Conditions: HIV-1 Infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 472
Healthy volunteers: no

Brief summary:
The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), or atazanavir (ATV) + ritonavir (RTV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in virologically suppressed HIV-1 infected women.

Detailed description:

Arms:
arm 1: Participants will switch to B/F/TAF FDC and receive treatment for 48 weeks. arm 2: Participants will remain on their baseline regimen of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF for 48 weeks. arm 3: Following Week 48, participants in countries where B/F/TAF is not available may have the option to receive B/F/TAF for up to 48 additional weeks.

Interventions: intervention 1: E/C/F/TAF intervention 2: E/C/F/TDF intervention 3: ATV intervention 4: RTV intervention 5: FTC/TDF intervention 6: B/F/TAF
Intervention descriptions: intervention 1: 150/150/200/10 mg FDC tablet administered orally once daily with food intervention 2: 150/150/200/300 mg FDC administered orally once daily with food intervention 3: ATV 300 mg capsules administered orally once daily with food intervention 4: RTV 100 mg tablets administered orally once daily with food intervention 5: 200/300 mg tablet administered orally once daily with food intervention 6: 50/200/25 mg FDC tablet administered orally once daily without regard to food

Protocol document:
SAP_004.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3, Randomized, Open Label Study to Evaluate the Safety 
and Efficacy of Switching to a Fixed Dose Combination (FDC) of 
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) 
from Elvitegravir/Cobicistat/Emtricitabine/
Tenofovir Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/
Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) or 
Atazanavir + Ritonavir + Emtricitabine/Tenofovir Disoproxil 
Fumarate (ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV-1 Infected Women
Name of Test Drug:
Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF; 
GS-9883/F/TAF)
Study Number:
GS-US-380-1961
Protocol Version (Date):
Amendment 2 (10 November 2016)
Analysis Type:
Final
Analysis Plan Version:
1.0
Analysis Plan Date:
21 December 2018
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF ABBREVIATIONS........................................................................................................................................5
1.
INTRODUCTION ................................................................................................................................................7
1.1.
Study Objectives ......................................................................................................................................7
1.2.
Study Design............................................................................................................................................7
1.3.
Sample Size and Power............................................................................................................................9
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................10
2.1.
Data Monitoring Committee Analysis ...................................................................................................10
2.2.
Week 48 Interim Analysis......................................................................................................................10
2.3.
Final Analysis ........................................................................................................................................10
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................11
3.1.
Analysis Sets..........................................................................................................................................11
3.1.1.
All Randomized Analysis Set...............................................................................................11
3.1.2.
All B/F/TAF Analysis Set ....................................................................................................11
3.2.
Subject Grouping ...................................................................................................................................12
3.3.
Strata and Covariates..............................................................................................................................12
3.4.
Examination of Subject Subgroups........................................................................................................12
3.5.
Multiple Comparisons............................................................................................................................12
3.6.
Missing Data and Outliers......................................................................................................................13
3.6.1.
Missing Data ........................................................................................................................13
3.6.2.
Outliers.................................................................................................................................13
3.7.
Data Handling Conventions and Transformations .................................................................................13
3.8.
Analysis Windows .................................................................................................................................14
3.8.1.
Definitions............................................................................................................................14
3.8.2.
Analysis Windows................................................................................................................15
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window................................................................................................................................17
4.
SUBJECT DISPOSITION ..................................................................................................................................18
4.1.
Subject Enrollment and Disposition.......................................................................................................18
4.1.1.
Subject Enrollment...............................................................................................................18
4.1.2.
Subject Disposition ..............................................................................................................18
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................18
4.2.1.
Duration of Exposure to B/F/TAF........................................................................................18
4.2.2.
Adherence to Study Drug Regimen......................................................................................19
4.3.
Protocol Deviations................................................................................................................................20
5.
BASELINE CHARACTERISTICS....................................................................................................................21
5.1.
Demographics and Baseline Characteristics ..........................................................................................21
5.2.
Baseline Disease Characteristics............................................................................................................21
5.3.
Medical History......................................................................................................................................21
6.
EFFICACY ANALYSES ...................................................................................................................................22
6.1.
Definition of Efficacy Endpoints ...........................................................................................................22
6.1.1.
Primary Efficacy Endpoint...................................................................................................22
6.1.2.
Secondary Efficacy Endpoints .............................................................................................22


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6.1.3.
Tertiary Efficacy Endpoints .................................................................................................22
6.2.
Analysis of the Efficacy Endpoints........................................................................................................22
6.2.1.
Analysis of CD4 Cell Count and CD4% ..............................................................................22
6.2.2.
Analysis of the Proportion of Subjects with HIV-1 RNA < 50 copies/mL 
by Missing = Excluded Approach........................................................................................23
6.3.
Changes From Protocol-Specified Efficacy Analyses............................................................................23
7.
SAFETY ANALYSES........................................................................................................................................24
7.1.
Adverse Events and Deaths....................................................................................................................24
7.1.1.
Adverse Event Dictionary ....................................................................................................24
7.1.2.
Adverse Event Severity........................................................................................................24
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................24
7.1.4.
Serious Adverse Events........................................................................................................24
7.1.5.
Treatment-Emergent Adverse Events...................................................................................24
7.1.6.
Summaries of Adverse Events and Death ............................................................................25
7.1.7.
Additional Analysis of Adverse Events ...............................................................................26
7.2.
Laboratory Evaluations ..........................................................................................................................27
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................27
7.2.2.
Graded Laboratory Values ...................................................................................................28
7.2.3.
Metabolic Laboratory Evaluations .......................................................................................29
7.2.4.
Liver-Related Laboratory Evaluations .................................................................................30
7.2.5.
Renal-Related Laboratory Evaluations.................................................................................30
7.3.
Body Weight, Height, and Vital Signs...................................................................................................31
7.4.
Prior and Concomitant Medications.......................................................................................................31
7.4.1.
Antiretroviral Medications ...................................................................................................31
7.4.2.
Concomitant Non-Antiretroviral Medications......................................................................31
7.5.
Electrocardiogram Results .....................................................................................................................32
7.6.
Other Safety Measures ...........................................................................................................................32
7.7.
Subgroup Analyses for Safety Endpoints...............................................................................................32
7.8.
Changes From Protocol-Specified Safety Analyses...............................................................................32
8.
PHARMACOKINETIC ANALYSES ................................................................................................................33
9.
REFERENCES ...................................................................................................................................................34
10.
SOFTWARE.......................................................................................................................................................35
11.
SAP REVISION..................................................................................................................................................36
12.
APPENDICES ....................................................................................................................................................37
Appendix 1.
Study Procedures Table..........................................................................................................38
Appendix 2.
TFL Mocks.............................................................................................................................41
Appendix 3.
Cardiovascular or Cerebrovascular Events.............................................................................42
Appendix 4.
Hepatic Events........................................................................................................................43
Appendix 5.
Programming Specification....................................................................................................44


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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 .............................................................................................................................15
Table 3-2.
Analysis Windows for Metabolic Assessments......................................................................16
Table 3-3.
Analysis Windows for TSH, Renal Function, and HCV RNA Assessments..........................16
Table 3-4.
Analysis Windows for ECG Assessments..............................................................................16


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LIST OF ABBREVIATIONS
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
Atazanavir
BIC
Bictegravir, GS-9883, B
B/F/TAF
single-tablet regimen of bictegravir (BIC; B) 50 mg / emtricitabine (FTC) 200 mg /
tenofovir alafenamide (TAF) 25 mg; GS-9883/F/TAF
BMI
body mass index
BSA
body surface area
CG
Cockroft-Gault
CRF
case report form
CSR
clinical study report 
DNA
Deoxyribonucleic Acid
DOB
date of birth
E/C/F/TAF
Elvitegravir /Cobicistat /Emtricitabine/ Tenofovir Alafenamide; Genvoya; GEN
E/C/F/TDF
Elvitegravir /Cobicistat /Emtricitabine / Tenofovir Disoproxil Fumarate; Stribild; 
STB
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFR(CG)
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
full analysis set
FDA
Food and Drug Administration
FDC
fixed dose combination
FTC/TDF
single-tablet regimen of emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg
FTC
Emtricitabine; F
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
Gilead
Gilead Sciences, Inc.
GS-9883
Bictegravir; BIC; B
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


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HCVAb
HCV antibody
HDL
high density lipoprotein
HIV-1
human immunodeficiency virus (Type 1) 
HLGT
high level group term
HLT
high level term
ID
identification
IDMC
independent data monitoring committee
INR
international normalized ratio
KM
Kaplan-Meier
LDL
low density lipoprotein
LLT
lowest level term
MedDRA
Medical Dictionary for Regulatory Activities
OLE
open-label extension
PK
pharmacokinetic
PT
preferred term
PT
prothrombin time
PVE
pharmacovigilance and epidemiology
Q
quartile
Q1
first quartile
Q3
third quartile
RBP
retinol binding protein
RNA
ribonucleic acid
RTV
Ritonavir
SAE
serious adverse events
SAP
statistical analysis plan
SBR
stay on baseline regimen
SD
standard deviation
SE
standard error
SMQ
Standardised MedDRA Query
SOC
system organ class
TAF
tenofovir alafenamide 
TEAE
treatment-emergent AE
TFL
tables, figures, and listings
TSH
thyroid stimulating hormone
ULN
upper limit of normal
UACR
urine albumin to creatinine ratio
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 final analysis for Study 
GS-US-380-1961, which will be performed when all subjects have completed the study or 
prematurely discontinued from the study. This SAP is based on the study protocol amendment 2
dated 10 November 2016 and the electronic case report form (eCRF). The SAP will be finalized 
before data finalization for the final 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 switching to a fixed dose combination (FDC) of bictegravir
(GS-9883; BIC; B) /emtricitabine (FTC; F) /tenofovir alafenamide (TAF) versus continuing 
on a regimen consisting of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF in 
virologically suppressed HIV-1 infected women as determined by the proportion of subjects
with HIV-1 RNA ≥50 copies/mL at Week 48.
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups through Week 48.
1.2.
Study Design
Design Configuration and Subject Population
GS-US-380-1961 is a randomized, open-label, multicenter, active-controlled study to evaluate 
the safety and efficacy of switching to an FDC of B/F/TAF in HIV-1 infected women who are 
virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥ 12 consecutive weeks prior to screening.
All subjects will be HIV-1 infected women drawn from pre-defined Gilead Sciences (Gilead)
clinical studies and must be virologically suppressed. Women in Study GS-US-236-0128 who
completed the Week 48 open-label extension (OLE) visit or any post Week 48 OLE visits,
women in Study GS-US-292-0109 who completed the Week 96 visit or any post Week 96 visits, 
or women in Studies GS-US-292-0104 or GS-US-292-0111 who completed the Week 144 visit 
or any post Week 144 visits may be eligible to enroll in Study GS-US-380-1961.


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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 receive open-label medication as follows:
Treatment Group 1: FDC of BIC 50 mg/FTC 200 mg/TAF 25 mg (B/F/TAF) administered 
orally, once daily, without regard to food (approximately n = 235)
Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (approximately n = 235)
Key Eligibility Criteria
Medically stable HIV-1 infected women who meet the following criteria:

Currently on a stable antiretroviral regimen consisting of E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF continuously for ≥12 consecutive weeks preceding the screening 
visit

Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥12 weeks preceding the 
Screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by re-suppression to < 50 copies/mL is allowed

HIV-1 RNA <50 copies/mL at screening

Estimated glomerular filtration rate (eGFR) ≥50 mL/min according to the Cockcroft-Gault 
(C-G) formula at the screening visit
Study Periods / Phases
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, subjects in a country where 
B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC for an 
additional 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.
Subjects who complete the study through the Week 48 Visit and do not continue participation in 
the study will be required to return to the clinic 30 days after the Week 48 Visit for a 30 Day 
Follow-Up Visit.
Schedule of Assessments
After screening procedures, eligible subjects will be randomized 1:1 to Treatment Group 1 or 
Treatment Group 2 and treated for 48 weeks. Following the Screening and Day 1 visits, subjects 
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For all eligible subjects, blood and urine will be collected at Day 1, Weeks 4, 8, 12, and then 
every 12 weeks through the Week 48 visit. Laboratory analyses (including hematology, 
chemistry, and urinalysis), HIV-1 RNA, CD4+ cell count, and complete or symptom-directed 
physical examinations will be performed at the Screening, Day 1, and all subsequent study visits.
Adverse events and concomitant medications will be assessed at each visit.
Pharmacokinetics
For all subjects on B/F/TAF (Treatment Group 1), a single anytime pre or post-dose PK blood
sample will be collected at Weeks 8, 24, and 36.
For all subjects on B/F/TAF (Treatment Group 1), a trough PK blood sample will be obtained 
20-28 hours following the last dose at Weeks 4 and 12. Following an observed dose, one PK 
blood sample will be collected between 1 and 4 hours post-dose.
The concentration of BIC may be summarized using descriptive statistics.
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 the prior treatment regimen group 
(ie, E/C/F/TAF, E/C/F/TDF, and ATV+RTV+FTC/TDF).
Site and/or Stratum Enrollment Limits
Approximately 57 study sites in North America, Dominican Republic, Thailand, Russia, and 
Uganda participated. There was no enrollment limit for individual sites.
Study Duration
The randomized phase of this study is 48 weeks in duration.
1.3.
Sample Size and Power
A total of approximately 470 HIV-1 infected women, randomized in a 1:1 ratio to 2 treatment 
groups (approximately 235 subjects per treatment group), achieves at least 87% power to detect a 
non-inferiority margin of 4% difference in the percentage of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 between the 2 treatment groups.
For sample size and power computation, it is assumed that both treatment groups have 2% of 
subjects with HIV-1 RNA ≥50 copies/mL at Week 48 (based on the historical Gilead Genvoya®
[GEN; E/C/F/TAF] and Stribild® [STB; E/C/F/TDF] studies), that a non-inferiority margin is 
4%, 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).


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee Analysis
The Week 24 Independent Data Monitoring Committee (IDMC) analysis was conducted after all
subjects enrolled completed their Week 24 visit of the study or prematurely discontinued the 
study drug. The purpose of this interim analysis 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 result or to consider 
early termination of the study even if there is early evidence of favorable efficacy for B/F/TAF.
2.2.
Week 48 Interim Analysis
The Week 48 interim analysis was conducted after all subjects either completed their Week 48 
visit or prematurely discontinued 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 SAP describes the analysis plan for the final analysis, which will only include the all 
B/F/TAF analysis: safety and efficacy assessments for B/F/TAF only, not for other study drugs.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
The final analysis will include only the all B/F/TAF analysis in tables and figures, unless 
specified otherwise. The analysis for the randomized phase data exposed to SBR group was 
included in the Week 48 interim analysis and will not be repeated in this final analysis. However, 
data collected from the entire study will be included in data listings.
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.
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 actual treatment group 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 in data listings, age on the date 
of randomization 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.
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 data 
finalization. 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 were randomized into the study.
This is the primary analysis set for by-subject listings.
3.1.2.
All B/F/TAF Analysis Set
The All B/F/TAF Analysis Set includes all subjects who (1) were randomized to B/F/TAF and 
have received at least 1 dose of B/F/TAF during the randomized phase or (2) have received at 
least 1 dose of B/F/TAF during the extension phase. This is the primary analysis set for all 
B/F/TAF efficacy and safety analyses.


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3.2.
Subject Grouping
For the all B/F/TAF analysis including extension phase, subjects will be grouped into the 
following groups:

B/F/TAF group: This group includes all subjects who were randomized to B/F/TAF in the 
randomized phase of this study. All data from both the randomized and extension phases 
(if applicable) will be included.

Stay on Baseline Regimen (SBR) to B/F/TAF group: This group includes all subjects who 
were randomized to continuing pre-existing regimen in the randomized phase of this study, 
and who then switched to B/F/TAF in the extension phase. Only data collected on and after 
the extension phase first dose date of B/F/TAF will be included, except that data collected on 
or prior to the extension phase first dose date of B/F/TAF will be used to derive the baseline 
value for the all B/F/TAF analysis.

All B/F/TAF group: This group includes all subjects who are in the All B/F/TAF Analysis 
Set, which combines the two groups above.
3.3.
Strata and Covariates
There is no stratification for analysis.
3.4.
Examination of Subject Subgroups
In order to explore the effect of switching from TDF to TAF on renal functions,, subgroup 
analysis by prior treatment regimen (ie, TDF-containing regimen versus non-TDF containing 
regimen) will be performed for the following endpoints:

Urine retinal binding protein (RBP) to creatinine ratio

beta-2 microglobulin to creatinine ratio

Urine albumin to creatinine ratio (UACR)
3.5.
Multiple Comparisons
Multiple comparisons and alpha adjustment were applied for the primary endpoint analysis 
conducted at Week 48. No alpha level adjustment is applied in the final analysis.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
A missing datum for a given study analysis window may be due to any of the following reasons:

A visit occurring in the window but data were not collected or were unusable 

A visit not occurring in the window

A subject prematurely discontinuing from the study before reaching the window
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.
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 non-antiretroviral (ARV) medications in Section 7.4.2.
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.
Logarithm (base 10) transformation will be applied to HIV-1 RNA data for efficacy analysis. 
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.


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3.8.
Analysis Windows
For subjects who were randomized to SBR and discontinued study drug in the randomized phase
(ie, subjects who were in the All Randomized Analysis Set, but not in the All B/F/TAF Analysis 
Set), the definition and derivation of the necessary variables presented in the data listings
(eg, first dose date, last dose date, study date, etc.) can be found in Appendix 4.
For the all B/F/TAF analysis that only evaluates the efficacy and safety of B/F/TAF, the study 
drug mentioned in the following only refers to B/F/TAF.
3.8.1.
Definitions
Study Day 1 is defined as the day when the first dose of B/F/TAF (either in the randomized 
phase or extension phase) was taken. For subjects randomized to the B/F/TAF group, the 
first dose date is the same as the randomized phase first dose date. For subjects randomized to 
the SBR group, the first dose date is defined as the earliest nonmissing start date of B/F/TAF 
recorded on the Study Drug Administration eCRF.
Study Days are calculated relative to Study Day 1 for the all B/F/TAF analysis. For events that 
occur on or after the Study Day 1 date, study days are calculated as (visit date minus date of the 
first dose plus 1). For events that occur prior to Study Day 1, study days are calculated as 
(visit date minus date of the first dose).
Last Dose Date is defined as the maximum, nonmissing end date of B/F/TAF, recorded on the 
Study Drug Administration eCRF form with “Study Drug Permanently Discontinued” box 
checked for subjects who prematurely discontinued study drug or who completed study drug 
according to the Study Drug Completion eCRF.
If the date of last dose is missing (eg, due to lost to follow-up) for subjects who prematurely 
discontinued study drug, the maximum of nonmissing 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.
Last Study Date is the maximum of nonmissing 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 or completed the study according to the Study Completion eCRF.
Baseline value is defined as the last nonmissing value obtained on or prior to the Study Day 1 
for all assessments.


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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 analysis window. Since the final analysis only includes the all 
B/F/TAF analysis, only data included in the all B/F/TAF analysis will be assigned analysis 
windows.
For data listings, the observations collected from the randomized phase of the study for the 
subjects who were randomized to SBR group will not have analysis window assigned and will be 
included in listings with derived visit as blank.
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 3-1.
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
Visit ID
B/F/TAF
SBR to B/F/TAF
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 4
28
2
42
Week 8
56
43
70
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
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 3-2.


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Table 3-2.
Analysis Windows for Metabolic Assessments
Visit ID
B/F/TAF
SBR to B/F/TAF
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 12
84
2
126
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
The analysis windows for thyroid stimulating hormone (TSH; thyrotropin) and renal function 
(including urine albumin, urine creatinine, urine RBP, and urine beta-2 microglobulin, and 
derived ratios assessments) are presented in Table 3-3.
Table 3-3.
Analysis Windows for TSH, Renal Function, and HCV RNA 
Assessments
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 k
k*7
(k-12)*7+1
(k+12)*7
The analysis windows for ECG assessments are presented in Table 3-4.
Table 3-4.
Analysis Windows for ECG Assessments
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 24
168
2
252
Week 48
336
253
504
Week 96
672
505
756
Week k
k*7
(k-12)*7+1
(k+12)*7


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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 B/F/TAF will be 
selected. If there are multiple records with the same collection time or no collection 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 and CD4%, the record(s) collected on the latest day in the window 
will be selected for analysis.
For other numeric observations (eg, except HIV-1 RNA, CD4+ cell count, and CD4%), 
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 arithmetic mean will be used.

For baseline and postbaseline HIV-1 RNA, the latest (considering both collection 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 B/F/TAF will be 
selected. If there are multiple records with the same collection time or no collection 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 summaries on subject enrollment have been performed as part of the Week 48 analysis, and 
will not be repeated in the final analysis.
4.1.2.
Subject Disposition
The summary of subject disposition will be provided by treatment group and overall using the 
All Randomized Analysis Set for all B/F/TAF analysis (Appendix 2; Appendix Table 1). This 
summary will include the number of subjects who were randomized, randomized but not treated, 
randomized and treated, subjects who prematurely discontinued study treatment in the 
randomized phase, subjects who completed the randomized phase but not entered the extension 
phase, subjects who entered the extension phase, who received B/F/TAF in either the 
randomized or extension phase (ie, All B/F/TAF Analysis Set).
In addition, the number and percentage of the subjects from the All B/F/TAF Analysis Set in the 
following categories will be summarized:

Completed B/F/TAF

Prematurely discontinuing B/F/TAF (with summary of reasons for discontinuing study
treatment)

Completed study 

Prematurely discontinuing (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 All B/F/TAF Analysis Set.
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation from both phases will be provided.
4.2.
Extent of Study Drug Exposure and Adherence
4.2.1.
Duration of Exposure to B/F/TAF
Duration of exposure to B/F/TAF is defined as (the last dose date of B/F/TAF – the first dose 
date of B/F/TAF + 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).


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Duration of exposure to B/F/TAF 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], etc.
Summaries will be provided by treatment group for subjects in the All B/F/TAF Analysis Set. No 
inferential statistics will be provided.
Time to premature discontinuation of study drug will be analyzed using the Kaplan-Meier 
method by treatment group based on the All B/F/TAF Analysis Set. No statistical comparisons 
will be made 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
Study drug regimen adherence will be computed based on pill counts for B/F/TAF only. The 
numbers of pills of B/F/TAF dispensed and returned are captured on Study Drug Accountability 
eCRF. Adherence will be summarized for B/F/TAF during the entire study (including both the 
randomized and extension phase if applicable).
Adherence (%) of B/F/TAF will be calculated as follows:
prescribed
pills
of
Number 
 taken
pills
of
Number 
100
(%)
Adherence


[2]
period
dispensing
each
at 
prescribed
pills
of
No.
of
Sum
[1]
period
dispensing
each
at 
 taken
pills
of
No.
of
Sum
100

[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 of the same dispensing date, 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 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 of the same dispensing date. Total number of pills prescribed is determined by 
summing the number of pills prescribed from all evaluable dispensing periods.


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The duration of treatment at a dispensing period for a study drug is calculated as the minimum of 
(a) the last returned date of the same dispensing period for the study drug, (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, all records in that dispensing period for that study drug will be excluded from 
both denominator and numerator calculation.
Adherence to the study drug B/F/TAF will be calculated for each subject in the All B/F/TAF 
Analysis Set for the entire B/F/TAF dosing period up to the date of permanent discontinuation of 
B/F/TAF for subjects who prematurely discontinued B/F/TAF or using all data available for 
subjects completing B/F/TAF.
Descriptive statistics for overall adherence for B/F/TAF (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 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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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex, 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. Age is 
calculated as age in years at first dose of B/F/TAF. The summaries of demographic data and 
baseline subject characteristics will be provided using the All B/F/TAF Analysis Set.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized:

HIV-1 RNA categories (copies/mL): (a) < 50, (b) ≥ 50

CD4+ cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, (d) ≥350 to 
< 500, and (e) ≥500

CD4 percentage (%)

Mode of infection (HIV risk factors)

HIV disease status

eGFRCG (mL/min)
No statistical comparisons will be made for the all B/F/TAF analysis.
5.3.
Medical History
Medical history data were presented in the original studies from which subjects were rolled over. 
Thus, medical history data will not be summarized in this study.


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6.
EFFICACY ANALYSES
6.1.
Definition of Efficacy Endpoints
6.1.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects with virologic failure (HIV-1 RNA 
≥50 copies/mL) at Week 48 as defined by the modified FDA snapshot algorithm. 
The analyses of the primary efficacy endpoint were performed in the Week 48 interim analyses,
and will not be repeated in the final analysis.
6.1.2.
Secondary Efficacy Endpoints
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA 50 copies/mL at Week 48 as determined by 
the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
6.1.3.
Tertiary Efficacy Endpoints
 
 
 
6.2.
Analysis of the Efficacy Endpoints
Analyses of the proportions of subjects determined by the US FDA-defined Snapshot Algorithm
(the primary efficacy endpoint at Week 48 and part of the secondary 
 efficacy 
endpoints) were performed in the Week 48 interim analyses and will not be repeated in this final 
analysis.
6.2.1.
Analysis of CD4 Cell Count and CD4%
CD4 cell count and CD4% will be summarized using observed, on-treatment data (ie, data 
collected up to 1 day after the last dose date of B/F/TAF) for subjects in the All B/F/TAF 
Analysis Set.
CCI
CCI
I 
I 
I 
I 
-


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The changes from baseline in CD4 cell count and CD4% at each visit will be summarized by 
treatment group using descriptive statistics based on observed data (ie, missing will be excluded) 
using the All B/F/TAF Analysis Set.
The mean and 95% CI of change from baseline in CD4 cell count over time will be plotted using
observed data for the All B/F/TAF Analysis Set.
6.2.2.
Analysis of the Proportion of Subjects with HIV-1 RNA < 50 copies/mL by 
Missing = Excluded Approach
The proportion of subjects with HIV-1 RNA < 50 copies/mL will be analyzed using the 
Missing = Excluded (M = E) for imputing missing HIV-1 RNA values:
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.
For M = E analysis, the number and percentage of subjects with HIV-1 RNA in the following 
categories will be summarized:

< 50 copies/mL
< 20 copies/mL
■
< 20 Not Detectable
■
< 20 Detectable
20 to < 50 copies/mL

50 to < 200 copies/mL

200 to < 400 copies/mL

400 to < 1000 copies/mL

≥ 1000 copies/mL
The 95% CI of the proportion of subjects with HIV-1 RNA < 50 copies/mL within each subject 
group will be provided using the Clopper-Pearson Exact method. 
6.3.
Changes From Protocol-Specified Efficacy Analyses
No change from protocol-specified efficacy analysis is planned.


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7.
SAFETY ANALYSES
Safety data for the all B/F/TAFanalysis will be summarized by treatment group and overall for 
the subjects in the all B/F/TAF analysis, unless specified otherwise. All safety data from the 
entire study including both randomized phase and extension phase 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 
lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe) or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will be categorized as 
“missing” for tabular summaries and data listings and will be considered the least severe for the 
purpose of sorting for data presentation.
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 SAE database 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 B/F/TAF start date and no later than 30 days after 
permanent discontinuation of B/F/TAF, or

Any AEs leading to premature discontinuation of B/F/TAF.


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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 B/F/TAF, 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 B/F/TAF, 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 B/F/TAF
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 B/F/TAF, will be considered as a 
TEAE. 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 B/F/TAF 
will be considered as a TEAE.
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 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
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 all B/F/TAF phase will be also included in this summary.
Treatment-emergent death refers to deaths that occurred between the first and last dose date of 
B/F/TAF plus 30 days (inclusive).


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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 TEAEs, Grade 3 or 4 TEAEs, 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.
Data listings for all AEs regardless of the study phases 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 5). 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 3).
The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
provided by treatment group based on the All B/F/TAF Analysis Set. A data listing of 
cardiovascular or cerebrovascular events will be provided.


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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 4).
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. A data listing of hepatic events will be provided.
7.2.
Laboratory Evaluations
Laboratory data will be analyzed and summarized using both quantitative and qualitative 
methods using 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.
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

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 B/F/TAF. 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.


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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 x (4.0 - albumin (g/dL)).
Toxicity grading for calcium will be applied based on the corrected values.
Estimate GFR
The following formulae will be used to calculate eGFRCG:

eGFR(CG) (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / 
(SCr (mg/dL) × 72), where weight is total body mass in kilograms.
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, 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.
For the international normalized ratio (INR) of prothrombin time (PT), protocol-specified 
toxicity grading scale depends on the upper limit of normal range (ULN). While the ULN of INR 
depends on whether the subject is taking anticoagulant medication or not (ie, Not taking oral 
anticoagulant: 0.8 – 1.2; Taking oral anticoagulant: 2.0 – 3.0), this information is not collected 
by the reference laboratory. As a result, INR will be graded by assuming subject is not taking an 
oral anticoagulant, which is a conservative approach that may lead to over-reporting of 
abnormalities for INR. Consequently, INR and PT will not be included in summaries of 
laboratory abnormalities, but will be included in listings for the following reasons: 1) INR and 
PT are reflexive tests; 2) only the absolute values, not the toxicity grade, are needed for subject
management purposes; and 3) more importantly, the toxicity grades for INR may be 
over-reported.


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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 from the last dose 
date of B/F/TAF. 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 the last dose date of B/F/TAF.
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 metabolite 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 by treatment group and visit using descriptive statistics.


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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 collected in the all B/F/TAF phase of this study:

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 date
of B/F/TAF. 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.
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.
7.2.5.2.
Urine Creatinine, Urine Retinol Binding Protein to Creatinine Ratio, and 
Beta-2-Microglobulin to Creatinine Ratio
Baseline, postbaseline, and change from baseline in urine creatinine will be summarized by
treatment group and visit using descriptive statistics.
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.


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7.2.5.3.
Albuminuria by Quantitative Assessment
The baseline, postbaseline, changes from baseline, and percentage change from baseline in 
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, 72, 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 of B/F/TAF) 
{KDIGO Guideline Development Staff 2013}.
7.3.
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 at 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 B/F/TAF. 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.
7.4.
Prior and Concomitant Medications
7.4.1.
Antiretroviral Medications
Any nonstudy ARV medications used prior to, during, or after the study (if collected) are all 
recorded on the ARV eCRF. All ARV medications recorded on the ARV eCRF will be coded 
using the Gilead-modified World Health Organization (WHO) Drug Dictionary for ARV 
medication. The WHO preferred name and drug code will be attached to the clinical database. 
All ARV medications recorded on the ARV eCRF will be listed. No inferential statistics will be 
provided.
7.4.2.
Concomitant Non-Antiretroviral Medications
Concomitant non-ARV medications are defined as non-ARV medications taken while a subject 
took study drug. Use of concomitant non-ARV medications from the first dose date to the last 
dose date of B/F/TAF will be summarized by preferred name using the number and percentage 
of subjects for each treatment group. Multiple drug use (by preferred name) will be counted only 
once per subject. The summary will be sorted by decreasing order of total frequency.


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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. The medication is concomitant if the month and year of the start 
or stop (or year of the start or stop, if month is not recorded) of the medication does not meet 
either of the following criteria:

The month and year of start of the medication is after the last dose date of B/F/TAF

The month and year of stop of the medication is before the first dose date of B/F/TAF
If the start and stop date of non-ARV medications are complete, the start date is not after the last 
dose date and the stop date is not before the first dose date, or the non-ARV medications are 
marked as ongoing and start date is on or before the last dose date, the non-ARV medications are 
concomitant for the all B/F/TAF phase of the study.
Summaries of non-ARV concomitant medications will be provided for the All B/F/TAF Analysis 
Set. Subjects with any non-ARV concomitant medications will be listed including Anatomical 
Therapeutic Chemical (ATC) drug class level 2. No inferential statistics will be provided.
7.5.
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 groups 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.
7.6.
Other Safety Measures
A data listing will be provided for subjects experiencing pregnancy during the study. Physical 
examination was not collected in the eCRF. Therefore, it will not be included in the analysis.
7.7.
Subgroup Analyses for Safety Endpoints
Subgroup analysis by prior treatment regimen (ie, TDF-containing regimen versus non-TDF 
containing regimen) will be performed for renal endpoints including urine RBP to creatinine 
ratio, beta-2 microglobulin to creatinine ratio, and UACR using All B/F/TAF Analysis Set, as 
described in Section 7.2.5 above.
7.8.
Changes From Protocol-Specified Safety Analyses
No change from protocol-specified safety analysis is planned.


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8.
PHARMACOKINETIC ANALYSES
All necessary PK analyses have been performed as part of the Week 48 analysis and will not be 
repeated in this analysis.


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9.
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.


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10.
SOFTWARE
SASVersion 9.4 (SAS Institute Inc., Cary, NC, USA) 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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11.
SAP REVISION
Revision Date
(dd month, yyyy)
Section
Summary of Revision
Reason for Revision


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12.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
TFL Mocks
Appendix 3.
Cardiovascular or Cerebrovascular Events
Appendix 4.
Hepatic Events
Appendix 5.
Programming Specification


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Appendix 1.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48d,v
30 Day 
Follow-Upe
ESDDf
4
8
12
24
36
48
Every 12 Weeks
Informed Consent
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam 
X
X
X
X
X
Symptom-Directed Physical Exam
X
X
X
X
X
X
12-Lead ECG 
X
X
X
X
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Chemistryh
X
X
X
Xw
Urine Pregnancy Testi
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testi
X
Chemistry Profilej
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentsk
X
X
X
X
Xw
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilel
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAm
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Planeln
X


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Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48d,v
30 Day 
Follow-Upe
ESDDf
4
8
12
24
36
48
Every 12 Weeks
Plasma HBV DNAo
X
X
X
X
Xw
X
HCVAbp
X
HCV RNAp
X
X
X
Xw
HIV-1 Genotype/Phenotypeq
Xq
Xq
Single PK Drawr
X
X
X
Trough PK Draws
X
X
PK Sample (post-dose)s
X
X
Observed In-Clinic Doses
X
X
Provide Dosing Diaryu
X
X
X
X
X
Collect Dosing Diaryx
X
X
X
X
X
Randomization
X
Study Drug Dispensation 
X
X
X
X
X
X
Xv
Xv
Study Drug Accountability
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Subjects should initiate dosing of study drug on the same day as the Day 1 visit.
c
All study visits should be ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days at Week 24 and Week 36, 
unless otherwise specified. The visit window at Week 48 will be ± 6 weeks of the protocol-specified visit date.
d
At the Week 48 Visit, subjects in a country where GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/TAF FDC for an additional 48 weeks, 
or until the product becomes accessible to subjects through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.
Study visits are to be completed every 12 weeks, within ± 6 days of the protocol-specified visit date unless otherwise specified. 
CCI
CCI


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e
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. Required for subjects 
who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Subjects who participate 
post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit.  
f
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Week 48 Visit even if the subject discontinues study drug.
g
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature
h
Urine Chemistry includes urine albumin, urine creatinine, urine protein, retinol binding protein, and beta-2 microglobulin
i
Women of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.  
j
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN). At Day 1, 
Weeks 24, and 48 and every 24 weeks during the post Week 48 period, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of the 
chemistry profile. TSH will be collected at Screening, Day 1, Weeks 24, and 48, as well as every 24 weeks post Week 48, and ESDD if applicable. 
k
Fasting glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the subject must 
return within 72 hours in a fasted state to draw blood for the metabolic assessments.
l
CBC with differential and platelet count.
m
If the HIV-1 RNA value is ≥ 50 copies/mL at Week 48, a retest HIV-1 RNA value must be collected within two to three weeks of the initial test.
n
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb). 
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex HBeAb), and quantitative HBsAg. If positive HBcAb with negative HBsAg and negative 
HBsAb, reflex testing for plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to be negative, reflex HBeAb.
o
For subjects who meet the definition of HBV infection, the following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) and HBeAg 
(if negative, reflex HBeAb) at Days 1, 12, 24 and then every 24 weeks.
p
Subjects who are HCVAb positive will have a HCV RNA test performed at screening and every 24 weeks.
q
HIV-1 genotype/phenotype testing for subjects with HIV-1 RNA ≥ 200 copies/mL and virologic rebound, at early study drug discontinuation or Week 48. Following 
unconfirmed virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to the next scheduled visit or at the next scheduled study visit, for a 
HIV-1 RNA and HIV-1 genotype/phenotype (reverse transcriptase, protease and integrase) blood draw. Based on the results of this testing, subjects should be managed 
according to the Virologic Rebound Schema (Section 6.13.1).
r
All subjects on GS-9883/F/TAF (Treatment Group 1 only) will have a single anytime PK blood sample collected at Weeks 8, 24 and 36. 
s
Subjects on GS-9883/F/TAF (Treatment Group 1 only) will have a Trough PK blood sample collected between 20-28 hours following their last dose at Weeks 4 and 12. 
Subjects must be instructed to not take their study drugs on the morning of their visit for the trough sample collection. If the subject has taken their dose of study drugs prior 
to the visit, the visit may proceed, but the subject must return within 72 hours for the single trough PK blood sample collection. In the event a subject routinely takes their 
study drug in the evening, a single anytime sample may be drawn at Weeks 4 and 12 as the subject will not be instructed to change their dosing time to accommodate this 
trough PK draw. A post-dose PK blood sample will be collected between 1 and 4 hours post dose following an observed, in-clinic dose.
 
u
A dosing diary will be dispensed for all Treatment Group 1 subjects to complete prior to each of the PK sample visits.
v
Open-label GS-9883/F/TAF FDC will be dispensed to subjects participating in the study post Week 48 starting at the Week 48 Visit.
w
Every 24 weeks only.
x
Dosing diaries will be collected from subjects for the single anytime PK and trough PK collection (Treatment Group 1 only). If a dosing diary is not returned the site may ask 
the subject for the time of the last dose and if it was taken with or without food.
CCII 


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Appendix 2.
TFL Mocks
Appendix Table 1.
Subject Disposition (All Randomized Subjects)
B/F/TAF
SBR
All B/F/TAF
Subjects Randomized
xx
xx
xx
Subjects Randomized and Never Treated
xx
xx
xx
Subjects Randomized and Treated in the Randomized Phase
xx
xx
xx
Subjects Prematurely Discontinuing Study Drug in the 
Randomized Phase
xx 
xx 
xx 
Subjects Completed the Randomized Phase but not Entered 
into the Extension Phase
xx
xx
xx
Subjects Entering the Extension Phase and B/F/TAF Treated
xx 
xx 
xx 
Subjects Receiving B/F/TAF in the Randomized or Extension 
Phase (All B/F/TAF Analysis Set)
xx
xx
xx
Subjects Completing B/F/TAF
xx (xx%)
xx (xx%)
xx (xx%)
Subjects Prematurely Discontinuing B/F/TAF
xx (xx%)
xx (xx%)
xx (xx%)
Reasons for Prematurely Discontinuing B/F/TAF
    Adverse Event
xx (xx%)
xx (xx%)
xx (xx%)
    …
…
…
…
Subjects Completing Study
xx (xx%)
xx (xx%)
xx (xx%)
Subjects Prematurely Discontinuing from Study
x (x.x%)
x (x.x%)
x (x.x%)
Reasons for Prematurely Discontinuing from Study 
    Adverse Event
x (x.x%)
x (x.x%)
x (x.x%)
    …
…
…
…
The denominator for percentages for each category is the number of subjects in the All B/F/TAF Analysis Set.
Appendix Table 2.
Summary of Laboratory Test (unit) by Visit
All B/F/TAF Analysis Set
B/F/TAF
(N=xxx)
SBR to B/F/TAF
(N=xxx)
All B/F/TAF
(N=xxx)
N
Mean
SD
Q1
Median
Q3
N
Mean
SD
Q1
Median
Q3
…
Baseline
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
…
Week x 
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
…
…
…
…
…
…
…
…
…
…
…
…
…
…
…
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
…
Change 
from 
Baseline 
at Week
x 
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
…
…
…
…
…
…
…
…
…
…
…
…
…
…
Note to programmer: the parameters include N, Mean, SD, Q1, Median and Q3 for each treatment group. If space is available, 
min and max will also be included. The format of the last column “All B/F/TAF” is the same as the other 2 columns.


