of Subjects with HIV-1 RNA < 50 copies/mL by 
Missing = Excluded and Missing = Failure Approaches
The proportion of subjects with HIV-1 RNA < 50 copies/mL will be analyzed using M = E and 
M=F for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all 
B/F/TAF analysis, respectively. 

Missing = Excluded (M = E) 
In this approach, all missing data will be excluded in the computation of the percentages 
(ie, missing data points will be excluded from both the numerator and denominator in the 
computation). The denominator for percentages at a visit is the number of subjects in the all 
B/F/TAF analysis set with non-missing HIV-1 RNA value at that visit.

Missing = Failure (M = F) 
In this approach, all missing data will be treated as HIV-1 RNA  50 copies/mL. The 
denominator for percentages is the number of subjects in all B/F/TAF analysis set.
For both M = E and M = F analyses, the number and percentage of subjects with HIV-1 RNA in 
the following categories will be summarized:

< 50 copies/mL
< 20 copies/mL
■
< 20 copies/mL Not Detectable
■
< 20 copies/mL Detectable
20 to < 50 copies/mL 


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
50 to < 200 copies/mL 

200 to < 400 copies/mL

400 to < 1000 copies/mL

≥ 1000 copies/mL 

Missing (only applicable for M = F analysis)
For all B/F/TAF analyses, the 95% CI for the proportion of subjects with HIV-1 RNA 
< 50 copies/mL for a treatment group will be constructed using the Clopper-Pearson exact 
method. For M =F analysis, results will be summarized by visit up to Week 240 for B/F/TAF 
group and up to Week 96 for ABC/DTG/3TC to B/F/TAF group. For the M = E analysis, results 
will be summarized by treatment group for all visits through the end of study. No statistical 
comparison will be made for the all B/F/TAF analysis. 
6.3.2.2. Analysis of CD4+ Cell Count and CD4%
The analysis of CD4 cell count will be based on on-treatment data (ie, up to 1 day after the 
last dose date of study drug) using the all B/F/TAF Analysis Set for the all B/F/TAF analysis.
The changes from baseline in CD4+ cell count at each visit will be summarized by treatment group 
using descriptive statistics. No statistical comparisons will be made for the all B/F/TAF analysis.
Similar analysis will be conducted for CD4% using the all B/F/TAF Analysis Set for the all 
B/F/TAF analysis.
In addition, the mean and 95% CI of change from baseline in CD4+ cell count over time while 
receiving B/F/TAF will be plotted.
6.4.
Changes From Protocol-Specified Efficacy Analyses
No change from the protocol-specified efficacy analysis is planned.


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7.
SAFETY ANALYSES
Safety data will be summarized by treatment for the subjects in the All B/F/TAF Analysis Set for 
the all B/F/TAF analysis, unless specified otherwise. All safety data collected up to 30 days after 
permanent discontinuation of study drug B/F/TAF will be summarized by treatment group, 
unless specified otherwise. All safety data will be included in data listings.
For the all B/F/TAF analysis, the terms “study drug start date (ie, the first dose date)”, “study 
drug stop date (ie, the last dose date)”, and “baseline” in the text below refer to the first dose 
date, the last dose date, and baseline defined for the all B/F/TAF phase analysis; the term “study 
drug” in the text below refer to B/F/TAF.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of MedDRA. System organ 
class (SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and 
lowest-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will be left as 
“missing” for data listings. 
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAEs from the Gilead Global Patient Safety (GLPS) 
database before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of the study drug, or 

Any AEs leading to premature discontinuation of study drug.


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For the all B/F/TAF analysis, the AE onset date will be compared with the first and last dose 
dates for the All B/F/TAF phase analysis.
7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The month and year (or year) of the AE onset is the same as or after the month and year 
(or year) of the first dosing date of study drug, and

The month and year (or year) of the AE onset is the same as or before the month and year 
(or year) of the date corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date marked as ongoing or on or after the first dosing date of study drug, will be considered to be 
treatment emergent. In addition, an AE with the onset date missing and incomplete stop date 
with the same or later month and year (or year alone if month is not recorded) as the first dosing 
date of study drug will be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Death
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group using all B/F/TAF Analysis Set. For other 
AEs described below, summaries will be provided by SOC, PT, and treatment group using the 
All B/F/TAF Analysis Set:

Any Grade 2, 3, or 4 treatment-emergent AEs

Any Grade 3 or 4 treatment-emergent AEs

All treatment-emergent study drug-related AEs 

Any Grade 2, 3, or 4 treatment-emergent study drug-related AEs

Any Grade 3 or 4 treatment-emergent study drug-related AEs

All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs

All treatment-emergent AEs that caused premature discontinuation from study drug


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A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs. Treatment-emergent 
deaths observed in the study will be also included in this summary.
Treatment-emergent death refers to deaths that occurred between the first dose date and the 
last dose date plus 30 days (inclusive).
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study. 
In addition to the above summary tables, all treatment-emergent AEs, Grade 3 or 4 
treatment-emergent AEs, treatment-emergent study drug-related AEs, Grade 2, 3, or 4 
treatment-emergent study drug-related AEs, and treatment-emergent SAEs will be summarized 
by PT only, in descending order of total frequency.
In addition, data listings will be provided for the following:

All AEs

Grade 3 and 4 AEs

SAEs

Study Drug-Related SAEs

Deaths report

AEs leading to premature discontinuation of study drug
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Stage 3 Opportunistic Illnesses in HIV
On an ongoing basis, AEs will be reviewed for events that might meet the definition of stage 3 
opportunistic illnesses in HIV that are indicative of an AIDS-defining diagnoses (see Protocol 
Appendix 6). The Gilead medical monitor will review the possible stage 3 opportunistic illnesses 
and approve the events that meet the definition. Events that meet the stage 3 opportunistic illness 
definition of an AIDS-Defining Diagnosis will be listed.
7.1.7.2.
Cardiovascular or Cerebrovascular Events
Preferred terms for defining cardiovascular or cerebrovascular events are from relevant 
Standardised MedDRA Query (SMQ). The selected PT listing was provided by Gilead GLPS 
and reviewed by Gilead medical monitors (see details in Appendix 2).


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The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
summarized for the All B/F/TAF Analysis Set. No statistical comparisons of the subject 
incidence rates between the 2 treatment groups will be performed. A data listing of 
cardiovascular or cerebrovascular events will be provided.
7.1.7.3.
Hepatic Events
Preferred terms for defining hepatic events are from 15 relevant SMQs, which are identified as 
non-infectious and non-congenital hepatobiliary disorders. The selected PT listing was provided 
by Gilead GLPS and reviewed by Gilead medical monitors (see details in Appendix 3).
The number and percentage of subjects with treatment-emergent hepatic events and serious 
hepatic events by PT will be summarized by treatment group based on the All B/F/TAF Analysis 
Set. No statistical comparisons of the subject incidence rates between the 2 treatment groups will 
be performed. A data listing of hepatic events will be provided.
7.1.7.4.
COVID-19
A data listing of AEs of COVID-19 (see definition in 
Appendix 4.) will be provided.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the All 
B/F/TAF Analysis Set only, except that the summaries (number and percentage of subjects) for 
treatment-emergent laboratory abnormalities will be provided for All B/F/TAF Analysis Set. The 
analysis will be based on values reported in conventional units. When values are below the LOQ, 
they will be listed as such, and the imputed value will be used for the purpose of calculating 
summary statistics as specified in Section 3.7.
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately for all data 
collected from both phases of the study. Values falling outside of the reference range and/or 
having a severity grade of 1 or higher on the Gilead Grading Scale for Severity of Adverse 
Events and Laboratory Abnormalities will be flagged in the data listings, as appropriate. 
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values 

Values at each postbaseline analysis window

Change from baseline at each postbaseline analysis window


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
Percentage change from baseline to each postbaseline analysis window (if specified)
A baseline laboratory value will be defined as the last nonmissing value obtained on or prior to 
the date of first dose of study drug. Change from baseline to a postbaseline visit will be defined 
as the postbaseline value minus the baseline value. The mean, median, Q1, Q3, minimum, and 
maximum values will be displayed to the reported number of digits; SD values will be displayed 
to the reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 

Calcium corrected for albumin (mg/dL) = serum calcium (mg/dL) + 0.8 × (4.0 – albumin (g/dL))
Toxicity grading for calcium will be applied based on the corrected values.
Estimated GFR
The following formula will be used to calculate eGFRCG: 

eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / (SCr (mg/dL) × 72), 
where weight is total body mass in kilograms, and SCr is serum creatinine.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used for assigning toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction (ie, increased, 
decreased) will be presented separately. 
If there is any laboratory toxicity grading scale overlapping with the normal reference ranges 
(eg, grade 1 scale overlaps with normal reference ranges), laboratory values that are within the 
normal range will be grade 0, except for lipid tests. 
For triglycerides, LDL, and cholesterol, the protocol-specified toxicity grading scale is for 
fasting test values, so nonfasting lipid results (or lipid results without a known fasting status) will 
not be graded or summarized by toxicity grades. 


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7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to 30 days after permanent 
discontinuation of study drug. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment-emergent. Notice that the baseline toxicity grade for all B/F/TAF analysis 
will be based on the first dose date of B/F/TAF.
Fasting glucose and nonfasting glucose (including glucose results without a known fasting 
status) are graded based on different grading scales as specified in the protocol. 
Treatment-emergent laboratory abnormalities will be summarized for fasting glucose. Maximum 
postbaseline grade, instead of treatment-emergent grade, for nonfasting glucose (including 
glucose results without a known fasting status) will be summarized, as nonfasting glucose was 
not assessed at baseline visit for most of the subjects; therefore, an abnormality is 
treatment-emergent or not cannot be determined for these subjects.
7.2.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities

Treatment-emergent Grade 2, 3 and 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
any nonmissing postbaseline values up to 30 days after last dosing date.
A by-subject listing of all treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities will be provided by subject ID number and visit in 
chronological order. 
7.2.3.
Metabolic Laboratory Evaluations
For metabolic assessments, including fasting glucose and the lipid panel (ie, total cholesterol, 
triglycerides, LDL, HDL, total cholesterol to HDL ratio), only those measurements under fasting 
status will be summarized. 
In addition, the number and percentage of subjects who took lipid-modifying medication at the 
first dose of B/F/TAF and subjects who initiated the lipid modifying medication while receiving 
B/F/TAF will be provided. 
A lipid-modifying medication is defined as a medication with ATC2 term = “LIPID 
MODIFYING AGENTS” and CMDECOD containing the wording of “STATIN”.


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Median (Q1, Q3) of change from baseline in fasting metabolic assessments over time will be 
plotted by treatment group. 
7.2.4.
Liver-Related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of subjects who were reported to have the following laboratory 
test values for postbaseline measurements:

Aspartate aminotransferase (AST): (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, 
(d) > 20 × ULN

Alanine aminotransferase (ALT): (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, 
(d) > 20 × ULN

AST or ALT: (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, (d) > 20 × ULN

Total bilirubin: (a) > 1 × ULN, (b) > 2 × ULN

Alkaline phosphatase (ALP) > 1.5 × ULN

AST or ALT > 3 × ULN and total bilirubin: (a) > 1.5 × ULN, (b) > 2 × ULN

AST or ALT > 3 × ULN and total bilirubin > 2 × ULN and ALP < 2 × ULN
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
study drug. For individual laboratory tests, subjects will be counted once based on the most 
severe postbaseline value. For both the composite endpoint of AST or ALT and total bilirubin, 
and the composite endpoint of AST or ALT, total bilirubin, and ALP, subjects will be counted 
once when the criteria are met at the same postbaseline visit date. The denominator is the number 
of subjects in the all B/F/TAF analysis set with nonmissing postbaseline value of the tests in 
evaluation at the same postbaseline visit date. Subjects with AST or ALT > 3 × ULN will also be 
listed.
In addition, baseline, postbaseline, and change from baseline in AST, ALT, ALP, and total 
bilirubin will be summarized by treatment group and visit using descriptive statistics. 
Listings of liver-related laboratory tests will be provided for subjects with any AST or ALT 
> 3 x ULN, TB > 1 x ULN, or ALP > 1.5 x ULN while receiving B/F/TAF or subjects with 
treatment-emergent Grade 3 or 4 ALT, AST, ALP, and TB for all B/F/TAF analysis set.
7.2.5.
Renal-Related Laboratory Evaluations
7.2.5.1.
Serum Creatinine and eGFRCG
Baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG will be 
summarized by treatment group and visit using descriptive statistics. 


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Median (Q1, Q3) of change from baseline in serum creatinine and eGFRCG over time will be 
plotted by treatment group. 
7.2.5.2.
Urine Retinol Binding Protein to Creatinine Ratio, Beta-2-Microglobulin to 
Creatinine Ratio, and Urine Creatinine
Baseline, postbaseline, change from baseline, and percentage change from baseline in urine RBP 
to creatinine ratio and beta-2-microglobulin to creatinine ratio will be summarized by treatment 
group and visit using descriptive statistics. 
Median (Q1, Q3) percentage change from baseline in urine RBP to creatinine ratio and 
beta-2-microglobulin to creatinine ratio over time will be plotted by treatment group. 
Baseline, postbaseline, and change from baseline in urine creatinine will be summarized by 
treatment group and visit using descriptive statistics. 
7.2.5.3.
Albuminuria by Quantitative Assessment
The baseline, postbaseline, changes from baseline, and percentage change from baseline in urine 
albumin to creatinine ratio (UACR) will be summarized by treatment group and visit using 
descriptive statistics. 
The number and percentage of subjects with UACR < 30 mg/g versus ≥ 30 mg/g will be 
summarized by baseline category at Weeks 24, 48, 96, 144, Week 192 (ie, OL week 48), 
Week 240 (ie, OL week 96) and based on the last on-treatment value (ie, data collected after the 
first dose date up to 1 day after the last dose date) {KDIGO Guideline Development Staff 2013}. 
Median (Q1, Q3) percentage change from baseline in UACR over time will be plotted by 
treatment group.
7.3.
Bone Safety Analyses
7.3.1.
Bone Mineral Density 
7.3.1.1
Percentage Change from Baseline in Hip and Spine Bone Mineral Density
The percentage change from baseline in hip BMD and spine BMD will be summarized by visit 
using descriptive statistics for subjects in the hip and spine DXA Analysis Sets for all B/F/TAF 
analysis, respectively. 
Median (Q1, Q3) and mean (95% CI) of the percentage change from baseline in observed hip 
BMD and spine BMD over time for subjects in the hip and spine DXA Analysis Sets for all 
B/F/TAF analysis will be plotted by visit. Listings of hip and spine DXA results will be 
provided.


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7.3.1.2
Hip and Spine BMD Clinical Status
Analysis of hip and spine BMD clinical status will based on the observed BMD values 
(ie, missing will be excluded). 
For each subject and each visit, the BMD clinical status will be defined for hip BMD and spine 
BMD as follows based on the t-score:
Table 7-1.
Normal, Osteopenia, and Osteoporosis as Defined by T-score
Clinical Status
BMD T-score
Normal
T-score ≥ -1.0
Osteopenia
-2.5 ≤ T-score < -1.0
Osteoporosis
T-score < -2.5
The number and percentage of subjects in each BMD clinical status (normal, osteopenia, and 
osteoporosis) will be summarized by visit and by baseline clinical status for both hip and spine, 
using the hip and spine DXA Analysis Sets for all B/F/TAF analysis, respectively. 
7.3.1.3
Gradation of the Percentage Change in Hip, Femur Neck, and Spine BMD
For each subject and each visit, percentage change from baseline in spine BMD will be classified 
into 6 categories: ≥ 5% decrease, ≥ 3% to < 5% decrease, > 0% to < 3% decrease, ≥ 0% to 
< 3% increase, ≥ 3% to < 5% increase, and ≥ 5% increase. Similarly, the percentage change from 
baseline in Hip BMD and Femur Neck BMD will be classified into 6 categories: ≥ 7% decrease, 
≥ 3% to < 7% decrease, > 0% to < 3% decrease, ≥ 0% to < 3% increase, ≥ 3% to < 7% increase, 
and ≥ 7% increase. The number and percentage of subjects in each category will be summarized 
by visit using the hip and spine DXA Analysis Sets for all B/F/TAF analysis, respectively. 
7.4.
Body Weight, Height, and Vital Signs
Descriptive statistics will be provided by treatment group for vital signs and body weight as 
follows using the All B/F/TAF Analysis Set:

Baseline values

Values at each postbaseline analysis window

Change from baseline to each postbaseline analysis window 
A baseline value will be defined as the last nonmissing value obtained on or prior to the date of 
first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.


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A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. In the same listing, a by-subject listing of body weight, height, and BMI 
will be provided. 
7.5.
Prior and Concomitant Medications
7.5.1.
Nonstudy Drug Antiretroviral Medications
Any nonstudy drug ARV medications used prior to, during, or after the study (if collected) will 
be coded using the Gilead-modified World Health Organization (WHO) Drug Dictionary for 
ARV medications. The WHO preferred drug name and drug code will be attached to the clinical 
database. All nonstudy drug ARV medications will be listed. No inferential statistics will be 
provided.
7.5.2.
Concomitant Non-ARV Medications
Concomitant non-ARV medications (ie, medications other than study drug that are taken while 
receiving study drug) will be coded using the WHO Drug Dictionary. The WHO preferred drug 
name and drug code will be attached to the clinical database. Use of concomitant medications 
from Study Day 1 for all B/F/TAF analysis up to the date of last dose of study drug will be 
summarized (number and percentage of subjects) by treatment group, and preferred drug name. 
Multiple drug use (by preferred drug name) will be counted only once per subject. The summary 
will be sorted by decreasing total frequency of preferred drug name. For drug with the same 
frequency, sorting will be done alphabetically.
If the start or stop date of non-ARV medications is incomplete, the month and year (or year alone 
if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARVs are concomitant or not. The medication is concomitant if the month and year of the 
start or stop (or year of the start or stop, if month is not recorded) of the medication does not 
meet either of the following criteria:

The month and year of start of the medication is after the date of the last dose of study drug 

The month and year of stop of the medication is before the date of the first dose of study drug 
If the start and stop date of non-ARV medications are complete, the start date is not after 
last dose date and the stop date is not before first dose date, or the non-ARV medications are 
marked as ongoing and start date is on or before last dose date, the non-ARV medications are 
concomitant.
Summaries of non-ARV concomitant medications will be provided for the All B/F/TAF Analysis 
Set. Subjects with any concomitant non-ARV medications will be listed. No inferential statistics 
will be provided.


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7.6.
Electrocardiogram Results
A shift table for all B/F/TAF analysis of the investigators’ assessment of ECG results at each 
scheduled postbaseline visit compared with baseline values will be presented by treatment group 
using the following categories: normal; abnormal, not clinically significant; abnormal, clinically 
significant; or missing. The number and percentage of subjects in each cross-classification group 
of the shift table will be presented. Subjects with a missing value at baseline or postbaseline will 
not be included in the denominator for percentage calculation. Summary of ECG results will be 
presented by treatment groups for the All B/F/TAF Analysis Set. No inferential statistics will be 
provided.
A by-subject listing for ECG assessment results will be provided by subject ID number and visits 
in chronological order. 
7.7.
Other Safety Measures
A data listing will be provided for subjects experiencing pregnancy during the study. Physical 
examination data was not collected in the eCRF. Therefore, it will not be included in the 
analysis. 
7.8.
Changes From Protocol-Specified Safety Analyses
No change from the protocol-specified safety analysis is planned.


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8.
PHARMACOKINETIC ANALYSES
All necessary summaries on pharmacokinetic analyses have been performed as part of Week 48 
CSR, and will not be repeated in the Final Analysis.


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9.
SPECIAL POPULATION ANALYSES
Special population analyses will be performed using for all B/F/TAF analysis set only.
9.1.
Analyses for HIV/HBV Coinfected Subjects
For all B/F/TAF analyses, subjects with HIV/HBV coinfection at baseline (ie, at the first dose of 
B/F/TAF) are defined as subjects who meet any of the following two criteria: 

Positive HBsAg on or prior to the first dose date of B/F/TAF (including both phases), or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) on or prior to the first dose date of B/F/TAF (including both 
phases).
The listing of AEs will be provided for subjects with incident HIV/HBV coinfection at baseline 
(if any).
Subjects with incident HIV/HBV coinfection while on study drug (if any) are defined as subjects 
who are not HIV/HBV coinfected at baseline for all B/F/TAF analyses and meet any of the 
following criteria:

Positive HBsAg after the first dose date of B/F/TAF (including both phases) and on or prior 
to the date of permanent discontinuation of B/F/TAF (including both phases), or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) after the first dose date of B/F/TAF (including both phases) and 
on or prior to the date of permanent discontinuation of B/F/TAF (including both phases), or

Experience any of the following adverse events (ie, selected MedDRA preferred terms from 
the SMQ of “Liver Infections”) after the first dose date and on or prior to the date of 
permanent discontinuation of B/F/TAF (including both phases): Acute hepatitis B, Chronic 
hepatitis B, Congenital hepatitis B infection, Hepatitis B, Hepatitis B core antibody positive, 
Hepatitis B DNA assay positive, Hepatitis B surface antigen positive, Hepatitis B virus test 
positive.
The following listings will be provided for subjects with incident HIV/HBV coinfection while on 
study drug B/F/TAF (if any): 

Listing of AEs

Listing of liver-related laboratory tests and HBV DNA results


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9.2.
Analyses for HIV/HCV Coinfected Subjects
For all B/F/TAF analysis, subjects with HIV/HCV coinfection at baseline (ie, at the first dose of 
B/F/TAF) are defined as subjects with positive HCVAb and quantifiable HCV RNA (ie, HCV 
RNA ≥ 15 IU/mL) on or prior to the first dose date of B/F/TAF (including both phases). The 
following listings will be provided for subjects with HIV/HCV coinfection at baseline: 

Listing of AEs

Listing of liver-related laboratory tests and HCV RNA results
Subjects with incident HIV/HCV coinfection while on study drug for all B/F/TAF analysis are 
defined as subjects who are not HIV/HCV coinfected at baseline for all B/F/TAF analysis and 
meet any of the following criteria:

Positive HCVAb after the first dose date of B/F/TAF (including both phases) and on or prior 
to the date of permanent discontinuation of B/F/TAF (including both phases) with baseline 
HCVAb Negative or missing, or

Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the first dose date of B/F/TAF 
(including both phases) and on or prior to the date of permanent discontinuation of B/F/TAF 
(including both phases), or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections” ) after the first dose date of B/F/TAF (including both phases) and on or 
prior to the date of permanent discontinuation of B/F/TAF (including both phases): Acute 
hepatitis C, Chronic hepatitis C, Hepatitis C, Hepatitis C antibody positive, Hepatitis C RNA 
positive, Hepatitis C virus test positive.
The following listings will be provided for subjects with incident HIV/HCV coinfection while on 
study drug B/F/TAF: 

Listing of AE events

Listing of liver-related laboratory tests and HCV RNA results


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10.
REFERENCES
KDIGO Guideline Development Staff. KDIGO 2012 Clinical Practice Guideline for the 
Evaluation and Management of Chronic Kidney Disease. Kidney international. 
Supplement 2013;3 (1):v-150.
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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11.
SOFTWARE
SAS® Version 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
nQuery Advisor® Version 6.0 (Statistical Solutions, Cork, Ireland.) is to be used for sample size 
and power calculation.


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12.
SAP REVISION
Revision Date
(dd month, yyyy)
Section
Summary of Revision
Reason for Revision


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13.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Cardiovascular or Cerebrovascular Events
Appendix 3.
Hepatic Events
Appendix 4.
Adverse Events of COVID-19
Appendix 5.
Determining Missing and Virtual Visits Due to COVID-19
Appendix 6.
Programming Specification


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Appendix 1.
Study Procedures Table
Appendix Table 1.
Study Procedures Table (Blinded Phase)
End of Weeke, r
Post-
Week 144e, s
Study Procedures
Screeninga
Day 1b
4
8
12
24
36
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
Informed Consent
X
Medical History
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-
Directed Physical 
Exam
X
X
Xd
Xd
Xd
X
Xd
X
Xd
Xd
Xd
X
Xd
Xd
Xd
X
Xx, Xd
X
Xd,f
Xf
12-Lead ECG 
(performed supine)
X
X
X
X
X
X
Xx
X
X
Questionnaires
X
X
X
X
DXA scan (spine & 
hip)g
X
X
X
X
X
X
X
Height
X
Vital signs (blood 
pressure, pulse, 
respiration rate, and 
temperature), including 
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profilei
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic 
Assessmentsj
X
X
X
X
X
X
X
X
Xt
X


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End of Weeke, r
Post-
Week 144e, s
Study Procedures
Screeninga
Day 1b
4
8
12
24
36
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
Estimated Glomerular 
Filtration Rate
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HLA-B*5701w
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluations of 
inflammation and 
immune activation, 
platelet function and 
renal tubular function
X
X
X
X
X
X
X
Xt
X
HBV and HCV 
Serology
X
X
X
X
XX
HIV-1 Genotypel
Xl
HIV-1 
Genotype/Phenotypee
Xe
Single PK Samplem
X
X
X
Trough PK Samplesn
X
X
Randomizationv
X
Provide subject dosing 
diary to subjects
X
X
X
X
X
CCI
CCI
CCI
CCI
_______.___
-
_____.________.
--
____.____.____.
---
____.____.____.
---
____.____...___
---
____.______.___
--......._____.__
- - -
______.__
-
_____.___
-
____.____ 


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Study Procedul'es 
Screening' 
Day l b 
Study Drug 
)Cb 
Dispensation 
Study Drug 
Accountability 
4 
8 
12 
X 
X 
X 
X 
X 
X 
a 
Evaluations to be completed within 30 days prior to Day 1. 
24 
36 
48 
60 
72 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Post-
End of Week'•• 
Week 144., , 
End of 
Blinded 
Eve1-y 
Tl'eatment 
84 
96 
108 
120 
132 
144 
12 Weeks 
Visit' 
X 
X 
X 
X 
X 
X 
X 
XU 
X 
X 
X 
X 
X 
X 
X 
X 
b 
Initiation of the first dose of study dmg is to take place in-clinic following completion of study procedures at the Day 1 visit, with the exception ofDXA. 
Version 1.0 
Eal'ly 
Study 
30-Day 
D.-ugs 
Follow-up• 
DC' 
X 
c 
Early Study Dmgs Discontinuation visit to occtu· within 72 hours oflast dose of study dmg. Subjects will be asked to continue attending the scheduled study visits tlu·ough the 
End of Blinded Treatment Visit even if the subject discontinues study dmg. 
d 
Symptom-dit·ected physical examination as needed. 
e 
HIV-1 genotype and phenotype testing for subjects with vit·ologic failure. Following vit·ologic rebound, subjects will be asked to retum to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Protocol Sections 16.4.1. and 16.4.2.). 
f 
Any adverse event or test showing abno1mal results that is believed to have a possible or probable causal relationship with the study dmg will be repeated weekly ( or as often 
as deemed pmdent by the Investigator) until the abno1mality is resolved, rettuns to baseline, or is othe1w ise explained. 
g 
DXA scans to be pe1fo1med in all eligible subjects on study dmg dtuing blinded treatment only, except for those in Germany, prior to or within 24 hotu-s of the Day 1 Visit, 
Weeks 24, 48, 96, 144 (±10 days), and at the End of Blinded Treatment Visit (±10 days) and the ESDD visit (if the last scan was acquit·ed > 12 weeks from the date of the 
ESDD Visit). 
h 
Females of childbea1ing potential only. Positive mine pregnancy tests will be confomed with a senun test. 
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilit·ubin, direct and indirect bilimbin, total protein, albtu1w, LDH, CPK, bicarbonate, BUN, calcitun, 
chloride, creatinine, glucose, phosphoms, magnesitun, potassitun, soditun, tu-ic acid and amylase (reflex lipase testing is pe1fon11ed in subjects with total amylase 
> 1.5 x ULN). At Day 1, Weeks 12, 24, 48, 72, 96, 120, 144, and eve1y 24 weeks post Week 144, and End of Blinded Treatment Visit, analyses of glucose will be done as pa1t 
of the fasting metabolic assessments and not as pa1t of the chemistry profile. Additionally: TSH will be analyzed at Screening, Day 1, Weeks 24, 48, 72, 96, 120, 144, and 
eve1y 24 weeks post Week 144, End of Blinded Treatment Visit and Early Study Dmgs Discontinuation visit. 
Fasting (no food or di-inks, except water, at least 8 hotu·s prior to blood collection) glucose and lipid panel (total cholesterol, HDL, dit·ect LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must rettun within 72 hours in a fasted state to draw blood for the metabolic assessments. 
k 
CBC with differential and platelet cotu1t. 
1 
The Investigator must have received the results from the screening genotype report before proceeding with the Day 1 visit. Screening genotype repo1t must show sensitivity to 
TFV, FTC, 3TC and ABC. If genotype results from a local laborato1y obtained ::; 90 days prior to screening visit date show sensitivity to these diugs, this genotype will be 
acceptable to fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been 
confomed. 
m 
A single PK blood sample w-ill be collected at any tune pre or post-dose 
n 
A trough PK blood sample will be collected between 20-28 hotu·s following the last dose. Following an observed dose, a single post dose blood sample will be collected 
between 1 and 4 hotu·s est dose. 
r 
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q
Only required for those subjects not enrolling in the open-label rollover extension or those subjects who prematurely discontinue study drugs and do not continue in the study 
through at least one subsequent visit after the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a  6 days window may be 
used.
r
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to 
Week 132, unless otherwise specified. The visit window at Weeks 48 and 96, 144 will be ± 6 weeks of the protocol-specified visit date.
s
After Week 144, subjects will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Visit window of  6 days 
for study visits post Week 144.
t
To be performed every 24 weeks after Week 144 until End of Blinded Treatment Visit.
u
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for 96 weeks.
v
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit, provided that all screening procedures have been completed and subject eligibility has been 
confirmed.
w
The Investigator must have received a negative screening test for HLA-B*5701 allele before proceeding with the Day 1 visit. If HLA-B*5701 results are available from a 
local laboratory prior to screening, this report will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result obtained at screening is not yet 
available and all other inclusion/exclusion criteria have been confirmed.
x
To be performed every 48 weeks after Week 144 until the End of Blinded Treatment Visit. 
y
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension phase for 96 weeks (Week 96 
OL). After Week 96 OL, subjects in a country where GS-9883/F/TAF is not available will be given the option to continue OL GS-9883/F/TAF until the product becomes 
accessible to subjects through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever comes first.


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Appendix Table 2.
Study Procedures Table (Open Label Rollover Extension)
End of Weeke, l
Study Procedures
End of 
Blinded 
Treatment 
Visita
12 
OL
24 
OL
36 
OL
48 
OL
60 
OL
72 
OL
84 
OL
96 
OL
30-Day Follow-upk
Early Study 
Drugs DCc
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed 
Physical Exam
X
Xd
Xd
Xd
X
Xd
Xd
Xd
X
Xd,f
Xf
12-Lead ECG (performed supine)
X
X
X
DXA scan (spine & hip)m
X
Xo
Xo
Vital signs (blood pressure, pulse, 
respiration rate, and temperature), 
including Weight
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
X
Estimated Glomerular Filtration Rate
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilej
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
Evaluations of inflammation and 
immune activation, platelet function 
and renal tubular function
X
Xn
Xn
Xn
Xn
HBV and HCV Serology
X
X
CCI
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End of Weeke, l
Study Procedures
End of 
Blinded 
Treatment 
Visita
12 
OL
24 
OL
36 
OL
48 
OL
60 
OL
72 
OL
84 
OL
96 
OL
30-Day Follow-upk
Early Study 
Drugs DCc
HIV-1 Genotype/Phenotypee
Xe
Study Drug Dispensation
Xb
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
X
X
a.
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension phase for 96 weeks (Week 96 
OL). After Week 96 OL, subjects in a country where GS-9883/F/TAF is not available will be given the option to continue OL GS-9883/F/TAF until the product becomes 
accessible to subjects through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever comes first.
b.
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for 96 weeks.
c.
Subjects who discontinue study drug during the open label rollover extension portion of the study will be asked to return to the clinic within 72 hours of stopping study drugs 
for the Early Study Drugs Discontinuation Visit followed by a 30-Day Follow-Up Visit. The subject will not continue attending the scheduled study visits.
d.
Symptom-directed physical examination as needed.
e.
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Protocol Figure 6-1.) 
f.
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained. 
g.
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
 1.5  ULN). At Weeks 24 OL, 48 OL, 72 OL, 96 OL, and End of Blinded Treatment Visit, analyses of glucose will be done as part of the fasting metabolic assessments and 
not as part of the chemistry profile. For all subjects, TSH will be done at the End of Blinded Treatment Visit, Weeks 24 OL, 48 OL, 72 OL, 96 OL, and Early Study Drug 
Discontinuation Visit.
i.
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
j.
CBC with differential and platelet count.
k.
Subjects who complete the open-label rollover extension will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit. 
Subjects who prematurely discontinue study drugs during the open-label rollover extension will be asked to return to the clinic 30 days after the completion of the Early Study 
Drugs Discontinuation Visit for the 30-Day Follow-Up Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used.
l.
Study visits are to be completed within ± 6 days of the protocol-specified visit date every 12 weeks thereafter, unless otherwise specified
m.
DXA scans to be performed in all eligible subjects on study drug, except for those in Germany, only at the End of Blinded Treatment Visit (±10 days).
n.
Only urine albumin, urine creatinine, urine protein, retinol binding protein and beta-2-microglobulin to be collected.
o.
DXA scans to be performed at Weeks 48 OL and 96 OL for subjects who were randomized to GS-9883/F/TAF, complete the blinded phase and enter the OL extension phase, 
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Appendix 2.
Cardiovascular or Cerebrovascular Events
An adverse event record will be flagged as a cardiovascular or cerebrovascular event if its 
MedDRA PT is included in the pre-specified PT list, which includes all PTs from the narrow 
search of the following 3 SMQs under MedDRA version 24.0 provided by Gilead GLPS and 
reviewed by Gilead medical monitors.
SMQ Source
Ischaemic central nervous system vascular conditions (SMQ) – 
Narrow Scope Term
Myocardial infarction (SMQ) - Narrow Scope Term
Cardiovascular or Cerebrovascular 
Events 
Other ischaemic heart disease (SMQ) - Narrow Scope Term


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Appendix 3.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT is included in the 
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA version 24.0 provided by Gilead GLPS, and reviewed by Gilead medical 
monitors.
SMQ Source
Biliary neoplasms benign (incl cysts and polyps) (SMQ)
Biliary malignant tumours (SMQ)
Biliary tumours of unspecified malignancy (SMQ)
Biliary system related investigations, signs and symptoms (SMQ)
Biliary tract disorders (SMQ)
Gallbladder related disorders (SMQ)
Gallstone related disorders (SMQ)
Cholestasis and jaundice of hepatic origin (SMQ)
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ)
Hepatitis, non-infectious (SMQ)
Liver neoplasms, benign (incl cysts and polyps) (SMQ)
Liver malignant tumours (SMQ)
Liver tumours of unspecified malignancy (SMQ)
Liver related investigations, signs and symptoms (SMQ)
Hepatic Events (HEP)
Liver-related coagulation and bleeding disturbances (SMQ)


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Appendix 4.
Adverse Events of COVID-19 
An adverse event record will be flagged as adverse events for COVID-19 if its MedDRA PT is 
included in the pre-specified PT list, which includes all PTs from the narrow search of the 
following COVID-19 SMQs under MedDRA version 24.0 provided by Gilead GLPS 
(search name: COVID-19 (SMQ) – Narrow ), and reviewed by Gilead medical monitors.
SMQ Source
AEs of COVID-19 
COVID-19 (SMQ) (Narrow Scope)


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Appendix 5.
Determining Missing and Virtual Visits Due to COVID-19
This appendix describes the site collection of COVID-19 data as pertains to missed/virtual visits 
and the data processing algorithm used to determine which visits were missing and which visits 
were virtual.
Data collection
A COVID-19 supplement to the eCRF Completion Guidelines (CCG) was provided by data 
management to instruct clinical trial sites with respect to data entry expectations pertaining to 
scenarios related to the COVID-19 pandemic. If a visit was missed, sites should enter 
“Visit missed due to COVID-19.” If a visit which was to be conducted in-person was conducted 
virtually, sites should enter “Virtual visit due to COVID-19.”
Determination of Missed and Virtual visits
Natural Language Processing (NLP) was used to search the CRF comment fields to identify 
instances of “COVID-19” (or synonyms, see Table X 1) and “Virtual” (or synonyms, 
see Table X 1). The search terms are maintained in a global lookup and can be modified and/or 
corrected to tune the NLP model. For each comment field the following algorithm was applied:
STEP 1: Eliminate extraneous text from each comment field, e.g. “and”, “or”, “for”, etc. This is 
done using the list of extraneous terms given in Table X 2.
STEP 2: Check each of the remaining comment text strings against the “COVID-19” terms and 
“Virtual” terms with the Levenshtein distance, using SAS function COMPGED (Computes a 
generalized edit distance using the Levenshtein operations to compute/summarize the degree of 
difference between two text strings): 
i.
If Levenshtein distance < 149 for any of the “COVID-19” terms then COVIDFL = 1, 
else COVIDFL = 0
ii. If Levenshtein distance < 149 for any of the “Virtual” terms then VIRTFL = 1, 
else VIRTFL = 0
STEP 3: For any comments with COVIDFL = 1, assign “Missed visit” or “Virtual visit as 
follows
i.
IF COVIDFL =1 and the visit date is missing then result is ‘Missed Visit’
ii. IF COVIDFL =1 and VIRTFL = 1 then result is = ‘Virtual Visit’
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Table X 1.
Examples of search terms for “COVID-19” and “Virtual” used to 
identify missed and virtual visits.
Search terms for “COVID-19”
Search terms for “Virtual”
COVID19
VIRTUAL
CORONA
TELEMED
CORONAVIRUS
TELEHEALTH
PANDEMIC
TELEPHONE
OUTBREAK
REMOTE
CRISIS
TELEMEDICINE
LOCKDOWN
TELECONSULTATION
QUARANTINE
TELEPHONICALLY
PHONE
HOME VISIT
ZOOM
SHELTER
SKYPE


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


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Appendix 6.
Programming Specification
1) AGE calculated as follows: 
I, AGE (years) for all B/F/TAF phase analysis is calculated from the number of days between 
the date of birth (DOB) and Day 1 (Study Day 1 for all B/F/TAF phase analysis);
a) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
b) Divide the result in (b) by 12,
c) AGE = the integer of the result in (c),
d) If the DOB and randomized phase Day 1 have the month in common and the birthday is 
later in the month than the date of randomized phase Study Day 1, then subtract one from 
the AGE result above.
For subjects randomized and never dosed with study drug, age will be calculated from the 
date of randomization.
2) All screened subjects refer to all subjects who are screened (ie, with nonmissing screening 
date) and have a screening number. For summaries, the same subject is counted only once. 
DOB and other demographic information such as sex, race, ethnicity, country, and initials 
will be used to identify unique screened subjects.
3) Screen failure subjects are the subjects who are screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the subject was consent to. 
4) Subjects in the randomized Analysis Set are defined as subjects randomized into the study. 
IXRSRAND is the source to determine whether the subject is randomized (ie, subject with 
nonmissing RGMNDTN in the IXRSRAND dataset) and confirmed by the eCRF ENROLL 
dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) The Safety Analysis Set will include all subjects who (1) are randomized into the randomized 
phase of the study and (2) have received at least 1 dose of the randomized study drug. 
Subjects will be grouped according to the treatment they actually received. 
6) The Full Analysis Set (FAS) will include all subjects who (1) are randomized into the 
randomized phase of the study and (2) have received at least 1 dose of the randomized study 
drug. Subjects will be grouped according to the treatment to which they were randomized.
7) The Hip DXA Analysis Set will include all subjects who (1) are randomized into the study, 
(2) have received at least 1 dose of study drug, and (3) have nonmissing baseline hip BMD 
values. Subjects will be grouped according to the treatment they actually received.


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8) The Spine DXA Analysis Set will include all subjects who (1) are randomized into the study, 
(2) have received at least 1 dose of study drug, and (3) have nonmissing baseline spine BMD 
values. Subjects will be grouped according to the treatment they actually received.
9) Randomized treatment (ie, TRT01P in ADSL) are derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if subject 
took at least 1 dose of study drug and assigned as blank if subject never dosed.
10) Enrollment by Stratum: using actual HIV-1 RNA or CD4+ cell count screening value, the 
last screening value (with visitnum < 0) prior to randomization date and time.
11) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.
12) Body mass index (BMI) and Body Surface Area (BSA)
BMI and BSA will be calculated only at baseline as follows:

BMI = (weight [kg]) / (height [meters]2)

BSA (m2) = SQRT( [Height(cm) × Weight(kg) ] / 3600 )
Baseline height and weight will be used for this calculation. 
13) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded for 
percentage calculation and also excluded for p value generation for categorical data analysis 
(eg, CMH test or Fisher exact test). Except for Mode of infection (HIV Risk Factors), where 
“Unknown” will be included for percentage calculation, since a subject may fit more than 
1 HIV risk factors, therefore percentage may add to more than 100% and no p-value will be 
generated. 
Subjects with Race = “Not Permitted” will also be excluded to define Race subgroup 
(ie, black vs. nonblack) for efficacy subgroup analysis. 
14) Last Dose Date and Last Study Date
a) Last Dose Date (ie, TR01EDTC and TR01EDT for randomized phase last dose date, and 
TR02EDTC and TR02EDT for extension phase last dose date) in ADSL.
Randomized Phase Last Dose Date:
For B/F/TAF or ABC/DTG/3TC subjects with a partial last dosing date (ie, month and year 
of last dose are known), the minimum of {(extension phase first dose date – 1 day, if 
available), (the latest of the dispensing dates of study drug bottles, study drug start dates and 
end dates (based on EX dataset with study drug in randomized phase and the imputed last 
dose date [day imputed as 15])} will be used as the final imputed last dose date. However, if 
dispensing date’s month is after last dose date’s month, data query is needed. If subject died 
and the death date is complete (ie, not partial date) and before the imputed last dose date, the 
complete death date should be used as the imputed last dose date.


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Extension Phase Last Dose Date:
For subjects with a partial last dosing date (ie, month and year of last dose are known), the 
minimum of { (the latest of the dispensing dates of study drug bottles, study drug start dates 
and end dates (based on EX dataset with study drug in extension phase), and the imputed last 
dose date [day imputed as 15])} will be used as the final imputed last dose date. However, if 
dispensing date’s month is after last dose date’s month, data query is needed. If subject died 
and the death date is complete (ie, not partial date) and before the imputed last study date, the 
complete death date should be used as the imputed last study date. 
b) Last Study Date is the latest of the randomized or extension phase (if available) study 
drug start dates and end dates, the clinic visit dates, and the laboratory visit dates, 
including the 30-day follow-up visit date. If study drug start dates or end dates is partially 
missing (ie, only year and month are known), the day will be imputed as 15 for the 
purpose of this analysis.
If subject died and the death date is complete (ie, not partial date) and before the imputed 
last study date, the complete death date should be used as the imputed last study date. 
15) Toxicity Grades:
Two type of treatment emergent lab abnormalities flag variables will be derived for 
laboratory data as applicable. For treatment emergent flag used in listing for randomized 
analysis set, the baseline toxicity grade will be based on baseline value defined as the last 
nonmissing value obtained on or prior to the first dose of randomized study drug. For 
treatment emergent flag used for the All B/F/TAF analysis summary and listing using all 
B/F/TAF analysis set, the baseline toxicity grade will be based on baseline value defined as 
the last nonmissing value obtained on or prior to the first dose of B/F/TAF.
Treatment-emergent laboratory abnormalities will be summarized for all B/F/TAF analysis, 
following the same rule bellows.
a) For toxicity grade summaries, include all postbaseline graded results up to 30 days after 
the last dose of study drug B/F/TAF, not just those used in by-visit summaries.
b) For glucose grading, as specified in this program specification Section 7.1, the 
treatment-emergent flag cannot be determined for nonfasting glucose (including glucose 
results without a known fasting status). As a result, these records will be excluded from 
the “Maximum Treatment-emergent Toxicity Grade” summary in the “Treatment-
emergent Laboratory Abnormalities” or “Treatment-emergent Grade 3 or 4 Laboratory 
Abnormalities” summary tables. In addition, fasting glucose and non-fasting glucose will 
be listed as two separate laboratory tests in the “Laboratory Abnormalities” and “Grade 3 
or 4 Laboratory Abnormalities” listings. Only a maximum postbaseline toxicity flag will 
be displayed and the treatment-emergent flag will not be displayed for nonfasting glucose 
as the treatment-emergent flag cannot be determined for nonfasting glucose. 


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16) DXA Analysis: 
a) Variable used for analysis:
i)
Variable CORRBMD when Region = “SpineTotalAdequate” for spine, Region 
= “FemurTotal” for hip, and Region = “FemurNeck” for femur neck will be used for 
percentage change from baseline in BMD analysis.
ii) Variable CORRTSCR when Region = “SpineTotalAdequate” for spine and Region 
= “FemurTotal” for hip will be used for defining the BMD clinical status.
17) TEAE
Events with Missing Onset Day and/or Month
An AE is treatment emergent if the following 3 criteria are met:
1) The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
2) The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
3) End date is as follows: 
a) The (complete) end date is on or after the first dose date, or
b) The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
c) End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
criteria specified in 3) above.


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18) Graded Laboratory Abnormalities Summary
The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Hemoglobin
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
Hematology
WBC
Decrease
WBC (Decreased)
Albumin 
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
GGT
Increase
GGT (Increased)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Fasting) 
Decrease
Serum Glucose (Fasting, Hypoglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Decrease
Serum Glucose (Nonfasting, Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Total Cholesterol (Fasting)
Increase
Total Cholesterol (Fasting, Hypercholesterolemia)
Triglycerides (Fasting) 
Increase
Triglycerides (Fasting, Increased)
LDL (Fasting)
Increase
LDL (Fasting, Increased)
Urea Nitrogen (BUN)
Increase
Urea Nitrogen (Increased)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Chemistry
Uric Acid
Decrease
Uric Acid (Hypouricemia)


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Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Urine Blood (Dipstick)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine Protein
Increase
Urine Protein (Proteinuria)
Urinalysis
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
*
Due to the reflexive nature of the quantitative urine RBC test, results will be combined with the dipstick test of urine blood 
as described below. General rule is that urine RBC (Quantitative) should always be used first (if available), no matter it is 
collected at the same time of Urine Blood (Dipstick) or not. The combined Urine RBC (hematuria, Quantitative or Dipstick) 
toxicity grade will be used for “Maximum treatment-emergent toxicity grade” summary.
Is Post-BL 
Urine RBC 
(Quant.) 
Result 
Available?
Is BL Urine 
RBC (Quant.) 
Result 
Available?
Is Post-BL 
Urine Blood 
(Dipstick) 
Result 
Available?
Is BL Urine 
Blood 
(Dipstick) 
Result 
Available?
How to Determine 
Treatment-Emergent Toxicity for 
“Urine RBC (Hematuria, 
Quantitative or Dipstick)”
Yes
Yes
-
-
Compare post-BL Urine RBC 
(Quant.) toxicity grade to BL Urine 
RBC (Quant.) toxicity grade. If 
post-BL toxicity is greater than BL 
toxicity, then treatment-emergent
Yes
No
-
-
Treatment-emergent. Use post-BL 
Urine RBC (Quant.) toxicity grade.
No
-
Yes
Yes
Compare post-BL Urine Blood 
(Dipstick) toxicity grade to BL Urine 
Blood (Dipstick) toxicity grade. If 
post-BL toxicity is greater than BL 
toxicity, then treatment-emergent
No
-
Yes
No
Treatment-emergent. Use post-BL 
Urine Blood (Dipstick) toxicity 
grade.
No
-
No
-
Do not count subject in the 
denominator for “Urine RBC 
(Hematuria, Quantitative or 
Dipstick)”
BL = Baseline. Quant = Quantitative. “-” means any value can be present (or it can be missing), as it does not affect the 
classification
19) Renal related laboratory evaluation
a) Unit conversion for renal safety tests derived from related tests with conventional units

Urine RBP (ug/L) to creatinine (mg/dL) ratio: 1 (ug/L) / (mg/dL) = 100 × ug/g

Urine Beta-2-microglobulin (mg/L) to creatinine (mg/dL) ratio: 1 (mg/L) / (mg/dL) 
= 105 ug/g 

Urine Albumin (mg/dL) to creatinine (mg/dL) ratio: 1 (mg/dL) / (mg/dL) 
= 1000 × mg/g


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b) Calculation of ratios: 
To calculate laboratory ratios (eg, urine RBP to creatinine ratio), the lab value of each 
test in the ratio needs to be from the same accession number; if any test value used for the 
ratio calculation from the same accession number is missing , then the ratio is not 
calculable (ie, missing).
20) Concomitant nonstudy-drug ARV medications for all B/F/TAF analysis (ie, ARV 
medications other than study drug that are taken while receiving study drug B/F/TAF) will be 
flagged in “Nonstudy-Drug Antiviral Medication” listing. The logic to define concomitant 
nonstudy-drug ARV is similar to concomitant non-ARV Medications (see details in 
Section 7.5.2)
21) Lipid modifying medication analyses for All B/F/TAF analysis:
Lipid modifying medication is defined to be the concomitant medication with ATC2 
term = “LIPID MODIFYING AGENTS” and CMDECOD contains wording of “STATIN” in 
the ADCM dataset.
Subjects who took lipid modifying medications at first dose of B/F/TAF (including both 
phases) refer to the subjects who use of the lipid modifying agents at study day 1 of all 
B/F/TAF analysis. More specifically, subjects with “Lipid Modifying Agent Use at 
First Dose of B/F/TAF” include those subjects in all B/F/TAF analysis set with: 1) any 
selected CM record with the start date ≤ the first dose date of B/F/TAF (including both 
phases), and 2) the end date of the selected CM record is ongoing or the end date of the 
selected CM record ≥ the first dose date of B/F/TAF (including both phases).
Subjects who initiated lipid modifying medications while subject receiving B/F/TAF includes 
the following subjects in the all B/F/TAF analysis set: (1) for subjects who permanently 
discontinued study drug with any selected CM record started after the first dose date of 
B/F/TAF (including both phases) and on or prior to last dose of B/F/TAF (including both 
phases). (2) for subjects who meet criteria (1) above, if they took lipid modification 
medications before first dose of B/F/TAF (including both phases), they will NOT be 
considered initiated lipid modifications while receiving B/F/TAF for the all B/F/TAF 
analysis.
For lipid modifying medications with start date completely unknown, we assume the start 
date is on or before the first dose date of B/F/TAF (including both phases), lipid modifying 
medication was considered as being taken at first dose of B/F/TAF (including both phases) if 
the end date is not prior to the first dose date of B/F/TAF (including both phases) (ie, the end 
date is on or after the first dose date of B/F/TAF (including both phases), completely 
unknown, or ongoing).
22) For figures, if at a visit where n (sample size) for any treatment group ≤ 5, data for that 
treatment group will not be displayed at the visit in figure (except the Kaplan-Meier figure), 
but all data will be included in the corresponding table summary.


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23) HIV/HBV and HIV/HCV Coinfection:

The following table presents the HBV and HCV tests with all possible values. Values that 
have an asterisk after them denote a “positive” (or “quantifiable” for HBV DNA and 
HCV RNA) result while all others denote a “negative” result.
Label
LBTESTCD
LBTEST
Possible Values
HBsAg
CNT550
Hep. B Surface Ag2
“Positive”*, “Positive, Confirmed”*,“Negative”
HBsAg
ATT2
Hep. B Surf. Ag Qual(-70)-
PS
“Repeat reactive, confirmed”*, “Repeat Reactive 
Unconfirmed”, “Non-Reactive”
HBsAb
CNT353
anti-Hep B Surface Ag2 
Qual
“Positive”*, “Negative”
HBcAb
CNT68
Hepatitis B Core Total
“Positive”*, “Negative”
HBV 
DNA
GET1883
HBV DNA CAP/CTM 
2.0-EDTA-CL
“No HBV DNA detected”, “<20 IU/mL HBV DNA 
detected”, “>170000000”*, NUMERICAL VALUE*
HCVAb
CNT350
Hepatitis C Virus Antibody
“Positive”*, “Indeterminate”, “Negative”
HCV 
RNA
GET1881
HCV RNA CAP/CTM 
2.0EDTA-CL
“No HCV RNA detected”, “<15 IU/mL HCV RNA 
detected”, NUMERICAL VALUE*

For baseline coinfection, for all B/F/TAF analysis, the baseline would be adjusted based 
on the first dose of B/F/TAF (including both phases), when considering the different 
laboratory tests, take the latest, non-missing record on or prior to the first dose date of 
B/F/TAF (including both phases) for each test (eg, HBsAg, HBsAb, HBcAb, and HBV 
DNA)
The baseline coinfection status will be one of the three values: Yes/No/Null
The following tables provide combinations of HBV and HCV tests and the 
corresponding baseline coinfection status


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HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
-
-
-
Y
Positive
-
-
N
Quantifiable
Y
Not Quantifiable
N
Positive
Missing
Null
Negative
-
N
Quantifiable
Null
Not Quantifiable
N
Negative
Missing
Missing
Null
Quantifiable
Null
Not Quantifiable
N
Positive
Missing
Null
Negative
-
N
Quantifiable
Null
Not Quantifiable
N
Negative
Missing
Missing
Missing
Null
Positive
-
-
Null
Quantifiable
Y
Not Quantifiable
Null
Positive
Missing
Null
Negative
-
Null
Negative
Missing
-
Null
Missing
Missing
-
-
Null
HCVAb
HCV RNA
Coinfection Status
Quantifiable
Y
Not Quantifiable
N
Positive
Missing
Null
Negative
-
N
Quantifiable
Null
Not Quantifiable
N
Missing
Missing
Null
“-” means any value can be present, as it does not affect the classification


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
For incident coinfection, all laboratory tests must share the same accession number and if 
any set of values meets the criteria, then the subject is considered to have incident 
coinfection
The incident coinfection status will be one of two values: Yes/Null
The following tables provide combinations of HBV and HCV tests that are 
considered “Y” for incident coinfection status (all others are considered Null)
HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
-
-
-
Y
Negative
Negative
Positive
Quantifiable
Y
Missing
Negative
Positive
Quantifiable
Y
HCVAb
HCV RNA
Coinfection Status
Positive*
-
Y
-
Quantifiable
Y
*
Subjects with positive HCVAb postbaseline must also have negative or missing HCVAb at baseline in order to be 
considered as having incident HIV/HCV coinfection.
“-” means any value can be present, as it does not affect the classification
For adverse events, the start date must be after the first dose date of B/F/TAF 
(including both phases) and on or prior to the last dose date
For incomplete AE start dates, please follow the logic specified in Section 7.1.5.2, but 
modify the second criterion to read, “The month and year (or year) of the AE onset is 
the same as or before the month and year (or year) of the date of the last dose of study 
drug”.
24) HBV DNA test codes: If the result of the lab test code GET1883 (HBV DNA CAP/CTM 
2.0-EDTA-CL) is listed as “>170000000”, then a reflexive test code GET1884 (HBV DNA 
CAP/CTM 2.0Dil-EDTA-CL) should be performed and will share the same accession 
number as the original GET1883 test. In this instance, use the result from GET1884 instead 
of GET1883 when determining HBV DNA.
25) Clarification for TEAE 
The TEAE definitions will be applied to the double-blind randomized phase data and the OL 
extension phase data, separately. When randomized phase data are used, AEs onset date will 
be compared with the randomized phase first dose date and last dose date and premature 
discontinuation of study drug refers to study drug discontinuation in the randomized phase. 
An AE meeting the TEAE criteria will be considered as a TEAE in the randomized phase. 
When OL extension phase data are used, AEs onset date will be compared with the extension 
phase first dose date and last dose date and premature discontinuation of study drug refers to 
study drug discontinuation in the extension phase. AE meeting the TEAE criteria will be 
considered as a TEAE in the OL extension phase.


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One AE will be included either in the double-blind randomized phase or OL extension phase, 
but not both, except that an AE is treatment-emergent in the randomized phase, but 
continuing into extension phase and leading to prematurely discontinuation of the study drug 
in the extension phase, which will be counted as treatment-emergent for both phases.
When an AE with missing onset date and according to the following rules for incomplete 
dates, an AE is treatment emergent in the OL extension phase, then the AE will be included 
in OL extension phase and considered treatment emergent in OL extension phase only.
Events with Missing Onset Day and/or Month
An AE is treatment emergent if the following 3 criteria are met:
1) The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
2) The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
3) End date is as follows: 
a.
The (complete) end date is on or after the first dose date, or
b. The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
c.
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
criteria specified in 3) above.
26) LDL: Conversions between 2nd and 3rd generations
LDL was analyzed by 2 different assays in the study: 2nd generation (including RCT2394, 
RCT2312, and RCT2811) and 3rd generation (RCT3870). Samples collected at earlier visits 
were analyzed using LDL 2nd generation assay. Samples collected at later visits were 
analyzed using LDL 3rd generation assay. The conversion formulas are as follow:
2nd Gen (mmol/L) = (3rd Gen - 0.0626)/0.882
3rd Gen (mmol/L) = (0.882 x 2nd Gen) + 0.0626
For this analysis, since LDL samples were analyzed by 2nd generation assay at Baseline, we 
only requested conversion from 3rd generation to 2nd generation.


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For the analysis of change from baseline in fasting direct LDL: the sample analyzed by LDL 
3rd generation assay will be converted to 2nd generation as a new record with test codes of 
LIP.LDL.00.02 in raw data. During ADaM stage, a derived parameter code (FLDL2) for 
“Fasting LDL Cholesterol 2ND GEN Combined” will be generated to pool the records from 
both original (including test codes RCT2394, RCT2312, and RCT2811) and converted 
(LIP.LDL.00.02) 2nd generation results to calculate the change from baseline in fasting 
direct LDL.
For the analysis of toxicity grade for fasting direct LDL: toxicity grade will be based on the 
Gilead grading results (ie, toxgrg) from original values before conversion. In another words, 
during ADaM stage, a derived parameter code (FLDLTOX) for “Fasting LDL Cholesterol 
for Toxicity” will be generated to pool the records from 2nd generation (including RCT2394, 
RCT2312, and RCT2811) and 3rd generation (ie, RCT3870) to derive treatment-emergent 
toxicity grades, maximum postbaseline toxicity grades, etc.
27) Correction for serum creatinine and eGFR (corrected)
For serum creatine, the calibrator lot used in the quantitative assay for the measurement of serum 
creatinine was changed globally on 01JUL2018 local time. Each regional lab center conducted 
its own alternate (quantitative) method comparison, comparable results as noted in the table 
below: 1, For test results reported on or after 01JUL2018 (RPTDTM), please use the inverse 
conversion formula in the below table. 2, The correction is based on unit of umol/L, after 
correction by regular regression, covert to mg/dL by multiplying 0.0113.
Regional Lab Center
Accession Number
Regular Regression for 
Correction (umol/L)
Inverse Conversion 
Formula (umol/L)
Indy
start with 65
Y=1.002*X+1.77
Y=(X-1.77)/1.002
GVA
start with 62 or 63
Y=1.025*X+2.62
Y=(X-2.62)/1.025
SHANGHAI
start with 67
Y=0.971*X+5.42
Y=(X-5.42)/0.971
SINGAPORE
start with 64 or 66
Y=1.009*X-1.42
Y=(X+1.42)/1.009
JAPAN
start with 68
Y=1.033*X+7.25
Y=(X-7.25)/1.033
Recalculate eGFR using the corrected serum creatinine, using the following formula:

eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / 
(SCr (mg/dL) × 72), where weight is total body mass in kilograms, and SCr is serum 
creatinine. Here age refers to the age at the sample collection date. Use the derived visit to 
align serum creatinine and weight. For multiple records, choose the one with analysis flag.
For this analysis, since serum creatinine samples were analyzed before lot change at Baseline, we 
only requested conversion to the results with previous lot for serum creatine and eGFR.


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For the analysis of change from baseline in serum creatine and eGFR: the sample analyzed by 
updated calibration lot will be converted to the results assuming old calibration lot used as a new 
record. During ADaM stage, a derived parameter code (SCREA2) for “Serum Creatine before 
and after calibration change combined” and (EGFR2) for “eGFR before and after calibration 
change combined” will be generated to pool the records from both original and converted results 
to calculate the change from baseline in serum creatine and eGFR.
For the analysis of toxicity grade for serum creatine and eGFR: toxicity grade will be based on 
the Gilead grading results (ie, toxgrg) from original values before conversion. In another words, 
during ADaM stage, derived parameter codes (SCREATOX and EGFRTOX) for “Serum 
Creatine for Toxicity” and “eGFR for Toxicity” will be generated to pool the records from after 
calibration change and before calibration change to derive treatment-emergent toxicity grades, 
maximum postbaseline toxicity grades, etc.
28) Study and/or study drug discontinuations due to COVID-19
a) Study Drug Discontinuation

Run NLP algorithm on the comment field from Study Drug Completion eCRF, 
checking for “COVID-19” text

In COCOVID19 data set if COFORM = “Study Drug Completion” , then subject 
discontinued study drug due to COVID-19

If study drug discontinued due to an AE, check if corresponding AE flagged as a 
COVID-19
b) Study Discontinuation

Run NLP algorithm on the comment field from general comments for “COVID-19” 
text

In COCOVID19 data set if COFORM = “Study Completion”, then subject 
discontinued study due to COVID-19

If study discontinued due to an AE, check if corresponding AE flagged as a 
COVID-19


SAP-Final- GS-US-380-1489
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
22-Sep-2021
19:56:22
Project Team
Leader eSigned
22-Sep-2021
21:23:44
PPD
PPD

Prot_005.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Clinical 
Program Manager: 
Gilead Medical 
Monitor: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emu·icitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV -1 Infected, 
Antireu·oviral Treatment-Naive Adults 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
125589 
2015-004024-54 
NCT02607930 
HIV -1 Infection 
GS-US-380-1489 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Hal Mrui in, MD, MPH 
PPD 
Fax: 
Pager: 
Original: 
Amendment 1: 
PPD 
PPD 
21 October 2015 
19 Febmruy 2016 
CONFIDENTIALITY STATEMENT 
The inf01mation contained in this document, prui iculru·ly unpublished data, is the prope1iy or 
under conu·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 inf01mation 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 infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessruy to obtain infonned consent from those 
persons to whom the dmg may be administered. 