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Appendix 3.
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 21.1 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 4.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT included in the 
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA 21.1 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 5.
Programming Specification
1) For subjects who were randomized to SBR and permanently discontinued study drug in the 
randomized phase (subjects who were in the All Randomized Analysis Set but not in the All 
B/F/TAF Analysis Set), since the analysis will not include these subjects (except the 
disposition table and data listings), any derived variables for these subjects that will be used 
in the disposition table and data listings are defined as follows:
a) Subjects in the All 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).
b) Study Day 1 (Randomized Phase) is defined as the day when the first dose of the 
randomized study drug (ie, SBR) was taken, as recorded on the “Randomized Phase” 
Study Drug Administration eCRF.
c) Last Dose Date (Randomized Phase) is defined as the latest of the randomized study 
drug end dates recorded on the “Randomized Phase” Study Drug Administration eCRF 
with “Permanently withdrawn” box checked for subjects who prematurely discontinued 
or completed the randomized study drug in the “Randomized Phase” according to the 
Study Drug Completion eCRF.
d) Last Study Date is the latest of the study drug (SBR) 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 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.
2) 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 of B/F/TAF for subjects in the All B/F/TAF Analysis Set and first 
dose date of SBR or randomization date if never dosed for other subjects in the All 
Randomized Analysis Set),
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.


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3) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.
4) Body mass index (BMI) and Body Surface Area (BSA)
BMI and BSA will be calculated as follows:

BMI = (weight [kg])/ (height [meters]
2)

BSA (m2) = SQRT( [Height(cm) x Weight(kg) ]/ 3600 )
All B/F/TAF baseline height and weight of the study will be used for this calculation.
5) Last Dose Date of B/F/TAF and Last Study Date
Last Dose Date in ADSL was defined in Section 3.8.1.
For subjects with a partial last dosing date of B/F/TAF (ie, month and year of last dose are 
known), the minimum of {(death date, if available), (the latest of the dispensing dates of 
B/F/TAF bottles, B/F/TAF start dates and end dates (based on EX dataset), 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.
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 dates is partially missing (ie, only year and month are 
known), the day will be imputed as 15 for the purpose of this analysis.
6) Treatment Group Presented in the Listings
In data listings, the treatment group will be presented as follows:
B/F/TAF: subjects who were randomized into B/F/TAF group in the randomized phase, 
either entered into the extension phase or not;
SBR: subjects who were randomized into SBR group in the randomized phase and did not 
enter into the extension phase of B/F/TAF;
SBR to B/F/TAF: subjects who were randomized into SBR group in the randomized phase 
and entered into the extension phase of B/F/TAF.


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7) Toxicity Grades:
i)
For toxicity grade summaries, include all postbaseline graded results up to 30 days after 
the last dose of B/F/TAF, not just those used in by-visit summaries.
ii) 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 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.
8) 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)


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Battery
Lab Test Label 
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label Used in t-labtox Table
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)
Uric Acid
Decrease
Uric Acid (Hypouricemia)
Prothrombin Intl. 
Normalized Ratio (INR)
Increase
N/A
Prothrombin Time (PT)
Increase
N/A
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
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.


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9) Renal related laboratory evaluation
a) Unit conversion for renal safety tests derived from related tests with conventional units
i)
Urine RBP (ug/L) to creatinine (mg/dL) ratio: 1 (ug/L) / (mg/dL) = 100 x ug/g
ii) Urine Beta-2-microglobulin (mg/L) to creatinine (mg/dL) ratio: 1 (mg/L) / (mg/dL) 
= 105 ug/g
iii) Urine Albumin (mg/dL) to creatinine (mg/dL) ratio: 1 (mg/dL) / (mg/dL) 
= 1000 x 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).
Is Post-BL Urine 
Is BL Urine 
Is Post-BL Urine 
Is BL 
rine 
How to Determine Treatment-
RBC (Quant.) 
RBC (Quant.) 
Bloocl (Dipstick) Blood (Dipstick) 
Emergent Toxicity for "Urine RBC 
Result 
Result 
Result 
Result 
(Hematuria, Quantitative or 
Availab~e? 
Available? 
Available? 
Available? 
Dipstick)" 
Yes 
Yes 
-
-
Compare post-BL Urine RBC (Quant.) 
toxicity grade to BL U1ine 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 U1ine 
Blood (Dipstick) toxicity grade. If 
post-BL toxicity is greater than BL 
toxicity. then treatment-emergent 
No 
-
Yes 
0 
Treatment-emergent. Use post-BL 
Urine Blood (Dipstick) toxicity grade. 
No 
-
0 
-
Do not count subject in the 
denominator for "U1ine RBC 
(Hemaniria, 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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10) 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.
11) Puerto Rico was combined with the United States when we evaluate the treatment effect 
across countries.
12) 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 most of the LDL tests were from the 2nd generation, 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_Final_GS-US-380-1961_V1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
22-Dec-2018
00:00:48
Clinical Research eSigned 22-Dec-2018
00:47:59
PPD
PPD-

Prot_002.pdf: 
(fJ GILEAiJ 
CLINICAL STUDY PROTOCOL 
Study Title: 
A Phase 3, Randomized, Open Label Study to Evaluate the 
Safety and Efficacy of Switching to a Fixed Dose Combination 
(FDC) of GS-9883/Emtricitabine/Tenofovir Alafenamide 
(GS-9883/F IT AF) from Elvitegravir/Cobicistat/Emtricitabine/ 
Tenofovir Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/ 
Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) or 
Atazanavir + Ritonavir + Emtricitabine/T enofovir Disoproxil 
Fumarate (ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV -1 Infected Women 
Sponsor: 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
IND Number: 
125589 
EudraCT Number: 
Not Applicable 
Clinical Trials.gov Identifier: 
NCT02652624 
Indication: 
HIV -1 Infection 
Protocol ID: 
GS-US-380-1961 
Gilead Clinical Program 
Manager: 
Gilead Medical Monitor: 
Protocol Version/Date: 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Mobile: 
Original: 
Amendment 1: 
Amendment 2: 
PPD 
PPD 
PPD 
Huyen Cao, MD 
P-D 
PPD 
PPD 
20 November 2015 
30 June 2016 (withdrawn) 
10 November 2016 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this document, particularly 1mpublished 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 infonnation is only to be used 
by you in collllection with authorized clinical studies of the investigational drug described in the 
protocol. You will not disclose any of the inf01m ation to others without written authorization 
from Gilead Sciences, Inc., except to the extent necessruy to obtain inf01m ed consent from those 
persons to whom the dmg may be administered. 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 2
10 November 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....................................................................11
1.
INTRODUCTION ..............................................................................................................................................14
1.1.
Background ............................................................................................................................................14
1.2.
GS-9883 .................................................................................................................................................15
1.2.1.
General Information .............................................................................................................15
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................15
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................17
1.3.
Information About Emtricitabine (Emtriva®, FTC) ...............................................................................26
1.4.
Information About Tenofovir Alafenamide (TAF, GS-7340)................................................................26
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide 
(FTC/TAF)...........................................................................................................................26
1.4.2.
Clinical Trials of FTC/TAF as Part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF).........................................................................................................................28
1.5.
Information About GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) .......................30
1.5.1.
GS-US-141-1233: Relative Bioavailability of GS-9883, FTC, and TAF 
Between GS-9883/F/TAF and GS-9883 + F/TAF ...............................................................30
1.6.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)...................................................................................31
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®) ..................................................31
1.8.
Ritonavir (RTV, /r, Norvir®)..................................................................................................................31
1.9.
Atazanavir (ATV, Reyataz®)..................................................................................................................31
1.10.
Rationale for This Study ........................................................................................................................32
1.11.
Risk/Benefit Assessment for the Study..................................................................................................32
1.12.
Rationale for Dose Selection..................................................................................................................33
1.13.
Compliance ............................................................................................................................................35
2.
OBJECTIVES.....................................................................................................................................................36
3.
STUDY DESIGN................................................................................................................................................37
3.1.
Endpoints ...............................................................................................................................................37
3.2.
Study Design..........................................................................................................................................37
3.3.
Study Treatments ...................................................................................................................................37
3.4.
Duration of Treatment............................................................................................................................38
3.5.
Biomarker Testing..................................................................................................................................38
3.5.1.
Biomarker Samples for Optional Future Research...............................................................38
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................43
5.1.
Randomization .......................................................................................................................................43
5.2.
Description and Handling.......................................................................................................................43


GS-9883/F/TAF
Protocol GS-US-380-1961
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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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5.2.1.
Formulation..........................................................................................................................43
5.2.2.
Packaging and Labeling .......................................................................................................45
5.2.3.
Storage and Handling...........................................................................................................46
5.3.
Dosage and Administration of GS-9883/F/TAF, E/C/F/TAF, E/C/F/TDF and 
ATV+RTV+FTC/TDF...........................................................................................................................46
5.4.
Prior and Concomitant Medications.......................................................................................................46
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................48
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................48
6.
STUDY PROCEDURES ....................................................................................................................................49
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................49
6.2.
Pretreatment Assessments......................................................................................................................49
6.2.1.
Screening Visit .....................................................................................................................49
6.2.2.
Day 1 Assessments...............................................................................................................51
6.3.
Randomization .......................................................................................................................................53
6.4.
Treatment Assessments (Weeks 4-48) ...................................................................................................53
6.5.
Treatment Assessments (Post Week 48) ................................................................................................55
6.5.1.
Post Week 48 Assessments ..................................................................................................55
6.6.
Post-Treatment Assessments..................................................................................................................57
6.6.1.
Early Study Drugs Discontinuation (ESDD) Assessments...................................................57
6.6.2.
30 Day Follow Up................................................................................................................59
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................60
6.8.
Other Evaluations...................................................................................................................................60
6.8.1.
Markers of Renal Tubular Function .....................................................................................60
6.9.
Blood and Urine Storage........................................................................................................................61
6.10.
Assessments for Premature Discontinuation from Study.......................................................................61
6.11.
End of Study...........................................................................................................................................61
6.12.
Post Study Care......................................................................................................................................61
6.13.
Virologic Failure....................................................................................................................................61
6.13.1.
Management of Virologic Rebound .....................................................................................61
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation or 
Week 48 ...............................................................................................................................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 Potential Hepatobiliary Toxicity ................................................................69
7.5.5.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................70


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Amendment 2
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7.5.6.
Management of Hyperbilirubinemia ....................................................................................71
7.5.7.
On-Treatment Hepatitis C Management...............................................................................72
7.5.8.
Management of Potential Nephrotoxicity.............................................................................72
7.6.
Special Situations Reports......................................................................................................................72
7.6.1.
Definitions of Special Situations..........................................................................................72
7.6.2.
Instructions for Reporting Special Situations.......................................................................73
8.
STATISTICAL CONSIDERATIONS................................................................................................................75
8.1.
Analysis Objectives and Endpoints........................................................................................................75
8.1.1.
Analysis Objectives..............................................................................................................75
8.1.2.
Primary Endpoint .................................................................................................................75
8.1.3.
Secondary Endpoint .............................................................................................................75
8.2.
Analysis Conventions.............................................................................................................................75
8.2.1.
Analysis Sets ........................................................................................................................75
8.3.
Data Handling Conventions ...................................................................................................................76
8.4.
Demographic Data and Baseline Characteristics ...................................................................................77
8.5.
Efficacy Analysis ...................................................................................................................................77
8.5.1.
Primary Analysis..................................................................................................................77
8.5.2.
Secondary Analyses .............................................................................................................78
8.6.
Safety Analysis.......................................................................................................................................79
8.6.1.
Extent of Exposure...............................................................................................................79
8.6.2.
Adverse Events.....................................................................................................................79
8.6.3.
Laboratory Evaluations ........................................................................................................80
8.6.4.
Other Safety Evaluations......................................................................................................80
8.7.
Pharmacokinetic Analysis......................................................................................................................80
8.8.
Sample Size............................................................................................................................................80
8.9.
Independent Data Monitoring Committee..............................................................................................80
8.10.
Analysis Schedule ..................................................................................................................................81
9.
RESPONSIBILITIES..........................................................................................................................................82
9.1.
Investigator Responsibilities ..................................................................................................................82
9.1.1.
Good Clinical Practice..........................................................................................................82
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................82
9.1.3.
Informed Consent.................................................................................................................82
9.1.4.
Confidentiality......................................................................................................................83
9.1.5.
Study Files and Retention of Records ..................................................................................83
9.1.6.
Case Report Forms...............................................................................................................84
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................85
9.1.8.
Inspections............................................................................................................................85
9.1.9.
Protocol Compliance............................................................................................................85
9.2.
Sponsor Responsibilities ........................................................................................................................85
9.2.1.
Protocol Modifications.........................................................................................................85
9.2.2.
Study Report and Publications .............................................................................................86
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................86
9.3.1.
Payment Reporting...............................................................................................................86
9.3.2.
Access to Information for Monitoring..................................................................................86
9.3.3.
Access to Information for Auditing or Inspections ..............................................................87
9.3.4.
Study Discontinuation..........................................................................................................87
10.
REFERENCES ...................................................................................................................................................88


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 5
10 November 2016
11.
APPENDICES ....................................................................................................................................................89
Appendix 1.
Investigator Signature Page....................................................................................................90
Appendix 2.
Study Procedures Table..........................................................................................................91
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) ...........................118
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) ...........19
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................20
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................21
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)........................................................................................22
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.................................................................................................34
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)..........................................47
Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens) .........................................................................................47
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................22
Figure 3-1.
Study Schema.........................................................................................................................38
Figure 6-1.
Virologic Rebound Schema....................................................................................................63


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Amendment 2
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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety 
and Efficacy of Switching to a Fixed Dose Combination (FDC) of
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) 
from Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir
Disoproxil Fumarate (E/C/F/TDF) or Atazanavir + Ritonavir + 
Emtricitabine/Tenofovir Disoproxil Fumarate 
(ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV-1 Infected Women
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
Not Applicable
NCT02652624
Study Centers Planned:
Approximately 30 centers in North America
Approximately 2 centers in Dominican Republic
Approximately 6 centers in Thailand
Approximately 20 centers in Russia
Approximately 1 center in Uganda
Objectives:
The primary objective of this study is:

To evaluate the efficacy of switching to an FDC of 
GS-9883/F/TAF versus continuing on a regimen consisting of 
E/C/F/TAF, E/C/F/TDF or ATV+RTV+FTC/TDF in 
virologically suppressed HIV-1 infected women as determined 
by the proportion of subjects with HIV-1 RNA ≥50 copies/mL 
at Week 48
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups 
through Week 48


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Amendment 2
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Study Design:
Randomized, open label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to an FDC of 
GS-9883/F/TAF in HIV-1 infected women who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting 
of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF for 
≥12 consecutive weeks prior to screening. 
All subjects will be HIV-1 infected women drawn from pre-defined 
Gilead clinical studies and must be virologically suppressed. 
Women in Gilead study GS-US-236-0128 who completed the 
Week 48 open-label extension (OLE) visit or any post Week 48 
OLE visits, women in study GS-US-292-0109 who completed the 
Week 96 visit or any post Week 96 visits, or women in studies 
GS-US-292-0104 or GS-US-292-0111 who completed the 
Week 144 visit or any post Week 144 visits may be eligible to 
enroll. 
Subjects who provide written consent and meet all eligibility 
criteria will be randomized in a 1:1 ratio to receive open label 
medication as follows: 

Treatment Group 1: FDC of GS-9883 50 mg/
emtricitabine 200 mg/tenofovir alafenamide 25 mg 
(GS-9883/F/TAF) administered orally, once daily, without 
regard to food (approximately n = 235) 

Treatment Group 2: Stay on baseline regimen (SBR), 
including E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF
administered orally, once daily, with food (approximately 
n = 235) 
Randomization will be stratified by the prior treatment regimen 
group (ie, E/C/F/TAF, E/C/F/TDF and ATV+RTV+FTC/TDF).
Number of Subjects 
Planned:
Approximately 470 subjects total
Approximately 235 subjects each in Treatment Group 1 and 
Treatment Group 2 
Target Population:
HIV-1 infected women who are virologically suppressed 
(HIV-1 RNA < 50 copies/mL) on a stable regimen of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥12 weeks prior to 
screening
Duration of Treatment:
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, 
subjects in a country where GS-9883/F/TAF FDC is not available 
will be given the option to receive GS-9883/F/TAF FDC for an 
additional 48 weeks, or until the product becomes accessible to 
subjects through an access program, or until Gilead Sciences elects 
to discontinue the study in that country, whichever occurs first.


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Amendment 2
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Subjects who complete the study through the Week 48 Visit and 
do not continue participation in the study will be required to return 
to the clinic 30 days after the Week 48 Visit for a 30 Day 
Follow-Up Visit.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected women who meet the following 
criteria:

Currently on a stable antiretroviral regimen consisting of 
E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF continuously 
for ≥12 consecutive weeks preceding the screening visit

Documented plasma HIV-1 RNA levels < 50 copies/mL for 
≥12 weeks preceding the Screening visit. After reaching 
HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by re-suppression to < 50 copies/mL 
is allowed

HIV-1 RNA <50 copies/mL at screening

Estimated glomerular filtration rate (eGFR) ≥50 mL/min 
according to the Cockcroft-Gault (C-G) formula at the 
screening visit
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 
48 weeks. Following the Screening and Day 1 visits, subjects will 
return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
until the Week 48 visit. 
For all eligible subjects, blood and urine will be collected at Day 1, 
Weeks 4, 8, 12, and then every 12 weeks through the Week 48 visit. 
Laboratory analyses (including hematology, chemistry, 
and urinalysis), HIV-1 RNA, CD4+ cell count, and complete or 
symptom directed physical examinations will be performed at the 
Screening, Day 1, and all subsequent study visits. 
Adverse events and concomitant medications will be assessed at 
each visit.
Test Product, Dose, and 
Mode of Administration:
FDC of GS-9883 50 mg/emtricitabine 200 mg/
tenofovir alafenamide 25 mg (GS-9883/F/TAF) administered 
orally, once daily, without regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Current antiretroviral drug regimen consisting of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF administered orally,
once daily, with food.


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Criteria for Evaluation:
Safety:
Adverse events and clinical laboratory tests to evaluate the safety 
and tolerability of the treatment regimens.  
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as determined by the United States (US) Food and 
Drug Administration (FDA)-defined snapshot algorithm.
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as determined by the US FDA-defined snapshot 
algorithm

The change from baseline in CD4+ cell count at Week 48
Pharmacokinetics:
For all subjects on GS-9883/F/TAF (Treatment Group 1), a single 
anytime pre or post-dose PK blood sample will be collected at 
Weeks 8, 24, and 36. 
For all subjects on GS-9883/F/TAF (Treatment Group 1), a trough 
PK blood sample will be obtained 20-28 hours following the last 
dose at Weeks 4 and 12. Following an observed dose, one PK blood 
sample will be collected between 1 and 4 hours post-dose. 
The concentration of GS-9883 may be summarized using 
descriptive statistics. 
Statistical Methods:
The primary analysis will consist of a non-inferiority test of 
switching to GS-9883/F/TAF FDC versus SBR with respect to the 
proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 
as determined by the US FDA-defined snapshot algorithm. It will be 
concluded that GS-9883/F/TAF is non-inferior to SBR if the upper 
bound of the 2-sided 95% confidence interval (CI) of the difference 
between treatment groups (GS-9883/F/TAF – SBR) in the 
proportion of subjects with HIV-1 RNA ≥50 copies/mL is less than 
4%; ie, a margin of 4% is applied to non-inferiority assessment. The 
2-sided 95% CIs will be constructed based on the exact method.
The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as determined 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. 


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Amendment 2
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The change from baseline in CD4+ cell count at Week 48 will be 
summarized by treatment using descriptive statistics. The 
differences and the associated 95% CIs will be constructed using 
Analysis of Variance (ANOVA) model, including treatment 
(GS-9883/F/TAF vs. SBR) as a fixed effect in the model. 
Adverse events and clinical laboratory assessments will be
summarized using descriptive statistics.
A total of approximately 470 HIV-1 infected women, randomized 
in a 1:1 ratio to 2 treatment groups (approximately 235 subjects per 
treatment group), achieves at least 87% power to detect a 
non-inferiority margin of 4% difference in the percentage of 
subjects with HIV-1 RNA ≥50 copies/mL at Week 48 between the 
2 treatment groups. 
For sample size and power computation, it is assumed that both 
treatment groups have 2% of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 (based on the historical Gilead
Genvoya®(GEN) and Stribild® (STB) studies), that a non-inferiority 
margin is 4%, and that the significance level of the test is at a 
one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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Amendment 2
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq®
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir, Reyataz®
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration versus 
time curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, C, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
DTG
dolutegravir, Tivicay®
EC50
50% effective inhibitory concentration
ECG
electrocardiogram
eCRF
electronic case report form(s)
EVG, E
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, Genvoya®
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild®
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination


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FSH
follicle-stimulating hormone
FTC, F
emtricitabine, Emtriva®
FTC/TAF 
emtricitabine/tenofovir alafenamide, Descovy®
FTC/TDF
emtricitabine/tenofovir disoproxil fumarate, Truvada®
GCP
Good Clinical Practice (Guidelines)
GGT
gamma glutamyl transferase
GSI
Gilead Sciences, Inc.
GS-9883/F/TAF
GS-9883/emtricitabine/tenofovir alafenamide
HAART
highly active antiretroviral therapy
HBV
hepatitis B virus
HBcAb
hepatitis B core antibody
HBeAb
hepatitis Be antibody
HBeAg
hepatitis Be antigen
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDPE
high-density polyethylene
hERG
human Ether-à-go-go-Related Gene
HIV
Human Immunodeficiency Virus
HIV Sx
HIV Symptoms Distress Module
HLA
human leukocyte antigen
IB
investigator’s brochure
IC50
50% maximal inhibitory concentration
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
institutional ethics committee
IND
Investigational New Drug (Application)
INSTI
integrase strand-transfer inhibitors
IRB
institutional review board
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LDH
lactate dehydrogenase
LLN
lower limit of the normal range
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
MH
Mantel-Haenszel
min
minute
mmHg
millimeters mercury
MT4
human t cell leukemia cell line
nM
nanoMolar


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NNRTI
non-nucleoside reverse transcriptase inhibitor
NOAEL
no observed adverse effect level
NOEL
no observed effect level
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
OCT2
organic cation transporter 2
PI
protease inhibitor
PK
pharmacokinetic
PT
preferred term 
PT
prothrombin time 
QD
once daily 
RAL
raltegravir
RNA
ribonucleic acid
RTV
ritonavir, Norvir®
SAE
serious adverse event
STB
Stribild®, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
STR
single tablet regimen
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide, GS-7340
TDF
tenofovir disoproxil fumarate, Viread®
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase 
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {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 et al 1998, 
Palella 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 {Aldir et al 2013, Sterrantino et al 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 half maximal inhibitory concentration (IC50)values ranging from 1.5 to 2.4 nM, 
similar to the inhibitory effect of DTG and EVG. GS-9883 is highly potent against HIV 
replication in the human T cell leukemia MT4 cell line with an EC50 (50% effective inhibitory 
concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. GS-9883 does not 
show significant cytotoxicity against dividing and non-dividing human PBMCs, primary human 
hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 μM. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter organic cation transporter 2 (OCT2)
(IC50 = 0.42 μM). As a result, GS-9883 is not expected to significantly interfere with the key 


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


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


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Protocol GS-US-380-1961
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Gilead Sciences, Inc.
Amendment 2
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
GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)

GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled 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 1 Randomized, Open Label, Drug Interaction Study Evaluating 
the Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (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.


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
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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.
Increases in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2. In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort. In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF. All 
changes returned to baseline after discontinuation of GS-9883.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood. All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.
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)


GS-9883/F/TAF
Protocol GS-US-380-1961
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Amendment 2
CONFIDENTIAL
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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, which is 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.


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
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Amendment 2
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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.


GS-9883/F/T AF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Final 
Amendment 2 
Based on PK infonnation collected in study GS-US-141-1219, which was in line with PK 
obse1ved in study GS-US-141-1218, the median IQ for each dose were calculated and aTe 
presented in the table below. 
Table 1-4. 
GS-9883 Dose 
5 mg 
25 mg 
50mg 
100 mg 
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) 
N 
Median (range) C1au,SS (ng/mL) 
Median (mnge) paiQ95• 
4 
206.5 (146.0 to 342.0) 
1.3 (0.9 to 2.1) 
4 
797.5 (714.0 to 1900.0) 
4.9 (4.4 to 11.7) 
4 
2170.0 (852.0 to 3020.0) 
13.4 (5.3 to 18.6) 
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 vitro 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 Figme 1-1. 
Figure 1-1. 
::; 2 
~ 
.~ 8 
0 c;, 
g 
0 
<( 
z 
a:: 
-1 
~ 
:z:: 
.£ 
-2 
., 
c 
~ 
d1! 
-3 
g 
., -4 
g> ., 
.t::. 
(.) 
-5 
GS-9883 5 mg (n=): 
GS-9883 25 mg (n=): 
GS-9883 50 mg (n=): 
GS-9883100 rrg (n=): 
Placebo(n=t. 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
f 
------
• 
= GS-9883 5 mg 
0 = GS-9883 25 mg 
b. = GS-9883 50 mg 
D = GS-9883100 mg 
0 = Placebo 
BL 
2 
3 
4 
7 
8 
9 
10 
11 
14 
17 
Day 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
4 
3 
4 
3 
4 
4 
4 
4 
4 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
NOTE: Baseline value was the last available value collected prior to the tin1e of the ftrst dose of study drug. 
2 
0 
-1 
-2 
-3 
-4 
-5 
CONFIDENTIAL 
Page22 
10 November 2016 


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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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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
Week 24 interim data are summarized below. 
1.2.3.4.
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24
data analysis, 2 subjects (2.0%) had prematurely discontinued study treatment, one in each 
treatment group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and estimated glomerular 
filtration rate [eGFR] using the Cockcroft-Gault method [eGFRCG]) were similar between the 
2 treatment groups.
Median (Q1, Q3) baseline HIV-1 RNA was 4.45 (3.96, 4.79) log10 copies/mL, with 
82.7% of subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had > 400,000 copies/mL 
at baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 1 subject was 
randomized to DTG+F/TAF.

Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 
41.8% of subjects having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 
125.3 (105.7, 147.0) mL/min.


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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1.2.3.5.
Efficacy Results
Virologic success at Week 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 was considered a virologic failure by US FDA-defined
snapshot algorithm with 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 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 at 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.
1.2.3.6.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 58.5%, 38 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common TEAEs (occurring in > 1 subject) by treatment group were as follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE, and 1 other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator, resulted in study 
drug discontinuation, or required interruption of study drug, and both SAEs resolved.
The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 25
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6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883/F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs that were considered related to study 
drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation 
were reported in either treatment group.
Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least
1 grade level increase from baseline in graded abnormality) was similar between treatment groups 
as follows: GS-9883+F/TAF 76.6%, 49 subjects; DTG+F/TAF 78.1%, 25 subjects. The majority 
of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The percentage of 
subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality was similar 
between treatment groups as follows: GS-9883+F/TAF 17.2%, 11 subjects; DTG+F/TAF 12.5%, 
4 subjects. Grade 3 or 4 treatment-emergent laboratory abnormalities occurring in at least 
2 subjects in either treatment group were as follows: creatine kinase (GS-9883+F/TAF, 3.1% 
[2 subjects]), and fasting low-density lipoprotein (LDL) (GS-9883+F/TAF, 3.1% [2 subjects]). 
The only Grade 4 laboratory abnormalities were for creatine kinase, reported in 2 subjects (3.1%) 
in the GS-9883+F/TAF group. All increased creatine kinase values appeared to be transient, and 
none were associated with AEs. Of the 2 subjects with increased AST, 1 subject had Grade 3 AST 
and Grade 3 ALT at Week 24 in the setting of alcohol abuse; the other subject had Grade 3 AST 
at Week 8 that returned to normal by Week 24.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. There were 
similar increases from baseline in median (Q1, Q3) serum creatinine in both treatment groups at 
Week 24: GS-9883+F/TAF 0.12 (0.06, 0.18) mg/dL; DTG+F/TAF 0.13 (0.05, 0.21) mg/dL. 
There were decreases in median (Q1, Q3) eGFRCG at Week 24, which were smaller in the 
GS-9883+F/TAF compared with the DTG+F/TAF group: GS-9883+F/TAF 
−13.3 (−19.9, −4.0) mL/min; DTG+F/TAF −17.2 (−25.7, −6.9) mL/min.
Conclusions
Key Week 24 conclusions from Study GS-US-141-1475 include the following:

Virologic success at Week 24 when assessed using the 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 Food and Drug Administration (FDA) for marketing 
on 2 July 2003 and is available under the name Emtriva®. In the European Union (EU), marketing 
authorization was granted for both the 200 mg Emtriva® capsule formulation and a 10 mg/mL 
Emtriva® oral Solution formulation on 24 October 2003, with indications for the treatment of HIV 
infection concurrently with other antiretroviral drugs in both adult and pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information About Tenofovir Alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) or 
Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide (FTC/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected subjects (completed)


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
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)

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 single tablet 
regimen (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)


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
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 P-gp-mediated intestinal 
secretion of TAF by COBI.
Study GS-US-292-0103 is a completed Phase 1 healthy volunteer study which evaluated the PK 
and relative bioavailability of the E/C/F/TAF STR relative to the individual components at TAF 
doses of 10 (STR) or 25 mg SA. Results indicate that when dosed as the E/C/F/TAF 10 mg STR, 
TAF and TFV exposures were comparable to those observed with TAF 25 mg dosed alone. 
Exposures of EVG, COBI, and FTC were also comparable between the STR and individually 
dosed formulations. 
Study GS-US-292-0102 is an ongoing, randomized, active-controlled Phase 2 study, compares 
E/C/F/TAF (10 mg) versus Stribild® (STB, E/C/F/TDF) in treatment-naïve, HIV-1 infected 
subjects. At Week 48, the E/C/F/TAF demonstrated potent antiviral efficacy 
(HIV-1 RNA < 50 copies/mL) similar to STB (88.4% [99/112] vs 87.9% [51/58] using the 
snapshot algorithm); in the E/C/F/TAF group, no patient had emergent resistance to 
1 or more components of the E/C/F/TAF. Importantly, E/C/F/TAF demonstrated a potential 
benefit over E/C/F/TDF in terms of renal and bone safety: smaller median decreases in eGFR 
(mL/min) (at Week 48, E/C/F/TAF −5.5 vs E/C/F/TDF −10.0 [P < 0.001) and smaller median 
percentage decreases in BMD (at Week 48, spine E/C/F/TAF −1.00 vs E/C/F/TDF 
−3.37 [p < 0.001], hip −0.62 vs −2.39 [p < 0.001]).
Studies GS-US-292-0104 and GS-US-292-0111 are ongoing, Phase 3 randomized, 
double-blinded studies of the safety and efficacy of E/C/F/TAF versus E/C/F/TDF in HIV-1 
infected, antiretroviral treatment-naive adults. The interim Week 48 key conclusions from pooled 


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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: Relative Bioavailability of GS-9883, FTC, and TAF 
Between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is a 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. 
Cohort 1 Results:
Pharmacokinetic Results
Under fasted conditions, GS-9883 AUCinf and Cmax were 27% and 31% higher, respectively, 
following GS-9883/F/TAF (75/200/25 mg) FDC administration than following administration of 
single-agent GS-9883 (75 mg) with the F/TAF (200/25 mg) FDC. FTC and TAF exposure was 
similar following administration of GS-9883/F/TAF (75/200/25 mg) or single-agent GS-9883 
(75 mg) with the F/TAF (200/25 mg) FDC. Compared with administration under fasted 
conditions, administration of the GS-9883/F/TAF (75/200/25 mg) FDC with a high-fat meal 
resulted in a 46% higher GS-9883 AUCinf and a 27% higher GS-9883 Cmax. The impact of food 
on TAF and FTC exposure was similar to that previously observed for F/TAF 
(Study GS-US-311-1386). GS-9883/F/TAF may be taken without regard to food. Based on these 
results, Cohort 2 was added to the study via protocol amendment to evaluate the relative BA of 
the GS-9883/F/TAF (50/200/25 mg) FDC tablet compared with the single-agent GS-9883 
(75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered simultaneously.


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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 GS-9883/F/TAF (50/200/25 mg) 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 
50/200/25 mg and 75/200/25 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 in the 50/200/25 mg FDC with AUCinf increasing by 24%. The steady state 
paIQ95 of GS-9883/F/TAF (50/200/25 mg) following multiple doses was predicted to be 
17 (fasted)-23 (fed). The exposures of TAF and FTC following administration of the 
GS-9883/F/TAF (50/200/25 mg) FDC were similar to those of GS-9883 75 mg single agent with 
F/TAF FDC, and the food effect on TAF and FTC in the GS-9883/F/TAF (50/200/25 mg) FDC 
was similar to 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.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)
Further information is available in the US Prescribing Information and Investigator’s Brochure 
for E/C/F/TDF.
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®)
Further information is available in the Prescribing Information for Truvada®.
1.8.
Ritonavir (RTV, /r, Norvir®)
Further information is available in the Prescribing Information for Norvir®.
1.9.
Atazanavir (ATV, Reyataz®)
Further information is available in the Prescribing Information for Reyataz®.


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1.10.
Rationale for This Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 
HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.
The GS-9883/F/TAF FDC has the potential to offer a simple, once-daily regimen containing a 
second generation INSTI that provides a high barrier to resistance, does not require a boosting 
agent, and offers an effective and safer alternative to standard nucleos(t)ide based regimens, 
without the need for HLA testing or close monitoring of renal or bone toxicities. It could provide 
an FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute to an 
increased risk of cardiovascular events, could be used in patients with chronic hepatitis B or C 
infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities.Approximately 50% of the global population of HIV-infected 
persons are women, however they remain under-represented in most clinical HIV studies. In 
general, studies to date have not shown gender differences in virologic responses to antiretroviral 
therapy (ART), but a number of studies have suggested that gender may influence the frequency, 
presentation, and severity of selected ARV-related adverse events. Although data are limited, the
pharmacokinetics for some ARV drugs may differ between men and women, possibly because of 
variations in factors such as body weight, plasma volume, gastric emptying time, plasma protein 
levels, CYP450 activity, drug transporter function, and excretion activity. It is important to 
understand potential gender-specific safety and efficacy issues in women when assessing 
virologic response, tolerability, and adherence. This study will ensure that there is adequate 
safety data in HIV-1-infected women in the Phase 3 program for GS-9883/F/TAF.
The objective of this study is to evaluate the safety and efficacy of an FDC containing 
GS-9883/F/TAF versus continuing on a regimen consisting of E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF in women who are virologically suppressed. Switching to 
GS-9883/F/TAF offers the advantages of a single-tablet FDC containing the unboosted, 
next-generation INSTI, GS-9883, combined with a TAF-based nucleotide backbone.
GS-9883/F/TAF FDC which includes TAF, has the potential to offer an effective and safer 
alternative to standard nucleos(t)ide based regimens, without the need for close monitoring of 
renal or bone toxicities or increase risk of cardiovascular complications as patients age and 
confront non HIV-related comorbidities.
1.11.
Risk/Benefit Assessment for the Study
All patients with HIV-1 infection should receive effective anti-retroviral therapy. Potential risks
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and
lactic acidosis with steatosis. The risk of class effects is considered to be low. Important
identified risks appropriately managed by study inclusion/exclusion criteria as well as through


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close clinical and laboratory monitoring during the study are as follows: allergy to any 
components of the tablets. Protease inhibitors may be associated with increased lipid levels and 
gastrointestinal side effects. If patients are currently infected with hepatitis B and discontinue 
their existing or new therapy, there is a risk of severe acute exacerbations of hepatitis B. Interim 
data will also be reviewed by an independent data monitoring committee. Potential benefits of 
GS-9883/F/TAF may include provision of a new antiretroviral therapy that is not currently 
available and which may have fewer side effects than alternative therapies. Other potential 
benefits include provisions of fixed dose combination therapy, and the knowledge that patient 
participation will contribute to the body of knowledge of HIV therapies.
Following a chronic 39 week study in monkeys, animals administered the highest dose of 
GS-9883 (1000 mg/kg/day) had bile duct hyperplasia (increased cell growth) and hypertrophy 
(increased cell size), and some increased cell growth and inflammation in nearby liver cells. 
These effects were not seen in monkeys administered the mid-level dose (200 mg/kg/day), and 
these animals had plasma GS-9883 exposures that were approximately 5-fold above human 
exposures when given the GS-9883/F/TAF FDC. No adverse drug reactions associated with liver 
or bile duct problems 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 7.5.4). 
The overall benefit-risk assessment for GS-9883/F/TAF is favorable at this time.
1.12.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.


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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) 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 24 interim data from this study, support the safety and efficacy of GS-9883 exposures 
obtained with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF 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.
E/C/F/TAF
EVG/COBI/FTC/TAF (150/150/200/10 mg) is a fixed dose combination, with only one dose 
combination available; and has been approved by the United States Food and Drug 
Administration (FDA) for the treatment of human immunodeficiency virus type 1 (HIV-1) 
infection in adults and pediatric patients 12 years of age and older with no ARV treatment 
history or to replace the current ARV regimen in those who are virologically suppressed on a 
stable ARV regimen with no history of treatment failure and no known substitutions associated 
with resistance. This FDC contains the equivalent doses of EVG, COBI and FTC in the marketed 
product, Stribild® (STB).
E/C/F/TDF (STB)
EVG/COBI/FTC/TDF (150/150/200/300 mg) is a fixed dose combination, with only one dose 
combination available; and is approved for use (Stribild®) in the United States by the 
Food and Drug Administration (FDA), for the treatment of HIV-1 infection in treatment-naïve 
adults.
ATV+RTV+FTC/TDF
ATV (300 mg), RTV (100 mg) and FTC/TDF (200/300 mg) represent the current marketed 
doses of these products.
1.13.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.  


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of switching to an FDC of GS-9883/F/TAF versus continuing on a 
regimen consisting of E/C/F/TAF, E/C/F/TDF or ATV+RTV+FTC/TDF in virologically 
suppressed HIV-1 infected women as determined by the proportion of subjects with 
HIV-1 RNA ≥ 50 copies/mL at Week 48.
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups through Week 48.


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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

The proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 as determined by
the US FDA-defined snapshot algorithm. 
The secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined by 
the US FDA-defined snapshot algorithm.

The change from baseline in CD4+ cell count at Week 48. 
3.2.
Study Design
This protocol describes a randomized, open label, multicenter, active-controlled study to evaluate 
the safety and efficacy of switching to a GS-9883/F/TAF FDC in HIV-1 infected women who 
are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of 
E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥ 12 consecutive weeks prior to 
screening.
3.3.
Study Treatments
Subjects who complete the following criteria will be given the option to participate in this study:

Completion of the Week 48 OLE visit or any post Week 48 OLE visits in study
GS-US-236-0128, or

Completion of the Week 96 visit or any post Week 96 visits in study GS-US-292-0109, or

Completion of the Week 144 visit or any post Week 144 visits in studies GS-US-292-0104 or 
GS-US-292-0111
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to receive open label medication:

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food 
(approximately n = 235)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or
ATV+RTV+FTC/TDF administered orally, once daily, with food (approximately n = 235)


GS-9883/F/T AF 
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3.4. 
Duration of Treatment 
Final 
Amendment 2 
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, subjects in a colliltly where 
GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/TAF FDC 
for an additional48 weeks and attend study visits evety 12 weeks, or lllltil the product becomes 
accessible to subjects through an access program, or until Gilead Sciences elects to discontinue 
the study in that colliltty, whichever occurs first. 
Subjects who complete the study through the Week 48 Visit and do not continue post Week 48 
will be required to retum to the clinic 30 days after the Week 48 Visit for a 30 Day Follow-Up 
Visit. 
Figure 3-1. 
Screening 
~ 30 days pl'iot· 
to Day 1 
Study Schema 
Day l 
a 
Treatment Group 1: GS-9883/F/TAF FDC 
N=235 
Treatment Group 2: Stay on baseline 
regimen (E/C/F/TAF, EICIFITDF or 
ATV+RTV+FTCITDF) N=235 
b 
Wet>k48 
30 
Day 
Ftu' 
a 
Following the Day 1 visit, subjects will be required to retum for study visits at Weeks 4, 8, 12 and then every 12 weeks 
tlu·ough Week 48 
b 
Aftet· Week 48, subjects in a cmmtry where GS-9883/F!TAF FDC is not available will be given the option to receive 
GS-9883/F!TAF for an additional48 weeks, or tmtil the product becomes accessible to subjects through an access program, 
or tmtil Gilead Sciences elects to discontinue the study in that cmmtry, whichever occurs fu·st 
c 
Subjects who complete the study tlu·ough Week 48 and do not wish to receive GS-9883/F!TAF FDC will be required to 
rettun to the clinic 30 days after the completion of study dmg for a 30-day follow-up visit 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Future Research 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 470 subjects who meet the eligibility criteria will be enrolled. 
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Female, (at birth), Age ≥18 years
3) Currently on a stable antiretroviral regimen of E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF continuously for ≥12 consecutive weeks preceding the screening 
visit
4) Completion of the Week 48 OLE visit or any post Week 48 OLE visits in 
study GS-US-236-0128, completion of the Week 96 visit or any post Week 96 visits in study 
GS-US-292-0109, or completion of the Week 144 visit or any post Week 144 visits in studies 
GS-US-292-0104 or GS-US-292-0111
5) Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥ 12 weeks preceding the 
Screening Visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by resuppression to < 50 copies/mL are allowed
6) HIV-1 RNA < 50 copies/mL at screening
7) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) 
8) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥ 0.83 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft et al 1976}:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg) × 0.85
72 (serum creatinine in μmol/L) ×  0.6786
CrCL (mL/sec)
9) Hepatic transaminases (AST and ALT) ≤5 × upper limit of normal (ULN).
10) Total bilirubin 1.5 mg/dL (26 μmol/L), or normal direct bilirubin.


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11) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L)).
12) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN).
13) Women of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Women who utilize hormonal contraceptive as one of their birth control methods must 
have used the same method for at least 3 months prior to study drug dosing. 
b) Female subjects who have stopped menstruating for ≥12 months but do not have 
documentation of ovarian hormonal failure must have a serum follicle stimulating 
hormone (FSH) level at screening within the post-menopausal range based on the 
Central Laboratory reference range.
14) Have no documented or suspected resistance to FTC, TFV, ATV or EVG including, but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
2) Subjects experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or 
variceal bleeding)
3) Have been treated with immunosuppressant therapies or chemotherapeutic agents within 
3 months of study screening, or expected to receive these agents or systemic steroids 
during the study (eg, corticosteroids, immunoglobulins, and other immune- or 
cytokine-based therapies)  
4) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance  
5) A history of or ongoing malignancy (including untreated carcinoma in-situ) other than 
cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous 
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must 
not have received any systemic therapy for KS within 30 days of Day 1 and are not 
anticipated to require systemic therapy during the study


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6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1 
7) Participation in any clinical trial other than GS-US-236-0128, GS-US-292-0109, 
GS-US-292-0104, or GS-US-292-0111, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC, E/C/F/TAF, E/C/F/TDF, 
ATV, RTV, or FTC/TDF
10) Women who are pregnant (as confirmed by positive serum pregnancy test)
11) Women who are breastfeeding  
12) Subjects receiving ongoing therapy with any of the medications in Table 5-1 or Table 5-2.
Administration of any disallowed agent must be discontinued at least 30 days prior to the 
Day 1 visit and for the duration of the study
13) Acute hepatitis in the 30 days prior to study entry
14) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visit cannot occur until subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day 1 visit the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2. 

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food 
(approximately n = 235)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (approximately n = 235)
The IWRS will assign study drug bottle numbers of open label FDC of GS-9883/F/TAF, 
open label E/C/F/TAF, open label E/C/F/TDF or open label ATV+RTV+FTC/TDF at each study 
visit for each subject. 
Randomization will be stratified by the prior treatment regimen group (ie, E/C/F/TAF, E/C/F/TDF 
and ATV+RTV+FTC/TDF).
5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Tablets
GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.


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


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg
(GS-9883/F/TAF) Tablets
GS-9883/F/TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each 
bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.2.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Alafenamide 10 mg (E/C/F/TAF) Tablets
E/C/F/TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.3.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Disoproxil Fumarate 300 mg (E/C/F/TDF, Stribild®) Tablets
E/C/F/TDF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets and a silica gel desiccant with or without polyester coil fiber. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.4.
Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg 
(FTC/TDF, Truvada®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.5.
Ritonavir (RTV, Norvir®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.6.
Atazanavir (ATV, Reyataz®) Capsules
Refer to commercially available Prescribing Information.
All study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice −Annex 13 (Investigational Medicinal 
Products), and/or other local regulations.


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5.2.3.
Storage and Handling
Study drugs GS-9883/F/TAF FDC, E/C/F/TAF and E/C/F/TDF should be stored at controlled 
room temperature of 25 °C (77 °F); excursions are permitted between 15 °C and 30 °C 
(59 °F and 86 °F). Storage conditions are specified on the label. Until dispensed to the subjects, 
all bottles of study drugs should be stored in a securely locked area, accessible only to authorized 
site personnel.
Commercial product of Norvir® (RTV), Reyataz® (ATV), and Truvada® (FTC/TDF) will be used 
for the study. Further information regarding storage and handling are available in the 
Prescribing Information for commercial products.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/F/TAF, E/C/F/TAF, E/C/F/TDF and 
ATV+RTV+FTC/TDF
Study drugs GS-9883/F/TAF FDC, E/C/F/TAF, E/C/F/TDF, and ATV+RTV+FTC/TDF will be 
provided by Gilead Sciences.

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food 
(approximately n = 235)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (approximately n = 235)
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability. The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return. 
5.4.
Prior and Concomitant Medications
The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following tables and use of herbal/natural supplements are excluded or 
should be used with caution while subjects are participating in the study. Subjects will refrain 
from consumption of grapefruit juice and Seville orange juice throughout participation in the 
study. 


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Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids 
(eg, Tums or Rolaids); the ulcer medication 
sucralfate (Carafate); or vitamin or mineral 
supplements that contain calcium, iron or zinc for 
a minimum of 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 either when starting or at study entry.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study. 
Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens)
Drug Class
Agents Disallowed*
Alpha-1 Adrenoreceptor Antagonist 
Alfuzosin
Antiarrhythmic Agent 
Amiodarone, Dronedarone
Anticonvulsants 
Phenytoin, Carbamazepine and Phenytoin
Antimycobacterials 
Rifampin
Antipsychotics
Lurasidone, Pimozide
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements 
St. John’s Wort
Anticancer drugs
Irinotecana
Ergot Derivatives
Ergotamine, Ergonovine, Dihydroergotamine, Methylergonovine, Ergometrine
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Phosphodiesterase-5 Inhibitors
Sildenafil (for PAH)
Sedatives/Hypnotics 
Midazolam (PO), Triazolam
Calcium Channel Blockers 
Bepridil
Chronic angina 
Ranolazine
a
Applied to ATV regimen only
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study


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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 the study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30 days before Day 1 to determine eligibility for participation in 
the study. The screening visit may coincide with the Week 48 OLE visit or any post-Week 48
OLE visits in study GS-US-236-0128 or the Week 96 visit or any post-Week 96 visits in 
study GS-US-292-0109, or may be conducted after completion of the Week 144 visit or any post 
Week 144 visits for studies GS-US-292-0104 or GS-US-292-0111. The following will be 
performed and documented at screening: 

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events and prior 
medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis


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
Blood sample collection for the following laboratory analyses:
Serum pregnancy test (women of childbearing potential only). If the test is positive, the 
subject will not be enrolled
FSH test is required for women who have stopped menstruating for ≥12 months but do 
not have documentation of ovarian hormonal failure
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, amylase (reflex lipase 
testing is performed in subjects with total amylase > 1.5 × ULN), and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg) x 0.85
72 (serum creatinine in μmol/L) x  0.6786
CrCL (mL/sec)
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
Plasma HIV-1 RNA 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), 
Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)
The following will be conducted by the central laboratory if the following criteria are met:
■
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, 
reflex HBeAb), and quantitative HBsAg
■
If positive HBcAb with negative HBsAg and negative HBsAb, reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to 
be negative, reflex HBeAb
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed

Review of adverse events and concomitant medications


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Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30 days after screening for the Day 1 visit. Subjects must continue to take their 
current study treatment regimen up until their scheduled Day 1 visit. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. 
See Section 7 Adverse Events and Toxicity Management for additional details.
6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
confirmed eligibility before proceeding with the Day 1 visit. The subject must complete all 
study procedures before being administered the study drug:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

12-lead ECG performed supine

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.
Urine storage sample for possible additional clinical testing


GS-9883/F/T AF 
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• 
Blood sample collection for the following laborat01y analyses: 
Final 
Amendment 2 
-
Chemistly profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
phosphoms, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing 
is perf01med in subjects with total amylase > 1.5 x ULN), and TSH, PTIINR 
(prothrombin time/international n01malized ratio) 
-
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
u·iglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must retum within 72 hours in a fasted state to draw blood for the metabolic 
assessments. 
-
Estimated glomerular filtration rate according to the Cockcroft-Gault fonnula 
-
Hematology profile: complete blood cmmt (CBC) with differential and platelet cmmt 
-
Plasma HIV -1 RNA 
-
CD4+ cell count 
-
Plasma storage samples for safety, virology, or PK testing 
-
Whole blood sample for potential virologic resistance testing and/or HIV DNA 
genotyping 
-
Subjects who meet the definition ofHBV infection at Screening Visit (positive serum 
HBsAg or positive HBcAb with quantifiable HBV DNA), will have plasma HBV DNA 
tested 
• 
PPD 
• 
Provide subject dosing diary to all subjects in Treatment Group 1 
• 
Dispense study drug 
• 
Subjects in treatment group 1 should be instlucted to take study drugs without regard to food. 
Subjects in treatment group 2 should be instructed to take study dr11g with food. Subjects ar·e 
required to initiate dosing of study drugs the day of the Day 1 visit. The subject should be 
counseled regar·ding the impotiance of adherence ar1d taking their study medications at 
approximately the same time each day as directed by the Investigator. 
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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 (Weeks 4-48)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, and 48 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 at Week 24 and Week 36, unless 
otherwise specified. The visit window at Week 48 will be ± 6 weeks of the protocol-specified 
visit date, and these clinical visit windows coincide with the Week 48 statistical analysis window 
for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24 and 48) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

12-lead ECG performed supine (Weeks 24 and 48)

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin (Weeks 24 and 48)
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, subjects on 
GS-9883/F/TAF will be discontinued.
Urine storage sample for possible additional clinical testing


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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN). At 
Weeks 12, 24 and 48, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. At Weeks 24 and 48, TSH will also 
be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24 and 48)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula 
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
For subjects who meet the definition of HBV Infection at any visit:
■
The following will be conducted by the central laboratory: HBsAb, HBsAg 
(qualitative and quantitative) and HBeAg (if negative, reflex HBeAb). 
(Weeks 12, 24, and 48)
■
Plasma HBV DNA 
For subjects who do NOT meet the definition of HBV infection at any visit:
■
The following will be conducted by the central laboratory: HBsAb, HBcAb, and 
HBsAg. Subjects who are HBsAg and/or HBcAb positive will have a reflex test for 
HBV DNA (viral load) (Week 48)
For subjects with positive HCVAb at screening:
■
HCV RNA (Weeks 24 and 48)
For subjects who do NOT have a positive HCVAb at screening:
■
The following will be conducted by the central laboratory: Hepatitis C virus 
(HCVAb) serology. Subjects who are HCVAb positive will have a HCV RNA test 
performed (Week 48)
Plasma storage sample for safety, virology, or PK testing


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
Pharmacokinetic Blood Collection for all subjects on GS-9883/F/TAF only 
(Treatment Group 1). Details of pharmacokinetic blood sampling procedures and sample 
management will be documented in the study’s laboratory manual.
Single Anytime, Trough and Post-Dose PK Samples: 
(GS-9883/F/TAF - Treatment Group 1 only)
■
Subjects will have a single anytime pre or post-dose PK blood sample at 
Weeks 8, 24 and 36
■
Observed dosing at the clinic: If possible, subjects will have a trough PK blood 
sample collected between 20-28 hours following the last dose at Weeks 4 and 12.
Subjects must be instructed to not take their study drugs on the morning of their visit 
for the trough sample collection. Subjects will then take an observed dose of study 
drug at the clinic. If the subject has taken their dose of study drugs prior to the visit, 
the visit may proceed, but the subject must return within 72 hours for the single 
trough PK blood sample collection. In the event a subject routinely takes their study 
drug in the evening, a single anytime sample may be drawn at Weeks 4 and 12 as the 
subject will not be instructed to change their dosing time to accommodate this trough 
PK draw. A single PK blood sample will be collected between 1 and 4 hours post 
dose.
■
Dosing diaries will be collected from subjects for the single anytime PK and trough
PK collection. If a dosing diary is not returned the site may ask the subject for the 
time of the last dose and if it was taken with or without food.

Provide subject dosing diary to all subjects in Treatment Group 1 (Weeks 4, 8, 12 and 24)

Document study drug dispensation and accountability for all study drugs dispensed

Subjects who meet the criteria for virologic rebound will be managed according to the 
Management of Virologic Rebound Section 6.13.1.

HIV-1 genotype/phenotype testing for subjects with virologic failure (Week 48)
6.5.
Treatment Assessments (Post Week 48)
6.5.1.
Post Week 48 Assessments
At the Week 48 Visit, subjects who completed 48 weeks of study drug treatment and are in a 
country where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for an additional 48 weeks and attend study visits every 12 weeks or until 
the product becomes accessible to subject through an access program, or until Gilead Sciences 
elects to discontinue the study in that country, whichever occurs first. 


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Subjects who continue participation in the study and receive GS-9883/F/TAF will return for 
study visits every 12 weeks. Study visits are to be completed within ± 6 days of the 
protocol-specified visit date unless otherwise specified.
Subjects participating in the study post Week 48 will be required to return for study visits 
according to the schedule presented in Appendix 2 Study Procedures Table and described in the 
text below:

Review of AEs and changes in concomitant medications

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, subjects on 
GS-9883/F/TAF will be discontinued
Urine storage sample for possible additional clinical testing 

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN) TSH will 
be analyzed every 24 weeks.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 Weeks)


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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
For subjects who meet the definition of HBV Infection at any visit:
■
The following will be conducted by the central laboratory: HBsAb, HBsAg 
(qualitative and quantitative) and HBeAg (if negative, reflex HBeAb) 
(Every 24 weeks)
■
Plasma HBV DNA 
For subjects who do NOT meet the definition of HBV infection at any visit:
■
The following will be conducted by the central laboratory: HBsAb, (HBcAb), and 
HBsAg. Subjects who are HBsAg and/or HBcAb positive will have a reflex test for 
HBV DNA (viral load). (Every 48 weeks)
For subjects with positive HCVAb at screening or at the Week 48 visit:
■
HCV RNA (Every 24 weeks)
For subjects who do NOT have a positive HCVAb at screening or at the Week 48 visit:
■
The following will be conducted by the central laboratory: Hepatitis C virus 
(HCVAb) serology. Subjects who are HCVAb positive will have a HCV RNA test 
performed (Every 48 weeks)
Plasma storage samples for safety, virology, or PK testing

Subjects who meet the criteria for virologic rebound will be managed according to the 
Management of Virologic Rebound Section 6.13.1

Document study drug dispensation and accountability for all study drugs dispensed.
6.6.
Post-Treatment Assessments
6.6.1.
Early Study Drugs Discontinuation (ESDD) Assessments
If the subject discontinues study drug prior to the Week 48 Visit, the subject will be asked to 
return to the clinic within 72 hours of stopping study drug for the Early Study Drugs 
Discontinuation Visit. The subject will be asked to continue attending the scheduled study visits 
through the Week 48 Visit.


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At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will 
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drugs Discontinuation Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN), and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage samples for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability


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6.6.2.
30 Day Follow Up
Subjects who complete the study through the Week 48 visit and do not continue participation in
the study will be required to return to the clinic 30 days after the completion of study drug for the 
30-Day Follow-Up Visit. 
Subjects who prematurely discontinue study drug and refuse to continue in the study through the 
Week 48 visit will be asked to return to the clinic 30 days after the completion of the 
Early Study Drugs Discontinuation Visit for the 30-Day Follow-Up Visit.
Those subjects who prematurely discontinue study drug and continue in the study through 
at least one subsequent visit after the Early Study Drug Discontinuation Visit will not be 
required to complete the 30-Day Follow-Up Visit.
Subjects who participate post Week 48 will complete a 30-Day Follow-Up Visit 30 days after 
last dose of study drug.
For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight 

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
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 may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator.

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Lack of efficacy 

Subject request to discontinue for any reason

Subject noncompliance

Breastfeeding

Pregnancy during the study; refer to Appendix 6

Development of active tuberculosis infection

Discontinuation of the study at the request of Gilead, a regulatory agency or an 
institutional review board or independent ethics committee (IRB/IEC)
6.8.
Other Evaluations
6.8.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include but are not limited to urine albumin, urine creatinine, urine protein, retinol binding 
protein and beta-2-microglobulin at the Day 1 Visit, Weeks 24, 48, and every 24 weeks post 
Week 48. At the conclusion of this study, these samples may be retained in storage by
Gilead Sciences for a period up to 15 years.


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6.9.
Blood and Urine Storage
A portion of the blood and urine samples drawn at all visits (except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its research partners to help answer questions about the 
study drug, about the disease and its associated conditions and/or to provide additional safety 
data. No human genetic testing will be performed without expressed consent of study subjects. 
At the conclusion of this study, these samples may be retained in storage by Gilead Sciences for 
a period up to 15 years. 
6.10.
Assessments for Premature Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.7, Criteria for Discontinuation of Study Treatment). If 
this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study.
6.11.
End of Study
The end of study will be the last patient’s last observation (or visit). 
6.12.
Post Study Care
After a subject has completed/terminated their participation in the study, long-term care for the 
subject will remain the responsibility of their primary treating physician. 
6.13.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation or Week 48.
6.13.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any post Day 1 visit, a rebound in HIV-1 RNA ≥ 50 copies/mL, which is subsequently
confirmed at the following scheduled or unscheduled visit; 
OR

Any subject with HIV RNA ≥ 50 copies/mL at study drug discontinuation
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 


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


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Figure 6-1.
Virologic Rebound Schema
a
If virologic rebound is not confirmed, the subject will remain on their current regimen.
b
If virologic rebound is confirmed and the HIV-1 RNA is ≥200 copies/mL, the HIV-1 genotype and phenotype 
(reverse transcriptase, protease, and integrase) will be analyzed.
c
Based on the results of the genotype and phenotype assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping fails, a new ARV regimen may be configured at the discretion of the 
Investigator.
d
If no resistance is detected, HIV-1 RNA will be repeated (2-3 weeks later). Investigator reviews study drug 
continuation/discontinuation options and discuss with the Medical Monitor prior to study drug discontinuation.
e
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study. 
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation or 
Week 48
Subjects with HIV-1 RNA ≥ 50 copies/mL at study drug discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 will be 
asked to return for an unscheduled visit within the visit window for a retest. 
Subjects with HIV-1 RNA ≥ 200 copies/mL at study drug discontinuation, last visit or Week 48
will also have resistance testing conducted.  


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


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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to IMP interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 7.5.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to IMP
therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the IMP.


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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg, venipuncture)
7.2.2.
Assessment of Severity
AE severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events.
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): 

All SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30 days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.


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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of study IMP, regardless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period; 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of Study IMP, he/she should promptly document and 
report the event to Gilead DSPH.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the eCRF 
database is not functioning, site personnel should record the SAE on the paper Serious 
Adverse Event reporting form and submit within 24 hours to:
Gilead DSPH 
contact information:
Fax:
E-mail:
+1 (650) 522-5477
Safety_FC@gilead.com

As soon as it is possible to do so, any SAE reported via paper form must be transcribed into 
the eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.


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
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax only when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document only 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 a 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 lab result 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 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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7.5.5.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management
An On-Treatment ALT Flare is defined as:

Confirmed (within 3 days of receipt of initial laboratory results) serum ALT > 2 × Day 1 
value and >10 × ULN, with or without associated symptoms
7.5.5.1.
Management of ALT Flare in Subjects Receiving Study Medication
If laboratory results indicate elevation of ALT > 2 × Day 1 value and > 10 × ULN, the following 
is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally within 3 days after 
initial laboratory results were drawn). During the visit, a clinical assessment of the subject 
will be performed. The assessment should include a physical examination and evaluation of 
the subject’s mental status.

If the ALT elevation is confirmed, request the central clinical laboratory to conduct reflex 
testing for plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM, and 
HCV serology
Check the following laboratory parameters: serum ALT and AST, total bilirubin, INR, and serum 
albumin. Based on the results of the confirmatory tests, the following treatment modifications are 
recommended:
Elevated Liver Enzymes, Normal or Stable Relative to Day 1 Liver Function Tests
If ALT levels are elevated (i.e., 2 × Day 1 and 10 × ULN) with normal or stable total 
bilirubin and INR relative to Day 1, the subject may remain on study medication and should be 
monitored weekly as long as ALT levels return to normal or Day 1 level. During monitoring, if 
the ALT values remain persistently elevated, the Investigator should discuss with the 
Gilead Medical Monitor whether the study drug should be discontinued.
Elevated Liver Enzymes, Elevated Liver Function Tests
If ALT values are elevated (i.e., > 2 × Day 1 and > 10 × ULN), and total bilirubin is confirmed to 
be 2 x Day 1 value, and INR is 0.5 above Day 1, provided both are > ULN, the investigator 
should consider discontinuing study medication (upon discussion with the 
Gilead Medical Monitor, unless the safety of the patient is of immediate concern). The subject 
should be monitored weekly as long as ALT, total bilirubin, and INR values remain elevated or 
above Day 1 values.
During monitoring, if the ALT values and the liver function tests remain persistently elevated, 
the Investigator should discuss with the Gilead Medical Monitor whether the study drug should 
be discontinued.


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7.5.5.2.
Management of Exacerbation of Hepatitis B in Subjects Who Have Discontinued 
Study Medication
If laboratory results indicate (1) an ALT elevation > 2 × Day 1 and > 10 × ULN alone OR 
associated with (2) abnormal laboratory parameters suggestive of worsening hepatic function 
(total bilirubin 2 × Day 1, INR 0.5 above Day 1, provided both are > ULN) and the subject is on 
no post-study therapy for HBV, the following is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally no later than 3 days 
after the initial laboratory values were drawn). During the visit, perform a clinical assessment 
of the subject.

Check the following laboratory parameters: serum ALT and AST, bilirubin, INR, and albumin.

If the ALT elevation is confirmed, request the clinical laboratory to conduct reflex testing for 
plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM and HCV. If 
serum HBV DNA is increasing, the investigator should consider immediate initiation of 
approved therapy.

The subject should be followed until laboratory parameters (ALT, total bilirubin, INR) return 
to normal or Day 1 up to a maximum of 6 months after the initial occurrence of the event.
7.5.6.
Management of Hyperbilirubinemia
Most patients taking atazanavir sulfate experience asymptomatic elevations in indirect 
(unconjugated) bilirubin related to inhibition of UDP-glucuronyl transferase (UGT). Hepatic 
transaminase elevations that occur with hyperbilirubinemia should be evaluated for alternative 
etiologies. Dose modification of atazanavir sulfate is not permitted. Subjects who experience 
unacceptable jaundice/scleral icterus can be discontinued from study at the discretion of the 
Investigator.

Subjects with bilirubin levels of 5-10 × ULN, if isolated and not accompanied by 
unacceptable clinical jaundice (scleral icterus or cutaneous jaundice) may continue on study, 
if agreed upon by the subject and the Investigator. All subjects with serum bilirubin levels 
5-10 × ULN must have bilirubin, AST and ALT repeated at least once within 7 days of the 
Investigator being notified of the elevated bilirubin level. Thereafter, serum bilirubin levels 
5-10 × ULN without clinically significant elevation in AST or ALT should be followed 
according to the clinical judgment of the Investigator.

Subjects whose hyperbilirubinemia (5-10 × ULN) is accompanied by ≥ Grade 2 ALT or AST 
elevation or who experience a one Grade worsening in ALT or AST do not qualify as having 
isolated hyperbilirubinemia and will be discontinued.

Confirmed hyperbilirubinemia > 10 × ULN will require discontinuation.

Elevation of conjugated (direct) bilirubin > 2 mg/dL in association with Grade 2 ALT or 
AST elevation will require discontinuation.


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7.5.7.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose interruption. 
Should the Investigator decide to initiate Hepatitis C treatment the Investigator must contact the 
Gilead Medical Monitor to confirm that no drug-drug interactions are expected. Subjects should 
return to the clinic for scheduled or unscheduled follow up visit(s) according to local medical 
practice for laboratory evaluations. If Hepatitis C treatment is initiated, Investigators should use 
the Gilead provided retest laboratory kits to manage the active Hepatitis C.
7.5.8.
Management of Potential Nephrotoxicity
Estimated glomerular filtration rate according to the Cockcroft-Gault formula (eGFRC-G), will be 
followed post-baseline during the study. All subjects with estimated GFR < 50 mL/min 
(0.83 mL/sec) must have serum creatinine and subject’s weight measured again within 
3 calendar days of receipt of results.
If a subject has confirmed eGFRC-G < 50 mL/min, the Gilead Medical Monitor should be notified 
and discontinuation of the study drug should be discussed. For subjects with confirmed eGFRC-G
< 50 mL/min who are not discontinued based on toxicity management procedures above and are 
considered to have stable renal function per Principal Investigator and Gilead Medical Monitor, 
it is not mandatory to repeat eGFR assessments within 3 days.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, 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 


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


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7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.6 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is to evaluate the efficacy of switching to a GS-9883/F/TAF 
FDC versus staying on baseline regimen (SBR) in virologically suppressed HIV-1 infected 
women as determined by the proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48. 
The secondary objective of this study is to evaluate the safety, and tolerability of the 
two treatment groups through Week 48.
8.1.2.
Primary Endpoint
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as determined by the FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
Secondary endpoints include:

The proportion of subjects withHIV-1 RNA < 50 copies/mL at Week 48 as determined by the 
US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.
8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study (2) have received at least 1 dose of 
study drug. Subjects will be grouped according to the treatment to which they were randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug (3) have not committed any major protocol violation, including the violation 
of key entry criteria. Subjects will be grouped according to the treatment they actually received.


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Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis
set:

Subjects who do not have an on-treatment HIV-1 RNA laboratory test in the Week 48
analysis window, except when missing is due to discontinuation of study drug for lack of 
efficacy. 

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 5 including drugs not to be used with 
GS-9883, FTC, TAF, EVG, COBI, ATV and RTV.

Non adherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile.
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose of 
GS-9883/F/TAF, and (3) have at least 1 non missing PK concentration data for any analyte of 
interest reported by the PK lab. 
8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose. Laboratory data that are continuous in nature 
but are less than the lower limit of quantitation or above the upper limit of quantitation will be 
imputed to the value of the lower or upper limit plus or minus one significant digit, respectively 
(e.g., if the result of a continuous laboratory test is < 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (ie, no toxicity grade) for the laboratory abnormality summary.
All available data for subjects that do not complete the study will be included in data listings.


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8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include race, ethnicity, and age. 
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline 
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects with 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 include subjects 
a) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window, or 
b) Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and 
1) Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or 
2) Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than lack of efficacy and have the last available on-treatment 
HIV-1 RNA ≥50 copies/mL  


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
No Virologic Data in the Week 48 Analysis Window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following: 
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL or,
b) Missing data during the window but on study drug 
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 in the GS-9883/F/TAF group is at least 4% higher than that in the SBR group; the 
alternative hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 copies/mL in the 
GS-9883/F/TAF group is less than 4% higher than that in the SBR group.
Non-inferiority will be assessed using the conventional confidence interval (CI) approach. The 
point estimate of treatment difference (GS-9883/F/TAF – SBR) and the associated 2-sided 
95% CI will be constructed based on the exact method.  
It will be concluded that GS-9883/F/TAF is non-inferior to E/C/F/TAF if the upper bound of the 
2-sided 95% CI of the difference between treatment groups (GS-9883/F/TAF – SBR) in the 
percentage of subjects with HIV-1 RNA ≥50 copies/mL is less than 4% (ie, a margin of 4% is 
applied to non-inferiority assessment).
If non-inferiority of GS-9883/F/TAF to SBRis established, the upper bound of the 95% CI will 
be compared to 0; if the upper bound of the 95% CI is less than 0, superiority of GS-9883/F/TAF
over SBR will be established.
8.5.2.
Secondary Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined by the
US FDA-defined snapshot algorithm will also be evaluated. The 95% CIs will be constructed in 
the same manner as for the primary efficacy endpoint. However, non-inferiority will be assessed 
using a margin of 10%. It will be concluded that GS-9883/F/TAF is non- inferior to SBR if the 
lower bound of the 2-sided 95% CI of the difference between treatment groups 
(GS-9883/F/TAF - SBR) in the response rate is greater than −10%.
The changes from baseline in CD4+ cell count at Week 48 will be summarized by treatment 
using descriptive statistics. The differences in changes from baseline in CD4+ cell count between 
the 2 treatment groups and the associated 95% CIs will be constructed using ANOVA models, 
including treatment (GS-9883/F/TAF vs. SBR) as a fixed effect in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.


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8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise, will be summarized 
for subjects in the safety analysis set according to the study drug received.
Data for the pretreatment period and the period post the date of last dose of study drug plus 
30 days will be included in data listings for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug
administration page in eCRF. Exposure data will be summarized by treatment.
Duration of exposure to study drug will be expressed as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration and summarized by treatment.
Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study drug start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illnesses definition of 
an AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.


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8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum post baseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the PK analyses, the pharmacokinetics of GS-9883 may be evaluated using descriptive 
statistics or population approaches.
TAF and FTC concentrations may be analyzed as applicable.  
8.8.
Sample Size
A total of approximately 470 HIV-1 infected subjects, randomized in a 1:1 ratio to 
2 treatment groups (approximately 235 subjects per treatment group), achieves at least 87%
power to detect a non-inferiority margin of 4% difference in percentage of subjects with HIV-1 
RNA ≥50 copies/mL at Week 48 between the 2 treatment groups. For the sample size and power 
computation, it is assumed that both treatment groups have 2% of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 (based on the historical Gilead GEN and STB studies), that the
non-inferiority margin is 4%, and that the significance level of the test is at a one-sided 
0.025 level.
8.9.
Independent Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after all 
subjects enrolled complete Week 24 of the study or prematurely discontinue the study drug. 
However, Gilead will defer to the IDMC for any decision to convene earlier or more frequently. 
The IDMC will examine the safety results of the trial and also focus on logistical issues such as 
accrual, retention, quality of clinical and laboratory data, and implications of results of external 
studies.


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No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
An analysis for the Week 24 IDMC meeting will be conducted after the last subjects enrolled 
completes Week 24 of the study. For each IDMC analysis performed prior to analysis for the 
primary efficacy endpoint, an alpha penalty of 0.00001 will be applied for the primary analysis 
of the primary efficacy endpoint.
8.10.
Analysis Schedule
The Week 48 analysis will be conducted after all subjects either complete their Week 48 visit or 
prematurely discontinue from the study drug. 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. 


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


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


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responding to the queries in a timely manner, within the system, either by confirming the data as 
correct or updating the original entry, and providing the reason for the update 
(e.g. data entry error). Original entries as well as any changes to data fields will be stored in the 
audit trail of the system. Prior to any interim time points or database lock (as instructed by 
Gilead), the investigator will use his/her log in credentials to confirm that the forms have been 
reviewed, and that the entries accurately reflect the information in the source documents. At the 
conclusion of the trial, Gilead will provide the site with a read-only archive copy of the data 
entered by that site. This archive must be stored in accordance with the records retention 
requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files. 
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP 
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs/IECs or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.