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 2
19 February 2016
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....................................................................13
1.
INTRODUCTION ..............................................................................................................................................16
1.1.
Background ............................................................................................................................................16
1.2.
GS-9883 .................................................................................................................................................17
1.2.1.
General Information .............................................................................................................17
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................17
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................19
1.3.
Information about Emtricitabine (Emtriva®, FTC) ...............................................................................28
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)..................................................................28
1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) 
or Fixed Dose Combination emtricitabine/tenofovir alafenamide 
(FTC/TAF)...........................................................................................................................29
1.4.2.
Clinical Trials of FTC/TAF as part of 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) ...........................30
1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) ...........................32
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, 
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................32
1.6.
Information about abacavir/dolutegravir/lamivudine (ABC/DTG/3TC Triumeq®)...............................33
1.7.
Rationale for this Study..........................................................................................................................33
1.8.
Risk/Benefit Assessment for the Study..................................................................................................34
1.9.
Rationale for Dose Selection..................................................................................................................35
1.10.
Compliance ............................................................................................................................................36
2.
OBJECTIVES.....................................................................................................................................................37
3.
STUDY DESIGN................................................................................................................................................38
3.1.
Endpoints ...............................................................................................................................................38
3.2.
Study Design..........................................................................................................................................38
3.3.
Study Treatments ...................................................................................................................................38
3.4.
Duration of Treatment............................................................................................................................39
3.5.
Biomarker Testing..................................................................................................................................39
3.5.1.
Biomarker Samples for Optional Pharmacogenomic Research............................................39
3.5.2.
Additional Sample Storage...................................................................................................40
4.
SUBJECT POPULATION..................................................................................................................................41
4.1.
Number of Subjects and Subject Selection ............................................................................................41
4.2.
Inclusion Criteria....................................................................................................................................41
4.3.
Exclusion Criteria...................................................................................................................................42
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................45
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................45
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................45
5.2.
Description and Handling.......................................................................................................................46
5.2.1.
Formulation..........................................................................................................................46
5.2.2.
Packaging and Labeling .......................................................................................................46


GS-9883/F/TAF
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Gilead Sciences, Inc.
Amendment 1
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5.2.3.
Storage and Handling...........................................................................................................47
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide and 
Abacavir/Dolutegravir/Lamivudine .......................................................................................................47
5.4.
Prior and Concomitant Medications.......................................................................................................48
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................49
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................49
6.
STUDY PROCEDURES ....................................................................................................................................50
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................50
6.2.
Pretreatment Assessments......................................................................................................................50
6.2.1.
Screening Visit .....................................................................................................................50
6.2.2.
Day 1 Assessments...............................................................................................................52
6.3.
Randomization .......................................................................................................................................54
6.4.
Treatment Assessments (Week 4 - 96)...................................................................................................54
6.5.
Treatment Assessments (Post Week 96 until the Unblinding Visit) ......................................................57
6.5.1.
Post Week 96 Assessments ..................................................................................................57
6.5.2.
Unblinding Visit...................................................................................................................58
6.6.
Post-treatment Assessments ...................................................................................................................60
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................60
6.6.2.
30 Day Follow Up................................................................................................................61
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................62
6.8.
Bone Mineral Density Evaluations.........................................................................................................63
6.9.
Other Evaluations...................................................................................................................................63
6.9.1.
Markers of Renal Tubular Function .....................................................................................63
6.9.2.
Markers of Inflammation and Immune Activation...............................................................63
6.9.3.
Markers of Platelet Function ................................................................................................63
6.10.
Blood and Urine Storage........................................................................................................................63
6.11.
Assessments for Premature Discontinuation from Study.......................................................................64
6.12.
End of Study...........................................................................................................................................64
6.13.
Post Study Care......................................................................................................................................64
6.14.
Virologic Failure....................................................................................................................................64
6.14.1.
Management of Virologic Rebound .....................................................................................64
6.14.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48 or Week 96............................................................................................................66
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................67
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................67
7.1.1.
Adverse Events.....................................................................................................................67
7.1.2.
Serious Adverse Events........................................................................................................67
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................68
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................68
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................68
7.2.2.
Assessment of Severity ........................................................................................................69
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................69
7.3.1.
Adverse Events.....................................................................................................................69
7.3.2.
Serious Adverse Events........................................................................................................70
7.4.
Gilead Reporting Requirements.............................................................................................................71
7.5.
Toxicity Management ............................................................................................................................71
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................71
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................72
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................72
7.5.4.
Management of Possible Abacavir Hypersensitivity Reaction.............................................72


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7.5.5.
Management of Potential Hepatobiliary Toxicity ................................................................73
7.5.6.
On-Treatment Hepatitis C Management...............................................................................73
7.6.
Special Situations Reports......................................................................................................................74
7.6.1.
Definitions of Special Situations..........................................................................................74
7.6.2.
Instructions for Reporting Special Situations.......................................................................74
8.
STATISTICAL CONSIDERATIONS................................................................................................................76
8.1.
Analysis Objectives and Endpoints........................................................................................................76
8.1.1.
Analysis Objectives..............................................................................................................76
8.1.2.
Primary Endpoint .................................................................................................................76
8.1.3.
Secondary Endpoint .............................................................................................................76
8.2.
Analysis Conventions.............................................................................................................................76
8.2.1.
Analysis Sets ........................................................................................................................76
8.3.
Data Handling Conventions ...................................................................................................................78
8.4.
Demographic Data and Baseline Characteristics ...................................................................................79
8.5.
Efficacy Analysis ...................................................................................................................................79
8.5.1.
Primary Analysis..................................................................................................................79
8.5.2.
Secondary Analyses .............................................................................................................80
8.6.
Safety Analysis.......................................................................................................................................81
8.6.1.
Extent of Exposure...............................................................................................................81
8.6.2.
Adverse Events.....................................................................................................................81
8.6.3.
Laboratory Evaluations ........................................................................................................82
8.6.4.
Bone Safety Evaluations ......................................................................................................82
8.6.5.
Other Safety Evaluations......................................................................................................82
8.7.
Pharmacokinetic Analysis......................................................................................................................82
8.8.
Biomarker Analysis................................................................................................................................83
8.9.
Patient Report Outcomes (PRO) ............................................................................................................83
8.10.
Sample Size............................................................................................................................................83
8.11.
Data Monitoring Committee ..................................................................................................................83
8.12.
Analysis Schedule ..................................................................................................................................84
9.
RESPONSIBILITIES..........................................................................................................................................85
9.1.
Investigator Responsibilities ..................................................................................................................85
9.1.1.
Good Clinical Practice..........................................................................................................85
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................85
9.1.3.
Informed Consent.................................................................................................................85
9.1.4.
Confidentiality......................................................................................................................86
9.1.5.
Study Files and Retention of Records ..................................................................................86
9.1.6.
Case Report Forms...............................................................................................................87
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................88
9.1.8.
Inspections............................................................................................................................88
9.1.9.
Protocol Compliance............................................................................................................88
9.2.
Sponsor Responsibilities ........................................................................................................................89
9.2.1.
Protocol Modifications.........................................................................................................89
9.2.2.
Study Report and Publications .............................................................................................89
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................89
9.3.1.
Payment Reporting...............................................................................................................89
9.3.2.
Access to Information for Monitoring..................................................................................90
9.3.3.
Access to Information for Auditing or Inspections ..............................................................90
9.3.4.
Study Discontinuation..........................................................................................................90
10.
REFERENCES ...................................................................................................................................................91
11.
APPENDICES ....................................................................................................................................................92


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Appendix 1.
Investigator Signature Page....................................................................................................93
Appendix 2.
Study Procedures Table (Blinded Phase) ...............................................................................94
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................98
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............99
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................121
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................122
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........21
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................22
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................23
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)...............................................................................24
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................35
Table 5-1.
Prior and Concomitant Medications.......................................................................................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).......................................................................................24
Figure 3-1.
Study Schema.........................................................................................................................39
Figure 6-1.
Virologic Rebound Schema....................................................................................................66


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, 
Antiretroviral Treatment-Naïve Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004024-54
NCT02607930
Study Centers 
Planned:
Approximately 150 centers in North America, Europe and
Latin America 
Objectives:
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) 
containing GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 
infected, antiretroviral treatment naïve-adult subjects as 
determined by the achievement of HIV-1 RNA < 50 copies/mL at 
Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the two 
treatment groups through Weeks 48 and 96

To evaluate the bone safety of the two treatment groups as 
determined by the percentage change from baseline in hip and 
spine bone mineral density (BMD) through Weeks 48 and 96
Study Design:
Randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus 
ABC/DTG/3TC FDC in HIV-1 infected, antiretroviral treatment-naïve 
adult subjects. Subjects who provide written consent and meet all 
eligibility criteria will be randomized in a 1:1 ratio to one of the 
following two treatment groups:


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Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 
200 mg/ tenofovir alafenamide 25 mg (GS-9883/F/TAF) + Placebo to 
match FDC of abacavir 600 mg/ dolutegravir 50 mg/lamivudine 
300 mg (ABC/DTG/3TC) administered orally, once daily, without 
regard to food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 
50 mg/ lamivudine 300 mg (ABC/DTG/3TC) + Placebo to match 
FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without 
regard to food (n=300)
Randomization will be stratified by HIV-1 RNA level 
(≤100,000 copies/mL, > 100,000 to ≤ 400,000 copies/mL, or 
> 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. 
Ex-US) at randomization.
Number of Subjects 
Planned:
Approximately 600 subjects in total. 300 subjects in each Treatment 
Group 1 and Treatment Group 2
Target Population:
Antiretroviral treatment-naïve (except the use for pre-exposure 
prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to 
one month prior to screening), HLA-B*5701 negative, HIV-1 infected 
adults with plasma HIV-1 RNA levels ≥ 500 copies/mL and a 
screening genotype showing sensitivity to FTC, TFV, 3TC, and ABC.
Duration of 
Treatment:
Subjects will be treated for at least 96 weeks. Subjects’ treatments 
will be unblinded after the last subject completes the Week 96 visit
and Gilead completes the Week 96 analysis. Subjects will continue to 
take their blinded study drug and attend visits every 12 weeks until 
treatment assignments have been unblinded. At the Unblinding 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 in an open label 
extension phase for 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.
Subjects who complete the study through the Unblinding Visit and do
not continue on the open-label GS-9883/F/TAF FDC extension phase, 
will be required to return to the clinic 30 days after unblinding visit 
for a 30-Day Follow-Up Visit.


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Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening

Antiretroviral treatment naïve (≤ 10 days of prior therapy with any 
antiretroviral agent following a diagnosis of HIV-1 infection) 
except the use for PrEP or PEP, up to one month prior to 
screening.

Screening genotype report must show sensitivity to FTC, TFV, 
3TC, and ABC

Negative screening test for HLA-B*5701 allele

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance

No chronic Hepatitis B Virus (HBV) infection, as determined by 
either
Positive HBV surface antigen and negative HBV surface 
antibody, regardless of HBV core antibody status, at the 
screening visit
Positive HBV core antibody and negative HBV surface 
antibody, regardless of HBV surface antigen status, at the 
screening visit
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 96 weeks. 
Following the Day 1 visit, subjects will be required to return for study 
visits at Weeks 4, 8, and 12, and then every 12 weeks from Week 12 
through Week 96.  After 96 weeks, subjects will continue to take their 
blinded study drugs and attend study visits every 12 weeks until 
treatment assignments have been unblinded.
For all eligible subjects, blood will be collected at Day 1, Weeks 4, 8, 
12, and then every 12 weeks through the Unblinding Visit.  
Laboratory analyses (hematology, chemistry, and urinalysis), HIV-1 
RNA, CD4+ cell count, and complete or symptom directed physical 
examinations will be performed at Screening, Day 1 and all 
subsequent visits. In addition, blood will be collected and stored for 
possible evaluation of markers of inflammation and immune 
activation, which may include but are not limited to: cystatin-C, IL-6, 
hs-CRP, d-dimer, sCD14, and sCD163. Platelet function evaluations 
may also be assessed, including but not limited to soluble 
glycoprotein VI (sGPVI), P-selectin, and soluble CD40 ligand.  Urine 
will be collected for evaluations of renal tubular function including 
urine albumin, urine creatinine, urine protein, retinol binding protein 
and beta-2 microglobulin.


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For all subjects on study drug, except subjects located in Germany,
dual energy x-ray absorptiometry (DXA) scans will be performed 
prior to or within 24 hours of the Day 1 Visit , and then at Weeks 24, 
48, 96, and at the Unblinding Visit or Early Study Drug 
Discontinuation Visit, if > 12 weeks since last scan. DXA scan results 
will be provided to study sites when available.
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:
FDC of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg 
(ABC/DTG/3TC) administered orally, once daily without regard to 
food.
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests and DXA
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 48 as defined by the United States (US) 
Food and Drug Administration (FDA)-defined snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 96 as defined by the US FDA-defined
snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA 
< 20 copies/mL at Weeks 48 and 96 as defined by the US 
FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell 
count at Weeks 48 and 96
Pharmacokinetics:
An intensive pharmacokinetic (PK) substudy will be performed at the 
Weeks 4 or 8 visits in a subset of subjects (target n=30) at study sites 
able to conduct this testing.
For all subjects on study drug a single anytime pre or post-dose PK 
blood sample will be collected at Weeks 8, 24 and 36.


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Amendment 1 
For all subjects on study dmg a u·ough PK blood sample will be 
obtained 20-28 homs following the last dose at Weeks 4 and 12. 
Following an observed dose, one post-dose PK blood sample will be 
collected between 1 and 4 homs post-dose. 
For intensive PK substudy, the following PK parameters for GS-9883 
may be explored as applicable: 
Cmax, Tmax, Clast, T!ast, Ctau,T!I2, AUCtau,AUCo-!ast, VzJF, CLss/F. 
The concenu·ation of GS-9883 may be summarized using descriptive 
statistics. The phannacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concenu·ations may be analyzed 
and PK parameters may be smnmarized as applicable. 
Optional Genomic 
PD 
Testing: 
Optional Peripheral 
Blood Mononuclear 
Cell Substudy: 
Patient Reported 
Outcome: 
Statistical Methods: 
CONFIDENTIAL 
Sh01i F01m 36 Health Smvey (SF-36), HIV Symptoms Disu·ess 
Module, Work Productivity and Activity Impainnent Questionnaire 
(WP AI) and Pittsbmgh Sleep Quality Index (PSQI) will be 
administered at Day 1, Weeks 4, 12, and 48. 
The primruy analysis will consist of a non-inferiority test of 
GS-9883/F/TAF versus ABC/DTG/3TC, with respect to the 
prop01iion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defmed snapshot algorithm. 
Page 10 
19 Febmaty 2016 


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It will be concluded that GS-9883/F/TAF is non-inferior to 
ABC/DTG/3TC if the lower bound of the 2-sided 95% confidence 
interval (CI) of the difference (GS-9883/F/TAF – ABC/DTG/3TC) in 
the response rate (HIV-1 RNA < 50 copies/mL as defined by the US
FDA-defined snapshot algorithm) is greater than -12%; ie, a margin of 
12% is applied to non-inferiority assessment. The 95% CI will be 
constructed using a normal approximation method based on stratified 
Mantel-Haenszel proportions, where stratification factors include 
baseline HIV-1 RNA level (≤ 100,000 copies/mL vs. 
> 100,000 copies/mL) and region (US vs. Ex-US).
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL 
at Week 96 and the proportion of subjects who achieve HIV-1 RNA 
< 20 copies/mL at Weeks 48 and 96 as defined by the US 
FDA-defined snapshot algorithm will also be summarized. The 95% 
CIs will be constructed in the same manner as described for the 
primary efficacy endpoint.
The change from baseline in log10 HIV-1 RNA and CD4+ cell count 
at Weeks 48 and 96 will be summarized by treatment using 
descriptive statistics. The differences and the associated 2-sided 95% 
CIs will be constructed using an Analysis of Variance (ANOVA) 
model, including treatment (GS-9883/F/TAF vs. ABC/DTG/3TC), 
baseline HIV-1 RNA level (100,000 copies/mL vs.
100,000 copies/mL), and region (US vs. Ex-US) as fixed effects in 
the model.
The percentage change from baseline in hip and spine BMD at 
Weeks 48 and 96 will be summarized by treatment using descriptive 
statistics. The differences and the associated 2-sided 95% CIs will be 
conducted using an ANOVA model including treatment as a fixed 
effect in the model.  Adverse events, clinical laboratory assessments, 
and pharmacokinetic parameters will be summarized using descriptive 
statistics.
A total of approximately 600 HIV-1 infected subjects, randomized in 
a 1:1 ratio to 2 treatment groups (300 subjects per treatment group), 
achieves at least 95% power to detect a non-inferiority margin of 12% 
in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined by 
the US FDA-defined snapshot algorithm) difference between the 
2 treatment groups. For sample size and power computation, it is 
assumed that both treatment groups have a response rate of 91%
(based on Gilead Studies GS-US-292-0104 and GS-US-292-0111), 
that a non-inferiority margin is 12%, and that the significance level of 
the test is at a one-sided 0.025 level.


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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/3TC
abacavir/lamivudine, EpzicomKivexa
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration 
versus time curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
DTG
dolutegravir, Tivicay
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
EVG
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination


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


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


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {The Joint United Nations Programme 2014}. The infection, if left untreated or 
suboptimally treated, is characterized by deterioration in immune function, ultimately resulting 
in death. Therapeutic strategies for the treatment of HIV-1 disease have been significantly 
advanced by the availability of highly active antiretroviral therapy (HAART); the introduction of 
HAART was associated with a dramatic decrease in acquired immune deficiency syndrome 
(AIDS)-related morbidity and mortality {Palella et al 1998}, {Mocroft et al 1998}, {Sterne et al 
2005}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {Costagliola 2014}. In addition, there remains a significant 
medical need for new, effective therapies that take into consideration HIV genetic variability, the 
aging HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen 
simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {Department for 
Health and Human Services (DHHS) 2015}. Virologically suppressed, HIV-infected patients 
may switch from their current regimen because of safety or tolerability concerns or for regimen 
simplification. All patient populations may benefit from once-daily fixed-dose combination 
(FDC) regimens as these have been shown to provide increased adherence and improved clinical 
and virologic outcomes {Sterrantino et al 2012}, {Aldir et al 2013}
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 


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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.
Gilead Sciences (Gilead) has coformulated GS-9883 with the NRTI emtricitabine (FTC; F) and 
the NtRTI tenofovir alafenamide (TAF) into an FDC tablet that is suitable for once-daily use. 
This GS-9883/F/TAF FDC may provide a potent, convenient, tolerable, and practical regimen 
for the long-term treatment of patients with HIV infection.
1.2.
GS-9883
1.2.1.
General Information
GS-9883, a potent inhibitor of HIV-1 integrase is being evaluated for the treatment of HIV 
infection. Antiviral testing has shown that GS-9883 is active against a broad panel of HIV-1 viral 
lab strains and clinical isolates. GS-9883 is fully active against a panel of mutant viruses with 
resistance to NRTIs, NNRTIs, and PIs. Integrase mutant viruses that are resistant to the INSTIs
RAL and EVG remain largely sensitive to GS-9883.
1.2.2.
Preclinical Pharmacology and Toxicology
A core battery of safety pharmacology studies have been conducted with GS-9883. These 
include assessments of cytotoxicity, off-target receptor and ion-channel binding, effects on 
human Ether-à-go-go-Related Gene (hERG) potassium current and papillary muscle action 
potential, and in vivo studies in rats and dogs that evaluated effects of GS-9883 on all major 
organ systems. The volume of distribution of GS-9883 ranged between 0.09 and 0.22 L/kg in the 
preclinical species, which indicates that the distribution of GS-9883 is limited to the extracellular 
compartment due to its high binding to plasma proteins. The projected half-life of GS-9883 in 
humans is approximately 20 hours based upon the estimates of clearance and volume of 
distribution.
1.2.2.1.
Pharmacology
GS-9883 has IC50 values ranging from 1.5 to 2.4 nM, similar to the inhibitory effect of DTG and 
EVG. GS-9883 is highly potent against HIV replication in MT4 cells with an EC50 (50% 
effective inhibitory concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. 
GS-9883 does not show significant cytotoxicity against dividing and non-dividing human 
PBMCs, primary human hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 M. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter OCT2 (IC50 = 0.42 M). As a result, 
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 M 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.
1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL, 
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day.  At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males.  The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy.
No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL). The estimated margin of exposure at the NOEL 
was approximately 5.1-fold based on expected human exposure with the once daily dosing of the 
GS-9883/F/TAF (50/200/25 mg) tablet.


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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 (in life portion 
completed)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)

GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled Phase 1 Study 
Evaluating the Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular 
Filtration Rate (in life portion completed)


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
GS-US-311-1790, a Phase 1Randomized, Open Label, Drug Interaction Study Evaluating the 
Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (completed)

GS-US-380-1761, a Phase 1 Study to Evaluate Pharmacokinetic Drug-Drug Interaction 
Potential between GS-9883/Emtricitabine/Tenofovir Alafenamide Fumarate 
(GS-9883/F/TAF) and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-Dose Combination (FDC) 
Tablets (completed)

GS-US-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.
Changes in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2. In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort. In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF. All 
changes returned to baseline after discontinuation of GS-9883.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood. All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.


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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.


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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
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 1-4 below.


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Table 1-4. 
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ9s Values (GS-9883 PK Analysis 
Set) 
GS-9883 dose 
N 
Median (range) C 1au, ss (ng!mL) 
Median (range) pai Q95• 
5mg 
4 
206.5 (146.0 to 342.0) 
1.3 (0.9 to 2.1) 
25mg 
4 
797.5 (714.0 to 1900.0) 
4.9 ( 4.4 to 11. 7) 
50mg 
4 
2170.0 (852.0 to 3020.0) 
13.4 (5.3 to 18.6) 
100mg 
4 
4190.0 (3730.0 to 5970.0) 
25.9 (23.0 to 36.9) 
a. 
The protein adjusted IQ95 (pal09s) value is estimated based on steady-state C1au values and the in vitJ:o paiC95 value for 
wild-type HIV-1 (162 ng/ml). 
The mean and 95% Cis of change from baseline in HIV -1 RNA (log10 copies/mL) are presented 
in Figure 1-1. 
Figure 1-1. 
2 
:; 
~ 
-~ 1 
8 
GS-9883 5 mg (~ ) : 
Gs-9883 25 mg (~): 
Gs-9883 50 mg (~): 
G$-9883 100 mg (~ ): 
Placebo (n= ): 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
• = GS-9883 5 mg 
0 = GS-9883 25 mg 
6 = GS-9883 50 mg 
0 = GS-9883100 mg 
0 =Placebo 
Bl 
2 
3 
3 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
3 
3 
4 
3 
4 
7 
8 
9 
10 
11 
Day 
3 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
--
- -
--
14 
17 
3 
3 
4 
3 
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 
-1 
-2 
-3 
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Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group.
1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, ART-naive adult subjects.
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to 
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 50 mg 
once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 75 mg 
once daily
Week 24 interim data are summarized below. 
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24 
data analysis, 2 subjects (2.0%) had prematurely discontinued from the study, 1 in each treatment 
group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and eGFRCG) were similar 
between the 2 treatment groups.
Median (first quartile [Q1], third quartile [Q3]) baseline HIV-1 RNA was 4.45 (3.96, 4.79) 
log10 copies/mL, with 82.7% of subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had 
> 400,000 copies/mL at baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 
1 subject was randomized to DTG+F/TAF.
Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 41.8% of subjects 
having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 125.3 (105.7, 
147.0) mL/min.


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Efficacy Results
Virologic success at Weeks 12 and 24 was assessed using the US FDA-defined snapshot 
algorithm, defined as plasma HIV-1 RNA < 50 copies/mL. At Weeks 12 and 24, virologic 
success was high and similar between the 2 treatment groups as follows: Week 12 
GS-9883+F/TAF 93.8%, DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79); Week 24 GS-9883+F/TAF 95.4%, DTG+F/TAF 
93.9% (1.0%; 95% CI: −10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 had HIV-1 RNA of 60 copies/mL. 
Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF, +170 (150.0) cells/μL; DTG+F/TAF, +173 (220.5) cells/μL 
(difference in least squares mean [LSM]: 0; 95% CI: −76 to 76; p = 1.00). There were similar 
increases in the mean (SD) CD4 cell count in both treatment groups Week 24: GS-9883+F/TAF, 
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).
Interim Virology Resistance Data
Through Week 24, no emergent drug resistance was detected.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 66.2%, 43 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common treatment-emergent AEs (occurring in > 2 subjects) by treatment group were as 
follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE. One other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator or resulted in 
study drug discontinuation or interruption, and both SAEs resolved.


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The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883+F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs reported that were considered related to 
study drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation 
were reported in either treatment group.
Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least 
1 grade level increase from baseline in graded abnormality) was similar between treatment 
groups as follows: GS-9883+F/TAF 76.6%, 49 subjects; DTG+F/TAF 78.1%, 25 subjects. The 
majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The 
percentage of subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality 
was similar between treatment groups as follows: GS-9883+F/TAF 17.2%, 11 subjects; 
DTG+F/TAF 12.5%, 4 subjects. Grade 3 or 4 laboratory abnormalities occurring in at least 
2 subjects in either treatment group were as follows: creatine kinase (GS-9883+F/TAF, 7.8% 
[5 subjects]), fasting serum glucose (DTG+F/TAF, 6.3% [2 subjects]), aspartate 
aminotransferase (AST) (GS-9883+F/TAF, 3.1% [2 subjects]), and fasting low-density 
lipoprotein (LDL) (GS-9883+F/TAF, 3.1% [2 subjects]). The only Grade 4 laboratory 
abnormalities were for creatine kinase, reported in 2 subjects (3.1%) in the GS-9883+F/TAF 
group. All increased creatine kinase values appeared to be transient, and none were associated 
with AEs. Of the 2 subjects with increased AST, 1 subject had Grade 3 AST and Grade 3 ALT at 
Week 24 in the setting of alcohol abuse; the other subject had Grade 3 AST at Week 8 that 
returned to normal by Week 24.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. There were 
similar increases from baseline in median (Q1, Q3) serum creatinine in both treatment groups at 
Week 24: GS-9883+F/TAF 0.12 (0.06, 0.18) mg/dL; DTG+F/TAF 0.13 (0.05, 0.21) mg/dL. 
There were decreases in median (Q1, Q3) eGFRCG at Week 24, which were smaller in the 
GS-9883+F/TAF compared with the DTG+F/TAF group: GS-9883+F/TAF 
−13.3 (−19.9, −4.0) mL/min; DTG+F/TAF −17.2 (−25.7, −6.9) mL/min.
Conclusions
Key Week 24 conclusions from Study GS-US-141-1475 include the following:

Virologic success at Week 24 when assessed using the US FDA-defined snapshot algorithm, 
defined as plasma HIV-1 RNA < 50 copies/mL, was similar between the 2 treatment groups 
as follows: GS-9883+F/TAF 95.4%; DTG+F/TAF 93.9%; stratum-adjusted difference in 
percentages: 1.0%; 95% CI: −10.7% to 12.7%; p = 0.84. There was a similar increase in the 
mean (SD) CD4 cell count between the 2 treatment groups, GS-9883+F/TAF,
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).


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
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. 
1.3.
Information about Emtricitabine (Emtriva®, FTC)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US FDA for marketing on 2 July 2003 and is available 
under the name Emtriva®. In the European Union (EU), marketing authorization was granted for 
both the 200 mg Emtrivacapsule formulation and a 10 mg/mL Emtrivaoral Solution 
formulation on 24 October 2003, with indications for the treatment of HIV infection concurrently 
with other antiretroviral drugs in both adult and pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.


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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-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).


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


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


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in > 90% lower plasma TFV and higher intracellular TFV-DP relative to STB.  E/C/F/TAF 
showed an improved renal and bone safety profile with significantly less decline in hip and spine 
BMD, less increase in serum creatinine and reduction in estimated glomerular filtration rate 
(eGFR).
1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF)
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, FTC, and 
TAF between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is an ongoing Phase 1, open-label, 2-cohort, multiple-period,
fixed-sequence, crossover study conducted at a single center in the US to evaluate 1) the relative 
bioavailability (BA) of 2 GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets 
compared with the GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered 
simultaneously and 2) the effect of food on the PK of GS-9883, FTC, and TAF when 
administered as GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets.
Cohort 1 evaluated the relative BA and food effect of GS-9883/F/TAF (75/200/25 mg) FDC 
tablet in a 3-period sequence. Following review of preliminary data from Cohort 1, Cohort 2 was 
added to the study via protocol amendment. Cohort 2 evaluated the relative BA and food effect 
of GS-9883/F/TAF (50/200/25 mg) FDC tablet in a 4-period sequence.
The in-life portion of Cohorts 1 and 2 are complete. Preliminary results are summarized below. 
Cohort 1 Results:
Pharmacokinetic Results
Under fasted conditions, GS-9883 AUCinf and Cmax were 27% and 31% higher, respectively, 
following GS-9883/F/TAF (75/200/25 mg) FDC administration than following administration of 
single-agent GS-9883 (75 mg ) with the F/TAF (200/25 mg) FDC. FTC and TAF exposure was 
similar following administration of GS-9883/F/TAF (75/200/25 mg) or single-agent GS-9883 
(75 mg) with the F/TAF (200/25 mg) FDC.
Compared with administration under fasted conditions, administration of the GS-9883/F/TAF 
(75/200/25 mg) FDC with a high-fat meal resulted in a 46% higher GS-9883 AUCinf and a 27% 
higher GS-9883 Cmax. The impact of food on TAF and FTC exposure was similar to that 
previously observed for F/TAF (Study GS-US-311-1386). GS-9883/F/TAF may be taken 
without regard to food.  Based on these results, Cohort 2 was added to the study via protocol 
amendment to evaluate the relative BA of the GS-9883 (75 mg) tablet and the F/TAF 
(200/25 mg) FDC tablet administered simultaneously.


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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.
Cohort 2 Results:
Pharmacokinetic Results
The PK results from Study GS-US-141-1233 demonstrated that the GS-9883 AUCinf and Cmax
following administration of the 50mg GS-9883 FDC tablets was 79% and 78%, respectively of 
those observed in the same study following co-administration of GS-9883 75 mg single agent 
with F/TAF (200/25 mg) under fasted conditions. The GS-9883 exposures of 50 and 75 mg fixed 
dose combination tablets were approximately dose proportional under fasted and fed conditions, 
and a high fat and moderate fat meal had similar impact on GS-9883 with AUCinf increasing by 
24%. The steady state paIQ95 of GS-9883/F/TAF (50/200/25 mg) was predicted to be 17 (fasted)-
23 (fed). The exposures of TAF and FTC of the 50 mg GS-9883 FDC were similar to those of 
GS-9883 75 mg single agent with F/TAF FDC, and the food effect on TAF and FTC was similar 
to the historical results.  
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 2, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
1.6.
Information about abacavir/dolutegravir/lamivudine (ABC/DTG/3TC
Triumeq®)
For more detailed information, refer to the current Prescribing Information and local product 
labeling for abacavir/dolutegravir/lamivudine.
1.7.
Rationale for this Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 
HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.


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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 
a FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute to an
increased risk of cardiovascular events, could be used in patients with chronic hepatitis B or C 
infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities.
The objective of this study is to evaluate the safety and efficacy of a FDC containing 
GS-9883/F/TAF versus ABC/DTG/3TC. ABC/DTG/3TC was selected as the active comparator 
for this study as it is a second-generation integrase inhibitor-based, once-daily fixed dose 
combination, and is a DHHS Guidelines preferred regimen. Use of ABC/DTG/3TC as a 
comparator in this study will therefore allow comparison of two single tablet regimens
containing second generation, unboosted INSTIs.
1.8.
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: hypersensitivity 
reaction to abacavir and allergy to any components of the tablets. Some observational studies 
have shown increased risk of cardiovascular disease with abacavir. Interim data will also be 
reviewed by an independent data monitoring committee. 
In a study of GS-9883 in monkeys, administration of 1000 mg/kg/day (highest dose) for 
39 weeks resulted in histologic findings of bile duct hyperplasia and hepatocyte hypertrophy.  No 
adverse effects were noted at the mid-dose group (200 mg/kg/day), which resulted in exposures 
of GS-9883 5.1 times higher than the expected human exposure with administration of 
GS-9883/F/TAF (50/200/25 mg) tablets. No such findings were seen in rats at any dose.  
However, the risk of liver or biliary abnormalities in humans receiving GS-9883/F/TAF 
(50/200/25 mg) for chronic use is unknown. Potential hepatobiliary toxicity is appropriately 
managed by study inclusion/exclusion criteria, close clinical and laboratory monitoring, as well 
as specific toxicity management guidance to investigators (Refer to Section 7.5.5.).  
Potential benefits of GS-9883 may include provision of a new antiretroviral therapy that is not 
currently available and which may have fewer side effects than alternative therapies. Other 
potential benefits include provisions of fixed dose combination therapy, and the knowledge that 
patient participation will contribute to the body of knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF and ABC/DTG/3TC is favorable at this 
time.


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1.9.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady 
State Following GS-9883 Administration Under Fasting Conditions 
and Corresponding Protein-Adjusted IQ95 Values
GS-9883 dose
n
Median (range) Ctau,SS (ng/mL)
Median (range) 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 data from this study support the safety and efficacy of GS-9883 exposures obtained 
with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF was developed for use in Phase 3 studies. 
Preliminary results from the relative bioavailability (rBA) study (GS-US-141-1233) of 
GS-9883/F/TAF (75/200/25 mg) showed that GS-9883 plasma exposure was higher (with Cmax
and AUCinf increase of 31% and 27%, respectively) following administration of the FDC as 
compared with exposure following administration of GS-9883 (75 mg) + F/TAF (200/25 mg) 
under fasted conditions. The increase in GS-9883 exposures associated with the FDC 
formulation results in an estimated mean paIQ95 of 24.3, compared to an estimated mean paIQ95
of 19.2 for the GS-9883 (75 mg) single agent coadministered with F/TAF, in the fasted state.
In order to bridge exposures of GS-9883 in the FDC to the exposure observed with GS-9883 
75 mg administered as a single agent, and to bridge to the safe and effective exposures observed 
in the Phase 2 study GS-US-141-1475, a lower strength GS-9883/F/TAF FDC was developed for 
use in the Phase 3 studies. Comparability of GS-9883 exposures was confirmed in an rBA study 
of GS-9883/F/TAF (50/200/25 mg) and GS-9883 (75 mg) + F/TAF prior to initiation of dosing 
in the Phase 3 studies.
1.10.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) containing 
GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral 
treatment naïve-adult subjects as determined by the achievement of HIV-1 RNA 
< 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the two treatment groups through 
Weeks 48 and 96

To evaluate the bone safety of the two treatment groups as determined by the percentage 
change from baseline in hip and spine BMD through Weeks 48 and Week 96


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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint is:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 as defined 
by the US FDA-defined snapshot algorithm
The secondary endpoints of this study include:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 96 as defined 
by the US FDA-defined snapshot algorithm

the proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48 and 96 as 
defined by the US FDA-defined snapshot algorithm

the change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48 and 96

the percentage change from baseline in hip and spine BMD at Weeks 48 and 96
3.2.
Study Design
This protocol describes a randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus ABC/DTG/3TC FDC in HIV-1 
infected, antiretroviral treatment-naïve adult subjects.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food
(n=300)
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. Ex-US) at randomization.


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3.4. 
Duration of Treatment 
Final 
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Subjects will be tr·eated for at least 96 weeks. Subjects' tr·eatments will be lmblinded after the last 
subject completes the Week 96 visit and Gilead completes the Week 96 analysis. Subjects will 
continue to take their blinded study dmg and attend visits eve1y 12 weeks until tr·eatment 
assignments have been unblinded. At the Unblinding 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 
in an open label extension phase for 48 weeks, or lmtil 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. 
Figure 3-1. 
Study Schema 
Week 96b 
Day 1' 
Week 48" 
Primary Endpoint 
Secondary Endpoint 
Unblindingt,d 
Screening 
s 30 dafs prior 
IO Oan 
Treatment Group 1: GS-9883/F!fAF FDC QD +Placebo to match 
ABC/DTG/3TC FDC QD (N"'300) 
Treatment Group 2: ABC/DTG/3TC FDC QD +Placebo to 
match GS-9883/FTC!fAF FDC QD (N"'300) 
30D•y Fit' 
a 
Following the Day 1 visit, subjects will be required to retwn for study visits at Weeks 4, 8, 12, and then evety 12 weeks 
through Week 96. 
b 
After Week 96, subjects will continue to take their blinded study drug and attend visits evety 12 weeks until treatment 
assignments have been unblinded. Subjects' treatments will be unblinded after the last subject completes the Week 96 visit 
and Gilead completes the Week 96 analysis. 
c 
Once Gilead Sciences provides unblinded treatment assignments to the Investigators, all subjects willrettun to the clinic 
(preferably within 30 days) for an Unblinding Visit. At the Unblinding Visit, subjects in a countly where GS-9883/F/TAF 
FDC is not available will be given the option to receive GS-9883/F/TAF FDC in an open label extension for 48 weeks, or 
tmtil the product becomes accessible to subjects through an access program, or tmtil Gilead Sciences elects to discontinue 
the study in that cotmtly, whichever occurs first. 
d 
Subjects who complete the stttdy through the Unblinding Visit and do not continue on the open-label GS-9883/F/TAF FDC 
extension phase will be required to rettun to the clinic 30 days after the completion of stttdy drugs for a 30-Day Follow-Up 
Visit 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Pharmacogenomic Research 
PPD 
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3.5.2. 
Additional Sample Storage 
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For subjects who provide additional consent, residual blood and urine samples taken throughout 
the study will be stored. Stored samples may be used by the Sponsor or its research partners to 
help answer questions about the study dmg, and HIV disease and its associated conditions, or to 
provide additional safety data. 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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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 600 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Age 18 years
3) Antiretroviral treatment naïve (≤ 10 days of prior therapy with any antiretroviral agent 
following a diagnosis of HIV-1 infection) except the use for PrEP (pre-exposure prophylaxis) 
or PEP (post-exposure prophylaxis), up to one month prior to screening
4) Plasma HIV-1 RNA levels 500 copies/mL at screening
5) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥0.83 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft et al 1976}:
i)
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
ii) Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)      0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8) Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin


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9) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))
10) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11) Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12) Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 6) throughout the study period and for 
90 days following the last dose of study drug
13) Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14) Life expectancy ≥ 1 year
15) Screening genotype report must show sensitivity to FTC, TFV, 3TC, and ABC. This report 
will be provided by Gilead Sciences. Alternatively, if genotype results from a local 
laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, 
this genotype will be acceptable to fulfill this inclusion criterion in the event that the 
genotype obtained at screening is not yet available and all other inclusion/exclusion criteria 
have been confirmed.
16) Negative screening test for HLA-B*5701 allele provided by Gilead Sciences. Alternatively, 
if HLA-B*5701 results are available from a local laboratory prior to screening, this report 
will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result 
obtained at screening is not yet available and all other inclusion/exclusion criteria have been 
confirmed.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
17) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
18) Subjects experiencing decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal 
bleeding)


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19) 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 (e.g, corticosteroids, immunoglobulins, and other immune- or cytokine-based 
therapies)
20) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance
21) 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
22) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
23) Participation in any other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
24) 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
25) Any known allergies to the excipients of GS-9883/F/TAF FDC or ABC/DTG/3TC FDC 
tablets
26) Females who are pregnant (as confirmed by positive serum pregnancy test)
27) Females who are breastfeeding
28) Subjects receiving ongoing therapy with any of the following medications in the table below, 
including drugs not to be used with FTC, TAF, GS-9883, DTG, ABC and 3TC
Drug Class
Agents Disallowed*
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study.
29) Acute hepatitis in the 30 days prior to study entry


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30) Chronic Hepatitis B Virus (HBV) infection, as determined by either:
a) Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit
b) Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
31) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until the Investigator has received the results of the allele testing and 
screening genotype report and subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening and region (US vs. Ex-US) at randomization.
The IWRS will assign study drug bottle numbers of blinded FDC of GS-9883/F/TAF + Placebo 
to match FDC of ABC/DTG/3TC or FDC of ABC/DTG/3TC + Placebo to match FDC of
GS-9883/F/TAF at each study visit for each subject.
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the IWRS system 
for that subject. Gilead strongly recommends but does not require that the investigator contact 
the Gilead medical monitor before breaking the blind. Treatment assignment should remain 
blinded unless that knowledge is necessary to determine subject emergency medical care. The 
rationale for unblinding must be clearly explained in source documentation and on the electronic 
case report form (eCRF), along with the date on which the treatment assignment was 
obtained. The investigator is requested to contact the Gilead medical monitor promptly in case of 
any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Drug Safety and Public Health (DSPH) may independently unblind cases for expedited 
reporting of suspected unexpected serious adverse reactions (SUSARs).


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5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.
The placebo to match (PTM) GS-9883/F/TAF tablets are capsule-shaped, film-coated 
purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the other side and 
are identical in physical appearance to GS-9883/F/TAF tablets. The placebo tablets contain 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. 
The tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, 
polyvinyl alcohol, talc, and titanium dioxide.
5.2.1.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
Abacavir 600 mg/Dolutegravir 50 mg/Lamivudine 300 mg tablets are oval, film coated purple, 
and debossed with “572 Tri” on one side. Each tablet core contains 600 mg of abacavir, 50 mg of 
dolutegravir, and 300 mg of lamivudine. In addition to the active ingredients, the 
ABC/DTG/3TC tablets contain the inactive ingredients D-mannitol, magnesium stearate, 
microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet cores are film 
coated with iron oxide black, iron oxide red, polyethylene glycol, polyvinyl alcohol, talc, and 
titanium oxide.
The PTM ABC/DTG/3TC tablets are oval, film coated purple, and debossed with “572 Tri” on 
one side. The placebo tablets are identical in physical appearance to ABC/DTG/3TC tablets. The 
placebo tablets contain microcrystalline cellulose, lactose monohydrate, croscarmellose sodium 
and magnesium stearate. The tablet cores are film-coated with iron oxide black, iron oxide red, 
polyethylene glycol, polyvinyl alcohol, talc, and titanium oxide.
5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883/F/TAF tablets and PTM GS-9883/F/TAF tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester 
packing material.  Each bottle is enclosed with a white, continuous thread, child-resistant 
polypropylene screw cap with an induction-sealed and aluminum-faced liner.


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Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations
5.2.2.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
ABC/DTG/3TC tablets and PTM ABC/DTG/3TC tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets and silica gel desiccant. Each bottle 
is enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both 
FDCs should be stored at controlled room temperature of 25°C (77°F); excursions are permitted 
between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label. Until 
dispensed to the subjects, all bottles of study drugs should be stored in a securely locked area, 
accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide 
and Abacavir/Dolutegravir/Lamivudine
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both
FDCs will be provided by Gilead Sciences.
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food. 
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 


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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 table and use of herbal/natural supplements are excluded 
or should be used with caution while subjects are participating in the study. Subjects will 
refrain from consumption of grapefruit juice and Seville orange juice throughout 
participation in the study.
Table 5-1.
Prior and Concomitant Medications
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 
when initiating study medication or if initiating 
metformin while on study drug.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.


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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 study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events, smoking history
and prior medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.


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Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)       CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) 
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
HLA-B*5701
Plasma HIV-1 RNA
Hepatitis B virus surface antigen serology (HBsAg)
Hepatitis B surface antibody (HBsAb)
Hepatitis B virus core antibody (HBcAb)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.
HIV-1 genotype testing (protease and reverse transcriptase). The HIV-1 PR/RT genotype 
testing may not be performed for subjects that fail to meet other screening criteria.

Review of adverse events and concomitant medications
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for the Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. See 
Section 7 Adverse Events and Toxicity Management for additional details.


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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 
received the results from the allele testing and screening genotype report and confirmed 
eligibility before proceeding with the Day 1 visit. The subject must complete all study 
procedures, except DXA, before being administered the study drug:

DXA Scan (spine and hip).  For subjects in Germany, DXA scans will not be performed.
The DXA scan will be performed on subjects once eligibility is confirmed. The scan may 
be performed prior to or within 24 hours of the Day 1 Visit.

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject.  Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN) and TSH


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Metabolic assessments: Fasting (no food or drinks, except water, at least 8 homs 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 retum within 72 homs in a fasted state to draw blood for the metabolic 
assessments. 
-
Estimated glomemlar filtration rate according to the Cockcroft-Gault f01mula 
-
Hematology profile: complete blood cmmt (CBC) with differential and platelet cmmt 
-
Plasma HIV-1 RNA 
-
CD4+ cell count 
-
Evaluations of inflammation and immlme activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 
-
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand 
-
Plasma storage sample for safety, virology, or PK testing 
• 
Optional Peripheral Blood Mononuclear cell (PBMC) Substudy: 
• 
• 
Optional blood sample collection for the following laboratory analyses if 
pharmacogenomic consent is obtained 
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6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 - 96)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, 48, 60, 72, 
84, and 96 unless otherwise specified.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 96, unless otherwise specified.  The visit window at Weeks 48 and 96 will be 
± 6 weeks of the protocol-specified visit date, and these clinical visit windows coincide with the 
Week 48 and Week 96 statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (Weeks 24, 48 and 
96 ±10 days). For subjects in Germany, DXA scans will not be performed.

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)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject at Weeks 4, 12 and 48.  Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin. (Weeks 24, 48, 72 and 96)


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Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 12, 24, 48, 72 and 96 analyses of glucose will be done as part of the fasting 
metabolic assessments and not as part of the chemistry profile. At Weeks 24, 48, 72 
and 96 TSH will also be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24, 48, 72 and 96)
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
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (Weeks 24, 48, 72 and 96)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (Weeks 24, 48, 72 and 96)
Plasma storage sample for safety, virology, or PK testing

Pharmacokinetic Blood Collection for subjects who are on study drug. Details of 
pharmacokinetic blood sampling procedures and sample management will be documented in 
the Pharmacokinetic Sample Collection, Processing, Storage, and Shipment Manual.
Single Anytime, Trough and Post Dose PK Samples for all subjects on study drug:
■
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 and 36.


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Observed dosing at the clinic: Subjects will have a trough PK blood sample collected 
between 20-28 homs following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study <hu gs on the moming of their visit for the ti·ough 
sample collection. Subjects will then take an observed dose of study <hu g at the 
clinic. A single post dose PK blood sample will be collected between 1 and 4 homs 
post dose. If the subject has taken their dose of study dmgs prior to the visit, the visit 
may proceed, but the subject must retum within 72 homs for the n·ough PK blood 
sample collection. In the event a subject routinely takes their study <hu g in the 
evening, a single post dose sample may be <h·awn at Weeks 4 and 12 as the subject 
will not be insti11cted to change their dosing time to accommodate this n·ough PK 
<h·aw. 
• 
Dosing diaries will be collected from subjects for the single anytime PK and n·ough 
PK collection. If a dosing diaty is not retumed the site may ask the subject for the 
time of the last dose and if it was taken with or without food. 
-
Optional Phrumacokinetic (PK) Substudy: 
• 
Optional Peripheral Blood Mononuclear cell (PBMC) Substudy: 
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6.5.
Treatment Assessments (Post Week 96 until the Unblinding Visit)
6.5.1.
Post Week 96 Assessments
After Week 96, subjects will continue to take their blinded study drugs and attend visits every 
12 weeks until treatment assignments have been unblinded, at which point they will return for an 
Unblinding Visit (refer to Section 6.5.2). Study visits are to be completed within 6 days of the 
protocol-specified visit date unless otherwise specified.

Review of AEs and changes in concomitant medications

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, the subject 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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula


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Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (Every 24 weeks)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (Every 24 weeks)
Plasma storage sample for safety, virology, or PK testing

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.14.1 and 6.14.2.

Document study drug dispensation and accountability for all study drugs dispensed.
6.5.2.
Unblinding Visit
Once Gilead Sciences provides unblinded treatment assignments to the Investigators, all subjects 
will return to the clinic (within 30 days ± 6 days) for an Unblinding Visit. At the Unblinding 
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 in an open label extension phase for 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.
Subjects who receive the open-label GS-9883/F/TAF FDC will return for study visits every 
12 weeks.

Subjects who choose to not receive the open label GS-9883/F/TAF FDC will be required to 
return to the clinic for a 30-Day Follow-up visit following the Unblinding Visit. Subjects 
who have discontinued drug study prior to the Unblinding Visit will not be eligible for the 
open-label rollover extension; these subjects will be asked to continue attending the 
scheduled study visits through the Unblinding Visit and discontinue the study after the 
Unblinding Visit.
The following will be performed at the Unblinding Visit:

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (±10 days). For subjects in 
Germany, DXA scans will not be performed.


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
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 (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN), and TSH
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand
Plasma storage sample for safety, virology, or PK testing


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
Document study drug dispensation, if applicable and accountability for all study drugs 
dispensed

Subjects who wish to continue in the Open-Label Rollover extension study will receive open 
label GS-9883/F/TAF.
6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
If the subject discontinues study drug prior to the Unblinding Visit, the subject will be asked to 
return to the clinic within 72 hours of stopping study drugs for the Early Study Drugs 
Discontinuation Visit. The subject will be asked to continue attending the scheduled study visits 
through the Unblinding Visit.
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to Day 1, 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

DXA scan required (spine and hip) for all subjects who are on study drug (±10 days) if last 
scan was acquired > 12 weeks from the date of the ESDD Visit.   For subjects in Germany, 
DXA scans will not be performed.

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 (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30 Day Follow Up
Subjects who complete the study through the Unblinding visit and who do not participate in the 
open-label rollover extension, will be required to return to the clinic 30 days after the completion 
of study drug for the 30 Day Follow Up visit.
Subjects who permanently discontinue study drug during the blinded phase and refuse to 
continue in the study through the Unblinding 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.
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


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
Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly (or as 
often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained.
6.7.
Criteria for Discontinuation of Study Treatment
Study medication will be discontinued in the following instances:

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Subject request to discontinue for any reason

Pregnancy during the study; refer to Appendix 6

Development of active tuberculosis infection
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


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
Lack of efficacy

Subject noncompliance

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)
6.8.
Bone Mineral Density Evaluations
For all subjects who are on study drug, excluding those enrolled in sites based in Germany, dual 
energy x-ray absorptiometry (DXA) scans will be performed prior to or within 24 hours of 
Day 1, Weeks 24, 48, 96, Unblinding Visit and the Early Study Drug Discontinuation Visit (if 
the last scan was acquired > 12 weeks from the date of the ESDD Visit). Scans will cover the 
spine and hip to measure changes in bone mineral density. DXA scan results will be provided to 
study sites.
A complete description of the procedures performed for the DXA scans will be provided in a 
DXA manual.
6.9.
Other Evaluations
6.9.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin at Day 1 Visit, Weeks 24, 48, every 24 weeks post Week 48 and the 
Unblinding Visit.
6.9.2.
Markers of Inflammation and Immune Activation
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48 and the Unblinding Visit for selected evaluations of inflammation and immune 
activation, which may include but not limited to cystatin-C, IL 6, hs CRP, d-dimer, sCD14, and 
sCD163.
6.9.3.
Markers of Platelet Function
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48 and the Unblinding Visit for selected evaluations of platelet function, which may
include but not limited to soluble glycoprotein VI (sGPVI), P-selectin, and soluble CD40 ligand.
6.10.
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 for HIV-1 genotyping/phenotyping 
assays or their development, for retesting the amount of HIV-1 in the blood, for measurement of 


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antiviral drug levels in the blood, or for testing to learn more about how the study drug has 
worked against HIV-1 or clinical laboratory testing 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.
6.11.
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.
6.12.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.13.
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.
6.14.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation, Week 48 or Week 96.
6.14.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any visit, after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA 
≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled 
visit; OR

At any visit, a 1 log10 increase in HIV-1 RNA from the nadir which is subsequently 
confirmed at the following scheduled or unscheduled visit
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing. Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-baseline resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.


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If no resistance is detected from the genotype or phenotype, the subject may remain on study 
drugs and a repeat HIV-1 RNA should be repeated (2 to 3 weeks after date of test with HIV-1 
RNA ≥ 50 copies/mL). Investigators should carefully evaluate the benefits and risks of 
remaining on study drug for each individual subject and document this assessment in the on-site 
medical record.
Subjects who are noncompliant on an ongoing basis will be considered for discontinuation per 
the Investigator’s discretion or local treatment guidelines. Investigators who opt to discontinue 
study drugs for an individual subject must discuss with the Medical Monitor prior to study drug 
discontinuation.
For subjects who are off study drug but remain on study, it will be the Investigator’s discretion to 
manage virologic rebound.
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
rebound.


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Figure 6-1.
Virologic Rebound Schema
a
If virologic rebound is not confirmed, the subject will remain on their current regimen.
b
If virologic rebound is confirmed and the HIV-1 RNA is ≥ 200 copies/mL, the HIV-1 genotype and phenotype (reverse 
transcriptase, protease and integrase) will be analyzed.
c
Based on the results of the genotypic and phenotypic assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping assay fails, a new ARV regimen may be configured at the discretion of the 
Investigator.
d
If no resistance is detected, HIV-1 RNA will be repeated (2-3 weeks later).  Investigator reviews study drug 
continuation/discontinuation options and discusses with the Medical Monitor prior to study drug discontinuation
e
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study.
6.14.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, Week 48 
or Week 96
Subjects with HIV-1 RNA ≥ 50 copies/mL at study discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 or Week 96 
will be asked to return for an unscheduled visit within the visit window for a retest.
Subjects with HIV-1 RNA ≥ 200 copies/mL at study drug discontinuation, last visit, Week 48, or 
Week 96 will also have resistance testing conducted.


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.6.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is 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 (e.g., 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, (e.g., 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 eCRF:

all SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30-days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.


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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead 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 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 it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study start), record the 
SAE on the paper serious adverse event report form and submit by e-mail or fax within 
24 hours of the investigator’s knowledge of the event to:
Gilead DSPH contact information:
Email:
Safety_FC@gilead.com
Fax:
+1 (650) 522-5477

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 CRF/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 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 to
investigational medicinal product.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to investigational medicinal product, 
investigational medicinal product will be withheld until the toxicity returns to Grade 2.When 
restarting investigational medicinal product following resolution of the adverse event, the 
investigational medicinal product should be restarted at full dose upon discussion with the 
Gilead Sciences Medical Monitor.

If a laboratory abnormality recurs to Grade 3 following rechallenge with investigational 
medicinal product and is considered related to investigational medicinal product, then 
investigational medicinal product will be permanently discontinued and the subject managed 
according to local practice. Recurrence of laboratory abnormalities considered unrelated to 
investigational medicinal product may not require permanent discontinuation but requires
discussion with the Gilead Sciences Medical Monitor.
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event

For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to investigational medicinal product, 
investigational medicinal product will be permanently discontinued and the subject managed 
according to local practice. The subject should be followed as clinically indicated until the 
laboratory abnormality returns to baseline or is otherwise explained, whichever occurs first. 
A clinically significant Grade 4 laboratory abnormality that is not confirmed by repeat testing 
should be managed according to the algorithm for the new toxicity grade.

Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant Grade 4 laboratory abnormality (eg, Grade 4 CK after strenuous exercise, or 
triglyceride elevation that is nonfasting or that can be medically managed) or a clinical event 
considered unrelated to investigational medicinal product requires discussion with the 
Gilead Sciences Medical Monitor.
7.5.4.
Management of Possible Abacavir Hypersensitivity Reaction
Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to increased 
risk of hypersensitivity reaction, unless no other therapeutic option is available based on the 
treatment history and resistance testing.
In a clinical study, 3.4 % of subjects with a negative HLA-B*5701 status receiving abacavir 
developed a hypersensitivity reaction. Therefore, even in the absence of HLA-B*5701 allele, it is 
important to permanently discontinue abacavir and not rechallenge with abacavir if a 
hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe 
or even fatal reaction.


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Hypersensitivity reactions are characterized by the appearance of symptoms indicating 
multi-organ system involvement. Almost all hypersensitivity reactions will have fever and/or 
rash as part of the syndrome. Other signs and symptoms may include respiratory signs and 
symptoms such as dyspnoea, sore throat, cough, and abnormal chest x-ray findings 
(predominantly infiltrates, which can be localized), gastrointestinal symptoms, such as nausea, 
vomiting, diarrhea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as 
respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis. Other frequently 
observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and
musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia). The symptoms related to this 
hypersensitivity reaction worsen with continued therapy and can be life-threatening. 
These symptoms usually resolve upon discontinuation of abacavir.
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. Patients 
should be monitored closely, especially during the first two months of treatment with abacavir.
Regardless of their HLA-B*5701 status, patients who are diagnosed with a hypersensitivity 
reaction whilst on therapy MUST discontinue study drug immediately and MUST NEVER be 
restarted. Restarting study drug following a hypersensitivity reaction results in a prompt return of 
symptoms within hours. This recurrence is usually more severe than on initial presentation, and 
may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimize 
the risk of a life-threatening hypersensitivity reaction, study drug must be permanently 
discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible 
(respiratory diseases, flu-like illness, gastroenteritis or reactions to other medicinal products) 
{Ezzati et al 2003}.
7.5.5.
Management of Potential Hepatobiliary Toxicity
Monkeys given a high dose (1000 mg/kg/day) for 39 weeks had evidence of biliary hyperplasia 
and hepatocyte hypertrophy on histopathologic examination. The risk to humans given the 
clinical dose of GS-9883 (50 mg/day) is unknown. Investigators should be aware of this potential 
toxicity. Any study subject exhibiting signs/symptoms or laboratory abnormalities suggestive of 
possible hepatobiliary toxicity should undergo thorough examination and clinical workup as 
deemed appropriate by the Investigator, and the Investigator must communicate promptly with 
the Gilead Medical Monitor. Consideration should be given to appropriate imaging studies (for 
example, ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. Management of graded 
laboratory and clinical abnormalities will be managed as outlined in Section 7.5.
7.5.6.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose 
interruption. Should the Investigator decide to initiate Hepatitis C treatment the Investigator 
must contact the Gilead Medical Monitor to confirm that no drug-drug interactions are expected.


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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.
7.6.
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.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to 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.


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Any premature termination of pregnancy (e.g., a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead 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.
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH,
fax number +1 650 522-5477 or email Safety_FC@gilead.com.
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead 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 7.3.2 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 a FDC of GS-9883/F/TAF
versus a FDC of ABC/DTG/3TC in HIV-1 infected, antiretroviral treatment naïve-adult subjects 
as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety and tolerability of the two treatment groups through 
Weeks 48 and 96

To evaluate the bone safety of the two treatment groups as determined by the percentage
change from baseline in hip and spine BMD through Weeks 48 and 96
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 96 as defined 
by the US FDA-defined snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48 and 96 as 
defined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48 and 96

The percentage change from baseline in hip and spine BMD at Weeks 48 and 96
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.


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8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis
set:

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 do not meet the inclusion criterion that the screening genotype report must 
show sensitivity to FTC, TFV, ABC, and 3TC.

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 4.3 including drugs not to be used with 
GS-9883, FTC, TAF, ABC, 3TC, and DTG.

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Substudy Analysis Set
The primary analysis set for intensive PK analyses is defined as the PK substudy analysis set, 
which will include all subjects who (1) are randomized into the study, (2) enrolled into the PK 
Substudy, (3) have received at least 1 dose of study drug, and (4) have at least 1 nonmissing 
intensive PK concentration data for the analyte under evaluation reported by the PK lab.


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8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose of 
study drug, and (3) have at least 1 nonmissing PK concentration data for the analyte under 
evaluation reported by the PK lab.
8.2.1.5.
DXA
8.2.1.5.1.
Hip DXA Analysis Set
The primary analysis set for hip BMD analyses is defined as the Hip DXA analysis set, which
will include all subjects who (1) are randomized into the study, (2) have received at least 1 dose 
of study drug, and (3) have nonmissing baseline hip BMD value. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.5.2.
Spine DXA Analysis Set
The primary analysis set for spine BMD analyses is defined as the Spine DXA analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have nonmissing baseline spine BMD value. Subjects will be 
grouped according to the treatment they actually received.
8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.  Logarithm (base 10) transformation will be 
applied to HIV-1 RNA levels for efficacy analysis.
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (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 (i.e., 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 sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects who achieve HIV-1 RNA 
50 copies/mL at Week 48 as determined by the US FDA-defined snapshot algorithm. The 
primary analysis of the efficacy will be based on the FAS.
8.5.1.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378, 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:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window

HIV-1 RNA 50 copies/mL: this includes 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 adverse event (AE), death, or lack of efficacy and have the last 
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
No Virologic Data in the Week 48 analysis window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following: 
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to AE or 
death (regardless of whether the last available on-treatment HIV-1 RNA < 50 copies/mL 
or not) or,
b) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
c) 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 achieving HIV-1 RNA < 50 copies/mL 
(as defined by the US FDA-defined snapshot algorithm) at Week 48 in GS-9883/F/TAF is at 
least 12% lower than the response rate in ABC/DTG/3TC; the alternative hypothesis is that the 
response rate in GS-9883/F/TAF is less than 12% lower than that in ABC/DTG/3TC.
Non-inferiority will be assessed using the conventional confidence interval approach. The point 
estimate of treatment difference (GS-9883/F/TAF – ABC/DTG/3TC) and the associated 2-sided 
95% confidence interval will be constructed using a normal approximation method based on 
stratified Mantel-Haenszel proportions, where stratification factors include baseline HIV-1 RNA 
level (100,000 copies/mL vs. 100,000 copies/mL) and region (US vs. Ex-US). Note that to 
avoid small or missing cells in analysis strata, CD4+ cell count is not stratified in analysis 
because HIV-1 RNA and CD4+ cell count are highly correlated.
It will be concluded that GS-9883/F/TAF is non-inferior to ABC/DTG/3TC if the lower bound of 
the 2-sided 95% CI of the difference (GS-9883/F/TAF – ABC/DTG/3TC) in the response rate is 
greater than -12%.
If non-inferiority of GS-9883/F/TAF to ABC/DTG/3TC is established, the lower bound of the 
95% CI will be compared to 0; if the lower bound of the 95% CI is greater than 0, then 
superiority of GS-9883/F/TAF over ABC/DTG/3TC will be established.
8.5.2.
Secondary Analyses
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 96 and the 
proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48 and 96, as defined 
by the US FDA-defined snapshot algorithm, will be analyzed using the same method as for the 
primary efficacy endpoint.
The changes from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48 and 96 will be 
summarized by treatment using descriptive statistics. The differences in changes from baseline in 
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95% confidence intervals will be constructed using ANOVA models, including treatment 
(GS-9883/F/TAF vs. ABC/DTG/3TC), baseline HIV-1 RNA level (100,000 copies/mL vs.
100,000 copies/mL), and region (US vs. Ex-US) as fixed effects in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.
8.6.
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, 
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On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV, can be found in Appendix 5.
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.
Bone Safety Evaluations
The percentage changes from baseline in hip/spine BMD at Weeks 48 and 96 will be 
summarized by treatment using descriptive statistics. The differences in percentage changes from 
baseline in hip/spine BMD between 2 treatment groups and the associated 95% confidence 
intervals will be constructed using ANOVA models, including treatment as a fixed effect in the 
model.
In addition, missing values for BMD will be imputed using LOCF method and analyzed 
similarly.
8.6.5.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the intensive PK substudy, plasma concentrations of GS-9883 may be summarized by 
nominal sampling time using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Ctau, 
AUCtau, and T½, as appropriate) will be listed and summarized using descriptive statistics 
(eg, sample size, arithmetic mean, geometric mean, coefficient of variation %, SD, median, Q1, 
Q3, minimum, and maximum). Plasma concentrations over time will be plotted in 
semi-logarithmic and linear formats as mean ± standard deviation, and median (Q1, Q3).


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For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
descriptive statistics or population approaches.
TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.
8.8.
Biomarker Analysis
For each biomarker of inflammation, immune activation, platelet function and renal tubular 
function, the percentage change from baseline will be summarized by treatment and visit using
descriptive statistics. Differences in percentage changes from baseline in each biomarker 
between the 2 treatment groups will be tested using a Wilcoxon rank sum test.
8.9.
Patient Report Outcomes (PRO)
The PRO measures based on questionnaires (eg, SF-36 and HIV Distress Module) will be 
summarized by treatment and visit using descriptive statistics.
8.10.
Sample Size
A total of approximately 600 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (300 subjects per treatment group), achieves at least 95% power to detect a 
non-inferiority margin of 12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined 
by the US FDA-defined snapshot algorithm) difference between the 2 treatment groups. For the 
sample size and power computations, it is assumed that both treatment groups have a response 
rate of 91% (based on Gilead Studies GS-US-292-0104 and GS-US-292-0111), that the 
non-inferiority margin is 12%, and that the significance level of the test is at a one-sided 
0.025 level.
8.11.
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 the 
first 300 subjects enrolled have completed Week 12 of the study or prematurely discontinues 
from the study drug, as well as after all subjects have completed Week 24 of the study or 
prematurely discontinues from the study drug. However, Gilead will defer to the IDMC for any 
decision to convene earlier or more frequently. The IDMC will examine the safety results of the 
trial and also focus on logistical issues such as accrual, retention, quality of clinical and 
laboratory data, and implications of results of external studies. Blinding will be preserved during 
the conduct of the study and access to unblinded data will be limited to designated parties.
No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
For each IDMC analysis performed prior to the analysis of the primary efficacy endpoint, an 
alpha penalty of 0.00001 will be applied for the primary analysis of the primary endpoint.


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8.12.
Analysis Schedule
The Weeks 48 and 96 analyses will be conducted after all subjects either complete their Week 48 
and 96 visits or prematurely discontinue from the study drug, respectively. Final analysis will be 
performed after all subjects complete the study or prematurely discontinue from the study.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject: These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 


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investigator must use the most current IRB- or IEC-approved consent form for documenting 
written informed consent. Each informed consent (or assent as applicable) will be appropriately 
signed and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB or IEC or
local requirements. 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, eCRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);


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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 


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data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), 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. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files.
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs or IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.


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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB or IEC 
in accordance with local requirements and receive documented IRB or IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(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.


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Amendment 1
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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.