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


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


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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.
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
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


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Switching to a 
Fixed Dose Combination (FDC) of GS-9883/Emtricitabine/Tenofovir Alafenamide 
(GS-9883/F/TAF) from Elvitegravir/Cobicistat/Emtricitabine!Tenofovir Alafenamide 
(E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) 
or Atazanavir + Ritonavir + Emtricitabine/Tenofovir Disoproxil Fumarate 
(ATV+RTV+FTC!TDF) in Virologically Suppressed HIV-1 Infected Women 
GS·US-380-1961, Amendment 2, 10 November 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
'De-vi s Wt~ ~~ 
I /M l;xM,.J f { ' 
Huyen Cao, MD (Printed) 
Author 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary details 
for me and my staff to conduct this study as described. 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 90 
10 November 2016 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 91
10 November 2016
Appendix 2.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48d,v
30 Day 
Follow-Upe
ESDDf
4
8
12
24
36
48
Every 12 Weeks
Informed Consent
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam 
X
X
X
X
Xy
X
Symptom-Directed Physical Exam
X
X
X
X
X
12-Lead ECG 
X
X
X
X
Xy
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Chemistryh
X
X
X
Xw
Urine Pregnancy Testi
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testi
X
Chemistry Profilej
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentsk
X
X
X
X
Xw
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilel
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAm
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Planel
Xn
Xo
Xo
Xo,z
Xo,z
Plasma HBV DNAaa
X
X
X
X
X
X
X
X
X
HCVAbp
X
X
Xy
HCV RNAp
X
X
X
Xw


GS-9883/F/T AF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Study Procedure 
HN -1 Genotype/Phenotypeq 
Single PK Draw 
Trough PK Draw• 
PK Sample (post-dose)• 
s 
Observed In-Clinic Dose 
Provide Dosing Diaryu 
Collect Dosing Diaryx 
Plasma Sample Storage
1 
t 
Urine Sample Storage 
Whole Blood Storage Sample' 
rPD 
n 
I 
Randomization 
Study Drug Dispensation 
Study Dmg Accotmtability 
Scrl'l'ning• 
I 
a 
Evaluations to be completed within 30 days prior to Day 1. 
Day 1b 
4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b 
Subjects should initiate dosing of study dmg on the same day as the Day 1 visit. 
8 
X 
X 
X 
X 
X 
X 
X 
End ofWeE'kc 
12 
24 
36 
48 
X'l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
xv 
X 
X 
X 
X 
Post Week 48d,v 
Every 12 Weeks 
X 
X 
xv 
X 
30Day 
Final 
Amendment 2 
Follow-up• 
ESDDr 
xq 
X 
X 
X 
c 
All study visits should be± 2 days of the protocol-spe.cified visit date based on the Day 1 visit through Week 12 and completed within± 6 days at Week 24 and Week 36, 
tmless otherwise specified. The visit window at Week 48 will be± 6 weeks of the protocol-specified visit date. 
d 
At the Week 48 Visit, subjects in a cotmtry where GS-9883/F/TAF FDC is not available wiii be given the option to receive GS-9883/F/TAF FDC for an additional 48 weeks, 
or until the product becomes accessible to subjects tiu·ough an access program, or tmtil Gilead Sciences elects to discontinue the study in that cotmtry, whichever occms first. 
Study visits are to be completed every 12 weeks, witiun ± 6 days of ti1e protocol-specified visit date tmless othenvise specified. 
e 
Must be completed 30 days after discontinuing study drug. For the ptupose of scheduling a 30-Day Follow-Up Visit, a± 6 days window may be used. Required for subjects 
who permanently discontinue study dmg prior to Week 48 and do not c.ontinue in the study tlu·ough at least one subsequent visit after the ESDD visit. Subjects who participate 
post Week 48 wiii be required to retm11 to the clinic 30 days after ti1e completion of study drugs for the 30-Day Follow-Up Visit. 
f 
Early Study Drug Discontinuation visit to occur within 72 horu-s of last dose of study dmg. Subjects will be asked to continue attending the scheduled study visits through ti1e 
Week 48 Visit even if the subject discontinues study dtug. 
g 
Vital signs measw·ements including blood pressure, pulse, respiratory rate, and temperature 
h 
Urine Chenustty includes urine albtmlin, w·ine creatitline, urit1e protein, retinol binding proteit1, and beta-2 nucroglobulit1 
Women of childbearing potential only. Positive urine pregnancy tests will be confumed with a semm test. 
CONFIDENTIAL 
Page 92 
10 November 2016 


GS-9883/F/TAF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Final 
Amendment 2 
Chemistry profile: alkaline phosphatase, AST, AL T, GGT, total bilirubin, direct and indirect bilirubin, total protein, alblll11in, bicarbonate, BUN, calcilll11, chloride, creatinine, 
glucose, phosphorus, magnesilll11, potassilll11, sodilll11, uric acid, and amylase (reflex lipase testing is performed in subjects with total amylase > 1.5 x ULN). At Day 1, 
Weeks 24, and 48 and every 24 weeks during the post Week 48 period, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of the 
chemistry profile. TSH will be collected at Screening, Day 1, Weeks 24, and 48, as well as every 24 weeks post Week 48, and ESDD if applicable. PT/INR will be performed 
at Day 1. 
k 
Fasting glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the subject must 
return within 72 homs in a fasted state to draw blood for the metabolic assessments. 
CBC with differential and platelet count. 
m 
If the HIV-1 RNA value is ~ 50 copies/mL at Week 48, a retest HIV-1 RNA value must be collected within two to three weeks of the initial test. 
n 
Hepatitis B Virus (HBV) blood panel will be performed at screening: Hepatitis B virus smface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B 
virus core antibody (HBcAb ). If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex HBeAb), and quantitative HBsAg. If positive HBcAb with 
negative HBsAg and negative HBsAb, reflex testing for plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to be negative, reflex HBeAb. 
o 
At Weeks 12, 24, 48, 72, and 96, for subjects who meet the definition of HBV infection at any visit, the following will be conducted by the central laboratory: HBsAb, 
HBsAg (qualitative and quantitative) and HBeAg (if negative, reflex HBeAb). 
p 
Subjects who are HCV Ab positive at screening or at Week 48 will have a HCV RNA test performed at screening or at Week 48 and every 24 weeks thereafter. Subjects who 
are HCVAb positive at the Week 96 visit will also have a HCV RNA test performed. 
q 
HIV-1 genotype/phenotype testing for subjects with HIV-1 RNA ~ 200 copies/mL and virologic rebound, at early study drug discontinuation or Week 48. Following 
unconfirmed virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to the next scheduled visit or at the next scheduled study visit, for a 
HIV-1 RNA and HIV-1 genotype/phenotype (reverse transcriptase, protease and integrase) blood draw. Based on the results of this testing, subjects should be managed 
according to the Virologic Rebound Schema (Section 6.13.1). 
r 
All subjects on GS-9883/F/TAF (Treatment Group 1 only) will have a single anytime PK blood sample collected at Weeks 8, 24 and 36. 
s 
Subjects on GS-9883/F/TAF (Treatment Group 1 only) 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 drugs on the morning of their visit for the trough sample collection. If the subject has taken their dose of study drugs prior 
to the visit, the visit may proceed, but the subject must return within 72 homs for the single trough PK blood sample collection. In the event a subject routinely takes their 
study drug in the evening, a single anytime sample may be drawn at Weeks 4 and 12 as the subject will not be instructed to change their dosing time to accommodate this 
trough PK draw. A post-dose PK blood sample will be collected between 1 and 4 hours post dose following an observed, in-clinic dose. 
Plasma storage samples banked for possible futme protocol-related testing (safety, virology, pharmacokinetic analysis). Urine storage samples banked for possible futme 
protocol-related safety testing including mine chemistry. Whole blood sample for potential virologic resistance testing and/or HIV DNA genotyping. PO 
...._ _____ ..... 
u 
A dosmg diary will be dispensed for all Treatment Group 1 subJects to complete prior to each of the PK sample visits. 
v 
Open-label GS-9883/F/T AF FDC will be dispensed to subjects participating in the study post Week 48 starting at the Week 48 Visit. 
w 
Every 24 weeks only. 
x 
Dosing diaries will be collected from subjects for the single anytime PK and trough PK collection (Treatment Group 1 only). If a dosing diary is not returned the site may ask 
the subject for the time of the last dose and if it was taken with or without food. 
y 
To be performed every 48 weeks post Week 48 visit. 
z 
At Weeks 48 and 96, for subjects who do NOT meet the definition ofHBV infection at any visit, the following will be performed by the central laboratory: HBsAb, HBcAb, 
and HBsAg. Subjects who are not HBsAg and/or HBcAb positive will have a reflex test for HBV DNA (viral load). 
aa 
To be performed for subjects who meet the definition ofHBV infection. 
CONFIDENTIAL 
Page 93 
10 November 2016 


GS-9883/F/TAF 
Protocol GS-US-380-1961 
Final 
Gilead Sciences, Inc. 
Amendment 2 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
Grade I 
~-----G_r_a_d_e_2----~~ 
~
~ ______ G_r_a_de-3------~~ 
~~ __________ a_m_d_e_4--------~ 
! 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
If confirmed and possibly and/or probably related to investigational 
medicinal products: 
1. 
Withhold investigational medicinal products until ::; Grade 2 
2. 
Restart all investigational medicinal products at full dose 
l 
If Grade 3 or 4 recurrence that is con tinned and possibly or probably 
related to investigational medicinal products, discontinue a11 
investigational medicinal products dosing permanently 
Repeat lab to 
confirm toxicity 
grade 
1 
1 
lfc 
elated to 
inve 
dicinal products, 
onfrrmed and unr 
stigationalme 
ng may contin 
he investigator 
dosi 
ue at the discretion 
oft 
If confirmed and 
possibly or probably 
I-+ related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
Page 94 
10 November 2016 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 95
10 November 2016
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count  
(ANC)
Adult and Pediatric, 
≥ 7 Months#
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 96
10 November 2016
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects. Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.  


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 97
10 November 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 98
10 November 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL                       
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL              
1.74 to <1.94 mmolL
6.1 to  <7.0 mg/dL                    
1.51 to < 1.74 mmolL
< 6.1 mg/dL                           
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 99
10 November 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (corrected for 
albumin if appropriate*)
Adult and Pediatric 7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to  <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63  to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to <LLN mg/dL
1.12 to <LLN mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 100
10 November 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyperbilirubinemia 
Adult and Pediatric > 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 101
10 November 2016
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-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 102
10 November 2016
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 103
10 November 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-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 104
10 November 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-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 105
10 November 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 106
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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-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 107
10 November 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-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 108
10 November 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 109
10 November 2016
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Dysphagia-Odynophagia 
Symptomatic but able to eat 
usual diet
Symptoms causing altered 
dietary intake without 
medical intervention 
indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention 
indicated
Life-threatening reduction in 
oral intake
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, Dysphagia-
Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal 
bleeding OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 24–
48 hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening 
consequences (eg, 
hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening 
consequences (eg, sepsis, 
circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ Stomatitis 
for Clinical Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities OR 
Medical intervention 
indicated 
Symptoms causing inability 
to perform usual social/ 
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences (eg, 
perforation)
Vomiting
Transient or intermittent 
vomiting with no or minimal 
interference with oral intake
Frequent episodes of 
vomiting with no or mild 
dehydration
Persistent vomiting resulting 
in orthostatic hypotension 
OR Aggressive rehydration 
indicated
Life-threatening 
consequences (eg, 
hypotensive shock)


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 110
10 November 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 111
10 November 2016
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
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 112
10 November 2016
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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Protocol GS-US-380-1961
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Amendment 2
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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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
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Amendment 2
CONFIDENTIAL
Page 114
10 November 2016
SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Acute Systemic Allergic 
Reaction 
Localized urticaria (wheals) 
with no medical intervention 
indicated
Localized urticaria with 
medical intervention 
indicated OR Mild 
angioedema with no medical 
intervention indicated
Generalized urticaria OR 
Angioedema with medical 
intervention indicated OR 
Symptomatic mild 
bronchospasm
Acute anaphylaxis OR Life-
threatening bronchospasm 
OR laryngeal edema
Chills
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities 
Symptoms causing inability 
to perform usual social & 
functional activities
NA
Fatigue
Malaise
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities
Symptoms causing inability 
to perform usual social & 
functional activities
Incapacitating 
fatigue/malaise symptoms 
causing inability to perform 
basic self-care functions
Fever (nonaxillary)
37.7C to 38.6C
99.8F to 101.5F
38.7C to 39.3C
101.6F to 102.8F
39.4C to 40.5C
102.9F to 104.9F
40.5C 
104.9F
Pain- Indicate Body Site
See also Injection Site Pain, 
Headache, Arthralgia, and 
Myalgia
Pain causing no or minimal 
interference with usual social 
& functional activities
Pain causing greater than 
minimal interference with 
usual social & functional 
activities
Pain causing inability to 
perform usual social & 
functional activities
Disabling pain causing 
inability to perform basic 
self-care functions OR 
Hospitalization (other than 
ER visit) indicated
Unintentional Weight Loss
NA
5% to 9% loss in body 
weight from baseline
10% to 19% loss in body 
weight from baseline
20% loss in body weight 
from baseline OR  
Aggressive intervention 
indicated [eg, tube feeding or 
total parenteral nutrition]


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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 116
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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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 117
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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.


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 118
10 November 2016
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV 
(CDC Guidelines)
1) Candidiasis of bronchi, trachea, or lungs
2) Candidiasis of esophagus
3) Cervical cancer, invasive
4) Coccidioidomycosis, disseminated or extrapulmonary
5) Cryptococcosis, extrapulmonary
6) Cryptosporidiosis, chronic intestinal (> 1 month duration)
7) Cytomegalovirus disease (other than liver, spleen or nodes)
8) Cytomegalovirus retinitis (with loss of vision)
9) Encephalopathy, HIV-related
10) Herpes simplex: chronic ulcer(s) (> 1 month duration); or bronchitis, pneumonitis or 
esophagitis
11) Histoplasmosis, disseminated or extrapulmonary
12) Isosporiasis, chronic intestinal (> 1 month duration)
13) Kaposi’s sarcoma
14) Lymphoma, Burkitt’s (or equivalent term)
15) Lymphoma, immunoblastic (or equivalent term)
16) Lymphoma, primary, of brain
17) Mycobacterium avium complex or Myobacterium kansasii, disseminated or extrapulmonary
18) Mycobacterium tuberculosis, of any site,  pulmonary, disseminated or extrapulmonary
19) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
20) Pneumocystis jirovecii (previously known as “Pneumocystis carinii) pneumonia
21) Pneumonia, recurrent
22) Progressive multifocal leukoencephalopathy


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Gilead Sciences, Inc.
Amendment 2
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23) Salmonella septicemia, recurrent
24) Toxoplasmosis of brain
25) Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection −2014 {Schneider et al 2008}


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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.
Females are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, females of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
2) Contraception Requirements for Women
a. Study Drug Effects on Pregnancy and Hormonal Contraception
The data on GS-9883/F/TAF in pregnant women is limited or not available. There is no 
suspicion of human teratogenicity based on class effects or genotoxic potential. Relevant 
non-clinical reproductive studies for human pregnancy do not indicate a strong suspicion of 
human teratogenicity/fetotoxicity. Data from clinical pharmacokinetic interaction studies of 
GS-9883 and F/TAF have demonstrated that there is no reduction in the clinical efficacy of 
hormonal contraception or that the effect on hormonal contraception is insignificant. Please refer 
to the latest version of the GS-9883/F/TAF investigator’s brochure and the latest versions of the 
E/C/F/TAF, E/C/F/TDF, ATV, RTV and FTC/TDF package inserts or investigator’s brochures
for additional information.
b. Contraception Requirements for Women of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Day 1 visit prior to randomization. At a minimum a pregnancy 
test will be performed at the end of relevant systemic exposure. In the event of a delayed 
menstrual period (over one month between menstruations), a pregnancy test must be performed 
to rule out pregnancy. This is true even for women of childbearing potential with infrequent or 
irregular periods. Female subjects must agree to one of the following from Screening until 
30 days following the end of relevant systemic exposure.


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Gilead Sciences, Inc.
Amendment 2
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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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Final
Gilead Sciences, Inc.
Amendment 2
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3) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM). Female condom and male condom should not be used 
together.
4) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator immediately. The investigator will counsel the subject regarding 
pregnancy management options. Counseling will be provided regarding alternative anti-HIV 
treatment. Information on the risks and benefits of antiretroviral therapies will be discussed, 
including the risk of ongoing fetal exposure to the study drug versus the new alternative therapy 
and the risk of discontinuing maternal therapy.
If the subject is on GS-9883/F/TAF, they must discontinue study drug immediately. Subjects 
may be allowed to continue on study drug if they are taking E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF and an additional informed consent will be required.
If the subject elects to discontinue study drugs but remain in the study, a new ARV regimen will 
be constructed at the Investigator’s discretion. 
The Investigator should counsel the subject on the need to inform the study site of the outcome 
of the pregnancy. Information collected will include gestational dating, ultrasound report, records 
of maternal, fetal complications and pregnancy outcome. 
Instructions for reporting pregnancy and pregnancy outcome are outlined in Section 7.6.

SAP_003.pdf: 
Study Title: 
Name of Test Drug: 
Study N urn ber: 
Protocol Version (Date): 
Analysis Type: 
Analysis Plan Version: 
Analysis Plan Date: 
Analysis Plan Author(s): 
[!') G I LEAL> 
STATISTICAL ANALYSIS PLAN 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety 
and Efficacy of Switching to a Fixed Dose Combination (FDC) of 
GS-9883/Emtricitabine!fenofovir Alafenamide (GS-9883/F!f AF) 
fi·om Elvitegravir/Cobicistat/Emtricitabine/ 
Tenofovir Alafenamide (E/C/F!f AF), Elvitegravir/Cobicistat/ 
Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) or 
Atazanavir + Ritonavir + Emtricitabine/Tenofovir Disoproxil 
Fumarate (A TV+RTV+FTC/TDF) in Virologically Suppressed 
HIV -1 Infected Women 
Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F!f AF~ 
GS-9883/F/TAF) 
GS-US-380-1961 
Amendment 2 (10 November 2016) 
Week 48 Interim Analysis 
Version 1.0 
19 October 2017 
PPD 
CONFIDENTIAL AND PROPRIETARY INFORMATION 


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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF 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..........................................................................................................................10
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................11
2.1.
Data Monitoring Committee Analysis ...................................................................................................11
2.2.
Week 48 Interim Analysis......................................................................................................................11
2.3.
Final Analysis ........................................................................................................................................11
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................12
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.....................................................................................................13
3.1.4.
Safety Analysis Set...............................................................................................................14
3.1.5.
Pharmacokinetic (PK) Analysis Set .....................................................................................14
3.2.
Subject Grouping ...................................................................................................................................14
3.3.
Strata and Covariates..............................................................................................................................15
3.4.
Examination of Subject Subgroups........................................................................................................15
3.4.1.
Subject Subgroups for Efficacy Analyses ............................................................................15
3.4.2.
Subject Subgroups for Safety Analyses ...............................................................................15
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................................................................................................................19
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window................................................................................................................................21
4.
SUBJECT DISPOSITION ..................................................................................................................................22
4.1.
Subject Enrollment and Disposition.......................................................................................................22
4.1.1.
Subject Enrollment...............................................................................................................22
4.1.2.
Subject Disposition ..............................................................................................................22
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................23
4.2.1.
Duration of Exposure to Randomized Study Drug...............................................................23
4.2.2.
Adherence to Study Drug Regimen......................................................................................23
4.3.
Protocol Deviations................................................................................................................................25
5.
BASELINE CHARACTERISTICS....................................................................................................................26
5.1.
Demographics and Baseline Characteristics ..........................................................................................26
5.2.
Baseline Disease Characteristics............................................................................................................26
5.3.
Medical History......................................................................................................................................27


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6.
EFFICACY ANALYSES ...................................................................................................................................28
6.1.
Primary Efficacy Endpoint.....................................................................................................................28
6.1.1.
Definition of the Primary Efficacy Endpoint .......................................................................28
6.1.2.
US FDA-defined Snapshot Algorithm .................................................................................28
6.1.3.
Statistical Hypothesis for the Primary Efficacy Endpoint....................................................29
6.1.4.
Primary Analysis of the Primary Efficacy Endpoint ............................................................29
6.1.5.
Secondary Analysis of the Primary Efficacy Endpoint ........................................................30
6.2.
Secondary Efficacy Endpoints ...............................................................................................................30
6.2.1.
Definition of the Secondary Efficacy Endpoints..................................................................30
6.2.2.
Analysis of the Secondary Efficacy Endpoints ....................................................................30
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............................................................................34
7.
SAFETY ANALYSES........................................................................................................................................35
7.1.
Adverse Events and Deaths....................................................................................................................35
7.1.1.
Adverse Event Dictionary ....................................................................................................35
7.1.2.
Adverse Event Severity........................................................................................................35
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................35
7.1.4.
Serious Adverse Events........................................................................................................35
7.1.5.
Treatment-Emergent Adverse Events...................................................................................35
7.1.6.
Summaries of Adverse Events and Death ............................................................................37
7.1.7.
Additional Analysis of Adverse Events ...............................................................................38
7.2.
Laboratory Evaluations ..........................................................................................................................38
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................39
7.2.2.
Graded Laboratory Values ...................................................................................................40
7.2.3.
Metabolic Laboratory Evaluations .......................................................................................41
7.2.4.
Liver-Related Laboratory Evaluations .................................................................................42
7.2.5.
Renal-Related Laboratory Evaluations.................................................................................43
7.3.
Body Weight, Height, and Vital Signs...................................................................................................44
7.4.
Prior and Concomitant Medications.......................................................................................................44
7.4.1.
Antiretroviral Medications ...................................................................................................44
7.4.2.
Prior Antiretroviral Medications ..........................................................................................44
7.4.3.
Concomitant Non-Antiretroviral Medications......................................................................44
7.5.
Electrocardiogram Results .....................................................................................................................45
7.6.
Other Safety Measures ...........................................................................................................................45
7.7.
Subject Subgroup for Safety Endpoints .................................................................................................45
7.8.
Changes From Protocol-Specified Safety Analyses...............................................................................45
8.
PHARMACOKINETIC ANALYSES ................................................................................................................46
8.1.
Analysis for Trough and Postdose PK (PK Analysis Set)......................................................................46
8.2.
Changes from Protocol-Specified Pharmacokinetic Analysis................................................................46
9.
SPECIAL POPULATION ANALYSES.............................................................................................................47
9.1.
Analyses for HIV/HBV Coinfected Subjects.........................................................................................47
9.2.
Analyses for HIV/HCV Coinfected Subjects.........................................................................................48
10.
REFERENCES ...................................................................................................................................................50
11.
SOFTWARE.......................................................................................................................................................51
12.
SAP REVISION..................................................................................................................................................52
13.
APPENDICES ....................................................................................................................................................53


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Appendix 1.
Study Procedures Table..........................................................................................................54
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm..............................................................57
Appendix 3.
Selected Medical History .......................................................................................................58
Appendix 4.
Hepatic Events........................................................................................................................77
Appendix 5.
Programming Specification....................................................................................................78
LIST OF TABLES
Table 3-1.
Subjects Excluded from Week 48 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA Assessment in Week 48 
Analysis Window ...................................................................................................................14
Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, HBV DNA, 
Hematology, Chemistry, Urinalysis, and Urine Pregnancy Laboratory Tests, 
eGFRCG, Vital Signs, and Weight...........................................................................................19
Table 3-3.
Analysis Windows for Metabolic Assessments and HBV Serology ......................................20
Table 3-4.
Analysis Windows for TSH, Renal Function, and Safety ECG .............................................20
Table 3-5.
Analysis Windows for HCV Serology and HCV RNA Assessments.....................................20


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LIST OF ABBREVIATIONS
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
Atazanavir
B2M
beta-2 microglobulin
BIC
Bictegravir, GS-9883, B
B/F/TAF
single-tablet regimen of bictegravir (BIC; B) 50 mg / emtricitabine (FTC) 200 mg /
tenofovir alafenamide (TAF) 10 mg; GS-9883/F/TAF
BLQ
below limit of quantitation
BMI
body mass index
BSA
body surface area
CG
Cockroft-Gault
CI
confidence interval
CMH
Cochran-Mantel-Haenszel 
CRF
case report form
CSR
clinical study report 
DNA
Deoxyribonucleic Acid
DOB
date of birth
DSPH
Drug Safety and Public Health Department
E/C/F/TAF
Elvitegravir /Cobicistat /Emtricitabine/ Tenofovir Alafenamide; Genvoya; GEN
E/C/F/TDF
Elvitegravir /Cobicistat /Emtricitabine / Tenofovir Disoproxil Fumarate; Stribild; 
STB
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFR(CG)
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
full analysis set
FDA
Food and Drug Administration
FDC
fixed dose combination
FTC/TDF
single-tablet regimen of emtricitabine 200 mg/ tenofovir alafenamide 10 mg
FTC
Emtricitabine; F
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
Gilead
Gilead Sciences, Inc.
GS-9883
Bictegravir; BIC; B
HBcAb
hepatitis B core antibody


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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
HCV antibody
HDL
high density lipoprotein
HIV-1
human immunodeficiency virus (Type 1) 
HLGT
high level group term
HLT
high level term
ID
identification
IDMC
independent data monitoring committee
INR
international normalized ratio
IWRS
interactive web response system
KM
Kaplan-Meier
LDL
low density lipoprotein
LLOQ
lower limit of quantitation
LLT
lowest level term
LOCF
last observation carried forward
MedDRA
Medical Dictionary for Regulatory Activities
MH
Mantel-Haenszel 
OLE
open-label extension
PK
pharmacokinetic
PP
per protocol
PT
preferred term
PT
prothrombin time
Q
quartile
Q1
first quartile
Q3
third quartile
RBP
retinol binding protein
RNA
ribonucleic acid
RTV
Ritonavir
SAE
serious adverse events
SAP
statistical analysis plan
SBR
stay on baseline regimen
SD
standard deviation
SE
standard error
SMQ
Standardised MedDRA Query
SOC
system organ class


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TAF
tenofovir alafenamide 
TEAE
treatment-emergent AE
TFL
tables, figures, and listings
TFV
tenofovir
TSH
thyroid stimulating hormone
ULN
upper limit of normal
UACR
urine albumin to creatinine ratio
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 48 interim analysis 
for Study GS-US-380-1961, which will be performed when all subjects have completed their 
Week 48 visit or prematurely discontinued from the study drug. This SAP is based on the study 
protocol amendment 2 dated 10 November 2016 and the electronic case report form (eCRF). The 
SAP will be finalized before data 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 switching to a fixed dose combination (FDC) of bictegravir
(GS-9883; BIC; B) /emtricitabine (FTC; F) /tenofovir alafenamide (TAF) versus continuing 
on a regimen consisting of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF in 
virologically suppressed HIV-1 infected women as determined by the proportion of subject 
with HIV-1 RNA ≥50 copies/mL at Week 48.
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups through Weeks 48.
1.2.
Study Design
Design Configuration and Subject Population
GS-US-380-1961 is a randomized, open label, multicenter, active-controlled study to evaluate 
the safety and efficacy of switching to an FDC of B/F/TAF in HIV-1 infected women who are 
virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥ 12 consecutive weeks prior to screening.
All subjects will be HIV-1 infected women drawn from pre-defined Gilead Sciences In. (Gilead)
clinical studies and must be virologically suppressed. Women in Gilead study GS-US-236-0128 
who completed the Week 48 open-label extension (OLE) visit or any post Week 48 OLE visits,
women in study GS-US-292-0109 who completed the Week 96 visit or any post Week 96 visits, 
or women in studies GS-US-292-0104 or GS-US-292-0111 who completed the Week 144 visit 
or any post Week 144 visits may be eligible to enroll.
Treatment Groups
Subjects who provide written consent and meet all eligibility criteria will be randomized in a 
1:1 ratio to receive open label medication as follows:
Treatment Group 1: FDC of BIC 50 mg/FTC 200 mg/TAF 25 mg (B/F/TAF) administered 
orally, once daily, without regard to food (approximately n = 235)


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Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (approximately n = 235)
Key Eligibility Criteria
Medically stable HIV-1 infected women who meet the following criteria:

Currently on a stable antiretroviral regimen consisting of E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF continuously for ≥12 consecutive weeks preceding the screening 
visit

Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥12 weeks preceding the 
Screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by re-suppression to < 50 copies/mL is allowed

HIV-1 RNA <50 copies/mL at screening

Estimated glomerular filtration rate (eGFR) ≥50 mL/min according to the Cockcroft-Gault 
(C-G) formula at the screening visit
Study Periods / Phases
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, subjects in a country where 
B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC for an 
additional 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.
Subjects who complete the study through the Week 48 Visit and do not continue participation in 
the study will be required to return to the clinic 30 days after the Week 48 Visit for a 30 Day 
Follow-Up Visit.
Schedule of Assessments
After screening procedures, eligible subjects will be randomized 1:1 to Treatment Group 1 or 
Treatment Group 2 and treated for 48 weeks. Following the Screening and Day 1 visits, subjects 
will return for study visits at Weeks 4, 8, 12, and then every 12 weeks until the Week 48 visit.
For all eligible subjects, blood and urine will be collected at Day 1, Weeks 4, 8, 12, and then 
every 12 weeks through the Week 48 visit. Laboratory analyses (including hematology, 
chemistry, and urinalysis), HIV-1 RNA, CD4+ cell count, and complete or symptom directed 
physical examinations will be performed at the Screening, Day 1, and all subsequent study visits.
Adverse events and concomitant medications will be assessed at each visit.
Pharmacokinetics
For all subjects on B/F/TAF (Treatment Group 1), a single anytime pre or post-dose PK blood
sample will be collected at Weeks 8, 24, and 36.


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For all subjects on B/F/TAF (Treatment Group 1), a trough PK blood sample will be obtained 
20-28 hours following the last dose at Weeks 4 and 12. Following an observed dose, one PK 
blood sample will be collected between 1 and 4 hours post-dose.
The concentration of BIC may be summarized using descriptive statistics.
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 the prior treatment regimen group (ie, 
E/C/F/TAF, E/C/F/TDF, and ATV+RTV+FTC/TDF).
Site and/or Stratum Enrollment Limits
Approximately 57 study sites in North America, Dominican Republic, Thailand, Russia, and 
Uganda participated. There was no enrollment limit for individual sites.
Study Duration
The randomized phase of this study is 48 weeks in duration.
1.3.
Sample Size and Power
A total of approximately 470 HIV-1 infected women, randomized in a 1:1 ratio to 2 treatment 
groups (approximately 235 subjects per treatment group), achieves at least 87% power to detect a 
non-inferiority margin of 4% difference in the percentage of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 between the 2 treatment groups.
For sample size and power computation, it is assumed that both treatment groups have 2% of 
subjects with HIV-1 RNA ≥50 copies/mL at Week 48 (based on the historical Gilead
Genvoya®[GEN; E/C/F/TAF] and Stribild® [STB; E/C/F/TDF] studies), that a non-inferiority 
margin is 4%, 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).


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee Analysis
The Week 24 Independent Data Monitoring Committee (IDMC) analysis was conducted after all
subjects enrolled completed their Week 24 visit of the study or prematurely discontinued the 
study drug. The purpose of this interim analysis 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 result or to consider 
early termination of the study even if there is early evidence of favorable efficacy for B/F/TAF.
2.2.
Week 48 Interim Analysis
The Week 48 interim analysis will be conducted after all subjects either complete their Week 48 
visit or prematurely discontinue from the study drug.
This statistical analysis plan describes the analysis plan for the Week 48 interim analysis, the 
primary analysis of this study.
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
The Week 48 interim analysis will include all data collected from the randomized and the 
extension phases of the study. Only data collected in the randomized phase (ie, randomized 
phase data) will be summarized by treatment group, if not specified otherwise. Data collected 
from both phases will be included in data listings. Data included in each phase are defined as 
follows:
Randomized Phase Data

For subjects who are never treated in the extension phase of the study, all available data are 
considered as the randomized phase data.

For subjects treated in the extension phase of the study, randomized phase data are defined as 
data collected up to the extension phase first dose date except for data on adverse events 
(AEs), concomitant medications, pregnancy, and death. For AEs, concomitant medications, 
pregnancy, and death, only data collected prior to the extension phase first dose date are 
included.
Extension Phase Data

Extension phase data are only available from subjects who enter the extension phase of the 
study. Extension phase data are defined as data collected after the extension phase first dose 
date except for data on AEs, concomitant medications, pregnancy, and death. For AEs, 
concomitant medications, pregnancy, and death, data collected on or after the extension 
phase first dose date are included.
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.


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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 study drug refers to premature 
discontinuation of the extension study drug or completion of the extension 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 data 
finalization. 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 randomized study drug. Subjects will be grouped according 
to the treatment to which they were randomized. For the FAS, all randomized phase efficacy data
will be included, unless specified otherwise. This is the primary analysis set for efficacy 
analyses.
3.1.3.
Per Protocol Analysis Set
The Week 48 Per Protocol (PP) Analysis Set will include all subjects who (1) are randomized 
into the study, (2) have received at least 1 dose of randomized 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,
randomized phase efficacy data collected up to 1 day after the randomized phase last dose date
will be included. The Week 48 PP analysis set is the secondary analysis set for efficacy analysis.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis
set:

Subjects who do not have an 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. (Note: lack 
of efficacy is defined as having the check-box for Lack of Efficacy marked as the reason for 
premature study drug discontinuation on the Randomized Phase Study Drug Completion
eCRF page; Table 3-1).


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Table 3-1.
Subjects Excluded from Week 48 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA 
Assessment in Week 48 Analysis Window
Discontinuation from Study Drug prior to or on the 
Upper Bound of Week 48 Analysis Window
HIV-1 RNA Data on Randomized Treatment 
Available in Week 48 Analysis Window
Yes
No
Yes
Due to Lack of Efficacy
+
+
Due to Other Reasons
+
-
No
+
-
+ = Inclusion of Subjects in Week 48 PP analysis set; - = Exclusion of Subjects in Week 48 PP analysis set.

Subjects who do not meet the inclusion criteria for no documented or suspected resistance to 
FTC, TFV, ATV, or EVG, including but not limited to the reverse transcriptase resistance 
mutations K65R and M184V/I.

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in Tables 5-1 and 5-2 in protocol Section 5.4.

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile.
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 randomized study drug. All randomized phase safety data
collected up to 30 days from the randomized phase last dose date 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.
Pharmacokinetic (PK) Analysis Set
The PK Analysis Set will include all subjects who (1) are randomized into the B/F/TAF 
treatment group, (2) have received at least 1 dose of B/F/TAF in the randomized phase of the 
study, and (3) have at least 1 nonmissing PK concentration value for any analyte of interest
reported by the PK lab. The PK analysis set will be used for general PK analyses.
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.


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3.3.
Strata and Covariates
There is no stratification for analysis.
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 48 as 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

Race: (a) black and (b) nonblack

Region: (a) US and (b) Ex-US

Study drug adherence (%): (a) < 95 and (b) ≥ 95 (based on adherence up to Week 48 visit)
The proportion of subjects with hepatitis B virus (HBV) Deoxyribonucleic Acid (DNA) 
< 29 IU/mL at baseline and Week 48, and the change from baseline in log10 HBV DNA by visit 
will be analyzed for the following subject subgroup:

Subjects with HIV/HBV coinfection at baseline
3.4.2.
Subject Subgroups for Safety Analyses
Incidence of all treatment-emergent AEs (TEAEs) will be analyzed for the following subject 
subgroups:

Age (years): (a) < 50 and (b) ≥ 50

Race: (a) black and (b) nonblack

Region: (a) US and (b) Ex-US
Selected safety endpoints may be analyzed for the following subject subgroups (see Section 9.1
for details):

Subjects with HIV/HBV coinfection at baseline

Subjects with incident HIV/HBV coinfection while on study drug (if any)


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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)
Lastly, subgroup analysis by prior treatment regimen (ie, TDF-containing regimen versus 
non-TDF containing regimen) will be performed for the following endpoints:

Urine retinal binding protein (RBP) to creatinine ratio

beta-2 microglobulin to creatinine ratio

Urine albumin to creatinine ratio (UACR)
3.5.
Multiple Comparisons
The noninferiority evaluation of the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as determined by the US FDA-defined snapshot algorithm was the prespecified primary 
comparison. However, the Week 24 interim IDMC analysis was performed prior to the analysis 
for the primary endpoint and an alpha penalty of 0.00001 was applied for the Week 24 interim 
IDMC meeting. Therefore, the alpha level for the primary endpoint (ie, the proportion of subjects 
with HIV-1 RNA ≥ 50 copies/mL at Week 48 as determined by the US FDA-defined snapshot 
algorithm) was adjusted to 0.04999 (corresponding to 95.001% confidence interval [CI]) using 
both the FAS and the Week 48 PP analysis set. The alpha level for the key secondary efficacy 
endpoint, the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined 
by the US FDA-defined snapshot algorithm, will also be adjusted to 0.04999 (corresponding to 
95.001% CI) to be conservative using both the FAS and the Week 48 PP analysis set. No alpha 
level adjustment is applied other than for the primary and key secondary endpoints listed above.
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 non-antiretroviral (ARV) medications in Section 7.4.3.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be 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.
Logarithm (base 10) transformation will be applied to HIV-1 RNA and HBV DNA data for 
efficacy analysis. 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. HBV DNA results of 
“<20 IU/mL HBV DNA detected” or “No HBV DNA detected” will be imputed as 19 IU/mL for 
analysis purpose. HCV RNA results of “<15 IU/mL HCV RNA detected” or “No HCV RNA 
detected” will be imputed as 14 IU/mL for analysis purpose.
Natural logarithm transformation will be used for analyzing concentrations in plasma samples. 
Concentration values that are below the lower limit of quantitation (BLQ) will be presented as 
“BLQ” in the concentration listing.