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Amendment 1
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10.
REFERENCES
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? 
Curr Med Res Opin 2013;30 (1):89-97.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
Costagliola D. Demographics of HIV and aging. Curr Opin HIV AIDS 2014;9 (4):294-301.
Department for Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents. Developed by the DHHS 
Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working 
Group of the Office of AIDS Research Advisory Council (OARAC). Downloaded 
from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 08 April, 
2015.
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet 
2003;362 (9387):847-52.
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.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised 
surveillance case definitions for HIV infection among adults, adolescents, and 
children aged <18 months and for HIV infection and AIDS among children aged 
18 months to <13 years--United States, 2008. MMWR Recomm Rep 2008;57 
(RR-10):1-12.
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84.
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported adherence supports 
patient preference for the single tablet regimen (STR) in the current cART era. 
Patient preference and adherence 2012;6:427-33.
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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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table (Blinded Phase)
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-9883/F/TAF 
Protocol GS-US-380-1489 
Final 
Gilead Sciences, Inc. 
Amendment I 
Appendix l. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 
GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine 
in HIV-1 Infected, Antiretroviral Treatment-Naive Adults 
GS-US-380-1489 Amendment 1, 19 February 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Hal Martin, MD (Printed) 
Author 
Date 
PPD 
Signature 
INVESTIGATOR STATEMENT 
1 have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
T will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFJDENTIAL 
Page 93 
19 February 2016 


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Appendix 2.
Study Procedures Table (Blinded Phase)
Study Procedures
Screeninga
Day 1b
End of Weeke, r
Post-Week
96e, s
Unblinding 
Visit
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
4
8
12
24
36
48
60
72
84
96
Every 
12 Weeks
Informed Consent
X
Medical History
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-
Directed Physical Exam
X
X
Xd
Xd
Xd
X
Xd
X
Xd
Xd
Xd
Xd
Xd
X
Xd,f
Xf
12-Lead ECG 
(performed supine)
X
X
X
X
X
X
Questionnaires
X
X
X
X
DXA scan (spine & hip)g
X
X
X
X
X
X
Height
X
Vital signs (blood 
pressure, pulse, 
respiration rate, and 
temperature), including 
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profilei
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsj
X
X
X
X
X
X
Xt
X


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Amendment 1
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Study Procedures
Screeninga
Day 1b
End of Weeke, r
Post-Week
96e, s
Unblinding 
Visit
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
4
8
12
24
36
48
60
72
84
96
Every 
12 Weeks
Estimated Glomerular 
Filtration Rate
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HLA-B*5701w
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluations of 
inflammation and 
immune activation, 
platelet function and 
renal tubular function
X
X
X
X
X
Xt
X
Plasma & Urine Storage 
Sample 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HBV and HCV Serology
X
HIV-1 Genotypel
Xl
HIV-1 
Genotype/Phenotypee
Xe
Single PK Samplem
X
X
X
Trough PK Samplesn
X
X
Optional Whole 
blood/EDTA for HLA 
testing, UGT1A1 and 
biomarkers
X


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Amendment 1
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Study Procedures
Screeninga
Day 1b
End of Weeke, r
Post-Week
96e, s
Unblinding 
Visit
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
4
8
12
24
36
48
60
72
84
96
Every 
12 Weeks
Randomizationv
X
Provide subject dosing 
diary to subjects
X
X
X
X
X
Optional PK Substudyo
X
X
Optional PBMC 
Substudyp
X
X
X
Study Drug Dispensation
Xb
X
X
X
X
X
X
X
X
X
X
X
Xu
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures at the Day 1 visit, with the exception of DXA.
c
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Unblinding Visit even if the subject discontinues study drug.
d
Symptom-directed physical examination as needed.
e
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Section 6.14.1 and Section 6.14.2).
f
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to Day 1, or is otherwise explained.
g
DXA scans to be performed in all eligible subjects on study drug, except for those in Germany, prior to or within 24 hours of the Day 1 Visit, Weeks 24, 48, 96 (±10 days), 
and at Unblinding Visit (±10 days) and the ESDD visit (if the last scan was acquired > 12 weeks from the date of the ESDD Visit).
h
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
i
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN) At Day 1, Weeks 12, 24, 48, 72 and 96, and Unblinding Visit, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of 
the chemistry profile. Additionally: TSH will be analyzed at Screening, Day 1, Weeks 24, 48, 72 and 96 followed by every 24 weeks post Week 96, Unblinding Visit and 
Early Study Drugs Discontinuation visit.
j
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
k
CBC with differential and platelet count.


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Amendment 1
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l
The Investigator must have received the results from the screening genotype report before proceeding with the Day 1 visit.  Screening genotype report must show sensitivity 
to TFV, FTC, 3TC and ABC. If genotype results from a local laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype will be 
acceptable to fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been 
confirmed.
m
A single PK blood sample will be collected at any time pre or post-dose
n
A trough PK blood sample will be collected between 20-28 hours following the last dose. Following an observed dose, a single post dose blood sample will be collected 
between 1 and 4 hours post dose.
o
A PK substudy will be performed in a subset of subjects (n=30) at selected study sites.  The pharmacokinetic substudy visit must occur at the Week 4 or Week 8 visits. The 
substudy will include intensive PK profiling in plasma
p
A PBMC substudy will be performed in a subset of subjects (n=50) at selected study sites.   A PBMC sample will be collected at Day 1 and Weeks 36 and 84.
q
Only required for those subjects not enrolling in the open-label rollover extension or those subjects who permanently discontinue study drugs and do not continue in the study 
through at least one subsequent visit after the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be 
used.
r
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to
Week 96, unless otherwise specified. The visit window at Weeks 48 and 96 will be ± 6 weeks of the protocol-specified visit date.
s
After Week 96, subjects will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded.  Visit window of 
6 days for study visits post Week 96.  
t
To be performed every 24 weeks after Week 96 until Unblinding Visit.
u
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension.
v
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit, provided that all screening procedures have been completed and subject eligibility has been 
confirmed.
w
The Investigator must have received a negative screening test for HLA-B*5701 allele before proceeding with the Day 1 visit. If HLA-B*5701 results are available from a 
local laboratory prior to screening, this report will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result obtained at screening is not yet 
available and all other inclusion/exclusion criteria have been confirmed.


GS-9883/Fff AF 
Protocol GS-US-380-1489 
Final 
Gilead Sciences, Inc. 
Amendment 1 
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 
confrrm 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 
1 
If Grade 3 or 4 recurrence that is confirmed and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
1 
Repeat lab to 
confirm toxicity 
grade 
1 
lfc 
inve 
dosi 
oft 
onfirmed and unrelated to 
stigational medicinal products, 
ng may continue at the discretion 
he investigator 
If confirmed and 
possibly or probably 
-. related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
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Amendment 1
CONFIDENTIAL
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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


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Amendment 1
CONFIDENTIAL
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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
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-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 101
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L                
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L                 
2.0 t o <2.5 mmolL
2.0 mEq/L                         
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant <1 Year
>ULN to 6.0 mEq/L           
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L             
6.5 to 7.0 mmol/L
7.0 mEq/L                  
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 102
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 103
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 104
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L
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


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 105
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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.
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-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 106
19 February 2016
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
                              Females
>ULN - 10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
                              Males
6-10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 h
>1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
>499 to 799 mg/m2/24 h
>799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes:

Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by Covance Laboratory, however for other laboratories, toxicity grades will only be assigned to 
Dipstick Hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.

If the severity of a clinical AE could fall under either one of two grades (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 107
19 February 2016
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Arrhythmia (general)
(By ECG or physical exam)
Asymptomatic AND No 
intervention indicated
Asymptomatic AND Non-
urgent medical intervention 
indicated
Symptomatic, non-life-
threatening AND Non-
urgent medical intervention 
indicated 
Life-threatening arrhythmia 
OR Urgent intervention 
indicated
Cardiac-ischemia/Infarction
NA
NA
Symptomatic ischemia 
(stable angina) OR Testing 
consistent with ischemia 
Unstable angina OR Acute 
myocardial infarction
Hemorrhage (significant acute 
blood loss)
NA
Symptomatic AND No 
transfusion indicated
Symptomatic AND 
Transfusion of 2 units 
packed RBCs (for children 
10 cc/kg) indicated 
Life-threatening hypotension 
OR Transfusion of 2 units 
packed RBCs indicated (for 
children 10 cc/kg) indicated
Hypertension (with repeat 
testing at same visit)
140–159 mmHg systolic 
OR 
90–99 mmHg diastolic
159–179 mmHg systolic 
OR 
99–109 mmHg diastolic
179 mmHg systolic 
OR 
109 mmHg diastolic
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization (other than 
ER visit) indicated
Pediatric 17 Years (with 
repeat testing at same visit)
NA
91st–94th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
≥95th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization indicated 
(other than emergency room 
visit)
Hypotension
NA
Symptomatic, corrected with 
oral fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure
Pericardial Effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, moderate or 
larger effusion requiring no 
intervention
Effusion with non-life-
threatening physiologic 
consequences OR Effusion 
with nonurgent intervention 
indicated
Life-threatening consequences 
(eg, tamponade) OR Urgent 
intervention indicated


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 108
19 February 2016
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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Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced to 
70% to 80%
FEV1 or peak flow 50% to 69%
FEV1 or peak flow 25% to 
49% 
Cyanosis OR FEV1 or peak flow 
25% OR Intubation
Dyspnea or Respiratory 
Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities 
Dyspnea on exertion causing 
greater than minimal interference 
with usual social & functional 
activities 
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate for 
age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 
90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
OR Pulse oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis OR 
Medical intervention indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in affected 
eye(s) 
Visual Changes (from 
baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing greater 
than minimal interference with 
usual social & functional 
activities
Visual changes causing 
inability to perform usual 
social & functional activities
Disabling visual loss in affected 
eye(s)


GS-9883/F/TAF
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Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 110
19 February 2016
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-380-1489
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 111
19 February 2016
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Anorexia
Loss of appetite without 
decreased oral intake
Loss of appetite associated with 
decreased oral intake without 
significant weight loss 
Loss of appetite associated 
with significant weight loss 
Life-threatening consequences 
OR Aggressive intervention 
indicated [eg, tube feeding or 
total parenteral nutrition]
Ascites
Asymptomatic
Symptomatic AND Intervention
indicated (eg, diuretics or 
therapeutic paracentesis)
Symptomatic despite 
intervention
Life-threatening consequences
Cholecystitis
NA
Symptomatic AND Medical 
intervention indicated
Radiologic, endoscopic, or 
operative intervention 
indicated
Life-threatening consequences 
(eg, sepsis or perforation) 
Constipation 
NA
Persistent constipation requiring 
regular use of dietary 
modifications, laxatives, or 
enemas 
Obstipation with manual 
evacuation indicated
Life-threatening consequences 
(eg, obstruction)
Diarrhea 
Adult and Pediatric 
1 Year
Transient or intermittent 
episodes of unformed stools 
OR Increase of 3 stools 
over baseline/24 hr
Persistent episodes of unformed 
to watery stools OR Increase of 
4–6 stools over baseline per 
24 hrs. 
Bloody diarrhea OR Increase 
of 7 stools per 24-hour 
period OR IV fluid 
replacement indicated
Life-threatening consequences 
(eg, hypotensive shock)
Pediatric 1 Year
Liquid stools (more 
unformed than usual) but 
usual number of stools
Liquid stools with increased 
number of stools OR Mild 
dehydration
Liquid stools with moderate 
dehydration
Liquid stools resulting in 
severe dehydration with 
aggressive rehydration 
indicated OR Hypotensive 
shock
Dysphagia-Odynophagia 
Symptomatic but able to eat 
usual diet
Symptoms causing altered 
dietary intake without medical 
intervention indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention indicated
Life-threatening reduction in 
oral intake


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


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Alteration in Personality-
Behavior or in Mood (eg, 
agitation, anxiety, 
depression, mania, 
psychosis)
Alteration causing no or 
minimal interference with 
usual social & functional 
activities 
Alteration causing greater than 
minimal interference with 
usual social & functional 
activities 
Alteration causing inability to 
perform usual social & 
functional activities 
Behavior potentially harmful 
to self or others (eg, 
suicidal/homicidal ideation or 
attempt, acute psychosis) OR 
Causing inability to perform 
basic self-care functions
Altered Mental Status 
For Dementia, see Cognitive 
and Behavioral/Attentional 
Disturbance (including 
dementia and ADD)
Changes causing no or 
minimal interference with 
usual social & functional 
activities
Mild lethargy or somnolence 
causing greater than minimal 
interference with usual social 
& functional activities
Confusion, memory 
impairment, lethargy, or 
somnolence causing inability 
to perform usual social & 
functional activities
Delirium OR obtundation, OR 
coma
Ataxia 
Asymptomatic ataxia 
detectable on exam OR 
Minimal ataxia causing no 
or minimal interference with 
usual social & functional 
activities
Symptomatic ataxia causing 
greater than minimal 
interference with usual social 
& functional activities
Symptomatic ataxia causing 
inability to perform usual 
social & functional activities 
Disabling ataxia causing 
inability to perform basic self-
care functions
Cognitive and 
Behavioral/Attentional 
Disturbance (including 
dementia and Attention 
Deficit Disorder) 
Disability causing no or 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources not indicated
Disability causing greater than 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources on part-time basis 
indicated
Disability causing inability to 
perform usual social & 
functional activities OR 
Specialized resources on a 
full-time basis indicated
Disability causing inability to 
perform basic self-care 
functions OR 
Institutionalization indicated
CNS Ischemia
(acute)
NA
NA
Transient ischemic attack
Cerebral vascular accident 
(CVA, stroke) with 
neurological deficit 
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
23. Salmonella septicemia, recurrent
24. Toxoplasmosis of brain
25. Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {Schneider et al 2008}


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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.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b)
Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2)
Contraception Requirements for Female Subjects
a)
Study Drug Effects on Pregnancy and Hormonal Contraception
The 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 current Prescribing 
Information and local product labeling for ABC/DTG/3TC for additional information.
b)
Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Day 1 visit prior to randomization. At 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)
Contraception Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment and until 90 days after the 
end of relevant systemic exposure.  Additional contraception recommendations should also be 
considered if the female partner is not pregnant.
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
4)
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM).  Female condom and male condom should not 
be used together.
5)
Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Subjects whose partner 
has become pregnant or suspects she is pregnant during the study must report the information to 
the investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy 
outcome are outlined in Section 7.3.

Prot_008.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, 
Antiretroviral Treatment-Naïve Adults
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004024-54
NCT02607930
Indication:
HIV-1 Infection
Protocol ID:
GS-US-380-1489
Gilead Study Clinical 
Program Manager:
Name:
Telephone:
Fax:
Gilead Medical 
Monitor:
Name:
Telephone:
Fax:
Protocol Version/Date:
Original:
21 October 2015
Amendment 1:
19 February 2016
Amendment 2:
19 October 2016
Amendment 3:
06 May 2019
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The information is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol. 
You will not disclose any of the information to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered.
PPD
PPD
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GS-9883/F/TAF
Protocol GS-US-380-1489
Final
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Amendment 3
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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....................................................................13
1.
INTRODUCTION ..............................................................................................................................................16
1.1.
Background ............................................................................................................................................16
1.2.
GS-9883 .................................................................................................................................................17
1.2.1.
General Information .............................................................................................................17
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................17
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................19
1.3.
Information about Emtricitabine (Emtriva®, FTC).................................................................................28
1.4.
Information about Tenofovir Alafenamide (TAF, GS-7340).................................................................29
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide 
(FTC/TAF)...........................................................................................................................29
1.4.2.
Clinical Trials of FTC/TAF as part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF).........................................................................................................................30
1.5.
Information about GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) ........................32
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, 
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................32
1.6.
Information about Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®)............................34
1.7.
Rationale for this Study..........................................................................................................................34
1.8.
Risk/Benefit Assessment for the Study..................................................................................................34
1.9.
Rationale for Dose Selection..................................................................................................................35
1.10.
Compliance ............................................................................................................................................37
2.
OBJECTIVES.....................................................................................................................................................38
3.
STUDY DESIGN................................................................................................................................................39
3.1.
Endpoints ...............................................................................................................................................39
3.2.
Study Design..........................................................................................................................................39
3.3.
Study Treatments ...................................................................................................................................39
3.4.
Duration of Treatment............................................................................................................................40
3.5.
Biomarker Testing..................................................................................................................................41
3.5.1.
.41
3.5.2.
Additional Sample Storage...................................................................................................42
4.
SUBJECT POPULATION..................................................................................................................................43
4.1.
Number of Subjects and Subject Selection ............................................................................................43
4.2.
Inclusion Criteria....................................................................................................................................43
4.3.
Exclusion Criteria...................................................................................................................................44
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................47
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................47
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................47
5.2.
Description and Handling.......................................................................................................................48
5.2.1.
Formulation..........................................................................................................................48
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5.2.2.
Packaging and Labeling .......................................................................................................49
5.2.3.
Storage and Handling...........................................................................................................49
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide and 
Abacavir/Dolutegravir/Lamivudine .......................................................................................................50
5.4.
Prior and Concomitant Medications.......................................................................................................50
5.4.1.
Prior and Concomitant Medications (Blinded Phase through End of 
Blinded Treatment Visit)......................................................................................................50
5.4.2.
Prior and Concomitant Medications (Open-Label Rollover Extension 
Phase)...................................................................................................................................51
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................53
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................53
6.
STUDY PROCEDURES ....................................................................................................................................54
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................54
6.2.
Pretreatment Assessments......................................................................................................................54
6.2.1.
Screening Visit .....................................................................................................................54
6.2.2.
Day 1 Assessments...............................................................................................................56
6.3.
Randomization .......................................................................................................................................58
6.4.
Treatment Assessments (Week 4 - 144).................................................................................................58
6.5.
Treatment Assessments (Post Week 144 until the Open Label Rollover Extension).............................61
6.5.1.
Post Week 144 Assessments ................................................................................................61
6.5.2.
End of Blinded Treatment Visit ...........................................................................................63
6.5.3.
Treatment Assessments (Open-Label Rollover Extension)..................................................65
6.6.
Post-treatment Assessments ...................................................................................................................66
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................66
6.6.2.
30 Day Follow Up................................................................................................................68
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................69
6.8.
Bone Mineral Density Evaluations.........................................................................................................70
6.9.
Other Evaluations...................................................................................................................................70
6.9.1.
Markers of Renal Tubular Function .....................................................................................70
6.9.2.
Markers of Inflammation and Immune Activation...............................................................70
6.9.3.
Markers of Platelet Function ................................................................................................70
6.10.
70
6.11.
Assessments for Premature Discontinuation from Study.......................................................................71
6.12.
End of Study...........................................................................................................................................71
6.13.
Post Study Care......................................................................................................................................71
6.14.
Virologic Failure....................................................................................................................................71
6.14.1.
Management of Virologic Rebound .....................................................................................71
6.14.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48, Week 96,  Week 144, Week 48 OL or Week 96 OL............................................73
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................74
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................74
7.1.1.
Adverse Events.....................................................................................................................74
7.1.2.
Serious Adverse Events........................................................................................................74
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................75
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................75
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................75
7.2.2.
Assessment of Severity ........................................................................................................76
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................76
7.3.1.
Adverse Events.....................................................................................................................76
7.3.2.
Serious Adverse Events........................................................................................................77
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7.4.
Gilead Reporting Requirements.............................................................................................................78
7.5.
Toxicity Management ............................................................................................................................78
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................79
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................79
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................79
7.5.4.
Management of Possible Abacavir Hypersensitivity Reaction.............................................79
7.5.5.
Management of Potential Hepatobiliary Toxicity ................................................................80
7.5.6.
On-Treatment Hepatitis C Management...............................................................................81
7.6.
Special Situations Reports......................................................................................................................81
7.6.1.
Definitions of Special Situations..........................................................................................81
7.6.2.
Instructions for Reporting Special Situations.......................................................................82
8.
STATISTICAL CONSIDERATIONS................................................................................................................84
8.1.
Analysis Objectives and Endpoints........................................................................................................84
8.1.1.
Analysis Objectives..............................................................................................................84
8.1.2.
Primary Endpoint .................................................................................................................84
8.1.3.
Secondary Endpoint .............................................................................................................84
8.2.
The change from baseline in CD4+ cell count at Week 48 OL and 96 OL. Analysis 
Conventions ...........................................................................................................................................85
8.2.1.
Analysis Sets ........................................................................................................................85
8.3.
Data Handling Conventions ...................................................................................................................87
8.4.
Demographic Data and Baseline Characteristics ...................................................................................87
8.5.
Efficacy Analysis ...................................................................................................................................88
8.5.1.
Primary Analysis..................................................................................................................88
8.5.2.
Secondary Analyses .............................................................................................................89
8.5.3.
Efficacy Analyses for All GS-9883/F/TAF Analysis...........................................................90
8.6.
Safety Analysis.......................................................................................................................................90
8.6.1.
Extent of Exposure...............................................................................................................90
8.6.2.
Adverse Events.....................................................................................................................90
8.6.3.
Laboratory Evaluations ........................................................................................................91
8.6.4.
Bone Safety Evaluations ......................................................................................................91
8.6.5.
Other Safety Evaluations......................................................................................................91
8.7.
Pharmacokinetic Analysis......................................................................................................................92
8.8.
Inflammation, Immune Activation, Platelet and Renal Tubular Function Analysis...............................92
8.9.
Patient Report Outcomes (PRO) ............................................................................................................92
8.10.
Sample Size............................................................................................................................................92
8.11.
Data Monitoring Committee ..................................................................................................................92
8.12.
Analysis Schedule ..................................................................................................................................93
9.
RESPONSIBILITIES..........................................................................................................................................94
9.1.
Investigator Responsibilities ..................................................................................................................94
9.1.1.
Good Clinical Practice..........................................................................................................94
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................94
9.1.3.
Informed Consent.................................................................................................................95
9.1.4.
Confidentiality......................................................................................................................95
9.1.5.
Study Files and Retention of Records ..................................................................................95
9.1.6.
Case Report Forms...............................................................................................................97
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................97
9.1.8.
Inspections............................................................................................................................97
9.1.9.
Protocol Compliance............................................................................................................98
9.2.
Sponsor Responsibilities ........................................................................................................................98
9.2.1.
Protocol Modifications.........................................................................................................98
9.2.2.
Study Report and Publications .............................................................................................98


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9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................98
9.3.1.
Payment Reporting...............................................................................................................98
9.3.2.
Access to Information for Monitoring..................................................................................99
9.3.3.
Access to Information for Auditing or Inspections ..............................................................99
9.3.4.
Study Discontinuation..........................................................................................................99
10.
REFERENCES .................................................................................................................................................100
11.
APPENDICES ..................................................................................................................................................102
Appendix 1.
Investigator Signature Page..................................................................................................103
Appendix 2.
Study Procedures Table (Blinded Phase) .............................................................................104
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)..................................................108
Appendix 4.
Management of Clinical and Laboratory Adverse Events....................................................110
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.............111
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................133
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................134
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........21
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................22
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................23
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)...............................................................................24
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.................................................................................................36
Table 5-1.
Prior and Concomitant Medications (Blinded Phase through End of Blinded 
Treatment Visit) .....................................................................................................................51
Table 5-2.
Prior and Concomitant Medications (Open-Label Rollover Extension Phase) ......................52
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................24
Figure 3-1.
Study Schema.........................................................................................................................41
Figure 6-1.
Virologic Rebound Schema....................................................................................................72


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, 
Antiretroviral Treatment-Naïve Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004024-54
NCT02607930
Study Centers 
Planned:
Approximately 150 centers in North America, Europe and
Latin America 
Objectives:
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) 
containing GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 
infected, antiretroviral treatment naïve-adult subjects as 
determined by the achievement of HIV-1 RNA < 50 copies/mL
at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the 
two treatment groups through Weeks 48, 96, and 144

To evaluate the bone safety of the two treatment groups as 
determined by the percentage change from baseline in hip and 
spine bone mineral density (BMD) through Weeks 48, 96, 
and 144

To evaluate the long term efficacy and safety of FDC 
GS-9883/F/TAF through open-label (OL) Weeks 48 and 96. 


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Study Design:
Randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus 
ABC/DTG/3TC FDC in HIV-1 infected, antiretroviral 
treatment-naïve adult subjects. Subjects who provide written consent 
and meet all eligibility criteria will be randomized in a 1:1 ratio to 
one of the following two treatment groups:
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 
200 mg/ tenofovir alafenamide 25 mg (GS-9883/F/TAF) + Placebo to 
match FDC of abacavir 600 mg/ dolutegravir 50 mg/lamivudine 
300 mg (ABC/DTG/3TC) administered orally, once daily, without 
regard to food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 
50 mg/ lamivudine 300 mg (ABC/DTG/3TC) + Placebo to match 
FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without 
regard to food (n=300)
Randomization will be stratified by HIV-1 RNA level 
(≤100,000 copies/mL, > 100,000 to ≤ 400,000 copies/mL, or 
> 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. 
Ex-US) at randomization.
Number of Subjects 
Planned:
Approximately 600 subjects in total. 300 subjects in each Treatment 
Group 1 and Treatment Group 2
Target Population:
Antiretroviral treatment-naïve (except the use for pre-exposure 
prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to 
one month prior to screening), HLA-B*5701 negative, HIV-1 
infected adults with plasma HIV-1 RNA levels ≥ 500 copies/mL and 
a screening genotype showing sensitivity to FTC, TFV, 3TC, and 
ABC.
Duration of 
Treatment:
Subjects will be treated for at least 144 weeks during the blinded 
treatment phase.  After Week 144, all subjects will continue to take 
their blinded study drug and attend visits every 12 weeks until the 
End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all 
subjects will return to the clinic (preferably within 30 days) for an
End of Blinded Treatment Visit. At the End of Blinded Treatment 
Visit, subjects will be given GS-9883/F/TAF FDC in an open label 
(OL) extension phase for 96 weeks (Week 96 OL). After Week 96 
OL, subjects will discontinue the study drug, transition onto
commercially available treatment and complete a 30-Day Follow-up 
Visit. In a country where GS-9883/F/TAF is not available, subjects


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will be given the option to continue OL GS-9883/F/TAF until the 
product becomes accessible to subjects through an access program, or 
until Gilead Sciences elects to discontinue the study in that country, 
whichever occurs first.
All subjects participating in the open label extension phase, without 
regard to their blinded treatment regimen, will return for study visits 
at Week 12 OL and every 12 weeks thereafter for at least 96 weeks.
Subjects who complete the study through the End of Blinded 
Treatment Visit and do not continue on the open label 
GS-9883/F/TAF FDC extension phase will be required to return to 
the clinic after the End of Blinded Treatment Visit for a 30-Day 
Follow-Up Visit. 
Treatment assignments will be provided to the investigators within 
30 days of the last subject completing the End of Blinded Treatment 
Visit.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening

Antiretroviral treatment naïve (≤ 10 days of prior therapy with 
any antiretroviral agent following a diagnosis of HIV-1 infection) 
except the use for PrEP or PEP, up to one month prior to 
screening.

Screening genotype report must show sensitivity to FTC, TFV, 
3TC, and ABC

Negative screening test for HLA-B*5701 allele

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance

No chronic Hepatitis B Virus (HBV) infection, as determined by 
either
Positive HBV surface antigen and negative HBV surface 
antibody, regardless of HBV core antibody status, at the 
screening visit
Positive HBV core antibody and negative HBV surface 
antibody, regardless of HBV surface antigen status, at the 
screening visit


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Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 
1:1 to Treatment Group 1 or Treatment Group 2 and treated for 
144 weeks. Following the Day 1 visit, subjects will be required to 
return for study visits at Weeks 4, 8, and 12, and then every 12 weeks 
from Week 12 through Week 144.  After Week 144, all subjects will 
continue to take their blinded study drugs and attend study visits 
every 12 weeks until the End of Blinded Treatment Visit. All subjects 
participating in the open label extension phase, without regard to their 
blinded treatment regimen, will return for study visits at Week 12 OL 
and every 12 weeks thereafter for at least 96 weeks.
For all eligible subjects, blood will be collected at Day 1, Weeks 4, 8, 
12, and then every 12 weeks through the End of Blinded Treatment 
Visit.  Blood will also be collected at Week 12 OL and every 
12 weeks thereafter for at least 96 weeks during open label extension 
phase. Laboratory analyses (hematology, chemistry, and urinalysis), 
HIV-1 RNA, CD4+ cell count, and complete or symptom directed 
physical examinations will be performed at Screening, Day 1 and all 
subsequent visits. In addition, blood will be collected and stored for 
possible evaluation of markers of inflammation and immune 
activation, which may include but are not limited to: cystatin-C, IL-6, 
hs-CRP, d-dimer, sCD14, and sCD163. Platelet function evaluations 
may also be assessed, including but not limited to soluble 
glycoprotein VI (sGPVI), P-selectin, and soluble CD40 ligand.  Urine 
will be collected for evaluations of renal tubular function including 
urine albumin, urine creatinine, urine protein, retinol binding protein 
and beta-2 microglobulin.
For all subjects on study drug, except subjects located in Germany, 
dual energy x-ray absorptiometry (DXA) scans will be performed 
prior to or within 24 hours of the Day 1 Visit, and then at Weeks 24, 
48, 96, 144 and at the End of Blinded Treatment Visit or Early Study 
Drug Discontinuation Visit (blinded treatment phase only), if 
> 12 weeks since last scan. DXA will be performed at Week 48 OL 
and Week 96 OL for subjects who were randomized to GS-
9883/F/TAF, complete the blinded phase and enter the OL extension 
phase, except subjects located in Germany. DXA scan results will be 
provided to study sites when available.
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.


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Reference Therapy, 
Dose, and Mode of 
Administration:
FDC of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg 
(ABC/DTG/3TC) administered orally, once daily without regard to 
food.
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests and DXA
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 48 as defined by the United States (US) 
Food and Drug Administration (FDA)-defined snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 96 and 144 as defined by the US 
FDA-defined snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA 
< 20 copies/mL at Weeks 48, 96, and 144 as defined by the 
US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and 
CD4+ cell count at Weeks 48, 96, and 144.

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 48 OL and 96 OL as defined by 
Missing = Excluded and Missing = Failure algorithm

The change from baseline in CD4+ cell count at Week 48 OL and 
96 OL. 
 
 
 
 
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The concentration of GS-9883 may be summarized using descriptive 
statistics. The pharmacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concentrations may be 
analyzed and PK parameters may be summarized as applicable.
 
 
 
 
 
 
 
 
 
 
Patient Reported 
Outcome:
Short Form 36 Health Survey (SF-36), HIV Symptoms Distress 
Module, Work Productivity and Activity Impairment Questionnaire 
(WPAI) and Pittsburgh Sleep Quality Index (PSQI) will be 
administered at Day 1, Weeks 4, 12, and 48.
Statistical Methods:
The primary analysis will consist of a non-inferiority test of 
GS-9883/F/TAF versus ABC/DTG/3TC, with respect to the 
proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm.
It will be concluded that GS-9883/F/TAF is non-inferior to 
ABC/DTG/3TC if the lower bound of the 2-sided 95% confidence 
interval (CI) of the difference (GS-9883/F/TAF – ABC/DTG/3TC) in 
the response rate (HIV-1 RNA < 50 copies/mL as defined by the
US FDA-defined snapshot algorithm) is greater than -12%; ie, a 
margin of 12% is applied to non-inferiority assessment. The 95% CI 
will be constructed using a normal approximation method based on 
stratified Mantel-Haenszel proportions, where stratification factors 
include baseline HIV-1 RNA level (≤ 100,000 copies/mL vs. 
> 100,000 copies/mL) and region (US vs. Ex-US).
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The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL 
at Weeks 96 and 144 and the proportion of subjects who achieve 
HIV-1 RNA < 20 copies/mL at Weeks 48, 96, and 144 as defined by 
the US FDA-defined snapshot algorithm will also be summarized. 
The 95% CIs will be constructed in the same manner as described for 
the primary efficacy endpoint.
The change from baseline in log10 HIV-1 RNA and CD4+ cell count 
at Weeks 48, 96, and 144 will be summarized by treatment using 
descriptive statistics. The differences and the associated 2-sided
95% CIs will be constructed using an Analysis of Variance 
(ANOVA) model, including treatment (GS-9883/F/TAF vs. 
ABC/DTG/3TC), baseline HIV-1 RNA level (100,000 copies/mL 
vs. 100,000 copies/mL), and region (US vs. Ex-US) as fixed effects 
in the model.
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL 
at Weeks 48 OL and 96 OL will be summarized, where missing 
HIV-1 RNA will be excluded and treated as failure, respectively. The 
changes from baseline in CD4+ cell count and percentage at 
Weeks 48 OL and 96 OL will be summarized using descriptive 
statistics.
The percentage change from baseline in hip and spine BMD at 
Weeks 48, 96, and 144 will be summarized by treatment using 
descriptive statistics. The differences and the associated 2-sided
95% CIs will be conducted using an ANOVA model including 
treatment as a fixed effect in the model.  Adverse events, clinical 
laboratory assessments, and pharmacokinetic parameters will be 
summarized using descriptive statistics.
A total of approximately 600 HIV-1 infected subjects, randomized in 
a 1:1 ratio to 2 treatment groups (300 subjects per treatment group), 
achieves at least 95% power to detect a non-inferiority margin of 
12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as 
defined by the US FDA-defined snapshot algorithm) difference 
between the 2 treatment groups. For sample size and power 
computation, it is assumed that both treatment groups have a response 
rate of 91% (based on Gilead Studies GS-US-292-0104 and 
GS-US-292-0111), that a non-inferiority margin is 12%, and that the 
significance level of the test is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
ABC/3TC
abacavir/lamivudine, EpzicomKivexa
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration 
versus time curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DTG
dolutegravir, Tivicay
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
EVG
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination


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


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


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {The Joint United Nations Programme on HIV/AIDS (UNAIDS) 2014}. The 
infection, if left untreated or suboptimally treated, is characterized by deterioration in immune 
function, ultimately resulting in death. Therapeutic strategies for the treatment of HIV-1 disease 
have been significantly advanced by the availability of highly active antiretroviral therapy 
(HAART); the introduction of HAART was associated with a dramatic decrease in acquired 
immune deficiency syndrome (AIDS)-related morbidity and mortality {Mocroft 1998, 
Palella 1998, Sterne 2005}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {Costagliola 2014}. In addition, there remains a significant 
medical need for new, effective therapies that take into consideration HIV genetic variability, the 
aging HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen 
simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {Department for 
Health and Human Services (DHHS) 2015}. Virologically suppressed, HIV-infected patients
may switch from their current regimen because of safety or tolerability concerns or for regimen 
simplification. All patient populations may benefit from once-daily fixed-dose combination 
(FDC) regimens as these have been shown to provide increased adherence and improved clinical 
and virologic outcomes {Aldir 2014, Sterrantino 2012}
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other NRTIs. Tenofovir alafenamide (TAF) is also an 
oral prodrug of TFV. TAF is more stable in plasma than TDF, provides higher intracellular 
levels of the active phosphorylated metabolite tenofovir diphosphate (TFV-DP), and 
approximately 90% lower circulating levels of TFV relative to TDF at the clinical doses. 
The distinct metabolism of TAF offers the potential for an improved clinical profile compared 
with TDF.
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 


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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.
Gilead Sciences (Gilead) has coformulated GS-9883 with the NRTI emtricitabine (FTC; F) and 
the NtRTI tenofovir alafenamide (TAF) into an FDC tablet that is suitable for once-daily use. 
This GS-9883/F/TAF FDC may provide a potent, convenient, tolerable, and practical regimen 
for the long-term treatment of patients with HIV infection.
1.2.
GS-9883
1.2.1.
General Information
GS-9883, a potent inhibitor of HIV-1 integrase is being evaluated for the treatment of HIV 
infection. Antiviral testing has shown that GS-9883 is active against a broad panel of HIV-1 viral 
lab strains and clinical isolates. GS-9883 is fully active against a panel of mutant viruses with 
resistance to NRTIs, NNRTIs, and PIs. Integrase mutant viruses that are resistant to the INSTIs
RAL and EVG remain largely sensitive to GS-9883.
1.2.2.
Preclinical Pharmacology and Toxicology
A core battery of safety pharmacology studies have been conducted with GS-9883. These 
include assessments of cytotoxicity, off-target receptor and ion-channel binding, effects on 
human Ether-à-go-go-Related Gene (hERG) potassium current and papillary muscle action 
potential, and in vivo studies in rats and dogs that evaluated effects of GS-9883 on all major 
organ systems. The volume of distribution of GS-9883 ranged between 0.09 and 0.22 L/kg in the 
preclinical species, which indicates that the distribution of GS-9883 is limited to the extracellular 
compartment due to its high binding to plasma proteins. The projected half-life of GS-9883 in 
humans is approximately 20 hours based upon the estimates of clearance and volume of 
distribution.
1.2.2.1.
Pharmacology
GS-9883 has IC50 values ranging from 1.5 to 2.4 nM, similar to the inhibitory effect of DTG and 
EVG. GS-9883 is highly potent against HIV replication in MT4 cells with an EC50 (50% 
effective inhibitory concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. 
GS-9883 does not show significant cytotoxicity against dividing and non-dividing human 
PBMCs, primary human hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 M. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter OCT2 (IC50 = 0.42 M). As a result, 
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 M 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.
1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL, 
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day.  At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal 
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males.  The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy.
No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL). The estimated margin of exposure at the NOEL 
was approximately 5.1-fold based on expected human exposure with the once daily dosing of the
GS-9883/F/TAF (50/200/25 mg) tablet.


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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 (completed)

GS-US-141-1478, a Phase 1, Open Label, Parallel Group, Adaptive, Single-Dose Study to 
Evaluate the Pharmacokinetics of GS-9883 in Subjects with Normal and Impaired Hepatic 
Function (in life portion completed)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)


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


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


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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).
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.


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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
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 1-4 below.


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Table 1-4. 
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ9s Values 
(GS-9883 PK Analysis Set) 
GS-9883 dose 
N 
Median (range) C tau, ss (ng!mL) 
Median (range) pai Qgs• 
5mg 
4 
206.5 (146.0 to 342.0) 
1.3 (0.9 to 2.1) 
25mg 
4 
797.5 (714.0 to 1900.0) 
4.9 ( 4.4 to 11. 7) 
50mg 
4 
2170.0 (852.0 to 3020.0) 
13.4 (5.3 to 18.6) 
100mg 
4 
4190.0 (3730.0 to 5970.0) 
25.9 (23.0 to 36.9) 
a. 
The protein adjusted IQ95 (paiQ9s) value is estimated based on steady-state Ctau values and the in vitJ:o paiC95 value for 
wild-type HIV-1 (162 ng/ml). 
The mean and 95% Cis of change from baseline in HIV -1 RNA (log10 copies/mL) are presented 
in Figure 1-1. 
Figure 1-1. 
2 
:; 
~ 
-~ 1 
8 
GS-9883 5 mg (~): 
G$-9883 25 mg (~): 
GS-9883 50 mg (~): 
G$-9883 100 mg (~) : 
Placebo (~ 
): 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log1o copies/mL) (PP Analysis Set) 
• = GS-9883 5 mg 
0 = GS-9883 25 mg 
6 = GS-9883 50 mg 
0 = GS-9883 100 mg 
0 =Placebo 
Bl 
2 
3 
3 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
3 
3 
4 
3 
4 
7 
8 
9 
10 
11 
Day 
3 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
--
- -
--
14 
17 
3 
3 
4 
3 
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 
-1 
-2 
-3 
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Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group.
1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing 
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, ART-naive adult subjects.
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to 
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 50 mg 
once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 75 mg 
once daily
Week 24 interim data are summarized below. 
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24 
data analysis, 2 subjects (2.0%) had prematurely discontinued from the study, 1 in each treatment 
group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and eGFRCG) were similar 
between the 2 treatment groups.
Median (first quartile [Q1], third quartile [Q3]) baseline HIV-1 RNA was 4.45 (3.96, 4.79) 
log10 copies/mL, with 82.7% of subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had 
> 400,000 copies/mL at baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 
1 subject was randomized to DTG+F/TAF. 
Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 41.8% of subjects 
having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 125.3 
(105.7, 147.0) mL/min.


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Efficacy Results
Virologic success at Weeks 12 and 24 was assessed using the US FDA-defined snapshot 
algorithm, defined as plasma HIV-1 RNA < 50 copies/mL. At Weeks 12 and 24, virologic 
success was high and similar between the 2 treatment groups as follows: Week 12 
GS-9883+F/TAF 93.8%, DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79); Week 24 GS-9883+F/TAF 95.4%, DTG+F/TAF 
93.9% (1.0%; 95% CI: −10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 had HIV-1 RNA of 60 copies/mL. 
Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF, +170 (150.0) cells/μL; DTG+F/TAF, +173 (220.5) cells/μL 
(difference in least squares mean [LSM]: 0; 95% CI: −76 to 76; p = 1.00). There were similar 
increases in the mean (SD) CD4 cell count in both treatment groups Week 24: GS-9883+F/TAF, 
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 
95% CI: −35 to 113; p = 0.30).
Interim Virology Resistance Data
Through Week 24, no emergent drug resistance was detected.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 66.2%, 43 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common treatment-emergent AEs (occurring in > 2 subjects) by treatment group were as 
follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE. One other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator or resulted in 
study drug discontinuation or interruption, and both SAEs resolved.


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The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883+F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs reported that were considered related to 
study drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation 
were reported in either treatment group.
Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least 
1 grade level increase from baseline in graded abnormality) was similar between treatment 
groups as follows: GS-9883+F/TAF 76.6%, 49 subjects; DTG+F/TAF 78.1%, 25 subjects. The 
majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The 
percentage of subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality
was similar between treatment groups as follows: GS-9883+F/TAF 17.2%, 11 subjects; 
DTG+F/TAF 12.5%, 4 subjects. Grade 3 or 4 laboratory abnormalities occurring in at least 
2 subjects in either treatment group were as follows: creatine kinase (GS-9883+F/TAF, 
7.8% [5 subjects]), fasting serum glucose (DTG+F/TAF, 6.3% [2 subjects]), aspartate 
aminotransferase (AST) (GS-9883+F/TAF, 3.1% [2 subjects]), and fasting low-density 
lipoprotein (LDL) (GS-9883+F/TAF, 3.1% [2 subjects]). The only Grade 4 laboratory 
abnormalities were for creatine kinase, reported in 2 subjects (3.1%) in the GS-9883+F/TAF 
group. All increased creatine kinase values appeared to be transient, and none were associated 
with AEs. Of the 2 subjects with increased AST, 1 subject had Grade 3 AST and Grade 3 ALT at 
Week 24 in the setting of alcohol abuse; the other subject had Grade 3 AST at Week 8 that 
returned to normal by Week 24.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. There were 
similar increases from baseline in median (Q1, Q3) serum creatinine in both treatment groups at 
Week 24: GS-9883+F/TAF 0.12 (0.06, 0.18) mg/dL; DTG+F/TAF 0.13 (0.05, 0.21) mg/dL. 
There were decreases in median (Q1, Q3) eGFRCG at Week 24, which were smaller in the 
GS-9883+F/TAF compared with the DTG+F/TAF group: GS-9883+F/TAF 
−13.3 (−19.9, −4.0) mL/min; DTG+F/TAF −17.2 (−25.7, −6.9) mL/min.


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Conclusions
Key Week 24 conclusions from Study GS-US-141-1475 include the following:

Virologic success at Week 24 when assessed using the US FDA-defined snapshot algorithm, 
defined as plasma HIV-1 RNA < 50 copies/mL, was similar between the 2 treatment groups 
as follows: GS-9883+F/TAF 95.4%; DTG+F/TAF 93.9%; stratum-adjusted difference in 
percentages: 1.0%; 95% CI: −10.7% to 12.7%; p = 0.84. There was a similar increase in the 
mean (SD) CD4 cell count between the 2 treatment groups, GS-9883+F/TAF, 
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 
95% CI: −35 to 113; p = 0.30).

No resistance to any INSTIs, NRTIs, NNRTIs, or PIs was detected through Week 24.

No AEs led to study drug discontinuation in either treatment group.

Both GS-9883+F/TAF and DTG+F/TAF were generally well tolerated through 24 weeks of 
treatment. The most commonly reported treatment-emergent AEs were diarrhea and 
headache (7.7% each) in the GS-9883+F/TAF group and nausea (12.1%) and diarrhea 
(9.1%) in the DTG+F/TAF group. There were 2 SAEs, 1 of which was also a Grade 3 AE; 
neither of these events was considered related to study drug by the investigator, or led to 
study drug discontinuation. There were no other Grade 3 or 4 AEs, and no deaths, 
pregnancies, or AEs leading to premature study drug discontinuation reported. The 
percentage of subjects with at least 1 treatment-emergent laboratory abnormality was similar 
between treatment groups. The majority of treatment-emergent laboratory abnormalities were 
Grade 1 or 2 in severity. There were similar increases from baseline in serum creatinine in 
both treatment groups at Week 24. 
1.3.
Information about Emtricitabine (Emtriva®, FTC)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US FDA for marketing on 2 July 2003 and is available 
under the name Emtriva®. In the European Union (EU), marketing authorization was granted for 
both the 200 mg Emtrivacapsule formulation and a 10 mg/mL Emtrivaoral Solution 
formulation on 24 October 2003, with indications for the treatment of HIV infection concurrently 
with other antiretroviral drugs in both adult and pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.


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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-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in
healthy subjects (completed)

GS-US-120-1538, a Fixed-Sequence, Open-Label, Study Evaluating the Pharmacokinetics 
and Drug Interaction Potential between Tenofovir Alafenamide and Midazolam (Oral and 
Intravenous) in Healthy Volunteers (completed) 


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
GS-US-120-1554, a Fixed-Sequence, Randomized, Open-Label, 2-Cohort, 2-Period, 
Multiple-Dose Study Evaluating the Pharmacokinetics and Drug Interaction Potential 
between Tenofovir Alafenamide and Rilpivirine in Healthy Subjects (completed)

GS-US-311-1386, a Phase 1 study to determine the effect of food on the pharmacokinetics of 
tenofovir alafenamide when administered as F/TAF FDC in healthy volunteers (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz (EFV) or
COBI-boosted darunavir (DRV) (completed)

GS-US-311-1088, a Phase 1, Relative Bioavailability Study of Emtricitabine/Tenofovir
Alafenamide Fixed Dose Combination Tablet to evaluate the formulation performance of
emtricitabine (FTC) and tenofovir alafenamide (TAF) fixed dose combination tablets relative
to co-administration of individual agents (completed)

GS-US-311-1089, a Phase 3 study of the safety and efficacy of FTC/TAF in HIV infected,
virologically suppressed patients (ongoing).
In Study GS-US-311-1386, the effect of food (high-calorie, high-fat meal) on the PK of the TAF 
component of the F/TAF FDC was evaluated. The GLSM ratio of the AUClast of TAF when 
administered with a high-fat meal was 177% (90% CI: 166% to 188%), and the TAF Cmax 
GLSM ratio was 84.5% (90% CI: 74.9% to 95.4%). This ~75% increase in TAF plasma 
exposure and ~15% decrease in TAF plasma Cmax when administered with food was 
accompanied by a delay in Tmax (increase from 1.00 hour under fasted conditions to 2.00 hours 
under fed conditions). The exposures of TAF observed under fed or fasted conditions in this 
study are within the range of exposures observed in the E/C/F/TAF clinical development 
program and are commensurate with safe and effective plasma levels of TAF (see investigator 
brochure for further details). Therefore, the changes in TAF exposures when F/TAF is 
administered with food should not result in differences in efficacy and thus are not clinically 
relevant. TAF can be administered without regard for food and these findings can be 
extrapolated to F/TAF (as FTC can be taken without regard to food).
1.4.2.
Clinical Trials of FTC/TAF as part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF)
Clinical trials using tenofovir alafenamide, coformulated into the E/C/F/TAF STR include:

GS-US-292-0101, a Phase 1 healthy volunteer study evaluating the relative bioavailability of 
EVG, FTC, TFV, and COBI administered as E/C/F/TAF STR relative to E/C/F/TDF or TAF 
(completed)

GS-US-292-0103, a Phase 1 healthy volunteer study to evaluate the pharmacokinetics and 
relative bioavailability of the E/C/F/TAF STR relative to the individual components at 
GS-7340 doses of 10 mg (STR) or 25 mg Single Agent (SA) (completed)


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
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)
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 Pgp-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.


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Study GS-US-292-0102 is an ongoing, randomized, active-controlled Phase 2 study, compares 
E/C/F/TAF (10 mg) versus Stribild® (STB, E/C/F/TDF) in treatment-naïve, HIV-1 infected 
subjects. At Week 48, the E/C/F/TAF demonstrated potent antiviral efficacy (HIV-1 RNA 
< 50 copies/mL) similar to STB (88.4% [99/112] vs 87.9% [51/58] using the snapshot 
algorithm); in the E/C/F/TAF group, no patient had emergent resistance to 1 or more components 
of the E/C/F/TAF. Importantly, E/C/F/TAF demonstrated a potential benefit over E/C/F/TDF in 
terms of renal and bone safety: smaller median decreases in eGFR (mL/min) (at Week 48, 
E/C/F/TAF -5.5 vs E/C/F/TDF -10.0 [p<0.001) and smaller median percentage decreases in 
BMD (at Week 48, spine E/C/F/TAF -1.00 vs E/C/F/TDF -3.37 [p<0.001], hip -0.62 
vs -2.39 [p<0.001]).
Studies GS-US-292-0104 and GS-US-292-0111 are ongoing, Phase 3 randomized, 
double-blinded studies of the safety and efficacy of E/C/F/TAF versus E/C/F/TDF in HIV-1 
infected, antiretroviral treatment-naive adults. The interim Week 48 key conclusions from pooled 
data showed that E/C/F/TAF once daily was noninferior to STB once daily when administered 
for 48 weeks to HIV-infected, ART-naive adults, as assessed using the US FDA-defined 
snapshot algorithm with HIV-1 RNA < 50 copies/mL (E/C/F/TAF 92.4%; STB 90.4%; 
difference in percentages: 2.0%, 95% CI: -0.7% to 4.7%). Administration of E/C/F/TAF resulted 
in > 90% lower plasma TFV and higher intracellular TFV-DP relative to STB.  E/C/F/TAF 
showed an improved renal and bone safety profile with significantly less decline in hip and spine 
BMD, less increase in serum creatinine and reduction in estimated glomerular filtration rate 
(eGFR).
1.5.
Information about GS-9883/Emtricitabine/Tenofovir Alafenamide 
(GS-9883/F/TAF)
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, FTC, and 
TAF between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is an ongoing Phase 1, open-label, 2-cohort, multiple-period,
fixed-sequence, crossover study conducted at a single center in the US to evaluate 1) the relative 
bioavailability (BA) of 2 GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets 
compared with the GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered 
simultaneously and 2) the effect of food on the PK of GS-9883, FTC, and TAF when 
administered as GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets.
Cohort 1 evaluated the relative BA and food effect of GS-9883/F/TAF (75/200/25 mg) FDC 
tablet in a 3-period sequence. Following review of preliminary data from Cohort 1, Cohort 2 was 
added to the study via protocol amendment. Cohort 2 evaluated the relative BA and food effect 
of GS-9883/F/TAF (50/200/25 mg) FDC tablet in a 4-period sequence.
The in-life portion of Cohorts 1 and 2 are complete. Preliminary results are summarized below. 


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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 (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.
Cohort 2 Results:
Pharmacokinetic Results
The PK results from Study GS-US-141-1233 demonstrated that the GS-9883 AUCinf and Cmax
following administration of the 50mg GS-9883 FDC tablets was 79% and 78%, respectively of 
those observed in the same study following co-administration of GS-9883 75 mg single agent 
with F/TAF (200/25 mg) under fasted conditions. The GS-9883 exposures of 50 and 75 mg fixed 
dose combination tablets were approximately dose proportional under fasted and fed conditions, 
and a high fat and moderate fat meal had similar impact on GS-9883 with AUCinf increasing by 
24%. The steady state paIQ95 of GS-9883/F/TAF (50/200/25 mg) was predicted to be 
17 (fasted)-23 (fed). The exposures of TAF and FTC of the 50 mg GS-9883 FDC were similar 
to those of GS-9883 75 mg single agent with F/TAF FDC, and the food effect on TAF and FTC 
was similar to the historical results.  
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 2, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.


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1.6.
Information about Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC
Triumeq®)
For more detailed information, refer to the current Prescribing Information and local product 
labeling for abacavir/dolutegravir/lamivudine.
1.7.
Rationale for this Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 
HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.
The GS-9883/F/TAF FDC has the potential to offer a simple, once-daily regimen containing a 
second generation INSTI that provides a high barrier to resistance, does not require a boosting 
agent, and offers an effective and safer alternative to standard nucleos(t)ide based regimens, 
without the need for HLA testing or close monitoring of renal or bone toxicities. It could provide 
a FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute to an
increased risk of cardiovascular events, could be used in patients with chronic hepatitis B or C 
infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities.
The objective of this study is to evaluate the safety and efficacy of a FDC containing 
GS-9883/F/TAF versus ABC/DTG/3TC. ABC/DTG/3TC was selected as the active comparator 
for this study as it is a second-generation integrase inhibitor-based, once-daily fixed dose 
combination, and is a DHHS Guidelines preferred regimen. Use of ABC/DTG/3TC as a 
comparator in this study will therefore allow comparison of two single tablet regimens
containing second generation, unboosted INSTIs.
1.8.
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: hypersensitivity 
reaction to abacavir and allergy to any components of the tablets. Some observational studies 
have shown increased risk of cardiovascular disease with abacavir. Interim data will also be 
reviewed by an independent data monitoring committee. 


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Following a chronic 39 week study in monkeys, animals administered the highest dose of 
GS-9883 (1000 mg/kg/day) had bile duct hyperplasia (increased cell growth) and hypertrophy 
(increased cell size), and some increased cell growth and inflammation in nearby liver cells. 
These effects were not seen in monkeys administered the mid-level dose (200 mg/kg/day), and 
these animals had plasma GS-9883 exposures that were approximately 5-fold above human 
exposures when given the  GS-9883/F/TAF FDC. No adverse drug reactions associated with 
liver or bile duct problems has been identified in humans treated with GS-9883. Potential 
hepatobiliary toxicity is appropriately managed by study inclusion/exclusion criteria, close 
clinical and laboratory monitoring, as well as specific toxicity management guidance to 
investigators (Refer to Section 7.5.5).
Potential benefits of GS-9883 may include provision of a new antiretroviral therapy that is not 
currently available and which may have fewer side effects than alternative therapies. Other 
potential benefits include provisions of fixed dose combination therapy, and the knowledge that 
patient participation will contribute to the body of knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF and ABC/DTG/3TC is favorable at this 
time.
1.9.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC. 


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GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady 
State Following GS-9883 Administration Under Fasting Conditions 
and Corresponding Protein-Adjusted IQ95 Values
GS-9883 dose
n
Median (range) Ctau,SS (ng/mL)
Median (range) paIQ95a
5 mg
4
206.5 (146.0 – 342.0)
1.3 (0.9 – 2.1)
25 mg
4
797.5 (714.0 – 1900.0)
4.9 (4.4 – 11.7)
50 mg
4
2170.0 (852.0 – 3020.0)
13.4 (5.3 – 18.6)
100 mg
4
4190.0 (3730.0 – 5970.0)
25.9 (23 – 36.9)
a.
The paIQ95 value is estimated based on steady-state Ctau values and the in vitro paIC95 value for wild-type HIV-1 
(162 ng/mL).
Source: Data on File
Single-agent GS-9883 was well tolerated at all doses administered. The range of GS-9883 
plasma exposure at steady state (Ctau,SS) observed in the 50-mg cohort correlated with protein 
adjusted 95% inhibitory quotient (paIQ95) values ranging from 5.3 to 19, while the range of 
GS-9883 plasma exposure at steady state (Ctau,SS) observed in the 100-mg cohort correlated with 
paIQ95 values ranging from 23 to 37 Table 1-5).
Based on PK/PD analyses, exposure following a 75-mg dose of single-agent GS-9883 is 
expected to provide near-maximal virologic response, with a predicted paIQ95 of approximately 
20, providing considerable coverage above the target concentration of 162 ng/mL (paIC95).
GS-9883 (75 mg) single agent coadministered with F/TAF (200/25 mg) is currently being 
evaluated in a Phase 2 study, GS-US-141-1475 (GS-9883+F/TAF vs DTG+F/TAF). The 
Week 24 data from this study support the safety and efficacy of GS-9883 exposures obtained 
with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF was developed for use in Phase 3 studies. 
Preliminary results from the relative bioavailability (rBA) study (GS-US-141-1233) of 
GS-9883/F/TAF (75/200/25 mg) showed that GS-9883 plasma exposure was higher (with Cmax
and AUCinf increase of 31% and 27%, respectively) following administration of the FDC as 
compared with exposure following administration of GS-9883 (75 mg) + F/TAF (200/25 mg) 
under fasted conditions. The increase in GS-9883 exposures associated with the FDC 
formulation results in an estimated mean paIQ95 of 24.3, compared to an estimated mean paIQ95
of 19.2 for the GS-9883 (75 mg) single agent coadministered with F/TAF, in the fasted state.


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In order to bridge exposures of GS-9883 in the FDC to the exposure observed with GS-9883 
75 mg administered as a single agent, and to bridge to the safe and effective exposures observed 
in the Phase 2 study GS-US-141-1475, a lower strength GS-9883/F/TAF FDC was developed for 
use in the Phase 3 studies. Comparability of GS-9883 exposures was confirmed in an rBA study 
of GS-9883/F/TAF (50/200/25 mg) and GS-9883 (75 mg) + F/TAF prior to initiation of dosing 
in the Phase 3 studies.
1.10.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) containing 
GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral 
treatment naïve-adult subjects as determined by the achievement of HIV-1 RNA 
< 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the two treatment groups through 
Weeks 48 and 96, and 144

To evaluate the bone safety of the two treatment groups as determined by the percentage 
change from baseline in hip and spine BMD through Weeks 48 and 96, and 144

To evaluate the long term efficacy and safety of FDC GS-9883/F/TAF through OL Weeks 48 
and 96.


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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint is:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 as defined 
by the US FDA-defined snapshot algorithm
The secondary endpoints of this study include:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 as 
defined by the US FDA-defined snapshot algorithm

the proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96,
and 144 as defined by the US FDA-defined snapshot algorithm

the change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, and 144

the percentage change from baseline in hip and spine BMD at Weeks 48, 96, and 144

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 OL and 96 
OL as defined by Missing = Excluded and Missing = Failure algorithm

the change from baseline in CD4+ cell count at Weeks 48 OL and 96 OL. 
3.2.
Study Design
This protocol describes a randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus ABC/DTG/3TC FDC in HIV-1 
infected, antiretroviral treatment-naïve adult subjects.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food
(n=300)


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Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. Ex-US) at randomization.
3.4.
Duration of Treatment
Subjects will be treated for at least 144 weeks during the blinded treatment phase.  After 
Week 144, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic 
(preferably within 30 days) for an End of Blinded Treatment Visit. At the End of Blinded 
Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension 
phase for 96 weeks (Week 96 OL). After Week 96 OL, subjects will discontinue the study drug, 
transition onto commercially available treatment and complete a 30-Day Follow-up Visit. In a 
country where GS-9883/F/TAF is not available, subjects  will be given the option to continue OL 
GS-9883/F/TAF until the product becomes accessible to subjects through an access program, or 
until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.
All subjects participating in the open label extension phase, without regard to their blinded 
treatment regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for
at least 96 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit. 
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.


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


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3.5.2.
Additional Sample Storage
 
 
CCI


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 600 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Age 18 years
3) Antiretroviral treatment naïve (≤ 10 days of prior therapy with any antiretroviral agent 
following a diagnosis of HIV-1 infection) except the use for PrEP (pre-exposure prophylaxis) 
or PEP (post-exposure prophylaxis), up to one month prior to screening
4) Plasma HIV-1 RNA levels 500 copies/mL at screening
5) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥0.83 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft 1976}:
i)
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) 
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
ii) Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)
0.85 CLcr 
(mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8) Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin


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9) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥ 0.75 GI/L); 
platelets ≥50,000/mm3 (≥ 50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))
10) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11) Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 7) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12) Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 7) throughout the study period and for 
90 days following the last dose of study drug
13) Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14) Life expectancy ≥ 1 year
15) Screening genotype report must show sensitivity to FTC, TFV, 3TC, and ABC. This report 
will be provided by Gilead Sciences. Alternatively, if genotype results from a local 
laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, 
this genotype will be acceptable to fulfill this inclusion criterion in the event that the 
genotype obtained at screening is not yet available and all other inclusion/exclusion criteria 
have been confirmed.
16) Negative screening test for HLA-B*5701 allele provided by Gilead Sciences. Alternatively, 
if HLA-B*5701 results are available from a local laboratory prior to screening, this report 
will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result 
obtained at screening is not yet available and all other inclusion/exclusion criteria have been 
confirmed.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 6)
2) Subjects experiencing decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal 
bleeding)


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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 (e.g, 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
6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
7) Participation in any other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC or ABC/DTG/3TC FDC 
tablets
10) Females who are pregnant (as confirmed by positive serum pregnancy test)
11) Females who are breastfeeding
12) Subjects receiving ongoing therapy with any of the following medications in the table below, 
including drugs not to be used with FTC, TAF, GS-9883, DTG, ABC and 3TC
Drug Class
Agents Disallowed*
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study.


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13) Acute hepatitis in the 30 days prior to study entry
14) Chronic Hepatitis B Virus (HBV) infection, as determined by either:
a) Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit
b) Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
15) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until the Investigator has received the results of the allele testing and 
screening genotype report and subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening and region (US vs. Ex-US) at randomization.
The IWRS will assign study drug bottle numbers of blinded FDC of GS-9883/F/TAF + Placebo 
to match FDC of ABC/DTG/3TC or FDC of ABC/DTG/3TC + Placebo to match FDC of
GS-9883/F/TAF at each study visit for each subject.
At the End of Blinded Treatment Visit the IWRS will assign open-label GS-9883/F/TAF FDC.
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject or in the case of pregnancy that occurs while on study drug, the investigator may 
obtain treatment assignment directly from the IWRS system for that subject. Gilead strongly 
recommends but does not require that the investigator contact the Gilead medical monitor before 
breaking the blind. Treatment assignment should remain blinded unless that knowledge is 
necessary to determine subject emergency medical care or in the event of pregnancy that occurs 
while on study drug. The rationale for unblinding must be clearly explained in source 
documentation and on the electronic case report form (eCRF), along with the date on which the 
treatment assignment was obtained. The investigator is requested to contact the Gilead medical 
monitor promptly in case of any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Pharmacovigilance and Epidemiology (PVE) may independently unblind cases for 
expedited reporting of suspected unexpected serious adverse reactions (SUSARs).


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5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.
The placebo to match (PTM) GS-9883/F/TAF tablets are capsule-shaped, film-coated 
purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the other side and 
are identical in physical appearance to GS-9883/F/TAF tablets. The placebo tablets contain 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. 
The tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, 
polyvinyl alcohol, talc, and titanium dioxide.
5.2.1.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
Abacavir 600 mg/Dolutegravir 50 mg/Lamivudine 300 mg tablets are oval, film coated purple, 
and debossed with “572 Tri” on one side. Each tablet core contains 600 mg of abacavir, 50 mg of 
dolutegravir, and 300 mg of lamivudine. In addition to the active ingredients, the 
ABC/DTG/3TC tablets contain the inactive ingredients D-mannitol, magnesium stearate, 
microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet cores are film 
coated with iron oxide black, iron oxide red, polyethylene glycol, polyvinyl alcohol, talc, and 
titanium oxide.
The PTM ABC/DTG/3TC tablets are oval, film coated purple, and debossed with “572 Tri” on 
one side. The placebo tablets are identical in physical appearance to ABC/DTG/3TC tablets. The 
placebo tablets contain microcrystalline cellulose, lactose monohydrate, croscarmellose sodium 
and magnesium stearate. The tablet cores are film-coated with iron oxide black, iron oxide red, 
polyethylene glycol, polyvinyl alcohol, talc, and titanium oxide.