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3.8.
Analysis Windows
3.8.1.
Definition of Study Day
Study Day 1 (Randomized Phase) is defined as the day when the first dose of the randomized 
study drug (ie, B/F/TAF or SBR) was taken, as recorded on the “Randomized Phase” Study Drug 
Administration eCRF.
Study Day 1 (Extension Phase) is defined as the day when the first dose of extension phase 
study drug (ie, B/F/TAF) was taken, as recorded on the “Extension Phase” Study Drug 
Administration eCRF. This day will only be available for subjects treated in the extension phase 
of the study.
Study Days are calculated relative to randomized phase Study Day 1. For events that occurred 
on or after the randomized phase Study Day 1, study days are calculated as (visit date minus 
randomized phase Study Day 1 plus 1). For events that occurred prior to the randomized phase 
Study Day 1, study days are calculated as (visit date minus randomized phase Study Day 1). All 
study days will be calculated from randomized phase Study Day 1 including observations 
collected from the extension phase of the study.
Last Dose Date (Randomized Phase) is defined as the latest of the randomized study drug end 
dates recorded on the “Randomized Phase” Study Drug Administration eCRF with “Permanently 
withdrawn” box checked for subjects who prematurely discontinued or completed the 
randomized study drug in the “Randomized Phase” according to the Study Drug Completion 
eCRF.
If the last dose date for randomized phase 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 study 
drug or completed the study drug at the data cut date, the latest of nonmissing randomized 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, from the randomized phase data, will be used to impute the 
randomized phase last dose date. For other partial missing last dose date, please see 
programming specification for imputation rule details. For subjects who are still on the 
randomized phase study drug, the data cut date will be used to impute the last dose date.
Last Dose Date (Extension Phase) is defined as the latest of the extension phase study drug end 
dates recorded on the “Extension Phase” Study Drug Administration eCRF with “Permanently 
Withdrawn” box checked for subjects who prematurely discontinued study drug according to the 
“Extension Phase” Study Drug Completion eCRF. This date will only be available for subjects 
treated in the extension phase of the study.
If the last dose date is missing for subjects who prematurely discontinued study drug in the 
extension phase of the study, the latest of nonmissing extension phase 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, from the extension phase data, will be used to impute the extension phase last 
dose date. For subjects who are still on the extension phase study drug, the data cut date will be 
used to impute the last dose date.


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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, for subjects who prematurely discontinued study or who completed study 
according to the Study Completion eCRF. For subjects still on study, the last study date is 
defined to be the latest of data cut date, the clinic visit dates, and the laboratory visit dates, 
including the 30-day follow-up visit date. 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.
Baseline value is defined as the last value obtained on or prior to the randomized phase Study 
Day 1 for all assessments.
3.8.2.
Analysis Windows
Subject visits might not occur on protocol specified days. Therefore, for the purpose of analysis, 
observations collected from the randomized phase of the study (ie, randomized phase data) will 
be assigned to analysis window. Observations collected from the extension phase of the study 
(ie, extension phase data) will not have analysis window assigned and will be included in listings 
with derived visit marked as “Extension”. Any observations from the randomized phase in the 
“Post Week 48” window defined in Tables 3-2 to 3-5 will not be summarized in tables and 
figures, but included in listings.
The analysis windows for HIV-1 RNA, CD4+ cell count, CD4 %, HBV DNA, hematology, 
chemistry, urinalysis, urine pregnancy laboratory tests, eGFRCG, vital signs, and weight are 
presented in Table 3-2.
Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, HBV 
DNA, Hematology, Chemistry, Urinalysis, and 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
Post Week 48
NA
379
Note: HBV DNA collection schedules are as follows: (1) For subjects who meet the definition of HBV infection at screening, 
HBV DNA will be collected at baseline, Weeks 4, 8, 12, 24, 36, and 48. (2) For subjects who meet the definition of HBV 
infection at any postbaseline visit, HBV DNA test will be performed at all subsequent visits. (3) For subjects who do not meet the 
definition of HBV infection at any visit, HBV DNA will be collected at baseline and Week 48.


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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) and HBV serology (including hepatitis B surface antibody 
[HBsAb], hepatitis B surface antigen [HBsAg], hepatitis B e-antigen [HBeAg], hepatitis B 
e-antibody [HBeAb], and hepatitis B core antibody [HBcAb]) are presented in Table 3-3.
Table 3-3.
Analysis Windows for Metabolic Assessments and HBV Serology
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
Post Week 48
NA
421
Note: HBV serology collection schedules are as follows: (1) For subjects who meet the definition of HBV infection at screening, 
HBV serology will be collected at Weeks 12, 24, and Week 48. (2) For subjects who meet the definition of HBV infection at 
any postbaseline visit, HBV serology will be performed at all subsequent visits. (3) For subjects who do not meet the 
definition of HBV infection at any visit, HBV serology will be collected at baseline and Week 48.
The analysis windows for thyroid stimulating hormone (TSH; thyrotropin), renal function 
(including: urine albumin, urine creatinine, urine RBP, and urine beta-2 microglobulin, and 
derived ratios), and safety electrocardiogram (ECG) are presented in Table 3-4.
Table 3-4.
Analysis Windows for TSH, Renal Function, and Safety ECG
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 24
168
2
252
Week 48
336
253
420
Post Week 48
NA
421
The analysis windows for HCV serology and HCV RNA assessments are presented in Table 3-5.
Table 3-5.
Analysis Windows for HCV Serology and HCV RNA Assessments 
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 48
336
2
504
Post Week 48
NA
505


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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 collected from the 
randomized phase of the study will be chosen as follows:

For baseline, the latest available record on or prior to the first dose date of randomized study 
drug will be selected. If there are multiple records with the same collection time or no 
collection 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 HBV DNA, the record(s) collected on the latest day in 
the window will be selected for analysis.
For other numeric observations (eg, except HIV-1 RNA, CD4+ cell count, CD4%, and 
HBV DNA), 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 arithmetic mean will be used.

For baseline and postbaseline HIV-1 RNA, the latest (considering both collection 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 randomized study 
drug will be selected. If there are multiple records with the same collection time or no 
collection 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
The number and percentage of subjects randomized at each country, and investigator will be 
summarized by treatment group and overall using safety analysis set. The denominator for this 
calculation will be the number of subjects in the safety analysis set. Similarly, the number and 
percentage of subjects enrolled in each randomization stratum will be summarized using stratum 
assignment captured in the interactive web response system (IWRS).
If there are discrepancies between IWRS and ARV data with regard to stratum assignment, a 
listing of the discrepancies will be provided.
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 FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:

Still on study drug in the randomized phase, if applicable

Completing study drug in the randomized phase

Prematurely discontinuing study drug in the randomized phase (with summary of reasons for 
discontinuing study drug)

Still on study in the randomized phase, if applicable

Completing study in the randomized phase

Prematurely discontinuing from study in the randomized phase (with summary of reasons for 
discontinuing study)

Entering and treated in the extension phase

Subjects still on study drug in the extension phase

Prematurely discontinuing study drug in the extension phase


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The denominator for the percentages of subjects in each category, except for the categories of 
“subjects still on study drug in the extension phase” and “prematurely discontinuing study drug 
in the extension phase”, will be the number of subjects in the safety analysis set. The 
denominator for the percentage of subjects in the categories of “subjects still on study drug in the 
extension phase” and “prematurely discontinuing study drug in the extension phase” will be the 
numbers of subjects entering and treated in the extension phase.
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 Randomized Study Drug
Duration of exposure to randomized study drug is defined as (the randomized phase last dose 
date – the randomized phase 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 the randomized 
phase of the study at the time of the data cut date.
Duration of exposure to randomized 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), 
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 randomized 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 randomized 
treatment groups. Subjects who completed 48-week randomized phase of the study treatment 
will be censored at the last dose date of the randomized study drug. Subjects who are still on the
randomized study drug will be censored at the imputed last dose date (ie, data cut date). A plot of 
KM estimates for the time to premature discontinuation of the randomized 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 of each randomized study 
drug included in that study drug regimen. The numbers of pills of randomized phase study drug
(ie, B/F/TAF, GEN, STB, ATV, RTV, or FTC/TDF) dispensed and returned are captured on 
study drug accountability eCRF.


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Adherence (%) of a study drug regimen (Note: study drug regimen only includes 1 study drug for 
B/F/TAF, GEN, STB, and 3 study drugs for ATV+RTV+FTC/TDF) will be calculated as follows
for pills dispensed in the randomized phase of the study:






[2]
]
1
[
drug
each
for 
period
dispensing
each
at 
prescribed
pills
of
No.
drug
each
for 
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 of the same dispensing date, 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 for each study drug 
contained in the study drug regimen 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 of the same dispensing date. Total number of pills prescribed is determined by 
summing the number of pills prescribed for each study drug contained in the study drug regimen 
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 the same dispensing period for the study drug, (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, all records in that dispensing period for that study drug will be excluded from 
both denominator and numerator calculation.
Adherence up to Week 48 visit (ie, overall adherence for the randomized phase of the study) will
be calculated using all data from the entire dosing period up to the date of permanent 
discontinuation of the randomized study drugs.
Descriptive statistics for adherence up to Week 48 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 randomized phase of the study in the safety analysis set. No inferential 
statistics will be provided.


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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 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:

HIV-1 RNA categories (copies/mL): (a) < 50, (b) ≥ 50

CD4+ cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, (d) ≥350 to 
< 500, and (e) ≥500

CD4 percentage (%)

Mode of infection (HIV risk factors)

HIV disease status

eGFRCG (mL/min )

Medical history: diabetes mellitus (Yes/No), hypertension (Yes/No), cardiovascular disease 
(Yes/No), and hyperlipidemia (Yes/No) (see Appendix 3 for details)

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 5 for details)

Prior ARV regimen: (a) E/C/F/TAF, (b) E/C/F/TDF; (c) RTV boosted ATV + FTC/TDF (see 
Section 7.4.2 and Appendix 5 for details)


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For categorical data, the Cochran-Mantel-Haenszel (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
6.1.
Primary Efficacy Endpoint
6.1.1.
Definition of the 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.
6.1.2.
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, data collected up to1 day after the randomized 
phase last dose date) 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 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 AE or 
death and have the last available on-treatment HIV-1 RNA 50 copies/mL, or
3) Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than 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 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 and the last available on-treatment HIV-1 RNA < 50 copies/mL, or


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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.
The flowchart of the US FDA-defined snapshot algorithm is provided in Appendix 2.
The Week 48 virologic outcomes for the US FDA-defined snapshot algorithm will be listed.
Note: For switch trials, the US FDA-defined snapshot algorithm classifies subjects who 
discontinue study drug due to AE or death and have the last available on-treatment HIV-1 RNA 
value ≥50 copies/mL in the “HIV-1 RNA ≥50 copies/mL” category. For treatment naive study
population, these subjects will be classified in the “No Virologic Data in the Week 48 Window” 
category.
6.1.3.
Statistical Hypothesis for the Primary Efficacy Endpoint
Null hypothesis: the B/F/TAF group (Treatment Group 1) is at least 4% higher than the SBR 
group (Treatment Group 2) with respect to the proportion of subjects with HIV-1 RNA 
≥50 copies/mL as determined by the US FDA-defined snapshot algorithm at Week 48.
Alternative hypothesis:  the B/F/TAF group (Treatment Group 1) is less than 4% higher than 
the SBR group (Treatment Group 2) with respect to the proportion of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48.
6.1.4.
Primary Analysis of the Primary Efficacy Endpoint
The analysis purpose of the primary efficacy endpoint is to assess the noninferiority of switching 
to B/F/TAF relative to continuing on SBR. Noninferiority will be assessed using a conventional 
95% CI approach, with a noninferiority margin of 4%.
For the interim analysis performed for the IDMC at Week 24, an alpha of 0.00001 has been 
spent. Therefore, the significance level for the 2-sided test in the primary analysis at Week 48 
will be 0.04999 (corresponding to 95.001% CI).
The point estimate of treatment difference (B/F/TAF group – SBR group) in the percentage of 
subjects with HIV-1 RNA ≥ 50 copies/mL and the associated 2-sided 95.001% CI will be 
constructed based on an unconditional exact method using 2 inverted 1-sided tests.
It will be concluded that B/F/TAF is noninferior to SBR if the upper bound of the 2-sided 
95.001% CI of the difference (B/F/TAF group – SBR group) in the percentage of subjects with 
HIV-1 RNA ≥ 50 copies/mL is less than 4%.
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 48 will be summarized.


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If noninferiority of B/F/TAF versus SBR is established, the same 95.001% CI used in evaluating 
noninferiority at Week 48 will be used to evaluate superiority. If the upper bound of the 95.001% 
CI is less than 0, superiority of B/F/TAF over SBR is established. The 2-sided Fisher’s exact test 
will also be used to assess superiority as a secondary assessment.
The FAS will be used for the primary efficacy endpoint analysis and the superiority evaluation.
6.1.5.
Secondary Analysis of the Primary Efficacy Endpoint
A secondary analysis based on the Week 48 PP analysis set will also be performed to evaluate 
the robustness of the primary analysis of the primary endpoint. For this secondary analysis, 
95.001% CI for the treatment difference in the primary efficacy endpoint will also be evaluated 
based on an unconditional exact method using 2 inverted 1-sided tests.
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 Week 48 as determined by 
the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
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 proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined by the
US FDA-defined snapshot algorithm will be analyzed similarly to the primary efficacy endpoint. 
However, the noninferiority margin used for this endpoint will be 10%.
Similarly to the primary efficacy endpoint, noninferiority will be assessed using the conventional 
CI approach. The point estimate of treatment difference (B/F/TAF group – SBR group) in the 
percentage of subjects with HIV-1 RNA < 50 copies/mL and the associated 2-sided 95.001% CI 
will be constructed based on an unconditional exact method using 2 inverted 1-sided tests.
It will be concluded that B/F/TAF is noninferior to SBR if the lower bound of the 2-sided 
95.001% CI of the difference between treatment groups (B/F/TAF group – SBR group) in the 
percentage of subjects with HIV-1 RNA < 50 copies/mL is greater than -10%.
The above analysis will be performed using both the FAS and the Week 48 PP analysis set.


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In addition, the following analyses will be performed using the FAS to evaluate the interaction 
between country and treatment to assess homogeneity of treatment effect across different 
countries.
For each country, 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 on an unconditional exact 
method using 2 inverted 1-sided tests.
The CMH analysis will be used to estimate the odds ratio and corresponding 95% CI for each 
country and overall. The homogeneity of the odds ratios across different countries will be tested 
using a Breslow-Day test and a corresponding p-value will be reported.
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 proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 as determined by the US 
FDA-defined snapshot algorithm (primary endpoint) is expected to be very low (around 2%). The 
efficacy analysis by subgroup will be conducted by assessing the proportion of subjects with 
HIV-1 RNA < 50 copies/mL, determined by the US FDA-defined snapshot algorithm at 
Week 48 (a secondary efficacy endpoint) within each subgroup specified in Section 3.4.1 based 
on the FAS.
For each level of subgroup factors, the proportion difference between treatment groups and the 
associated 2-sided 95% CIs will be computed based on an unconditional exact method using 
2 inverted 1-sided tests.
Additionally, a logistic regression model will be performed which include subgroup factor, 
treatment, and treatment by subgroup factor. 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 48 and their associated 95% CIs for each subgroup will be 
generated.
6.2.2.3.
Analysis of CD4+ Cell Count
All CD4+ cell count will be summarized using observed, on-treatment data (ie, data collected up 
to 1 day after the randomized phase last dose date) for subjects in the FAS and in the Week 48 
PP analysis set, respectively.
The changes from baseline in CD4+ cell count at Week 48 will be summarized by treatment 
group using descriptive statistics. The differences in changes from baseline in 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 as a fixed effect. The change from 
baseline in CD4+ cell count will also be summarized at visits other than Week 48 by treatment 
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The mean and 95% CI of change from baseline in CD4+ cell count over time will be plotted for 
the FAS. 
In addition, the change fi·om baseline in CD4+ cell counts with missing values imputed using the 
last observation canied f01ward (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 the randomized phase last dose 
date) obse1ved 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 nomnissing postbaseline obse1vation collected prior to that visit. 
6.3. 
Tertiary Efficacy Endpoints 
6.3.1. 
Definition of the Tertiary Efficacy Endpoints 
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6.4. 
Changes From Protocol-Specified Efficacy Analyses 
No change from protocol-specified efficacy analysis is planned. 
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7.
SAFETY ANALYSES
Safety data from the randomized phase of the study (ie, randomized phase data) will be 
summarized for the subjects in the safety analysis set. All safety data collected up to 30 days 
after the randomized phase last dose date will be summarized by treatment group, unless 
specified otherwise. All safety data from both phases of the study 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 
lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe) or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will be left as 
“missing” 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 SAE database from the Gilead Drug Safety and Public 
Health (DSPH) Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 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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The TEAE definitions will be applied to the randomized phase data and the 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 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. An AE meeting the TEAE criteria will be considered as a TEAE in the extension phase.
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 randomized study drug, 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 for the randomized phase 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 randomized 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 the minimum of (1) the randomized phase last dose 
date plus 30 days  AND (2) the extension phase first dose date minus 1 day
The event is considered treatment emergent for the extension phase if both of the following 
2 criteria are met:

The month and year (or year) of the AE onset is after the month and year (or year) of the 
first dosing date of extension phase 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 extension 
phase 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 randomized study drug, will be 
considered as a TEAE for the randomized phase. 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 the randomized study drug will be considered as a TEAE for 
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7.1.6.
Summaries of Adverse Events and Death
Only TEAEs in the randomized phase will be included in the summary tables. 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 reported in the randomized phase and 
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 randomized phase will be also included in this summary.
Treatment-emergent death refers to deaths that occurred between the randomized phase first dose 
date and the randomized phase 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 TEAEs, Grade 3 or 4 TEAEs, 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 for all AEs regardless of the study phases will be provided for the
following:

All AEs

Grade 3 and 4 AEs


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
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 5). 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 DSPH 
and reviewed by Gilead medical monitors, which is the same PT listing used to search 
“Cardiovascular Disease” medical history (see details in Appendix 3).
The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
provided 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 the 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 DSPH and reviewed by Gilead medical monitors (see details in Appendix 4).
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 randomized phase of 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 
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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.
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

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 randomized 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 x (4.0 –
albumin (g/dL)).
Toxicity grading for calcium will be applied based on the corrected values.
Estimate GFR
The following formulae will be used to calculate eGFRCG:

eGFR(CG) (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / 
(SCr (mg/dL) × 72), where weight is total body mass in kilograms.


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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, 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.
For the international normalized ratio (INR) of prothrombin time (PT), protocol-specified 
toxicity grading scale depends on the upper limit of normal range (ULN). While the ULN of INR 
depends on whether the subject is taking anticoagulant medication or not (ie, Not taking oral 
anticoagulant: 0.8 – 1.2; Taking oral anticoagulant: 2.0 – 3.0), this information is not collected 
by the reference laboratory. As a result, INR will be graded by assuming subject is not taking an 
oral anticoagulant, which is a conservative approach that may lead to over-reporting of 
abnormalities for INR. Consequently, INR and PT will not be included in summaries of 
laboratory abnormalities, but will be included in listings for the following reasons: 1) INR and 
PT are reflexive tests; 2) only the absolute values, not the toxicity grade, are needed for subject
management purposes; and 3) more importantly, the toxicity grades for INR may be 
over-reported.
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 from the randomized 
phase last dose date. 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.


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Both urine RBC based on microscopic examination, labeled as Hematuria (Quantitative), and 
urine blood based on dipstick, labeled as Hematuria (Dipstick), are assessed routinely and 
assigned a toxicity grade in this study. Urine RBC based on microscopic examination will be 
presented in laboratory toxicity summary tables and listings while urine blood based on dipstick 
will be presented in the listings only.
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 the randomized phase last dose 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 metabolite 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 the 
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 randomized phase of 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.
A lipid modifying medication is defined as a medication with drug class = “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 randomized 
phase of the study: baseline values, Week 48 values, and changes from baseline at Week 48 will 
be summarized by treatment group using descriptive statistics. Baseline and change from 
baseline at Week 48 will be compared between the 2 treatment groups using a 2-sided Wilcoxon 
rank sum test. Only subjects with both baseline and Week 48 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.


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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 collected in the randomized phase of this study:

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 randomized 
phase last dose date. 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.
Furthermore, ALT flare, defined as subjects with ALT elevation > 2 x Baseline ALT and 
> 10 x ULN and confirmed at 2 consecutive visits, will be evaluated and listed for subjects with 
HIV/HBV coinfection at baseline.


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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 Creatinine, Urine Retinol Binding Protein to Creatinine Ratio, and 
Beta-2-Microglobulin to Creatinine Ratio
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 
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, and based on the last on-treatment value (ie, 
data collected after the first dose date up to 1 day after the randomized phase 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.
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 at 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 randomized 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.
7.4.
Prior and Concomitant Medications
7.4.1.
Antiretroviral Medications
Any nonstudy ARV medications used prior to, during, or after the study (if collected) are all 
recorded on the ARV eCRF. All ARV medications recorded on the ARV eCRF will be coded 
using the Gilead-modified World Health Organization (WHO) Drug Dictionary for ARV 
medication. The WHO preferred name and drug code will be attached to the clinical database. 
All ARV medications recorded on the ARV eCRF will be listed. No inferential statistics will be
provided.
7.4.2.
Prior Antiretroviral Medications
Prior ARV medications are defined as ARV medications taken on or up to 2 days prior to the 
first dose date of randomized study drug based on ARVs reported on ARV eCRF (see 
Appendix 5 for details). The number and percentage of subjects in each prior ARV regimen will
be summarized as part of baseline disease characteristics table.
7.4.3.
Concomitant Non-Antiretroviral 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 name 
and drug code will be attached to the clinical database. Use of concomitant medications from the 
randomized phase first dose date to the randomized phase last dose date will be summarized 


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(number and percentage of subjects) by treatment group and preferred name. Multiple drug use 
(by preferred name) will be counted only once per subject. The summary will be sorted by 
decreasing order of total frequency.
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 for the randomized phase of the study. 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 randomized phase last dose date

The month and year of stop of the medication is before the randomized phase first dose date
If the start and stop date of non-ARV medications are complete, the start date is not after the 
randomized phase last dose date and the stop date is not before the randomized phase first dose 
date, or the non-ARV medications are marked as ongoing and start date is on or before the 
randomized phase last dose date, the non-ARV medications are concomitant for the randomized 
phase of the study.
Summaries of non-ARV concomitant medications will be provided for the safety analysis set. 
Subjects with any non-ARV concomitant medications will be listed. No inferential statistics will 
be provided.
7.5.
Electrocardiogram Results
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.
7.6.
Other Safety Measures
A data listing will be provided for subjects experiencing pregnancy during the study. Physical 
examination was not collected in the eCRF. Therefore, it will not be included in the analysis.
7.7.
Subject Subgroup for Safety Endpoints
Incidence of all treatment-emergent AEs will be repeated within each subgroup defined in 
Section 3.4.2 using the safety analysis set. In addition, subgroup analysis by prior treatment 
regimen (ie, TDF-containing regimen versus non-TDF containing regimen) will be performed for 
renal endpoints including urine RBP to creatinine ratio, beta-2 microglobulin to creatinine ratio, 
and UACR.
7.8.
Changes From Protocol-Specified Safety Analyses
No change from protocol-specified safety analysis is planned.


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8.
PHARMACOKINETIC ANALYSES
8.1.
Analysis for Trough and Postdose PK (PK Analysis Set)
The following listings will be provided for trough and postdose PK analysis for subjects in the 
PK analysis set:

Listing of PK sampling details (“Trough” PK samples [defined as samples collected within a 
range of 20.0 to 28.0 hours, inclusive, after previous dosing time] will be marked in the 
listing)

Listing of study drug administration record for PK dosing
PK sampling details for single PK, trough PK, and postdose PK samples will be included in one 
listing. Similarly, study drug administration records for single PK, trough PK, and postdose PK 
samples will also be included in one listing.
8.2.
Changes from Protocol-Specified Pharmacokinetic Analysis
No change from protocol-specified PK analyses is planned.


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9.
SPECIAL POPULATION ANALYSES
Only randomized phase data will be included for the special population analyses.
9.1.
Analyses for HIV/HBV Coinfected Subjects
Subjects with HIV/HBV coinfection at baseline are defined as subjects meet any of the following 
two criteria:

Positive HBsAg on or prior to the randomized phase 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 randomized phase first dose date.
The following analyses will be provided by treatment and overall for subjects with HIV/HBV 
coinfection at baseline:

The proportion of subjects with HBV DNA < 29 IU/mL at baseline and Week 48

Treatment-emergent adverse events overall summary

Treatment-emergent adverse events by SOC, HLT, and PT

Treatment-emergent laboratory abnormalities

The change from baseline for liver-related laboratory tests, including ALT, AST, ALP, total 
bilirubin, direct and indirect bilirubin

Listing of adverse events

Listing of liver-related laboratory tests and HBV DNA results
HBV DNA will be analyzed using observed, on-treatment data (ie, data collected up to the 1 day 
after the randomized phase last dose date) for subject in the FAS with HIV/HBV coinfection at 
baseline.
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 randomized phase first dose date and on or prior to the randomized 
phase last dose date, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA (ie, HBV 
DNA ≥ 20 IU/mL) after the randomized phase first dose date and on or prior to the 
randomized phase last dose date, or


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
Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the randomized phase first dose date and on or prior to the 
randomized phase last dose date: 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 HCV 
antibody (HCVAb) and quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) on or prior to the 
randomized phase first dose date. The following analyses will be conducted for subjects with 
HIV/HCV coinfection at baseline:

Treatment-emergent adverse events overall summary

Treatment-emergent adverse events by SOC, HLT, and PT

Treatment-emergent laboratory abnormalities

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results
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 randomized phase first dose date and on or prior to the randomized 
phase last dose date with baseline HCVAb Negative or missing, or

Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the randomized phase first dose 
date and on or prior to the randomized phase last dose date, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the randomized phase first dose date and on or prior to the 
randomized phase last dose date: Acute hepatitis C, Chronic hepatitis C, Hepatitis C,  
Hepatitis C antibody positive, Hepatitis C RNA positive, Hepatitis C virus test positive


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
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CONFIDENTIAL
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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


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
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19 October 2017
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.


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
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19 October 2017
11.
SOFTWARE
SASVersion 9.4 (SAS Institute Inc., Cary, NC, USA) 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.
Phoenix WinNonlin® Version 6.4 (Certara USA Inc., Princeton, NJ, USA) is to be used for all 
PK analyses.


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
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12.
SAP REVISION
Revision Date
(dd month, yyyy)
Section
Summary of Revision
Reason for Revision


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
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13.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm
Appendix 3.
Selected Medical History
Appendix 4.
Hepatic Events
Appendix 5.
Programming Specification


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
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Appendix 1.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48d,v
30 Day 
Follow-Upe
ESDDf
4
8
12
24
36
48
Every 12 Weeks
Informed Consent
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam 
X
X
X
X
X
Symptom-Directed Physical Exam
X
X
X
X
X
X
12-Lead ECG 
X
X
X
X
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Chemistryh
X
X
X
Xw
Urine Pregnancy Testi
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testi
X
Chemistry Profilej
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentsk
X
X
X
X
Xw
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilel
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAm
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Planeln
X


B/F/TAF 
GS-US-380-1961 
Statistical Analysis Plan - Week 48 Interim Analysis 
Study Procedurt' 
Sc.ret'ning• 
Plasma HBV DNA
0 
HCVAb" 
X 
HCVRNAP 
X 
HN -1 Genotype/Phenotypeq 
Single PK Draw 
Trough PK Draw• 
PK Sample (post-dose)' 
Observed In-Clinic Dose• 
Provide Dosing Diatyu 
Collect Dosing DiarY' 
Plasma Sample Storage
1 
Urine Satnple Storage
1 
Whole Blood Storage Sample
1 
~PD 
n 
I 
I 
Randomization 
Study Drug Dispensation 
Study Drug Accountability 
a 
Evaluations to be completed within 30 days prior to Day 1. 
Day l b 
4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b 
Subjects should initiate dosing of study dmg on the same day as the Day 1 visit. 
8 
X 
X 
X 
X 
X 
X 
X 
Version 1.0 
End ofWt't'kc 
Post Week 48d,v 
30Day 
12 
24 
36 
48 
Every 12 Wet'ks 
Follow-u p• 
ESDDr 
X 
X 
X 
xw 
X 
X 
X 
xw 
~ 
xq 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
xv 
xv 
X 
X 
X 
X 
X 
X 
c 
All study visits should be± 2 days of the protocol-specified visit date based on the Day 1 visit through We.ek 12 and completed \.,-ithin ± 6 days at We.ek 24 and Week 36, 
lmless otherwise specified. The visit window at Week 48 will be± 6 weeks of the protocol-specified visit date. 
d 
At the Week 48 Visit, subjects in a cmmtry where GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/T AF FDC for an additional48 weeks, 
or until the product becomes accessible to subjects through an access program, or lmtil Gilead Sciences elects to discontinue the study in that colmtry, whichever occm-s first. 
Study visits are to be completed every 12 weeks, within ± 6 days of the protocol-spe.cified visit date lmless otherwise specified. 
CONFIDENTIAL 
Page 55 
19 October 2017 


BIF!TAF 
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Statistical Analysis Plan- Week 48 Interim Analysis 
Version 1.0 
e 
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30-Day Follow-Up Visit, a± 6 days window may be used. Required for subjects 
who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Subjects who participate 
post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit. 
f 
Early Study Drug Discontinuation visit to occur within 72 hours oflast dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Week 48 Visit even if the subject discontinues study drug. 
g 
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature 
h 
Urine Chemistry includes urine albumin, urine creatinine, urine protein, retinol binding protein, and beta-2 microglobulin 
Women of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test. 
Chemistry profile: alkaline phosphatase, AST, AL T, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing is performed in subjects with total amylase > 1.5 x ULN). At Day 1, 
Weeks 24, and 48 and every 24 weeks during the post Week 48 period, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of the 
chemistry profile. TSH will be collected at Screening, Day 1, Weeks 24, and 48, as well as every 24 weeks post Week 48, and ESDD if applicable. 
k 
Fasting glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the subject must 
return within 72 hours in a fasted state to draw blood for the metabolic assessments. 
CBC with differential and platelet count. 
m 
If the HIV-1 RNA value is 2: 50 copies/mL at Week 48, a retest HIV -1 RNA value must be collected within two to three weeks of the initial test. 
n 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb). 
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex HBeAb), and quantitative HBsAg. If positive HBcAb with negative HBsAg and negative 
HBsAb, reflex testing for plasma HBV DNA (if positive, reflex HBeAg). IfHBeAg is performed and found to be negative, reflex HBeAb. 
o 
For subjects who meet the definition ofHBV infection, the following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) and HBeAg 
(if negative, reflex HBeAb) at Days 1, 12, 24 and then every 24 weeks. 
p 
Subjects who are HCV Ab positive will have a HCV RNA test performed at screening and every 24 weeks. 
q 
HIV-1 genotype/phenotype testing for subjects with HIV-1 RNA 2: 200 copies/mL and virologic rebound, at early study drug discontinuation or Week 48. Following 
unconfirmed virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to the next scheduled visit or at the next scheduled study visit, for a 
HIV-1 RNA and HIV-1 genotype/phenotype (reverse transcriptase, protease and integrase) blood draw. Based on the results of this testing, subjects should be managed 
according to the Virologic Rebound Schema (Section 6.13.1 ). 
r 
All subjects on GS-9883/F/T AF (Treatment Group 1 only) will have a single anytime PK blood sample collected at Weeks 8, 24 and 36. 
s 
Subjects on GS-9883/F/T AF (Treatment Group 1 only) will have a Trough PK blood sample collected between 20-28 hours following their last dose at Weeks 4 and 12. 
Subjects must be instructed to not take their study drugs on the morning of their visit for the trough sample collection. If the subject has taken their dose of study drugs prior 
to the visit, the visit may proceed, but the subject must return within 72 hours for the single trough PK blood sample collection. In the event a subject routinely takes their 
study drug in the evening, a single anytime sample may be drawn at Weeks 4 and 12 as the subject will not be instructed to change their dosing time to accommodate this 
trough PK draw. A post-dose PK blood sample will be collected between 1 and 4 hours post dose following an observed, in-clinic dose. 
Plasma storage samples banked for possible future protocol-related testing (safety, virology, pharmacokinetic analysis). Urine storage samples banked for ~;.;.;..;.;;.;..;;.;;.;.;;;;..;;......, 
IJrotocol-related safety testi11g includi11g urine chemist:ry. Whole blood sampl:::::.Jotential virologic resistance testing and/or HIV DNA genotyping . .__P_o_· _____ __. 
u 
A dos1ng diary will be dispensed for all Treatment Group 1 sUDJects to complete pnor to each of the PK sample visits. 
v 
Open-label GS-9883/F/T AF FDC will be dispensed to subjects participating in the study post Week 48 starting at the Week 48 Visit. 
w 
Every 24 weeks only. 
x 
Dosing diaries will be collected from subjects for the single anytime PK and trough PK collection (Treatment Group 1 only). If a dosing diary is not returned the site may ask 
the subject for the time of the last dose and if it was taken with or without food. 
CONFIDENTIAL 
Page 56 
190ctober2017 


B/F/TAF 
GS-US-380-1961 
Statistical Analysis Plan - Week 48 Interim Analysis 
Version 1.0 
Appendix 2. 
Flowchart of US FDA-defined Snapshot Algorithm 
The following flowchali for US FDA-defined snapshot algorithm is based on the US FDA 
Guidance on Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for 
Treatment {U. S. Department of Health and HUlllan Services 2015} 
Is there at least I on-
treatment• HJV-1 RNA data 
------~ 
~------, 
Yes 
collected in the Snapshot 
o 
Is the last available on-treatment• 
HIV-l RNA in the Snapshot 
window< 50 copieslmL? 
Yes 
HIV-1 RNA < 
50 copics/ml"' 
HIV-1 R,'IA ~ 
50 copies/m L 
window? 
1r 
Is study drug premanuely 
discontinued on <>r prior to the 
upper linlit of Lhc Snapshot 
window? 
.I 
Yes .. 
ls discontinuation of the study 
drug due to Lack of Efficacy'! 
~0 
Is discontinuation of the study 
drug due to 1\I<;JOcath'? 
Yes 
1s the last available on-
Is the last available on-
treatment• HJY·I RNA < trearment• HfV-1 RNA < 
50 copies.lmL 
No Virologic Data: 
Discontinued Study 
Drug Due to Other 
Reason and Last mV-1 
R~A <50 copics/mL 
50 copieslmL 
No Virologic Data: 
Discontinued Study 
Drug Due to AE/Death 
and Last HIV-1 RNA < 
50 copics/mt~ 
No 
No Virologic Data: 
Missing Da t~ during 
Window but on Study 
Drug 
• On-Treatment HI V-I RNA data include all HI V-I RNA data for subjects who are on-going and HJ V-1 RNA data up to I 
day after the last dose date of study drug for subjects who prematurely discontinue or complete study drug. 
CONFIDENTIAL 
Page 57 
19 October 2017 


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
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19 October 2017
Appendix 3.
Selected Medical History
Number and percentage of subjects with selected medical history of Diabetes Mellitus, 
Hypertension, Cardiovascular Disease, and Hyperlipidemia will be summarized by treatment as 
baseline disease characteristics. A subject who had medical history of one of these diseases is a 
subject who experience at least one of the following events:

At least 1 medical history record with MedDRA PT (mh.MDRPT) in the following selected 
PT listing for the corresponding disease with start date on or prior to the randomized phase 
first dose date.

At least 1 AE record with MedDRA PT (ae.MDRPT) in the following selected PT listing for 
the corresponding disease with start date on or prior to the randomized phase first dose date.