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883/F/TAF tablets and PTM GS-9883/F/TAF tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester 
packing material.  Each bottle is enclosed with a white, continuous thread, child-resistant 
polypropylene screw cap with an induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations
5.2.2.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
ABC/DTG/3TC tablets and PTM ABC/DTG/3TC tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets and silica gel desiccant. Each bottle 
is enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both 
FDCs should be stored at controlled room temperature of 25°C (77°F); excursions are permitted 
between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label. Until 
dispensed to the subjects, all bottles of study drugs should be stored in a securely locked area, 
accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.


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5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide 
and Abacavir/Dolutegravir/Lamivudine
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both
FDCs will be provided by Gilead Sciences.
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food. 
After the End of Blinded Treatment Visit, all subjects who choose to participate in the open label 
extension will receive GS-9883/F/TAF FDC once daily.
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability. The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return.
5.4.
Prior and Concomitant Medications
5.4.1.
Prior and Concomitant Medications (Blinded Phase through End of Blinded 
Treatment Visit)

The use of medications for the treatment of HIV, other than study drug, is prohibited.

Medications listed in the following table and use of herbal/natural supplements are excluded 
or should be used with caution while subjects are participating in the study. Subjects will 
refrain from consumption of grapefruit juice and Seville orange juice throughout 
participation in the study.


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Table 5-1.
Prior and Concomitant Medications (Blinded Phase through End of 
Blinded Treatment Visit)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids (eg, Tums or 
Rolaids); the ulcer medication sucralfate (Carafate); 
or vitamin or mineral supplements that contain 
calcium, iron or zinc for a minimum of 6 hours 
before and 2 hours after any dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, 
Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural 
Supplements
St. John’s Wort, Echinaccea
Oral Hypoglycemic Agent
Metformin: close monitoring is recommended. A 
dose adjustment of Metformin may be necessary.  
Limit total daily doses of Metformin to 1000mg 
when initiating study medication or if initiating 
metformin while on study drug.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Sciences Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead Sciences as soon as he/she is aware of the use of the excluded 
medication.
5.4.2.
Prior and Concomitant Medications (Open-Label Rollover Extension Phase)
The use of medications for the treatment of HIV-1 infection, other than GS-9883/F/TAF, is 
prohibited.
Medications listed in the following table and use of herbal/natural supplements are excluded or 
should be used with caution while participants are participating in the study.  This list should be 
utilized in jurisdictions in which GS-9883/F/TAF has NOT been approved.


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Table 5-2.
Prior and Concomitant Medications (Open-Label Rollover Extension 
Phase)
Drug Class
Agents Disallowed*
To Be Used With Caution
Medications or oral 
supplements containing 
polyvalent cations 
(e.g., Mg, Al, Ca, Fe): 
Calcium or iron 
supplements 
Cation-containing antacids 
or laxatives 
Buffered medications
Antacids containing Al/Mg or Calcium:
GS-9883/F/TAF can be taken under fasting 
conditions 2 hours before antacids containing 
Al/Mg or calcium.
Routine administration of GS-9883/F/TAF 
simultaneously with, or 2 hours after, antacids 
containing Al/Mg or calcium is not 
recommended.
Supplements containing Calcium or Iron:
GS-9883/F/TAF and supplements containing 
calcium or iron can be taken together with food. 
Routine administration of GS-9883/F/TAF under 
fasting conditions simultaneously with, or 
2 hours after, supplements containing calcium or 
iron is not recommended.
Antiarrhythmic Agent
dofetilide
Anticonvulsants
phenobarbital, phenytoin, 
carbamazepine, oxcarbazepine
Antimycobacterials
rifampin, rifapentine, rifabutin
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
Hypoglycemic agent
Metformin:
Refer to the prescribing information of 
metformin for assessing the benefit and risk of 
concomitant use of BIKTARVY and metformin.
Herbal/Natural 
Supplements
St. John’s Wort
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study. 
In jurisdictions in which GS-9883/F/TAF has been approved, consult the local prescribing 
information for GS-9883/F/TAF dose recommendations with concomitant medications.
Should participants have a need to initiate treatment with any excluded concomitant medication, 
the Gilead Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead as soon as he/she is aware of the use of the excluded medication.


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5.5.
Accountability for Investigational Medicinal Product (IMP)
The investigator is responsible for ensuring adequate accountability of all used and unused IMP.
This includes acknowledgement of receipt of each shipment of IMP (quantity and condition). All 
used and unused IMP dispensed to subjects must be returned to the site.
Study Drug accountability records will be provided to each study site to:

Record the date received and quantity of IMP kits

Record the date, subject number, subject initials, the IMP kit number dispensed

Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
Study drug return and disposal will be performed as outlined in Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that subjects are eligible for study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events, smoking history
and prior medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.


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Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)       CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) 
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
HLA-B*5701
Plasma HIV-1 RNA
Hepatitis B virus surface antigen serology (HBsAg)
Hepatitis B surface antibody (HBsAb)
Hepatitis B virus core antibody (HBcAb)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.
HIV-1 genotype testing (protease and reverse transcriptase). The HIV-1 PR/RT genotype 
testing may not be performed for subjects that fail to meet other screening criteria.

Review of adverse events and concomitant medications
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for the Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. See 
Section 7 Adverse Events and Toxicity Management for additional details.


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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 
received the results from the allele testing and screening genotype report and confirmed 
eligibility before proceeding with the Day 1 visit. The subject must complete all study 
procedures, except DXA, before being administered the study drug:

DXA Scan (spine and hip).  For subjects in Germany, DXA scans will not be performed.
The DXA scan will be performed on subjects once eligibility is confirmed. The scan may 
be performed prior to or within 24 hours of the Day 1 Visit.

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject.  Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN) and TSH
CCI


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Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA 
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163  
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand
Plasma storage sample for safety, virology, or PK testing
 
 
 
 

Provide subject dosing diary to all subjects

Dispense study drug.

Observed first dose administration of the assigned study drugs as described in Section 5.3

Subjects should be instructed to take study drugs without regard to food. The subject should 
be counseled regarding the importance of adherence and taking their study medications at 
approximately the same time each day as directed by the Investigator.
CCI


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6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 - 144)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, 48, 60, 72, 
84, 96, 108, 120, 132, and 144 unless otherwise specified.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 132, unless otherwise specified.  The visit window at Weeks 48, 96, and 144 will 
be ± 6 weeks of the protocol-specified visit date, and these clinical visit windows coincide with 
the Week 48, 96, and Week 144 statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (Weeks 24, 48, 96
and 144 ±10 days). For subjects in Germany, DXA scans will not be performed.

Complete physical examination (Weeks 24, 48, 96, and 144) (urogenital/anorectal exams 
will be performed at the discretion of the Investigator) or symptom-directed physical 
examination as needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Weeks 24, 48. 96, and 144)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject at Weeks 4, 12 and 48.  Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.


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
Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin. (Weeks 24, 48, 72, 96, 120, and 144)
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 12, 24, 48, 72, 96, 120, and 144 analyses of glucose will be done as part of the 
fasting metabolic assessments and not as part of the chemistry profile. At Weeks 24, 48, 
72, 96, 120, and 144 TSH will also be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24, 48, 72, 96, 120, and 144)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (Weeks 24, 48, 72, 96, 120, 
and 144)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (Weeks 24, 48, 72, 96 120, and 144)
Hepatitis B virus surface antigen serology (HBsAg). Subjects who have HBVsAg 
positive will have a reflex test for HBV DNA (viral load). Hepatitis B surface antibody 
(HBsAb). Hepatitis B virus core antibody (HBcAb). (Weeks 48, 96, and 144)
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Hepatitis C virus (HCVAb) serology. Subjects who are Hepatitis C virus antibody 
(HCVAb) positive will have a HCV RNA test performed. (Weeks 48, 96, and 144)
Plasma storage sample for safety, virology, or PK testing

Pharmacokinetic Blood Collection for subjects who are on study drug. Details of 
pharmacokinetic blood sampling procedures and sample management will be documented in 
the Pharmacokinetic Sample Collection, Processing, Storage, and Shipment Manual.
Single Anytime, Trough and Post Dose PK Samples for all subjects on study drug:
■
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 and 36.
■
Observed dosing at the clinic: Subjects will have a trough PK blood sample collected 
between 20-28 hours following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study drugs on the morning of their visit for the trough 
sample collection.   Subjects will then take an observed dose of study drug at the 
clinic.  A single post dose PK blood sample will be collected between 1 and 4 hours 
post dose. If the subject has taken their dose of study drugs prior to the visit, the visit 
may proceed, but the subject must return within 72 hours for the trough PK blood 
sample collection.  In the event a subject routinely takes their study drug in the 
evening, a single post dose sample may be drawn at Weeks 4 and 12 as the subject 
will not be instructed to change their dosing time to accommodate this trough PK 
draw.
■
Dosing diaries will be collected from subjects for the single anytime PK and trough 
PK collection.  If a dosing diary is not returned the site may ask the subject for the 
time of the last dose and if it was taken with or without food.
 
 
 
 
 
 
 
 
 
 
 
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
Provide subject dosing diary to all subjects (Weeks 4, 8, 12 and 24)

Document study drug dispensation and accountability for all study drugs dispensed.

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.14.1 and Section 6.14.2
6.5.
Treatment Assessments (Post Week 144 until the Open Label Rollover 
Extension)
6.5.1.
Post Week 144 Assessments
After Week 144, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic 
(preferably within 30 days) for an End of Blinded Treatment Visit. Study visits are to be 
completed within 6 days of the protocol-specified visit date unless otherwise specified.

Review of AEs and changes in concomitant medications

Complete physical examination (every 48 weeks) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (every 48 weeks)

Urine collection for the following laboratory procedures:
Urinalysis 
Urine 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, the subject will be 
discontinued.
CCI
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Amendment 3
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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (every 24 weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (every 24 weeks)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (every 24 weeks)
Hepatitis B virus surface antigen serology (HBsAg). Subjects who have HBVsAg 
positive will have a reflex test for HBV DNA (viral load). Hepatitis B surface antibody 
(HBsAb). Hepatitis B virus core antibody (HBcAb). (every 48 weeks)
Hepatitis C virus (HCVAb) serology. Subjects who are Hepatitis C virus antibody 
(HCVAb) positive will have a HCV RNA test performed. (every 48 weeks)
Plasma storage sample for safety, virology, or PK testing

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Sections 6.14.1 and 6.14.2.

Document study drug dispensation and accountability for all study drugs dispensed.


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6.5.2.
End of Blinded Treatment Visit
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, 
all subjects will return to the clinic (preferably within 30 days) for an End of Blinded Treatment 
Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an 
open label (OL) extension phase for 96 weeks (Week 96 OL). After Week 96 OL, subjects will 
discontinue the study drug, transition onto commercially available treatment and complete a 
30-Day Follow-up Visit. In a country where GS-9883/F/TAF is not available, subjects will be 
given the option to continue OL GS-9883/F/TAF until the product becomes accessible to 
subjects through an access program, or until Gilead Sciences elects to discontinue the study in 
that country, whichever occurs first.
Subjects who receive the open-label GS-9883/F/TAF FDC will return for study visits every 
12 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit. 
Subjects who have discontinued drug study prior to the End of Blinded Treatment Visit will not 
be eligible for the open-label rollover extension; these subjects will be asked to continue 
attending the scheduled study visits through the End of Blinded Treatment Visit and discontinue 
the study after the End of Blinded Treatment Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
The following will be performed at the End of Blinded Treatment Visit:

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (±10 days) if last scan was 
acquired > 12 weeks from the date of the end of blinded treatment visit. For subjects in 
Germany, DXA scans will not be performed.

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


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
Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin.
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN), and TSH
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand
Plasma storage sample for safety, virology, or PK testing

Document study drug dispensation, if applicable and accountability for all study drugs 
dispensed

Subjects who wish to continue in the Open-Label Rollover extension study will receive open 
label GS-9883/F/TAF FDC.
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6.5.3.
Treatment Assessments (Open-Label Rollover Extension)
For purposes of study visit identification during the open-label rollover extension, study visits 
will be identified by the number of weeks that have elapsed between the End of Blinded 
Treatment Visit and the corresponding open-label study visit, and labeled with “OL” 
(eg. Week 12 OL, Week 24 OL, etc.)
All subjects participating in the open label extension phase, without regard to their blinded 
treatment regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for 
96 weeks.
Study visits are to be completed within ± 6 days of the protocol-specified visit date every 
12 weeks thereafter, unless otherwise specified.
The following will be performed at the Open-Label Extension Visit:

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for subjects who were randomized to GS-9883/F/TAF, completed 
the blinded phase and entered the OL extension phase (Weeks 48 and 96 OL ±10 days). For 
subjects in Germany, DXA scans will not be performed.

Complete physical examination (Week 48 OL, Week 96 OL) (urogenital/anorectal exams 
will be performed at the discretion of the Investigator) or symptom-directed physical 
examination as needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Week 48 OL, Week 96 OL)

Urine collection for the following laboratory procedures:
Urinalysis 
Urine 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, the subject will be 
discontinued.
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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Week 24 OL, = 48 OL, 72 OL and 96 OL, analyses of glucose will be done as part of 
the fasting metabolic assessments and not as part of the chemistry profile. In addition, 
TSH will also be analyzed at Week 24 OL48 OL, 72 OL and 96 OL.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Week 24, 48, 72 and 96 OL)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Hepatitis B virus surface antigen serology (HBsAg). Subjects who have HBVsAg 
positive will have a reflex test for HBV DNA (viral load). Hepatitis B surface antibody 
(HBsAb). Hepatitis B virus core antibody (HBcAb). (Week 48 and Week 96 OL)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed. (Week 48 and Week 96 OL)
Plasma storage sample for safety, virology, or PK testing

Document study drug dispensation and accountability for all study drugs dispensed.

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Sections 6.14.1 and 6.14.2.
6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
Subjects who have discontinued study drug prior to the End of Blinded Treatment Visit will not 
be eligible for the open-label rollover extension; these subjects will be asked to return to the 
clinic within 72 hours of stopping the study drug for the Early Study Drugs Discontinuation 
Visit. The subject will be asked to continue attending the scheduled study visits through the End 
of Blinded Treatment Visit and discontinue the study after the End of Blinded Treatment Visit.


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If the subject discontinues study drug during the Open Label rollover extension, the subject will 
be asked to return to the clinic within 72 hours of stopping the study drug for the Early Study 
Drugs Discontinuation Visit.
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will 
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns 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

DXA scan required (spine and hip) for all subjects who are on study drug (±10 days) if last 
scan was acquired > 12 weeks from the date of the ESDD Visit (blinded treatment phase 
only).   For subjects in Germany, DXA scans will not be performed.

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine (blinded treatment phase only)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH
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 storage sample for safety, virology, or PK testing
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30 Day Follow Up
Subjects who prematurely discontinue study drug during the blinded phase and refuse to 
continue in the study through the End of Blinded Treatment Visit will be asked to return to the 
clinic 30 days after the completion of the Early Study Drugs Discontinuation Visit for the 
30-Day Follow-Up Visit.
Those subjects who prematurely discontinue study drug during the blinded phase and 
continue in the study through at least one subsequent visit after the Early Study Drugs 
Discontinuation Visit will not be required to complete the 30-Day Follow-Up Visit.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Subjects who prematurely discontinue study drug during the Open Label rollover extension will 
be asked to return to the clinic 30 days after the completion of the Early Study Drugs 
Discontinuation Visit for the 30-day Follow-Up Visit. The subject will not continue attending the 
scheduled study visits.
Subjects who complete the Open Label rollover extension will be asked to return to the clinic 
30 days after the completion of study drugs for the 30-day Follow-Up Visit.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight 

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.


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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly (or as 
often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained.
6.7.
Criteria for Discontinuation of Study Treatment
Study medication will be discontinued in the following instances:

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Subject request to discontinue for any reason

Pregnancy during the study; refer to Appendix 7

Development of active tuberculosis infection
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator

Lack of efficacy

Subject noncompliance

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)


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6.8.
Bone Mineral Density Evaluations
For all subjects who are on study drug, excluding those enrolled in sites based in Germany, dual 
energy x-ray absorptiometry (DXA) scans will be performed prior to or within 24 hours of 
Day 1, Weeks 24, 48, 96, 144, End of Blinded Treatment Visit and the Early Study Drug 
Discontinuation Visit (if the last scan was acquired > 12 weeks from the date of the ESDD Visit)
during the blinded treatment phase. DXA will be performed at Week 48 OL and Week 96 OL for 
subjects who were randomized to GS-9883/F/TAF, complete the blinded phase and enter the OL 
extension phase, excluding subjects located in Germany.  Scans will cover the spine and hip to 
measure changes in bone mineral density. DXA scan results will be provided to study sites.
A complete description of the procedures performed for the DXA scans will be provided in a 
DXA manual.
6.9.
Other Evaluations
6.9.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include urine albumin, urine creatinine, urine protein,  retinol binding protein and 
beta-2-microglobulin at Day 1 Visit, Weeks 24, 48, every 24 weeks post Week 48, the End of 
Blinded Treatment Visit, and OL Weeks 24, 48, 72 and 96. Samples may be stored for a period 
of 15 years at the end of the study.
6.9.2.
Markers of Inflammation and Immune Activation
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48, and the End of Blinded Treatment Visit for selected evaluations of inflammation and 
immune activation, which may include but not limited to cystatin-C, IL 6, hs CRP, d-dimer, 
sCD14, and sCD163. Samples may be stored for a period of 15 years at the end of the study.
6.9.3.
Markers of Platelet Function
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48, and the End of Blinded Treatment Visit for selected evaluations of platelet function,
which may include but not limited to soluble glycoprotein VI (sGPVI), P-selectin, and soluble 
CD40 ligand. Samples may be stored for a period of 15 years at the end of the study.
 
 
 
 
 
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6.11.
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.
6.12.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.13.
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.
6.14.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation, Week 48, Week 96, Week 144, Week 48 OL or Week 96 OL.
6.14.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any visit, after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA 
≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled 
visit; OR

At any visit, a 1 log10 increase in HIV-1 RNA from the nadir which is subsequently 
confirmed at the following scheduled or unscheduled visit
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing. Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-baseline resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.
If no resistance is detected from the genotype or phenotype, the subject may remain on study 
drugs and a repeat HIV-1 RNA should be repeated (2 to 3 weeks after date of test with HIV-1 
RNA ≥ 50 copies/mL). Investigators should carefully evaluate the benefits and risks of 
remaining on study drug for each individual subject and document this assessment in the on-site 
medical record.


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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.
Figure 6-1.
Virologic Rebound Schema
a
If virologic rebound is not confirmed, the subject will remain on their current regimen.
b
If virologic rebound is confirmed and the HIV-1 RNA is ≥ 200 copies/mL, the HIV-1 genotype and phenotype (reverse 
transcriptase, protease and integrase) will be analyzed.
c
Based on the results of the genotypic and phenotypic assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping assay fails, a new ARV regimen may be configured at the discretion of the 
Investigator.
d
If no resistance is detected, HIV-1 RNA will be repeated (2-3 weeks later).  Investigator reviews study drug 
continuation/discontinuation options and discusses with the Medical Monitor prior to study drug discontinuation
e
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study.


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6.14.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48, Week 96, Week 144, Week 48 OL or Week 96 OL
Subjects with HIV-1 RNA ≥ 50 copies/mL at study discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48, Week 96,
Week 144, Week 48 OL or Week 96 OL will be asked to return for an unscheduled visit within 
the visit window for a retest.
Subjects with HIV-1 RNA ≥ 200 copies/mL at study drug discontinuation, last visit, Week 48, 
Week 96, Week 144, Week 48 OL or Week 96 OL will also have resistance testing conducted.


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.6.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is 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 (e.g., 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, (e.g., venipuncture)
7.2.2.
Assessment of Severity
AE severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 5). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events.
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the eCRF:

all SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events 
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30-days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.


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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Pharmacovigilance and Epidemiology (PVE) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30-days of the 
last dose of study IMP, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period; 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of IMP, he/she should promptly document and report 
the event to GileadPVE.
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 PVEwithin 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study start), record the 
SAE on the paper serious adverse event report form and submit by e-mail or fax within 
24 hours of the investigator’s knowledge of the event to:
Gilead PVEcontact information:
Email:
Fax:

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.
PPD
PPD


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
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/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 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, EU Summary of Product Characteristics 
(SmPC), or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 4 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 5).

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat
testing within 3 calendar days of receipt of results and before investigational medicinal 
product discontinuation, unless such a delay is not consistent with good medical practice

Any questions regarding toxicity management should be directed to the Gilead Medical 
Monitor.


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7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, investigational 
medicinal product may be continued if the event is considered to be unrelated to
investigational medicinal product.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to investigational medicinal product, 
investigational medicinal product will be withheld until the toxicity returns to Grade 2.When 
restarting investigational medicinal product following resolution of the adverse event, the 
investigational medicinal product should be restarted at full dose upon discussion with the 
Gilead Sciences Medical Monitor.

If a laboratory abnormality recurs to Grade 3 following rechallenge with investigational 
medicinal product and is considered related to investigational medicinal product, then 
investigational medicinal product will be permanently discontinued and the subject managed 
according to local practice. Recurrence of laboratory abnormalities considered unrelated to 
investigational medicinal product may not require permanent discontinuation but requires
discussion with the Gilead Sciences Medical Monitor.
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event

For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to investigational medicinal product, 
investigational medicinal product will be permanently discontinued and the subject managed 
according to local practice. The subject should be followed as clinically indicated until the 
laboratory abnormality returns to baseline or is otherwise explained, whichever occurs first. 
A clinically significant Grade 4 laboratory abnormality that is not confirmed by repeat testing 
should be managed according to the algorithm for the new toxicity grade.

Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant Grade 4 laboratory abnormality (eg, Grade 4 CK after strenuous exercise, or 
triglyceride elevation that is nonfasting or that can be medically managed) or a clinical event 
considered unrelated to investigational medicinal product requires discussion with the 
Gilead Sciences Medical Monitor.
7.5.4.
Management of Possible Abacavir Hypersensitivity Reaction
Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to increased 
risk of hypersensitivity reaction, unless no other therapeutic option is available based on the 
treatment history and resistance testing.


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In a clinical study, 3.4 % of subjects with a negative HLA-B*5701 status receiving abacavir 
developed a hypersensitivity reaction. Therefore, even in the absence of HLA-B*5701 allele, it is 
important to permanently discontinue abacavir and not rechallenge with abacavir if a 
hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe 
or even fatal reaction.
Hypersensitivity reactions are characterized by the appearance of symptoms indicating 
multi-organ system involvement. Almost all hypersensitivity reactions will have fever and/or 
rash as part of the syndrome. Other signs and symptoms may include respiratory signs and 
symptoms such as dyspnoea, sore throat, cough, and abnormal chest x-ray findings 
(predominantly infiltrates, which can be localized), gastrointestinal symptoms, such as nausea, 
vomiting, diarrhea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as 
respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis. Other frequently 
observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and 
musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia). The symptoms related to this 
hypersensitivity reaction worsen with continued therapy and can be life-threatening. 
These symptoms usually resolve upon discontinuation of abacavir.
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. Patients 
should be monitored closely, especially during the first two months of treatment with abacavir.
Regardless of their HLA-B*5701 status, patients who are diagnosed with a hypersensitivity 
reaction whilst on therapy MUST discontinue study drug immediately and MUST NEVER be 
restarted. Restarting study drug following a hypersensitivity reaction results in a prompt return of 
symptoms within hours. This recurrence is usually more severe than on initial presentation, and 
may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimize 
the risk of a life-threatening hypersensitivity reaction, study drug must be permanently 
discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible 
(respiratory diseases, flu-like illness, gastroenteritis or reactions to other medicinal products) 
{Ezzati 2003}.
7.5.5.
Management of Potential Hepatobiliary Toxicity
Monkeys given a high dose (1000 mg/kg/day) for 39 weeks had evidence of biliary hyperplasia 
and hepatocyte hypertrophy on histopathologic examination. The risk to humans given the 
clinical dose of GS-9883 (50 mg/day) is unknown. Investigators should be aware of this potential 
toxicity. Any study subject exhibiting signs/symptoms or laboratory abnormalities suggestive of 
possible hepatobiliary toxicity should undergo thorough examination and clinical workup as 
deemed appropriate by the Investigator, and the Investigator must communicate promptly with 
the Gilead Medical Monitor. Consideration should be given to appropriate imaging studies 
(for example, ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. Management of graded 
laboratory and clinical abnormalities will be managed as outlined in Section 7.5.


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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.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, reports of adverse reactions in infants 
following exposure from breastfeeding, occupational exposure with an adverse event, and 
pregnancy reports regardless of an associated AE.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.


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7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to the Gilead PVE using the pregnancy report form within 24 hours of becoming aware 
of the pregnancy.
The subject’s treatment assignment will be unblinded by the Investigator as described in Protocol 
Section 5.1.1.
Refer to below and the eCRF completion guidelines for full instructions on the mechanism of 
pregnancy reporting.The pregnancy itself is not considered an AE nor is an induced elective 
abortion to terminate a pregnancy without medical reasons.
Any premature termination of pregnancy (e.g., a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead PVE.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. Any complications during pregnancy and the outcome should be reported to Gilead 
PVE using the pregnancy outcome report form. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead PVE. Gilead PVE contact 
information is as follows: Email:
 and Fax: 
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead PVE using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead PVE,
fax number
or email 
Refer to Appendix 7 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications.
PPD
PPD
PPD
PPD


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Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3.2 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 a FDC of GS-9883/F/TAF
versus a FDC of ABC/DTG/3TC in HIV-1 infected, antiretroviral treatment naïve-adult subjects 
as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety and tolerability of the two treatment groups through 
Weeks 48, 96, and 144

To evaluate the bone safety of the two treatment groups as determined by the percentage 
change from baseline in hip and spine BMD through Weeks 48, 96, and 144

To evaluate the long term efficacy and safety of FDC GS-9883/F/TAF through OL Weeks 48 
and 96. 
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 as 
defined by the US FDA-defined snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96,
and 144 as defined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96,
and 144

The percentage change from baseline in hip and spine BMD at Weeks 48, 96, and 144

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 OL 
and 96 OL as defined by Missing = Excluded and Missing = Failure algorithm


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8.2.
The change from baseline in CD4+ cell count at Week 48 OL and 96 OL. 
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 and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis 
set:

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 do not meet the inclusion criterion that the screening genotype report must 
show sensitivity to FTC, TFV, ABC, and 3TC.

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 4.3 including drugs not to be used with 
GS-9883, FTC, TAF, ABC, 3TC, and DTG.

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile


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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
 
 
8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose of 
active GS-9883/F/TAF,  and (3) have at least 1 nonmissing PK concentration data for any
analyte of interest reported by the PK lab.
8.2.1.5.
DXA
8.2.1.5.1.
Hip DXA Analysis Set
The primary analysis set for hip BMD analyses is defined as the Hip DXA analysis set, which 
will include all subjects who (1) are randomized into the study, (2) have received at least 1 dose 
of study drug, and (3) have nonmissing baseline hip BMD value. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.5.2.
Spine DXA Analysis Set
The primary analysis set for spine BMD analyses is defined as the Spine DXA analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have nonmissing baseline spine BMD value. Subjects will be 
grouped according to the treatment they actually received.
CCI


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8.2.1.6.
All GS-9883/F/TAFAnalysis Set
All GS-9883/F/TAFanalysis set will include all subjects who (1) are randomized into the study 
and (2) have received at least 1 dose of the blinded GS-9883/F/TAF or OL GS-9883/F/TAF. 
Subjects will be grouped into two groups: (1) All GS-9883/F/TAF group, including all subjects 
who randomized into GS-9883/F/TAFand received at least 1 dose of GS-9883/F/TAF; 
(2) ABC/DTG/3TC to GS-9883/F/TAF group, including all subjects who randomized to 
ABC/DTG/3TC in the double-blinded phase and received at least 1 dose of OL 
GS-9883/F/TAFin the extension phase. This is the primary analysis set for the all 
GS-9883/F/TAF efficacy and safety analyses.
8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.  Logarithm (base 10) transformation will be 
applied to HIV-1 RNA levels for efficacy analysis.
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (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 (i.e., 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.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.


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8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects who achieve HIV-1 RNA 
50 copies/mL at Week 48 as determined by the US FDA-defined snapshot algorithm. The 
primary analysis of the efficacy endpoint will be based on the FAS.
8.5.1.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378, 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:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window

HIV-1 RNA 50 copies/mL: this includes 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
i)
Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or
ii) Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than adverse event (AE), death, or lack of efficacy and have the last 
available on-treatment HIV-1 RNA 50 copies/mL

No Virologic Data in the Week 48 analysis window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the
following: 
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to AE or 
death (regardless of whether the last available on-treatment HIV-1 RNA < 50 copies/mL 
or not) or,
b) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
c) Missing data during the window but on study drug.


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8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects achieving HIV-1 RNA < 50 copies/mL 
(as defined by the US FDA-defined snapshot algorithm) at Week 48 in GS-9883/F/TAF is at 
least 12% lower than the response rate in ABC/DTG/3TC; the alternative hypothesis is that the 
response rate in GS-9883/F/TAF is less than 12% lower than that in ABC/DTG/3TC.
Non-inferiority will be assessed using the conventional confidence interval approach. The point 
estimate of treatment difference (GS-9883/F/TAF – ABC/DTG/3TC) and the associated 2-sided 
95% confidence interval will be constructed using a normal approximation method based on 
stratified Mantel-Haenszel proportions, where stratification factors include baseline HIV-1 RNA 
level (100,000 copies/mL vs. 100,000 copies/mL) and region (US vs. Ex-US). Note that to 
avoid small or missing cells in analysis strata, CD4+ cell count is not stratified in analysis 
because HIV-1 RNA and CD4+ cell count are highly correlated.
It will be concluded that GS-9883/F/TAF is non-inferior to ABC/DTG/3TC if the lower bound of 
the 2-sided 95% CI of the difference (GS-9883/F/TAF – ABC/DTG/3TC) in the response rate is 
greater than -12%.
If non-inferiority of GS-9883/F/TAF to ABC/DTG/3TC is established, the lower bound of the 
95% CI will be compared to 0; if the lower bound of the 95% CI is greater than 0, then 
superiority of GS-9883/F/TAF over ABC/DTG/3TC will be established.
8.5.2.
Secondary Analyses
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 and 
the proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96, and 144, as 
defined by the US FDA-defined snapshot algorithm, will be analyzed using the same method as 
for the primary efficacy endpoint.
The changes from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, and 144 
will be summarized by treatment using descriptive statistics. The differences in changes from 
baseline in log10 HIV-1 RNA and CD4+ cell count between 2 treatment groups and the 
associated 95% confidence intervals will be constructed using ANOVA models, including 
treatment (GS-9883/F/TAF vs. ABC/DTG/3TC), baseline HIV-1 RNA level 
(100,000 copies/mL vs. 100,000 copies/mL), and region (US vs. Ex-US) as fixed effects in 
the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.


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8.5.3.
Efficacy Analyses for All GS-9883/F/TAF Analysis
The following analyses will be conducted for all GS-9883/F/TAF analysis using all 
GS-9883/F/TAF analysis set: (1) the proportion of subjects with HIV-1 RNA < 50 copies/mL by 
Missing = Excluded and Missing = Failure approaches by visit, (2) the change from baseline in 
CD4+ Cell Count by visits, and (3) the change from baseline in CD4 % by visits. No statistical 
comparison will be conducted for all GS-9883/F/TAF analysis. 
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set for the double-blinded phase 
analysis and using all GS-9883/F/TAF analysis set for the all GS-9883/F/TAFanalysis, unless 
specified otherwise.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise will be summarized 
for subjects in the safety analysis set according to the study drug received.
Data for the pretreatment period and the period post the date of last dose of study drug plus 
30 days will be included in data listings for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration page in eCRF. Exposure data will be summarized by treatment.
Duration of exposure to study drug will be expressed as the number of weeks between the first 
and last dose of the study drug, inclusive, regardless of temporary interruptions in study drug 
administration and summarized by treatment.
Dosing information for individual subjects will be listed.
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, 
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On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV, can be found in Appendix 6.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 5.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum post baseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Bone Safety Evaluations
The percentage changes from baseline in hip/spine BMD at Weeks 48, 96, and 144 will be 
summarized by treatment using descriptive statistics. The differences in percentage changes from 
baseline in hip/spine BMD between 2 treatment groups and the associated 95% confidence 
intervals will be constructed using ANOVA models, including treatment as a fixed effect in the 
model. The percentage changes from baseline in hip/spine BMD at OL Weeks 48 and 96 will 
also be summarized using descriptive statistics for subjects randomized to GS-9883/F/TAF 
group.
In addition, missing values for BMD will be imputed using LOCF method and analyzed 
similarly.
8.6.5.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.


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8.7.
Pharmacokinetic Analysis
 
 
 
For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
descriptive statistics or population approaches.
TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.
8.8.
Inflammation, Immune Activation, Platelet and Renal Tubular Function 
Analysis
For each selected test of inflammation, immune activation, platelet function and renal tubular 
function, the percentage change from baseline may be summarized by treatment and visit using 
descriptive statistics. Differences in percentage changes from baseline in each selected test
between the 2 treatment groups will be tested using a Wilcoxon rank sum test.
8.9.
Patient Report Outcomes (PRO)
The PRO measures based on questionnaires (eg, SF-36 and HIV Distress Module) may be 
summarized by treatment and visit using descriptive statistics.
8.10.
Sample Size
A total of approximately 600 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (300 subjects per treatment group), achieves at least 95% power to detect a 
non-inferiority margin of 12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined 
by the US FDA-defined snapshot algorithm) difference between the 2 treatment groups. For the 
sample size and power computations, it is assumed that both treatment groups have a response 
rate of 91% (based on Gilead Studies GS-US-292-0104 and GS-US-292-0111), that the 
non-inferiority margin is 12%, and that the significance level of the test is at a one-sided 
0.025 level. Sample size and power calculations were made using the statistical software package 
nQuery Advisor (Version 6.0).
8.11.
Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after
approximately the first 50% of subjects enrolled have completed their Week 12 visit or 
prematurely discontinued from the study drug, as well as after all subjects have completed 
Week 24 visit or prematurely discontinued from the study drug. However, Gilead will defer to 
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the IDMC for any decision to convene earlier or more frequently. The IDMC will examine the 
safety results of the trial and also focus on logistical issues such as accrual, retention, quality of 
clinical and laboratory data, and implications of results of external studies. Blinding will be 
preserved during the conduct of the study and access to unblinded data will be limited to 
designated parties.
No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
For each IDMC analysis performed prior to the analysis of the primary efficacy endpoint, an 
alpha penalty of 0.00001 will be applied for the primary analysis of the primary endpoint.
8.12.
Analysis Schedule
The Week 48 OL analyses will be conducted after all subjects either complete their Week 48 OL 
visits or prematurely discontinue from the study drug. Final analysis and/or Week 96 OL 
analyses will be performed after all subjects complete the study or prematurely discontinue from 
the study.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject: These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.


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9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IRB- or IEC-approved consent form for documenting 
written informed consent. Each informed consent (or assent as applicable) will be appropriately 
signed and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB or IEC or
local requirements.
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, or laboratory. Laboratory specimens must 
be labeled in such a way as to protect subject identity while allowing the results to be recorded to 
the proper subject. Refer to specific laboratory instructions. NOTE: The investigator must keep a 
screening log showing codes, names, and addresses for all subjects screened and for all subjects 
enrolled in the trial. Subject data will be processed in accordance with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, and any other study information, remain the 
sole and exclusive property of Gilead during the conduct of the study and thereafter. This 
information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
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The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.


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9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF 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. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), 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. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files.
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs or IECs, or to regulatory authority or health authority 
inspectors.


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9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB or IEC 
in accordance with local requirements and receive documented IRB or IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(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.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? 
Curr Med Res Opin 2014;30 (1):89-97.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
Costagliola D. Demographics of HIV and aging. Curr Opin HIV AIDS 2014;9 (4):294-301.
Department for Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents. Developed by the DHHS 
Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working 
Group of the Office of AIDS Research Advisory Council (OARAC). Downloaded 
from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 08 April, 
2015.
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet 
2003;362 (9387):847-52.
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.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised 
surveillance case definitions for HIV infection among adults, adolescents, and 
children aged <18 months and for HIV infection and AIDS among children aged 
18 months to <13 years--United States, 2008. MMWR Recomm Rep 2008;57 
(RR-10):1-12.
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84.
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported adherence supports 
patient preference for the single tablet regimen (STR) in the current cART era. 
Patient preference and adherence 2012;6:427-33.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
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The Joint United Nations Programme on HIV/AIDS (UNAIDS). Fact Sheet: 2014 Global 
Statistics. Available at: 
http://www.unaids.org/sites/default/files/media_asset/20150714_FS_MDG6_Rep
ort_en.pdf.  2014.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
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06 May 2019
11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table (Blinded Phase)
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


PPDPPD
PPD
GS-9883/F/TAF 
Protocol GS-US-380-1489 
Final 
Gilead Sciences, Inc. 
Amendment 3 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 
GS-9883/Em tricitabine/Tenofovir Alafenamide Versus Abacavir/Dolu tegravir/Lamivudine 
in HIV-llufected, Antiretroviral Treatment-Naive Adults 
GS-US-380-1489 Amendment 3, 06 May 2019 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Author 
INVESTIGATOR STATEMENT 
( have read the protocol, including all appendices, and J agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 103 
06 May 2019 


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 104
06 May 2019
Appendix 2.
Study Procedures Table (Blinded Phase)
Study Procedures
Screeninga
Day 1b
4
8
12
24
36
End of Weeke, r
Post-
Week
144e, s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12Weeks
Informed Consent
X
Medical History
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-
Directed Physical 
Exam
X
X
Xd
Xd
Xd
X
Xd
X
Xd
Xd
Xd
X
Xd
Xd
Xd
X
Xx, Xd
X
Xd,f
Xf
12-Lead ECG 
(performed supine)
X
X
X
X
X
X
Xx
X
X
Questionnaires
X
X
X
X
DXA scan (spine & 
hip)g
X
X
X
X
X
X
X
Height
X
Vital signs (blood 
pressure, pulse, 
respiration rate, and 
temperature), 
including Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy 
Testh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy 
Test
X
Chemistry Profilei
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic 
Assessmentsj
X
X
X
X
X
X
X
X
Xt
X


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 105
06 May 2019
Study Procedures
Screeninga
Day 1b
4
8
12
24
36
End of Weeke, r
Post-
Week
144e, s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12Weeks
Estimated 
Glomerular Filtration 
Rate
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HLA-B*5701w
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluations of 
inflammation and 
immune activation, 
platelet function and 
renal tubular function
X
X
X
X
X
X
X
Xt
X
HBV and HCV 
Serology
X
X
X
X
XX
HIV-1 Genotypel
Xl
HIV-1 
Genotype/Phenotypee
Xe
Single PK Samplem
X
X
X
Trough PK Samplesn
X
X
Randomizationv
X
Provide subject 
dosing diary to 
subjects
X
X
X
X
X
CCI
CCI


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 106
06 May 2019
Study Procedures
Screeninga
Day 1b
4
8
12
24
36
End of Weeke, r
Post-
Week
144e, s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12Weeks
Study Drug 
Dispensation
Xb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xu
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures at the Day 1 visit, with the exception of DXA.
c
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
End of Blinded Treatment Visit even if the subject discontinues study drug.
d
Symptom-directed physical examination as needed.
e
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Section 6.14.1 and Section 6.14.2).
f
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained. 
g
DXA scans to be performed in all eligible subjects on study drug during blinded treatment only, except for those in Germany, prior to or within 24 hours of the Day 1 Visit, 
Weeks 24, 48, 96, 144 (±10 days), and at the End of Blinded Treatment Visit (±10 days) and the ESDD visit (if the last scan was acquired > 12 weeks from the date of the 
ESDD Visit).
h
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
i
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN). At Day 1, Weeks 12, 24, 48, 72, 96, 120, 144, and every 24 weeks post Week 144, and End of Blinded Treatment Visit, analyses of glucose will be done as part 
of the fasting metabolic assessments and not as part of the chemistry profile. Additionally: TSH will be analyzed at Screening, Day 1, Weeks 24, 48, 72, 96, 120, 144, and 
every 24 weeks post Week 144, End of Blinded Treatment Visit and Early Study Drugs Discontinuation visit.
j
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
k
CBC with differential and platelet count.
l
The Investigator must have received the results from the screening genotype report before proceeding with the Day 1 visit.  Screening genotype report must show sensitivity 
to TFV, FTC, 3TC and ABC. If genotype results from a local laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype will be 
acceptable to fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been 
confirmed.
CCI


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 107
06 May 2019
m
A single PK blood sample will be collected at any time pre or post-dose
n
A trough PK blood sample will be collected between 20-28 hours following the last dose. Following an observed dose, a single post dose blood sample will be collected 
between 1 and 4 hours post dose.
 
q
Only required for those subjects not enrolling in the open-label rollover extension or those subjects who prematurely discontinue study drugs and do not continue in the study 
through at least one subsequent visit after the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be 
used.
r
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to
Week 132, unless otherwise specified. The visit window at Weeks 48 and 96, 144 will be ± 6 weeks of the protocol-specified visit date.
s
After Week 144, subjects will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit.  Visit window of 6 days 
for study visits post Week 144.  
t
To be performed every 24 weeks after Week 144 until End of Blinded Treatment Visit.
u
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for 96 weeks.
v
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit, provided that all screening procedures have been completed and subject eligibility has been 
confirmed.
w
The Investigator must have received a negative screening test for HLA-B*5701 allele before proceeding with the Day 1 visit. If HLA-B*5701 results are available from a 
local laboratory prior to screening, this report will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result obtained at screening is not yet 
available and all other inclusion/exclusion criteria have been confirmed.
x
To be performed every 48 weeks after Week 144 until the End of Blinded Treatment Visit.
y
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension phase for 96 weeks (Week 96 
OL). After Week 96 OL, subjects will discontinue the study drug, transition onto commercially available treatment and complete a 30-Day Follow-up Visit. In a country 
where GS-9883/F/TAF is not available, subjects  will be given the option to continue OL GS-9883/F/TAF until the product becomes accessible to subjects through an access 
program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first..
CCI
CCI


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 108
06 May 2019
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)
Study Procedures
End of 
Blinded 
Treatment 
Visita
End of Weeke, l, p
30-Day Follow-upk
Early Study 
Drugs DCc
12 
OL
24 
OL
36 
OL
48 
OL
60 
OL
72 
OL
84 
OL
96 
OL
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed Physical 
Exam
X
Xd
Xd
Xd
X
Xd
Xd
Xd
X
Xd,f
Xf
12-Lead ECG (performed supine)
X
X
X
DXA scan (spine & hip)m
X
Xo
Xo
Vital signs (blood pressure, pulse, 
respiration rate, and temperature), 
including Weight
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
X
Estimated Glomerular Filtration Rate
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilej
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
Evaluations of inflammation and 
immune activation, platelet function 
and renal tubular function
X
Xn
Xn
Xn
Xn
HBV and HCV Serology
X
X
HIV-1 Genotype/Phenotypee
Xe
Study Drug Dispensation
Xb
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
X
X
CCI


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 109
06 May 2019
a.
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension phase for 96 weeks (Week 96 
OL). After Week 96 OL, subjects will discontinue the study drug, transition onto commercially available treatment and complete a 30-Day Follow-up Visit. In a country 
where GS-9883/F/TAF is not available, subjects  will be given the option to continue OL GS-9883/F/TAF until the product becomes accessible to subjects through an access 
program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.
b.
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for 96 weeks.
c.
Subjects who discontinue study drug during the open label rollover extension portion of the study will be asked to return to the clinic within 72 hours of stopping study drugs 
for the Early Study Drugs Discontinuation Visit followed by a 30-Day Follow-Up Visit.  The subject will not continue attending the scheduled study visits.
d.
Symptom-directed physical examination as needed.
e.
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Figure 6-1)
f.
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained. 
g.
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN). Weeks 24 OL, 48 OL, 72 OL, 96 OL, and End of Blinded Treatment Visit, analyses of glucose will be done as part of the fasting metabolic assessments and 
not as part of the chemistry profile. For all subjects, TSH will be done at the End of Blinded Treatment Visit, Weeks 24 OL, 48 OL, 72 OL, 96 OL, and Early Study Drug 
Discontinuation Visit.
i.
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
j.
CBC with differential and platelet count.
k.
Subjects who complete the open-label rollover extension will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit.
Subjects who prematurely discontinue study drugs during the open-label rollover extension will be asked to return to the clinic 30 days after the completion of the Early Study 
Drugs Discontinuation Visit for the 30-Day Follow-Up Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used.
l.
Study visits are to be completed within ± 6 days of the protocol-specified visit date every 12 weeks thereafter, unless otherwise specified
m.
DXA scans to be performed in all eligible subjects on study drug, except for those in Germany, only at the End of Blinded Treatment Visit (±10 days).
n.
Only urine albumin, urine creatinine, urine protein, retinol binding protein and beta-2-microglobulin to be collected.
o.
DXA scans to be performed at Weeks 48 OL and 96 OL for subjects who were randomized to GS-9883/F/TAF, complete the blinded phase and enter the OL extension phase, 
except subjects located in Germany.
p.
After Week 96 OL, if subject is in a country where GS-9883/F/TAF is not available, the study procedures completed by the subject will be the same at every 48 weeks 
(i.e. OL Weeks 48, 96) and at every 12 weeks (i.e. OL Weeks 12, 24. 36, 60, 72, 84) until the product becomes accessible to subjects through an access program, or until 
Gilead Sciences elects to discontinue the study in that country, whichever occurs first.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 110
06 May 2019
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Grade 1 
~-----G-ra-d-e-2----~~ 
~~-----G-ra_d_e_3----~~~ ~ ---------G-r-ad-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 confirmed and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
l 
If c 
Repeat lab to 
confirm toxicity 
grade 
l 
mve 
onfirmed and unrelated to 
stigational medicinal products, 
ng may continue at the discretion 
he investigator 
dosi 
oft 
If confirmed and 
possibly or probably 
----+ related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 111
06 May 2019
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 
Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 
Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 
≥ 7 Months# 
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 112
06 May 2019
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects.  Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 113
06 May 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant  <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L
2.0 t o <2.5 mmolL
2.0 mEq/L
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant  <1 Year
>ULN to 6.0 mEq/L
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L 
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 114
06 May 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL
1.74 to <1.94 mmolL
6.1 to  <7.0 mg/dL
1.51 to < 1.74 mmolL
< 6.1 mg/dL
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia (corrected for 
albumin if appropriate*)
Adult and Pediatric 
7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to  <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 115
06 May 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63  to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to <LLN mg/dL
1.12 to <LLN mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia 
Adult and Pediatric 
> 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia 
Adult and Pediatric
≥ 1 year
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 116
06 May 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L
LDL (Fasting)
Adult
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
LDL (Fasting)
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to  4.92 mmol/L
>4.92 mmol/L
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects >70 yrs.  Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 117
06 May 2019
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 118
06 May 2019
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
Females
>ULN - 10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Males
6-10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 h
>1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
>499 to 799 mg/m2/24 h
>799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes:

Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by Covance Laboratory, however for other laboratories, toxicity grades will only be assigned to 
Dipstick Hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.

If the severity of a clinical AE could fall under either one of two grades (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 119
06 May 2019
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Arrhythmia (general)
(By ECG or physical exam)
Asymptomatic AND No 
intervention indicated
Asymptomatic AND 
Non-urgent medical 
intervention indicated
Symptomatic, 
non-life-threatening AND 
Non-urgent medical 
intervention indicated 
Life-threatening arrhythmia 
OR Urgent intervention 
indicated
Cardiac-ischemia/Infarction
NA
NA
Symptomatic ischemia 
(stable angina) OR Testing 
consistent with ischemia 
Unstable angina OR Acute 
myocardial infarction
Hemorrhage (significant acute 
blood loss)
NA
Symptomatic AND No 
transfusion indicated
Symptomatic AND 
Transfusion of 2 units 
packed RBCs (for children 
10 cc/kg) indicated 
Life-threatening hypotension 
OR Transfusion of 2 units 
packed RBCs indicated (for 
children 10 cc/kg) indicated
Hypertension (with repeat 
testing at same visit)
140–159 mmHg systolic 
OR 
90–99 mmHg diastolic
159–179 mmHg systolic 
OR 
99–109 mmHg diastolic
179 mmHg systolic 
OR 
109 mmHg diastolic
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization (other than 
ER visit) indicated
Pediatric 17 Years (with 
repeat testing at same visit)
NA
91st–94th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
≥95th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization indicated 
(other than emergency room 
visit)
Hypotension
NA
Symptomatic, corrected with 
oral fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure
Pericardial Effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, moderate or 
larger effusion requiring no 
intervention
Effusion with non-life-
threatening physiologic 
consequences OR Effusion 
with nonurgent intervention 
indicated
Life-threatening consequences 
(eg, tamponade) OR Urgent 
intervention indicated


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 120
06 May 2019
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV 
block OR Ventricular pause 
3.0 sec
Complete AV block 
Pediatric 16 Years
1st degree AV block
(PR > normal for age and 
rate)
Type I 2nd degree AV block 
Type II 2nd degree AV 
block 
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc interval 
0.50 sec OR Increase in 
interval 0.06 sec above 
baseline
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Pediatric 16 Years
Asymptomatic, QTc interval 
0.450 to 0.464 sec 
Asymptomatic, QTc interval 
0.465 to 0.479 sec 
Asymptomatic, QTc interval 
0.480 sec 
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated 
(eg, anticoagulation, lysis 
filter, invasive procedure) 
Deep vein thrombosis AND 
Intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Embolic event (eg, pulmonary 
embolism, life-threatening 
thrombus) 
Vasovagal Episode (associated 
with a procedure of any kind)
Present without loss of 
consciousness 
Present with transient loss of 
consciousness
NA 
NA
Ventricular Dysfunction 
(congestive heart failure, 
CHF)
NA
Asymptomatic diagnostic 
finding AND intervention 
indicated
New onset with symptoms 
OR Worsening symptomatic 
CHF
Life-threatening CHF


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 121
06 May 2019
RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced to 
70% to 80%
FEV1 or peak flow 50% to 69%
FEV1 or peak flow 25% to 
49% 
Cyanosis OR FEV1 or peak flow 
25% OR Intubation
Dyspnea or Respiratory 
Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities 
Dyspnea on exertion causing 
greater than minimal 
interference with usual social & 
functional activities 
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities 
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate for 
age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 
90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities OR Pulse 
oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis OR 
Medical intervention indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in affected 
eye(s) 
Visual Changes (from 
baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing greater 
than minimal interference with 
usual social & functional 
activities
Visual changes causing 
inability to perform usual 
social & functional 
activities
Disabling visual loss in affected 
eye(s)


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


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


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


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


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


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


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


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


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


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


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


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


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Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1)
Definitions
a)
Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b)
Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2)
Contraception Requirements for Female Subjects
a)
Study Drug Effects on Pregnancy and Hormonal Contraception
The 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 current Prescribing 
Information and local product labeling for ABC/DTG/3TC for additional information.
b)
Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Day 1 visit prior to randomization. At 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.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 136
06 May 2019
3)
Contraception Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment and until 90 days after the 
end of relevant systemic exposure.  Additional contraception recommendations should also be 
considered if the female partner is not pregnant.
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
4)
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM).  Female condom and male condom should not 
be used together.
5)
Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Subjects whose partner 
has become pregnant or suspects she is pregnant during the study must report the information to 
the investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy 
outcome are outlined in Section 7.3.

Prot_004.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Clinical 
Program Manager: 
Gilead Medical 
Monitor: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emu·icitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV -1 Infected, 
Antireu·oviral Treatment-Naive Adults 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
125589 
2015-004024-54 
Not Available 
HIV -1 Infection 
GS-US-380-1489 
Name: 
PD 
Telephone: 
t-'t-'U 
Fax: 
PPD 
Name: 
Hal Mrui in, MD, MPH 
Telephone: 
PPD 
Fax: 
PPD 
Pager: 
PPD 
Original: 
21 October 2015 
CONFIDENTIALITY STATEMENT 
The inf01mation contained in this document, prui iculru·ly unpublished data, is the prope1iy or 
under conu·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 infonnation 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 infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessruy to obtain infonned consent from those 
persons to whom the dmg may be administered. 


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Original
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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................12
1.
INTRODUCTION ..............................................................................................................................................15
1.1.
Background ............................................................................................................................................15
1.2.
GS-9883 .................................................................................................................................................16
1.2.1.
General Information .............................................................................................................16
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................16
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................18
1.3.
Information about Emtricitabine (Emtriva®, FTC) ...............................................................................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)...........................................................................................................................27
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) ...........................30
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, 
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................30
1.6.
Information about abacavir/dolutegravir/lamivudine (ABC/DTG/3TC Triumeq®)...............................31
1.7.
Rationale for this Study..........................................................................................................................31
1.8.
Risk/Benefit Assessment for the Study..................................................................................................31
1.9.
Rationale for Dose Selection..................................................................................................................32
1.10.
Compliance ............................................................................................................................................34
2.
OBJECTIVES.....................................................................................................................................................35
3.
STUDY DESIGN................................................................................................................................................36
3.1.
Endpoints ...............................................................................................................................................36
3.2.
Study Design..........................................................................................................................................36
3.3.
Study Treatments ...................................................................................................................................36
3.4.
Duration of Treatment............................................................................................................................37
3.5.
Biomarker Testing..................................................................................................................................38
3.5.1.
Biomarker Samples for Optional Pharmacogenomic Research............................................38
3.5.2.
Additional Sample Storage...................................................................................................38
4.
SUBJECT POPULATION..................................................................................................................................39
4.1.
Number of Subjects and Subject Selection ............................................................................................39
4.2.
Inclusion Criteria....................................................................................................................................39
4.3.
Exclusion Criteria...................................................................................................................................40
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................42
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................42
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................42
5.2.
Description and Handling.......................................................................................................................43
5.2.1.
Formulation..........................................................................................................................43
5.2.2.
Packaging and Labeling .......................................................................................................43


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5.2.3.
Storage and Handling...........................................................................................................44
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide and 
Abacavir/Dolutegravir/Lamivudine .......................................................................................................44
5.4.
Prior and Concomitant Medications.......................................................................................................45
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................46
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................46
6.
STUDY PROCEDURES ....................................................................................................................................47
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................47
6.2.
Pretreatment Assessments......................................................................................................................47
6.2.1.
Screening Visit .....................................................................................................................47
6.2.2.
Day 1 Assessments...............................................................................................................49
6.3.
Randomization .......................................................................................................................................51
6.4.
Treatment Assessments (Week 4 - 96)...................................................................................................51
6.5.
Treatment Assessments (Post Week 96 until the Unblinding Visit) ......................................................54
6.5.1.
Post Week 96 Assessments ..................................................................................................54
6.5.2.
Unblinding Visit...................................................................................................................55
6.6.
Post-treatment Assessments ...................................................................................................................57
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................57
6.6.2.
30 Day Follow Up................................................................................................................58
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................59
6.8.
Bone Mineral Density Evaluations.........................................................................................................60
6.9.
Other Evaluations...................................................................................................................................60
6.9.1.
Markers of Renal Tubular Function .....................................................................................60
6.9.2.
Markers of Inflammation and Immune Activation...............................................................60
6.9.3.
Markers of Platelet Function ................................................................................................60
6.10.
Blood and Urine Storage........................................................................................................................61
6.11.
Assessments for Premature Discontinuation from Study.......................................................................61
6.12.
End of Study...........................................................................................................................................61
6.13.
Post Study Care......................................................................................................................................61
6.14.
Virologic Failure....................................................................................................................................61
6.14.1.
Management of Virologic Rebound .....................................................................................61
6.14.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48 or Week 96............................................................................................................63
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................64
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................64
7.1.1.
Adverse Events.....................................................................................................................64
7.1.2.
Serious Adverse Events........................................................................................................64
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................65
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................65
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................65
7.2.2.
Assessment of Severity ........................................................................................................66
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................66
7.3.1.
Adverse Events.....................................................................................................................66
7.3.2.
Serious Adverse Events........................................................................................................67
7.4.
Gilead Reporting Requirements.............................................................................................................68
7.5.
Toxicity Management ............................................................................................................................68
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................68
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................69
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................69
7.5.4.
Management of Possible Abacavir Hypersensitivity Reaction.............................................69


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7.5.5.
On-Treatment Hepatitis C Management...............................................................................70
7.6.
Special Situations Reports......................................................................................................................70
7.6.1.
Definitions of Special Situations..........................................................................................70
7.6.2.
Instructions for Reporting Special Situations.......................................................................71
8.
STATISTICAL CONSIDERATIONS................................................................................................................73
8.1.
Analysis Objectives and Endpoints........................................................................................................73
8.1.1.
Analysis Objectives..............................................................................................................73
8.1.2.
Primary Endpoint .................................................................................................................73
8.1.3.
Secondary Endpoint .............................................................................................................73
8.2.
Analysis Conventions.............................................................................................................................73
8.2.1.
Analysis Sets ........................................................................................................................73
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.
Bone Safety Evaluations ......................................................................................................79
8.6.5.
Other Safety Evaluations......................................................................................................79
8.7.
Pharmacokinetic Analysis......................................................................................................................79
8.8.
Biomarker Analysis................................................................................................................................80
8.9.
Patient Report Outcomes (PRO) ............................................................................................................80
8.10.
Sample Size............................................................................................................................................80
8.11.
Data Monitoring Committee ..................................................................................................................80
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 ........................................................................................................................85
9.2.1.
Protocol Modifications.........................................................................................................85
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..................................................................................86
9.3.3.
Access to Information for Auditing or Inspections ..............................................................86
9.3.4.
Study Discontinuation..........................................................................................................86
10.
REFERENCES ...................................................................................................................................................87
11.
APPENDICES ....................................................................................................................................................88


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Gilead Sciences, Inc.
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Appendix 1.
Investigator Signature Page....................................................................................................89
Appendix 2.
Study Procedures Table (Blinded Phase) ...............................................................................90
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................94
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............95
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................119
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................120
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) ...........20
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) ...........................................................................................................21
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................22
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following GS-9883 
Administration Under Fasting Conditions and Corresponding Protein-Adjusted 
IQ95 Values (GS-9883 PK Analysis Set)...............................................................................23
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................33
Table 5-1.
Prior and Concomitant Medications.......................................................................................45
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).......................................................................................23
Figure 3-1.
Study Schema.........................................................................................................................37
Figure 6-1.
Virologic Rebound Schema....................................................................................................63


GS-9883/F/TAF
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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, 
Antiretroviral Treatment-Naïve Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004024-54
Not Available
Study Centers 
Planned:
Approximately 75 centers in North America
Approximately 2 centers in Asia
Approximately 25 centers in Europe
Objectives:
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) 
containing GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 
infected, antiretroviral treatment naïve-adult subjects as 
determined by the achievement of HIV-1 RNA < 50 copies/mL at 
Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the two 
treatment groups through Weeks 48 and 96

To evaluate the bone safety of the two treatment groups as 
determined by the percentage change from baseline in hip and 
spine bone mineral density (BMD) through Weeks 48 and 96
Study Design:
Randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus 
ABC/DTG/3TC FDC in HIV-1 infected, antiretroviral treatment-naïve 
adult subjects. Subjects who provide written consent and meet all 
eligibility criteria will be randomized in a 1:1 ratio to one of the 
following two treatment groups:


GS-9883/F/TAF
Protocol GS-US-380-1489
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Gilead Sciences, Inc.
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Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 
200 mg/ tenofovir alafenamide 25 mg (GS-9883/F/TAF) + Placebo to 
match FDC of abacavir 600 mg/ dolutegravir 50 mg/lamivudine 
300 mg (ABC/DTG/3TC) administered orally, once daily, without 
regard to food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 
50 mg/ lamivudine 300 mg (ABC/DTG/3TC) + Placebo to match 
FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without 
regard to food (n=300)
Randomization will be stratified by HIV-1 RNA level 
(≤100,000 copies/mL, > 100,000 to ≤ 400,000 copies/mL, or 
> 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. 
Ex-US) at randomization.
Number of Subjects 
Planned:
Approximately 600 subjects in total. 300 subjects in each Treatment 
Group 1 and Treatment Group 2
Target Population:
Antiretroviral treatment-naïve (except the use for pre-exposure 
prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to 
one month prior to screening), HLA-B*5701 negative, HIV-1 infected 
adults with plasma HIV-1 RNA levels ≥ 500 copies/mL and a 
screening genotype showing sensitivity to FTC, TFV, 3TC, and ABC.
Duration of 
Treatment:
Subjects will be treated for at least 96 weeks. Subjects’ treatments 
will be unblinded after the last subject completes the Week 96 visit
and Gilead completes the Week 96 analysis. Subjects will continue to 
take their blinded study drug and attend visits every 12 weeks until 
treatment assignments have been unblinded. At the Unblinding 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 in an open label 
extension phase for 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.
After Week 96 Visit, subjects in the United Kingdom (UK) will stop 
taking study drug and complete a 30 day follow up visit and return to 
the standard of care.
Subjects who complete the study through the Unblinding Visit and do
not continue on the open-label GS-9883/F/TAF FDC extension phase, 
will be required to return to the clinic 30 days after unblinding visit 
for a 30-Day Follow-Up Visit.


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Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening

Antiretroviral treatment naïve (≤ 10 days of prior therapy with any 
antiretroviral agent following a diagnosis of HIV-1 infection) 
except the use for PrEP or PEP, up to one month prior to 
screening.

Screening genotype report must show sensitivity to FTC, TFV, 
3TC, and ABC

Negative screening test for HLA-B*5701 allele

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance

No chronic Hepatitis B Virus (HBV) infection, as determined by 
either
―
Positive HBV surface antigen and negative HBV surface 
antibody, regardless of HBV core antibody status, at the 
screening visit
―
Positive HBV core antibody and negative HBV surface 
antibody, regardless of HBV surface antigen status, at the 
screening visit
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 96 weeks. 
Following the Day 1 visit, subjects will be required to return for study 
visits at Weeks 4, 8, and 12, and then every 12 weeks from Week 12 
through Week 96.  After 96 weeks, subjects will continue to take their 
blinded study drugs and attend study visits every 12 weeks until 
treatment assignments have been unblinded (except the UK).
For all eligible subjects, blood will be collected at Day 1, Weeks 4, 8, 
12, and then every 12 weeks through the Unblinding Visit.  
Laboratory analyses (hematology, chemistry, and urinalysis), HIV-1 
RNA, CD4+ cell count, and complete or symptom directed physical 
examinations will be performed at Screening, Day 1 and all 
subsequent visits. In addition, blood will be collected and stored for 
possible evaluation of markers of inflammation and immune 
activation, which may include but are not limited to: cystatin-C, IL-6, 
hs-CRP, d-dimer, sCD14, and sCD163. Platelet function evaluations 
may also be assessed, including but not limited to soluble 
glycoprotein VI (sGPVI), P-selectin, and soluble CD40 ligand.  Urine 
will be collected for evaluations of renal tubular function including 
urine albumin, urine creatinine, urine protein, retinol binding protein 
and beta-2 microglobulin.


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For all subjects on study drug, except subjects located in Germany,
dual energy x-ray absorptiometry (DXA) scans will be performed 
prior to or within 24 hours of the Day 1 Visit , and then at Weeks 24, 
48, 96, and at the Unblinding Visit or Early Study Drug 
Discontinuation Visit, if > 12 weeks since last scan. DXA scan results 
will be provided to study sites when available.
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:
FDC of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg 
(ABC/DTG/3TC) administered orally, once daily without regard to 
food.
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests and DXA
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 48 as defined by the United States (US) 
Food and Drug Administration (FDA) snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 96 as defined by the US FDA snapshot 
algorithm

The proportion of subjects who achieve HIV-1 RNA 
< 20 copies/mL at Weeks 48 and 96 as defined by the US FDA 
snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell 
count at Weeks 48 and 96
Pharmacokinetics:
An intensive pharmacokinetic (PK) substudy will be performed at the 
Weeks 4 or 8 visits in a subset of subjects (target n=30) at study sites 
able to conduct this testing.
For all subjects on study drug a single anytime pre or post-dose PK 
blood sample will be collected at Weeks 8, 24 and 36.