At least 1 concomitant medications record with medication class and indication in the 
following selected listing for the corresponding disease with start date on or prior to the 
randomized phase first dose date.
If the start date is incomplete but the month and year (or year alone) of the start date is the same 
as or before the month and year (or year alone) of the first dosing date of randomized study drug, 
the event will be included. If the start date is completely missing, the event will be included.
Four variables (ie, DIABETES, HTENSION, CARDDIS, and HLIPDEM) will be added to raw 
Medical History and Adverse Events datasets. A medical history or an AE record will be flagged 
for a disease of interest if its MedDRA PT included in the following pre-specified PT list for the 
corresponding disease of interest, which include all PTs from the narrow or broad search of the 
following SMQs under MedDRA 19.1 provided by Gilead DSPH and reviewed by Gilead 
medical monitors.
Disease of Interest
SMQ Source
Diabetes Mellitus (DIABETES)
Hyperglycaemia/new onset diabetes mellitus (SMQ) – Narrow Scope Term
Hyperlipidemia (HLIPDEM)
Dyslipidaemia (SMQ)
Hypertension (HTENSION) 
Hypertension (SMQ)
Cardiovascular disease (CARDDIS)
Ischaemic central nervous system vascular conditions (SMQ) – Narrow Scope 
Term
Myocardial infarction (SMQ) - Narrow Scope Term
Other ischaemic heart disease (SMQ) - Narrow Scope Term
Similarly, two variables (ie, DRUGF and DRUGTYP) will be added to raw Concomitant 
Medication dataset. A concomitant medication record will be flagged for a disease of interest if 
its medication class and indication included in the following listing for the corresponding disease 
of interest.
The selected combination of medication class and indication are listed as follows, which was 
reviewed by Gilead medical monitors.


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
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19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
Hypertension (HTENSION) 
1
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
LISINOPRIL
2
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ANTI-HYPERTENSIVE
LOSARTAN
3
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPENTENSION
RAMIPRIL
4
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION
CAPTOPRIL
5
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION
ENALAPRIL
6
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION
HYDROCHLOROTHIAZIDE 
W/OLMESARTAN
7
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION
OLMESARTAN MEDOXOMIL
8
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION
RAMIPRIL
9
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION
SALUTEC
10
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION
VALSARTAN
11
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION 
STAGE  I
CAPTOPRIL
12
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ARTERIAL HYPERTENSION 
STAGE 1
CANDESARTAN
13
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
BENIGN ESSENTIAL 
HYPERTENSION
LISINOPRIL
14
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
BENIGN ESSENTIAL 
HYPERTENSION
LOSARTAN
15
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL 
(PRIMARY)HYPERTESION
ZESTORETIC
16
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL HYPERTENSION
COROVAL B
17
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL HYPERTENSION
ENALAPRIL MALEATE
18
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL HYPERTENSION
LISINOPRIL
19
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL HYPERTENSION
LOSARTAN
20
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL HYPERTENSION
TRIBENZOR
21
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL HYPERTENSION
ZESTORETIC
22
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ESSENTIAL PRIMARY
HYPERTENSION
IRBESARTAN
23
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BLOOD PRESSURE
COVERAM


B/F/TAF
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Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
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Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
24
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BLOOD PRESSURE
ENALAPRIL
25
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BLOOD PRESSURE
IRBESARTAN
26
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BLOOD PRESSURE
LISINOPRIL
27
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BLOOD PRESSURE
LOSARTAN
28
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BLOOD PRESSURE
LOSARTAN POTASSIUM
29
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BLOOD PRESSURE
RAMIPRIL
30
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HIGH BOLD PRESSURE
LOSARTAN
31
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HISTORY OF MYOCARDITIS
RAMIPRIL
32
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HTN
ZESTORETIC
33
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERRTENSION
ZESTORETIC
34
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTEENSION
LISINOPRIL
35
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
AMLODIPINE 
W/HYDROCHLOROTHIAZIDE/VALS
ARTAN
36
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
AMLODIPINE W/VALSARTAN
37
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
BENAZEPRIL
38
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
BENAZEPRIL HYDROCHLORIDE
39
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
BENICAR HCT
40
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
BI PREDONIUM
41
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
CANDESARTAN
42
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
CANDESARTAN CILEXETIL
43
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
CAPTOPRIL
44
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
CO-DIOVAN
45
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
COROVAL B
46
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
DIOVAN AMLO


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Version 1.0
CONFIDENTIAL
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19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
47
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
DIOVAN TRIPLE
48
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
EDARBYCLOR
49
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
ENALAPRIL
50
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
ENALAPRIL MALEATE
51
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
FOSINOPRIL
52
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
HYDROCHLOROTHIAZIDE 
W/LOSARTAN
53
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
HYZAAR
54
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
IRBESARTAN
55
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
KARVEA HCT
56
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
LISINOPRIL
57
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
LOSARTAN
58
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
LOSARTAN POTASSIUM
59
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
NAPRIX A
60
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
OLMESARTAN MEDOXOMIL
61
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
PERINDOPRIL ERBUMINE
62
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
PRITORPLUS
63
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
QUINAPRIL
64
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
RAMIPRIL
65
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
SALUTEC
66
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
TELMISARTAN
67
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
TRIBENZOR
68
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
VALSARTAN
69
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
VASERETIC
70
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION
ZESTORETIC


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 62
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
71
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION ESSENTIAL
CANDESARTAN CILEXETIL
72
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION ESSENTIAL
DIOVAN TRIPLE
73
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION, BENIGN
LISINOPRIL
74
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION, BILATERAL 
LOWER LEG SWELLING
LISINOPRIL
75
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION, ESSENTIAL
ZESTORETIC
76
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSION, WORSENING 
HYPERTENSION
LISINOPRIL
77
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSIONPROPHYLAXI
S
RAMIPRIL
78
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSIVE
RAMIPRIL
79
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENSIVE CRISIS
CAPTOPRIL
80
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTENTION
LISINOPRIL
81
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTONIA
RAMIPRIL
82
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPOKALEMIA
LOSARTAN POTASSIUM
83
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
POOR CONTROL OF BLOOD 
PRESSURE
LISINOPRIL
84
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
PREVENTATIVE FOLLOWING 
ACUTE MYCARDIAL 
INFARCTION
PERINDOPRIL
85
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
PRIMARY ESSENTIAL 
HYPERTENSION
ENALAPRIL MALEATE
86
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
PROTEINURIA
BENAZEPRIL
87
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
PROTEINURIA
ENALAPRIL
88
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
PROTEINURIA
LISINOPRIL
89
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
WORSENING HYPERTENSION
BENAZEPRIL
90
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
WORSENING HYPERTENSION
PERINDOPRIL
91
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
WORSENING HYPERTENSION
PRETERAX ARGININE
92
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
WORSENING OF 
HYPERTENSION
LISINOPRIL
93
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
WORSENING OF 
HYPERTENSION
RAMIPRIL


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 63
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
94
ANTIHYPERTENSIVES
BENIGN HIGH BLOOD 
PRESSURE
DOXAZOSIN
95
ANTIHYPERTENSIVES
EXACERBATION OF 
HYPERTENSION
CLONIDINE
96
ANTIHYPERTENSIVES
HEADACHE
HYDRALAZINE
97
ANTIHYPERTENSIVES
HIGH BLOOD PRESSURE
CLONIDINE HYDROCHLORIDE
98
ANTIHYPERTENSIVES
HIGH BLOOD PRESSURE
RILMENIDINE
99
ANTIHYPERTENSIVES
HYPERTENSION
CLONIDINE
100
ANTIHYPERTENSIVES
HYPERTENSION
CLONIDINE HYDROCHLORIDE
101
ANTIHYPERTENSIVES
HYPERTENSION
DOXAZOSIN
102
ANTIHYPERTENSIVES
HYPERTENSION
DOXAZOSIN MESILATE
103
ANTIHYPERTENSIVES
HYPERTENSION
HYDRALAZINE
104
ANTIHYPERTENSIVES
HYPERTENSION
HYDRALAZINE HYDROCHLORIDE
105
ANTIHYPERTENSIVES
HYPERTENSION
METHYLDOPA
106
ANTIHYPERTENSIVES
HYPERTENSION
TADALAFIL
107
ANTIHYPERTENSIVES
PULMONARY HYPERTENSION
TADALAFIL
108
ANTIHYPERTENSIVES
VASODILATION-STENT 
PROCEDURE
HYDRALAZINE
109
ANTIHYPERTENSIVES
WORSENING HYPERTENSION
HYDRALAZINE HYDROCHLORIDE
110
BETA BLOCKING AGENTS
ARTERIAL HYPERTENSION
ATENOLOL
111
BETA BLOCKING AGENTS
ARTERIAL HYPERTENSION
METOPROLOL SUCCINATE
112
BETA BLOCKING AGENTS
ARTERIAL HYPERTENSION / 
ICHEMIC HEART DISEASE
BISOPROLOL
113
BETA BLOCKING AGENTS
ESSENTIAL HYPERTENSION
METOPROLOL
114
BETA BLOCKING AGENTS
HEART FAILURE AND 
HYPERTENSION
CARVEDILOL
115
BETA BLOCKING AGENTS
HEART HEALTH
ATENOLOL
116
BETA BLOCKING AGENTS
HIGH BLOOD PRESSURE
ATENOLOL
117
BETA BLOCKING AGENTS
HIGH BLOOD PRESSURE
BISOPROLOL 
W/HYDROCHLOROTHIAZIDE
118
BETA BLOCKING AGENTS
HIGH BLOOD PRESSURE
METOPROLOL
119
BETA BLOCKING AGENTS
HISTORY OF MYOCARDITIS
BISOPROLOL
120
BETA BLOCKING AGENTS
HYPERTENSION
ATENOLOL
121
BETA BLOCKING AGENTS
HYPERTENSION
BISOPROLOL FUMARATE
122
BETA BLOCKING AGENTS
HYPERTENSION
CARVEDILOL
123
BETA BLOCKING AGENTS
HYPERTENSION
LABETALOL
124
BETA BLOCKING AGENTS
HYPERTENSION
METOPROLOL
125
BETA BLOCKING AGENTS
HYPERTENSION
METOPROLOL SUCCINATE
126
BETA BLOCKING AGENTS
HYPERTENSION
METOPROLOL TARTRATE
127
BETA BLOCKING AGENTS
HYPERTENSION
NEBICARD V
128
BETA BLOCKING AGENTS
HYPERTENSION
NEBICARD-H
129
BETA BLOCKING AGENTS
HYPERTENSION
NEBIVOLOL
130
BETA BLOCKING AGENTS
HYPERTENSION
NEBIVOLOL HYDROCHLORIDE


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 64
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
131
BETA BLOCKING AGENTS
HYPERTENSION
PROPRANOLOL
132
BETA BLOCKING AGENTS
HYPERTENSION
PROPRANOLOL HYDROCHLORIDE
133
BETA BLOCKING AGENTS
HYPERTENSION AND 
MIGRAINE
ATENOLOL
134
BETA BLOCKING AGENTS
HYPERTENSION ESSENTIAL
ATENOLOL
135
BETA BLOCKING AGENTS
HYPERTENTION
METOPROLOL SUCCINATE
136
BETA BLOCKING AGENTS
HYPETENSION
BISOPROLOL
137
BETA BLOCKING AGENTS
PAROXYSM OF SINUS 
TACHYCARDIA
PROPRANOLOL
138
BETA BLOCKING AGENTS
PRIMARY ESSENTIAL 
HYPERTENSION
CARVEDILOL
139
BETA BLOCKING AGENTS
RAPID HEART BEAT
METOPROLOL SUCCINATE
140
CALCIUM CHANNEL BLOCKERS
ANTIHYPERTENSIVE
AMLODIPINE
141
CALCIUM CHANNEL BLOCKERS
ARTERIAL HYPERTENSION
AMLODIPINE
142
CALCIUM CHANNEL BLOCKERS
ARTERIAL HYPERTENSION
VERAPAMIL
143
CALCIUM CHANNEL BLOCKERS
ATRIAL FIBRILLATION
DILTIAZEM
144
CALCIUM CHANNEL BLOCKERS
ELEVATED BLOOD PRESSURE
AMLODIPINE
145
CALCIUM CHANNEL BLOCKERS
ELEVATED BLOOD PRESSURE
AMLODIPINE BESILATE
146
CALCIUM CHANNEL BLOCKERS
ESSENTIAL HYPERTENSION
AMLODIPINE
147
CALCIUM CHANNEL BLOCKERS
ESSENTIAL HYPERTENSION
AMLODIPINE BESILATE
148
CALCIUM CHANNEL BLOCKERS
ESSENTIAL HYPERTENSION
FELODIPINE
149
CALCIUM CHANNEL BLOCKERS
ESSENTIAL PRIMARY 
HYPERTENSION
AMLODIPINE
150
CALCIUM CHANNEL BLOCKERS
HIGH BLOOD PRESSURE
AMLODIPINE
151
CALCIUM CHANNEL BLOCKERS
HTN
AMLODIPINE
152
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
AMLODIPINE
153
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
AMLODIPINE BESILATE
154
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
BARNIDIPINE HYDROCHLORIDE
155
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
DILTIAZEM
156
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
DILTIAZEM HYDROCHLORIDE
157
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
FELODIPINE
158
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
NIFEDIPINE
159
CALCIUM CHANNEL BLOCKERS
HYPERTENSION
VERAPAMIL
160
CALCIUM CHANNEL BLOCKERS
HYPERTENSION 
(ESSENTIAL/PRIMARY)
VERAPAMIL HYDROCHLORIDE
161
CALCIUM CHANNEL BLOCKERS
HYPERTENSION ESSENTIAL
FELODIPINE
162
CALCIUM CHANNEL BLOCKERS
HYPERTNESION
AMLODIPINE BESILATE
163
CALCIUM CHANNEL BLOCKERS
HYPTERTENSION
AMLODIPINE
164
CALCIUM CHANNEL BLOCKERS
PRESTUDY HYPERTENSION
AMLODIPINE
165
CALCIUM CHANNEL BLOCKERS
SECONDARY STROKE 
PREVENTION
AMLODIPINE
166
CALCIUM CHANNEL BLOCKERS
SICK SINUS SYNDROME
VERAPAMIL


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 65
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
167
CALCIUM CHANNEL BLOCKERS
WORSENING OF 
HYPERTENSION
AMLODIPINE
168
CARDIAC THERAPY
HYPERTENSION
UBIDECARENONE
169
DIURETICS
ARTERIAL HYPERTENSION
HYDROCHLOROTHIAZIDE
170
DIURETICS
BENIGN ESSENTIAL 
HYPERTENSION
HYDROCHLOROTHIAZIDE
171
DIURETICS
BORDERLINE HYPERTENSION
HYDROCHLOROTHIAZIDE
172
DIURETICS
DIURETIC
FUROSEMIDE
173
DIURETICS
ELEVATED BLOOD-PRESSURE 
READING, WITHOUT 
DIAGNOSIS OF 
HYPERTENSION
HYDROCHLOROTHIAZIDE
174
DIURETICS
ESSENTIAL HYPERTENSION
FUROSEMIDE
175
DIURETICS
ESSENTIAL HYPERTENSION
HYDROCHLOROTHIAZIDE
176
DIURETICS
HIGH BLOOD PRESSURE
HYDROCHLOROTHIAZIDE
177
DIURETICS
HYPERTENSION
AMILORIDE
178
DIURETICS
HYPERTENSION
BUMETANIDE
179
DIURETICS
HYPERTENSION
CHLORTALIDONE
180
DIURETICS
HYPERTENSION
DYAZIDE
181
DIURETICS
HYPERTENSION
FUROSEMIDE
182
DIURETICS
HYPERTENSION
HYDROCHLOROTHIAZIDE
183
DIURETICS
HYPERTENSION
INDAPAMIDE
184
DIURETICS
HYPERTENSION
MODURETIC
185
DIURETICS
HYPERTENSION
SPIRONOLACTONE
186
DIURETICS
HYPERTENSION
TRIAMTERENE
187
DIURETICS
HYPERTENSION, BENIGN
HYDROCHLOROTHIAZIDE
188
DIURETICS
HYPERTENTION
HYDROCHLOROTHIAZIDE
189
DIURETICS
WORSENING HYPERTENSION
HYDROCHLOROTHIAZIDE
190
LIPID MODIFYING AGENTS
HIGH BLOOD PRESSURE
PRAVASTATIN
191
LIPID MODIFYING AGENTS
HIGH BLOOD PRESSURE
PRAVASTATIN SODIUM
Diabetes Mellitus (DIABETES)
1
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
DIABETES MELLITUS TYPE II
LISINOPRIL
2
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
TYPE 2 DIABETES
LISINOPRIL
3
ANTIHYPERTENSIVES
UNCONTROLLED DIABETES 
MELLITUS 2
CLONIDINE HYDROCHLORIDE
4
ANTIHYPERTENSIVES
UNCONTROLLED DIABETES 
MELLITUS 2
HYDRALAZINE HYDROCHLORIDE
5
BETA BLOCKING AGENTS
TYPE 2 DIABETES
METOPROLOL TARTRATE
6
DRUGS USED IN DIABETES
BORDERLINE DIABETES
METFORMIN
7
DRUGS USED IN DIABETES
DIABETES
DULAGLUTIDE
8
DRUGS USED IN DIABETES
DIABETES
GLIBENCLAMIDE


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 66
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
9
DRUGS USED IN DIABETES
DIABETES
GLICLAZIDE
10
DRUGS USED IN DIABETES
DIABETES
GLIMEPIRIDE
11
DRUGS USED IN DIABETES
DIABETES
GLIPIZIDE
12
DRUGS USED IN DIABETES
DIABETES
HUMAN MIXTARD
13
DRUGS USED IN DIABETES
DIABETES
INSULIN
14
DRUGS USED IN DIABETES
DIABETES
INSULIN ASPART
15
DRUGS USED IN DIABETES
DIABETES
INSULIN DETEMIR
16
DRUGS USED IN DIABETES
DIABETES
INSULIN GLARGINE
17
DRUGS USED IN DIABETES
DIABETES
INSULIN HUMAN
18
DRUGS USED IN DIABETES
DIABETES
INSULIN LISPRO
19
DRUGS USED IN DIABETES
DIABETES
METAGLIP
20
DRUGS USED IN DIABETES
DIABETES
METFORMIN
21
DRUGS USED IN DIABETES
DIABETES
METFORMIN HYDROCHLORIDE
22
DRUGS USED IN DIABETES
DIABETES
PIOGLITAZONE
23
DRUGS USED IN DIABETES
DIABETES
PIOGLITAZONE HYDROCHLORIDE
24
DRUGS USED IN DIABETES
DIABETES
SITAGLIPTIN
25
DRUGS USED IN DIABETES
DIABETES - TYPE I
INSULIN GLARGINE
26
DRUGS USED IN DIABETES
DIABETES - TYPE I
INSULIN LISPRO
27
DRUGS USED IN DIABETES
DIABETES 2
GLICLAZIDE
28
DRUGS USED IN DIABETES
DIABETES II
METFORMIN
29
DRUGS USED IN DIABETES
DIABETES KETOACIDOSIS
INSULIN
30
DRUGS USED IN DIABETES
DIABETES MELL. TYPE 2
INSULIN DETEMIR
31
DRUGS USED IN DIABETES
DIABETES MELL. TYPE 2
INSULIN LISPRO
32
DRUGS USED IN DIABETES
DIABETES MELL. TYPE 2
METFORMIN
33
DRUGS USED IN DIABETES
DIABETES MELLITIS TYPE 2
EMPAGLIFLOZIN
34
DRUGS USED IN DIABETES
DIABETES MELLITIS TYPE 2
GLIBENCLAMIDE
35
DRUGS USED IN DIABETES
DIABETES MELLITIS TYPE 2
INSULIN DETEMIR
36
DRUGS USED IN DIABETES
DIABETES MELLITIS TYPE 2
INSULIN LISPRO
37
DRUGS USED IN DIABETES
DIABETES MELLITUS
DULAGLUTIDE
38
DRUGS USED IN DIABETES
DIABETES MELLITUS
EXENATIDE
39
DRUGS USED IN DIABETES
DIABETES MELLITUS
GLIPIZIDE
40
DRUGS USED IN DIABETES
DIABETES MELLITUS
HUMAN MIXTARD
41
DRUGS USED IN DIABETES
DIABETES MELLITUS
INSULIN ASPART
42
DRUGS USED IN DIABETES
DIABETES MELLITUS
INSULIN DETEMIR
43
DRUGS USED IN DIABETES
DIABETES MELLITUS
INSULIN GLARGINE
44
DRUGS USED IN DIABETES
DIABETES MELLITUS
INSULIN HUMAN
45
DRUGS USED IN DIABETES
DIABETES MELLITUS
INSULIN LISPRO
46
DRUGS USED IN DIABETES
DIABETES MELLITUS
LIRAGLUTIDE
47
DRUGS USED IN DIABETES
DIABETES MELLITUS
METFORMIN
48
DRUGS USED IN DIABETES
DIABETES MELLITUS
METFORMIN HYDROCHLORIDE
49
DRUGS USED IN DIABETES
DIABETES MELLITUS
RISTFOR


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 67
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
50
DRUGS USED IN DIABETES
DIABETES MELLITUS
SITAGLIPTIN PHOSPHATE
51
DRUGS USED IN DIABETES
DIABETES MELLITUS  TYP II
INSULIN LISPRO
52
DRUGS USED IN DIABETES
DIABETES MELLITUS  TYP II
VELMETIA
53
DRUGS USED IN DIABETES
DIABETES MELLITUS 1
INSULIN GLARGINE
54
DRUGS USED IN DIABETES
DIABETES MELLITUS 1
INSULIN LISPRO
55
DRUGS USED IN DIABETES
DIABETES MELLITUS 11
GLIPIZIDE
56
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
CANAGLIFLOZIN
57
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
DULAGLUTIDE
58
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
EXENATIDE
59
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
GLIBOMET
60
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
GLIMEPIRIDE
61
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
GLIPIZIDE
62
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
HUMAN MIXTARD
63
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
INSULIN ASPART
64
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
INSULIN DETEMIR
65
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
INSULIN GLARGINE
66
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
METFORMIN
67
DRUGS USED IN DIABETES
DIABETES MELLITUS 2
METFORMIN HYDROCHLORIDE
68
DRUGS USED IN DIABETES
DIABETES MELLITUS II
GLIPIZIDE
69
DRUGS USED IN DIABETES
DIABETES MELLITUS II
METFORMIN
70
DRUGS USED IN DIABETES
DIABETES MELLITUS II
SITAGLIPTIN
71
DRUGS USED IN DIABETES
DIABETES MELLITUS TYP 2
METFORMIN
72
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE 2
GLIPIZIDE
73
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE 2
INSULIN GLARGINE
74
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE 2
INSULIN LISPRO
75
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE 2
METFORMIN
76
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE 2
METFORMIN HYDROCHLORIDE
77
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE 2
SITAGLIPTIN PHOSPHATE
78
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
CANAGLIFLOZIN W/METFORMIN 
HYDROCHLORIDE
79
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
DULAGLUTIDE
80
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
GLIPIZIDE
81
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
HUMAN MIXTARD
82
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
INSULIN
83
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
INSULIN ASPART
84
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
INSULIN DETEMIR
85
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
INSULIN GLARGINE
86
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
INSULIN LISPRO
87
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
METFORMIN
88
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
METFORMIN HYDROCHLORIDE
89
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
NATEGLINIDE


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 68
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
90
DRUGS USED IN DIABETES
DIABETES MELLITUS TYPE II
SITAGLIPTIN PHOSPHATE
91
DRUGS USED IN DIABETES
DIABETES MELLITUS, TYPE II
METFORMIN HYDROCHLORIDE
92
DRUGS USED IN DIABETES
DIABETES TYPE 2
GLIPIZIDE
93
DRUGS USED IN DIABETES
DIABETES TYPE 2
HUMAN MIXTARD
94
DRUGS USED IN DIABETES
DIABETES TYPE 2
INSULIN ASPART
95
DRUGS USED IN DIABETES
DIABETES TYPE 2
INSULIN DETEMIR
96
DRUGS USED IN DIABETES
DIABETES TYPE 2
INSULIN GLARGINE
97
DRUGS USED IN DIABETES
DIABETES TYPE 2
INSULIN LISPRO
98
DRUGS USED IN DIABETES
DIABETES TYPE 2
KOMBIGLYZE
99
DRUGS USED IN DIABETES
DIABETES TYPE 2
METFORMIN
100
DRUGS USED IN DIABETES
DIABETES TYPE 2
SITAGLIPTIN PHOSPHATE
101
DRUGS USED IN DIABETES
DIABETES TYPE II
METFORMIN
102
DRUGS USED IN DIABETES
DIABETES, TYPE 2
GLIMEPIRIDE
103
DRUGS USED IN DIABETES
DIABETES, TYPE 2
LIRAGLUTIDE
104
DRUGS USED IN DIABETES
DIABETES, TYPE 2
PIOGLITAZONE
105
DRUGS USED IN DIABETES
DIABETIS
INSULIN GLARGINE
106
DRUGS USED IN DIABETES
DM2
GLIPIZIDE
107
DRUGS USED IN DIABETES
DM2
METFORMIN HYDROCHLORIDE
108
DRUGS USED IN DIABETES
HYPERGLICEMIA
GLIPIZIDE
109
DRUGS USED IN DIABETES
HYPERGLYCEMIA
INSULIN HUMAN
110
DRUGS USED IN DIABETES
HYPERGLYCEMIA
METFORMIN
111
DRUGS USED IN DIABETES
HYPERGLYCEMIA
METFORMIN HYDROCHLORIDE
112
DRUGS USED IN DIABETES
HYPERINSULINISM
METFORMIN
113
DRUGS USED IN DIABETES
HYPERTENSION
METFORMIN
114
DRUGS USED IN DIABETES
NONALCOHOLIC 
STEATOHEPATITIS
METFORMIN
115
DRUGS USED IN DIABETES
TYPE 1 DIABETES
INSULIN DEGLUDEC
116
DRUGS USED IN DIABETES
TYPE 1 DIABETES MELLITUS
INSULIN ASPART
117
DRUGS USED IN DIABETES
TYPE 1 DIABETES MELLITUS
INSULIN GLARGINE
118
DRUGS USED IN DIABETES
TYPE 2 DIABETES
GLICLAZIDE
119
DRUGS USED IN DIABETES
TYPE 2 DIABETES
HUMAN MIXTARD
120
DRUGS USED IN DIABETES
TYPE 2 DIABETES
INSULIN ASPART
121
DRUGS USED IN DIABETES
TYPE 2 DIABETES
INSULIN GLARGINE
122
DRUGS USED IN DIABETES
TYPE 2 DIABETES
INSULIN LISPRO
123
DRUGS USED IN DIABETES
TYPE 2 DIABETES
METFORMIN
124
DRUGS USED IN DIABETES
TYPE 2 DIABETES
METFORMIN HYDROCHLORIDE
125
DRUGS USED IN DIABETES
TYPE 2 DIABETES
SITAGLIPTIN PHOSPHATE
126
DRUGS USED IN DIABETES
TYPE 2 DIABETES MELLITUS
GLIMEPIRIDE
127
DRUGS USED IN DIABETES
TYPE 2 DIABETES MELLITUS
HUMAN MIXTARD
128
DRUGS USED IN DIABETES
TYPE 2 DIABETES MELLITUS
INSULIN HUMAN
129
DRUGS USED IN DIABETES
TYPE 2 DIABETES MELLITUS
LIRAGLUTIDE


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 69
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
130
DRUGS USED IN DIABETES
TYPE 2 DIABETES MELLITUS
METFORMIN HYDROCHLORIDE
131
DRUGS USED IN DIABETES
TYPE 2 DIABETES MELLITUS
PIOGLITAZONE
132
DRUGS USED IN DIABETES
TYPE II DIABETES
CANAGLIFLOZIN W/METFORMIN 
HYDROCHLORIDE
133
DRUGS USED IN DIABETES
TYPE II DIABETES
DAPAGLIFLOZIN PROPANEDIOL 
MONOHYDRATE W/METFO
134
DRUGS USED IN DIABETES
TYPE II DIABETES
GLIPIZIDE
135
DRUGS USED IN DIABETES
TYPE II DIABETES
INSULIN
136
DRUGS USED IN DIABETES
TYPE II DIABETES
INSULIN DETEMIR
137
DRUGS USED IN DIABETES
TYPE II DIABETES
INSULIN GLARGINE
138
DRUGS USED IN DIABETES
TYPE II DIABETES
LIRAGLUTIDE
139
DRUGS USED IN DIABETES
TYPE II DIABETES
METFORMIN
140
DRUGS USED IN DIABETES
TYPE II DIABETES
SITAGLIPTIN PHOSPHATE
141
DRUGS USED IN DIABETES
TYPE II DIABETES MELLITUS
EXENATIDE
142
DRUGS USED IN DIABETES
TYPE II DIABETES MELLITUS
METFORMIN
143
DRUGS USED IN DIABETES
TYPE II DIABETES MELLITUS
METFORMIN HYDROCHLORIDE
144
DRUGS USED IN DIABETES
UNCONTROLLED DIABETES 
MELLITUS 2
INSULIN LISPRO
145
DRUGS USED IN DIABETES
UNCONTROLLED DIABETES 
MELLITUS WITH 
HYPERGLICEMIA
GLIPIZIDE
146
DRUGS USED IN DIABETES
UNCONTROLLED DIABETES 
MELLITUS WITH 
HYPERGLICEMIA
HUMAN MIXTARD
147
DRUGS USED IN DIABETES
UNCONTROLLED DM2
INSULIN DETEMIR
148
UNSPECIFIED HERBAL AND 
TRADITIONAL MEDICINE
HERBAL SUPPLEMENT
GLYCINE MAX EXTRACT
149
LIPID MODIFYING AGENTS
DIABETES MELLITUS TYPE II
PRAVASTATIN
Cardiovascular (CARDDIS)
1
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
ACUTE MYOCARDIAL 
INFARCTION
IRBESARTAN
2
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
CARDIOMYOPATHY
LISINOPRIL
3
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
CARDIOMYOPATHY
RAMIPRIL
4
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
CONGESTIVE HEART 
FAILURE
LISINOPRIL
5
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
CORONARY ARTERY DISEASE
RAMIPRIL
6
BETA BLOCKING AGENTS
ACUTE MYOCARDIAL 
INFARCTION
BISOPROLOL FUMARATE
7
BETA BLOCKING AGENTS
ANTI-ARRHYTHMIC
SOTALOL
8
BETA BLOCKING AGENTS
ATHEROSCLEROTIC HEART 
DISEASE OF NATIVE 
CORONARY ARTERY 
WITHOUT ANGINA PECTORIS
CARVEDILOL


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 70
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
9
BETA BLOCKING AGENTS
ATRIAL FIBRILATION
ATENOLOL
10
BETA BLOCKING AGENTS
ATRIAL FIBRILATION
METOPROLOL
11
BETA BLOCKING AGENTS
ATRIAL FIBRILLATION
METOPROLOL
12
BETA BLOCKING AGENTS
ATRIAL FIBRILLATION
METOPROLOL TARTRATE
13
BETA BLOCKING AGENTS
ATYPICAL CHEST PAIN
LABETALOL
14
BETA BLOCKING AGENTS
BRUGADA SYNDROME
BISOPROLOL
15
BETA BLOCKING AGENTS
CAD
METOPROLOL SUCCINATE
16
BETA BLOCKING AGENTS
CADRIOMYOPATHY
BISOPROLOL
17
BETA BLOCKING AGENTS
CARDIAC PACEMAKER 
INSITU
METOPROLOL
18
BETA BLOCKING AGENTS
CARDIAC PROPHYLAXIS
CARVEDILOL
19
BETA BLOCKING AGENTS
CARDIOMYOPATHY
CARVEDILOL
20
BETA BLOCKING AGENTS
CHEST TIGHTNESS
BISOPROLOL
21
BETA BLOCKING AGENTS
CONGESTIVE HEART 
FAILURE
ATENOLOL
22
BETA BLOCKING AGENTS
CONGESTIVE HEART 
FAILURE
CARVEDILOL
23
BETA BLOCKING AGENTS
CONTROLLED 
HYPERTENSION
TENORETIC
24
BETA BLOCKING AGENTS
CORONARY ARTERY DISEASE
METOPROLOL
25
BETA BLOCKING AGENTS
CORONARY ARTERY DISEASE
METOPROLOL SUCCINATE
26
BETA BLOCKING AGENTS
CORONARY ARTERY 
STENOSIS
METOPROLOL
27
BETA BLOCKING AGENTS
DYSRHYTHMIA
BISOPROLOL FUMARATE
28
BETA BLOCKING AGENTS
HEART FAILURE AND 
HYPERTENSION
CARVEDILOL
29
BETA BLOCKING AGENTS
INTERMITTENT 
ARRHYTHMIA
BISOPROLOL
30
BETA BLOCKING AGENTS
MITRAL INSUFFICIENCY
BISOPROLOL
31
BETA BLOCKING AGENTS
PREVENTATIVE FOLLOWING 
ACUTE MYCARDIAL 
INFARCTION
BISOPROLOL
32
BETA BLOCKING AGENTS
SICK SINUS SYNDROME
METOPROLOL
33
BETA BLOCKING AGENTS
SUPRA VENTRICULAR 
TACHYCARDIA
ATENOLOL
34
BETA BLOCKING AGENTS
SUPRAVENTRICULAR 
TACHYCARDIA
ATENOLOL
35
BETA BLOCKING AGENTS
SUPRAVENTRICULAR 
TACHYCARDIA
METOPROLOL
36
BETA BLOCKING AGENTS
TACHYCARDIA
ATENOLOL
37
CALCIUM CHANNEL BLOCKERS
CORONARY ARTERY DISEASE
AMLODIPINE
38
CALCIUM CHANNEL BLOCKERS
CORONARY ARTERY DISEASE
AMLODIPINE BESILATE
39
CALCIUM CHANNEL BLOCKERS
SUPRAVENTRICULAR 
TACHYCARDIA
VERAPAMIL


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 71
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
40
CARDIAC THERAPY
ACUTE MYOCARDIAL 
INFARCTION
AMIODARONE HYDROCHLORIDE
41
CARDIAC THERAPY
ACUTE MYOCARDIAL 
INFARCTION
ISOSORBIDE DINITRATE
42
CARDIAC THERAPY
ALLERGIC REACTION
EPINEPHRINE
43
CARDIAC THERAPY
ANGINA
GLYCERYL TRINITRATE
44
CARDIAC THERAPY
ANGINA PECTORIS
RANOLAZINE
45
CARDIAC THERAPY
ANGIOGRAM/STENT
ADENOSINE
46
CARDIAC THERAPY
ANGIONEUROTIC EDEMA
EPINEPHRINE
47
CARDIAC THERAPY
ANTIARRHYTHMIC AGENT
FLECAINIDE ACETATE
48
CARDIAC THERAPY
ATRIAL FIBRILLATION
DIGOXIN
49
CARDIAC THERAPY
ATRIAL FIBRILLATION
FLECAINIDE ACETATE
50
CARDIAC THERAPY
ATYPICAL CHEST PAIN
GLYCERYL TRINITRATE
51
CARDIAC THERAPY
CAD
UBIDECARENONE
52
CARDIAC THERAPY
CARDIOMYOPATHY
ISOSORBIDE DINITRATE
53
CARDIAC THERAPY
CARDIOVASCULAR DISEASE 
PROPHYLAXIS
UBIDECARENONE
54
CARDIAC THERAPY
CHEST PAIN
GLYCERYL TRINITRATE
55
CARDIAC THERAPY
CHEST PAINS
GLYCERYL TRINITRATE
56
CARDIAC THERAPY
CHESTPAIN
GLYCERYL TRINITRATE
57
CARDIAC THERAPY
CORONARY ARTERY DISEASE
GLYCERYL TRINITRATE
58
CARDIAC THERAPY
CORONARY ARTERY DISEASE
ISOSORBIDE MONONITRATE
59
CARDIAC THERAPY
HYPERLIPIDEMIA
ISOSORBIDE MONONITRATE
60
CARDIAC THERAPY
NSTEMI
ISOSORBIDE DINITRATE
61
CARDIAC THERAPY
PERIOP STRESS TEST
REGADENOSON
62
CARDIAC THERAPY
PROPHYLAXIS
GLYCERYL TRINITRATE
63
CARDIAC THERAPY
PROPHYLAXIS FOR CARDIAC 
HEALTH
UBIDECARENONE
64
CARDIAC THERAPY
SUPRAVENTRICULAR 
TACHYCARDIA
ADENOSINE
65
CARDIAC THERAPY
UNCONTROLLED DIABETES 
MELLITUS 2
AMIODARONE HYDROCHLORIDE
66
CARDIAC THERAPY
UNCONTROLLED DIABETES 
MELLITUS 2
GLYCERYL TRINITRATE
67
DIURETICS
ACUTE RESPIRATORY 
FAILURE
FUROSEMIDE
68
DIURETICS
AORTIC VALVE 
REPLACEMENT
FUROSEMIDE
69
DIURETICS
CHF
BUMETANIDE
70
DIURETICS
CHF
HYDROCHLOROTHIAZIDE
71
DIURETICS
CHF
METOLAZONE
72
DIURETICS
CONGESTIVE HEART 
FAILURE
BUMETANIDE


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 72
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
73
DIURETICS
CONGESTIVE HEART 
FAILURE
FUROSEMIDE
74
DIURETICS
CONGESTIVE HEART 
FAILURE
HYDROCHLOROTHIAZIDE
75
DIURETICS
CONGESTIVE HEART 
FAILURE
METOLAZONE
76
DIURETICS
CONGESTIVE HEART 
FAILURE
SPIRONOLACTONE
77
DIURETICS
CORONARY ARTERY DISEASE
HYDROCHLOROTHIAZIDE
78
DIURETICS
CORONARY ARTERY 
DISEASE.
FUROSEMIDE
79
DIURETICS
ELEVATION OF BLOOD 
PRESSURE
FUROSEMIDE
80
DIURETICS
MITRAL INSUFFICIENCY
TORASEMIDE
81
DIURETICS
TRANSGENGER
SPIRONOLACTONE
82
LIPID MODIFYING AGENTS
ACUTE MYOCARDIAL 
INFARCTION
ATORVASTATIN CALCIUM
83
LIPID MODIFYING AGENTS
ACUTE MYOCARDIAL 
INFARCTION
OMEGA-3 TRIGLYCERIDES
84
LIPID MODIFYING AGENTS
ATHEROSCLEROTIC HEART 
DISEASE OF NATIVE 
CORONARY ARTERY 
WITHOUT ANGINA PECTORIS
SIMVASTATIN
85
LIPID MODIFYING AGENTS
BASILAR ARTERY 
THROMBUS
ATORVASTATIN CALCIUM
86
LIPID MODIFYING AGENTS
CAD
PRAVASTATIN SODIUM
87
LIPID MODIFYING AGENTS
CAD
ROSUVASTATIN CALCIUM
88
LIPID MODIFYING AGENTS
CARDIAC PROPHYLAXIS
ATORVASTATIN
89
LIPID MODIFYING AGENTS
CARDIAC PROPHYLAXIS
FISH OIL
90
LIPID MODIFYING AGENTS
CARDIOVASCULAR 
PROPHYLAXIS
ATORVASTATIN CALCIUM
91
LIPID MODIFYING AGENTS
CHEST TIGHTNESS
ATORVASTATIN
Hyperlipidemia (HLIPDEM)
1
AGENTS ACTING ON THE 
RENIN-ANGIOTENSIN SYSTEM
HYPERTRIGLYCERIDEMIA
LISINOPRIL
2
ANTIHYPERTENSIVES
HYPERCHOLESTEROLEMIA
DOXAZOSIN MESILATE
3
CARDIAC THERAPY
HYPERCHOLESTEROLEMIA
UBIDECARENONE
4
LIPID MODIFYING AGENTS
ABNORMAL LIPIDS
ATORVASTATIN
5
LIPID MODIFYING AGENTS
CARDIAC PROPHYLAXIS
ROSUVASTATIN
6
LIPID MODIFYING AGENTS
CHOLESTEROL
ROSUVASTATIN
7
LIPID MODIFYING AGENTS
CHOLESTEROL
ROSUVASTATIN CALCIUM
8
LIPID MODIFYING AGENTS
CHOLESTEROLEAMIA
ATORVASTATIN
9
LIPID MODIFYING AGENTS
CHOLESTERORL
ROSUVASTATIN CALCIUM
10
LIPID MODIFYING AGENTS
CORONARY ARTERY DISEASE
ATORVASTATIN
11
LIPID MODIFYING AGENTS
CORONARY ARTERY DISEASE
EZETIMIBE


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 73
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
12
LIPID MODIFYING AGENTS
CORONARY ARTERY DISEASE
FENOFIBRATE
13
LIPID MODIFYING AGENTS
CORONARY ARTERY DISEASE
ROSUVASTATIN CALCIUM
14
LIPID MODIFYING AGENTS
CORONARY ARTERY DISEASE 
PROPHYLAXIS
ATORVASTATIN
15
LIPID MODIFYING AGENTS
DIET SUPPLEMENT
FISH OIL
16
LIPID MODIFYING AGENTS
DIETARY SUPPLEMENT
FISH OIL
17
LIPID MODIFYING AGENTS
DIETARY SUPPLEMENTS
FISH OIL
18
LIPID MODIFYING AGENTS
DYSLIPEDEMIA
ROSUVASTATIN CALCIUM
19
LIPID MODIFYING AGENTS
DYSLIPIDAEMIA
ATORVASTATIN
20
LIPID MODIFYING AGENTS
DYSLIPIDEMIA
ATORVASTATIN
21
LIPID MODIFYING AGENTS
DYSLIPIDEMIA
FENOFIBRATE
22
LIPID MODIFYING AGENTS
DYSLIPIDEMIA
FISH OIL
23
LIPID MODIFYING AGENTS
DYSLIPIDEMIA
GEMFIBROZIL
24
LIPID MODIFYING AGENTS
DYSLIPIDEMIA
PRAVASTATIN
25
LIPID MODIFYING AGENTS
DYSLIPIDEMIA
ROSUVASTATIN
26
LIPID MODIFYING AGENTS
DYSLIPIDEMIA, WORSENING
ROSUVASTATIN
27
LIPID MODIFYING AGENTS
DYSLIPIDERMIA
PRAVASTATIN
28
LIPID MODIFYING AGENTS
ELEVATED CHOLESTEROL
SIMVASTATIN
29
LIPID MODIFYING AGENTS
ELEVATED LIPIDS
ATORVASTATIN
30
LIPID MODIFYING AGENTS
ELEVATED LIPIDS
ATORVASTATIN CALCIUM
31
LIPID MODIFYING AGENTS
ELEVATED TRIGLYCERIDES
FISH OIL
32
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
ATORVASTATIN
33
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
ATORVASTATIN CALCIUM
34
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
GEMFIBROZIL
35
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
LOVASTATIN
36
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
PRAVASTATIN
37
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
ROSUVASTATIN CALCIUM
38
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
SIMVASTATIN
39
LIPID MODIFYING AGENTS
HIGH CHOLESTROL
ATORVASTATIN
40
LIPID MODIFYING AGENTS
HIGH PLASMA LIPIDS
ATORVASTATIN
41
LIPID MODIFYING AGENTS
HIGH TRIGLYCERIDES
FENOFIBRATE
42
LIPID MODIFYING AGENTS
HIGH TRIGLYCERIDES AND 
HYPERCHOLESTEROLEMIA
ATORVASTATIN
43
LIPID MODIFYING AGENTS
HIPERCOLESTEROLEMIA
ATORVASTATIN
44
LIPID MODIFYING AGENTS
HIPERCOLESTEROLEMIA
ATORVASTATIN CALCIUM
45
LIPID MODIFYING AGENTS
HIPERCOLESTEROLEMIA
SIMVASTATIN
46
LIPID MODIFYING AGENTS
HYERLIPIDEMIA
OMEGA-3-ACID ETHYL ESTER
47
LIPID MODIFYING AGENTS
HYPERCHOLESTERIMIA
FENOFIBRATE
48
LIPID MODIFYING AGENTS
HYPERCHOLESTERINAEMIA
ATORVASTATIN
49
LIPID MODIFYING AGENTS
HYPERCHOLESTERINAEMIA
PRAVASTATIN
50
LIPID MODIFYING AGENTS
HYPERCHOLESTERINEMIA
PRAVASTATIN
51
LIPID MODIFYING AGENTS
HYPERCHOLESTERINEMIA
SIMVASTATIN


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 74
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
52
LIPID MODIFYING AGENTS
HYPERCHOLESTEROL
PRAVASTATIN
53
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLAEMIA
ATORVASTATIN
54
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLAEMIA
PRAVASTATIN
55
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLAEMIA
ROSUVASTATIN
56
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLAEMIA
SIMVASTATIN
57
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
ATORVASTATIN
58
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
ATORVASTATIN CALCIUM
59
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
EZETIMIBE
60
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
FENOFIBRATE
61
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
FISH OIL
62
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
LOVASTATIN
63
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
PITAVASTATIN CALCIUM
64
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
PRAVASTATIN
65
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
PRAVASTATIN SODIUM
66
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
ROSUVASTATIN
67
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
ROSUVASTATIN CALCIUM
68
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
SIMVASTATIN
69
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA 
(PURE) AND MIXED 
HYPERLIPIDEMIA
ROSUVASTATIN CALCIUM
70
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLMIA
PRAVASTATIN SODIUM
71
LIPID MODIFYING AGENTS
HYPERCHOLESTROLEMIA
ATORVASTATIN
72
LIPID MODIFYING AGENTS
HYPERCHOLESTROLEMIA
ATORVASTATIN CALCIUM
73
LIPID MODIFYING AGENTS
HYPERCHOLESTROLEMIA
FENOFIBRATE
74
LIPID MODIFYING AGENTS
HYPERCHOLSTEROAEMIA
ATORVASTATIN CALCIUM
75
LIPID MODIFYING AGENTS
HYPERCOLESTEROLEMIA
SIMVASTATIN
76
LIPID MODIFYING AGENTS
HYPERLIDEMIA
ROSUVASTATIN CALCIUM
77
LIPID MODIFYING AGENTS
HYPERLIDIPEMIA
ATORVASTATIN
78
LIPID MODIFYING AGENTS
HYPERLIPDEMIA
ROSUVASTATIN CALCIUM
79
LIPID MODIFYING AGENTS
HYPERLIPEDMIA-MIXED
ATORVASTATIN
80
LIPID MODIFYING AGENTS
HYPERLIPIDAEMIA
ATORVASTATIN
81
LIPID MODIFYING AGENTS
HYPERLIPIDAEMIA
FENOFIBRATE
82
LIPID MODIFYING AGENTS
HYPERLIPIDAEMIA
PRAVASTATIN
83
LIPID MODIFYING AGENTS
HYPERLIPIDAEMIA
PRAVASTATIN SODIUM
84
LIPID MODIFYING AGENTS
HYPERLIPIDAEMIA
ROSUVASTATIN
85
LIPID MODIFYING AGENTS
HYPERLIPIDAEMIA
ROSUVASTATIN CALCIUM
86
LIPID MODIFYING AGENTS
HYPERLIPIDEMA
ATORVASTATIN
87
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
ATORVASTATIN
88
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
ATORVASTATIN CALCIUM
89
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
COLESEVELAM HYDROCHLORIDE
90
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
EICOSAPENTAENOIC ACID ETHYL 
ESTER


B/F/TAF
GS-US-380-1961
Statistical Analysis Plan - Week 48 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 75
19 October 2017
Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
91
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
EZETIMIBE
92
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
FENOFIBRATE
93
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
FENOFIBRIC ACID
94
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
FISH OIL
95
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
GEMFIBROZIL
96
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
LOVASTATIN
97
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
OMEGA-3-ACID ETHYL ESTER
98
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
PELAGO
99
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
PRAVASTATIN
100
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
PRAVASTATIN SODIUM
101
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
ROSUVASTATIN
102
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
ROSUVASTATIN CALCIUM
103
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
SIMVASTATIN
104
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA 
PREVENTION
ROSUVASTATIN CALCIUM
105
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA,
PRAVASTATIN
106
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA, MIXED
ATORVASTATIN CALCIUM
107
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA, MIXED
FENOFIBRATE
108
LIPID MODIFYING AGENTS
HYPERTENSION
ATORVASTATIN
109
LIPID MODIFYING AGENTS
HYPERTENSION
PRAVASTATIN
110
LIPID MODIFYING AGENTS
HYPERTRIGLYCERDEMIA
ATORVASTATIN
111
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA
ATORVASTATIN CALCIUM
112
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA
FENOFIBRATE
113
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA
FENOFIBRIC ACID
114
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA
FIBRATES
115
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA
FISH OIL
116
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA
OMEGA-3 TRIGLYCERIDES
117
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA
PRAVASTATIN
118
LIPID MODIFYING AGENTS
HYPERTRIGLYCERIDEMIA,HY
PERCHOLESTEROLEMIA
ATORVASTATIN
119
LIPID MODIFYING AGENTS
HYPERTRIGLYERIDEMIA
GEMFIBROZIL
120
LIPID MODIFYING AGENTS
HYPERTRYGLYCERIDEMIA
PRAVASTATIN
121
LIPID MODIFYING AGENTS
INDICATION 
HYPERLIPIDEMIA
FENOFIBRATE
122
LIPID MODIFYING AGENTS
IRRITABLE BOWEL 
SYNDROME
FISH OIL
123
LIPID MODIFYING AGENTS
ISCHEMIC HEART DISEASE
ROSUVASTATIN CALCIUM
124
LIPID MODIFYING AGENTS
LDL-CHOLESTEROL GRADE 3 
ELEVATION
ROSUVASTATIN
125
LIPID MODIFYING AGENTS
MIXED DYSLIPIDEMIA
FENOFIBRATE
126
LIPID MODIFYING AGENTS
MIXED DYSLIPIDEMIA
ROSUVASTATIN CALCIUM
127
LIPID MODIFYING AGENTS
MIXED HYPERLIPDEMIA
ATORVASTATIN


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Medication Class (WHOATC2)
Indication (CMINDC)
WHOGEN
128
LIPID MODIFYING AGENTS
MIXED HYPERLIPIDEMIA
ATORVASTATIN
129
LIPID MODIFYING AGENTS
MIXED HYPERLIPIDEMIA
FENOFIBRATE
130
LIPID MODIFYING AGENTS
MIXED HYPERLIPIDEMIA
GEMFIBROZIL
131
LIPID MODIFYING AGENTS
NUTRITION SUPPLEMENT
FISH OIL
132
LIPID MODIFYING AGENTS
NUTRITIONAL SUPPLEMENT
FISH OIL
133
LIPID MODIFYING AGENTS
NUTRITIONAL SUPPLEMENT
OMEGA-3 FATTY ACIDS
134
LIPID MODIFYING AGENTS
PREVENTATIVE FOLLOWING 
ACUTE MYCARDIAL 
INFARCTION
ATORVASTATIN
135
LIPID MODIFYING AGENTS
PREVENTION FOR 
HYPERCHOLESTEROLEMIA
OMEGA-3 FATTY ACIDS
136
LIPID MODIFYING AGENTS
PREVENTIVE
FISH OIL W/LINUM 
USITATISSIMUM SEED OIL
137
LIPID MODIFYING AGENTS
PROPHYLAXIS
FISH OIL
138
LIPID MODIFYING AGENTS
PURE 
HYPERCHOLESTEROLEMIA
ATORVASTATIN
139
LIPID MODIFYING AGENTS
SECONDARY STROKE 
PREVENTION
ATORVASTATIN
140
LIPID MODIFYING AGENTS
STROKE PROPHYLAXIS
ATORVASTATIN
141
LIPID MODIFYING AGENTS
SUPPLEMENT
FISH OIL
142
LIPID MODIFYING AGENTS
SUPPLEMENT
OMEGA 3 6 9
143
LIPID MODIFYING AGENTS
SUPPLEMENT
OMEGA-3 FATTY ACIDS
144
LIPID MODIFYING AGENTS
SUPPLEMENT
OMEGA-3 FATTY ACIDS W/OMEGA-
6 FATTY ACIDS
145
LIPID MODIFYING AGENTS
SUPPLEMENT
OMEGA-3-ACID ETHYL ESTER
146
LIPID MODIFYING AGENTS
SUPPLEMENT/HYPERLIPIDEM
IA
FISH OIL
147
LIPID MODIFYING AGENTS
SUPPLEMENTAL USE
FISH OIL
148
LIPID MODIFYING AGENTS
SUPPLEMETN
FISH OIL
149
LIPID MODIFYING AGENTS
UNCONTROLLED DIABETES 
MELLITUS 2
ATORVASTATIN
150
LIPID MODIFYING AGENTS
WORSENING 
HYPERLIPIDEMIA
ATORVASTATIN
151
LIPID MODIFYING AGENTS
WORSENING OF 
HYPERLIPIDEMIA
FISH OIL
152
LIPID MODIFYING AGENTS
HIGH CHOLESTEROL
NICOTINIC ACID
153
LIPID MODIFYING AGENTS
HYPERCHOLESTEROLEMIA
NICOTINIC ACID
154
LIPID MODIFYING AGENTS
HYPERLIPIDEMIA
NICOTINIC ACID
155
LIPID MODIFYING AGENTS
MIXED HYPERLIPIDEMIA
NICOTINIC ACID


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Appendix 4.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT included in the 
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA 19.1 provided by Gilead DSPH 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 5.
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 (randomized phase 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 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. 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 randomized study drug and assigned as blank if subject never dosed.
6. In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.
7. Only 1 study completion form is collected for the entire study. Therefore, study disposition in 
the randomized phase of the study is defined as follows for subjects who were dosed with 
randomized study drug:


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a) Subjects who completed study in the randomized phase include the following two 
exclusive cases:
i)
Subjects who were dosed in the extension phase (ie, extension phase first dose date is 
present), OR
ii) Subjects who were not dosed in the extension phase and completed study (ie, 
extension phase first dose date is not present and study completion form is marked as 
“Yes”)
b) Subjects who are ongoing in the randomized phase of the study include subjects who 
were not dosed in the extension phase of the study, and study completion form was not 
filled.
c) Subjects who discontinued study in the randomized phase of the study include subjects 
who were not dosed in the extension phase of the study and study completion form was 
marked as “No”.
8. Body mass index (BMI) and Body Surface Area (BSA)
BMI and BSA will be calculated only at randomized phase baseline as follows:
o
BMI = (weight [kg])/ (height [meters]
2
)
o
BSA (m2) = SQRT( [Height(cm) x Weight(kg) ]/ 3600 )
Baseline height and weight in the randomized phase of the study will be used for this 
calculation.
9. SAS codes for the treatment comparison for demographics and baseline characteristics tables.
1) CMH test for nominal variable (Y), the p-value from general association test should be 
used for nominal variable:
proc freq order=adsl;
   tables trtgrp * Y /cmh /*general association test*/
run;
2) CMH test for ordinal variable (Y), the p-value from row mean score test should be used 
for ordinal variable:
proc freq order=adsl;
   tables trtgrp * Y / cmh2 ; /*row mean score test*/
run;
3) Wilcoxon rank sum test for continuous variable (Y), the p-value from the normal 
approximation two-sided test should be used for continuous variable:


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proc npar1way wilcoxon data=adsl;
     class trtgrp; 
     var Y;  
run;
Note: “Not Permitted”, “Unknown”, or missing categories will be excluded for percentage 
calculation and also be 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. For this variable, percentage may add up to be more than 100% and no 
p-value will be generated.
Subjects with Race = “Not Permitted” will also be excluded to define Race subgroup (ie, 
back vs. nonblack) for efficacy subgroup analysis.
10. 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); /*0 indicates censored observation*/
    Strata TRT01AN;
    label TRTDURD = "Duration of Exposure (Days)";
         run;
11. Last Dose Date and Last Study Date
1) 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 was 
defined in Section 3.8.1.
Randomized Phase Last Dose Date:
For subjects with a partial last dosing date (ie, month and year of last dose are 
known), the minimum of {(death date, if available), (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), 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.
Please note the follows: 

Last dose date is not defined for subjects still on randomized study drug. 
However, for the calculation of the duration of exposure to randomized study 
drug, the data cut date will be used to impute the last dose date for subjects 
who have not discontinued study drug by the data cut date. For Week 48 
interim analysis, 22 Sep 2017 will be the data cut date for subjects with 
Week 48 visit on or prior to 22 Sep 2017, subjects missing Week 48 visits 
while on study drug, or subjects who permanently discontinued the 


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randomized study drug. For subjects with Week 48 visit after 22 Sep 2017, the 
last subject’s Week 48 visit date will be used as the data cut date.

For time to premature discontinuation of study drug KM summary, if we have 
subjects with duration of exposure of study drug great than 378 days (ie, upper 
limit of the Week 48 visit window), please add Week 60, defined as Day 379 
– Day 462 (inclusive), to the table.
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 {(death date, if available), (the latest of the dispensing dates 
of study drug bottles, study drug start dates and end dates (based on EX dataset), 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.
Last dose date is not defined for subjects still on study drug in SAP. However, for 
programing purposes, the data cut date will be used to impute the last dose date for 
subjects still on study drug.
2) 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 dates is partially missing 
(ie, only year and month are known), the day will be imputed as 15 for the purpose of 
this analysis.
Last study date is not defined for subjects still on study in SAP. However, for 
programing purpose, 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.
12. Toxicity Grades:
1) For toxicity grade summaries, include all postbaseline graded results up to 30 days 
after the randomized phase last dose of study drug, not just those used in by-visit 
summaries.
2) 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 non-fasting glucose 
will be listed as two separate laboratory tests in the “Laboratory Abnormalities” and 


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“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.
13. Efficacy analyses:
1) For categorical efficacy response (eg, Subjects with HIV-1 RNA ≥ 50 copies/mL or 
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 2 treatment groups 
and its 95.001% CIs (or 95% CI for M=F and M=E analyses) are calculated based on the 
an unconditional exact method with 2 inverted 1-sided tests in SAS v9.3 or above. Please 
see example SAS codes below:
data example;
input  grp trt01a $  outcome $ count ;
datalines;
1       Treat-A        2-Fail        1     
1       Treat-A        1-Succ      189     
1       Treat-B        2-Fail        4     
1       Treat-B        1-Succ       88     
run;
proc freq data = example;
table trt01a*outcome /riskdiff(CL=(exact)) alpha=0.04999;
weight count; exact RISKDIFF(METHOD=SCORE);
output out=ciexact(keep=_RDIF1_ XL_RDIF1 XU_RDIF1) riskdiff;
run;
data final(keep=A1 B1 Estimate LowerCL UpperCL ocharc1);
set ciexact;
label Estimate ="Percentage Difference"
LowerCL = "95% Lower Confidence Limit"
UpperCL = "95% Upper Confidence Limit"
A1 = "Percentage of Success in Treat-A"
B1 = "Percentage of Success in Treat-B";
Estimate=100*_RDIF1_;
LowerCL = 100*XL_RDIF1;
UpperCL = 100*XU_RDIF1;
A1 = 100*_RSK11_;
B1 = 100*_RSK21_;
ocharc1 = right(compress(put(Estimate,8.1)) || '% (' || 
compress(put(LowerCL,8.1)) || '% to ' || compress(put(UpperCL,8.1)) || '%)');
run;
2) Homogeneity test: Homogeneity Test of Treatment Effect across country in HIV-1 RNA 
< 50 copies/mL at Week 48 (Snapshot Algorithm). For each country, 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 
country and treatment group as follows.


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proc freq data=xxx;
tables country*treat*Y/all; /*p value from Breslow Day test*/
run;
3) Homogeneity test: Homogeneity Test of Treatment Effect between Subgroups in HIV-1 
RNA < 50 copies/mL at Week 48 (Snapshot Algorithm)
For the subgroups of age, race, and region (US vs. Ex-US) the odds ratio and the 
associated 95% CIs are estimated for the response variable (response coded as 1 for 
success and 0 for nonsuccess) using a logistic regression model including treatment 
(trtgrp coded as 1 for active [ie, B/F/TAF] and 2 for control [ie, SBR]), 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;
class trtgrpn agegrp;
model response = trtgrpn agegrp trtgrpn*agegrp/dist=bin 
link=logit lrci;
estimate 'Group 1' trtgrpn 1 -1 trtgrpn*agegrp 1 0 -1 0/exp;
estimate 'Group 2' trtgrpn 1 -1 trtgrpn*agegrp 0 1 0 -1/exp;
run;
Note: P-value for the homogeneity test was based on the Wald test of the interaction 
between treatment and subgroup. Odds ratio is from L'Beta estimate, its 95%CI is 
from L'Beta confidence limits for each subgroup.
4) 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 treatment as fixed effects in the model.
proc glm data=adeff;
class trtgrp;
model CD4= trtgrp;
lsmeans trtgrp /alpha=0.05 cl pdiff;
run;


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5) 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:
a.
HIV-1 RNA >= 50 copies/mL - Discontinued Study Drug Due to AE or Death and 
Last Available HIV-1 RNA >= 50 copies/mL
b. HIV-1 RNA >= 50 copies/mL - Discontinued Study Drug Due to Other reason* and 
Last Available HIV-1 RNA >= 50 copies/mL
c.
No virologic Data  – Discontinued Study Drug Due to AE or Death and Last 
Available HIV-1 RNA < 50 copies/mL
d. No virologic Data  – Discontinued Study Drug Due to Other reason* and Last 
Available HIV-1 RNA < 50 copies/mL
Note: *Other reasons include subjects who discontinued study drug due to 
investigator’s discretion, subject decision, lost to follow-up, noncompliance with 
study drug, protocol violation, pregnancy, and study terminated by sponsor.
6) Snapshot definition clarification:
a.
For a subject who completed the randomized phase study with Week 48 HIV-1 
RNA missing for the randomized phase of the study, snapshot outcome for such 
subject would be “Missing data during the window but on study drug”.
14. Clarification of the LOCF algorithms for CD4: (1) baseline value will be carried forward; 
(2) if a value is missing in an analysis visit window, replace the missing value with the last 
on-treatment value observed before the analysis visit window that has the missing value.
15. 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: 


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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)
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)


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Battery
Lab Test Label 
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label Used in t-labtox Table
Uric Acid
Decrease
Uric Acid (Hypouricemia)
Prothrombin Intl. 
Normalized Ratio (INR)
Increase
N/A
Prothrombin Time (PT)
Increase
N/A
Urinalysis
Urine Blood
Increase
N/A
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine Protein
Increase
Urine Protein (Proteinuria)
Urine RBC
Increase
Urine RBC (Hematuria, Quantitative)
Note: Prothrombin Intl. Normalized Ratio (INR) and Prothrombin Time (PT) were graded based on the protocol defined toxicity 
grade scale. The results and toxicity grade will be listed in listing, but not be summarized in lab toxicity summary table.   
16. Renal related laboratory evaluation
1) Unit conversion for renal safety tests derived from related tests with conventional units
a) Urine RBP (ug/L) to creatinine (mg/dL) ratio: 1 (ug/L) / (mg/dL) = 100 x ug/g
b) Urine Beta-2-microglobulin (mg/L) to creatinine (mg/dL) ratio: 1 (mg/L) / (mg/dL) = 
105 ug/g
c) Urine Albumin (mg/dL) to creatinine (mg/dL) ratio: 1 (mg/dL) / (mg/dL) = 1000 x 
mg/g
2) 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).
17. Smoking history at baseline
Smoking history 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 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.


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c.
Finally, 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”; the subject will be flagged as a “Former” smoker, if 
all selected records have a flag of “Prior” or a combination of “Prior” and “Post”; 
Otherwise, the subject will be flagged as a “Current” smoker.
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 History 
Never
Never
Former
Former
Current
Current
Current
Current
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 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”.


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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 
and should be queried first. However, this record is flagged as “Present” if the start 
date is on the first dose date; this record is flagged as “Post” if the start date is after 
the first dose date.
Note: first dose date for smoking history definition at baseline refers to the randomized phase 
first dose date.
18. Clarification for “Pharmacokinetic Blood Sampling Time Record” listing

A new variable “Sample age” will be added in this listing, defined as the duration in day 
between sample collection date and assay date, ie, sample age = assay date – sample 
collection date + 1.

SAMTIME (hours) = sample collection time (xx:xx) - last dose time before sample 
collection (xx:xx).
19. Non-study drug ARV medications (ie, ARV medications other than study drug that are taken 
while receiving study drug) will be flagged in “Antiviral Medication” listing. Please note that 
for ARVs recorded on the “Prior ARV” eCRF will NOT be considered as ARVs taken during 
study. All Prior ARVs with missing end date will be queried to confirm the ARVs were 
stopped before the randomized phase 1st dose date.
20. Lipid modifying medication analyses:

Lipid modifying medication is defined to be the concomitant medication with 
CMCLAS = “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 randomized phase 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 randomized phase 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 randomized phase first dose date.

Subjects who initiated lipid modifying medications during the randomized phase study 
include the following subjects in the safety analysis set: (1) for subjects who permanently 
discontinued randomized phase study drug with any selected CM record started after the 
randomized phase first dose date and on and prior to the minimum of randomized phase 
last dose date and (extension phase first dose date minus 1 day); (2) for subjects who are 
still on randomized study drug (if applicable) with any selected CM records started after 
the randomized phase first dose date; (3) lastly, for subjects who meet criteria (1) or (2) 
above, if they took lipid modification medications at study entry, they will be NOT be
considered taking lipid modifications during the randomized phase study.


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
For lipid modifying medications with start date completely unknown, we assume the start 
date is on or before the randomized phase 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 on or prior to the randomized phase first 
dose date and the end date completely unknown were considered as being taken at study 
entry.
21. 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.
22. Prior ARV regimen
All subjects will have one of the following prior ARV regimen identified based on ARVs 
entered in the ARV eCRF: E/C/F/TAF, E/C/F/TDF, ATV+RTV+FTC/TDF.
Use ARV dataset and include all prior and/or current ARVs (ARV.CMSCAT = ‘Prior ARV’ 
or ‘Current ARV’) with taken on or up to 2 days prior to the randomized phase first dose date
meeting the following criteria:
If CMTRT contains Only the specified ARVs:
Re-code as follows for baseline regimen
E/C/F/TAF
E/C/F/TAF
GENVOYA
NRTI/INI: GENVOYA (EVG+COBI+FTC+TAF)
EVG/COBI/FTC/TDF
E/C/F/TDF
NRTI/INI: STRIBILD (EVG+COBI+FTC+TDF)
ATAZANAVIR/RITONAVIR+FTC+TDF
ATV+RTV+FTC/TDF
ATV/R+FTC/TDF
NRTI: TRUVADA (FTC+TDF) or PI: ATAZANAVIR 
(ATV) or PI: RITONAVIR (RTV)
TDF/FTC/ATV/R
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.


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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
when < 29 IU/mL, NUMERICAL VALUE when 
≥29 IU/nL *
HCVAb
CNT350
Hepatitis C Virus 
Antibody
“Positive”*, “Indeterminate”, “Negative”
HCVAb
CNT458
Hepatitis C 
AntibodyEDTApl-CL
“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, 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)
o
The baseline coinfection status will be one of the three values: Yes/No/Null
o
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


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HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
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
“-“ means any value can be present, as it does not affect the classification. 
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
o
The incident coinfection status will be one of two values: Yes/Null
o
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


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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
o
For adverse events, the start date must be after the first dose date and on or prior 
to the last dose date in the randomized phase
o
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”, 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. If reflexive test is not available, HBV DNA level
will be determined based on lab test code GET1883.
25. Puerto Rico was combined with the United States when we evaluate the treatment effect 
across countries.
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 most of the LDL tests were from the 2nd generation, 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.


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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. AE action taken for study drug regimen containing multiple pills (eg, ATV + RTV + 
FTC/TDF) is derived as the most severe actions from all pills in the regimen. The increasing 
order of severity of AE action taken is: Unknown, Not Applicable, Dose Not Changed, Drug 
Interrupted, and Drug Withdrawn.

Prot_001.pdf: 
(fJ GILEAiJ 
CLINICAL STUDY PROTOCOL 
Study Title: 
A Phase 3, Randomized, Open Label Study to Evaluate the 
Safety and Efficacy of Switching to a Fixed Dose Combination 
(FDC) of GS-9883/Emtricitabine/T enofovi.r Alafenamide 
(GS-9883/F IT AF) from Elvitegravir/Cobicistat/Emtricitabine/ 
Tenofovi.r Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/ 
Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) or 
Atazanavir + Ritonavi.r + Emtricitabine/Tenofovir Disoproxil 
Fumarate (ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV -1 Infected Women 
Sponsor: 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
IND Number: 
125589 
EudraCT Number: 
Not Applicable 
Clinical Trials.gov Identifier: 
NCT02652624 
Indication: 
HIV -1 Infection 
Protocol ID: 
GS-US-380-1961 
Gilead Clinical Program 
Manager: 
Gilead Medical Monitor: 
Protocol Version/Date: 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Mobile: 
Original: 
Amendment 1: 
PPD 
t-'t-'U 
PPD 
Huyen Cao, MD 
PPD 
PPD 
PPD 
20 November 2015 
30 Jlme 2016 
CONFIDENTIALITY STATEMENT 
The infonnation 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 info1mation is only to be used 
by you in connection with authorized clinical studies of the investigational dmg described in the 
protocol. You will not disclose any of the info1mation to others without written authorization 
from Gilead Sciences, Inc., except to the extent necessary to obtain info1med consent from those 
persons to whom the dmg may be administered. 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 2
30 June 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....................................................................11
1.
INTRODUCTION ..............................................................................................................................................14
1.1.
Background ............................................................................................................................................14
1.2.
GS-9883 .................................................................................................................................................15
1.2.1.
General Information .............................................................................................................15
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................15
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................17
1.3.
Information About Emtricitabine (Emtriva®, FTC) ...............................................................................26
1.4.
Information About Tenofovir Alafenamide (TAF, GS-7340)................................................................26
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide 
(FTC/TAF)...........................................................................................................................26
1.4.2.
Clinical Trials of FTC/TAF as Part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF).........................................................................................................................28
1.5.
Information About GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) .......................29
1.5.1.
GS-US-141-1233: Relative Bioavailability of GS-9883, FTC, and TAF 
Between GS-9883/F/TAF and GS-9883 + F/TAF ...............................................................30
1.6.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)...................................................................................31
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®) ..................................................31
1.8.
Ritonavir (RTV, /r, Norvir®)..................................................................................................................31
1.9.
Atazanavir (ATV, Reyataz®)..................................................................................................................31
1.10.
Rationale for This Study ........................................................................................................................31
1.11.
Risk/Benefit Assessment for the Study..................................................................................................32
1.12.
Rationale for Dose Selection..................................................................................................................33
1.13.
Compliance ............................................................................................................................................35
2.
OBJECTIVES.....................................................................................................................................................36
3.
STUDY DESIGN................................................................................................................................................37
3.1.
Endpoints ...............................................................................................................................................37
3.2.
Study Design..........................................................................................................................................37
3.3.
Study Treatments ...................................................................................................................................37
3.4.
Duration of Treatment............................................................................................................................38
3.5.
Biomarker Testing..................................................................................................................................38
3.5.1.
Biomarker Samples for Optional Future Research...............................................................38
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................43
5.1.
Randomization .......................................................................................................................................43
5.2.
Description and Handling.......................................................................................................................43


GS-9883/F/TAF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
6. 
7. 
5.3. 
5.4. 
5.5. 
5. 2. 1. 
F onnulation . 
. ............. . 
5.2.2. 
Packaging and Labeling 
5.2.3. 
Storage and Handling 
............... ............... ............... .............. . 
Dosage and Administration of GS-9883/F/TAF, E/C/F/TAF, E/C/F/TDF and 
ATV+RTV+FTC/TDF 
............... ............... ............... ............... .............. . 
Prior and Concomitant Medications 
............... .............. . 
Accountability for Investigational Medicinal Product (IMP) . .............. . 
5.5.1. 
Investigational Medicinal Product Return or Disposal 
STUDY PROCEDURES .... ............... ............... .............. . 
6.1. 
6.2. 
6.3. 
6.4. 
6.5. 
6.6. 
6.7. 
6.8. 
6.9. 
6.10. 
6.11. 
6.12. 
6.13. 
6.14. 
Subject Emollment and Treatment Assignment. 
Pretreatment Assessments 
............................. . 
6.2.1. 
Screening Visit 
6.2.2. 
Day 1 Assessments 
Randomization 
............................. . 
Treatment Assessments (Weeks 4-48) .. . 
Treatment Assessments (Post Week 48) 
6.5.1. 
Post Week 48 Assessments .. 
Post-Treatment Assessments ............................................................. . 
6.6.1. 
Early Study Drugs Discontinuation (ESDD) Assessments .. . 
6.6.2. 
30 Day Follow Up ........................................................... . 
Criteria for Discontinuation of Study Treatment 
Other Evaluations ... ............... ............... .............. . 
6.8.1. 
Markers of Renal Tubular Function 
PPD 
Blooa and Unne Storage 
............... ............... .............. . 
Assessments for Premature Discontinuation from Study 
End of Study 
............... ............... ............... .............. . 
Post Study Care 
. . . . . . . . . . . . . . . . ............. . 
Virologic Failure 
............... ............... .............. . 
6.14.1. 
Management of VirologicRebound 
............... ............... .............. . 
6.14.2. 
Subjects with HIV -1 RNA 2' 50 copies/mL at Study Discontinuation or 
Week 48 ............... ............... ............... ............... ............... .............. . 
ADVERSE EVENTS AND TOXICITY MANAGEMENT .............. ............... .............. . 
7.1. 
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events 
7.1.1. 
Adverse Events 
.......................................................................... . 
7. 1.2. 
Serious Adverse Events 
........................................................... . 
7.1.3. 
Clinical Laboratory Abnonnalities and Other Abnonnal Assessments as 
Adverse Events or Serious Adverse Events 
............................. . 
7.2. 
Assessment of Adverse Events and Serious Adverse Events ............... . 
7.2.1. 
Assessment of Causality for Study Drugs and Procedures 
Final 
Amendment 1 
. ... 43 
... .45 
. ... 46 
. ... 46 
. ... 46 
. ... 48 
.... 48 
.... 49 
. ... 49 
. ... 49 
.... 49 
.... 51 
. ... 52 
. ... 52 
.... 55 
. ... 55 
.... 56 
. ... 56 
. ... 58 
.... 59 
. ... 59 
.... 59 
.... 60 
. ... 60 
.... 60 
. ... 60 
. ... 60 
. ... 61 
. ... 61 
. ... 62 
. ... 63 
.... 63 
. ... 63 
. ... 63 
. ... 64 
7.2.2. 
Assessment of Severity 
.......................................................................... . 
. ... 64 
.... 64 
. ... 65 
7.3. 
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead 
......................................................................................... . 
. ... 65 
7.4. 
7.5. 
7.3.1. 
Adverse Events 
.............. . 
7.3.2. 
Serious Adverse Events 
Gilead Reporting Requirements 
Toxicity Management 
............... ............... ............... .............. . 
7.5.1. 
Grades 1 and 2 Laboratory Abnonnality or Clinical Event .. 
7.5.2. 
Grade 3 Laboratory Abnonnality or Clinical Event 
7.5.3. 
Grade 4 Laboratory Abnonnality or Clinical Event 
7.5.4. 
Management of Potential Hepatobiliary Toxicity 
CONFIDENTIAL 
Page 3 
. ... 65 
.. .. 66 
.... 67 
. ... 67 
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.... 68 
.... 68 
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Amendment 1
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7.5.5.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................69
7.5.6.
Management of Hyperbilirubinemia ....................................................................................70
7.5.7.
On-Treatment Hepatitis C Management...............................................................................71
7.5.8.
Management of Potential Nephrotoxicity.............................................................................71
7.6.
Special Situations Reports......................................................................................................................71
7.6.1.
Definitions of Special Situations..........................................................................................71
7.6.2.
Instructions for Reporting Special Situations.......................................................................72
8.
STATISTICAL CONSIDERATIONS................................................................................................................74
8.1.
Analysis Objectives and Endpoints........................................................................................................74
8.1.1.
Analysis Objectives..............................................................................................................74
8.1.2.
Primary Endpoint .................................................................................................................74
8.1.3.
Secondary Endpoint .............................................................................................................74
8.2.
Analysis Conventions.............................................................................................................................74
8.2.1.
Analysis Sets ........................................................................................................................74
8.3.
Data Handling Conventions ...................................................................................................................75
8.4.
Demographic Data and Baseline Characteristics ...................................................................................76
8.5.
Efficacy Analysis ...................................................................................................................................76
8.5.1.
Primary Analysis..................................................................................................................76
8.5.2.
Secondary Analyses .............................................................................................................77
8.6.
Safety Analysis.......................................................................................................................................78
8.6.1.
Extent of Exposure...............................................................................................................78
8.6.2.
Adverse Events.....................................................................................................................78
8.6.3.
Laboratory Evaluations ........................................................................................................79
8.6.4.
Other Safety Evaluations......................................................................................................79
8.7.
Pharmacokinetic Analysis......................................................................................................................79
8.8.
Sample Size............................................................................................................................................79
8.9.
Independent Data Monitoring Committee..............................................................................................79
8.10.
Analysis Schedule ..................................................................................................................................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 ........................................................................................................................84
9.2.1.
Protocol Modifications.........................................................................................................84
9.2.2.
Study Report and Publications .............................................................................................85
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................85
9.3.1.
Payment Reporting...............................................................................................................85
9.3.2.
Access to Information for Monitoring..................................................................................85
9.3.3.
Access to Information for Auditing or Inspections ..............................................................86
9.3.4.
Study Discontinuation..........................................................................................................86
10.
REFERENCES ...................................................................................................................................................87
11.
APPENDICES ....................................................................................................................................................88


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 5
30 June 2016
Appendix 1.
Investigator Signature Page....................................................................................................89
Appendix 2.
Study Procedures Table..........................................................................................................90
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................93
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............94
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................117
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................119
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........19
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................20
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................21
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)........................................................................................22
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.................................................................................................34
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)..........................................47
Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens) .........................................................................................48
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................22
Figure 3-1.
Study Schema.........................................................................................................................38
Figure 6-1.
Virologic Rebound Schema....................................................................................................62


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety 
and Efficacy of Switching to a Fixed Dose Combination (FDC) of 
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) 
from Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir
Disoproxil Fumarate (E/C/F/TDF) or Atazanavir + Ritonavir + 
Emtricitabine/Tenofovir Disoproxil Fumarate 
(ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV-1 Infected Women
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
Not Applicable
NCT02652624
Study Centers Planned:
Approximately 75 centers in North America, Dominican Republic, 
Thailand, Russia, and Uganda
Objectives:
The primary objective of this study is:

To evaluate the efficacy of switching to an FDC of 
GS-9883/F/TAF versus continuing on a regimen consisting of 
E/C/F/TAF, E/C/F/TDF or ATV+RTV+FTC/TDF in 
virologically suppressed HIV-1 infected women as determined 
by the proportion of subjects with HIV-1 RNA ≥50 copies/mL 
at Week 48
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups 
through Week 48
Study Design:
Randomized, open label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to an FDC of 
GS-9883/F/TAF in HIV-1 infected women who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting 
of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF for 
≥12 consecutive weeks prior to screening.    