GS-9883/F/T AF 
Protocol GS-US-380-1489 
Gilead Sciences, Inc. 
Final 
Original 
For all subjects on study dmg a u·ough PK blood sample will be 
obtained 20-28 homs following the last dose at Weeks 4 and 12. 
Following an observed dose, one post-dose PK blood sample will be 
collected between 1 and 4 homs post-dose. 
For intensive PK substudy, the following PK parameters for GS-9883 
may be explored as applicable: 
Cmax, Tmax, Clast, T!ast, Ctau,T!I2, AUCtau,AUCo-!ast, VzJF, CLss/F. 
The concenu·ation of GS-9883 may be summarized using descriptive 
statistics. The phannacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concenu·ations may be analyzed 
and PK parameters may be smnmarized as applicable. 
Optional Genomic 
PD 
Testing: 
Optional Peripheral 
Blood Mononuclear 
Cell Substudy: 
Patient Reported 
Outcome: 
Statistical Methods: 
CONFIDENTIAL 
Sh01i F01m 36 Health Smvey (SF-36), HIV Symptoms Disu·ess 
Module, Work Productivity and Activity Impainnent Questionnaire 
(WP AI) and Pittsbmgh Sleep Quality Index (PSQI) will be 
administered at Day 1, Weeks 4, 12, and 48. 
The primruy analysis will consist of a non-inferiority test of 
GS-9883/F/TAF versus ABC/DTG/3TC, with respect to the 
prop01iion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA snapshot algorithm. 
Page 10 
21 October 2015 


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It will be concluded that GS-9883/F/TAF is non-inferior to 
ABC/DTG/3TC if the lower bound of the 2-sided 95% confidence 
interval (CI) of the difference (GS-9883/F/TAF – ABC/DTG/3TC) in 
the response rate (HIV-1 RNA < 50 copies/mL as defined by the US
FDA snapshot algorithm) is greater than -12%; ie, a margin of 12% is 
applied to non-inferiority assessment. The 95% CI will be constructed 
using a normal approximation method based on stratified 
Mantel-Haenszel proportions, where stratification factors include 
baseline HIV-1 RNA level (≤ 100,000 copies/mL vs. 
> 100,000 copies/mL) and region (US vs. Ex-US).
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL 
at Week 96 and the proportion of subjects who achieve HIV-1 RNA 
< 20 copies/mL at Weeks 48 and 96 as defined by the US FDA 
snapshot algorithm will also be summarized. The 95% CIs will be 
constructed in the same manner as described for the primary efficacy 
endpoint.
The change from baseline in log10 HIV-1 RNA and CD4+ cell count 
at Weeks 48 and 96 will be summarized by treatment using 
descriptive statistics. The differences and the associated 95% CIs will 
be constructed using an Analysis of Variance (ANOVA) model, 
including treatment (GS-9883/F/TAF vs. ABC/DTG/3TC), baseline 
HIV-1 RNA level (100,000 copies/mL vs. 100,000 copies/mL),
and region (US vs. Ex-US) as fixed effects in the model.
The percentage change from baseline in hip and spine BMD at 
Weeks 48 and 96 will be summarized by treatment using descriptive 
statistics. The differences and the associated 95% CIs will be 
conducted using an ANOVA model including treatment as a fixed 
effect in the model.  Adverse events, clinical laboratory assessments, 
and pharmacokinetic parameters will be summarized using descriptive 
statistics.
A total of approximately 600 HIV-1 infected subjects, randomized in 
a 1:1 ratio to 2 treatment groups (300 subjects per treatment group), 
achieves at least 95% power to detect a non-inferiority margin of 12% 
in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined by 
the US FDA snapshot algorithm) difference between the 2 treatment 
groups. For sample size and power computation, it is assumed that 
both treatment groups have a response rate of 91% (based on 
Gilead Studies GS-US-292-0104 and GS-US-292-0111), that a 
non-inferiority margin is 12%, and that the significance level of the 
test is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
ABC/3TC
abacavir/lamivudine, EpzicomKivexa
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
Antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration 
versus time curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
DTG
dolutegravir, Tivicay
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
EVG
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination


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


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


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {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 IC50 values ranging from 1.5 to 2.4 nM, similar to the inhibitory effect of DTG and 
EVG. GS-9883 is highly potent against HIV replication in MT4 cells with an EC50 (50% 
effective inhibitory concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. 
GS-9883 does not show significant cytotoxicity against dividing and non-dividing human 
PBMCs, primary human hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 M. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter OCT2 (IC50 = 0.42 M). As a result, 
GS-9883 is not expected to significantly interfere with the key transporter responsible for 
creatinine tubular elimination at the clinically projected Cmax. Additionally, the risk that GS-9883 
will affect the OCT2-mediated excretion of co-administered drugs is considered to be low.
GS-9883 does not activate AhR and only weakly activates PXR at concentrations up to 50 M 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.


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1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL,
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day.  At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal 
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males.  The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy.
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.
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).


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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 study of the pharmacokinetics and antiviral activity of GS-7340 
(8 mg, 25 mg, 40 mg) in HIV infected subjects (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)

GS-US-311-1790, a Phase 1Randomized, Open Label, Drug Interaction Study Evaluating the 
Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (ongoing)


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
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.
Changes in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2. In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort. In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF. All 
changes returned to baseline after discontinuation of GS-9883.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood. All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.
Based on results in study GS-US-141-1218, pharmacokinetic profile of GS-9883 was 
characterized by rapid absorption with time to peak plasma concentrations (median tmax of 
cohorts) ranging between 1 and 4 hours following administration under fasted conditions. 


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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.


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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
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 1-4 below.


GS-9883/F/T AF 
Protocol GS-US-380-1489 
Final 
Gilead Sciences, Inc. 
Original 
Table 1-4. 
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ9s Values (GS-9883 PK Analysis 
Set) 
GS-9883 dose 
N 
Median (range) C 1au,ss (ng!mL) 
Median (range) paiQ95• 
5mg 
4 
206.5 (146.0 to 342.0) 
1.3 (0.9 to 2.1) 
25mg 
4 
797.5 (714.0 to 1900.0) 
4.9 ( 4.4 to 11. 7) 
50mg 
4 
2170.0 (852.0 to 3020.0) 
13.4 (5.3 to 18.6) 
100mg 
4 
4190.0 (3730.0 to 5970.0) 
25.9 (23.0 to 36.9) 
a. 
The protein adjusted IQ95 (pal09s) value is estimated based on steady-state C1au values and the in vitJ:o paiC95 value for 
wild-type HIV-1 (162 ng/ml). 
The mean and 95% Cis of change from baseline in HIV -1 RNA (log10 copies/mL) are presented 
in Figure 1-1. 
Figure 1-1. 
G$-9883 5 mg (n= ): 
G$-9883 25 mg (n= ): 
G$-9883 50 mg (n= ): 
G$-9883 100 mg (n=): 
Placebo (n=): 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
• = GS-9883 5 mg 
0 = GS-9883 25 mg 
b. = GS-9883 50 mg 
0 = GS-9883 100 mg 
0 =Placebo 
BL 
2 
3 
3 
3 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
7 
8 
3 
3 
3 
4 
4 
4 
4 
4 
3 
4 
4 
4 
4 
4 
9 
10 
11 
Day 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
14 
3 
4 
4 
4 
4 
17 
3 
3 
4 
4 
4 
NOTE: Baseline value was the last available value collected prior to the time of the ftrst dose of study drug. 
2 
-1 
-2 
-3 
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Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group.
1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, antiretroviral therapy 
(ART)-naive adult subjects.
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
Interim data at Week 12 are summarized below.  Data from the Week 24 primary endpoint are 
included in the GS-9883/F/TAF Investigator’s Brochure.
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 12 
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.


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1.2.3.5.
Efficacy Results
Virologic success at Week 12 when assessed using the US FDA snapshot algorithm, defined as 
plasma HIV-1 RNA < 50 copies/mL, was similar between the 2 treatment groups as follows: 
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).
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).
Interim Virology Resistance Data
Through Week 12, 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 (6.2%, 4 subjects each); and fatigue and nausea 
(3.1%, 2 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects); and fatigue, 
flatulence, and furuncle (6.1%, 2 subjects each)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (diabetic ketoacidosis); this event was also reported as an SAE, and 1 other SAE 
(appendicitis) 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 12.3%, 8 subjects; DTG+F/TAF 15.2%, 
5 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs (somnolence and headache) were reported in 
1 subject. No Grade 3 or 4 treatment-emergent AEs or treatment-emergent SAEs were 
considered related to study drug.
No deaths, pregnancies, or AEs leading to premature study drug discontinuation were reported.


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Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least 
1 grade level increase from baseline in graded abnormality) was similar between treatment 
groups as follows: GS-9883+F/TAF 70.3%, 45 subjects; DTG+F/TAF 75.0%, 24 subjects. The 
majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The 
percentage of subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality 
was similar between treatment groups as follows: GS-9883+F/TAF 10.9%, 7 subjects; 
DTG+F/TAF 12.5%, 4 subjects. Grade 4 treatment-emergent laboratory abnormalities 
(creatine kinase) were reported in only 2 subjects.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. Changes from 
baseline in serum creatinine were similar between treatment groups. Median (Q1, Q3) changes in 
serum creatinine at Week 12 were as follows: GS-9883+F/TAF 0.11 (0.06, 0.16) mg/dL; 
DTG+F/TAF 0.14 (0.06, 0.24) mg/dL. Changes from baseline in eGFR were similar between 
treatment groups. Median (Q1, Q3) changes in eGFR at Week 12 were as follows: 
GS-9883+F/TAF −12.2 (−18.0, −6.4) mL/min; DTG+F/TAF −15.8 (−30.1, −9.5) mL/min.
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.


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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-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).


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


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
GS-US-292-0119, a Phase 3 open-label study to evaluate switching from optimized stable 
antiretroviral regimens containing darunavir to 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) single tablet 
regimen (STR) plus darunavir (DRV) in treatment experienced HIV-1 positive adults
(ongoing)

GS-US-292-0106, a Phase 2/3, open-label study of the pharmacokinetics, safety, and 
antiviral activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected antiretroviral treatment-naive 
adolescents (ongoing)
Study GS-US-292-0101 is a Phase 1 study of 40 subjects evaluating the relative bioavailability 
of two different formulations of E/C/F/TAF STR, each with TAF dose of 25 mg or 40 mg, versus 
E/C/F/TDF STR or TAF 25 mg alone. Exposures of EVG, COBI, and FTC were comparable 
between E/C/F/TAF vs E/C/F/TDF regardless of formulation (monolayer or bi-layer). In 
contrast, TAF exposures were ~2.2-fold higher (and corresponding tenofovir exposures ~ 3-fold 
higher) when administered as E/C/F/TAF (25 mg) vs TAF single agent (SA) 25 mg for both 
formulations of the E/C/F/TAF, likely mediated by inhibition of Pgp-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%). 


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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.
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, FTC, and 
TAF between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is an ongoing Phase 1, open-label, 2-cohort, multiple-period,
fixed-sequence, crossover study conducted at a single center in the US to evaluate 1) the relative 
bioavailability (BA) of 2 GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets 
compared with the GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered 
simultaneously and 2) the effect of food on the PK of GS-9883, FTC, and TAF when 
administered as GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets.
Cohort 1 evaluated the relative BA and food effect of GS-9883/F/TAF (75/200/25 mg) FDC 
tablet in a 3-period sequence. Following review of preliminary data from Cohort 1, Cohort 2 was 
added to the study via protocol amendment. Cohort 2 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 (75 mg) tablet and the F/TAF 
(200/25 mg) FDC tablet administered simultaneously.


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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.
1.6.
Information about abacavir/dolutegravir/lamivudine (ABC/DTG/3TC
Triumeq®)
For more detailed information, refer to the current Prescribing Information and local product 
labeling for abacavir/dolutegravir/lamivudine.
1.7.
Rationale for this Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 
HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.
The GS-9883/F/TAF FDC has the potential to offer a simple, once-daily regimen containing a 
second generation INSTI that provides a high barrier to resistance, does not require a boosting 
agent, and offers an effective and safer alternative to standard nucleos(t)ide based regimens, 
without the need for HLA testing or close monitoring of renal or bone toxicities. It could provide 
a FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute to an
increased risk of cardiovascular events, could be used in patients with chronic hepatitis B or C 
infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities.
The objective of this study is to evaluate the safety and efficacy of a FDC containing 
GS-9883/F/TAF versus ABC/DTG/3TC. ABC/DTG/3TC was selected as the active comparator 
for this study as it is a second-generation integrase inhibitor-based, once-daily fixed dose 
combination, and is a DHHS Guidelines preferred regimen. Use of ABC/DTG/3TC as a 
comparator in this study will therefore allow comparison of two single tablet regimens 
containing second generation, unboosted INSTIs.
1.8.
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: hypersensitivity 


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reaction to abacavir and allergy to any components of the tablets. Some observational studies 
have shown increased risk of cardiovascular disease with abacavir. Interim data will also be 
reviewed by an independent data monitoring committee. Potential benefits may include provision 
of a new antiretroviral therapy that is not currently available and which may have fewer side 
effects than alternative therapies. Other potential benefits include provisions of fixed dose 
combination therapy, and the knowledge that patient participation will contribute to the body of 
knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF and ABC/DTG/3TC is favorable at this 
time.
1.9.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.


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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
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 12 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.


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1.10.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) containing 
GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral 
treatment naïve-adult subjects as determined by the achievement of HIV-1 RNA 
< 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the two treatment groups through 
Weeks 48 and 96

To evaluate the bone safety of the two treatment groups as determined by the percentage 
change from baseline in hip and spine BMD through Weeks 48 and Week 96


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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint is:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 as defined 
by the US FDA snapshot algorithm
The secondary endpoints of this study include:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 96 as defined 
by the US FDA snapshot algorithm

the proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48 and 96 as 
defined by the US FDA snapshot algorithm

the change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48 and 96

the percentage change from baseline in hip and spine BMD at Weeks 48 and 96
3.2.
Study Design
This protocol describes a randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus ABC/DTG/3TC FDC in HIV-1 
infected, antiretroviral treatment-naïve adult subjects.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food
(n=300)
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. Ex-US) at randomization.


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3.4.
Duration of Treatment
Subjects will be treated for at least 96 weeks. Subjects’ treatments will be unblinded after the last 
subject completes the Week 96 visit and Gilead completes the Week 96 analysis. Subjects will 
continue to take their blinded study drug and attend visits every 12 weeks until treatment 
assignments have been unblinded. At the Unblinding 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 
in an open label extension phase for 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.
After Week 96 Visit, subjects in the United Kingdom will stop taking study drug and complete a 
30 day follow up visit and return to the standard of care.
Figure 3-1.
Study Schema
a
Following the Day 1 visit, subjects will be required to return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
through Week 96.
b
After Week 96, subjects will continue to take their blinded study drug and attend visits every 12 weeks until treatment
assignments have been unblinded. Subjects’ treatments will be unblinded after the last subject completes the Week 96 visit
and Gilead completes the Week 96 analysis. After Week 96 Visit, subjects in the United Kingdom will stop taking study 
drug and complete a 30 day follow up visit and return to the standard of care.
c
Once Gilead Sciences provides unblinded treatment assignments to the Investigators, all subjects will return to the clinic
(preferably within 30 days) for an Unblinding Visit. At the Unblinding 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 in an open label extension for 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.
d
Subjects who complete the study through the Unblinding Visit and do not continue on the open-label GS-9883/F/TAF FDC
extension phase will be required to return to the clinic 30 days after the completion of study drugs for a 30-Day Follow-Up 
Visit


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3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Pharmacogenomic Research 
PPD 
3.5.2. 
Additional Sample Storage 
Final 
Original 
For subjects who provide additional consent, residual blood and urine samples taken throughout 
the study will be stored. Stored samples may be used by the Sponsor or its research partners to 
help answer questions about the study dmg, and HIV disease and its associated conditions, or to 
provide additional safety data. 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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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 600 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Age 18 years
3) Antiretroviral treatment naïve (≤ 10 days of prior therapy with any antiretroviral agent 
following a diagnosis of HIV-1 infection) except the use for PrEP (pre-exposure prophylaxis) 
or PEP (post-exposure prophylaxis), up to one month prior to screening
4) Plasma HIV-1 RNA levels 500 copies/mL at screening
5) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥0.83 mL/sec) according to the 
Cockcroft-Gault formula {2202}:
a) Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
b) Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) 0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8) Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin
9) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))


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10) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11) Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12) Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 6) throughout the study period and for 
90 days following the last dose of study drug
13) Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14) Life expectancy ≥ 1 year
15) Screening genotype report provided by Gilead Sciences must show sensitivity to FTC, TFV, 
3TC, and ABC
16) Negative screening test for HLA-B*5701 allele provided by Gilead Sciences
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 (e.g, 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 (e.g, 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 other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC or ABC/DTG/3TC FDC 
tablets
10) Females who are pregnant (as confirmed by positive serum pregnancy test)
11) Females who are breastfeeding
12) Subjects receiving ongoing therapy with any of the following medications in the table below, 
including drugs not to be used with FTC, TAF, GS-9883, DTG, ABC and 3TC
Drug Class
Agents Disallowed*
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinaccea
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study.
13) Acute hepatitis in the 30 days prior to study entry
14) Chronic Hepatitis B Virus (HBV) infection, as determined by either:
a) Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit
b) Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
15) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until the Investigator has received the results of the allele testing and 
screening genotype report and subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening and region (US vs. Ex-US) at randomization.
The IWRS will assign study drug bottle numbers of blinded FDC of GS-9883/F/TAF + Placebo 
to match FDC of ABC/DTG/3TC or FDC of ABC/DTG/3TC + Placebo to match FDC of
GS-9883/F/TAF at each study visit for each subject.
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the IWRS system 
for that subject. Gilead strongly recommends but does not require that the investigator contact 
the Gilead medical monitor before breaking the blind. Treatment assignment should remain 
blinded unless that knowledge is necessary to determine subject emergency medical care. The 
rationale for unblinding must be clearly explained in source documentation and on the electronic 
case report form (eCRF), along with the date on which the treatment assignment was 
obtained. The investigator is requested to contact the Gilead medical monitor promptly in case of 
any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Drug Safety and Public Health (DSPH) may independently unblind cases for expedited 
reporting of suspected unexpected serious adverse reactions (SUSARs).


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5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.
The placebo to match (PTM) GS-9883/F/TAF tablets are capsule-shaped, film-coated 
purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the other side and 
are identical in physical appearance to GS-9883/F/TAF tablets. The placebo tablets contain 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. 
The tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, 
polyvinyl alcohol, talc, and titanium dioxide.
5.2.1.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
Abacavir 600 mg/Dolutegravir 50 mg/Lamivudine 300 mg tablets are oval, film coated purple, 
and debossed with “572 Tri” on one side. Each tablet core contains 600 mg of abacavir, 50 mg of 
dolutegravir, and 300 mg of lamivudine. In addition to the active ingredients, the 
ABC/DTG/3TC tablets contain the inactive ingredients D-mannitol, magnesium stearate, 
microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet cores are film 
coated with iron oxide black, iron oxide red, polyethylene glycol, polyvinyl alcohol, talc, and 
titanium oxide.
The PTM ABC/DTG/3TC tablets are oval, film coated purple, and debossed with “572 Tri” on 
one side. The placebo tablets are identical in physical appearance to ABC/DTG/3TC tablets. The
placebo tablets contain microcrystalline cellulose, lactose monohydrate, croscarmellose sodium 
and magnesium stearate. The tablet cores are film-coated with iron oxide black, iron oxide red, 
polyethylene glycol, polyvinyl alcohol, talc, and titanium oxide.
5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883/F/TAF tablets and PTM GS-9883/F/TAF tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester 
packing material.  Each bottle is enclosed with a white, continuous thread, child-resistant 
polypropylene screw cap with an induction-sealed and aluminum-faced liner.


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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
5.2.2.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
ABC/DTG/3TC tablets and PTM ABC/DTG/3TC tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets and silica gel desiccant. Each bottle 
is enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal 
Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both 
FDCs should be stored at controlled room temperature of 25°C (77°F); excursions are permitted 
between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label. Until 
dispensed to the subjects, all bottles of study drugs should be stored in a securely locked area, 
accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide 
and Abacavir/Dolutegravir/Lamivudine
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both
FDCs will be provided by Gilead Sciences.
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food. 


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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 table and use of herbal/natural supplements are excluded 
or should be used with caution while subjects are participating in the study. Subjects will 
refrain from consumption of grapefruit juice and Seville orange juice throughout 
participation in the study.
Table 5-1.
Prior and Concomitant Medications
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 when initiating study 
medication or if initiating metformin 
while on study drug.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.


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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 study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events, smoking history
and prior medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.


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Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) 0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
HLA-B*5701
Plasma HIV-1 RNA
Hepatitis B virus surface antigen serology (HBsAg)
Hepatitis B surface antibody (HBsAb)
Hepatitis B virus core antibody (HBcAb)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.
HIV-1 genotype testing (protease and reverse transcriptase). The HIV-1 PR/RT genotype 
testing may not be performed for subjects that fail to meet other screening criteria.

Review of adverse events and concomitant medications
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for the Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. See 
Section 7 Adverse Events and Toxicity Management for additional details.


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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 
received the results from the allele testing and screening genotype report and confirmed 
eligibility before proceeding with the Day 1 visit. The subject must complete all study 
procedures, except DXA, before being administered the study drug:

DXA Scan (spine and hip).  For subjects in Germany, DXA scans will not be performed.
The DXA scan will be performed on subjects once eligibility is confirmed. The scan may 
be performed prior to or within 24 hours of the Day 1 Visit.

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject.  Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN) and TSH


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Metabolic assessments: Fasting (no food or drinks, except water, at least 8 homs 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 retum within 72 homs in a fasted state to draw blood for the metabolic 
assessments. 
-
Estimated glomemlar filtration rate according to the Cockcroft-Gault f01mula 
-
Hematology profile: complete blood cmmt (CBC) with differential and platelet cmmt 
-
Plasma HIV-1 RNA 
-
CD4+ cell count 
-
Evaluations of inflammation and immlme activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 
-
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand 
-
Plasma storage sample for safety, virology, or PK testing 
• 
Optional Peripheral Blood Mononuclear cell (PBMC) Substudy: 
• 
• 
Optional blood sample collection for the following laboratory analyses if 
pharmacogenomic consent is obtained 
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6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 - 96)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, 48, 60, 72, 
84, and 96 unless otherwise specified.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 96, unless otherwise specified.  The visit window at Weeks 48 and 96 will be 
± 6 weeks of the protocol-specified visit date, and these clinical visit windows coincide with the 
Week 48 and Week 96 statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (Weeks 24, 48 and 
96 ±10 days). For subjects in Germany, DXA scans will not be performed.

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)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject at Weeks 4, 12 and 48.  Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin. (Weeks 24, 48, 72 and 96)


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Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 12, 24, 48, 72 and 96 analyses of glucose will be done as part of the fasting 
metabolic assessments and not as part of the chemistry profile. At Weeks 24, 48, 72 and 
96 TSH will also be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24, 48, 72 and 96)
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
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (Weeks 24, 48, 72 and 96)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (Weeks 24, 48, 72 and 96)
Plasma storage sample for safety, virology, or PK testing

Pharmacokinetic Blood Collection for subjects who are on study drug. Details of 
pharmacokinetic blood sampling procedures and sample management will be documented in 
the Pharmacokinetic Sample Collection, Processing, Storage, and Shipment Manual.
Single Anytime, Trough and Post Dose PK Samples for all subjects on study drug:
■
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 and 36.


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Observed dosing at the clinic: Subjects will have a trough PK blood sample collected 
between 20-28 homs following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study <hugs on the moming of their visit for the ti·ough 
sample collection. Subjects will then take an observed dose of study <hug at the 
clinic. A single post dose PK blood sample will be collected between 1 and 4 homs 
post dose. If the subject has taken their dose of study dmgs prior to the visit, the visit 
may proceed, but the subject must retum within 72 homs for the n·ough PK blood 
sample collection. In the event a subject routinely takes their study <hug in the 
evening, a single post dose sample may be <h·awn at Weeks 4 and 12 as the subject 
will not be insti11cted to change their dosing time to accommodate this n·ough PK 
<h·aw. 
• 
Dosing diaries will be collected from subjects for the single anytime PK and n·ough 
PK collection. If a dosing diaty is not retumed the site may ask the subject for the 
time of the last dose and if it was taken with or without food. 
-
Optional Phrumacokinetic (PK) Substudy: 
• 
Optional Peripheral Blood Mononuclear cell (PBMC) Substudy: 
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6.5.
Treatment Assessments (Post Week 96 until the Unblinding Visit)
6.5.1.
Post Week 96 Assessments
After Week 96, subjects will continue to take their blinded study drugs and attend visits every 
12 weeks until treatment assignments have been unblinded, at which point they will return for an 
Unblinding Visit (refer to Section 6.5.2). Study visits are to be completed within 6 days of the 
protocol-specified visit date unless otherwise specified.
At the Week 96 Visit, subjects in the United Kingdom will stop taking study drug and complete a 
30 day follow up visit and return to the standard of care.

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, the subject 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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 weeks)


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Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (Every 24 weeks)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (Every 24 weeks)
Plasma storage sample for safety, virology, or PK testing

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.14.1 and 6.14.2.

Document study drug dispensation and accountability for all study drugs dispensed.
6.5.2.
Unblinding Visit
Once Gilead Sciences provides unblinded treatment assignments to the Investigators, all subjects 
will return to the clinic (within 30 days ± 6 days) for an Unblinding Visit. At the Unblinding 
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 in an open label extension phase for 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.
Subjects who receive the open-label GS-9883/F/TAF FDC will return for study visits every 
12 weeks.

Subjects who choose to not receive the open label GS-9883/F/TAF FDC will be required to 
return to the clinic for a 30-Day Follow-up visit following the Unblinding Visit. Subjects 
who have discontinued drug study prior to the Unblinding Visit will not be eligible for the 
open-label rollover extension; these subjects will be asked to continue attending the 
scheduled study visits through the Unblinding Visit and discontinue the study after the 
Unblinding Visit.
The following will be performed at the Unblinding Visit:

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (±10 days). For subjects in 
Germany, DXA scans will not be performed.


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
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 (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN), and TSH
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand
Plasma storage sample for safety, virology, or PK testing


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
Document study drug dispensation, if applicable and accountability for all study drugs 
dispensed

Subjects who wish to continue in the Open-Label Rollover extension study will receive open 
label GS-9883/F/TAF.
6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
If the subject discontinues study drug prior to the Unblinding Visit, the subject will be asked to 
return to the clinic within 72 hours of stopping study drugs for the Early Study Drugs 
Discontinuation Visit. The subject will be asked to continue attending the scheduled study visits 
through the Unblinding Visit.
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to Day 1, 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

DXA scan required (spine and hip) for all subjects who are on study drug (±10 days) if last 
scan was acquired > 12 weeks from the date of the ESDD Visit.   For subjects in Germany, 
DXA scans will not be performed.

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 (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30 Day Follow Up
Subjects who complete the study through the Unblinding visit and who do not participate in the 
open-label rollover extension, will be required to return to the clinic 30 days after the completion 
of study drug for the 30 Day Follow Up visit.
Subjects in the United Kingdom will complete a 30 day follow up visit after the completion of 
the Week 96 visit and return to the standard of care.
Subjects who permanently discontinue study drug during the blinded phase and refuse to 
continue in the study through the Unblinding 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.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination


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
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly (or as 
often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained.
6.7.
Criteria for Discontinuation of Study Treatment
Study medication 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


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
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.
Bone Mineral Density Evaluations
For all subjects who are on study drug, excluding those enrolled in sites based in Germany, dual 
energy x-ray absorptiometry (DXA) scans will be performed prior to or within 24 hours of 
Day 1, Weeks 24, 48, 96, Unblinding Visit and the Early Study Drug Discontinuation Visit (if 
the last scan was acquired > 12 weeks from the date of the ESDD Visit). Scans will cover the 
spine and hip to measure changes in bone mineral density. DXA scan results will be provided to 
study sites.
A complete description of the procedures performed for the DXA scans will be provided in a 
DXA manual.
6.9.
Other Evaluations
6.9.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin at Day 1 Visit, Weeks 24, 48, every 24 weeks post Week 48 and the 
Unblinding Visit.
6.9.2.
Markers of Inflammation and Immune Activation
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48 and the Unblinding Visit for selected evaluations of inflammation and immune 
activation, which may include but not limited to cystatin-C, IL 6, hs CRP, d-dimer, sCD14, and 
sCD163.
6.9.3.
Markers of Platelet Function
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48 and the Unblinding Visit for selected evaluations of platelet function, which may
include but not limited to soluble glycoprotein VI (sGPVI), P-selectin, and soluble CD40 ligand.


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6.10.
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 for HIV-1 genotyping/phenotyping 
assays or their development, for retesting the amount of HIV-1 in the blood, for measurement of 
antiviral drug levels in the blood, or for testing to learn more about how the study drug has 
worked against HIV-1 or clinical laboratory testing 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.
6.11.
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.
6.12.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.13.
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.
6.14.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation, Week 48 or Week 96.
6.14.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any visit, after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA 
≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled 
visit; OR

At any visit, a 1 log10 increase in HIV-1 RNA from the nadir which is subsequently 
confirmed at the following scheduled or unscheduled visit
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 


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confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing. Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-baseline resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.
If no resistance is detected from the genotype or phenotype, the subject may remain on study 
drugs and a repeat HIV-1 RNA should be repeated (2 to 3 weeks after date of test with HIV-1 
RNA ≥ 50 copies/mL). Investigators should carefully evaluate the benefits and risks of 
remaining on study drug for each individual subject and document this assessment in the on-site 
medical record.
Subjects who are noncompliant on an ongoing basis will be considered for discontinuation per 
the Investigator’s discretion or local treatment guidelines. Investigators who opt to discontinue 
study drugs for an individual subject must discuss with the Medical Monitor prior to study drug 
discontinuation.
For subjects who are off study drug but remain on study, it will be the Investigator’s discretion to 
manage virologic rebound.
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
rebound.


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Figure 6-1. 
Virologic Rebound Schema 
Scre.ening 
Treatment Peliod 
30-Day 
Follow-up 
Day 1 
Unconfrrmed 
virologic 
rebound: t·emain 
on current 
regimen 
3 
At any visit, after achieving HIV-1 RNA< 50 copies/mL, a rebound in HIV-1 RNA to 
<!: 50 copies/mL OR > llog1o increase in HIV-1 RNA from theit· nadir 
Retur n for scheduled/unscheduled HIV-1 
RNA and potential genotype/phenotype 
sampling (2-3 weeks later) 
Confirmed virologic. rebound 
and HIV-1 
Genotype and Phenotype b, < 
i 
I 
i 
If no t·everse tt·anscriptase or 
integt·ase resistance deteded, may 
continue on study drugs d 
Remain 
on 
study 
If reverse transcriptase or integ.-ase 
resistanc.e detected, discontinue 
study drugs and construct a new 
ARV regimen • 
a 
If virologic rebotmd is not confmned, the subject will remain on their Cllll'ent reginten. 
b 
If virologic rebonnd is confumed and the HIV -1 RNA is :0:: 200 copies/mL, the HIV -1 genotype and phenotype (reverse 
transcriptase, protease and integrase) will be analyzed. 
c 
Based on the results of the genotypic and phenotypic assays, d1e subject will remain on study dtugs or study dt·ugs will be 
discontinued. If genotyping or phenotyping assay fails, a new AR V regin1en may be configlll'ed at the discretion of the 
Investigator. 
d 
If no resistanc.e is detected, HIV-1 RNA will be repeated (2-3 weeks later). h1vestigator reviews study drug 
continuation/discontinuation options and discuss with the Medical Monitor prior to study dt·ug discontinuation 
e 
A new ARV reginten will be configured, at the Investigator's discretion, and the subject will remain in the study. 
6.14.2. 
Subjects with HIV-1 RNA 2:: 50 copies/mL at Study Discontinuation, Week 48 
orWeek96 
Subjects with HIV -1 RNA ~ 50 copies/mL at study discontinuation or last visit will be 
considered virologic failures. Subjects with HIV -1 RNA ~ 50 copies/mL at Week 48 or Week 96 
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 dmg discontinuation, last visit, Week 48, or 
Week 96 will also have resistance testing conducted. 
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.6.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is 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 (e.g., 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, (e.g., 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 eCRF:

all SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30-days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.


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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead 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 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 it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study start), record the 
SAE on the paper serious adverse event report form and submit by e-mail or fax within 
24 hours of the investigator’s knowledge of the event to:
Gilead DSPH contact information:
Email:
Safety_FC@gilead.com
Fax:
+1 (650) 522-5477

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 
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
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/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 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 to
investigational medicinal product.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to investigational medicinal product, 
investigational medicinal product 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.
Management of Possible Abacavir Hypersensitivity Reaction
Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to increased 
risk of hypersensitivity reaction, unless no other therapeutic option is available based on the 
treatment history and resistance testing.
In a clinical study, 3.4 % of subjects with a negative HLA-B*5701 status receiving abacavir 
developed a hypersensitivity reaction. Therefore, even in the absence of HLA-B*5701 allele, it is 
important to permanently discontinue abacavir and not rechallenge with abacavir if a 
hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe 
or even fatal reaction.


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Hypersensitivity reactions are characterized by the appearance of symptoms indicating 
multi-organ system involvement. Almost all hypersensitivity reactions will have fever and/or 
rash as part of the syndrome. Other signs and symptoms may include respiratory signs and 
symptoms such as dyspnoea, sore throat, cough, and abnormal chest x-ray findings 
(predominantly infiltrates, which can be localized), gastrointestinal symptoms, such as nausea, 
vomiting, diarrhea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as 
respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis. Other frequently 
observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and 
musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia). The symptoms related to this 
hypersensitivity reaction worsen with continued therapy and can be life-threatening. 
These symptoms usually resolve upon discontinuation of abacavir.
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. Patients 
should be monitored closely, especially during the first two months of treatment with abacavir.
Regardless of their HLA-B*5701 status, patients who are diagnosed with a hypersensitivity 
reaction whilst on therapy MUST discontinue study drug immediately and MUST NEVER be 
restarted. Restarting study drug following a hypersensitivity reaction results in a prompt return of 
symptoms within hours. This recurrence is usually more severe than on initial presentation, and 
may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimize 
the risk of a life-threatening hypersensitivity reaction, study drug must be permanently 
discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible 
(respiratory diseases, flu-like illness, gastroenteritis or reactions to other medicinal products) 
{25149}.
7.5.5.
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.
7.6.
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.


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Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to 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 (e.g., a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead 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.


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Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH,
fax number +1 650 522-5477 or email Safety_FC@gilead.com.
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead 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 7.3.2 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 a FDC of GS-9883/F/TAF
versus a FDC of ABC/DTG/3TC in HIV-1 infected, antiretroviral treatment naïve-adult subjects 
as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety and tolerability of the two treatment groups through 
Weeks 48 and 96

To evaluate the bone safety of the two treatment groups as determined by the percentage
change from baseline in hip and spine BMD through Weeks 48 and 96
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 96 as defined 
by the US FDA snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48 and 96 as 
defined by the US FDA snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48 and 96

The percentage change from baseline in hip and spine BMD at Weeks 48 and 96
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.


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8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis
set:

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 do not meet the inclusion criterion that the screening genotype report provided 
by Gilead Sciences must show sensitivity to FTC, TFV, ABC, and 3TC.

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 4.3 including drugs not to be used with 
GS-9883, FTC, TAF, ABC, 3TC, and DTG.

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Substudy Analysis Set
The primary analysis set for intensive PK analyses is defined as the PK substudy analysis set, 
which will include all subjects who (1) are randomized into the study, (2) enrolled into the PK 
Substudy, (3) have received at least 1 dose of study drug, and (4) have at least 1 nonmissing 
intensive PK concentration data for the analyte under evaluation reported by the PK lab.


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8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose of 
study drug, and (3) have at least 1 nonmissing PK concentration data for the analyte under 
evaluation reported by the PK lab.
8.2.1.5.
DXA
8.2.1.5.1.
Hip DXA Analysis Set
The primary analysis set for hip BMD analyses is defined as the Hip DXA analysis set, which
will include all subjects who (1) are randomized into the study, (2) have received at least 1 dose 
of study drug, and (3) have nonmissing baseline hip BMD value. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.5.2.
Spine DXA Analysis Set
The primary analysis set for spine BMD analyses is defined as the Spine DXA analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have nonmissing baseline spine BMD value. Subjects will be 
grouped according to the treatment they actually received.
8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.  Logarithm (base 10) transformation will be 
applied to HIV-1 RNA levels for efficacy analysis.
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (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 (i.e., 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 sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects who achieve HIV-1 RNA 
50 copies/mL at Week 48 as determined by the US FDA snapshot algorithm. The primary 
analysis of the efficacy will be based on the FAS.
8.5.1.1.
FDA Snapshot Algorithm
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 includes 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 adverse event (AE), death, or lack of efficacy and have the last 
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
No Virologic Data in the Week 48 analysis window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following: 
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to AE or 
death (regardless of whether the last available on-treatment HIV-1 RNA < 50 copies/mL 
or not) or,
b) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
c) 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 achieving HIV-1 RNA < 50 copies/mL 
(as defined by the US FDA snapshot algorithm) at Week 48 in GS-9883/F/TAF is at least 
12% lower than the response rate in ABC/DTG/3TC; the alternative hypothesis is that the 
response rate in GS-9883/F/TAF is less than 12% lower than that in ABC/DTG/3TC.
Non-inferiority will be assessed using the conventional confidence interval approach. The point 
estimate of treatment difference (GS-9883/F/TAF – ABC/DTG/3TC) and the associated 2-sided 
95% confidence interval will be constructed using a normal approximation method based on 
stratified Mantel-Haenszel proportions, where stratification factors include baseline HIV-1 RNA 
level (100,000 copies/mL vs. 100,000 copies/mL) and region (US vs. Ex-US). Note that to 
avoid small or missing cells in analysis strata, CD4+ cell count is not stratified in analysis 
because HIV-1 RNA and CD4+ cell count are highly correlated.
It will be concluded that GS-9883/F/TAF is non-inferior to ABC/DTG/3TC if the lower bound of 
the 2-sided 95% CI of the difference (GS-9883/F/TAF – ABC/DTG/3TC) in the response rate is 
greater than -12%.
If non-inferiority of GS-9883/F/TAF to ABC/DTG/3TC is established, the lower bound of the 
95% CI will be compared to 0; if the lower bound of the 95% CI is greater than 0, then 
superiority of GS-9883/F/TAF over ABC/DTG/3TC will be established.
8.5.2.
Secondary Analyses
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 96 and the 
proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48 and 96, as defined 
by the US FDA snapshot algorithm, will be analyzed using the same method as for the primary 
efficacy endpoint.
The changes from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48 and 96 will be 
summarized by treatment using descriptive statistics. The differences in changes from baseline in 
log10 HIV-1 RNA and CD4+ cell count between 2 treatment groups and the associated 


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95% confidence intervals will be constructed using ANOVA models, including treatment 
(GS-9883/F/TAF vs. ABC/DTG/3TC), baseline HIV-1 RNA level (100,000 copies/mL vs.
100,000 copies/mL), and region (US vs. Ex-US) as fixed effects in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.
8.6.
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.


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On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV, can be found in Appendix 5.
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.
Bone Safety Evaluations
The percentage changes from baseline in hip/spine BMD at Weeks 48 and 96 will be 
summarized by treatment using descriptive statistics. The differences in percentage changes from 
baseline in hip/spine BMD between 2 treatment groups and the associated 95% confidence 
intervals will be constructed using ANOVA models, including treatment as a fixed effect in the 
model.
In addition, missing values for BMD will be imputed using LOCF method and analyzed 
similarly.
8.6.5.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the intensive PK substudy, plasma concentrations of GS-9883 may be summarized by 
nominal sampling time using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Ctau, 
AUCtau, and T½, as appropriate) will be listed and summarized using descriptive statistics 
(eg, sample size, arithmetic mean, geometric mean, coefficient of variation %, SD, median, Q1, 
Q3, minimum, and maximum). Plasma concentrations over time will be plotted in 
semi-logarithmic and linear formats as mean ± standard deviation, and median (Q1, Q3).


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For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
descriptive statistics or population approaches.
TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.
8.8.
Biomarker Analysis
For each biomarker of inflammation, immune activation, platelet function and renal tubular 
function, the percentage change from baseline will be summarized by treatment and visit using 
descriptive statistics. Differences in percentage changes from baseline in each biomarker 
between the 2 treatment groups will be tested using a Wilcoxon rank sum test.
8.9.
Patient Report Outcomes (PRO)
The PRO measures based on questionnaires (eg, SF-36 and HIV Distress Module) will be 
summarized by treatment and visit using descriptive statistics.
8.10.
Sample Size
A total of approximately 600 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (300 subjects per treatment group), achieves at least 95% power to detect a 
non-inferiority margin of 12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined 
by the US FDA snapshot algorithm) difference between the 2 treatment groups. For the sample 
size and power computations, it is assumed that both treatment groups have a response rate of 
0.91 (based on Gilead Studies GS-US-292-0104 and GS-US-292-0111), that the non-inferiority 
margin is 0.12, and that the significance level of the test is at a one-sided 0.025 level.
8.11.
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 the 
first 300 subjects enrolled have completed Week 12 of the study or prematurely discontinues 
from the study drug, as well as after all subjects have completed Week 24 of the study or 
prematurely discontinues from the study drug. However, Gilead will defer to the IDMC for any 
decision to convene earlier or more frequently. The IDMC will examine the safety results of the 
trial and also focus on logistical issues such as accrual, retention, quality of clinical and 
laboratory data, and implications of results of external studies. Blinding will be preserved during 
the conduct of the study and access to unblinded data will be limited to designated parties.
No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
For each IDMC analysis performed prior to the analysis of the primary efficacy endpoint, an 
alpha penalty of 0.00001 will be applied for the primary analysis of the primary endpoint.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject: These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 


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investigator must use the most current IRB- or IEC-approved consent form for documenting 
written informed consent. Each informed consent (or assent as applicable) will be appropriately 
signed and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB or IEC or
local requirements. 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, eCRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);


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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 


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data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), 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. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files.
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs or IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.


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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB or IEC 
in accordance with local requirements and receive documented IRB or IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(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.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
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.
25149
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 
2000. Lancet 2003;362 (9387):847-52.
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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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table (Blinded Phase)
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-9883/Fff AF 
Protocol GS-US-380-1489 
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Original 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404. 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 
GS-9883/Emtricitabine/Tenofovir AJafenamide Versus Abacavir/Dolutegr avir/Lamivudine 
in HJV-1 Infected, Anti.retroviral Treatment-Naive Adults 
GS-US-380-1489 Original Protocol, 21 October 2015 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Hal Martin, MD (Printed) 
Author 
Date 
JPPD 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 89 
21 October 2015 


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Appendix 2.
Study Procedures Table (Blinded Phase)
Study Procedures
Screeninga
Day 
1b
End of Weeke, r
Post-
Week
96e, s
Unblinding 
Visit
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
4
8
12
24
36
48
60
72
84
96
Every 
12 Weeks
Informed Consent
X
Medical History
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed 
Physical Exam
X
X
X
d
Xd
Xd
X
Xd
X
Xd
Xd
Xd
Xd
Xd
X
Xd,f
Xf
12-Lead ECG (performed 
supine)
X
X
X
X
X
X
Questionnaires
X
X
X
X
DXA scan (spine & hip)g
X
X
X
X
X
X
Height
X
Vital signs (blood pressure, 
pulse, respiration rate, and 
temperature), including 
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profilei
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf


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Study Procedures
Screeninga
Day 
1b
End of Weeke, r
Post-
Week
96e, s
Unblinding 
Visit
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
4
8
12
24
36
48
60
72
84
96
Every 
12 Weeks
Metabolic Assessmentsj
X
X
X
X
X
X
Xt
X
Estimated Glomerular 
Filtration Rate
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HLA-B*5701
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluations of inflammation 
and immune activation, 
platelet function and renal 
tubular function
X
X
X
X
X
Xt
X
Plasma & Urine Storage 
Sample 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HBV and HCV Serology
X
HIV-1 Genotypel
Xl
HIV-1 Genotype/Phenotypee
Xe
Single PK Samplem
X
X
X
Trough PK Samplesn
X
X
Optional Whole blood/EDTA 
for HLA testing, UGT1A1 and 
biomarkers
X


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Study Procedures
Screeninga
Day 
1b
End of Weeke, r
Post-
Week
96e, s
Unblinding 
Visit
30-Day 
Follow-upq
Early 
Study 
Drugs 
DCc
4
8
12
24
36
48
60
72
84
96
Every 
12 Weeks
Randomizationv
X
Provide subject dosing diary to 
subjects
X
X
X
X
X
Optional PK Substudyo
X
X
Optional PBMC Substudyp
X
X
X
Study Drug Dispensation
Xb
X
X
X
X
X
X
X
X
X
X
X
Xu
Study Drug Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures at the Day 1 visit, with the exception of DXA.
c
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Unblinding Visit even if the subject discontinues study drug.
d
Symptom-directed physical examination as needed.
e
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Section 6.14.1 and Section 6.14.2).
f
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to Day 1, or is otherwise explained.
g
DXA scans to be performed in all eligible subjects on study drug, except for those in Germany, prior to or within 24 hours of the Day 1 Visit, Weeks 24, 48, 96 (±10 days), 
and at Unblinding Visit (±10 days) and the ESDD visit (if the last scan was acquired > 12 weeks from the date of the ESDD Visit).
h
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
i
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN) At Day 1, Weeks 12, 24, 48, 72 and 96, and Unblinding Visit, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of 
the chemistry profile. Additionally: TSH will be analyzed at Screening, Day 1, Weeks 24, 48, 72 and 96 followed by every 24 weeks post Week 96, Unblinding Visit and 
Early Study Drugs Discontinuation visit.
j
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.


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k
CBC with differential and platelet count.
l
The Investigator must have received the results from the screening genotype report before proceeding with the Day 1 visit.  Screening genotype report must show sensitivity 
to TFV, FTC, 3TC and ABC.
m
A single PK blood sample will be collected at any time pre or post-dose
n
A trough PK blood sample will be collected between 20-28 hours following the last dose. Following an observed dose, a single post dose blood sample will be collected 
between 1 and 4 hours post dose.
o
A PK substudy will be performed in a subset of subjects (n=30) at selected study sites.  The pharmacokinetic substudy visit must occur at the Week 4 or Week 8 visits. The 
substudy will include intensive PK profiling in plasma
p
A PBMC substudy will be performed in a subset of subjects (n=50) at selected study sites.   A PBMC sample will be collected at Day 1 and Weeks 36 and 84.
q
Only required for those subjects not enrolling in the open-label rollover extension or those subjects who permanently discontinue study drugs and do not continue in the study 
through at least one subsequent visit after the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be 
used.
r
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to
Week 96, unless otherwise specified. The visit window at Weeks 48 and 96 will be ± 6 weeks of the protocol-specified visit date.
s
After Week 96, subjects will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded.  Visit window of 
6 days for study visits post Week 96.  After Week 96 Visit, subjects in the United Kingdom will stop taking study drug and complete a 30 day follow up visit.
t
To be performed every 24 weeks after Week 96 until Unblinding Visit.
u
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension.
v
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit, provided that all screening procedures have been completed and subject eligibility has been 
confirmed.


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Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
Grade 1 
L------G-ra_d_e_2----~ 
~
~ ______ G_rn_d_e_3----~~ ~~ _________ G_rn_d_e_4--------~ 
! 
! 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
If confLITlled and possibly and/or probably related to investigational 
medicinal products: 
I. Withhold investigational medicinal products until ~ Grade 2 
2. 
Restart all investigational medicinal products at fi.11l dose 
1 
IF Grade 3 or 4 recurrence that is con finned and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
1 
If c 
Repeat lab to 
confirm toxicity 
grnde 
1 
inve 
onfll'lTied and unrelated to 
stigational medicinal products, 
mg may continue at the discretion 
1e investigator 
dos 
oft! 
IF confirmed and 
possibly or probably 
--. related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
IF Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
Page 94 
21 October 2015 


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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


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
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


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
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-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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21 October 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L                
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L                 
2.0 t o <2.5 mmolL
2.0 mEq/L                         
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant <1 Year
>ULN to 6.0 mEq/L           
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L             
6.5 to 7.0 mmol/L
7.0 mEq/L                  
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 99
21 October 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 100
21 October 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 101
21 October 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 102
21 October 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
LDL (Fasting)
Adult
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
LDL (Fasting)
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to  4.92 mmol/L
>4.92 mmol/L
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects >70 yrs.  Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.


GS-9883/F/TAF
Protocol GS-US-380-1489
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-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 104
21 October 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.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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21 October 2015
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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Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
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21 October 2015
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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RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced to 
70% to 80%
FEV1 or peak flow 50% to 69%
FEV1 or peak flow 25% to 
49% 
Cyanosis OR FEV1 or peak flow 
25% OR Intubation
Dyspnea or Respiratory 
Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities 
Dyspnea on exertion causing 
greater than minimal interference 
with usual social & functional 
activities 
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate for 
age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 
90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
OR Pulse oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis OR 
Medical intervention indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in affected 
eye(s) 
Visual Changes (from 
baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing greater 
than minimal interference with 
usual social & functional 
activities
Visual changes causing 
inability to perform usual 
social & functional activities
Disabling visual loss in affected 
eye(s)


GS-9883/F/TAF
Protocol GS-US-380-1489
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


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


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


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


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


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


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


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


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


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


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


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Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC 
Guidelines)
1. Candidiasis of bronchi, trachea, or lungs
2. Candidiasis of esophagus
3. Cervical cancer, invasive
4. Coccidioidomycosis, disseminated or extrapulmonary
5. Cryptococcosis, extrapulmonary
6. Cryptosporidiosis, chronic intestinal (1 month duration)
7. Cytomegalovirus disease (other than liver, spleen or nodes)
8. Cytomegalovirus retinitis (with loss of vision)
9. Encephalopathy, HIV-related
10. Herpes simplex: chronic ulcer(s) (1 month duration); or bronchitis, pneumonitis or 
esophagitis
11. Histoplasmosis, disseminated or extrapulmonary
12. Isosporiasis, chronic intestinal (1 month duration)
13. Kaposi’s sarcoma
14. Lymphoma, Burkitt’s (or equivalent term)
15. Lymphoma, immunoblastic (or equivalent term)
16. Lymphoma, primary, of brain
17. Mycobacterium avium complex or Myobacterium kansasii, disseminated or extrapulmonary
18. Mycobacterium tuberculosis, of any site, pulmonary, disseminated or extrapulmonary
19. Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
20. Pneumocystis jirovecii (previously known as “Pneumocystis carinii) pneumonia
21. Pneumonia, recurrent
22. Progressive multifocal leukoencephalopathy
23. Salmonella septicemia, recurrent
24. Toxoplasmosis of brain
25. Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {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.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b)
Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2)
Contraception Requirements for Female Subjects
a)
Study Drug Effects on Pregnancy and Hormonal Contraception
The 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 current Prescribing 
Information and local product labeling for ABC/DTG/3TC for additional information.
b)
Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Day 1 visit prior to randomization. At 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)
Contraception Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment and until 90 days after the 
end of relevant systemic exposure.  Additional contraception recommendations should also be 
considered if the female partner is not pregnant.
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
4)
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM).  Female condom and male condom should not 
be used together.
5)
Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Subjects whose partner 
has become pregnant or suspects she is pregnant during the study must report the information to 
the investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy 
outcome are outlined in Section 7.3.

SAP_007.pdf: 
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SAP_009.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the 
Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir 
Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 
Infected, Antiretroviral Treatment-Naïve Adults
Name of Test Drug:
Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF; GS-9883/F/TAF)
Study Number:
GS-US-380-1489
Protocol Version (Date):
Amendment 2 (19 October 2016)
Analysis Type:
Week 144 Interim Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
13 May 2019
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(rJ GILEAiJ 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF ABBREVIATIONS........................................................................................................................................5
1.
INTRODUCTION ................................................................................................................................................8
1.1.
Study Objectives ......................................................................................................................................8
1.2.
Study Design............................................................................................................................................8
1.3.
Sample Size and Power..........................................................................................................................11
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................12
2.1.
Data Monitoring Committee Analyses...................................................................................................12
2.2.
Interim Analyses ....................................................................................................................................12
2.2.1.
Week 48 Analysis.................................................................................................................12
2.2.2.
Week 96 Analysis.................................................................................................................12
2.2.3.
Week 144 Analysis...............................................................................................................12
2.3.
Final Analysis ........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................13
3.1.
Analysis Sets..........................................................................................................................................13
3.1.1.
All Randomized Analysis Set...............................................................................................13
3.1.2.
Full Analysis Set ..................................................................................................................13
3.1.3.
Per Protocol Analysis Set.....................................................................................................14
3.1.4.
Safety Analysis Set...............................................................................................................15
3.1.5.
DXA Analysis Set ................................................................................................................15
3.2.
Subject Grouping ...................................................................................................................................15
3.3.
Strata and Covariates..............................................................................................................................15
3.4.
Examination of Subject Subgroups........................................................................................................16
3.4.1.
Subject Subgroups for Efficacy Analyses ............................................................................16
3.4.2.
Subject Subgroups for Safety Analyses ...............................................................................16
3.5.
Multiple Comparisons............................................................................................................................16
3.6.
Missing Data and Outliers......................................................................................................................16
3.6.1.
Missing Data ........................................................................................................................16
3.6.2.
Outliers.................................................................................................................................17
3.7.
Data Handling Conventions and Transformations .................................................................................17
3.8.
Analysis Windows .................................................................................................................................18
3.8.1.
Definition of Study Day .......................................................................................................18
3.8.2.
Analysis Windows................................................................................................................18
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window................................................................................................................................22
4.
SUBJECT DISPOSITION ..................................................................................................................................23
4.1.
Subject Enrollment and Disposition.......................................................................................................23
4.1.1.
Subject Enrollment...............................................................................................................23
4.1.2.
Subject Disposition ..............................................................................................................23
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................23
4.2.1.
Duration of Exposure to Study Drug....................................................................................23
4.2.2.
Adherence to Study Drug Regimen......................................................................................24
4.3.
Protocol Deviations................................................................................................................................25
5.
BASELINE CHARACTERISTICS....................................................................................................................26
5.1.
Demographics and Baseline Characteristics ..........................................................................................26


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5.2.
Baseline Disease Characteristics............................................................................................................26
5.3.
Medical History......................................................................................................................................27
6.
EFFICACY ANALYSES ...................................................................................................................................28
6.1.
Primary Efficacy Endpoint.....................................................................................................................28
6.2.
Secondary Efficacy Endpoints ...............................................................................................................28
6.2.1.
Definition of the Secondary Efficacy Endpoints..................................................................28
6.2.2.
Analysis of the Secondary Efficacy Endpoints ....................................................................29
6.3.
Tertiary Efficacy Endpoints ...................................................................................................................32
6.3.1.
Definition of the Tertiary Efficacy Endpoints......................................................................32
6.3.2.
Analysis of the Tertiary Efficacy Endpoints ........................................................................32
6.4.
Changes From Protocol-Specified Efficacy Analyses............................................................................33
7.
SAFETY ANALYSES........................................................................................................................................34
7.1.
Adverse Events and Deaths....................................................................................................................34
7.1.1.
Adverse Event Dictionary ....................................................................................................34
7.1.2.
Adverse Event Severity........................................................................................................34
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................34
7.1.4.
Serious Adverse Events........................................................................................................34
7.1.5.
Treatment-Emergent Adverse Events...................................................................................34
7.1.6.
Summaries of Adverse Events and Death ............................................................................35
7.1.7.
Additional Analysis of Adverse Events ...............................................................................36
7.2.
Laboratory Evaluations ..........................................................................................................................37
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................37
7.2.2.
Graded Laboratory Values ...................................................................................................38
7.2.3.
Metabolic Laboratory Evaluations .......................................................................................39
7.2.4.
Liver-Related Laboratory Evaluations .................................................................................40
7.2.5.
Renal-Related Laboratory Evaluations.................................................................................41
7.3.
Bone Safety Analyses ............................................................................................................................42
7.3.1.
Bone Mineral Density ..........................................................................................................42
7.4.
Body Weight, Height, and Vital Signs...................................................................................................43
7.5.
Prior and Concomitant Medications.......................................................................................................43
7.5.1.
Nonstudy Drug Antiretroviral Medications..........................................................................43
7.5.2.
Concomitant Non-ARV Medications...................................................................................44
7.6.
Electrocardiogram Results .....................................................................................................................44
7.7.
Other Safety Measures ...........................................................................................................................44
7.8.
Changes From Protocol-Specified Safety Analyses...............................................................................45
8.
PHARMACOKINETIC ANALYSES ................................................................................................................46
9.
SPECIAL POPULATION ANALYSES.............................................................................................................47
9.1.
Analyses for HIV/HBV Coinfected Subjects.........................................................................................47
9.2.
Analyses for HIV/HCV Coinfected Subjects.........................................................................................47
10.
REFERENCES ...................................................................................................................................................49
11.
SOFTWARE.......................................................................................................................................................50
12.
SAP REVISION..................................................................................................................................................51
13.
APPENDICES ....................................................................................................................................................52
Appendix 1.
Study Procedures Table..........................................................................................................53
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for Naïve Trial)...................................59
Appendix 3.
Stratum-Adjusted Mantel-Haenszel Proportion Analysis.......................................................60
Appendix 4.
Region Definition...................................................................................................................61


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Appendix 5.
Cardiovascular or Cerebrovascular Events.............................................................................62
Appendix 6.
Hepatic Events........................................................................................................................63
Appendix 7.
Programming Specification....................................................................................................64
LIST OF IN-TEXT TABLES
Table 3-1.
Subjects Included or Excluded from Week 144 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA Assessment in Week 
144 Analysis Window ............................................................................................................14
Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, Hematology, 
Chemistry, Urinalysis, Urine Pregnancy Laboratory Tests, eGFRCG, Vital Signs, and 
Weight ....................................................................................................................................19
Table 3-3.
Analysis Windows for Metabolic Assessments......................................................................20
Table 3-4.
Analysis Windows for TSH and Renal Function....................................................................20
Table 3-5.
Analysis Windows for HBV and HCV Serology, HBV DNA, and HCV RNA 
Assessments............................................................................................................................21
Table 3-6.
Analysis Windows for Safety ECG........................................................................................21
Table 3-7.
Analysis Windows for DXA BMD ........................................................................................21
Table 7-1.
Normal, Osteopenia, and Osteoporosis as Defined by T-score ..............................................42


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LIST OF ABBREVIATIONS
3TC
lamivudine
ABC
abacavir
ABC/DTG/3TC
fixed dose combination of abacavir (ABC) 600 mg / dolutegravir (DTG) 50 mg / 
lamivudine (3TC) 300 mg
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARV
antiretroviral
ART
antiretroviral treatment
AST
aspartate aminotransferase
BIC
bictegravir
B/F/TAF
fixed dose combination of bictegravir (BIC; B) 50 mg / emtricitabine (FTC; F) 200 mg /
tenofovir alafenamide (TAF) 25 mg
BLQ
below limit of quantitation
BMD
bone mineral density
BMI
body mass index
CDER
Center for Drug Evaluation and Research
CG
Cockcroft-Gault
CI
confidence interval
CMH
Cochran-Mantel-Haenszel 
CRF
case report form
CSR
clinical study report 
CV
coefficient of variation
DC
premature study drug discontinuation
DNA
deoxyribonucleic acid
DTG
dolutegravir, tivicay
DXA
dual energy x-ray absorptiometry
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
full Analysis Set
FDA
Food and Drug Administration
FDC
fixed dose combination
F/TAF
fixed dose combination of emtricitabine (FTC; F)/ tenofovir alafenamide (TAF)
FTC, F
emtricitabine
GEN
Genvoya, E/C/F/TAF
GFR
glomerular filtration rate


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Gilead
Gilead Sciences, Inc.
GS-9883
bictegravir
HBcAb
hepatitis B core antibody 
HBeAb
hepatitis B e-antibody 
HBeAg
hepatitis B e-antigen
HBsAb
hepatitis B surface antibody 
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb
hepatitis C antibody
HDL
high density lipoprotein
HIV-1
human immunodeficiency virus (Type 1) 
HLGT
high level group term
HLT
high level term
ICH
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use
ID
identification
IDMC
independent data monitoring committee
IWRS
interactive web response system
LDL
low density lipoprotein
LLT
lowest level term
MedDRA
Medical Dictionary for Regulatory Activities
MH
Mantel-Haenszel 
PEP
post-exposure prophylaxis 
PrEP
pre-exposure prophylaxis
PK
pharmacokinetic
PP
per protocol
PT
preferred term
PVE
Pharmacovigilance and Epidemiology
Q
quartile
Q1
first quartile
Q3
third quartile
QD
once daily
RBP
retinol binding protein
RNA
ribonucleic acid
SAE
serious adverse events
SAP
statistical analysis plan
SD
standard deviation
SMQ
Standardised MedDRA Query
SOC
system organ class


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TAF
tenofovir alafenamide 
TFL
tables, figures, and listings
TFV
tenofovir
TSH
thyroid stimulating hormone; thyrotropin
ULN
upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) of the Week 144 interim analysis 
for Study GS-US-380-1489, which will be performed when all subjects have completed their 
Week 144 visit or prematurely discontinued from the study drug. This SAP is based on the study 
protocol amendment 2 dated 19 October 2016 and the electronic case report form (eCRF). The 
SAP will be finalized before database finalization for the interim analysis. Any changes made 
after the finalization of the SAP will be documented in the clinical study report (CSR).
1.1.
Study Objectives
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) containing bictegravir
(GS-9883; BIC; B) /emtricitabine (FTC; F) /tenofovir alafenamide (TAF) versus a FDC 
containing abacavir /dolutegravir /lamivudine (ABC/DTG/3TC) in HIV-1 infected, 
antiretroviral treatment (ART)-naïve adult subjects as determined by the achievement of 
HIV-1 ribonucleic acid (RNA) < 50 copies/mL at Week 48.
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the 2 treatment groups through 
Weeks 48, 96, and 144.

To evaluate the bone safety of the 2 treatment groups as determined by the percentage change 
from baseline in hip and spine bone mineral density (BMD) through Weeks 48, 96, and 144.
1.2.
Study Design
Design Configuration and Subject Population
GS-US-380-1489 is a randomized, double-blinded, multicenter, active-controlled study to 
evaluate the safety and efficacy of B/F/TAF FDC versus ABC/DTG/3TC FDC in HIV-1 infected
ART-naive adult subjects.


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Treatment Groups
Subjects who provide written consent and meet all eligibility criteria will be randomized in a 
1:1 ratio to one of the following 2 treatment groups:

Treatment Group 1: FDC of bictegravir 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (B/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard 
to food (n = 300)

Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of bictegravir 50 mg/ emtricitabine 
200 mg/ tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily, without 
regard to food (n = 300)
Key Eligibility Criteria
Medically stable HIV-1 infected subjects who meet the following criteria:

Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening

ART-naive (≤ 10 days of prior therapy with any antiretroviral [ARV] agent following a 
diagnosis of HIV-1 infection) except the use for pre-exposure prophylaxis (PrEP) or 
post-exposure prophylaxis (PEP), up to 1 month prior to screening.

Screening genotype report must show sensitivity to FTC, tenofovir (TFV), 3TC, and ABC

Negative screening test for HLA-B*5701 allele

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine 
clearance

No chronic Hepatitis B Virus (HBV) infection, as determined by either
Positive HBV surface antigen (HBsAg) and negative HBV surface antibody (HBsAb), 
regardless of HBV core antibody (HBcAb) status, at the screening visit
Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
Study Periods / Phases
Subjects will be treated for at least 144 weeks during the blinded treatment phase. After 
Week 144, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead Sciences Inc. (Gilead) completes the Week 144 analysis, all subjects 


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will return to the clinic (preferably within 30 days) for an End of Blinded Treatment Visit. At the 
End of Blinded Treatment Visit, if safety and efficacy of B/F/TAF FDC are demonstrated 
following review of unblinded data, subjects in a country where B/F/TAF FDC is not available 
will be given the option to receive B/F/TAF FDC in an open-label (OL) extension phase for up 
to 48 weeks, or until the product becomes accessible to subjects through an access program, or 
until Gilead elects to discontinue the study in that country, whichever occurs first. 
All subjects participating in the OL extension phase, without regard to their blinded treatment 
regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for up to 
48 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the OL B/F/TAF FDC extension phase will be required to return to the clinic after 
the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
Schedule of Assessments
After screening procedures, eligible subjects will be randomized 1:1 to Treatment Group 1 or 
Treatment Group 2 and treated for 144 weeks. Following the Day 1 visit, subjects will be 
required to return for study visits at Weeks 4, 8, and 12, and then every 12 weeks from Week 12 
through Week 144. After Week 144, all subjects will continue to take their blinded study drugs 
and attend study visits every 12 weeks until the End of Blinded Treatment Visit.
For all eligible subjects, blood will be collected at Day 1, Weeks 4, 8, 12, and then every 
12 weeks through the End of Blinded Treatment Visit. Laboratory analyses (hematology, 
chemistry, and urinalysis), HIV-1 RNA, CD4+ cell count, and complete or symptom directed 
physical examinations will be performed at Screening, Day 1, and all subsequent visits. In
addition, blood will be collected and stored for possible evaluation of markers of inflammation 
and immune activation, which may include but are not limited to: cystatin-C, IL-6, hs-CRP, 
d-dimer, sCD14, and sCD163. Platelet function evaluations may also be assessed, including but 
not limited to soluble glycoprotein VI (sGPVI), P-selectin, and soluble CD40 ligand. Urine will 
be collected for evaluations of renal function including urine albumin, urine creatinine, urine 
protein, retinol binding protein (RBP), and beta-2 microglobulin.
For all subjects on study drug, except subjects located in Germany, dual energy x-ray 
absorptiometry (DXA) scans will be performed prior to or within 24 hours of the Day 1 Visit, 
and then at Weeks 24, 48, 96, 144 and at the End of Blinded Treatment Visitor Early Study Drug 
Discontinuation Visit, if > 12 weeks since last scan. DXA scan results will be provided to study 
sites when available.
Adverse events and concomitant medications will be assessed at each visit.
More details for study procedures can be found in Appendix 1.


BIFITAF 
GS-US-380-1489 
Statistical Analysis Plan - Week 144 Interim Analysis 
Pharmacokinetics 
Version 1.0 
For all subjects on study chug, a single anytime pre- or post-dose PK blood sample will be 
collected at Weeks 8, 24, and 36. 
For all subjects on study chug, a trnugh PK blood sample will be obtained 20-28 hours following 
the last dose at Weeks 4 and 12. Following an observed dose, one post-dose PK blood sample 
will be collected between 1 and 4 hours post-dose. 
Randomization 
Subjects will be randomized in a 1: 1 ratio to 1 of 2 Treatment Groups (Treatment Group 1: 
Treatment Group 2). Randomization will be strntified by HIV-1 RNA level 
(~ 100,000 copies/mL, > 100,000 to ~ 400,000 copies/mL, or > 400,000 copies/mL) at screening, 
CD4+ cell count (< 50 cells/µL, 50- 199 cells/µL, or ~ 200 cells/µL) at screening, and region 
(US or Ex-US) at randomization. 
Site and/or Stratum Enrollment Limits 
Approximately 150 study sites in No1th America, Europe, and Latin America paiticipated. There 
was no emollment limit for individual sites. 
Study Duration 
The randomized, double-blind phase of this study is at least 144 weeks in duration. 
1.3. 
Sample Size and Power 
A total of approximately 600 HIV-1 infected subjects, randomized in a 1: 1 ratio to 2 treatment 
groups (300 subjects per treatment group), achieves at least 95% power to detect a noninferiority 
margin of 12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as detennined by the 
United States [US] Food and Drng Achninistration [FDA]-defined snapshot algorithm) difference 
between the 2 treatment groups. For sample size and power computation, it is assumed that both 
treatment groups have a response rate of 91 % (based on Gilead Genvoya [GEN; E/C/F IT AF] 
Studies GS-US-292-0104 and GS-US-292-0111), that a noninferiority margin is 12%, and that 
the significance level of the test is at a one-sided 0.025 level. Sample size and power calculations 
were made using the statistical softwai·e package nQue1y Advisor (Version 6.0). 
CONFIDENTIAL 
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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee Analyses
The Week 12 Independent Data Monitoring Committee (IDMC) analysis was conducted after 
approximately the first 50% of subjects enrolled completed their Week 12 visit or prematurely 
discontinued the study drug. The Week 24 IDMC analysis was conducted after all subjects 
enrolled completed their Week 24 visit or prematurely discontinued the study drug. The purpose 
of these interim analyses was to provide the IDMC with a statistical report for review. More 
details are documented in the IDMC charter.
Gilead does not have a prior intent to ask the IDMC to review Week 48 results or to consider 
early termination of the study even if there is early evidence of favorable efficacy for B/F/TAF. 
2.2.
Interim Analyses
2.2.1.
Week 48 Analysis
The Week 48 analysis was conducted after all subjects either completed their Week 48 visit or 
prematurely discontinued from the study drug.
2.2.2.
Week 96 Analysis
The Week 96 analysis was conducted after all subjects either completed their Week 96 visit or 
prematurely discontinued from the study drug.
2.2.3.
Week 144 Analysis
The Week 144 analysis will be conducted after all subjects either complete their Week 144 visit 
or prematurely discontinue from the study drug.
This statistical analysis plan describes the analysis plan for the Week 144 interim analysis. 
2.3.
Final Analysis
The final statistical analysis will be conducted after all subjects either complete the study or 
prematurely discontinue from the study.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set unless 
otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). Data 
collected on log forms, such as AEs, will be presented in chronological order within a subject. 
The treatment group to which subjects were randomized will be used in the listings. 
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. For randomized but never dosed subjects, age on the date of 
randomization will be used. For screen failures, age on the date of the informed consent was 
signed will be used. If only birth year is collected on the eCRF, “01 January” will be used for the 
unknown birth day and month for the purpose of age calculation, similarly, if only birth year and 
month are collected on the eCRF, “01” will be used for the unknown birth day for the purpose of 
age calculation.
In general, permanent discontinuation of study drug refers to premature discontinuation of study 
drug or completion of study drug.
3.1.
Analysis Sets
Analysis Sets define the subjects to be included in an analysis. Analysis Sets and their definitions 
are provided in this section. Subjects included in each Analysis Set will be determined before the 
study blind is broken for analysis. The Analysis Set will be included as a subtitle of each table, 
figure, and listing. A summary of the number and percentage of subjects in each Analysis Set
will be provided by treatment group and in total.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set will include all subjects who are randomized into the study.
This is the primary Analysis Set for by-subject listings.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) will include all subjects who (1) are randomized into the study and 
(2) have received at least 1 dose of study drug. Subjects will be grouped according to the 
treatment to which they were randomized. For the FAS, all efficacy data, including data 
collected after the last dose of study drug, will be included, unless specified otherwise. This is 
the primary Analysis Set for efficacy analyses.


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3.1.3.
Per Protocol Analysis Set
The Week 144 Per Protocol (PP) Analysis Set will include all subjects who (1) are randomized 
into the study, (2) have received at least 1 dose of study drug, and (3) have not committed any 
major protocol violation, including the violation of key entry criteria. Subjects will be grouped 
according to the treatment they actually received. For the PP analysis, efficacy data up to 1 day 
after permanent discontinuation of study drug will be included. The Week 144 PP Analysis Set is 
the secondary Analysis Set for efficacy analysis.  
Subjects meeting any of the following criteria will be excluded from the Week 144 PP Analysis 
Set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 144 analysis window, 
except when missing is due to discontinuation of study drug for lack of efficacy. (Note: lack 
of efficacy is defined as having the check-box for Lack of Efficacy marked as the reason for 
premature study drug discontinuation in the “Blinded Treatment” study phase on the study 
drug completion eCRF page; Table 3-1). 
Table 3-1.
Subjects Included or Excluded from Week 144 PP Analysis Set Due to 
Premature Discontinuation of Study Drug and/or Missing HIV-1 
RNA Assessment in Week 144 Analysis Window
Discontinuation from Study Drug prior to or on the 
Upper Bound of Week 144 Analysis Window
HIV-1 RNA Data on Randomized Treatment 
Available in Week 144 Analysis Window
Yes
No
Yes
Due to Lack of Efficacy
+
+
Due to Other Reasons
+
-
No
+
-
+ = Inclusion of Subjects in Week 144 PP Analysis Set; - = Exclusion of Subjects in Week 144 PP Analysis Set.

Subjects who do not meet the inclusion criterion that the screening genotype report must 
show sensitivity to FTC, TFV, ABC, and 3TC

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in Section 4.3 of the study protocol including drugs not to be 
used with BIC, FTC, TAF, DTG, ABC, and 3TC

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 144 Visit below the 2.5th percentile


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3.1.4.
Safety Analysis Set
The Safety Analysis Set 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 
permanent discontinuation of the study drug will be included in the safety summaries, unless 
specified otherwise. Subjects will be grouped according to the treatment they actually received.
This is the primary Analysis Set for safety analyses.
3.1.5.
DXA Analysis Set
3.1.5.1.
Hip DXA Analysis Set
The Hip DXA Analysis Set will include all subjects who (1) are randomized into the study, 
(2) have received at least 1 dose of study drug, and (3) have nonmissing baseline hip BMD 
values. Subjects will be grouped according to the treatment they actually received.
3.1.5.2.
Spine DXA Analysis Set
The Spine DXA Analysis Set will include all subjects who (1) are randomized into the study, 
(2) have received at least 1 dose of study drug, and (3) have nonmissing baseline spine BMD 
values. Subjects will be grouped according to the treatment they actually received.
For the hip DXA and spine DXA Analysis Sets, all data, including data collected after the last 
dose of study drug, will be used for analysis, unless specified otherwise.
3.2.
Subject Grouping
For analyses based on the All Randomized Analysis Set or the FAS, subjects will be grouped by 
randomized treatment. For other analyses, subjects will be grouped by actual treatment received. 
The actual treatment received will differ from the randomized treatment only when the actual 
treatment received differs from randomized treatment for the entire treatment duration.
3.3.
Strata and Covariates
Randomization was 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, CD4+ cell count (< 50 cells/μL, 
50 - 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US or Ex-US) at randomization.
Efficacy analyses will include 2-level HIV-1 RNA stratum (≤100,000 vs. > 100,000 copies/mL) 
at baseline and region stratum (US vs. Ex-US) at randomization as stratification factors. The 
CD4+ cell count stratum was excluded for the analysis due to the following reasons: 
(1) HIV-1 RNA level and CD4+ cell count are highly correlated; (2) a balanced CD4+ cell count 
distribution between treatment groups is expected since CD4+ cell count was one of the 
stratification factors used during the randomization; and (3) the risk of including small or 
missing stratum during the analysis will be reduced. The HIV-1 RNA stratum will be reclassified
using baseline HIV-1 RNA level for analysis purposes. Furthermore, since the number of 
subjects in the HIV-1 RNA > 400,000 copies/mL stratum is small, this stratum will be combined 
with HIV-1 RNA > 100,000 to ≤400,000 copies/mL stratum to form a 2-level HIV-1 RNA 
stratum (≤100,000 vs. > 100,000 copies/mL). This will prevent small or missing stratum during 
the analysis. 


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3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Efficacy Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 144 determined by the 
US FDA-defined snapshot algorithm {U. S. Department of Health and Human Services 2015}
will be analyzed for the following subject subgroups (see Section 6.2.2.2 for details):

Age (years): (a) < 50 and (b) ≥ 50

Sex: (a) male and (b) female

Race: (a) black and (b) nonblack

Baseline HIV-1 RNA level (copies/mL): (a) ≤ 100,000 and (b) > 100,000

Baseline CD4+ cell count (/μL): (a) < 200 and (b) ≥ 200

Region: (a) US and (b) Ex-US

Study drug adherence (%): (a) < 95 and (b) ≥ 95 (based on adherence up to Week 144 visit)
3.4.2.
Subject Subgroups for Safety Analyses 
Selected safety endpoints may be analyzed for the following subject subgroups (see Section 9.1
for details):

Subjects with incident HIV/hepatitis B virus (HBV) coinfection while on study drug (if any)
Selected safety endpoints will be analyzed for the following subject subgroups (see Section 9.2
for details):

Subjects with HIV/hepatitis C virus (HCV) coinfection at baseline

Subjects with incident HIV/HCV coinfection while on study drug (if any)
3.5.
Multiple Comparisons
No alpha level adjustment is applied other than for the primary endpoint.
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
A missing datum for a given study analysis window may be due to any of the following reasons:

A visit occurring in the window but data were not collected or were unusable 

A visit not occurring in the window

A subject prematurely discontinuing from the study before reaching the window


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In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.
For missing last dosing date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for 
concomitant medications in Section 7.5.1.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety 
outcomes, unless specified otherwise. All data will be included in the analyses.
3.7.
Data Handling Conventions and Transformations
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 as follows except for urine creatinine:

A value that is 1 unit less than the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “< x” (where x is considered the 
limit of quantitation). For example, if the values are reported as < 50 and < 5.0, values of 
49 and 4.9, respectively, will be used for calculation of summary statistics. An exception to 
this rule is any value reported as < 1 or < 0.1, etc. For values reported as < 1 or < 0.1, a value 
of 0.9 or 0.09, respectively, will be used for calculation of summary statistics.

A value that is 1 unit above the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “> x” (where x is considered the 
limit of quantitation). Values with decimal points will follow the same logic as above.

The limit of quantitation will be used for calculation of descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the limit of quantitation).
For urine creatinine, a value of “< 1” is handled as a missing value in its summary and the 
calculation of related ratios. 
Logarithmic (base 10) transformations will be applied to HIV-1 RNA and HBV DNA data for 
efficacy analyses. 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 purposes. HBV DNA results of 
“<20 IU/mL HBV DNA detected” or “No HBV DNA detected” will be imputed as 19 IU/mL for 
analysis purposes. HCV RNA results of “<15 IU/mL HCV RNA detected” or “No HCV RNA 
detected” will be imputed as 14 IU/mL for analysis purposes. 


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3.8.
Analysis Windows
3.8.1.
Definition of Study Day
Study Day 1 is defined as the day when the first dose of study drug (ie, B/F/TAF or Placebo,
ABC/DTG/3TC or Placebo) was taken, as recorded on the Study Drug Administration eCRF 
form.
Study Days are calculated relative to Study Day 1. For events that occurred on or after the Study 
Day 1 date, study days are calculated as (visit date minus Study Day 1 plus 1). For events that 
occurred prior to Study Day 1, study days are calculated as (visit date minus Study Day 1).
Last Dose Date is the latest of the blinded study drug end dates recorded on the Study Drug 
Administration eCRF form with “Permanently Withdrawn” box checked for subjects who 
prematurely discontinued or completed study drug in the “Blinded Treatment” study phase 
according to the Study Drug Completion eCRF. 
If last dose date is missing (eg, only year of last dose date is known or completely missing due to 
lost to follow-up) for subjects who prematurely discontinued or completed blinded study drug at 
the data cut date, the latest of the study drug start dates and end dates, the clinical visit dates, and 
the laboratory visit dates, excluding the date of 30-day follow-up visit, will be used to impute the 
last dose date. For other partial missing last dose date, please see the programming specifications
for imputation rule details.
Last Study Date is the latest of the study drug start dates and end dates, the clinic visit dates, 
and the laboratory visit dates, including the 30-day follow-up visit date, for subjects who 
prematurely discontinued study or who completed study according to the Study Completion 
eCRF.
Baseline value is defined as the last value obtained on or prior to Study Day 1 for all 
assessments, except for DXA BMD. The baseline value for DXA BMD is defined as the last 
value obtained on or prior to Study Day 14. 
3.8.2.
Analysis Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
The analysis windows for HIV-1 RNA, CD4+ cell count, CD4 %, hematology, chemistry, 
urinalysis, urine pregnancy laboratory tests, eGFRCG, vital signs, and weight are presented in
Table 3-2.


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Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %,
Hematology, Chemistry, Urinalysis, Urine Pregnancy Laboratory 
Tests, eGFRCG, Vital Signs, and Weight
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 4
28
2
42
Week 8
56
43
70
Week 12
84
71
126
Week 24
168
127
210
Week 36
252
211
294
Week 48
336
295
378
Week 60
420
379
462
Week 72
504
463
546
Week 84
588
547
630
Week 96
672
631
714
Week 108
756
715
798
Week 120
840
799
882
Week 132
924
883
966
Week 144
1008
967
1050
Week K
(K is every 12 weeks after previous visit)
K*7
(K-6)*7+1
(K+6)*7
The analysis windows for metabolic assessments (including fasting glucose and lipid panel: total 
cholesterol, high density lipoprotein [HDL], direct low density lipoprotein [LDL], triglycerides, 
and total cholesterol to HDL ratio) are presented in Table 3-3.


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Table 3-3.
Analysis Windows for Metabolic Assessments
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 12
84
2
126
Week 24
168
127
252
Week 48
336
253
420
Week 72
504
421
588
Week 96
672
589
756
Week 120
840
757
924
Week 144
1008
925
1092
Week K
(K is every 24 weeks after previous visit)
K*7
(K-12)*7+1
(K+12)*7
The analysis windows for thyroid stimulating hormone (TSH; thyrotropin) and renal function 
(including urine albumin, urine creatinine, urine protein, urine RBP, and urine beta-2 
microglobulin, and derived ratios) are presented in Table 3-4.
Table 3-4.
Analysis Windows for TSH and Renal Function
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 24
168
2
252
Week 48
336
253
420
Week 72
504
421
588
Week 96
672
589
756
Week 120
840
757
924
Week 144
1008
925
1092
Week K
(K is every 24 weeks after previous visit)
K*7
(K-12)*7+1
(K+12)*7
The analysis windows for HBV or HCV serology (including HBsAb, HBsAg, hepatitis B 
e-antigen [HBeAg], hepatitis B e-antibody [HBeAb], HBcAb, and HCV antibody [HCVAb]), 
HBV DNA, and HCV RNA assessments are presented in Table 3-5.


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Table 3-5.
Analysis Windows for HBV and HCV Serology, HBV DNA, and 
HCV RNA Assessments
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 48
336
2
504
Week 96
672
505
840
Week 144
1008
841
1176
Week K
(K is every 48 weeks after previous visit)
K*7
(K-24)*7+1
(K+24)*7
The analysis windows for safety electrocardiogram (ECG) are presented in Table 3-6.
Table 3-6.
Analysis Windows for Safety ECG
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 24
168
2
252
Week 48
336
253
504
Week 96
672
505
840
Week 144
1008
841
1176
Week K
(K is every 48 weeks after previous visit)
K*7
(K-24)*7+1
(K+24)*7
The analysis windows for DXA BMD are presented in Table 3-7.
Table 3-7.
Analysis Windows for DXA BMD
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
14
Week 24
168
15
252
Week 48
336
253
504
Week 96
672
505
840
Week 144
1008
841
1176
Post Week 144
NA
1177
NA
NA = Not Applicable.
Note: The baseline value of DXA BMD is defined as the last value obtained on or prior to Study Day 14.


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3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Window
Depending on the statistical analysis method, single values are required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time to event analysis would not require one value per analysis window. When a single value is 
needed, the following rule(s) will be used. 
If multiple nonmissing numeric observations exist in a window, then records will be chosen as 
follows:

For baseline, the latest available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, average will be used for the baseline value, except for HIV-1 RNA (see below). 

For postbaseline visits:
For CD4+ cell count, CD4%, and BMD data, the record(s) collected on the latest day in 
the window will be selected for analysis.
For other numeric observations (ie, except HIV-1 RNA, CD4+ cell count, CD4%, and 
BMD data), the record(s) collected on the day closest to the nominal day for that visit 
will be selected. If there are 2 days equidistant from the nominal day, the later day will be 
selected.
For any numeric observations except HIV-1 RNA, if there are multiple records on the 
selected day, the average will be taken.   

For baseline and postbaseline HIV-1 RNA, the latest (considering both date and time) 
record(s) in the window will be selected. If both “HIV RNA Taqman 2.0” and “HIV RNA 
Repeat” (ie, the HIV-1 RNA result obtained from an additional aliquot of the original sample) 
are available with the same collection time, the results from the “HIV RNA Repeat” will be 
selected for analysis purposes; otherwise, if there are multiple “HIV RNA Taqman 2.0” 
records with the same collection time, the geometric mean will be taken for analysis purposes. 
If multiple valid nonmissing categorical observations exist in a window, records will be chosen 
as follows:

For baseline, the last available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected (eg, normal will be selected over 
abnormal for safety ECG findings).

For postbaseline visits, the most conservative value within the window will be selected 
(eg, abnormal will be selected over normal for safety ECG findings).


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
4.1.1.
Subject Enrollment
All necessary summaries on subject enrollment have been performed as part of the Week 48 
CSR, and will not be repeated for the Week 144 analysis.
4.1.2.
Subject Disposition
The summary of subject disposition will be provided by treatment group and overall for all 
screened subjects. This summary will include the number of subjects screened, screen failure 
subjects who were not randomized, subjects who met all eligibility criteria and were not 
randomized, subjects randomized, subjects randomized but never treated, subjects in the Safety 
Analysis Set, and subjects in the FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:

Still on study drug up to the data cut date

Prematurely discontinuing study drug prior to the data cut date (with summary of reasons for 
discontinuing study drug)

Still on study up to the data cut date

Prematurely discontinuing from study prior to the data cut date (with summary of reasons for 
discontinuing study).
The denominator for the percentages of subjects in each category will be the number of subjects 
in the Safety Analysis Set.
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
4.2.
Extent of Study Drug Exposure and Adherence
4.2.1.
Duration of Exposure to Study Drug
Duration of exposure to study drug will be defined as (the last dose date – the first dose date + 1), 
regardless of temporary interruptions in study drug administration, and will be expressed in weeks 
using up to 1 decimal place (eg, 4.5 weeks). For the calculation of the duration of exposure to 
study drug, the data cut date will be used to impute the last dose date for subjects who have not 
permanently discontinued study drug at the time of the data cut date.


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Duration of exposure to study drug will be summarized using descriptive statistics (n, mean, SD, 
median, Q1, Q3, minimum, and maximum) and as the number and percentage of subjects
exposed for specified periods, eg, ≥4 weeks (28 days), ≥ 8 weeks (56 days), ≥12 weeks 
(84 days), ≥ 24 weeks (168 days), ≥ 36 weeks (252 days), ≥48 weeks (336 days), ≥60 weeks 
(420 days), ≥ 72 weeks (504 days), ≥ 84 weeks (588 days), ≥96 weeks (672 days), ≥108 weeks 
(756 days), ≥120 weeks (840 days), ≥ 132 weeks (924 days), ≥144 weeks (1008 days), etc.
Summaries will be provided by treatment group for subjects in the Safety Analysis Set. No 
inferential statistics will be provided. 
Time to premature discontinuation of study drug will be analyzed using the Kaplan-Meier (KM) 
method by treatment group based on the Safety Analysis Set. The log rank test will be used to 
compare the difference in study drug exposure between the 2 treatment groups. Subjects who are 
still on the randomized study drug will be censored on the imputed last dose date as defined in 
this section. A plot of KM estimates for the time to premature discontinuation of study drug by 
treatment group will be generated.
4.2.2.
Adherence to Study Drug Regimen
Study drug regimen adherence will be computed based on pill counts for active drug only 
(eg, study drug regimen in Treatment Group 1 includes 1 study drug: B/F/TAF active. Study drug 
regimen in Treatment Group 2 includes 1 study drug: ABC/DTG/3TC active). The numbers of 
pills of study drug dispensed and returned are captured on study drug accountability eCRF.
Adherence (%) of study drug regimen will be calculated as follows:






]
2
[
]
1
[
period
dispensing
each 
at 
prescribed
pills
of
No.
period
dispensing
each 
at 
 taken 
pills
of
No.
100
prescribed
pills
of
No.
Total
 taken
pills
of
No.
Total
100
(%)
Adherence
[1]
Number of pills taken at a distinct dispensing period for a study drug is calculated as the minimum of (a) the daily number 
of pills prescribed for the study drug multiplied by the duration of treatment at the dispensing period, and (b) the number of 
pills taken for the study drug (number of pills dispensed minus the number of pills returned). Total number of pills taken is 
determined by summing the number of pills taken from all evaluable dispensing periods.
[2]
Number of pills prescribed at a distinct dispensing period for a study drug is calculated as the daily number of pills 
prescribed for the study drug multiplied by the duration of treatment at the dispensing period. Total number of pills 
prescribed is determined by summing the number of pills prescribed from all evaluable dispensing periods.
The duration of treatment at a dispensing period for a study drug is calculated as the minimum of 
(a) the last returned date of study drug at a dispensing period, (b) date of premature 
discontinuation of the study drug, and (c) next pill dispensing date of the study drug, minus 
dispensing date of the study drug.
The next pill dispensing date is the following dispensing date of the study drug regardless of the 
bottle return date. 


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For a record where the number of pills returned was missing (with “Yes” answered for 
“Was Bottle returned?” question), it is assumed the number of pills returned was zero. If the 
number of pills dispensed was missing or any study drug bottle was not returned or the bottle 
return status was unknown, then all records in that dispensing period for that study drug will be 
excluded from both denominator and numerator calculation.
Adherence up to the data cut date will be calculated using all data from the entire dosing period 
up to the date of permanent discontinuation of the study drug for subjects who prematurely 
discontinued study drug or completed study drug, or using all data available for subjects who are 
ongoing on study drug. 
Adherence up to Week 144 visit will also be calculated using all data from the entire dosing 
period up to the date of permanent discontinuation of the study drug for subjects who 
prematurely discontinued study drug or completed study drug, or the Week 144 study drug 
dispensing date, whichever occurs earliest.
Descriptive statistics for adherence up to the data cut date and adherence up to Week 144 visit 
for a study drug regimen (n, mean, SD, median, Q1, Q3, minimum, and maximum) along with 
the number and percentage of subjects belonging to adherence categories (eg, < 80%, ≥80% to 
< 90%, ≥ 90% to < 95%, ≥ 95%) will be provided by treatment group for subjects who return at 
least 1 bottle and have calculable adherence during the study in the Safety Analysis Set. No 
inferential statistics will be provided.
4.3.
Protocol Deviations
A listing will be provided for all randomized subjects who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met. A listing of subjects who 
received the wrong study drug will also be provided.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, race, and ethnicity) and baseline characteristics 
(eg, body weight, height, and body mass index [BMI]) will be summarized by treatment group 
and overall using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
for continuous data and by the number and percentage of subjects for categorical data. The 
summaries of demographic data and baseline subject characteristics will be provided for the 
Safety Analysis Set.
For categorical data, the Cochran-Mantel-Haenszel (CMH) test (ie, general association statistic 
for nominal data) will be used to compare the 2 treatment groups. For continuous data, the 
2-sided Wilcoxon rank sum test will be used to compare the 2 treatment groups.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics:

HIV-1 RNA (log10 copies/mL)

HIV-1 RNA categories (copies/mL): (a) ≤ 100,000, (b) > 100,000 to ≤ 400,000, and 
(c) > 400,000 

CD4+ cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, 
(d) ≥350 to < 500, and (e) ≥500

CD4 percentage (%)

Mode of infection (HIV risk factors)

HIV disease status

eGFRCG (mL/min)

HIV/HBV coinfection status (Yes/No/Missing, see Section 9.1 for definition) 

HIV/HCV coinfection status (Yes/No/Missing, see Section 9.2 for definition) 

Smoking status: (a) Never Smoker, (b) Former Smoker, and (c) Current Smoker
(see Appendix 7 for details)

Hip BMD and Spine BMD.


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For categorical data, the CMH test (general association statistic for nominal data, and row means 
scores differ statistic for ordinal data) will be used to compare the 2 treatment groups. For 
continuous data, the 2-sided Wilcoxon rank sum test will be used to compare the 2 treatment 
groups.
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will be coded using the current version of Medical Dictionary for Regulatory 
Activities (MedDRA). 


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6.
EFFICACY ANALYSES 
All necessary summaries on the primary efficacy endpoint (at Week 48) and the secondary and 
tertiary efficacy endpoints at Weeks 48 and 96 have been performed as part of the Week 48 CSR
or Week 96 CSR, and will not be repeated for the Week 144 analysis. 
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as determined by the US FDA-defined snapshot algorithm {U. S. Department of Health 
and Human Services 2015}. The proportions are expressed as percentages for presentation 
purposes. 
The statistical analysis methods for the primary efficacy endpoint were described in the Week 48
SAP and the analysis was performed in the Week 48 analysis.
6.2.
Secondary Efficacy Endpoints
6.2.1.
Definition of the Secondary Efficacy Endpoints
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA 50 copies/mL at Weeks 96 and 144 as 
determined by the US FDA-defined snapshot algorithm

The proportion of subjects with HIV-1 RNA 20 copies/mL at Weeks 48, 96, and 144 as 
determined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96,
and 144
The analyses for the secondary efficacy endpoints will be conducted based on the FAS, unless
specified otherwise.


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6.2.2.
Analysis of the Secondary Efficacy Endpoints
6.2.2.1.
Analysis of the Proportion of Subjects with HIV-1 RNA < 50 copies/mL as 
Determined by US FDA-defined Snapshot Algorithm 
The analysis window at Week 144 is defined as from Study Day 967 to Study Day 1050, 
inclusive. All HIV-1 RNA data collected on-treatment (ie, data collected up to 1 day after 
permanent discontinuation of study drug or all available data for subjects who were still on study 
drug) will be used in the US FDA-defined snapshot algorithm. Virologic outcome will be 
defined as the following categories:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 144 analysis window

HIV-1 RNA ≥ 50 copies/mL: this includes subjects
a.
Who have the last available on-treatment HIV-1 RNA 50 copies/mL in the Week 144
analysis window, or
b. Who do not have on-treatment HIV-1 RNA data in the Week 144 analysis window and 
i.
Who discontinue study drug prior to or in the Week 144 analysis window due to lack 
of efficacy, or
ii.
Who discontinue study drug prior to or in the Week 144 analysis window due to 
reasons other than adverse event (AE), death, or lack of efficacy and have the last 
available on-treatment HIV-1 RNA ≥ 50 copies/mL

No Virologic Data in the Week 144 Window: this includes subjects who do not have 
on-treatment HIV-1 RNA data in the Week 144 analysis window because of the following: 
a.
Discontinuation of study drug prior to or in the Week 144 analysis window due to AE or 
death (regardless of whether the last available on-treatment HIV-1 RNA < 50 copies/mL 
or not) or,
b. Discontinuation of study drug prior to or in the Week 144 analysis window due to 
reasons other than AE, death, or lack of efficacy and the last available on-treatment HIV-
1 RNA < 50 copies/mL or,
c.
Missing data during the window but on study drug.
The flowchart of the US FDA-defined snapshot algorithm is provided in Appendix 2.
The number and percentage of subjects with HIV-1 RNA < 50 copies/mL , HIV-1 RNA 
≥50 copies/mL, and reasons for no virologic data at Week 144 will be summarized. The 
difference in proportion of subjects achieving HIV-1 RNA < 50 copies/mL at Week 144 between 
treatment groups and the corresponding 95% confidence interval (CI) will be calculated based on 


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stratum-adjusted Mantel-Haenszel (MH) proportion as described in Appendix 3, where
stratification factors include baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) 
and region stratum (US vs. ex-US). P-value for comparing the proportion of subjects achieving 
HIV-1 RNA < 50 copies/mL between treatment groups will be calculated from the CMH test 
stratified by baseline HIV-1 RNA stratum and region stratum. Above analyses will be performed 
using both the FAS and the Week 144 PP Analysis Sets. A sensitivity analysis of above 
secondary endpoint will be performed by excluding the subjects without any postbaseline HIV-1 
RNA assessments in the FAS.
In addition, the following analyses will be performed using the FAS to evaluate the interaction 
between region and treatment to assess homogeneity of treatment effect across different regions.  
A region is defined as multiple sites combined based on geographical locations (see Appendix 4
for the region definition).
For each region, the difference in the proportion of subjects with HIV-1 RNA < 50 copies/mL 
between treatment groups and its 95% CI will be calculated based upon baseline HIV-1 RNA 
(≤100,000 vs. > 100,000 copies/mL) stratum-adjusted MH proportion.
The CMH analysis will be used to estimate the odds ratio and corresponding 95% CI for each 
region and overall. The homogeneity of the odds ratios across different regions will be tested 
using a Breslow-Day test and a corresponding p-value will be reported. 
As for adjusting randomization stratification for other stratified analyses, region stratum 
(US vs. Ex-US) will be used.
6.2.2.2.
Subgroup Analysis of the Proportion of Subjects with HIV-1 RNA 
< 50 copies/mL as Determined by US FDA-defined Snapshot Algorithm
The analysis of virologic response (HIV-1 RNA < 50 copies/mL, US FDA-defined snapshot 
algorithm) at Week 144 will be performed within each subgroup specified in Section 3.4 based 
on the FAS.
All subgroup analyses will be conducted using the US FDA-defined snapshot algorithm described 
in 6.2.2, adjusting for baseline HIV-1 RNA stratum (≤100,000 vs. > 100,000 copies/mL) and 
region stratum (US vs. Ex-US), provided that they are not the factors defining the subgroup. For 
each level of subgroup factors, the proportion difference between the 2 treatment groups and 
95% CIs will be computed based on the MH proportions adjusted by baseline HIV-1 RNA 
stratum (≤100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US), provided that 
they are not the factor defining the subgroup.
If the sample size in a subgroup is too small to calculate the proportion difference between 
2 treatment groups and 95% CIs based on the stratum-adjusted MH proportions, then they will be 
computed based on normal approximation without stratification.


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Additionally, a logistic regression model will be performed which includes the baseline 
stratification factor(s), subgroup factor, treatment, and treatment by subgroup factor. 
The baseline stratification factor(s) will include baseline HIV-1 RNA stratum 
(≤100,000 vs. > 100,000 copies/mL) when analyzing region subgroup, region stratum 
(US vs. Ex-US) when analyzing baseline HIV-1 RNA subgroup, and both baseline HIV-1 RNA 
stratum (≤100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US) when analyzing 
other subgroups. The odds ratio and the associated 95% CI will be estimated within each 
subgroup. The homogeneity of the treatment effects between subgroups will be evaluated using a 
Wald test based on the interaction between treatment and the subgroup factor.
A forest plot of the treatment differences in HIV-1 RNA < 50 copies/mL (US FDA-defined 
snapshot algorithm) at Week 144 and their associated 95% CIs for each subgroup will be 
generated.
6.2.2.3.
Analysis of the Proportion of Subjects with HIV-1 RNA < 20 copies/mL as 
Determined by US FDA-defined Snapshot Algorithm
Similarly, the proportion of subjects with HIV-1 RNA < 20 copies/mL at Week 144 will be 
analyzed by the US FDA-defined snapshot algorithm based on FAS. Confidence intervals will be 
constructed at the 95% level. 
6.2.2.4.
Analysis of Log10 HIV-1 RNA copies/mL and CD4+ Cell Count
All log10 HIV-1 RNA data will be summarized using observed values (ie, missing will be 
excluded). CD4+ cell count will be summarized using observed, on-treatment data (ie, data 
collected up to 1 day after permanent discontinuation of study drug or all available data for 
subjects who were still on study drug) for subjects in the FAS.
The changes from baseline in log10 HIV-1 RNA and CD4+ cell count at Week 144 will be 
summarized by treatment group using descriptive statistics. The differences in changes from 
baseline in log10 HIV-1 RNA and CD4+ cell count between the 2 treatment groups and the 
associated 95% CI will be constructed using analysis of variance (ANOVA) models, including 
treatment group, baseline HIV-1 RNA stratum (≤100,000 vs. > 100,000 copies/mL), and region 
stratum (US vs. Ex-US) as fixed effects. The change from baseline in log10 HIV-1 RNA and 
CD4+ cell count will also be summarized at visits other than Week 144 by treatment group.
The change from baseline in CD4+ cell counts will also be analyzed based on the Week 144 PP 
Analysis Set.
The mean and 95% CI of change from baseline in log10 HIV-1 RNA and CD4+ cell count over 
time will be plotted for the FAS. 


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In addition, the change from baseline in CD4+ cell counts with missing values imputed using the 
last observation caITied fo1ward (LOCF) method will be summarized at each visit based on the 
FAS. The algorithm for LOCF is as follows: 
• 
If a value is missing in an analysis visit window, the missing value will be replaced with the 
last on-treatment value (ie, data collected up to 1 day after pennanent discontinuation of 
study diug or all available data for subjects who were still on study diug) observed before the 
analysis visit window that has the missing value. 
• 
Baseline values will be canied f01ward to impute the postbaseline value at a specific visit, if 
there is no nonmissing postbaseline observation collected prior to that visit. 
6.3. 
6.3.1. 
I 
I 
6.3.2. -
I 
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Tertiary Efficacy Endpoints 
Definition of the Tertiary Efficacy Endpoints 
Analysis of the Tertiary Efficacy Endpoints 
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Changes From Protocol-Specified Efficacy Analyses 
No change from the protocol-specified efficacy analysis is planned. 
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7.
SAFETY ANALYSES
Safety data will be summarized for the subjects in the Safety Analysis Set. All safety data 
collected up to 30 days after permanent discontinuation of study drug and all available data for 
subjects who were still on study drug will be summarized by treatment group, unless specified 
otherwise. All safety data will be included in data listings.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of MedDRA. System organ 
class (SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and 
lowest-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will be left as 
“missing” for data listings. 
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAEs from the Gilead Pharmacovigilance and Epidemiology
(PVE) database before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of the study drug, or 

Any AEs leading to premature discontinuation of study drug.


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The month and year (or year) of the AE onset is the same as or after the month and year 
(or year) of the first dosing date of study drug, and

The month and year (or year) of the AE onset is the same as or before the month and year 
(or year) of the date corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date marked as ongoing or on or after the first dosing date of study drug, will be considered to be 
treatment emergent. In addition, an AE with the onset date missing and incomplete stop date 
with the same or later month and year (or year alone if month is not recorded) as the first dosing 
date of study drug will be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Death
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group. For other AEs described below, summaries 
will be provided by SOC, PT, and treatment group using the Safety Analysis Set:

Any Grade 2, 3, or 4 treatment-emergent AEs

Any Grade 3 or 4 treatment-emergent AEs

All treatment-emergent study drug-related AEs

Any Grade 2, 3, or 4 treatment-emergent study drug-related AEs

Any Grade 3 or 4 treatment-emergent study drug-related AEs

All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs

All treatment-emergent AEs that caused premature discontinuation from study drug
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs. Treatment-emergent 
deaths observed in the study will be also included in this summary.


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Treatment-emergent death refers to deaths that occurred between the first dose date and the last 
dose date plus 30 days (inclusive).
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study.
In addition to the above summary tables, all treatment-emergent AEs, Grade 3 or 4 
treatment-emergent AEs, treatment-emergent study drug-related AEs, Grade 2, 3, or 4 
treatment-emergent study drug-related AEs, and treatment-emergent SAEs will be summarized 
by PT only, in descending order of total frequency.
In addition, data listings will be provided for the following:

All AEs

Grade 3 and 4 AEs

SAEs

Study Drug-Related SAEs

Deaths report

AEs leading to premature discontinuation of study drug
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Stage 3 Opportunistic Illnesses in HIV
On an ongoing basis, AEs will be reviewed for events that might meet the definition of stage 3 
opportunistic illnesses in HIV that are indicative of an AIDS-defining diagnoses (see Protocol 
Appendix 6). The Gilead medical monitor will review the possible stage 3 opportunistic illnesses
and approve the events that meet the definition. Events that meet the stage 3 opportunistic illness
definition of an AIDS-Defining Diagnosis will be listed.
7.1.7.2.
Cardiovascular or Cerebrovascular Events
Preferred terms for defining cardiovascular or cerebrovascular events are from relevant
Standardised MedDRA Query (SMQ). The selected PT listing was provided by Gilead PVE and 
reviewed by Gilead medical monitors (see details in Appendix 5).


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The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
summarized by treatment group based on the Safety Analysis Set. Statistical comparisons of the 
subject incidence rates between the 2 treatment groups will be performed using Fisher’s exact 
test. A data listing of cardiovascular or cerebrovascular events will be provided.
7.1.7.3.
Hepatic Events
Preferred terms for defining hepatic events are from 15 relevant SMQs, which are identified as 
non-infectious and non-congenital hepatobiliary disorders. The selected PT listing was provided 
by Gilead PVE and reviewed by Gilead medical monitors (see details in Appendix 6).
The number and percentage of subjects with treatment-emergent hepatic events and serious 
hepatic events by PT will be summarized by treatment group based on the Safety Analysis Set. 
Statistical comparisons of the subject incidence rates between the 2 treatment groups will be 
performed using Fisher’s exact test. A data listing of hepatic events will be provided.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set. The analysis will be based on values reported in conventional units. When 
values are below the LOQ, they will be listed as such, and the imputed value will be used for the 
purpose of calculating summary statistics as specified in Section 3.7. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the reference range and/or having a severity grade of 1 or higher on the Gilead 
Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be flagged in 
the data listings, as appropriate.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values 

Values at each postbaseline analysis window

Change from baseline at each postbaseline analysis window

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A baseline laboratory value will be defined as the last nonmissing value obtained on or prior to 
the date of first dose of study drug. Change from baseline to a postbaseline visit will be defined 
as the postbaseline value minus the baseline value. The mean, median, Q1, Q3, minimum, and 
maximum values will be displayed to the reported number of digits; SD values will be displayed 
to the reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 

Calcium corrected for albumin (mg/dL) = serum calcium (mg/dL) + 0.8 × (4.0 – albumin (g/dL))
Toxicity grading for calcium will be applied based on the corrected values.
Estimated GFR
The following formula will be used to calculate eGFRCG: 

eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / (SCr (mg/dL) × 72), 
where weight is total body mass in kilograms, and SCr is serum creatinine.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used for assigning toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction (ie, increased, 
decreased) will be presented separately.
If there is any laboratory toxicity grading scale overlapping with the normal reference ranges 
(eg, grade 1 scale overlaps with normal reference ranges), laboratory values that are within the 
normal range will be grade 0, except for lipid tests.
For triglycerides, LDL, and cholesterol, the protocol-specified toxicity grading scale is for 
fasting test values, so nonfasting lipid results (or lipid results without a known fasting status) will 
not be graded or summarized by toxicity grades. 


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7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to 30 days after permanent 
discontinuation of study drug or the last available date for subjects who were still on study drug 
at the time of an interim analysis. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment-emergent.
Fasting glucose and nonfasting glucose (including glucose results without a known fasting 
status) are graded based on different grading scales as specified in the protocol. 
Treatment-emergent laboratory abnormalities will be summarized for fasting glucose. Maximum 
postbaseline grade, instead of treatment-emergent grade, for nonfasting glucose (including 
glucose results without a known fasting status) will be summarized, as nonfasting glucose was 
not assessed at baseline visit for most of the subjects; therefore, an abnormality is 
treatment-emergent or not cannot be determined for these subjects.
7.2.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities

Treatment-emergent Grade 2, 3 and 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
any nonmissing postbaseline values up to 30 days after last dosing date.
A by-subject listing of all treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities will be provided by subject ID number and visit in 
chronological order. 
7.2.3.
Metabolic Laboratory Evaluations
For metabolic assessments, including fasting glucose and the lipid panel (ie, total cholesterol, 
triglycerides, LDL, HDL, total cholesterol to HDL ratio), only those measurements under fasting 
status will be summarized. P-values comparing the difference between the 2 treatment groups in 
baseline values and the change from baseline in metabolic assessment will be estimated from a 
2-sided Wilcoxon rank sum test.
In addition, the number and percentage of subjects who took lipid-modifying medications at 
study entry and initiated the medications during the study will be provided, respectively. 
Statistical comparisons of the subject incidence rates between the 2 treatment groups will be 
performed using Fisher’s exact test. 


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A lipid-modifying medication is defined as a medication with ATC2 term = “LIPID 
MODIFYING AGENTS” and CMDECOD containing the wording of “STATIN”.
A sensitivity analysis of fasting lipid tests will be performed by excluding subjects who took 
lipid-modifying medications at study entry or initiated the medications during the study: baseline 
values, Week 144 values, and changes from baseline at Week 144 will be summarized by 
treatment group using descriptive statistics. Baseline and change from baseline at Week 144 will 
be compared between the 2 treatment groups using a 2-sided Wilcoxon rank sum test. Only 
subjects with both baseline and Week 144 postbaseline values will be included in the analysis. 
Median (Q1, Q3) of change from baseline in fasting metabolic assessments over time will be 
plotted by treatment group. 
7.2.4.
Liver-Related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of subjects who were reported to have the following laboratory 
test values for postbaseline measurements:

Aspartate aminotransferase (AST): (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, 
(d) > 20 × ULN

Alanine aminotransferase (ALT): (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, 
(d) > 20 × ULN

AST or ALT: (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, (d) > 20 × ULN

Total bilirubin: (a) > 1 × ULN, (b) > 2 × ULN

Alkaline phosphatase (ALP) > 1.5 × ULN

AST or ALT > 3 × ULN and total bilirubin: (a) > 1.5 × ULN, (b) > 2 × ULN

AST or ALT > 3 × ULN and total bilirubin > 2 × ULN and ALP < 2 × ULN
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
study drug. For individual laboratory tests, subjects will be counted once based on the most 
severe postbaseline value. For both the composite endpoint of AST or ALT and total bilirubin, 
and the composite endpoint of AST or ALT, total bilirubin, and ALP, subjects will be counted 
once when the criteria are met at the same postbaseline visit date. The denominator is the number 
of subjects in the Safety Analysis Set with nonmissing postbaseline value of the tests in 
evaluation at the same postbaseline visit date. Subjects with AST or ALT > 3 × ULN will also be 
listed.
In addition, baseline, postbaseline, and change from baseline in AST, ALT, ALP, and total 
bilirubin will be summarized by treatment group and visit using descriptive statistics. Baseline 
and change from baseline will be compared between the 2 treatment groups using a 2-sided 
Wilcoxon rank sum test.


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7.2.5.
Renal-Related Laboratory Evaluations
7.2.5.1.
Serum Creatinine and eGFRCG
Baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG will be 
summarized by treatment group and visit using descriptive statistics. Baseline and change from 
baseline will be compared between the 2 treatment groups using a 2-sided Wilcoxon rank sum 
test. 
Median (Q1, Q3) of change from baseline in serum creatinine and eGFRCG over time will be 
plotted by treatment group. 
7.2.5.2.
Urine Retinol Binding Protein to Creatinine Ratio, Beta-2-Microglobulin to 
Creatinine Ratio, and Urine Creatinine
Baseline, postbaseline, change from baseline, and percentage change from baseline in urine RBP 
to creatinine ratio and beta-2-microglobulin to creatinine ratio will be summarized by treatment 
group and visit using descriptive statistics. Baseline and percentage change from baseline will be 
compared between the 2 treatment groups using a 2-sided Wilcoxon rank sum test.
Median (Q1, Q3) percentage change from baseline in urine RBP to creatinine ratio and 
beta-2-microglobulin to creatinine ratio over time will be plotted by treatment group. 
Baseline, postbaseline, and change from baseline in urine creatinine will be summarized by 
treatment group and visit using descriptive statistics. Baseline and change from baseline will be 
compared between the 2 treatment groups using a 2-sided Wilcoxon rank sum test.
7.2.5.3.
Albuminuria by Quantitative Assessment
The baseline, postbaseline, changes from baseline, and percentage change from baseline in urine 
albumin to creatinine ratio (UACR) will be summarized by treatment group and visit using 
descriptive statistics. Baseline and percentage change from baseline will be compared between 
the 2 treatment groups using a 2-sided Wilcoxon rank sum test. 
The number and percentage of subjects with UACR < 30 mg/g versus ≥30 mg/g will be 
summarized by baseline category at Weeks 24, 48, 96, 144 and based on the last on-treatment 
value (ie, data collected after the first dose date up to 1 day after the last dose date)
{KDIGO Guideline Development Staff 2013}.
Median (Q1, Q3) percentage change from baseline in UACR over time will be plotted by 
treatment group.


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7.3.
Bone Safety Analyses
7.3.1.
Bone Mineral Density 
7.3.1.1
Percentage Change from Baseline in Hip and Spine Bone Mineral Density
The percentage change from baseline in hip BMD and spine BMD will be summarized by 
treatment group and visit using descriptive statistics for subjects in the hip and spine DXA 
Analysis Sets, respectively, and compared between the 2 treatment groups at each visit using 
ANOVA, which includes treatment as a fixed effect.
As a sensitivity analysis, missing values for hip BMD and spine BMD will be imputed using the 
LOCF imputation method for the analyses of percentage change from baseline. The algorithm for 
LOCF is as follows:

If a value is missing in an analysis visit window, the missing value will be replaced with the 
last value observed before the analysis visit window that has the missing value.

Baseline values will be carried forward to impute the postbaseline value at a specific visit, if 
there is no nonmissing postbaseline observation collected prior to that visit. 
Similar to the analysis of observed data, the percentage change from baseline in hip BMD and 
spine BMD by LOCF will also be analyzed using the hip and spine DXA substudy Analysis Sets.
Median (Q1, Q3) and mean (95% CI) of the percentage change from baseline in observed hip 
BMD and spine BMD over time will be plotted by treatment group. Listings of hip and spine 
DXA results will be provided.
7.3.1.2
Hip and Spine BMD Clinical Status
Analysis of hip and spine BMD clinical status will based on the observed BMD values 
(ie, missing will be excluded).
For each subject and each visit, the BMD clinical status will be defined for hip BMD and spine 
BMD as follows based on the t-score:
Table 7-1.
Normal, Osteopenia, and Osteoporosis as Defined by T-score
Clinical Status
BMD T-score
Normal
T-score ≥ -1.0
Osteopenia
-2.5 ≤ T-score < -1.0
Osteoporosis
T-score < -2.5
The number and percentage of subjects in each BMD clinical status (normal, osteopenia, and 
osteoporosis) will be summarized by visit and by baseline clinical status for both hip and spine. 
The distribution of the BMD clinical status will be compared between the 2 treatment groups 
adjusting for baseline clinical status using rank analysis of covariance {LaVange 2008}.


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7.3.1.3
Gradation of the Percentage Change in Hip, Femur Neck, and Spine BMD
For each subject and each visit, percentage change from baseline in spine BMD will be classified 
into 6 categories: ≥5% decrease, ≥ 3% to < 5% decrease, > 0% to < 3% decrease, ≥ 0% to 
< 3% increase, ≥3% to < 5% increase, and ≥5% increase. Similarly, the percentage change from 
baseline in Hip BMD and Femur Neck BMD will be classified into 6 categories: ≥7% decrease, 
≥ 3% to < 7% decrease, > 0% to < 3% decrease, ≥0% to < 3% increase, ≥3% to < 7% increase, 
and ≥7% increase. The number and percentage of subjects in each category will be summarized 
by visit. The difference in the distribution of these categories between the treatment groups will 
be compared using a CMH test (row mean scores differ statistic).
In addition, the number and percentage of subjects with percentage change from baseline in each 
cumulative categories (ie, ≥5% decrease, ≥ 3% decrease, no decrease [≥ 0% increase], 
≥3% increase, and ≥5% increase for Spine BMD; ≥7% decrease, ≥ 3% decrease, no decrease
[≥0% increase], ≥3% increase, and ≥7% increase for Hip and Femur Neck BMD) will be 
compared between treatment groups using Fisher exact test based on the dichotomized response 
(eg, ≥5% decrease vs. < 5% decrease). 
7.4.
Body Weight, Height, and Vital Signs
Descriptive statistics will be provided by treatment group for vital signs and body weight as 
follows:

Baseline values

Values at each postbaseline analysis window

Change from baseline to each postbaseline analysis window 
A baseline value will be defined as the last nonmissing value obtained on or prior to the date of 
first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. In the same listing, a by-subject listing of body weight, height, and BMI 
will be provided.
7.5.
Prior and Concomitant Medications
7.5.1.
Nonstudy Drug Antiretroviral Medications
Any nonstudy drug ARV medications used prior to, during, or after the study (if collected) will 
be coded using the Gilead-modified World Health Organization (WHO) Drug Dictionary for 
ARV medications. The WHO preferred drug name and drug code will be attached to the clinical 
database. All nonstudy drug ARV medications will be listed. No inferential statistics will be 
provided.


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7.5.2.
Concomitant Non-ARV Medications
Concomitant non-ARV medications (ie, medications other than study drug that are taken while 
receiving study drug) will be coded using the WHO Drug Dictionary. The WHO preferred drug 
name and drug code will be attached to the clinical database. Use of concomitant medications 
from Study Day 1 up to the date of last dose of study drug will be summarized (number and 
percentage of subjects) by treatment group and preferred drug name. Multiple drug use (by 
preferred drug name) will be counted only once per subject. The summary will be sorted by 
decreasing total frequency. For drugs with the same frequency, sorting will be done 
alphabetically. 
If the start or stop date of non-ARV medications is incomplete, the month and year (or year 
alone, if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARVs are concomitant or not. The medication is concomitant if the month and year of the 
start or stop (or year of the start or stop, if month is not recorded) of the medication does not 
meet either of the following criteria:

The month and year of start of the medication is after the date of the last dose of study drug

The month and year of stop of the medication is before the date of the first dose of study drug
If the start and stop date of non-ARV medications are complete, the start date is not after last dose 
date and the stop date is not before first dose date, or the non-ARV medications are marked as 
ongoing and start date is on or before last dose date, the non-ARV medications are concomitant.
Summaries of non-ARV concomitant medications will be provided for the Safety Analysis Set. 
Subjects with any non-ARV concomitant medications will be listed. No inferential statistics will 
be provided.
7.6.
Electrocardiogram Results
A shift table of the investigators’ assessment of ECG results at each scheduled postbaseline visit 
compared with baseline values will be presented by treatment group using the following 
categories: normal; abnormal, not clinically significant; abnormal, clinically significant; or 
missing. The number and percentage of subjects in each cross-classification group of the shift 
table will be presented. Subjects with a missing value at baseline or postbaseline will not be 
included in the denominator for percentage calculation. No inferential statistics will be provided.
A by-subject listing for ECG assessment results will be provided by subject ID number and visits 
in chronological order. 
7.7.
Other Safety Measures
A data listing will be provided for subjects experiencing pregnancy during the study. Physical 
examination data was not collected in the eCRF. Therefore, it will not be included in the 
analysis.


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7.8.
Changes From Protocol-Specified Safety Analyses
No change from the protocol-specified safety analysis is planned.


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8.
PHARMACOKINETIC ANALYSES
All necessary summaries on pharmacokinetic analyses have been performed as part of Week 48 
CSR, and will not be repeated in the Week 144 analysis.


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9.
SPECIAL POPULATION ANALYSES
9.1.
Analyses for HIV/HBV Coinfected Subjects
Subjects with HIV/HBV coinfection at baseline are defined as subjects who meet any of the 
following two criteria:

Positive HBsAg on or prior to the first dose date, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) on or prior to the first dose date.
Subjects with incident HIV/HBV coinfection while on study drug (if any) are defined as subjects
who are not HIV/HBV coinfected at baseline and meet any of the following criteria:

Positive HBsAg after the first dose date and on or prior to the date of permanent 
discontinuation of study drug, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) after the first dose date and on or prior to the date of permanent 
discontinuation of study drug, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the first dose date and on or prior to the date of permanent 
discontinuation of study drug: Acute hepatitis B, Chronic hepatitis B, Congenital hepatitis B 
infection, Hepatitis B, Hepatitis B core antibody positive, Hepatitis B DNA assay positive, 
Hepatitis B surface antigen positive, Hepatitis B virus test positive.
The following listings will be provided for subjects with incident HIV/HBV coinfection while on 
study drug (if any): 

Listing of adverse events

Listing of liver-related laboratory tests and HBV DNA results
9.2.
Analyses for HIV/HCV Coinfected Subjects
Subjects with HIV/HCV coinfection at baseline are defined as subjects with positive HCVAb 
and quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) on or prior to the first dose date. The 
following analyses will be provided for subjects with HIV/HCV coinfection at baseline: 

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results  


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Subjects with incident HIV/HCV coinfection while on study drug are defined as subjects who are 
not HIV/HCV coinfected at baseline and meet any of the following criteria:

Positive HCVAb after the first dose date and on or prior to the date of permanent 
discontinuation of study drug with baseline HCVAb Negative or missing, or

Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the first dose date and on or prior 
to the date of permanent discontinuation of study drug , or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the first dose date and on or prior to the date of permanent 
discontinuation of study drug: Acute hepatitis C, Chronic hepatitis C, Hepatitis C, 
Hepatitis C antibody positive, Hepatitis C RNA positive, Hepatitis C virus test positive.
The following listings will be provided for subjects with incident HIV/HCV coinfection while on 
study drug: 

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results


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10.
REFERENCES
KDIGO Guideline Development Staff. KDIGO 2012 Clinical Practice Guideline for the 
Evaluation and Management of Chronic Kidney Disease. Kidney international. 
Supplement 2013;3 (1):v-150.
Koch GG, Carr GJ, Amara IA, Stokes ME, Uryniak TJ. Categorical Data Analysis. Chapter 13 in 
Berry, D.A. (ed.).  Statistical Methodology in the Pharmaceutical Sciences. New 
York: Marcel Dekker, Inc., 1989:pp. 414-21. 
LaVange LM, Koch GG. Randomization-Based Nonparametric (ANCOVA). In: D'Agostino Sr. 
RB, Sullivan LM, Massaro JM, eds.  Wiley Encyclopedia of Clinical Trials. John 
Wiley & Sons, Inc.; 2008: 31-8. vol 4).
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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11.
SOFTWARE
SAS® Version 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
nQuery Advisor® Version 6.0 (Statistical Solutions, Cork, Ireland.) is to be used for sample size 
and power calculation.


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12.
SAP REVISION
Revision Date
(dd month, yyyy)
Section
Summary of Revision
Reason for Revision


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13.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for Naïve Trial)
Appendix 3.
Stratum-Adjusted Mantel-Haenszel Proportion Analysis
Appendix 4.
Region Definition
Appendix 5.
Cardiovascular or Cerebrovascular Events
Appendix 6.
Hepatic Events
Appendix 7.
Programming Specification


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Appendix 1.
Study Procedures Table
Appendix Table 1.
Study Procedures Table (Blinded Phase)
Study Procedures
Screeninga
Day 
1b
4
8
12
24
36
End of Weeke,r
Post-
Week 144e,s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
Informed Consent
X
Medical History
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-
Directed Physical 
Exam
X
X
Xd
Xd
Xd
X
Xd
X
Xd
Xd
Xd
X
Xd
Xd
Xd
X
Xx, Xd
X
Xd,f
Xf
12-Lead ECG 
(performed supine)
X
X
X
X
X
X
Xx
X
X
Questionnaires
X
X
X
X
DXA scan 
(spine & hip)g
X
X
X
X
X
X
X
Height
X
Vital signs (blood 
pressure, pulse, 
respiration rate, and 
temperature), 
including Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy 
Testh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy 
Test
X


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Study Procedures
Screeninga
Day 
1b
4
8
12
24
36
End of Weeke,r
Post-
Week 144e,s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
Chemistry Profilei
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic 
Assessmentsj
X
X
X
X
X
X
X
X
Xt
X
Estimated 
Glomerular 
Filtration Rate
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HLA-B*5701w
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluations of 
inflammation and 
immune activation, 
platelet function and 
renal tubular function
X
X
X
X
X
X
X
Xt
X
Plasma & Urine 
Storage Sample 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HBV and HCV 
Serology
X
X
X
X
XX
HIV-1 Genotypel
Xl
HIV-1 Genotype/
Phenotypee
Xe
Single PK Samplem
X
X
X
Trough PK Samplesn
X
X


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Study Procedures
Screeninga
Day 
1b
4
8
12
24
36
End of Weeke,r
Post-
Week 144e,s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
Randomizationv
X
Provide subject 
dosing diary to 
subjects
X
X
X
X
X
Study Drug 
Dispensation
Xb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xu
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures at the Day 1 visit, with the exception of DXA.
c
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
End of Blinded Treatment Visit even if the subject discontinues study drug.
d
Symptom-directed physical examination as needed.
e
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Protocol Section 6.14.1 and 
Section 6.14.2).
f
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained. 
g
DXA scans to be performed in all eligible subjects on study drug during blinded treatment only, except for those in Germany, prior to or within 24 hours of the Day 1 Visit, 
Weeks 24, 48, 96, 144 (±10 days), and at the End of Blinded Treatment Visit (±10 days) and the ESDD visit (if the last scan was acquired > 12 weeks from the date of the 
ESDD Visit).
h
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
CCI
CCI


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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and indirect bilimbin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphoms, magnesium, potassium, sodium, tu-ic acid and amylase (reflex lipase testing is pe1fo1med in subjects with total amylase 
> 1.5 x ULN). At Day 1, Weeks 12, 24, 48, 72, 96, 120, 144, and eve,y 24 weeks post Week 144, and End of Blinded Treatment Visit, analyses of glucose will be done as 
pa,t of the fasting metabolic assessments and not as part of the chemistiy profile. Additionally: TSH will be analyzed at Screening, Day 1, Weeks 24, 48, 72, 96, 120, 144, and 
eve,y 24 weeks post Week 144, End of Blinded Treatment Visit and Early Study Dmgs Discontinuation visit. 
Fasting (no food or di-inks, except water, at least 8 hours p1-ior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, ti-iglyce,-ides). If the subject has 
not fasted p1-ior to the visit, the visit may proceed, but the subject must rettun within 72 hotu'S in a fasted state to draw blood for the metabolic assessments. 
k 
CBC with differential and platelet count. 
1 
The Investigator must have received the results from the screening genotype repo,t before proceeding with the Day 1 visit. Screening genotype repo,t must show sensitivity to 
TFV, FTC, 3TC and ABC. If genotype results from a local laborato,y obtained ::; 90 days prior to screening visit date show sensitivity to these diugs, this genotype will be 
acceptable to fulfill this inclusion c1-ite1-ion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion c1-ite1-ia have been 
confumed. 
m 
A single PK blood sample will be collected at any time pre or post-dose 
n 
A trough PK blood sample will be collected between 20-28 hours following the last dose. Following an observed dose, a single post dose blood sample will be collected 
between 1 and 4 hotu·s ost dose. 
I' 
I 
q 
y reqmre 
or 
ose su 1ects not enro mg Ill e open- a e ro over extension or ose su 1ects w o premature y 1scontmue stu y 
u gs an 
o not contmue Ill the study 
through at least one subsequent visit after the Early Study Dmgs Discontinuation Visit. For the ptupose of scheduling a 30-Day Follow-Up Visit, a± 6 days window may be 
used. 
r 
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within± 6 days through to 
Week 132, 1mless otherwise specified. The visit window at Weeks 48 and 96, 144 will be± 6 weeks of the protocol-specified visit date. 
s 
After Week 144, subjects will continue to take their blinded study di·ug and attend visits eveiy 12 weeks 1mtil the End of Blinded Treatment Visit. Visit window of± 6 days 
for study visits post Week 144. 
To be pe1fo1med every 24 weeks after Week 144 until End of Blinded Treatment Visit. 
u 
Open-label study di·ug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for up to 48 weeks. 
v 
Randomization may be performed up to 3 days p1-ior to the in-clinic Day 1 visit, provided that all screening procedures have been completed and subject eligibility has been 
confumed. 
w 
The Investigator must have received a negative screening test for HLA-B*5701 allele before proceeding with the Day 1 visit. IfHLA-B*5701 results are available from a 
local laboratory p1-ior to screening, this report will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result obtained at screening is not yet 
available and all other inclusion/exclusion criteria have been confumed. 
x 
To be pe1fo1med every 48 weeks after Week 144 until the End of Blinded Treatment Visit. 
y 
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will rettun to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety and efficacy of GS-9883/F/TAF FDC is demonsti·ated following review of unblinded data, subjects 
in a countiy where GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/TAF FDC in an OL extension phase for up to 48 weeks, or until the 
product becomes accessible to subjects through an access program, or until Gilead elects to discontinue the study in that countiy, whichever occurs fu-st. 
CONFIDENTIAL 
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Appendix Table 2.
Study Procedures Table (Open-Label Rollover Extension)
Study Procedures
End of Blinded 
Treatment Visita
End of Weeke,l
30-Day 
Follow-upk
Early Study 
Drugs DCc
12 OL
24 OL
36 OL
48 OL
Concomitant Medications
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed Physical Exam
X
Xd
Xd
Xd
X
Xd,f
Xf
12-Lead ECG (performed supine)
X
X
DXA scan (spine & hip)m
X
Vital signs (blood pressure, pulse, respiration rate, 
and temperature), including Weight
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
Chemistry Profileh
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
Estimated Glomerular Filtration Rate
X
X
X
X
X
Xf
X
Hematology Profilej
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
Evaluations of inflammation and immune activation, 
platelet function and renal tubular function
X
Plasma & Urine Storage Sample 
X
X
X
X
X
X
HBV and HCV Serology
X
HIV-1 Genotype/Phenotypee
Xe


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Study Procedures
End of Blinded 
Treatment Visita
End of Weeke,l
30-Day 
Follow-upk
Early Study 
Drugs DCc
12 OL
24 OL
36 OL
48 OL
Study Drug Dispensation
Xb
X
X
X
Study Drug Accountability
X
X
X
X
X
X
a
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety and efficacy of GS-9883/F/TAF FDC is demonstrated following review of unblinded data, 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 in an OL extension phase for up to 48 weeks, or until the 
product becomes accessible to subjects through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.
b
Open-label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for up to 48 weeks.
c
Subjects who discontinue study drug during the OL rollover extension portion of the study will be asked to return to the clinic within 72 hours of stopping study drugs for the 
Early Study Drugs Discontinuation Visit followed by a 30-Day Follow-Up Visit. The subject will not continue attending the scheduled study visits.
d
Symptom-directed physical examination as needed.
e
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Protocol Section 6.14.1 and 
Section 6.14.2) 
f
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained. 
g
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
> 1.5 ULN). At Week 24 OL and Week 48 OL, and End of Blinded Treatment Visit, analyses of glucose will be done as part of the fasting metabolic assessments and not as 
part of the chemistry profile. For all subjects, TSH will be done at the End of Blinded Treatment Visit, Week 24 OL, Week 48 OL, and Early Study Drug Discontinuation 
Visit.
i
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
j
CBC with differential and platelet count.
k
Subjects who complete the open-label rollover extension will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit. 
Subjects who prematurely discontinue study drugs during the open-label rollover extension will be asked to return to the clinic 30 days after the completion of the Early Study 
Drugs Discontinuation Visit for the 30-Day Follow-Up Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used.
l
Study visits are to be completed within ± 6 days of the protocol-specified visit date every 12 weeks thereafter, unless otherwise specified
m
DXA scans to be performed in all eligible subjects on study drug, except for those in Germany, only at the End of Blinded Treatment Visit (±10 days).


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Appendix 2. 
Flowchart of US FDA-defined Snapshot Algorithm (for Nai've Trial) 
The following flowchaii for US FDA-defined snapshot algorithm is based on the US FDA 
Guidance on Human Immunodeficiency Virns-1 Infection: Developing Antiretroviral Drngs for 
Treatment {U. S. Depai·tment of Health and Human Services 2015} 
Yes 
Is there at least 1 on-
treatment* HIV-1 RNA 
collected in the Snapshot 
window? 
Is the last available on-treatment* 
HIV-I RNA in the Snapshot 
window < 50 copies/mL? 
0 
ls study drug prematurely 
discontinued on or prior to the 
upper limit of the Snapshot 
window? 
Yes 
Yes 
ls discontinuation of the study 
drug due to Lack of Efficacy? 
HIV-1 RNA< 
50 copies/mL 
HIV-I RNA~ 
50 co1>ies/mL 
No 
No 
ls discontinuation of the study 
drug due to AE/Death? 
ls the last available on-
treatment* HIV-1 RNA < 
50 copies/mL 
Yes 
No Virologic Data: 
Discontinued Study Drug 
Due to Other Reasons and 
Last HIV-l RNA< 50 
copies/mL 
Yes 
No Virologic Data: 
Di.scontinued Study 
Drug Due to AE/Death 
No 
No Virologic Data: 
Missing Data during 
Window but on Study 
Drug 
* On-treatment data include all data collected up to 1 day after permanent discontinuation of study 
drug or all available data for subjects who were still on study drug. 
CONFIDENTIAL 
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Appendix 3.
Stratum-Adjusted Mantel-Haenszel Proportion Analysis 
The baseline stratum weighted difference in the response rate (P1 – P2) and its (1 - α/2)% CI will 
be calculated based on stratum-adjusted Mantel-Haenszel (MH) proportion as described as 
follows {Koch 1989}, where stratification factors include baseline HIV-1 RNA stratum 
(≤100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US):
P1 – P2 Z(1-α/2 ) * SE(P1 – P2),
where 

(P1 – P2) = 

h
h
h
w
d
w
, is the stratum-adjusted MH proportion difference, where 
h
d =
h
h
p
p
2
1 
is the difference in the response rate between of the 
Treatment Groups 1 and 2 in stratum h (h = 1 to 4). 

h
w = 
h
h
h
h
n
n
n
n
2
1
2
1

, is the weight based on the harmonic mean of sample size per treatment 
group for each stratum where 
h
n1 and 
h
n2
are the sample sizes of the 
Treatment Groups 1 and 2 in stratum h. 

SE(P1 – P2) = 
2
2
*
2
*
2
1
*
1
*
1
)
(
1
)
1(
1
)
1(











h
h
h
h
h
h
h
w
n
p
p
n
p
p
w
, where 
1
5.0
1
1
*
1



h
h
h
n
m
p
and 
1
5.0
2
2
*
2



h
h
h
n
m
p
.
h
m1 and 
h
m2
are the number of subjects with HIV-1 RNA 
< 50 copies/mL in the Treatment Groups 1 and 2 in stratum h. 

α = 0.05 for this study 

Z(1-α/2 ) = Z0.975 = 1.96 is the 97.5th percentile of the normal distribution
Note that if the computed lower confidence bound is less than –1, the lower bound is defined 
as -1. If the computed upper confidence bound is greater than 1, the upper bound is defined as 1. 
J--


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Appendix 4.
Region Definition
Region
Country Name
State
No. of Subjects in Safety 
Analysis Set or FAS
(N=629)
Total No. of Subjects 
by Region in Safety 
Analysis Set or FAS
(N=629)
Region 1
CANADA (CAN)
33
33
Region 2
BELGIUM (BEL)
6
132
FRANCE (FRA)
21
GERMANY (DEU)
13
ITALY (ITA)
18
SPAIN (ESP)
43
UNITED KINGDOM (GBR)
31
Region 3
UNITED STATES (USA)
CA
56
63
UNITED STATES (USA)
WA
7
Region 4
UNITED STATES (USA)
AZ
15
104
UNITED STATES (USA)
CO
6
UNITED STATES (USA)
NM
4
UNITED STATES (USA)
TX
79
Region 5
UNITED STATES (USA)
IN
3
53
UNITED STATES (USA)
MI
15
UNITED STATES (USA)
MN
6
UNITED STATES (USA)
MO
12
UNITED STATES (USA)
OH
16
UNITED STATES (USA)
WI
1
Region 6
UNITED STATES (USA)
DC
13
39
UNITED STATES (USA)
MA
3
UNITED STATES (USA)
NJ
5
UNITED STATES (USA)
NY
8
UNITED STATES (USA)
PA
10
Region 7
UNITED STATES (USA)
AL
14
106
UNITED STATES (USA)
GA
49
UNITED STATES (USA)
LA
3
UNITED STATES (USA)
NC
34
UNITED STATES (USA)
SC
6
Region 8
DOMINICAN REPUBLIC (DOM)
3
99
UNITED STATES (USA)
FL
89
UNITED STATES (USA)
PR*
7
*
PR = Puerto Rico.
Note: In general, a region is defined as multiple sites combined based on geographical locations. For example, for international 
studies, sites from each country or multiple neighboring counties were combined; and for US studies, sites from each state or 
multiple neighboring states were combined.


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Appendix 5.
Cardiovascular or Cerebrovascular Events
An adverse event record will be flagged as a cardiovascular or cerebrovascular event if its 
MedDRA PT is included in the pre-specified PT list, which includes all PTs from the narrow 
search of the following 3 SMQs under MedDRA 22.0 provided by Gilead PVE and reviewed by 
Gilead medical monitors.
SMQ Source
Cardiovascular or 
Cerebrovascular Events
Ischaemic central nervous system vascular conditions (SMQ) – Narrow Scope Term
Myocardial infarction (SMQ) - Narrow Scope Term
Other ischaemic heart disease (SMQ) - Narrow Scope Term


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Appendix 6.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT is included in the 
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs
under MedDRA 22.0 provided by Gilead PVE and reviewed by Gilead medical monitors.
SMQ Source
Hepatic Events
(HEP)
Biliary neoplasms benign (incl cysts and polyps) (SMQ)
Biliary malignant tumours (SMQ)
Biliary tumours of unspecified malignancy (SMQ)
Biliary system related investigations, signs and symptoms (SMQ)
Biliary tract disorders (SMQ)
Gallbladder related disorders (SMQ)
Gallstone related disorders (SMQ)
Cholestasis and jaundice of hepatic origin (SMQ)
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ)
Hepatitis, non-infectious (SMQ)
Liver neoplasms, benign (incl cysts and polyps) (SMQ)
Liver malignant tumours (SMQ)
Liver tumours of unspecified malignancy (SMQ)
Liver related investigations, signs and symptoms (SMQ)
Liver-related coagulation and bleeding disturbances (SMQ)


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Appendix 7.
Programming Specification
1) AGE calculated as follows:
a) AGE (years) is calculated from the number of days between the date of birth (DOB) and 
Day 1 (first dose date),
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
d) AGE = the integer of the result in (c),
e) If the DOB and Day 1 have the month in common and the birthday is later in the month 
than the date of Study Day 1, then subtract one from the AGE result above.
For subjects randomized and never dosed with study drug, age will be calculated from the 
date of randomization.
2) All screened subjects refer to all subjects who are screened (ie, with nonmissing screening 
date) and have a screening number. For summaries, the same subject is counted only once. 
DOB and other demographic information such as sex, race, ethnicity, country, and initials 
will be used to identify unique screened subjects.
3) Screen failure subjects are the subjects who are screened and answered “No” for any
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the subject was consent to.
4) Subjects in the randomized Analysis Set are defined as subjects randomized into the study. 
IXRSRAND is the source to determine whether the subject is randomized (ie, subject with 
nonmissing RGMNDTN in the IXRSRAND dataset) and confirmed by the eCRF ENROLL 
dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) are derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if subject 
took at least 1 dose of study drug and assigned as blank if subject never dosed.
6) Enrollment by Stratum: using actual HIV-1 RNA or CD4+ cell count screening value, the 
last screening value (with visitnum < 0) prior to randomization date and time.
7) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.


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8) Body mass index (BMI) and Body Surface Area (BSA)
BMI and BSA will be calculated only at baseline as follows:

BMI = (weight [kg]) / (height [meters]2)

BSA (m2) = SQRT( [Height(cm) × Weight(kg) ] / 3600 )
Baseline height and weight will be used for this calculation. 
9) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
a) CMH test for nominal variable (Y), the p-value from general association test should be 
used for nominal variable:
proc freq data=adsl;
tables trtgrp * Y /cmh /*general association test*/
run;
b) CMH test for ordinal variable (Y), the p-value from row mean score test should be used 
for ordinal variable:
proc freq data=adsl;
tables trtgrp * Y / cmh2 ; /*row mean score test*/
run;
c) Wilcoxon rank sum test for continuous variable (Y), the p-value from the normal 
approximation two-sided test should be used for continuous variable:
proc npar1way wilcoxon data=adsl;
class trtgrp; 
var Y;  
run;
10) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded for 
percentage calculation and also excluded for p value generation for categorical data analysis 
(eg, CMH test or Fisher exact test). Except for Mode of infection (HIV Risk Factors), where 
“Unknown” will be included for percentage calculation, since a subject may fit more than 
1 HIV risk factors, therefore percentage may add to more than 100% and no p-value will be 
generated. 
Subjects with Race = “Not Permitted” will also be excluded to define Race subgroup 
(ie, black vs. nonblack) for efficacy subgroup analysis. 


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11) SAS code for the treatment comparison for duration of exposure. The p-value from log rank 
test should be used.
proc lifetest data=ADSL method=km; 
time TRTDURD*ESDD(0); /*Derive ESDD from COMT01FL, where ESDD = 0 
indicates censored observation (ie, subject is still on study drug)*/
Strata TRT01AN;
label TRTDURD = "Duration of Exposure (Days)";
run;
12) Last Dose Date and Last Study Date
a) Last Dose Date (ie, TRTEDTC, TRTEDT, TR01EDT or TR01EDTC) in ADSL was 
defined in Section 3.8.1.
For subjects with a partial last dosing date (ie, month and year of last dose are known), 
the latest of the dispensing dates of study drug bottles, study drug start dates and end 
dates, and the imputed last dose date [day imputed as 15] will be used as the final 
imputed last dose date. However if dispensing date’s month is after last dose date’s 
month, data query is needed.
If subject died and the death date is complete (ie, not partial date) and before the imputed 
last dose date, the complete death date should be used as the imputed last dose date. 
Last dose date is not defined for subjects still on study drug in SAP. However, for the 
calculation of the duration of exposure to study drug, the data cut date will be used to 
impute the last dose date for subjects who have not permanently discontinued study drug 
at the time of the data cut date.
For Week 144 interim analysis, 04/19/2019 will be the data cut date for subjects with 
Week 144 visits on or prior to 04/19/2019, subjects missing Week 144 visits while on 
study drug, or subjects prematurely discontinued study drug. For subjects with Week 144
visit after 04/19/2019, the last subject’s Week 144 visit will be used as the data cut date 
as appropriate.
b) Last Study Date is the latest of the study drug start dates and end dates, the clinic visit 
dates, and the laboratory visit dates, including the 30-day follow-up visit date, for 
subjects who prematurely discontinued study or who completed study according to the 
Study Completion eCRF. If study drug start dates or end date is partially missing 
(ie, only year and month are known), the day will be imputed as 15 for the purpose of this 
analysis.
If subject died and the death date is complete (ie, not partial date) and before the imputed 
last study date, the complete death date should be used as the imputed last study date. 
Last study date is not defined for subjects still on study in SAP. However, for programing 
purposes, the latest of data cut date, the clinic visit dates, and the laboratory visit dates, 
including the 30-day follow-up visit date, will be used to impute the last study date for 
subjects still on study.


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13) Toxicity Grades:
a) For toxicity grade summaries, include all post-baseline graded results up to 30 days after 
the last dose of study drug, not just those used in by-visit summaries.
b) For glucose grading, as specified in SAP Section 7.2.2.1, the treatment-emergent flag 
cannot be determined for nonfasting glucose (including glucose results without a known 
fasting status). As a result, these records will be excluded from the “Maximum 
Treatment-emergent Toxicity Grade” summary in the “Treatment-emergent Laboratory 
Abnormalities” or “Treatment-emergent Grade 3 or 4 Laboratory Abnormalities” 
summary tables. In addition, fasting glucose and nonfasting glucose will be listed as 
two separate laboratory tests in the “Laboratory Abnormalities” and “Grade 3 or 4 
Laboratory Abnormalities” listings. Only a maximum postbaseline toxicity flag will be 
displayed and the treatment-emergent flag will not be displayed for nonfasting glucose as 
the treatment-emergent flag cannot be determined for nonfasting glucose. 
14) Efficacy analyses:
a) For categorical efficacy response (eg, Subjects with HIV-1 RNA < 50 copies/mL as 
determined by US FDA-defined snapshot algorithm, M=F, or M=E Analyses): the 
proportion difference between two treatment groups and its 95.002% or 95% CIs are 
calculated based on the MH proportion adjusted by baseline HIV-1 RNA stratum 
(≤100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US) (see Appendix 3
for details). To test superiority, the p-value from 2-sided CMH test (ie, general 
association test) stratified by baseline HIV-1 RNA stratum and region stratum should be 
used, where brnac is the baseline HIV-1 RNA stratum, region is the region stratum, 
trtgrp is the treatment, and response is the categorical efficacy response. The following 
SAS code will be used to compute cell counts and p-value. 
proc freq data=adeff;
tables brnac*region*trtgrp*response/cmh; /*p value from 
general association*/
run;
b) Homogeneity test: Homogeneity Test of Treatment Effect Across Region in HIV-1 RNA 
< 50 copies/mL at Week 144 (Snapshot Algorithm). For each region, the odds ratio and 
its 95% CI are calculated from the CMH test. For overall, the odds ratio and its 95% CI 
are calculated based on the common odds ratio estimate from the CMH test. The p-value 
for the homogeneity test is based on the Breslow-Day test of the interaction between 
region and treatment group as follows. 
proc freq data=adeff;
tables region2*trtgrp*response/all; /*p value from Breslow Day 
test*/
run;


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c) Subgroup analyses
i)
For the subgroups of age, sex, race, baseline CD4+ cell count, and study drug 
adherence, the proportion difference between two treatment groups and its 95% CIs 
are calculated based on the MH proportion adjusted by baseline HIV-1 RNA 
stratum and region stratum (see Appendix 3 for details). For example, for the age 
subgroup, the following SAS code will be used to compute cell counts. 
proc sort data=adeff;
by agegrp brnac region;
proc freq data=adeff;
by agegrp;
tables brnac*region*trtgrp*response/cmh;
run;
ii) For the baseline HIV-1 RNA subgroup, the proportion difference between 
two treatment groups and its 95% CIs are calculated based on the MH proportion 
adjusted by region stratum only. The following SAS code will be used to compute 
the cell counts.
proc sort data=adeff;
by brnac region;
proc freq data=adeff;
by brnac;
tables region*trtgrp*response/ cmh;
run;
iii) For the region subgroup, the proportion difference between two treatment groups and 
its 95% CIs are calculated based on the MH proportion adjusted by baseline HIV-1 
RNA stratum only. The following SAS code will be used to compute the cell counts.
proc sort data=adeff;
by region brnac;
proc freq data=adeff;
by region;
tables brnac*trtgrp*response/ cmh;
run;


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d) Homogeneity test: Homogeneity Test of Treatment Effect between Subgroups in 
HIV-1 RNA < 50 copies/mL at Week 144 (Snapshot Algorithm)
i)
For the subgroups of age, sex, race, baseline CD4+ cell count, and study drug 
adherence, the odds ratio and the associated 95% CIs are estimated for the response 
variable (response; coded as 1 for success and 0 for non-success) using a logistic 
regression model including treatment (trtgrp; coded as 1 for active [ie, B/F/TAF] and 
2 for control), baseline HIV-1 RNA stratum (brnac; coded as 1 for 
< 100,000 copies/mL and 2 for >= 100,000 copies/mL), region stratum (region; coded 
as 1 for “US” and 2 for “Ex-US”), subgroup factor (coded as 1 for the first subgroup 
and 2 for the second subgroup), and treatment by subgroup factor. For example, for
the age subgroup (agegrp; coded as 1 for < 50 and 2 for >= 50), the following SAS 
code will be used to generate the Odds Ratio and its 95% CI within the subgroup:
Note: For the following code, it is assumed that none of the variables have any 
formats applied to them. If they do, they must be removed before calling the code.
proc genmod data=data descending; /*model for success*/
class trtgrp brnac region agegrp;
model response = trtgrp brnac region agegrp 
trtgrp*agegrp/dist=bin 
link=logit lrci;                        
estimate 'Group 1' trtgrp 1 -1 trtgrp*agegrp 1 0 -1 0/exp;
estimate 'Group 2' trtgrp 1 -1 trtgrp*agegrp 0 1 0 -1/exp;
run;
ii) For the baseline HIV-1 RNA subgroups, the odds ratio and the associated 95% CIs 
are estimated using a logistic regression model including treatment, region stratum, 
subgroup factor, and treatment by subgroup factor. The following SAS code will be 
used to generate the Odds Ratio and its 95% CI within the subgroup (the same 
formats as described in (a) above are assumed):
proc genmod data=data descending; 
class trtgrp region brnac;
model response = trtgrp region brnac trtgrp* brnac/dist=bin   
link=logit lrci;
estimate 'Group 1' trtgrp 1 -1 trtgrp*brnac 1 0 -1 0/exp;
estimate 'Group 2' trtgrp 1 -1 trtgrp*brnac 0 1 0 -1/exp;
run;
iii) For the region subgroups, the odds ratio and the associated 95% CIs are estimated 
using a logistic regression model including treatment, baseline HIV-1 RNA stratum,
subgroup factor, and treatment by subgroup factor. The following SAS code will be 
used to generate the Odds Ratio and its 95% CI within the subgroup (the same 
formats as described in (a) above are assumed):
proc genmod data=data descending;
class trtgrp brnac region;
model response = trtgrp brnac region trtgrp*region/dist=bin 
link=logit lrci;                        
estimate 'Group 1' trtgrp 1 -1 trtgrp*region 1 0 -1 0/exp;
estimate 'Group 2' trtgrp 1 -1 trtgrp*region 0 1 0 -1/exp;
run;


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iv) Clarification for SE(P1-P2) Calculation in Appendix 3

if n1h or n2h > 1 the denominator n1h − 1 or n2h − 1 was calculated as indicated in 
the formula;

if n1h or n2h =1, the corresponding n1h or n2h will be adjusted to 2, then 
corresponding denominator [(n1h − 1) or (n2h − 1)] is 1;

if n1h or n2h = 0 but not both n1h and n2h = 0 then not calculable;

if both n1h and n2h = 0 then the corresponding stratum will be ignored, will not be 
included in the calculation, thus the proportion difference and 95% CI are still 
calculable.
If the sample size in a subgroup is too small to calculate the proportion difference 
between 2 treatment groups and its 95% CI based on the stratum-adjusted MH 
proportion, then a 95% CI based on the normal approximation will be used. For 
example, if the stratum-adjusted MH proportion cannot be calculated for 
sex = “Female” subgroup, the following code will be used to calculate the proportion 
difference and 95% CI based on the normal approximation, ie, riskdiff option in 
tables statement will provide the proportion difference and 95% CI estimations.
proc freq data = adeff;
  where sex = "F";
tables trtgrp*response/ riskdiff(CL=(WALD));
run;
e) ANOVA model for continuous efficacy variable (eg, CD4+): The differences in changes 
from baseline in CD4+ cell count between treatment groups and the associated 95% CI 
will be constructed using an ANOVA, including baseline HIV-1 RNA stratum, region 
stratum, and treatment as fixed effects in the model.
proc glm data=adeff;
class brnac region trtgrp;
model CD4=brnac region trtgrp;
lsmeans trtgrp /alpha=0.05 cl pdiff;
run;
f)
Listing for US FDA-defined snapshot outcome:
In addition to flagging the values of HIV-1 RNA < 50 or ≥ 50 copies/mL for virologic 
outcomes, flag the last available HIV-1 RNA value while on treatment for the following 
categories:
i)
HIV-1 RNA ≥ 50 copies/mL - Discontinued Study Drug Due to Other Reasons and 
Last Available HIV-1 RNA ≥ 50 copies/mL
ii) No virologic Data - Discontinued Study Drug Due to Other Reasons and Last 
Available HIV-1 RNA < 50 copies/mL


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15) DXA Analysis: 
a) Variable used for analysis:
i)
Variable CORRBMD when Region = “SpineTotalAdequate” for spine, Region 
= “FemurTotal” for hip, and Region = “FemurNeck” for femur neck will be used for 
percentage change from baseline in BMD analysis.
ii) Variable CORRTSCR when Region = “SpineTotalAdequate” for spine and Region 
= “FemurTotal” for hip will be used for defining the BMD clinical status.
b) BMD clinical status comparison: Rank Analysis of covariance. base is the baseline BMD 
clinical status and post is the post baseline clinical status (both coded as 0 for normal, 
1 for Osteopenia, 2 for Osteoporosis, . for missing). The p-value from row mean score 
test from the last proc freq procedure is the p-value for rank analysis of covariance. 
proc rank data=addxa nplus1 ties=mean out=ranks1;
var base post;
rank baserank postrank;
run;
proc reg data=ranks1;
model postrank=baserank;
output out=residual1 r=resid;
run;
proc freq data=residual1;
tables trtgrp*resid/noprint cmh2; /* row mean score test*/
run;
16) TEAE
Events with Missing Onset Day and/or Month
An AE is treatment emergent if the following 3 criteria are met:
1) The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
2) The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
3) End date is as follows: 
a) The (complete) end date is on or after the first dose date, or
b) The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
c) End date is completely missing 


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Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of 
the criteria specified in 3) above.
17) Graded Laboratory Abnormalities Summary
The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Hematology
Hemoglobin
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Chemistry
Albumin 
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
GGT
Increase
GGT (Increased)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Fasting) 
Decrease
Serum Glucose (Fasting, Hypoglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Decrease
Serum Glucose (Nonfasting, Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)


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Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Total Cholesterol (Fasting)
Increase
Total Cholesterol (Fasting, Hypercholesterolemia)
Triglycerides (Fasting) 
Increase
Triglycerides (Fasting, Increased)
LDL (Fasting)
Increase
LDL (Fasting, Increased)
Urea Nitrogen (BUN)
Increase
Urea Nitrogen (Increased)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Uric Acid
Decrease
Uric Acid (Hypouricemia)
Urinalysis
Urine Blood (Dipstick)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine Protein
Increase
Urine Protein (Proteinuria)
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
*
Due to the reflexive nature of the quantitative urine RBC test, results will be combined with the dipstick test of urine blood 
as described below. General rule is that urine RBC (Quantitative) should always be used first (if available), no matter it is 
collected at the same time of Urine Blood (Dipstick) or not. The combined Urine RBC (hematuria, Quantitative or Dipstick) 
toxicity grade will be used for “Maximum treatment-emergent toxicity grade” summary.  
Is Post-BL 
Urine RBC 
(Quant.) Result 
Available?
Is BL Urine 
RBC (Quant.) 
Result 
Available?
Is Post-BL 
Urine Blood 
(Dipstick) 
Result 
Available?
Is BL Urine 
Blood 
(Dipstick) 
Result 
Available?
How to Determine Treatment-
Emergent Toxicity for “Urine RBC 
(Hematuria, Quantitative or 
Dipstick)”
Yes
Yes
-
-
Compare post-BL Urine RBC 
(Quant.) toxicity grade to BL Urine 
RBC (Quant.) toxicity grade. If post-
BL toxicity is greater than BL 
toxicity, then treatment-emergent
Yes
No
-
-
Treatment-emergent. Use post-BL 
Urine RBC (Quant.) toxicity grade.
No
-
Yes
Yes
Compare post-BL Urine Blood 
(Dipstick) toxicity grade to BL Urine 
Blood (Dipstick) toxicity grade. If 
post-BL toxicity is greater than BL 
toxicity, then treatment-emergent
No
-
Yes
No
Treatment-emergent. Use post-BL 
Urine Blood (Dipstick) toxicity grade.
No
-
No
-
Do not count subject in the 
denominator for “Urine RBC 
(Hematuria, Quantitative or 
Dipstick)”
BL = Baseline. Quant = Quantitative. “-” means any value can be present (or it can be missing), as it does not affect the 
classification


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18) Renal related laboratory evaluation
a) Unit conversion for renal safety tests derived from related tests with conventional units

Urine RBP (ug/L) to creatinine (mg/dL) ratio: 1 (ug/L) / (mg/dL) = 100 × ug/g

Urine Beta-2-microglobulin (mg/L) to creatinine (mg/dL) ratio: 1 (mg/L) / (mg/dL) 
= 105 ug/g 

Urine Albumin (mg/dL) to creatinine (mg/dL) ratio: 1 (mg/dL) / (mg/dL) 
= 1000 × mg/g
b) Calculation of ratios: 
To calculate laboratory ratios (eg, urine RBP to creatinine ratio), the lab value of each 
test in the ratio needs to be from the same accession number; if any test value used for the 
ratio calculation from the same accession number is missing , then the ratio is not 
calculable (ie, missing).
19) Smoking status at baseline
Smoking status at baseline (ie, never smoker, former smoker, and current smoker) will be 
summarized as part of the baseline disease characteristics. How to classify a subject as never, 
former, or current smoker at baseline is specified as follows: 
a) First, select only records with Type of Substance Use = “Cigarettes” or “Cigars”. Records 
with Type of Substance Use = “Other” (including chew tobacco, e-cigarettes, etc) will not 
be considered as smoking.
b) Second, for each selected substance use record, flag whether it is “Prior”, “Present”, or 
“Post” relative to the first dose date according to the Algorithm below. 
c) Finally, (1) the subject will be flagged as “Never smoker”, if the subject has no record 
with Type of Substance Use = “Cigarettes” or “Cigars” or all selected records have a flag 
of “Post”; (2) the subject will be flagged as a “Former” smoker, if any selected records 
has a flag of “Prior” and no record of “Present”; (3) Otherwise, the subject will be 
flagged as a “Current” smoker, if any selected records has a flag of “Present”. 
Selected Substance Use Records
Prior
No
No
Yes
Yes
Yes
No
No
Yes
Present
No
No
No
No
Yes
Yes
Yes
Yes
Post
No
Yes
No
Yes
No
No
Yes
Yes
Smoking Status
Never
Never
Former
Former
Current
Current
Current
Current


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Algorithm to flag whether a selected record is “Prior”, “Present”, or “Post” relative 
to the first dose date:
1) the start and stop dates of the selected record are not completely missing (ie, at least 
year is known) or the start date is not missing and record is ongoing. The completed 
start or stop dates will be used to compare with the first dose date whenever possible. 
Otherwise, the month and year (or year alone if month is not recorded) of the start or 
stop dates will be used to compare with the first dose date when the start or stop date 
of the selected record is incomplete. 
a) The record is flagged as “Prior”, if the stop date is before (<) the first dose date; 
b) The record is flagged as “Present”, if the start date is on or before (≤) the first 
dose date and the stop date is on or after (≥) the first dose date, or the selected 
record is marked as ongoing and the start date is on or before (≤) the first dose
date; 
c) The record is flagged as “Post”, if the start date is after the first dose date;
2) the start date of the selected record is completely missing. We assume that the start 
date is before the first dose date, the stop date (or the month and/or year of the stop 
date, if stop date is incomplete) will be used to determine whether the selected record 
is “Prior” or “Present” as follows.
a) The record is flagged as “Prior”, if the stop date is before (<) the first dose date or 
the stop date is completed missing and the record is not marked as ongoing. 
b) The record is flagged as “Present”, if the stop date is on or after (≥) the first dose
date or the selected record is marked as ongoing.
3) the start date of the selected record is before (<) the first dose date, but the stop date is 
completely missing and the record is not marked as ongoing. We assume that the end 
date is before the first dose date, the record is flagged as “Prior”.
4) The start date of the selected record is on or after the first dose date, but the stop date 
is completely missing and the record is not marked as ongoing. This is a data issue, 
should be queried first. However, this record is flagged as “Present” if the start date is 
on the first dose; this record is flagged as “Post” if the start date is after the first dose.
20) Concomitant nonstudy-drug ARV medications (ie, ARV medications other than study drug 
that are taken while receiving study drug) will be flagged in “Nonstudy-Drug Antiviral 
Medication” listing. The logic to define concomitant nonstudy-drug ARV is similar to 
concomitant non-ARV Medications (see details in Section 7.5.2)


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21) Lipid modifying medication analyses:

Lipid modifying medication is defined to be the concomitant medication with ATC2 term = 
“LIPID MODIFYING AGENTS” and CMDECOD contains wording of “STATIN” in the 
ADCM dataset.

Subjects who took lipid-modifying medications at study entry refer to the subjects who use of 
the lipid-modifying agents at study day 1 (ie, the first dose date). More specifically, subjects 
with “Lipid Modifying Agent Use at Study Entry” include those subjects in Safety Analysis 
Set with: 1) any selected CM record with the start date ≤ the first dose date, and 2) the end 
date of the selected CM record is ongoing or the end date of the selected CM record ≥the 
first dose date.

Subjects who initiated lipid-modifying medications during the study include the subjects in 
the Safety Analysis Set who didn’t take lipid-modifying medications at study entry and met 
the following criteria: 1) for subjects who permanently discontinued study drug with any 
selected CM record started after the first dose date and on and prior to the last dose date; 2) 
for subjects who are still on study drug with any selected CM records started after the first 
dose date.

For lipid-modifying medications with the start date completely unknown, we assume the start 
date is on or before the first dose date, lipid-modifying medication was considered as being 
taken at study entry if the end date is not prior to the first dose date (ie, the end date is on or 
after the first dose date, completely unknown, or ongoing). 

Lipid modifying medications with the start date prior to the first dose date and the end date 
completely unknown were considered as being taken at study entry.
22) For figures, if at a visit where n (sample size) for any treatment group ≤ 5, data for that 
treatment group will not be displayed at the visit in figure (except the Kaplan-Meier figure), 
but all data will be included in the corresponding table summary.
23) HIV/HBV and HIV/HCV Coinfection:

The following table presents the HBV and HCV tests with all possible values. Values that 
have an asterisk after them denote a “positive” (or “quantifiable” for HBV DNA and HCV 
RNA) result while all others denote a “negative” result.
Label
LBTESTCD
LBTEST
Possible Values
HBsAg
CNT63
Hep B Surface Ag
“Positive”*, “Positive, Confirmed”*,“Negative”
HBsAg
ATT2
Hep. B Surf. Ag Qual(-70)-PS
“Repeat reactive, confirmed”*, “Repeat Reactive 
Unconfirmed”, “Non-Reactive”
HBsAb
CNT353
anti-Hep B Surface Ag2 Qual
“Positive”*, “Negative”
HBcAb
CNT68
Hepatitis B Core Total
“Positive”*, “Negative”
HBV DNA
GET1883
HBV DNA CAP/CTM 
2.0-EDTA-CL
“No HBV DNA detected”, “<20 IU/mL HBV DNA 
detected”, “>170000000”*, NUMERICAL VALUE*
HCVAb
CNT350
Hepatitis C Virus Antibody
“Positive”*, “Indeterminate”, “Negative”
HCV RNA
GET1881
HCV RNA CAP/CTM 
2.0EDTA-CL
“No HCV RNA detected”, “<15 IU/mL HCV RNA 
detected”, NUMERICAL VALUE*


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
For baseline coinfection, when considering the different laboratory tests, take the latest, 
non-missing record on or prior to the first dose date for each test (eg, HBsAg, HBsAb, 
HBcAb, and HBV DNA)
The baseline coinfection status will be one of the three values: Yes/No/Null
The following tables provide combinations of HBV and HCV tests and the 
corresponding baseline coinfection status
HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
-
-
-
Y
Negative
Positive
-
-
N
Negative
Positive
Quantifiable
Y
Not Quantifiable
N
Missing
Null
Negative
-
N
Missing
Quantifiable
Null
Not Quantifiable
N
Missing
Null
Missing
Positive
Quantifiable
Null
Not Quantifiable
N
Missing
Null
Negative
-
N
Missing
Quantifiable
Null
Not Quantifiable
N
Missing
Null
Missing
Positive
-
-
Null
Negative
Positive
Quantifiable
Y
Not Quantifiable
Null
Missing
Null
Negative
-
Null
Missing
-
Null
Missing
-
-
Null


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HCVAb
HCV RNA
Coinfection Status
Positive
Quantifiable
Y
Not Quantifiable
N
Missing
Null
Negative
-
N
Missing
Quantifiable
Null
Not Quantifiable
N
Missing
Null
“-” means any value can be present, as it does not affect the classification

For incident coinfection, all laboratory tests must share the same accession number and if any 
set of values meets the criteria, then the subject is considered to have incident coinfection
The incident coinfection status will be one of two values: Yes/Null
The following tables provide combinations of HBV and HCV tests that are 
considered “Y” for incident coinfection status (all others are considered Null)
HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
-
-
-
Y
Negative
Negative
Positive
Quantifiable
Y
Missing
Negative
Positive
Quantifiable
Y
HCVAb
HCV RNA
Coinfection Status
Positive*
-
Y
-
Quantifiable
Y
*
Subjects with positive HCVAb postbaseline must also have negative or missing HCVAb at baseline in order to be 
considered as having incident HIV/HCV coinfection.
“-” means any value can be present, as it does not affect the classification
For adverse events, the start date must be after the first dose date and on or prior to 
the last dose date
For incomplete AE start dates, please follow the logic specified in Section 7.1.5.2, but 
modify the second criterion to read, “The month and year (or year) of the AE onset is 
the same as or before the month and year (or year) of the date of the last dose of study 
drug”.
24) HBV DNA test codes: If the result of the lab test code GET1883 (HBV DNA CAP/CTM 
2.0-EDTA-CL) is listed as “>170000000”, then a reflexive test code GET1884 (HBV DNA 
CAP/CTM 2.0Dil-EDTA-CL) should be performed and will share the same accession 
number as the original GET1883 test. In this instance, use the result from GET1884 instead 
of GET1883 when determining HBV DNA.


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25) LDL: Conversions between 2nd and 3rd generations
LDL was analyzed by 2 different assays in the study: 2nd generation (including RCT2394, 
RCT2312, and RCT2811) and 3rd generation (RCT3870). Samples collected at earlier visits 
were analyzed using LDL 2nd generation assay. Samples collected at later visits were 
analyzed using LDL 3rd generation assay. The conversion formulas are as follow:
2nd Gen (mmol/L) = (3rd Gen - 0.0626)/0.882
3rd Gen (mmol/L) = (0.882 x 2nd Gen) + 0.0626
For this analysis, since LDL samples were analyzed by 2nd generation assay at Baseline, we 
only requested conversion from 3rd generation to 2nd generation.
For the analysis of change from baseline in fasting direct LDL: the sample analyzed by LDL 
3rd generation assay will be converted to 2nd generation as a new record with test codes of 
LIP.LDL.00.02 in raw data. During ADaM stage, a derived parameter code (FLDL2) for 
“Fasting LDL Cholesterol 2ND GEN Combined” will be generated to pool the records from 
both original (including test codes RCT2394, RCT2312, and RCT2811) and converted 
(LIP.LDL.00.02) 2nd generation results to calculate the change from baseline in fasting 
direct LDL.
For the analysis of toxicity grade for fasting direct LDL: toxicity grade will be based on the 
Gilead grading results (ie, toxgrg) from original values before conversion. In another words, 
during ADaM stage, a derived parameter code (FLDLTOX) for “Fasting LDL Cholesterol 
for Toxicity” will be generated to pool the records from 2nd generation (including RCT2394, 
RCT2312, and RCT2811) and 3rd generation (ie, RCT3870) to derive treatment-emergent 
toxicity grades, maximum postbaseline toxicity grades, etc.


SAP-Week144-GS-US-380-1489
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Research eSigned 14-May-2019
00:44:08
Biostatistics eSigned
15-May-2019
15:48:51
PPD
PPD

Prot_006.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Clinical 
Program Manager: 
Gilead Medical 
Monitor: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emu·icitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV -1 Infected, 
Antireu·oviral Treatment-Naive Adults 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
125589 
2015-004024-54 
NCT02607930 
HIV -1 Infection 
GS-US-380-1489 
Name: 
Telephone: 
Fax: 
PD 
PPD 
PPD 
Name: 
Telephone: 
Hal Mmi in, MD, MPH 
PPD 
Fax: 
Mobile: 
Original: 
Amendment 1: 
Amendment 2: 
PPD 
PPD 
21 October 2015 
19 Febmmy 2016 
19 October 2016 
CONFIDENTIALITY STATEMENT 
The inf01mation contained in this document, patiicularly unpublished data, is the propetiy or 
under conu·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 infonnation 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 infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessmy to obtain infonned consent from those 
persons to whom the dmg may be administered. 


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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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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....................................................................13
1.
INTRODUCTION ..............................................................................................................................................16
1.1.
Background ............................................................................................................................................16
1.2.
GS-9883 .................................................................................................................................................17
1.2.1.
General Information .............................................................................................................17
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................17
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................19
1.3.
Information about Emtricitabine (Emtriva®, FTC).................................................................................28
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)..................................................................28
1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) 
or Fixed Dose Combination emtricitabine/tenofovir alafenamide 
(FTC/TAF)...........................................................................................................................29
1.4.2.
Clinical Trials of FTC/TAF as part of 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) ...........................30
1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) ...........................32
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, 
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................32
1.6.
Information about abacavir/dolutegravir/lamivudine (ABC/DTG/3TC Triumeq®)...............................33
1.7.
Rationale for this Study..........................................................................................................................33
1.8.
Risk/Benefit Assessment for the Study..................................................................................................34
1.9.
Rationale for Dose Selection..................................................................................................................35
1.10.
Compliance ............................................................................................................................................36
2.
OBJECTIVES.....................................................................................................................................................37
3.
STUDY DESIGN................................................................................................................................................38
3.1.
Endpoints ...............................................................................................................................................38
3.2.
Study Design..........................................................................................................................................38
3.3.
Study Treatments ...................................................................................................................................38
3.4.
Duration of Treatment............................................................................................................................39
3.5.
Biomarker Testing..................................................................................................................................40
3.5.1.
Biomarker Samples for Optional Pharmacogenomic Research............................................40
3.5.2.
Additional Sample Storage...................................................................................................40
4.
SUBJECT POPULATION..................................................................................................................................41
4.1.
Number of Subjects and Subject Selection ............................................................................................41
4.2.
Inclusion Criteria....................................................................................................................................41
4.3.
Exclusion Criteria...................................................................................................................................42
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................45
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................45
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................45
5.2.
Description and Handling.......................................................................................................................46
5.2.1.
Formulation..........................................................................................................................46
5.2.2.
Packaging and Labeling .......................................................................................................46


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5.2.3.
Storage and Handling...........................................................................................................47
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide and 
Abacavir/Dolutegravir/Lamivudine .......................................................................................................47
5.4.
Prior and Concomitant Medications.......................................................................................................48
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................49
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................49
6.
STUDY PROCEDURES ....................................................................................................................................50
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................50
6.2.
Pretreatment Assessments......................................................................................................................50
6.2.1.
Screening Visit .....................................................................................................................50
6.2.2.
Day 1 Assessments...............................................................................................................52
6.3.
Randomization .......................................................................................................................................54
6.4.
Treatment Assessments (Week 4 - 144).................................................................................................54
6.5.
Treatment Assessments (Post Week 144 until the Open Label Rollover Extension).............................57
6.5.1.
Post Week 144 Assessments ................................................................................................57
6.5.2.
End of Blinded Treatment Visit ...........................................................................................59
6.5.3.
Treatment Assessments (Open-Label Rollover Extension)..................................................60
6.6.
Post-treatment Assessments ...................................................................................................................62
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................62
6.6.2.
30 Day Follow Up................................................................................................................63
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................65
6.8.
Bone Mineral Density Evaluations.........................................................................................................65
6.9.
Other Evaluations...................................................................................................................................66
6.9.1.
Markers of Renal Tubular Function .....................................................................................66
6.9.2.
Markers of Inflammation and Immune Activation...............................................................66
6.9.3.
Markers of Platelet Function ................................................................................................66
6.10.
Blood and Urine Storage........................................................................................................................66
6.11.
Assessments for Premature Discontinuation from Study.......................................................................66
6.12.
End of Study...........................................................................................................................................66
6.13.
Post Study Care......................................................................................................................................67
6.14.
Virologic Failure....................................................................................................................................67
6.14.1.
Management of Virologic Rebound .....................................................................................67
6.14.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48, Week 96, or Week 144.........................................................................................68
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................69
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................69
7.1.1.
Adverse Events.....................................................................................................................69
7.1.2.
Serious Adverse Events........................................................................................................69
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................70
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................70
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................70
7.2.2.
Assessment of Severity ........................................................................................................71
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................71
7.3.1.
Adverse Events.....................................................................................................................71
7.3.2.
Serious Adverse Events........................................................................................................72
7.4.
Gilead Reporting Requirements.............................................................................................................73
7.5.
Toxicity Management ............................................................................................................................73
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................73
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................74
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................74


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7.5.4.
Management of Possible Abacavir Hypersensitivity Reaction.............................................74
7.5.5.
Management of Potential Hepatobiliary Toxicity ................................................................75
7.5.6.
On-Treatment Hepatitis C Management...............................................................................75
7.6.
Special Situations Reports......................................................................................................................76
7.6.1.
Definitions of Special Situations..........................................................................................76
7.6.2.
Instructions for Reporting Special Situations.......................................................................76
8.
STATISTICAL CONSIDERATIONS................................................................................................................78
8.1.
Analysis Objectives and Endpoints........................................................................................................78
8.1.1.
Analysis Objectives..............................................................................................................78
8.1.2.
Primary Endpoint .................................................................................................................78
8.1.3.
Secondary Endpoint .............................................................................................................78
8.2.
Analysis Conventions.............................................................................................................................78
8.2.1.
Analysis Sets ........................................................................................................................78
8.3.
Data Handling Conventions ...................................................................................................................80
8.4.
Demographic Data and Baseline Characteristics ...................................................................................81
8.5.
Efficacy Analysis ...................................................................................................................................81
8.5.1.
Primary Analysis..................................................................................................................81
8.5.2.
Secondary Analyses .............................................................................................................82
8.6.
Safety Analysis.......................................................................................................................................83
8.6.1.
Extent of Exposure...............................................................................................................83
8.6.2.
Adverse Events.....................................................................................................................83
8.6.3.
Laboratory Evaluations ........................................................................................................84
8.6.4.
Bone Safety Evaluations ......................................................................................................84
8.6.5.
Other Safety Evaluations......................................................................................................84
8.7.
Pharmacokinetic Analysis......................................................................................................................84
8.8.
Inflammation, Immune Activation, Platelet and Renal Tubular Function Analysis...............................85
8.9.
Patient Report Outcomes (PRO) ............................................................................................................85
8.10.
Sample Size............................................................................................................................................85
8.11.
Data Monitoring Committee ..................................................................................................................85
8.12.
Analysis Schedule ..................................................................................................................................86
9.
RESPONSIBILITIES..........................................................................................................................................87
9.1.
Investigator Responsibilities ..................................................................................................................87
9.1.1.
Good Clinical Practice..........................................................................................................87
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................87
9.1.3.
Informed Consent.................................................................................................................87
9.1.4.
Confidentiality......................................................................................................................88
9.1.5.
Study Files and Retention of Records ..................................................................................88
9.1.6.
Case Report Forms...............................................................................................................89
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................90
9.1.8.
Inspections............................................................................................................................90
9.1.9.
Protocol Compliance............................................................................................................90
9.2.
Sponsor Responsibilities ........................................................................................................................91
9.2.1.
Protocol Modifications.........................................................................................................91
9.2.2.
Study Report and Publications .............................................................................................91
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................91
9.3.1.
Payment Reporting...............................................................................................................91
9.3.2.
Access to Information for Monitoring..................................................................................92
9.3.3.
Access to Information for Auditing or Inspections ..............................................................92
9.3.4.
Study Discontinuation..........................................................................................................92
10.
REFERENCES ...................................................................................................................................................93


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11.
APPENDICES ....................................................................................................................................................94
Appendix 1.
Investigator Signature Page....................................................................................................95
Appendix 2.
Study Procedures Table (Blinded Phase) ...............................................................................96
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)..................................................101
Appendix 4.
Management of Clinical and Laboratory Adverse Events....................................................103
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.............104
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................126
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................127
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........21
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................22
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................23
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)...............................................................................24
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................35
Table 5-1.
Prior and Concomitant Medications.......................................................................................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).......................................................................................24
Figure 3-1.
Study Schema.........................................................................................................................39
Figure 6-1.
Virologic Rebound Schema....................................................................................................68


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, 
Antiretroviral Treatment-Naïve Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004024-54
NCT02607930
Study Centers 
Planned:
Approximately 150 centers in North America, Europe and
Latin America 
Objectives:
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) 
containing GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 
infected, antiretroviral treatment naïve-adult subjects as 
determined by the achievement of HIV-1 RNA < 50 copies/mL at 
Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the two 
treatment groups through Weeks 48, 96, and 144

To evaluate the bone safety of the two treatment groups as 
determined by the percentage change from baseline in hip and 
spine bone mineral density (BMD) through Weeks 48, 96, 
and 144
Study Design:
Randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus 
ABC/DTG/3TC FDC in HIV-1 infected, antiretroviral treatment-naïve 
adult subjects. Subjects who provide written consent and meet all 
eligibility criteria will be randomized in a 1:1 ratio to one of the 
following two treatment groups:


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Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 
200 mg/ tenofovir alafenamide 25 mg (GS-9883/F/TAF) + Placebo to 
match FDC of abacavir 600 mg/ dolutegravir 50 mg/lamivudine 
300 mg (ABC/DTG/3TC) administered orally, once daily, without 
regard to food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 
50 mg/ lamivudine 300 mg (ABC/DTG/3TC) + Placebo to match 
FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without 
regard to food (n=300)
Randomization will be stratified by HIV-1 RNA level 
(≤100,000 copies/mL, > 100,000 to ≤ 400,000 copies/mL, or 
> 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. 
Ex-US) at randomization.
Number of Subjects 
Planned:
Approximately 600 subjects in total. 300 subjects in each Treatment 
Group 1 and Treatment Group 2
Target Population:
Antiretroviral treatment-naïve (except the use for pre-exposure 
prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to 
one month prior to screening), HLA-B*5701 negative, HIV-1 infected 
adults with plasma HIV-1 RNA levels ≥ 500 copies/mL and a 
screening genotype showing sensitivity to FTC, TFV, 3TC, and ABC.
Duration of 
Treatment:
Subjects will be treated for at least 144 weeks during the blinded 
treatment phase.  After Week 144, all subjects will continue to take 
their blinded study drug and attend visits every 12 weeks until the End 
of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all 
subjects will return to the clinic (preferably within 30 days) for an
End of Blinded Treatment Visit. At the End of Blinded Treatment 
Visit, if safety and efficacy of GS-9883/F/TAF FDC is demonstrated 
following review of unblinded data, 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 in an open label (OL) extension phase 
for up to 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.
All subjects participating in the open label extension phase, without 
regard to their blinded treatment regimen, will return for study visits 
at Week 12 OL and every 12 weeks thereafter for up to 48 weeks.


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Subjects who complete the study through the End of Blinded 
Treatment Visit and do not continue on the open label 
GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day 
Follow-Up Visit.
Treatment assignments will be provided to the investigators within 
30 days of the last subject completing the End of Blinded Treatment 
Visit.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening

Antiretroviral treatment naïve (≤ 10 days of prior therapy with any 
antiretroviral agent following a diagnosis of HIV-1 infection) 
except the use for PrEP or PEP, up to one month prior to 
screening.

Screening genotype report must show sensitivity to FTC, TFV, 
3TC, and ABC

Negative screening test for HLA-B*5701 allele

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance

No chronic Hepatitis B Virus (HBV) infection, as determined by 
either
Positive HBV surface antigen and negative HBV surface 
antibody, regardless of HBV core antibody status, at the 
screening visit
Positive HBV core antibody and negative HBV surface 
antibody, regardless of HBV surface antigen status, at the 
screening visit
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 
144 weeks. Following the Day 1 visit, subjects will be required to 
return for study visits at Weeks 4, 8, and 12, and then every 12 weeks 
from Week 12 through Week 144.  After Week 144, all subjects will 
continue to take their blinded study drugs and attend study visits every 
12 weeks until the End of Blinded Treatment Visit.
For all eligible subjects, blood will be collected at Day 1, Weeks 4, 8, 
12, and then every 12 weeks through the End of Blinded Treatment 
Visit.  Laboratory analyses (hematology, chemistry, and urinalysis), 


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HIV-1 RNA, CD4+ cell count, and complete or symptom directed 
physical examinations will be performed at Screening, Day 1 and all 
subsequent visits. In addition, blood will be collected and stored for 
possible evaluation of markers of inflammation and immune 
activation, which may include but are not limited to: cystatin-C, IL-6, 
hs-CRP, d-dimer, sCD14, and sCD163. Platelet function evaluations 
may also be assessed, including but not limited to soluble 
glycoprotein VI (sGPVI), P-selectin, and soluble CD40 ligand.  Urine 
will be collected for evaluations of renal tubular function including 
urine albumin, urine creatinine, urine protein, retinol binding protein 
and beta-2 microglobulin.
For all subjects on study drug, except subjects located in Germany,
dual energy x-ray absorptiometry (DXA) scans will be performed 
prior to or within 24 hours of the Day 1 Visit, and then at Weeks 24, 
48, 96, 144 and at the End of Blinded Treatment Visit or Early Study 
Drug Discontinuation Visit (blinded treatment phase only), if 
> 12 weeks since last scan. DXA scan results will be provided to 
study sites when available.
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:
FDC of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg 
(ABC/DTG/3TC) administered orally, once daily without regard to 
food.
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests and DXA
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 48 as defined by the United States (US) 
Food and Drug Administration (FDA)-defined snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 96 and 144 as defined by the US 
FDA-defined snapshot algorithm


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Protocol GS-US-380-1489 
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Gilead Sciences, Inc. 
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Phannacokinetics: 
Optional Genomic 
Testing: 
CONFIDENTIAL 
• 
The proportion of subjects who achieve HIV -1 RNA 
< 20 copies/mL at Weeks 48, 96, and 144 as defined by the US 
FDA-defined snapshot algorithm 
• 
The change from baseline in log10 HIV-1 RNA and CD4+ cell 
count at Weeks 48, 96, and 144. 
An intensive phannacokinetic (PK) substudy will be perfonned at the 
Weeks 4 or 8 visits in a subset of subjects (target n=30) at study sites 
able to conduct this testing. 
For all subjects on study dmg a single anytime pre or post-dose PK 
blood sample will be collected at Weeks 8, 24 and 36. 
For all subjects on study dmg a u·ough PK blood sample will be 
obtained 20-28 homs following the last dose at Weeks 4 and 12. 
Following an observed dose, one post-dose PK blood sample will be 
collected between 1 and 4 homs post-dose. 
For intensive PK substudy, the following PK parameters for GS-9883 
may be explored as applicable: 
Cmax, Tmax, Clast, T!ast, Ctau,T!I2, AUCtau,AUCo-!ast, VzJF, CLss/F. 
The concenu·ation of GS-9883 may be sUIIllnarized using descriptive 
statistics. The phannacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concenu·ations may be analyzed 
and PK parameters may be summarized as applicable. 
PPD 
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19 October 2016 


GS-9883/F/T AF 
Protocol GS-US-380-1489 
Gilead Sciences, Inc. 
Optional Peripheral 
Blood Mononuclear 
Cell Substudy: 
Patient Reported 
Outcome: 
Statistical Methods: 
CONFIDENTIAL 
PD 
Final 
Amendment2 
Sh01i F01m 36 Health Smvey (SF-36), HIV Symptoms Distress 
Module, Work Productivity and Activity Impainnent Questionnaire 
(WP AI) and Pittsbmgh Sleep Quality Index (PSQI) will be 
administered at Day 1, Weeks 4, 12, and 48. 
The primmy analysis will consist of a non-inferiority test of 
GS-9883/F/TAF versus ABC/DTG/3TC, with respect to the 
prop01iion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defmed snapshot algorithm. 
It will be concluded that GS-9883/F/TAF is non-inferior to 
ABC/DTG/3TC if the lower bmmd of the 2-sided 95% confidence 
interval (CI) of the difference (GS-9883/F/TAF - ABC/DTG/3TC) in 
the response rate (HIV -1 RNA < 50 copies/mL as defined by the US 
FDA-defmed snapshot algorithm) is greater than -12%; ie, a margin of 
12% is applied to non-inferiority assessment. The 95% CI will be 
constmcted using a n01mal approximation method based on stmtified 
Mantel-Haenszel prop01iions, where sti·atification factors include 
baseline HIV-1 RNA level (:::; 100,000 copies/mL vs. 
> 100,000 copies/mL) and region (US vs. Ex-US). 
The prop01iion of subjects who achieve HIV -1 RNA < 50 copies/mL 
at Weeks 96 and 144 and the prop01iion of subjects who achieve 
HIV-1 RNA < 20 copies/mL at Weeks 48, 96, and 144 as defmed by 
the US FDA-defmed snapshot algorithm will also be smnmm·ized. 
The 95% Cis will be consti11cted in the same manner as described for 
the primmy efficacy endpoint. 
The change from baseline in log10 HIV -1 RNA and CD4+ cell count 
at Weeks 48, 96, and 144 will be smnmm·ized by u·eatment using 
descriptive statistics. The differences and the associated 2-sided 95% 
Cis will be constructed using an Analysis ofVm·iance (ANOVA) 
model, including treatment (GS-9883/F/TAF vs. ABC/DTG/3TC), 
baseline HIV-1 RNA level c~ 100,000 copies/mL VS. 
> 100,000 copies/mL), and region (US vs. Ex-US) as fixed effects in 
the model. 
The percentage change from baseline in hip and spine BMD at 
Weeks 48, 96, and 144 will be summarized by u·eahnent using 
descriptive statistics. The differences and the associated 2-sided 95% 
Page 11 
19 October 2016 


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CIs will be conducted using an ANOVA model including treatment as 
a fixed effect in the model.  Adverse events, clinical laboratory 
assessments, and pharmacokinetic parameters will be summarized 
using descriptive statistics.
A total of approximately 600 HIV-1 infected subjects, randomized in 
a 1:1 ratio to 2 treatment groups (300 subjects per treatment group), 
achieves at least 95% power to detect a non-inferiority margin of 12% 
in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined by 
the US FDA-defined snapshot algorithm) difference between the 
2 treatment groups. For sample size and power computation, it is 
assumed that both treatment groups have a response rate of 91%
(based on Gilead Studies GS-US-292-0104 and GS-US-292-0111), 
that a non-inferiority margin is 12%, and that the significance level of 
the test is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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Amendment 2
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
ABC/3TC
abacavir/lamivudine, EpzicomKivexa
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration 
versus time curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
DTG
dolutegravir, Tivicay
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
EVG
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination


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


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


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {The Joint United Nations Programme on HIV/AIDS (UNAIDS) 2014}. The infection, if 
left untreated or suboptimally treated, is characterized by deterioration in immune function, 
ultimately resulting in death. Therapeutic strategies for the treatment of HIV-1 disease have been 
significantly advanced by the availability of highly active antiretroviral therapy (HAART); the 
introduction of HAART was associated with a dramatic decrease in acquired immune deficiency 
syndrome (AIDS)-related morbidity and mortality {Palella et al 1998}, {Mocroft et al 1998}, 
{Sterne et al 2005}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {Costagliola 2014}. In addition, there remains a significant 
medical need for new, effective therapies that take into consideration HIV genetic variability, the 
aging HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen 
simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {Department for 
Health and Human Services (DHHS) 2015}. Virologically suppressed, HIV-infected patients 
may switch from their current regimen because of safety or tolerability concerns or for regimen 
simplification. All patient populations may benefit from once-daily fixed-dose combination 
(FDC) regimens as these have been shown to provide increased adherence and improved clinical 
and virologic outcomes {Sterrantino et al 2012}, {Aldir et al 2014}
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 


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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.
Gilead Sciences (Gilead) has coformulated GS-9883 with the NRTI emtricitabine (FTC; F) and 
the NtRTI tenofovir alafenamide (TAF) into an FDC tablet that is suitable for once-daily use. 
This GS-9883/F/TAF FDC may provide a potent, convenient, tolerable, and practical regimen 
for the long-term treatment of patients with HIV infection.
1.2.
GS-9883
1.2.1.
General Information
GS-9883, a potent inhibitor of HIV-1 integrase is being evaluated for the treatment of HIV 
infection. Antiviral testing has shown that GS-9883 is active against a broad panel of HIV-1 viral
lab strains and clinical isolates. GS-9883 is fully active against a panel of mutant viruses with 
resistance to NRTIs, NNRTIs, and PIs. Integrase mutant viruses that are resistant to the INSTIs
RAL and EVG remain largely sensitive to GS-9883.
1.2.2.
Preclinical Pharmacology and Toxicology
A core battery of safety pharmacology studies have been conducted with GS-9883. These 
include assessments of cytotoxicity, off-target receptor and ion-channel binding, effects on 
human Ether-à-go-go-Related Gene (hERG) potassium current and papillary muscle action 
potential, and in vivo studies in rats and dogs that evaluated effects of GS-9883 on all major 
organ systems. The volume of distribution of GS-9883 ranged between 0.09 and 0.22 L/kg in the 
preclinical species, which indicates that the distribution of GS-9883 is limited to the extracellular 
compartment due to its high binding to plasma proteins. The projected half-life of GS-9883 in 
humans is approximately 20 hours based upon the estimates of clearance and volume of 
distribution.
1.2.2.1.
Pharmacology
GS-9883 has IC50 values ranging from 1.5 to 2.4 nM, similar to the inhibitory effect of DTG and 
EVG. GS-9883 is highly potent against HIV replication in MT4 cells with an EC50 (50% 
effective inhibitory concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. 
GS-9883 does not show significant cytotoxicity against dividing and non-dividing human 
PBMCs, primary human hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 M. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter OCT2 (IC50 = 0.42 M). As a result, 
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 M 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.
1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL, 
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day.  At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal 
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males.  The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy.
No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL). The estimated margin of exposure at the NOEL 
was approximately 5.1-fold based on expected human exposure with the once daily dosing of the 
GS-9883/F/TAF (50/200/25 mg) tablet.


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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 (completed)

GS-US-141-1478, a Phase 1, Open Label, Parallel Group, Adaptive, Single-Dose Study to 
Evaluate the Pharmacokinetics of GS-9883 in Subjects with Normal and Impaired Hepatic 
Function (in life portion completed)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)


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


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


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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).
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.


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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
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 1-4 below.


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Table 1-4. 
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ9s Values (GS-9883 PK Analysis 
Set) 
GS-9883 dose 
N 
Median (range) C 1au,ss (ng!mL) 
Median (range) pai Q95• 
5mg 
4 
206.5 (146.0 to 342.0) 
1.3 (0.9 to 2.1) 
25mg 
4 
797.5 (714.0 to 1900.0) 
4.9 ( 4.4 to 11. 7) 
50mg 
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 (pal09s) value is estimated based on steady-state C1au values and the in vitJ:o paiC95 value for 
wild-type HIV-1 (162 ng/ml). 
The mean and 95% Cis of change from baseline in HIV -1 RNA (log10 copies/mL) are presented 
in Figure 1-1. 
Figure 1-1. 
2 
:; 
~ 
-~ 1 
8 
GS-9883 5 mg (~ ) : 
Gs-9883 25 mg (~): 
Gs-9883 50 mg (~): 
G$-9883 100 mg (~ ): 
Placebo (n= ): 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
• = GS-9883 5 mg 
0 = GS-9883 25 mg 
6 = GS-9883 50 mg 
0 = GS-9883100 mg 
0 =Placebo 
Bl 
2 
3 
3 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
3 
3 
4 
3 
4 
7 
8 
9 
10 
11 
Day 
3 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
--
- -
--
14 
17 
3 
3 
4 
3 
4 
4 
4 
4 
4 
4 
NOTE: Baseline value. was the last available value collected prior to the time of tl1e first dose of study drug. 
2 
-1 
-2 
-3 
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Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group.
1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing 
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, ART-naive adult subjects.
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to 
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 50 mg 
once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 75 mg 
once daily
Week 24 interim data are summarized below. 
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24 
data analysis, 2 subjects (2.0%) had prematurely discontinued from the study, 1 in each treatment 
group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and eGFRCG) were similar 
between the 2 treatment groups.
Median (first quartile [Q1], third quartile [Q3]) baseline HIV-1 RNA was 4.45 (3.96, 4.79) 
log10 copies/mL, with 82.7% of subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had 
> 400,000 copies/mL at baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 
1 subject was randomized to DTG+F/TAF.
Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 41.8% of subjects 
having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 125.3 (105.7, 
147.0) mL/min.


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Efficacy Results
Virologic success at Weeks 12 and 24 was assessed using the US FDA-defined snapshot 
algorithm, defined as plasma HIV-1 RNA < 50 copies/mL. At Weeks 12 and 24, virologic 
success was high and similar between the 2 treatment groups as follows: Week 12 
GS-9883+F/TAF 93.8%, DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79); Week 24 GS-9883+F/TAF 95.4%, DTG+F/TAF 
93.9% (1.0%; 95% CI: −10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 had HIV-1 RNA of 60 copies/mL. 
Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF, +170 (150.0) cells/μL; DTG+F/TAF, +173 (220.5) cells/μL 
(difference in least squares mean [LSM]: 0; 95% CI: −76 to 76; p = 1.00). There were similar 
increases in the mean (SD) CD4 cell count in both treatment groups Week 24: GS-9883+F/TAF, 
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).
Interim Virology Resistance Data
Through Week 24, no emergent drug resistance was detected.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 66.2%, 43 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common treatment-emergent AEs (occurring in > 2 subjects) by treatment group were as 
follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE. One other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator or resulted in 
study drug discontinuation or interruption, and both SAEs resolved.


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The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883+F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs reported that were considered related to 
study drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation 
were reported in either treatment group.
Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least 
1 grade level increase from baseline in graded abnormality) was similar between treatment 
groups as follows: GS-9883+F/TAF 76.6%, 49 subjects; DTG+F/TAF 78.1%, 25 subjects. The 
majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The 
percentage of subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality 
was similar between treatment groups as follows: GS-9883+F/TAF 17.2%, 11 subjects; 
DTG+F/TAF 12.5%, 4 subjects. Grade 3 or 4 laboratory abnormalities occurring in at least 
2 subjects in either treatment group were as follows: creatine kinase (GS-9883+F/TAF, 7.8% 
[5 subjects]), fasting serum glucose (DTG+F/TAF, 6.3% [2 subjects]), aspartate 
aminotransferase (AST) (GS-9883+F/TAF, 3.1% [2 subjects]), and fasting low-density 
lipoprotein (LDL) (GS-9883+F/TAF, 3.1% [2 subjects]). The only Grade 4 laboratory 
abnormalities were for creatine kinase, reported in 2 subjects (3.1%) in the GS-9883+F/TAF 
group. All increased creatine kinase values appeared to be transient, and none were associated 
with AEs. Of the 2 subjects with increased AST, 1 subject had Grade 3 AST and Grade 3 ALT at 
Week 24 in the setting of alcohol abuse; the other subject had Grade 3 AST at Week 8 that 
returned to normal by Week 24.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. There were 
similar increases from baseline in median (Q1, Q3) serum creatinine in both treatment groups at 
Week 24: GS-9883+F/TAF 0.12 (0.06, 0.18) mg/dL; DTG+F/TAF 0.13 (0.05, 0.21) mg/dL. 
There were decreases in median (Q1, Q3) eGFRCG at Week 24, which were smaller in the 
GS-9883+F/TAF compared with the DTG+F/TAF group: GS-9883+F/TAF 
−13.3 (−19.9, −4.0) mL/min; DTG+F/TAF −17.2 (−25.7, −6.9) mL/min.
Conclusions
Key Week 24 conclusions from Study GS-US-141-1475 include the following:

Virologic success at Week 24 when assessed using the US FDA-defined snapshot algorithm, 
defined as plasma HIV-1 RNA < 50 copies/mL, was similar between the 2 treatment groups 
as follows: GS-9883+F/TAF 95.4%; DTG+F/TAF 93.9%; stratum-adjusted difference in 
percentages: 1.0%; 95% CI: −10.7% to 12.7%; p = 0.84. There was a similar increase in the 
mean (SD) CD4 cell count between the 2 treatment groups, GS-9883+F/TAF,
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).


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
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. 
1.3.
Information about Emtricitabine (Emtriva®, FTC)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US FDA for marketing on 2 July 2003 and is available 
under the name Emtriva®. In the European Union (EU), marketing authorization was granted for 
both the 200 mg Emtrivacapsule formulation and a 10 mg/mL Emtrivaoral Solution 
formulation on 24 October 2003, with indications for the treatment of HIV infection concurrently 
with other antiretroviral drugs in both adult and pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.


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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-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in
healthy subjects (completed)

GS-US-120-1538, a Fixed-Sequence, Open-Label, Study Evaluating the Pharmacokinetics 
and Drug Interaction Potential between Tenofovir Alafenamide and Midazolam (Oral and 
Intravenous) in Healthy Volunteers (completed) 

GS-US-120-1554, a Fixed-Sequence, Randomized, Open-Label, 2-Cohort, 2-Period, 
Multiple-Dose Study Evaluating the Pharmacokinetics and Drug Interaction Potential 
between Tenofovir Alafenamide and Rilpivirine in Healthy Subjects (completed)

GS-US-311-1386, a Phase 1 study to determine the effect of food on the pharmacokinetics of 
tenofovir alafenamide when administered as F/TAF FDC in healthy volunteers (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz (EFV) or
COBI-boosted darunavir (DRV) (completed)


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
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).
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)


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
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)
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 Pgp-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]).


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Studies GS-US-292-0104 and GS-US-292-0111 are ongoing, Phase 3 randomized, 
double-blinded studies of the safety and efficacy of E/C/F/TAF versus E/C/F/TDF in HIV-1 
infected, antiretroviral treatment-naive adults. The interim Week 48 key conclusions from pooled 
data showed that E/C/F/TAF once daily was noninferior to STB once daily when administered 
for 48 weeks to HIV-infected, ART-naive adults, as assessed using the US FDA-defined 
snapshot algorithm with HIV-1 RNA < 50 copies/mL (E/C/F/TAF 92.4%; STB 90.4%; 
difference in percentages: 2.0%, 95% CI: -0.7% to 4.7%). Administration of E/C/F/TAF resulted 
in > 90% lower plasma TFV and higher intracellular TFV-DP relative to STB.  E/C/F/TAF 
showed an improved renal and bone safety profile with significantly less decline in hip and spine 
BMD, less increase in serum creatinine and reduction in estimated glomerular filtration rate 
(eGFR).
1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF)
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, FTC, and 
TAF between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is an ongoing Phase 1, open-label, 2-cohort, multiple-period,
fixed-sequence, crossover study conducted at a single center in the US to evaluate 1) the relative 
bioavailability (BA) of 2 GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets 
compared with the GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered 
simultaneously and 2) the effect of food on the PK of GS-9883, FTC, and TAF when 
administered as GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets.
Cohort 1 evaluated the relative BA and food effect of GS-9883/F/TAF (75/200/25 mg) FDC 
tablet in a 3-period sequence. Following review of preliminary data from Cohort 1, Cohort 2 was 
added to the study via protocol amendment. Cohort 2 evaluated the relative BA and food effect 
of GS-9883/F/TAF (50/200/25 mg) FDC tablet in a 4-period sequence.
The in-life portion of Cohorts 1 and 2 are complete. Preliminary results are summarized below. 
Cohort 1 Results:
Pharmacokinetic Results
Under fasted conditions, GS-9883 AUCinf and Cmax were 27% and 31% higher, respectively, 
following GS-9883/F/TAF (75/200/25 mg) FDC administration than following administration of 
single-agent GS-9883 (75 mg ) with the F/TAF (200/25 mg) FDC. FTC and TAF exposure was 
similar following administration of GS-9883/F/TAF (75/200/25 mg) or single-agent GS-9883 
(75 mg) with the F/TAF (200/25 mg) FDC. 
Compared with administration under fasted conditions, administration of the GS-9883/F/TAF 
(75/200/25 mg) FDC with a high-fat meal resulted in a 46% higher GS-9883 AUCinf and a 27% 
higher GS-9883 Cmax. The impact of food on TAF and FTC exposure was similar to that 


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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 (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.
Cohort 2 Results:
Pharmacokinetic Results
The PK results from Study GS-US-141-1233 demonstrated that the GS-9883 AUCinf and Cmax
following administration of the 50mg GS-9883 FDC tablets was 79% and 78%, respectively of 
those observed in the same study following co-administration of GS-9883 75 mg single agent 
with F/TAF (200/25 mg) under fasted conditions. The GS-9883 exposures of 50 and 75 mg fixed 
dose combination tablets were approximately dose proportional under fasted and fed conditions, 
and a high fat and moderate fat meal had similar impact on GS-9883 with AUCinf increasing by 
24%. The steady state paIQ95 of GS-9883/F/TAF (50/200/25 mg) was predicted to be 17 (fasted)-
23 (fed). The exposures of TAF and FTC of the 50 mg GS-9883 FDC were similar to those of 
GS-9883 75 mg single agent with F/TAF FDC, and the food effect on TAF and FTC was similar 
to the historical results.  
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 2, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
1.6.
Information about abacavir/dolutegravir/lamivudine (ABC/DTG/3TC
Triumeq®)
For more detailed information, refer to the current Prescribing Information and local product 
labeling for abacavir/dolutegravir/lamivudine.
1.7.
Rationale for this Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 


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HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.
The GS-9883/F/TAF FDC has the potential to offer a simple, once-daily regimen containing a 
second generation INSTI that provides a high barrier to resistance, does not require a boosting 
agent, and offers an effective and safer alternative to standard nucleos(t)ide based regimens, 
without the need for HLA testing or close monitoring of renal or bone toxicities. It could provide 
a FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute to an
increased risk of cardiovascular events, could be used in patients with chronic hepatitis B or C 
infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities.
The objective of this study is to evaluate the safety and efficacy of a FDC containing 
GS-9883/F/TAF versus ABC/DTG/3TC. ABC/DTG/3TC was selected as the active comparator 
for this study as it is a second-generation integrase inhibitor-based, once-daily fixed dose 
combination, and is a DHHS Guidelines preferred regimen. Use of ABC/DTG/3TC as a 
comparator in this study will therefore allow comparison of two single tablet regimens
containing second generation, unboosted INSTIs.
1.8.
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: hypersensitivity 
reaction to abacavir and allergy to any components of the tablets. Some observational studies 
have shown increased risk of cardiovascular disease with abacavir. Interim data will also be 
reviewed by an independent data monitoring committee. 
Following a chronic 39 week study in monkeys, animals administered the highest dose of  
GS-9883 (1000 mg/kg/day) had bile duct hyperplasia (increased cell growth) and hypertrophy 
(increased cell size), and some increased cell growth and inflammation in nearby liver cells. 
These effects were not seen in monkeys administered the mid-level dose (200 mg/kg/day), and 
these animals had plasma GS-9883 exposures that were approximately 5-fold above human 
exposures when given the  GS-9883/F/TAF FDC.   No adverse drug reactions associated with 
liver or bile duct problems has been identified in humans treated with GS-9883. Potential 
hepatobiliary toxicity is appropriately managed by study inclusion/exclusion criteria, close 
clinical and laboratory monitoring, as well as specific toxicity management guidance to 
investigators (Refer to Section 7.5.5.).  
Potential benefits of GS-9883 may include provision of a new antiretroviral therapy that is not 
currently available and which may have fewer side effects than alternative therapies. Other 
potential benefits include provisions of fixed dose combination therapy, and the knowledge that 
patient participation will contribute to the body of knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF and ABC/DTG/3TC is favorable at this 
time.


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1.9.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady 
State Following GS-9883 Administration Under Fasting Conditions 
and Corresponding Protein-Adjusted IQ95 Values
GS-9883 dose
n
Median (range) Ctau,SS (ng/mL)
Median (range) 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 data from this study support the safety and efficacy of GS-9883 exposures obtained 
with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF was developed for use in Phase 3 studies. 
Preliminary results from the relative bioavailability (rBA) study (GS-US-141-1233) of 
GS-9883/F/TAF (75/200/25 mg) showed that GS-9883 plasma exposure was higher (with Cmax
and AUCinf increase of 31% and 27%, respectively) following administration of the FDC as 
compared with exposure following administration of GS-9883 (75 mg) + F/TAF (200/25 mg) 
under fasted conditions. The increase in GS-9883 exposures associated with the FDC 
formulation results in an estimated mean paIQ95 of 24.3, compared to an estimated mean paIQ95
of 19.2 for the GS-9883 (75 mg) single agent coadministered with F/TAF, in the fasted state.
In order to bridge exposures of GS-9883 in the FDC to the exposure observed with GS-9883 
75 mg administered as a single agent, and to bridge to the safe and effective exposures observed 
in the Phase 2 study GS-US-141-1475, a lower strength GS-9883/F/TAF FDC was developed for 
use in the Phase 3 studies. Comparability of GS-9883 exposures was confirmed in an rBA study 
of GS-9883/F/TAF (50/200/25 mg) and GS-9883 (75 mg) + F/TAF prior to initiation of dosing 
in the Phase 3 studies.
1.10.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) containing 
GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) versus a FDC containing 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral 
treatment naïve-adult subjects as determined by the achievement of HIV-1 RNA 
< 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety, and tolerability of the two treatment groups through 
Weeks 48 and 96, and 144

To evaluate the bone safety of the two treatment groups as determined by the percentage 
change from baseline in hip and spine BMD through Weeks 48 and 96, and 144


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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint is:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 as defined 
by the US FDA-defined snapshot algorithm
The secondary endpoints of this study include:

the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 as 
defined by the US FDA-defined snapshot algorithm

the proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96,
and 144 as defined by the US FDA-defined snapshot algorithm

the change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, and 144

the percentage change from baseline in hip and spine BMD at Weeks 48, 96, and 144
3.2.
Study Design
This protocol describes a randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus ABC/DTG/3TC FDC in HIV-1 
infected, antiretroviral treatment-naïve adult subjects.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food (n=300)
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food
(n=300)
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. Ex-US) at randomization.


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3.4.
Duration of Treatment
Subjects will be treated for at least 144 weeks during the blinded treatment phase.  After 
Week 144, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic
(preferably within 30 days) for an End of Blinded Treatment Visit. At the End of Blinded 
Treatment Visit, if safety and efficacy of GS-9883/F/TAF FDC is demonstrated following 
review of unblinded data, 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 in an open label (OL) extension phase for 
up to 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.
All subjects participating in the open label extension phase, without regard to their blinded 
treatment regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for 
up to 48 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
Figure 3-1.
Study Schema
a
Following the Day 1 visit, subjects will be required to return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
through Week 144.
b
After Week 144, all subjects will continue to take their blinded study drug and attend visits every 12 weeks until the End of 
Blinded Treatment Visit. 
c
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to 
the clinic (preferably within 30 days) for an End of Blinded Treatment Visit. At the End of Blinded Treatment Visit, if 
safety and efficacy of GS-9883/F/TAF FDC is demonstrated following review of unblinded data, 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 in an open label (OL)
extension phase for up to 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.
d
Subjects who complete the study through the End of Blinded Treatment Visit and do not continue on the open label 
GS-9883/F/TAF FDC extension phase will be required to return to the clinic after the End of Blinded Treatment Visit for a 
30-Day Follow-Up Visit. 


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3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Pharmacogenomic Research 
PPD 
3.5.2. 
Additional Sample Storage 
Final 
Amendment2 
For subjects who provide additional consent, residual blood and urine samples taken throughout 
the study will be stored. Stored samples may be used by the Sponsor or its research partners to 
help answer questions about the study dmg, and HIV disease and its associated conditions, or to 
provide additional safety data. 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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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 600 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Age 18 years
3) Antiretroviral treatment naïve (≤ 10 days of prior therapy with any antiretroviral agent 
following a diagnosis of HIV-1 infection) except the use for PrEP (pre-exposure prophylaxis) 
or PEP (post-exposure prophylaxis), up to one month prior to screening
4) Plasma HIV-1 RNA levels 500 copies/mL at screening
5) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥0.83 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft et al 1976}:
i)
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
ii) Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)      0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8) Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin


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9) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))
10) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11) Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 7) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12) Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 7) throughout the study period and for 
90 days following the last dose of study drug
13) Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14) Life expectancy ≥ 1 year
15) Screening genotype report must show sensitivity to FTC, TFV, 3TC, and ABC. This report 
will be provided by Gilead Sciences. Alternatively, if genotype results from a local 
laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, 
this genotype will be acceptable to fulfill this inclusion criterion in the event that the 
genotype obtained at screening is not yet available and all other inclusion/exclusion criteria 
have been confirmed.
16) Negative screening test for HLA-B*5701 allele provided by Gilead Sciences. Alternatively, 
if HLA-B*5701 results are available from a local laboratory prior to screening, this report 
will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result 
obtained at screening is not yet available and all other inclusion/exclusion criteria have been
confirmed.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 6)
2) Subjects experiencing decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal 
bleeding)


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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 (e.g, 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
6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
7) Participation in any other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC or ABC/DTG/3TC FDC 
tablets
10) Females who are pregnant (as confirmed by positive serum pregnancy test)
11) Females who are breastfeeding
12) Subjects receiving ongoing therapy with any of the following medications in the table below, 
including drugs not to be used with FTC, TAF, GS-9883, DTG, ABC and 3TC
Drug Class
Agents Disallowed*
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study.
13) Acute hepatitis in the 30 days prior to study entry


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14) Chronic Hepatitis B Virus (HBV) infection, as determined by either:
a) Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit
b) Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
15) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until the Investigator has received the results of the allele testing and 
screening genotype report and subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening and region (US vs. Ex-US) at randomization.
The IWRS will assign study drug bottle numbers of blinded FDC of GS-9883/F/TAF + Placebo 
to match FDC of ABC/DTG/3TC or FDC of ABC/DTG/3TC + Placebo to match FDC of
GS-9883/F/TAF at each study visit for each subject.
At the End of Blinded Treatment Visit the IWRS will assign open-label GS-9883/F/TAF FDC.
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the IWRS system 
for that subject. Gilead strongly recommends but does not require that the investigator contact 
the Gilead medical monitor before breaking the blind. Treatment assignment should remain 
blinded unless that knowledge is necessary to determine subject emergency medical care. The 
rationale for unblinding must be clearly explained in source documentation and on the electronic 
case report form (eCRF), along with the date on which the treatment assignment was 
obtained. The investigator is requested to contact the Gilead medical monitor promptly in case of 
any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Drug Safety and Public Health (DSPH) may independently unblind cases for expedited 
reporting of suspected unexpected serious adverse reactions (SUSARs).


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5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.
The placebo to match (PTM) GS-9883/F/TAF tablets are capsule-shaped, film-coated 
purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the other side and 
are identical in physical appearance to GS-9883/F/TAF tablets. The placebo tablets contain 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. 
The tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, 
polyvinyl alcohol, talc, and titanium dioxide.
5.2.1.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
Abacavir 600 mg/Dolutegravir 50 mg/Lamivudine 300 mg tablets are oval, film coated purple, 
and debossed with “572 Tri” on one side. Each tablet core contains 600 mg of abacavir, 50 mg of 
dolutegravir, and 300 mg of lamivudine. In addition to the active ingredients, the 
ABC/DTG/3TC tablets contain the inactive ingredients D-mannitol, magnesium stearate, 
microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet cores are film 
coated with iron oxide black, iron oxide red, polyethylene glycol, polyvinyl alcohol, talc, and 
titanium oxide.
The PTM ABC/DTG/3TC tablets are oval, film coated purple, and debossed with “572 Tri” on 
one side. The placebo tablets are identical in physical appearance to ABC/DTG/3TC tablets. The 
placebo tablets contain microcrystalline cellulose, lactose monohydrate, croscarmellose sodium 
and magnesium stearate. The tablet cores are film-coated with iron oxide black, iron oxide red, 
polyethylene glycol, polyvinyl alcohol, talc, and titanium oxide.
5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883/F/TAF tablets and PTM GS-9883/F/TAF tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester 
packing material.  Each bottle is enclosed with a white, continuous thread, child-resistant 
polypropylene screw cap with an induction-sealed and aluminum-faced liner.


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Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations
5.2.2.2.
Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC Triumeq®) 
600 mg/50 mg/300 mg and Placebo to Match Tablets
ABC/DTG/3TC tablets and PTM ABC/DTG/3TC tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets and silica gel desiccant. Each bottle 
is enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both 
FDCs should be stored at controlled room temperature of 25°C (77°F); excursions are permitted 
between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label. Until 
dispensed to the subjects, all bottles of study drugs should be stored in a securely locked area, 
accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide 
and Abacavir/Dolutegravir/Lamivudine
Study drug GS-9883/F/TAF FDC, ABC/DTG/3TC FDC and placebo-to-match tablets for both
FDCs will be provided by Gilead Sciences.
Treatment Group 1: FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match FDC of abacavir 600 mg/ dolutegravir 
50 mg/lamivudine 300 mg (ABC/DTG/3TC) administered orally, once daily, without regard to 
food
Treatment Group 2: FDC of abacavir 600 mg/dolutegravir 50 mg/ lamivudine 300 mg 
(ABC/DTG/3TC) + Placebo to match FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food. 


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After the End of Blinded Treatment Visit, all subjects who choose to participate in the open label 
extension will receive GS-9883/F/TAF FDC once daily.
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability. The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return.
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 table and use of herbal/natural supplements are excluded 
or should be used with caution while subjects are participating in the study. Subjects will 
refrain from consumption of grapefruit juice and Seville orange juice throughout 
participation in the study.
Table 5-1.
Prior and Concomitant Medications
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids (eg, Tums or 
Rolaids); the ulcer medication sucralfate (Carafate); 
or vitamin or mineral supplements that contain 
calcium, iron or zinc for a minimum of 6 hours 
before and 2 hours after any dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, 
Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural 
Supplements
St. John’s Wort, Echinaccea
Oral Hypoglycemic Agent
Metformin: close monitoring is recommended. A 
dose adjustment of Metformin may be necessary.  
Limit total daily doses of Metformin to 1000mg 
when initiating study medication or if initiating 
metformin while on study drug.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.


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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 study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events, smoking history
and prior medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.


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Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)       CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg) 
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
HLA-B*5701
Plasma HIV-1 RNA
Hepatitis B virus surface antigen serology (HBsAg)
Hepatitis B surface antibody (HBsAb)
Hepatitis B virus core antibody (HBcAb)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.
HIV-1 genotype testing (protease and reverse transcriptase). The HIV-1 PR/RT genotype 
testing may not be performed for subjects that fail to meet other screening criteria.

Review of adverse events and concomitant medications
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for the Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. See 
Section 7 Adverse Events and Toxicity Management for additional details.


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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 
received the results from the allele testing and screening genotype report and confirmed 
eligibility before proceeding with the Day 1 visit. The subject must complete all study 
procedures, except DXA, before being administered the study drug:

DXA Scan (spine and hip).  For subjects in Germany, DXA scans will not be performed.
The DXA scan will be performed on subjects once eligibility is confirmed. The scan may 
be performed prior to or within 24 hours of the Day 1 Visit.

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject.  Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN) and TSH


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Metabolic assessments: Fasting (no food or drinks, except water, at least 8 homs 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 retum within 72 homs in a fasted state to draw blood for the metabolic 
assessments. 
-
Estimated glomemlar filtration rate according to the Cockcroft-Gault f01mula 
-
Hematology profile: complete blood cmmt (CBC) with differential and platelet cmmt 
-
Plasma HIV-1 RNA 
-
CD4+ cell count 
-
Evaluations of inflammation and immlme activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 
-
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand 
-
Plasma storage sample for safety, virology, or PK testing 
• 
Optional Peripheral Blood Mononuclear cell (PBMC) Substudy: 
• 
• 
Optional blood sample collection for the following laboratory analyses if 
pharmacogenomic consent is obtained 
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6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 - 144)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, 48, 60, 72, 
84, 96, 108, 120, 132, and 144 unless otherwise specified.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 132, unless otherwise specified.  The visit window at Weeks 48, 96, and 144 will 
be ± 6 weeks of the protocol-specified visit date, and these clinical visit windows coincide with 
the Week 48, 96, and Week 144 statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (Weeks 24, 48, 96
and 144 ±10 days). For subjects in Germany, DXA scans will not be performed.

Complete physical examination (Weeks 24, 48, 96, and 144) (urogenital/anorectal exams 
will be performed at the discretion of the Investigator) or symptom-directed physical 
examination as needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Weeks 24, 48. 96, and 144)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject at Weeks 4, 12 and 48.  Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin. (Weeks 24, 48, 72, 96, 120, and 144)


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Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 12, 24, 48, 72, 96, 120, and 144 analyses of glucose will be done as part of the 
fasting metabolic assessments and not as part of the chemistry profile. At Weeks 24, 48, 
72, 96, 120, and 144 TSH will also be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24, 48, 72, 96, 120, and 144)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (Weeks 24, 48, 72, 96, 120,
and 144)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (Weeks 24, 48, 72, 96 120, and 144)
Hepatitis B virus surface antigen serology (HBsAg). Subjects who have HBVsAg 
positive will have a reflex test for HBV DNA (viral load). Hepatitis B surface antibody 
(HBsAb). Hepatitis B virus core antibody (HBcAb). (Weeks 48, 96, and 144)
Hepatitis C virus (HCVAb) serology. Subjects who are Hepatitis C virus antibody 
(HCVAb) positive will have a HCV RNA test performed. (Weeks 48, 96, and 144)
Plasma storage sample for safety, virology, or PK testing


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Phrumacokinetic Blood Collection for subjects who ru·e on study dmg. Details of 
phrumacokinetic blood sampling procedures and sample management will be documented in 
the Phan nacokinetic Sample Collection, Processing, Storage, and Shipment Manual. 
-
Single Anytime, Trough and Post Dose PK Sainples for all subjects on study dmg: 
• 
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 and 36. 
• 
Observed dosing at the clinic: Subjects will have a trough PK blood sainple collected 
between 20-28 hours following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study <hugs on the moming of their visit for the t:I·ough 
sainple collection. Subjects will then take an observed dose of study <hug at the 
clinic. A single post dose PK blood sample will be collected between 1 and 4 hours 
post dose. If the subject has taken their dose of study dmgs prior to the visit, the visit 
may proceed, but the subject must retum within 72 hours for the n·ough PK blood 
sainple collection. In the event a subject routinely takes their study <hug in the 
evening, a single post dose sainple may be <h·awn at Weeks 4 and 12 as the subject 
will not be inst:I11cted to change their dosing time to accommodate this n·ough PK 
<h·aw. 
• 
Dosing diaries will be collected from subjects for the single anytime PK and n·ough 
PK collection. If a dosing diruy is not retumed the site may ask the subject for the 
time of the last dose and if it was taken with or without food. 
-
Optional Phrumacokinetic (PK) Substudy: 
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6.5. 
Treatment Assessments (Post Week 144 until the Open Label Rollover 
Extension) 
6.5.1. 
Post Week 144 Assessments 
After Week 144, all subjects will continue to take their blinded study dmg and attend visits eve1y 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all subjects will retum to the clinic 
(preferably within 30 days) for an End of Blinded Treatment Visit. Study visits are to be 
completed within ± 6 days of the protocol-specified visit date lmless othe1w ise specified. 
• 
Review of AEs and changes in concomitant medications 
• 
Complete physical examination (every 48 weeks) (urogenitaVanorectal exams will be 
perf01med 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 perfonned supine (every 48 weeks) 
• 
Urine collection for the following laborat01y procedures: 
-
Urinalysis 
-
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-Inicroglobulin (eve1y 24 weeks) 
-
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confnmed with a sennn test. If the test is positive, the subject 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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (every 24 weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163 (every 24 weeks)
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand (every 24 weeks)
Hepatitis B virus surface antigen serology (HBsAg). Subjects who have HBVsAg 
positive will have a reflex test for HBV DNA (viral load). Hepatitis B surface antibody 
(HBsAb). Hepatitis B virus core antibody (HBcAb). (every 48 weeks)
Hepatitis C virus (HCVAb) serology. Subjects who are Hepatitis C virus antibody 
(HCVAb) positive will have a HCV RNA test performed. (every 48 weeks)
Plasma storage sample for safety, virology, or PK testing

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Sections 6.14.1 and 6.14.2.

Document study drug dispensation and accountability for all study drugs dispensed.


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6.5.2.
End of Blinded Treatment Visit
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, 
all subjects will return to the clinic (preferably within 30 days) for an End of Blinded Treatment
Visit. At the End of Blinded Treatment Visit, if safety and efficacy of GS-9883/F/TAF FDC is 
demonstrated following review of unblinded data, 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 in an open label
(OL) extension phase for up to 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.
Subjects who receive the open-label GS-9883/F/TAF FDC will return for study visits every 
12 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Subjects who have discontinued drug study prior to the End of Blinded Treatment Visit will not 
be eligible for the open-label rollover extension; these subjects will be asked to continue 
attending the scheduled study visits through the End of Blinded Treatment Visit and discontinue 
the study after the End of Blinded Treatment Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
The following will be performed at the End of Blinded Treatment Visit:

Review of AEs and changes in concomitant medications

DXA scans (spine and hip) for all subjects who are on study drug (±10 days) if last scan was 
acquired > 12 weeks from the date of the end of blinded treatment visit. For subjects in 
Germany, DXA scans will not be performed.

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.


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Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN), and TSH
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Evaluations of inflammation and immune activation, may include but not limited to 
cystatin-C, IL-6, hs-CRP, d-dimer, sCD14 and sCD163
Evaluations of platelet function, may include but not limited to soluble glycoprotein VI 
(sGPVI), P-selectin, and soluble CD40 ligand
Plasma storage sample for safety, virology, or PK testing

Document study drug dispensation, if applicable and accountability for all study drugs 
dispensed

Subjects who wish to continue in the Open-Label Rollover extension study will receive open 
label GS-9883/F/TAF FDC.
6.5.3.
Treatment Assessments (Open-Label Rollover Extension)
For purposes of study visit identification during the open-label rollover extension, study visits 
will be identified by the number of weeks that have elapsed between the End of Blinded 
Treatment Visit and the corresponding open-label study visit, and labeled with “OL” (eg. 
Week 12 OL, Week 24 OL, etc.)


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All subjects participating in the open label extension phase, without regard to their blinded 
treatment regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for 
up to 48 weeks.
Study visits are to be completed within ± 6 days of the protocol-specified visit date every 
12 weeks thereafter, unless otherwise specified.
The following will be performed at the Open-Label Extension Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (Week 48 OL) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Week 48 OL)

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued.
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Week 24 OL and Week 48 OL, analyses of glucose will be done as part of the fasting 
metabolic assessments and not as part of the chemistry profile. In addition, TSH will also 
be analyzed at Week 24 OL and Week 48 OL.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Week 24 OL and Week 48 OL)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula


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Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Hepatitis B virus surface antigen serology (HBsAg). Subjects who have HBVsAg 
positive will have a reflex test for HBV DNA (viral load). Hepatitis B surface antibody 
(HBsAb). Hepatitis B virus core antibody (HBcAb). (Week 48 OL)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed. (Week 48 OL)
Plasma storage sample for safety, virology, or PK testing

Document study drug dispensation and accountability for all study drugs dispensed.

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Sections 6.14.1 and 6.14.2
6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
Subjects who have discontinued study drug prior to the End of Blinded Treatment Visit will not 
be eligible for the open-label rollover extension; these subjects will be asked to return to the 
clinic within 72 hours of stopping the study drug for the Early Study Drugs Discontinuation 
Visit. The subject will be asked to continue attending the scheduled study visits through the End 
of Blinded Treatment Visit and discontinue the study after the End of Blinded Treatment Visit.
If the subject discontinues study drug during the Open Label rollover extension, the subject will 
be asked to return to the clinic within 72 hours of stopping the study drug for the Early Study 
Drugs Discontinuation Visit.
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns 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

DXA scan required (spine and hip) for all subjects who are on study drug (±10 days) if last 
scan was acquired > 12 weeks from the date of the ESDD Visit (blinded treatment phase 
only).   For subjects in Germany, DXA scans will not be performed.


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
Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine (blinded treatment phase only)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test
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, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30 Day Follow Up
Subjects who prematurely discontinue study drug during the blinded phase and refuse to 
continue in the study through the End of Blinded Treatment Visit will be asked to return to the 
clinic 30 days after the completion of the Early Study Drugs Discontinuation Visit for the 
30-Day Follow-Up Visit.


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Those subjects who prematurely discontinue study drug during the blinded phase and 
continue in the study through at least one subsequent visit after the Early Study Drugs
Discontinuation Visit will not be required to complete the 30-Day Follow-Up Visit.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Subjects who prematurely discontinue study drug during the Open Label rollover extension will 
be asked to return to the clinic 30 days after the completion of the Early Study Drugs 
Discontinuation Visit for the 30-day Follow-Up Visit. The subject will not continue attending the 
scheduled study visits.
Subjects who complete the Open Label rollover extension will be asked to return to the clinic 
30 days after the completion of study drugs for the 30-day Follow-Up Visit.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count


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At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly (or as 
often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained.
6.7.
Criteria for Discontinuation of Study Treatment
Study medication will be discontinued in the following instances:

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Subject request to discontinue for any reason

Pregnancy during the study; refer to Appendix 7

Development of active tuberculosis infection
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator

Lack of efficacy

Subject noncompliance

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)
6.8.
Bone Mineral Density Evaluations
For all subjects who are on study drug, excluding those enrolled in sites based in Germany, dual 
energy x-ray absorptiometry (DXA) scans will be performed prior to or within 24 hours of 
Day 1, Weeks 24, 48, 96, 144, End of Blinded Treatment Visit and the Early Study Drug 
Discontinuation Visit (if the last scan was acquired > 12 weeks from the date of the ESDD Visit)
during the blinded treatment phase. Scans will cover the spine and hip to measure changes in 
bone mineral density. DXA scan results will be provided to study sites.
A complete description of the procedures performed for the DXA scans will be provided in a 
DXA manual.


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6.9.
Other Evaluations
6.9.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin at Day 1 Visit, Weeks 24, 48, every 24 weeks post Week 48, and the End 
of Blinded Treatment Visit. Samples may be stored for a period of 15 years at the end of the 
study.
6.9.2.
Markers of Inflammation and Immune Activation
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48, and the End of Blinded Treatment Visit for selected evaluations of inflammation and 
immune activation, which may include but not limited to cystatin-C, IL 6, hs CRP, d-dimer, 
sCD14, and sCD163. Samples may be stored for a period of 15 years at the end of the study.
6.9.3.
Markers of Platelet Function
For all subjects, blood will be collected at Day 1 Visit, Weeks 24, 48, every 24 weeks post 
Week 48, and the End of Blinded Treatment Visit for selected evaluations of platelet function,
which may include but not limited to soluble glycoprotein VI (sGPVI), P-selectin, and soluble 
CD40 ligand. Samples may be stored for a period of 15 years at the end of the study.
6.10.
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 for HIV-1 genotyping/phenotyping 
assays or their development, for retesting the amount of HIV-1 in the blood, for measurement of 
antiviral drug levels in the blood, or for testing to learn more about how the study drug has 
worked against HIV-1 or clinical laboratory testing 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.
6.11.
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.
6.12.
End of Study
The end of study will be the last patient’s last observation (or visit).


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6.13.
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.
6.14.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation, Week 48, 96, or 144.
6.14.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any visit, after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA 
≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled 
visit; OR

At any visit, a 1 log10 increase in HIV-1 RNA from the nadir which is subsequently 
confirmed at the following scheduled or unscheduled visit
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing. Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-baseline resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.
If no resistance is detected from the genotype or phenotype, the subject may remain on study 
drugs and a repeat HIV-1 RNA should be repeated (2 to 3 weeks after date of test with HIV-1 
RNA ≥ 50 copies/mL). Investigators should carefully evaluate the benefits and risks of 
remaining on study drug for each individual subject and document this assessment in the on-site 
medical record.
Subjects who are noncompliant on an ongoing basis will be considered for discontinuation per 
the Investigator’s discretion or local treatment guidelines. Investigators who opt to discontinue 
study drugs for an individual subject must discuss with the Medical Monitor prior to study drug 
discontinuation.
For subjects who are off study drug but remain on study, it will be the Investigator’s discretion to 
manage virologic rebound.
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
rebound.


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Figure 6-1.
Virologic Rebound Schema
a
If virologic rebound is not confirmed, the subject will remain on their current regimen.
b
If virologic rebound is confirmed and the HIV-1 RNA is ≥ 200 copies/mL, the HIV-1 genotype and phenotype (reverse 
transcriptase, protease and integrase) will be analyzed.
c
Based on the results of the genotypic and phenotypic assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping assay fails, a new ARV regimen may be configured at the discretion of the 
Investigator.
d
If no resistance is detected, HIV-1 RNA will be repeated (2-3 weeks later).  Investigator reviews study drug 
continuation/discontinuation options and discusses with the Medical Monitor prior to study drug discontinuation
e
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study.
6.14.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48, Week 96, or Week 144
Subjects with HIV-1 RNA ≥ 50 copies/mL at study discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48, Week 96, 
or Week 144 will be asked to return for an unscheduled visit within the visit window for a retest.
Subjects with HIV-1 RNA ≥ 200 copies/mL at study drug discontinuation, last visit, Week 48, 
Week 96, or Week 144 will also have resistance testing conducted.


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.6.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is 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 (e.g., 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, (e.g., venipuncture)
7.2.2.
Assessment of Severity
AE severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 5). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events.
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the eCRF:

all SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30-days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.


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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead 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 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 it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study start), record the 
SAE on the paper serious adverse event report form and submit by e-mail or fax within 
24 hours of the investigator’s knowledge of the event to:
Gilead DSPH contact information:
Email:
Safety_FC@gilead.com
Fax:
+1 (650) 522-5477

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 CRF/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 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, EU Summary of Product Characteristics 
(SmPC), or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 4 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 5).

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat
testing within 3 calendar days of receipt of results and before investigational medicinal 
product discontinuation, unless such a delay is not consistent with good medical practice

Any questions regarding toxicity management should be directed to the Gilead Medical 
Monitor.
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.


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7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, investigational 
medicinal product may be continued if the event is considered to be unrelated to
investigational medicinal product.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to investigational medicinal product, 
investigational medicinal product will be withheld until the toxicity returns to Grade 2.When 
restarting investigational medicinal product following resolution of the adverse event, the 
investigational medicinal product should be restarted at full dose upon discussion with the 
Gilead Sciences Medical Monitor.

If a laboratory abnormality recurs to Grade 3 following rechallenge with investigational 
medicinal product and is considered related to investigational medicinal product, then 
investigational medicinal product will be permanently discontinued and the subject managed 
according to local practice. Recurrence of laboratory abnormalities considered unrelated to 
investigational medicinal product may not require permanent discontinuation but requires
discussion with the Gilead Sciences Medical Monitor.
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event

For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to investigational medicinal product, 
investigational medicinal product will be permanently discontinued and the subject managed 
according to local practice. The subject should be followed as clinically indicated until the 
laboratory abnormality returns to baseline or is otherwise explained, whichever occurs first. 
A clinically significant Grade 4 laboratory abnormality that is not confirmed by repeat testing 
should be managed according to the algorithm for the new toxicity grade.

Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant Grade 4 laboratory abnormality (eg, Grade 4 CK after strenuous exercise, or 
triglyceride elevation that is nonfasting or that can be medically managed) or a clinical event 
considered unrelated to investigational medicinal product requires discussion with the 
Gilead Sciences Medical Monitor.
7.5.4.
Management of Possible Abacavir Hypersensitivity Reaction
Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to increased 
risk of hypersensitivity reaction, unless no other therapeutic option is available based on the 
treatment history and resistance testing.
In a clinical study, 3.4 % of subjects with a negative HLA-B*5701 status receiving abacavir 
developed a hypersensitivity reaction. Therefore, even in the absence of HLA-B*5701 allele, it is 
important to permanently discontinue abacavir and not rechallenge with abacavir if a 
hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe 
or even fatal reaction.


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Hypersensitivity reactions are characterized by the appearance of symptoms indicating 
multi-organ system involvement. Almost all hypersensitivity reactions will have fever and/or 
rash as part of the syndrome. Other signs and symptoms may include respiratory signs and 
symptoms such as dyspnoea, sore throat, cough, and abnormal chest x-ray findings 
(predominantly infiltrates, which can be localized), gastrointestinal symptoms, such as nausea, 
vomiting, diarrhea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as 
respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis. Other frequently 
observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and 
musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia). The symptoms related to this 
hypersensitivity reaction worsen with continued therapy and can be life-threatening. 
These symptoms usually resolve upon discontinuation of abacavir.
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. Patients 
should be monitored closely, especially during the first two months of treatment with abacavir.
Regardless of their HLA-B*5701 status, patients who are diagnosed with a hypersensitivity 
reaction whilst on therapy MUST discontinue study drug immediately and MUST NEVER be 
restarted. Restarting study drug following a hypersensitivity reaction results in a prompt return of 
symptoms within hours. This recurrence is usually more severe than on initial presentation, and 
may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimize 
the risk of a life-threatening hypersensitivity reaction, study drug must be permanently 
discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible 
(respiratory diseases, flu-like illness, gastroenteritis or reactions to other medicinal products) 
{Ezzati et al 2003}.
7.5.5.
Management of Potential Hepatobiliary Toxicity
Monkeys given a high dose (1000 mg/kg/day) for 39 weeks had evidence of biliary hyperplasia 
and hepatocyte hypertrophy on histopathologic examination. The risk to humans given the 
clinical dose of GS-9883 (50 mg/day) is unknown. Investigators should be aware of this potential 
toxicity. Any study subject exhibiting signs/symptoms or laboratory abnormalities suggestive of 
possible hepatobiliary toxicity should undergo thorough examination and clinical workup as 
deemed appropriate by the Investigator, and the Investigator must communicate promptly with 
the Gilead Medical Monitor. Consideration should be given to appropriate imaging studies (for 
example, ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. Management of graded 
laboratory and clinical abnormalities will be managed as outlined in Section 7.5.
7.5.6.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose 
interruption. Should the Investigator decide to initiate Hepatitis C treatment the Investigator 
must contact the Gilead Medical Monitor to confirm that no drug-drug interactions are expected.


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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.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, reports of adverse reactions in infants 
following exposure from breastfeeding, occupational exposure with an adverse event, and 
pregnancy reports regardless of an associated AE.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to 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.


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Any premature termination of pregnancy (e.g., a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead 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.
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH,
fax number +1 650 522-5477 or email Safety_FC@gilead.com.
Refer to Appendix 7 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead 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 7.3.2 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 a FDC of GS-9883/F/TAF
versus a FDC of ABC/DTG/3TC in HIV-1 infected, antiretroviral treatment naïve-adult subjects 
as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48
The secondary objectives of this study are:

To evaluate the efficacy, safety and tolerability of the two treatment groups through 
Weeks 48, 96, and 144

To evaluate the bone safety of the two treatment groups as determined by the percentage
change from baseline in hip and spine BMD through Weeks 48, 96, and 144
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 as 
defined by the US FDA-defined snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96,
and 144 as defined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96,
and 144

The percentage change from baseline in hip and spine BMD at Weeks 48, 96, and 144
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.


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8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis
set:

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 do not meet the inclusion criterion that the screening genotype report must 
show sensitivity to FTC, TFV, ABC, and 3TC.

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 4.3 including drugs not to be used with 
GS-9883, FTC, TAF, ABC, 3TC, and DTG.

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Substudy Analysis Set
The primary analysis set for intensive PK analyses is defined as the PK substudy analysis set, 
which will include all subjects who (1) are randomized into the study, (2) enrolled into the PK 
Substudy, (3) have received at least 1 dose of active GS-9883/F/TAF, and (4) have at least 
1 nonmissing intensive PK concentration data for any analyte of interest reported by the PK lab.


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8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose of 
active GS-9883/F/TAF, and (3) have at least 1 nonmissing PK concentration data for any
analyte of interest reported by the PK lab.
8.2.1.5.
DXA
8.2.1.5.1.
Hip DXA Analysis Set
The primary analysis set for hip BMD analyses is defined as the Hip DXA analysis set, which
will include all subjects who (1) are randomized into the study, (2) have received at least 1 dose 
of study drug, and (3) have nonmissing baseline hip BMD value. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.5.2.
Spine DXA Analysis Set
The primary analysis set for spine BMD analyses is defined as the Spine DXA analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have nonmissing baseline spine BMD value. Subjects will be 
grouped according to the treatment they actually received.
8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.  Logarithm (base 10) transformation will be 
applied to HIV-1 RNA levels for efficacy analysis.
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (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 (i.e., 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 sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects who achieve HIV-1 RNA 
50 copies/mL at Week 48 as determined by the US FDA-defined snapshot algorithm. The 
primary analysis of the efficacy endpoint will be based on the FAS.
8.5.1.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378, 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:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window

HIV-1 RNA 50 copies/mL: this includes 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 adverse event (AE), death, or 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 AE or 
death (regardless of whether the last available on-treatment HIV-1 RNA < 50 copies/mL 
or not) or,
b) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
c) 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 achieving HIV-1 RNA < 50 copies/mL 
(as defined by the US FDA-defined snapshot algorithm) at Week 48 in GS-9883/F/TAF is at 
least 12% lower than the response rate in ABC/DTG/3TC; the alternative hypothesis is that the 
response rate in GS-9883/F/TAF is less than 12% lower than that in ABC/DTG/3TC.
Non-inferiority will be assessed using the conventional confidence interval approach. The point 
estimate of treatment difference (GS-9883/F/TAF – ABC/DTG/3TC) and the associated 2-sided 
95% confidence interval will be constructed using a normal approximation method based on 
stratified Mantel-Haenszel proportions, where stratification factors include baseline HIV-1 RNA 
level (100,000 copies/mL vs. 100,000 copies/mL) and region (US vs. Ex-US). Note that to 
avoid small or missing cells in analysis strata, CD4+ cell count is not stratified in analysis 
because HIV-1 RNA and CD4+ cell count are highly correlated.
It will be concluded that GS-9883/F/TAF is non-inferior to ABC/DTG/3TC if the lower bound of 
the 2-sided 95% CI of the difference (GS-9883/F/TAF – ABC/DTG/3TC) in the response rate is 
greater than -12%.
If non-inferiority of GS-9883/F/TAF to ABC/DTG/3TC is established, the lower bound of the 
95% CI will be compared to 0; if the lower bound of the 95% CI is greater than 0, then 
superiority of GS-9883/F/TAF over ABC/DTG/3TC will be established.
8.5.2.
Secondary Analyses
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 and 
the proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96, and 144, as 
defined by the US FDA-defined snapshot algorithm, will be analyzed using the same method as 
for the primary efficacy endpoint.
The changes from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, and 144 
will be summarized by treatment using descriptive statistics. The differences in changes from 
baseline in log10 HIV-1 RNA and CD4+ cell count between 2 treatment groups and the 


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associated 95% confidence intervals will be constructed using ANOVA models, including 
treatment (GS-9883/F/TAF vs. ABC/DTG/3TC), baseline HIV-1 RNA level 
(100,000 copies/mL vs. 100,000 copies/mL), and region (US vs. Ex-US) as fixed effects in 
the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.
8.6.
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.


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On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV, can be found in Appendix 6.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 5.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum post baseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Bone Safety Evaluations
The percentage changes from baseline in hip/spine BMD at Weeks 48, 96, and 144 will be 
summarized by treatment using descriptive statistics. The differences in percentage changes from 
baseline in hip/spine BMD between 2 treatment groups and the associated 95% confidence 
intervals will be constructed using ANOVA models, including treatment as a fixed effect in the 
model.
In addition, missing values for BMD will be imputed using LOCF method and analyzed 
similarly.
8.6.5.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the intensive PK substudy, plasma concentrations of GS-9883 may be summarized by 
nominal sampling time using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Ctau, 
AUCtau, and T½, as appropriate) will be listed and summarized using descriptive statistics 
(eg, sample size, arithmetic mean, geometric mean, coefficient of variation %, SD, median, Q1, 
Q3, minimum, and maximum). Plasma concentrations over time will be plotted in 
semi-logarithmic and linear formats as mean ± standard deviation, and median (Q1, Q3).


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For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
descriptive statistics or population approaches.
TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.
8.8.
Inflammation, Immune Activation, Platelet and Renal Tubular Function 
Analysis
For each selected test of inflammation, immune activation, platelet function and renal tubular 
function, the percentage change from baseline may be summarized by treatment and visit using 
descriptive statistics. Differences in percentage changes from baseline in each selected test
between the 2 treatment groups will be tested using a Wilcoxon rank sum test.
8.9.
Patient Report Outcomes (PRO)
The PRO measures based on questionnaires (eg, SF-36 and HIV Distress Module) may be 
summarized by treatment and visit using descriptive statistics.
8.10.
Sample Size
A total of approximately 600 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (300 subjects per treatment group), achieves at least 95% power to detect a 
non-inferiority margin of 12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined 
by the US FDA-defined snapshot algorithm) difference between the 2 treatment groups. For the
sample size and power computations, it is assumed that both treatment groups have a response 
rate of 91% (based on Gilead Studies GS-US-292-0104 and GS-US-292-0111), that the 
non-inferiority margin is 12%, and that the significance level of the test is at a one-sided 
0.025 level. Sample size and power calculations were made using the statistical software package 
nQuery Advisor (Version 6.0).
8.11.
Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after
approximately the first 50% of subjects enrolled have completed their Week 12 visit or 
prematurely discontinued from the study drug, as well as after all subjects have completed 
Week 24 visit or prematurely discontinued from the study drug. However, Gilead will defer to 
the IDMC for any decision to convene earlier or more frequently. The IDMC will examine the 
safety results of the trial and also focus on logistical issues such as accrual, retention, quality of 
clinical and laboratory data, and implications of results of external studies. Blinding will be 
preserved during the conduct of the study and access to unblinded data will be limited to 
designated parties.
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.


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For each IDMC analysis performed prior to the analysis of the primary efficacy endpoint, an 
alpha penalty of 0.00001 will be applied for the primary analysis of the primary endpoint.
8.12.
Analysis Schedule
The Weeks 48, 96, and 144 analyses will be conducted after all subjects either complete their 
Week 48, 96, and 144 visits or prematurely discontinue from the study drug, respectively. Final 
analysis will be performed after all subjects complete the study or prematurely discontinue from 
the study.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject: These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 


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investigator must use the most current IRB- or IEC-approved consent form for documenting 
written informed consent. Each informed consent (or assent as applicable) will be appropriately 
signed and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB or IEC or
local requirements. 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, eCRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);


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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data.  The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received.  Subsequent to data entry, a study monitor will perform source 


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data verification within the EDC system. Original entries as well as any changes to data fields 
will be stored in the audit trail of the system.  Prior to database lock (or any interim time points 
as described in the clinical data management plan), 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. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files.
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs or IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.


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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB or IEC 
in accordance with local requirements and receive documented IRB or IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(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.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? 
Curr Med Res Opin 2014;30 (1):89-97.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
Costagliola D. Demographics of HIV and aging. Curr Opin HIV AIDS 2014;9 (4):294-301.
Department for Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents. Developed by the DHHS 
Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working 
Group of the Office of AIDS Research Advisory Council (OARAC). Downloaded 
from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 08 April, 
2015.
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet 
2003;362 (9387):847-52.
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.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised 
surveillance case definitions for HIV infection among adults, adolescents, and 
children aged <18 months and for HIV infection and AIDS among children aged 
18 months to <13 years--United States, 2008. MMWR Recomm Rep 2008;57 
(RR-10):1-12.
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84.
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported adherence supports 
patient preference for the single tablet regimen (STR) in the current cART era. 
Patient preference and adherence 2012;6:427-33.
The Joint United Nations Programme on HIV/AIDS (UNAIDS). 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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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table (Blinded Phase)
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


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Amendmcnt2 
Appendix J. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 
GS-9883/Em tricitabineffenofovir Alafenam ide Versus Abacavir/Dolutegravir/Lam ivud inc 
in HJV-llnf'ected, Antiretroviral Treatment-Naive Adults 
GS-US-380-1489 Amendment 2, 19 October 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Hal Martin, MD (Printed) 
Author 
Date 
PPD 
Signature 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. J 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 
CONFlDENTIAL 
Page 95 
19 October 20 16 


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Appendix 2.
Study Procedures Table (Blinded Phase)
Study Procedures
Screeninga
Day 1b
4
8
12
24
36
End of Weeke, r
Post-
Week
144e, s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
Informed Consent
X
Medical History
X
Concomitant 
Medications
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Sympto
m-Directed 
Physical Exam
X
X
X
d
X
d
X
d
X
X
d
X
X
d
X
d
X
d
X
Xd
Xd
Xd
X
Xx, Xd
X
Xd,f
Xf
12-Lead ECG 
(performed supine)
X
X
X
X
X
X
Xx
X
X
Questionnaires
X
X
X
X
DXA scan (spine 
& hip)g
X
X
X
X
X
X
X
Height
X
Vital signs (blood 
pressure, pulse, 
respiration rate, 
and temperature), 
including Weight
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy 
Testh
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Study Procedures
Screeninga
Day 1b
4
8
12
24
36
End of Weeke, r
Post-
Week
144e, s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
Serum Pregnancy 
Test
X
Chemistry Profilei
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic 
Assessmentsj
X
X
X
X
X
X
X
X
Xt
X
Estimated 
Glomerular 
Filtration Rate
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
X
Hematology 
Profilek
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 
RNA
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HLA-B*5701w
X
CD4+ Cell Count 
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluations of 
inflammation and 
immune activation, 
platelet function 
and renal tubular 
function
X
X
X
X
X
X
X
Xt
X
Plasma & Urine 
Storage Sample 
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HBV and HCV 
Serology
X
X
X
X
XX
HIV-1 Genotypel
Xl


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Study Procedures
Screeninga
Day 1b
4
8
12
24
36
End of Weeke, r
Post-
Week
144e, s
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-
upq
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12 Weeks
HIV-1 
Genotype/Phenoty
pee
Xe
Single PK Samplem
X
X
X
Trough PK 
Samplesn
X
X
Optional Whole 
blood/EDTA for 
HLA testing, 
UGT1A1 and 
biomarkers
X
Randomizationv
X
Provide subject 
dosing diary to 
subjects
X
X X
X
X
Optional PK 
Substudyo
X X
Optional PBMC 
Substudyp
X
X
X
X
Study Drug 
Dispensation
Xb
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xu
Study Drug 
Accountability
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures at the Day 1 visit, with the exception of DXA.
c
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
End of Blinded Treatment Visit even if the subject discontinues study drug.


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d
Symptom-directed physical examination as needed.
e
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Section 6.14.1 and Section 6.14.2).
f
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained.
g
DXA scans to be performed in all eligible subjects on study drug during blinded treatment only, except for those in Germany, prior to or within 24 hours of the Day 1 Visit, 
Weeks 24, 48, 96, 144 (±10 days), and at the End of Blinded Treatment Visit (±10 days) and the ESDD visit (if the last scan was acquired > 12 weeks from the date of the 
ESDD Visit).
h
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
i
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN). At Day 1, Weeks 12, 24, 48, 72, 96, 120, 144, and every 24 weeks post Week 144, and End of Blinded Treatment Visit, analyses of glucose will be done as part 
of the fasting metabolic assessments and not as part of the chemistry profile. Additionally: TSH will be analyzed at Screening, Day 1, Weeks 24, 48, 72, 96, 120, 144, and 
every 24 weeks post Week 144, End of Blinded Treatment Visit and Early Study Drugs Discontinuation visit.
j
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
k
CBC with differential and platelet count.
l
The Investigator must have received the results from the screening genotype report before proceeding with the Day 1 visit.  Screening genotype report must show sensitivity 
to TFV, FTC, 3TC and ABC. If genotype results from a local laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype will be 
acceptable to fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been 
confirmed.
m
A single PK blood sample will be collected at any time pre or post-dose
n
A trough PK blood sample will be collected between 20-28 hours following the last dose. Following an observed dose, a single post dose blood sample will be collected 
between 1 and 4 hours post dose.
o
A PK substudy will be performed in a subset of subjects (n=30) at selected study sites.  The pharmacokinetic substudy visit must occur at the Week 4 or Week 8 visits. The 
substudy will include intensive PK profiling in plasma
p
A PBMC substudy will be performed in a subset of subjects (n=50) at selected study sites.   A PBMC sample will be collected at Day 1 and Weeks 36, 84, and 132.
q
Only required for those subjects not enrolling in the open-label rollover extension or those subjects who prematurely discontinue study drugs and do not continue in the study 
through at least one subsequent visit after the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be 
used.
r
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to
Week 132, unless otherwise specified. The visit window at Weeks 48 and 96, 144 will be ± 6 weeks of the protocol-specified visit date.
s
After Week 144, subjects will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit.  Visit window of 6 days 
for study visits post Week 144.  
t
To be performed every 24 weeks after Week 144 until End of Blinded Treatment Visit.
u
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for up to 48 weeks.
v
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit, provided that all screening procedures have been completed and subject eligibility has been 
confirmed.
w
The Investigator must have received a negative screening test for HLA-B*5701 allele before proceeding with the Day 1 visit. If HLA-B*5701 results are available from a 
local laboratory prior to screening, this report will be acceptable to fulfill this inclusion criterion in the event that the HLA-B*5701 result obtained at screening is not yet 
available and all other inclusion/exclusion criteria have been confirmed.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 100
19 October 2016
x
To be performed every 48 weeks after Week 144 until the End of Blinded Treatment Visit.
y
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety and efficacy of GS-9883/F/TAF FDC is demonstrated following review of unblinded data, 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 in an open label (OL) extension phase for up to 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.


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 101
19 October 2016
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)
Study Procedures
End of Blinded 
Treatment Visita
End of Weeke, l
30-Day Follow-upk
Early Study 
Drugs DCc
12 OL
24 OL
36 OL
48 OL
Concomitant Medications
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed Physical Exam
X
Xd
Xd
Xd
X
Xd,f
Xf
12-Lead ECG (performed supine)
X
X
DXA scan (spine & hip)m
X
Vital signs (blood pressure, pulse, respiration rate, 
and temperature), including Weight
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
Chemistry Profileh
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
Estimated Glomerular Filtration Rate
X
X
X
X
X
Xf
X
Hematology Profilej
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
Evaluations of inflammation and immune activation, 
platelet function and renal tubular function
X
Plasma & Urine Storage Sample 
X
X
X
X
X
X
HBV and HCV Serology
X
HIV-1 Genotype/Phenotypee
Xe
Study Drug Dispensation
Xb
X
X
X
Study Drug Accountability
X
X
X
X
X
X


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 102
19 October 2016
a.
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety and efficacy of GS-9883/F/TAF FDC is demonstrated following review of unblinded data, 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 in an open label (OL) extension phase for up to 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.
b.
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for up to 48 weeks.
c.
Subjects who discontinue study drug during the open label rollover extension portion of the study will be asked to return to the clinic within 72 hours of stopping study drugs 
for the Early Study Drugs Discontinuation Visit followed by a 30-Day Follow-Up Visit.  The subject will not continue attending the scheduled study visits.
d.
Symptom-directed physical examination as needed.
e.
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Figure 6-1)
f.
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained. 
g.
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN). At Week 24 OL and Week 48 OL, and End of Blinded Treatment Visit, analyses of glucose will be done as part of the fasting metabolic assessments and not as 
part of the chemistry profile. For all subjects, TSH will be done at the End of Blinded Treatment Visit, Week 24 OL, Week 48 OL, and Early Study Drug Discontinuation 
Visit.
i.
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
j.
CBC with differential and platelet count.
k.
Subjects who complete the open-label rollover extension will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit.
Subjects who prematurely discontinue study drugs during the open-label rollover extension will be asked to return to the clinic 30 days after the completion of the Early Study 
Drugs Discontinuation Visit for the 30-Day Follow-Up Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used.
l.
Study visits are to be completed within ± 6 days of the protocol-specified visit date every 12 weeks thereafter, unless otherwise specified
m.
DXA scans to be performed in all eligible subjects on study drug, except for those in Germany, only at the End of Blinded Treatment Visit (±10 days).


GS-9883/Fff AF 
Protocol GS-US-380-1489 
Final 
Gilead Sciences, Inc. 
Amendment 2 
Appendix 4. 
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 
confrrm 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 
1 
If Grade 3 or 4 recurrence that is confirmed and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
1 
Repeat lab to 
confirm toxicity 
grade 
1 
lfc 
inve 
dosi 
oft 
onfirmed and unrelated to 
stigational medicinal products, 
ng may continue at the discretion 
he investigator 
If confirmed and 
possibly or probably 
-. related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
Page 103 
19 October 2016 


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 104
19 October 2016
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 
≥ 7 Months#
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 105
19 October 2016
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
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-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 106
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L                
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L                 
2.0 t o <2.5 mmolL
2.0 mEq/L                         
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant <1 Year
>ULN to 6.0 mEq/L           
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L             
6.5 to 7.0 mmol/L
7.0 mEq/L                  
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 107
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


GS-9883/F/TAF
Protocol GS-US-380-1489
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 108
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L
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


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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 110
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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.
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


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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 111
19 October 2016
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
                              Females
>ULN - 10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
                              Males
6-10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 h
>1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
>499 to 799 mg/m2/24 h
>799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes:

Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by Covance Laboratory, however for other laboratories, toxicity grades will only be assigned to 
Dipstick Hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.

If the severity of a clinical AE could fall under either one of two grades (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.


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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 112
19 October 2016
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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Amendment 2
CONFIDENTIAL
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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV 
block OR Ventricular pause 
3.0 sec
Complete AV block 
Pediatric 16 Years
1st degree AV block
(PR > normal for age and 
rate)
Type I 2nd degree AV block 
Type II 2nd degree AV 
block 
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc interval 
0.50 sec OR Increase in 
interval 0.06 sec above 
baseline
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Pediatric 16 Years
Asymptomatic, QTc interval 
0.450 to 0.464 sec 
Asymptomatic, QTc interval 
0.465 to 0.479 sec 
Asymptomatic, QTc interval 
0.480 sec 
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Deep vein thrombosis AND 
Intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Embolic event (eg, pulmonary 
embolism, life-threatening 
thrombus) 
Vasovagal Episode (associated
with a procedure of any kind)
Present without loss of 
consciousness 
Present with transient loss of 
consciousness
NA 
NA
Ventricular Dysfunction 
(congestive heart failure, 
CHF)
NA
Asymptomatic diagnostic 
finding AND intervention 
indicated
New onset with symptoms 
OR Worsening symptomatic 
CHF
Life-threatening CHF


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


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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 115
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SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by 
study participant or  
caregiver (for disabled 
adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or morbilliform 
rash with vesicles or limited 
number of bullae OR 
Superficial ulcerations of 
mucous membrane limited to 
one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson syndrome 
OR Ulceration of mucous 
membrane involving two 
or more distinct mucosal 
sites OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA


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


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


GS-9883/F/TAF
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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 118
19 October 2016
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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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 119
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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)


GS-9883/F/TAF
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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 120
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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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Amendment 2
CONFIDENTIAL
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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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Amendment 2
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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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Gilead Sciences, Inc.
Amendment 2
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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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Gilead Sciences, Inc.
Amendment 2
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Page 125
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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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Gilead Sciences, Inc.
Amendment 2
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Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC 
Guidelines)
1. Candidiasis of bronchi, trachea, or lungs
2. Candidiasis of esophagus
3. Cervical cancer, invasive
4. Coccidioidomycosis, disseminated or extrapulmonary
5. Cryptococcosis, extrapulmonary
6. Cryptosporidiosis, chronic intestinal (1 month duration)
7. Cytomegalovirus disease (other than liver, spleen or nodes)
8. Cytomegalovirus retinitis (with loss of vision)
9. Encephalopathy, HIV-related
10. Herpes simplex: chronic ulcer(s) (1 month duration); or bronchitis, pneumonitis or 
esophagitis
11. Histoplasmosis, disseminated or extrapulmonary
12. Isosporiasis, chronic intestinal (1 month duration)
13. Kaposi’s sarcoma
14. Lymphoma, Burkitt’s (or equivalent term)
15. Lymphoma, immunoblastic (or equivalent term)
16. Lymphoma, primary, of brain
17. Mycobacterium avium complex or Myobacterium kansasii, disseminated or extrapulmonary
18. Mycobacterium tuberculosis, of any site, pulmonary, disseminated or extrapulmonary
19. Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
20. Pneumocystis jirovecii (previously known as “Pneumocystis carinii) pneumonia
21. Pneumonia, recurrent
22. Progressive multifocal leukoencephalopathy
23. Salmonella septicemia, recurrent
24. Toxoplasmosis of brain
25. Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {Schneider et al 2008}


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Amendment 2
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Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1)
Definitions
a)
Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b)
Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2)
Contraception Requirements for Female Subjects
a)
Study Drug Effects on Pregnancy and Hormonal Contraception
The 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 current Prescribing 
Information and local product labeling for ABC/DTG/3TC for additional information.
b)
Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Day 1 visit prior to randomization. At 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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Amendment 2
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3)
Contraception Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid.  Therefore, male subjects with female 
partners of childbearing potential must use condoms during treatment and until 90 days after the 
end of relevant systemic exposure.  Additional contraception recommendations should also be 
considered if the female partner is not pregnant.
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after the end of relevant systemic exposure.
4)
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM).  Female condom and male condom should not 
be used together.
5)
Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Subjects whose partner 
has become pregnant or suspects she is pregnant during the study must report the information to 
the investigator.  Instructions for reporting pregnancy, partner pregnancy, and pregnancy 
outcome are outlined in Section 7.3.