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Subjects will be HIV-1 infected women drawn from prior 
participation in Gilead clinical studies with ARV regimens 
consisting of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF
and must be virologically suppressed. Women who are currently 
suppressed on a commercially based ARV regimen, either Stribild®
(STB) or Genvoya®, may also be eligible. 
Subjects who provide written consent and meet all eligibility 
criteria will be randomized in a 1:1 ratio to receive open label 
medication as follows: 

Treatment Group 1: FDC of GS-9883 50 mg/
emtricitabine 200 mg/tenofovir alafenamide 25 mg 
(GS-9883/F/TAF) administered orally, once daily, without 
regard to food (n = 200) 

Treatment Group 2: Stay on baseline regimen (SBR), 
including E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF
administered orally, once daily, with food (n = 200) 
Randomization will be stratified by the prior treatment regimen 
group (ie, E/C/F/TAF, E/C/F/TDF, and ATV+RTV+FTC/TDF).
Number of Subjects 
Planned:
Approximately 400 subjects total
Approximately 200 subjects in each Treatment Group 1 and
Treatment Group 2
Target Population:
HIV-1 infected women who are virologically suppressed 
(HIV-1 RNA < 50 copies/mL) on a stable regimen of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥12 weeks prior to 
screening
Duration of Treatment:
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, 
subjects in a country where GS-9883/F/TAF FDC is not available 
will be given the option to receive GS-9883/F/TAF FDC for an 
additional 48 weeks, or until the product becomes accessible to 
subjects through an access program, or until Gilead Sciences elects 
to discontinue the study in that country, whichever occurs first.
Subjects who complete the study through the Week 48 Visit and 
do not continue participation in the study will be required to return 
to the clinic 30 days after the Week 48 Visit for a 30 Day 
Follow-Up Visit.


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Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected women who meet the following 
criteria:

Currently on a stable antiretroviral regimen consisting of 
E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF continuously 
for ≥12 consecutive weeks preceding the screening visit

Documented plasma HIV-1 RNA levels < 50 copies/mL for 
≥12 weeks preceding the Screening visit. After reaching 
HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by re-suppression to < 50 copies/mL 
is allowed

HIV-1 RNA <50 copies/mL at screening

Estimated glomerular filtration rate (eGFR) ≥50 mL/min 
according to the Cockcroft-Gault (C-G) formula at the 
screening visit
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 
48 weeks. Following the Screening and Day 1 visits, subjects will 
return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
until the Week 48 visit. 
For all eligible subjects, blood and urine will be collected at Day 1, 
Weeks 4, 8, 12, and then every 12 weeks through the Week 48 visit. 
Laboratory analyses (including hematology, chemistry, 
and urinalysis), HIV-1 RNA, CD4+ cell count, and complete or 
symptom directed physical examinations will be performed at the 
Screening, Day 1, and all subsequent study visits. 
Adverse events and concomitant medications will be assessed at 
each visit.
Test Product, Dose, and 
Mode of Administration:
FDC of GS-9883 50 mg/emtricitabine 200 mg/
tenofovir alafenamide 25 mg (GS-9883/F/TAF) administered 
orally, once daily, without regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Current antiretroviral drug regimen consisting of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF administered orally,
once daily, with food.
Criteria for Evaluation:
Safety:
Adverse events and clinical laboratory tests to evaluate the safety 
and tolerability of the treatment regimens.  


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Efficacy:
The primary efficacy endpoint is:

The proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as determined by the United States (US) Food and 
Drug Administration (FDA)-defined snapshot algorithm.
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as determined by the US FDA-defined snapshot 
algorithm

The change from baseline in CD4+ cell count at Week 48
Pharmacokinetics:
For all subjects on GS-9883/F/TAF (Treatment Group 1), a single 
anytime pre or post-dose PK blood sample will be collected at 
Weeks 8, 24, and 36. 
For all subjects on GS-9883/F/TAF (Treatment Group 1), a trough 
PK blood sample will be obtained 20-28 hours following the last 
dose at Weeks 4 and 12. Following an observed dose, one PK blood 
sample will be collected between 1 and 4 hours post-dose. 
Additionally, in a subset of subjects at selected sites who become 
pregnant, matching maternal and umbilical cord blood will be 
obtained at delivery to assess placental transfer of study drug.
The concentration of GS-9883 may be summarized using 
descriptive statistics. 
Statistical Methods:
The primary analysis will consist of a non-inferiority test of 
switching to GS-9883/F/TAF FDC versus SBR with respect to the 
proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as determined by the US FDA-defined snapshot 
algorithm. It will be concluded that GS-9883/F/TAF is non-inferior 
to SBR if the upper bound of the 2-sided 95% confidence interval 
(CI) of the difference between treatment groups (GS-9883/F/TAF –
SBR) in the proportion of subjects with HIV-1 RNA 
> 50 copies/mL is less than 4%; ie, a margin of 4% is applied to 
non-inferiority assessment. The 2-sided 95% CIs will be 
constructed based on the exact method.
The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as determined 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 CD4+ cell count at Week 48 will be 
summarized by treatment using descriptive statistics. The 
differences and the associated 95% CIs will be constructed using 
Analysis of Variance (ANOVA) model, including treatment 
(GS-9883/F/TAF vs. SBR) as a fixed effect in the model.


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Adverse events and clinical laboratory assessments will be 
summarized using descriptive statistics.
A total of approximately 400 HIV-1 infected women, randomized 
in a 1:1 ratio to 2 treatment groups (200 subjects per treatment 
group), achieves at least 80% power to detect a non-inferiority 
margin of 4% difference in the percentage of subjects with HIV-1 
RNA ≥50 copies/mL at Week 48 between the 2 treatment groups. 
For sample size and power computation, it is assumed that both 
treatment groups have 2% of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 (based on the historical Gilead 
Genvoya® and Stribild® (STB) studies), that a non-inferiority 
margin is 4%, and that the significance level of the test is at a 
one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq®
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir, Reyataz®
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration versus 
time curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, C, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
DTG
dolutegravir, Tivicay®
EC50
50% effective inhibitory concentration
ECG
electrocardiogram
eCRF
electronic case report form(s)
EVG, E
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, Genvoya®
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild®
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination


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FSH
follicle-stimulating hormone
FTC, F
emtricitabine, Emtriva®
FTC/TAF 
emtricitabine/tenofovir alafenamide, Descovy®
FTC/TDF
emtricitabine/tenofovir disoproxil fumarate, Truvada®
GCP
Good Clinical Practice (Guidelines)
GGT
gamma glutamyl transferase
GSI
Gilead Sciences, Inc.
GS-9883/F/TAF
GS-9883/emtricitabine/tenofovir alafenamide
HAART
highly active antiretroviral therapy
HBV
hepatitis B virus
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDPE
high-density polyethylene
hERG
human Ether-à-go-go-Related Gene
HIV
Human Immunodeficiency Virus
HIV Sx
HIV Symptoms Distress Module
HLA
human leukocyte antigen
IB
investigator’s brochure
IC50
50% maximal inhibitory concentration
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
institutional ethics committee
IND
Investigational New Drug (Application)
INSTI
integrase strand-transfer inhibitors
IRB
institutional review board
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LDH
lactate dehydrogenase
LLN
lower limit of the normal range
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
MH
Mantel-Haenszel
min
minute
mmHg
millimeters mercury
MT4
human t cell leukemia cell line
nM
nanoMolar
NNRTI
non-nucleoside reverse transcriptase inhibitor
NOAEL
no observed adverse effect level


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NOEL
no observed effect level
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
OCT2
organic cation transporter 2
PI
protease inhibitor
PK
pharmacokinetic
PT
preferred term 
PT
prothrombin time 
QD
once daily 
RAL
raltegravir
RNA
ribonucleic acid
RTV
ritonavir, Norvir®
SAE
serious adverse event
STB
Stribild®, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide, GS-7340
TDF
tenofovir disoproxil fumarate, Viread®
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase 
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {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 half maximal inhibitory concentration (IC50)values ranging from 1.5 to 2.4 nM, 
similar to the inhibitory effect of DTG and EVG. GS-9883 is highly potent against HIV 
replication in the human T cell leukemia MT4 cell line with an EC50 (50% effective inhibitory 
concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. GS-9883 does not 
show significant cytotoxicity against dividing and non-dividing human PBMCs, primary human 
hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 μM. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter organic cation transporter 2 (OCT2)
(IC50 = 0.42 μM). As a result, GS-9883 is not expected to significantly interfere with the key 


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


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No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL). The estimated margin of exposure at the NOEL 
was approximately 5.1-fold based on expected human exposure with the once daily dosing of the 
GS-9883/F/TAF (50/200/25 mg) tablet.
A standard battery of in vitro and in vivo studies was performed to assess the genotoxic potential 
of GS-9883. There was no evidence of mutagenic or clastogenic activity in an in vitro bacterial 
reverse mutation assay (Study TX-141-2026), a chromosomal aberration assay in human 
lymphocytes (Study TX-141-2027), or in a rat micronucleus test (Study TX-141-2029).
Study TX-141-2045 assessed the potential adverse effects of maternal GS-9883 exposure from 
implantation to weaning on the pregnancy, parturition, and lactation of the maternal Sprague 
Dawley Rats and on the growth, viability, and development of the neonates. No GS-9883-related 
effects were noted at any dosage level during the study. Therefore, a dosage level of 
300 mg/kg/day (the highest dosage level evaluated) was the NOEL for maternal systemic 
toxicity, F1 neonatal/developmental toxicity, F1 parental systemic toxicity, F1 reproductive 
toxicity, and F2 neonatal/early postnatal toxicity of GS-9883 when administered orally (gavage) 
to F0 maternal Crl:CD(SD) rats. The NOEL corresponds to mean Cmax values of 156 µg/mL 
and 48 µg/mL and mean AUC0-24 values of 100 µg•h/mL and 1120 µg•h/mL for F0 females 
(LD10) and F1 pups (PND 10), respectively.
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 (CSR available)


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
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 Study Evaluating the 
Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular Filtration Rate 
(CSR available)

GS-US-311-1790, a Phase 1 Randomized, Open Label, Drug Interaction Study Evaluating 
the Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (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.


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No deaths or pregnancies were reported. No Grade 3 or 4 AEs or SAEs, were reported in any 
cohort.
Increases in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2. In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort. In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF. All 
changes returned to baseline after discontinuation of GS-9883.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood. All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.
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, , which is 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 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 IQ95 Values 
(GS-9883 PK Analysis Set) 
GS-9883 Dose 
N 
Median (range) C1au,SS (nglmL) 
Median (range) paiQ95• 
5mg 
4 
206.5 (146.0 to 342.0) 
1.3 (0.9 to 2.1) 
25 mg 
4 
797.5 (714.0 to 1900.0) 
4.9 (4.4 to 11.7) 
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 vitro 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. 
GS-9883 5 ~ 
(~): 
GS-9883 25 ~ 
(~): 
GS-9883 50~(~): 
GS-9883 100 mg (~): 
Placebo(~): 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
• = GS-9883 5 mg 
0 = GS-9883 25mg 
!:; = GS-9883 50 mg 
D = GS-9883100 mg 
0 =Placebo 
BL 
2 
3 
4 
3 
3 
3 
3 
4 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
3 
4 
4 
4 
4 
7 
8 
9 
Day 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
10 
11 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
14 
3 
4 
4 
4 
4 
-- -........ 
--
--
17 
3 
3 
4 
4 
4 
NOTE: Baseline value was the last available value collected prior to the time of the ftrst dose of study drug. 
2 
-1 
-2 
-3 
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 (DA VG 11) was -0.92 log10 in the 5 mg coh01t, -1.33 log1o in the 25 mg coh01t, 
-1.37 log10 in the 50 mg coh01i and -1 .61log10 in the 100 mg coh01t. 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. 
CONFIDENTIAL 
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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
Week 24 interim data are summarized below. 
1.2.3.4.
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24
data analysis, 2 subjects (2.0%) had prematurely discontinued study treatment, one in each 
treatment group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and estimated glomerular 
filtration rate [eGFR] using the Cockcroft-Gault method [eGFRCG]) were similar between the 
2 treatment groups.
Median (Q1, Q3) baseline HIV-1 RNA was 4.45 (3.96, 4.79) log10 copies/mL, with 
82.7% of subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had > 400,000 copies/mL 
at baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 1 subject was 
randomized to DTG+F/TAF.

Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 
41.8% of subjects having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 
125.3 (105.7, 147.0) mL/min.
1.2.3.5.
Efficacy Results
Virologic success at Week 12 and 24 was assessed using the US FDA-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


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GS-9883+F/TAF 93.8%; DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79); Week 24 GS-9883+ F/TAF 95.4%, DTG+F/TAF 
93.9% (1.0%; 95%CI: -10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 was considered a virologic failure by US FDA-defined
snapshot algorithm with 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 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 at 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.
1.2.3.6.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 58.5%, 38 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common TEAEs (occurring in > 1 subject) by treatment group were as follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE, and 1 other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator, resulted in study 
drug discontinuation, or required interruption of study drug, and both SAEs resolved.
The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883/F/TAF 


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group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs that were considered related to study 
drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation
were reported in either treatment group.
Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least
1 grade level increase from baseline in graded abnormality) was similar between treatment groups 
as follows: GS-9883+F/TAF 76.6%, 49 subjects; DTG+F/TAF 78.1%, 25 subjects. The majority 
of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The percentage of 
subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality was similar 
between treatment groups as follows: GS-9883+F/TAF 17.2%, 11 subjects; DTG+F/TAF 12.5%, 
4 subjects. Grade 3 or 4 treatment-emergent laboratory abnormalities occurring in at least 
2 subjects in either treatment group were as follows: creatine kinase (GS-9883+F/TAF, 3.1% 
[2 subjects]), and fasting low-density lipoprotein (LDL) (GS-9883+F/TAF, 3.1% [2 subjects]). 
The only Grade 4 laboratory abnormalities were for creatine kinase, reported in 2 subjects (3.1%) 
in the GS-9883+F/TAF group. All increased creatine kinase values appeared to be transient, and 
none were associated with AEs. Of the 2 subjects with increased AST, 1 subject had Grade 3 AST 
and Grade 3 ALT at Week 24 in the setting of alcohol abuse; the other subject had Grade 3 AST 
at Week 8 that returned to normal by Week 24.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. There were 
similar increases from baseline in median (Q1, Q3) serum creatinine in both treatment groups at 
Week 24: GS-9883+F/TAF 0.12 (0.06, 0.18) mg/dL; DTG+F/TAF 0.13 (0.05, 0.21) mg/dL. 
There were decreases in median (Q1, Q3) eGFRCG at Week 24, which were smaller in the 
GS-9883+F/TAF compared with the DTG+F/TAF group: GS-9883+F/TAF 
−13.3 (−19.9, −4.0) mL/min; DTG+F/TAF −17.2 (−25.7, −6.9) mL/min.
Conclusions
Key Week 24 conclusions from Study GS-US-141-1475 include the following:

Virologic success at Week 24 when assessed using the 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.


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Amendment 1
CONFIDENTIAL
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
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 Food and Drug Administration (FDA) for 
marketing on 2 July 2003 and is available under the name Emtriva®. In the European Union 
(EU), marketing authorization was granted for both the 200 mg Emtriva® capsule formulation 
and a 10 mg/mL Emtriva® oral Solution formulation on 24 October 2003, with indications for the 
treatment of HIV infection concurrently with other antiretroviral drugs in both adult and 
pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information About Tenofovir Alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) or 
Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide (FTC/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected subjects (completed)

GS-US-120-0104, a Phase 1b study of the pharmacokinetics and antiviral activity of 
GS-7340 (8 mg, 25 mg, 40 mg) in HIV infected subjects (completed)


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GS-US-120-0107, a Phase 1, partially-blinded, randomized, placebo- and positive controlled 
study to evaluate the effect of GS-7340 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-120-0108, a Phase 1, open-label, parallel-design study to evaluate the 
pharmacokinetics of GS-7340 in subjects with severe renal impairment (completed)

GS-US-120-0109, a Phase 1 study to evaluate the pharmacokinetics, metabolism and 
excretion of GS-7340 (completed)

GS-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the 
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic 
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug 
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of 
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in 
healthy subjects (completed)

GS-US-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 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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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)

GS-US-292-0119, a Phase 3 open-label study to evaluate switching from optimized stable 
antiretroviral regimens containing darunavir to 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) single tablet 
regimen (STR) plus darunavir (DRV) in treatment experienced HIV-1 positive adults 
(ongoing)

GS-US-292-0106, a Phase 2/3, open-label study of the pharmacokinetics, safety, and 
antiviral activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected antiretroviral treatment-naive 
adolescents (ongoing)


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


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1.5.1.
GS-US-141-1233: Relative Bioavailability of GS-9883, FTC, and TAF 
Between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is a 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 CSR is available; results are summarized below.
Cohort 1 Results:
Pharmacokinetic Results
Under fasted conditions, GS-9883 AUCinf and Cmax were 27% and 31% higher, respectively, 
following GS-9883/F/TAF (75/200/25 mg) FDC administration than following administration of 
single-agent GS-9883 (75 mg) with the F/TAF (200/25 mg) FDC. FTC and TAF exposure was 
similar following administration of GS-9883/F/TAF (75/200/25 mg) or single-agent GS-9883 
(75 mg) with the F/TAF (200/25 mg) FDC. Compared with administration under fasted 
conditions, administration of the GS-9883/F/TAF (75/200/25 mg) FDC with a high-fat meal 
resulted in a 46% higher GS-9883 AUCinf and a 27% higher GS-9883 Cmax. The impact of food 
on TAF and FTC exposure was similar to that previously observed for F/TAF 
(Study GS-US-311-1386). GS-9883/F/TAF may be taken without regard to food. Based on these 
results, Cohort 2 was added to the study via protocol amendment to evaluate the relative BA of 
the GS-9883/F/TAF (50/200/25 mg) FDC tablet compared with the single-agent GS-9883 
(75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered simultaneously.
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 1, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.


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Cohort 2 Results:
Pharmacokinetic Results
The PK results from Study GS-US-141-1233 demonstrated that the GS-9883 AUCinf and Cmax
following administration of the 50 mg 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 in the 50 mg FDC with 
AUCinf increasing by 24%. The steady state paIQ95 of GS-9883/F/TAF (50/200/25 mg) following 
multiple doses 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 in the 50 mg FDC 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.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)
Further information is available in the US Prescribing Information and Investigator’s Brochure 
for E/C/F/TDF.
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®)
Further information is available in the Prescribing Information for Truvada®.
1.8.
Ritonavir (RTV, /r, Norvir®)
Further information is available in the Prescribing Information for Norvir®.
1.9.
Atazanavir (ATV, Reyataz®)
Further information is available in the Prescribing Information for Reyataz®.
1.10.
Rationale for This Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 
HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.


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The GS-9883/F/TAF FDC has the potential to offer a simple, once-daily regimen containing a 
second generation INSTI that provides a high barrier to resistance, does not require a boosting 
agent, and offers an effective and safer alternative to standard nucleos(t)ide based regimens, 
without the need for HLA testing or close monitoring of renal or bone toxicities. It could provide 
an FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute to an 
increased risk of cardiovascular events, could be used in patients with chronic hepatitis B or C 
infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities. In addition, the benefit/risk balance of administration of 
GS-9883/F/TAF to pregnant women is considered favorable as demonstrated by the lack of 
findings in pre and postnatal nonclinical studies. Approximately 50% of the global population of 
HIV-infected persons are women, however they remain under-represented in most clinical HIV 
studies. In general, studies to date have not shown gender differences in virologic responses to 
antiretroviral therapy (ART), but a number of studies have suggested that gender may influence 
the frequency, presentation, and severity of selected ARV-related adverse events. Although data 
are limited, the pharmacokinetics for some ARV drugs may differ between men and women, 
possibly because of variations in factors such as body weight, plasma volume, gastric emptying 
time, plasma protein levels, CYP450 activity, drug transporter function, and excretion activity. It 
is important to understand potential gender-specific safety and efficacy issues in women when 
assessing virologic response, tolerability, and adherence. This study will ensure that there is 
adequate safety data in HIV-1-infected women in the Phase 3 program for GS-9883/F/TAF.
The objective of this study is to evaluate the safety and efficacy of an FDC containing 
GS-9883/F/TAF versus continuing on a regimen consisting of E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF in women who are virologically suppressed. Switching to 
GS-9883/F/TAF offers the advantages of a single-tablet FDC containing the unboosted, 
next-generation INSTI, GS-9883, combined with a TAF-based nucleotide backbone.
GS-9883/F/TAF FDC which includes TAF, has the potential to offer an effective and safer 
alternative to standard nucleos(t)ide based regimens, without the need for close monitoring of 
renal or bone toxicities or increase risk of cardiovascular complications as patients age and 
confront non HIV-related comorbidities.
1.11.
Risk/Benefit Assessment for the Study
All patients with HIV-1 infection should receive effective anti-retroviral therapy. Potential risks
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and
lactic acidosis with steatosis. The risk of class effects is considered to be low. Important
identified risks appropriately managed by study inclusion/exclusion criteria as well as through
close clinical and laboratory monitoring during the study are as follows: allergy to any 
components of the tablets. Protease inhibitors may be associated with increased lipid levels and 
gastrointestinal side effects. If patients are currently infected with hepatitis B and discontinue 
their existing or new therapy, there is a risk of severe acute exacerbations of hepatitis B.
In a study of GS-9883 in monkeys, administration of 1000 mg/kg/day (high 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 had exposures of GS-9883 


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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.
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 is favorable at this time.
1.12.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as
single agent capsules (EMTRIVA) and as a component of a number of fixed dose combination
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.


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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 24 interim data from this study, support the safety and efficacy of GS-9883 exposures 
obtained with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF 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.  


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E/C/F/TAF
EVG/COBI/FTC/TAF (150/150/200/10 mg) is a fixed dose combination, with only one dose 
combination available; and has been approved by the United States Food and Drug Administration 
(FDA) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and 
pediatric patients 12 years of age and older with no ARV treatment history or to replace the current 
ARV regimen in those who are virologically suppressed on a stable ARV regimen with no history 
of treatment failure and no known substitutions associated with resistance. This FDC contains the 
equivalent doses of EVG, COBI and FTC in the marketed product, Stribild® (STB).
E/C/F/TDF (STB)
EVG/COBI/FTC/TDF (150/150/200/300 mg) is a fixed dose combination, with only one dose 
combination available; and is approved for use (Stribild®) in the United States by the 
Food and Drug Administration (FDA), for the treatment of HIV-1 infection in treatment-naïve 
adults.
ATV+RTV+FTC/TDF
ATV (300 mg), RTV (100 mg) and FTC/TDF (200/300 mg) represent the current marketed 
doses of these products.
1.13.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.  


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of switching to an FDC of GS-9883/F/TAF versus continuing on a 
regimen consisting of E/C/F/TAF, E/C/F/TDF or ATV+RTV+FTC/TDF in virologically 
suppressed HIV-1 infected women as determined by the proportion of subjects with HIV-1 
RNA ≥ 50 copies/mL at Week 48. 
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups through Week 48.  


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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

The proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 as determined by
US FDA-defined snapshot algorithm. 
The secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined by 
the US FDA-defined snapshot algorithm.

The change from baseline in CD4+ cell count at Week 48. 
3.2.
Study Design
This protocol describes a randomized, open label, multicenter, active-controlled study to evaluate 
the safety and efficacy of switching to a GS-9883/F/TAF FDC in HIV-1 infected women who 
are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of 
E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥ 12 consecutive weeks prior to 
screening.
3.3.
Study Treatments
Subjects who meet one of the following criteria will be given the option to participate in this 
study:

Completion of a primary or secondary endpoint visit in an ongoing Gilead study with ARV 
regimens consisting of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF, or

Currently suppressed on a commercially based, single tablet regimen (STR) consisting of
E/C/F/TAF (Genvoya®) or E/C/F/TDF (Stribild®)   
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to receive open label medication:

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food (n = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)


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3.4. 
Duration of Treatment 
Final 
Amendment 1 
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, subjects in a cmmtJ.y where 
GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/TAF FDC 
for an additional48 weeks and attend study visits evety 12 weeks, or until the product becomes 
accessible to subjects through an access program, or until Gilead Sciences elects to discontinue 
the study in that countly, whichever occurs first. 
Subjects who complete the study through the Week 48 Visit and do not continue post Week 48 
will be required to retum to the clinic 30 days after the Week 48 Visit for a 30 Day Follow-Up 
Visit. 
Figure 3-1. 
Screening 
::; 30 days prior 
to Day 1 
Study Schema 
Day 1 " 
Treatment Group 1: GS-9883/F/TAF FDC 
N=200 
Tre4ltment Group 2: Stay on baseline 
regimen (E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF) N=200 
Week48 b 
30 
Day 
F/Uc 
a 
Following the Day 1 visit, subje.cts will be required to retum for study visits at Weeks 4, 8, 12 and then every 12 weeks 
tlu·ough Week 48 
b 
Aftet· Week 48, subjects in a cmmtry where GS-9883/F !T AF FDC is not available will be given the option to receive 
GS-9883/F!TAF for an additional48 weeks, or lmtil the product becomes accessible to subjects t1u·ough an access program, 
or tmtil Gilead Sciences elects to discontinue the study in that cmmtry, whichever occurs fn·st 
c 
Subjects who complete the study tlu-ough We.ek 48 and do not wish to receive GS-9883/F/TAF FDC will be required to 
retmn to the clinic 30 days after the completion of study dmg for a 30-day follow-up visit 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Future Research 
p 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 400 subjects who meet the eligibility criteria will be enrolled. 
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Female, (at birth), Age ≥18 years
3) Currently on a stable antiretroviral regimen of E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF continuously for ≥12 consecutive weeks preceding the screening 
visit
4) Completion of the primary or secondary endpoint visit in an ongoing Gilead study, with 
ARV regimens consisting of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF. Women 
who are not current Gilead study participants should be on a stable, commercially based
ARV drug regimen consisting of E/C/F/TAF or E/C/F/TDF.
5) Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥ 12 weeks preceding the 
Screening Visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by resuppression to < 50 copies/mL are allowed
6)
HIV-1 RNA < 50 copies/mL at screening
7) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) 
8) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥ 0.83 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft et al 1976}:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg) x 0.85
72 (serum creatinine in μmol/L) x 0.6786
CrCL (mL/sec)
9) Hepatic transaminases (AST and ALT) ≤5 × upper limit of normal (ULN).


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10) Total bilirubin 1.5 mg/dL (26 μmol/L), or normal direct bilirubin.
11) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L)).
12) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN).
13) Women of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Women who utilize hormonal contraceptive as one of their birth control methods must 
have used the same method for at least 3 months prior to study drug dosing. 
b) Female subjects who have stopped menstruating for ≥12 months but do not have 
documentation of ovarian hormonal failure must have a serum follicle stimulating 
hormone (FSH) level at screening within the post-menopausal range based on the 
Central Laboratory reference range.
14) Have no documented or suspected resistance to FTC, TFV, ATV or EVG including, but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
2) Subjects experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or 
variceal bleeding)
3) Have been treated with immunosuppressant therapies or chemotherapeutic agents within 
3 months of study screening, or expected to receive these agents or systemic steroids 
during the study (eg, corticosteroids, immunoglobulins, and other immune- or 
cytokine-based therapies)  
4) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance  
5) A history of or ongoing malignancy (including untreated carcinoma in-situ) other than 
cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous 
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must 
not have received any systemic therapy for KS within 30 days of Day 1 and are not 
anticipated to require systemic therapy during the study


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6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1 
7) Participation in any clinical trial other than ongoing Gilead studies with ARV regimens 
consisting of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF, including observational 
studies, without prior approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC, E/C/F/TAF, E/C/F/TDF, 
ATV, RTV, or FTC/TDF
10) Women who are pregnant (as confirmed by positive serum pregnancy test)
11) Women who are breastfeeding  
12) Subjects receiving ongoing therapy with any of the medications in Table 5-1 or Table 5-2.
Administration of any disallowed agent must be discontinued at least 30 days prior to the 
Day 1 visit and for the duration of the study
13) Acute hepatitis in the 30 days prior to study entry
14) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visit cannot occur until subject eligibility has been confirmed.  
Once eligibility has been confirmed and prior to or during the Day 1 visit the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2. 

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food (n = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)
The IWRS will assign study drug bottle numbers of open label FDC of GS-9883/F/TAF, 
open label E/C/F/TAF, open label E/C/F/TDF or open label ATV+RTV+FTC/TDF at each study 
visit for each subject.  
Randomization will be stratified by the prior treatment regimen group (ie, E/C/F/TAF, E/C/F/TDF 
and ATV+RTV+FTC/TDF).
5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Tablets
GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.


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


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg
(GS-9883/F/TAF) Tablets
GS-9883/F/TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each 
bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.2.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Alafenamide 10 mg (E/C/F/TAF) Tablets
E/C/F/TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.3.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Disoproxil Fumarate 300 mg (E/C/F/TDF, Stribild®) Tablets
E/C/F/TDF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets and a silica gel desiccant with or without polyester coil fiber. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.4.
Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg 
(FTC/TDF, Truvada®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.5.
Ritonavir (RTV, Norvir®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.6.
Atazanavir (ATV, Reyataz®) Capsules
Refer to commercially available Prescribing Information.
All study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice – Annex 13 
(Investigational Medicinal Products), and/or other local regulations.


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5.2.3.
Storage and Handling
Study drugs GS-9883/F/TAF FDC, E/C/F/TAF and E/C/F/TDF should be stored at controlled 
room temperature of 25 °C (77 °F); excursions are permitted between 15 °C and 30 °C
(59 °F and 86 °F). Storage conditions are specified on the label. Until dispensed to the subjects, 
all bottles of study drugs should be stored in a securely locked area, accessible only to authorized 
site personnel.
Commercial product of Norvir® (RTV), Reyataz® (ATV), and Truvada® (FTC/TDF) will be used 
for the study. Further information regarding storage and handling are available in the 
Prescribing Information for commercial products.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/F/TAF, E/C/F/TAF, E/C/F/TDF and 
ATV+RTV+FTC/TDF
Study drugs GS-9883/F/TAF FDC, E/C/F/TAF, E/C/F/TDF, and ATV+RTV+FTC/TDF will be 
provided by Gilead Sciences.

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food (n = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability. The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return. 
5.4.
Prior and Concomitant Medications
The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following tables and use of herbal/natural supplements are excluded or 
should be used with caution while subjects are participating in the study. Subjects will refrain 
from consumption of grapefruit juice and Seville orange juice throughout participation in the 
study. 


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Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids 
(eg, Tums or Rolaids); the ulcer medication 
sucralfate (Carafate); or vitamin or mineral 
supplements that contain calcium, iron or zinc for 
a minimum of 2 hours before and 6 hours after any 
dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinaccea
Oral Hypoglycemic Agent
Metformin: close monitoring is recommended. 
A dose adjustment of Metformin may be 
necessary. Limit total daily doses of Metformin to 
1000mg either when starting or at study entry.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study. 


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Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens)
Drug Class
Agents Disallowed*
Alpha-1 Adrenoreceptor Antagonist 
Alfuzosin
Antiarrhythmic Agent 
Amiodarone, Dronedarone
Anticonvulsants 
Phenytoin, Carbamazepine and Phenytoin
Antimycobacterials 
Rifampin
Antipsychotics
Lurasidone, Pimozide
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements 
St. John’s Wort
Anticancer drugs
Irinotecana
Ergot Derivatives
Ergotamine, Ergonovine, Dihydroergotamine, Methylergonovine, Ergometrine
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Phosphodiesterase-5 Inhibitors
Sildenafil (for PAH)
Sedatives/Hypnotics 
Midazolam (PO), Triazolam
Calcium Channel Blockers 
Bepridil
Chronic angina 
Ranolazine
a
Applied to ATV regimen only
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Sciences Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead Sciences as soon as he/she is aware of the use of the excluded 
medication.
5.5.
Accountability for Investigational Medicinal Product (IMP)
The investigator is responsible for ensuring adequate accountability of all used and unused IMP. 
This includes acknowledgement of receipt of each shipment of IMP (quantity and condition). All 
used and unused IMP dispensed to subjects must be returned to the site.
Study Drug accountability records will be provided to each study site to:

Record the date received and quantity of IMP kits 

Record the date, subject number, subject initials, the IMP kit number dispensed

Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
Study drug return and disposal will be performed as outlined in Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that subjects are eligible for the study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30 days before Day 1 to determine eligibility for participation in 
the study. The screening visit may coincide with a primary or secondary endpoint visit for 
subjects in an ongoing Gilead study with ARV regimens consisting of E/C/F/TAF, E/C/F/TDF, 
or ATV+RTV+FTC/TDF. The following will be performed and documented at screening: 

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events and prior 
medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (women of childbearing potential only). If the test is positive, the 
subject will not be enrolled
FSH test is required for women who have stopped menstruating for ≥12 months but do 
not have documentation of ovarian hormonal failure


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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, amylase (reflex lipase 
testing is performed in subjects with total amylase > 1.5 × ULN), and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg) x 0.85
72 (serum creatinine in μmol/L) x 0.6786
CrCL (mL/sec)
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
Plasma HIV-1 RNA 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), 
Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)
The following will be conducted by the central laboratory if the following criteria are met:

If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, 
reflex HBeAb), and quantitative HBsAg

If positive HBcAb with negative HBsAg and negative HBsAb, reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to 
be negative, reflex HBeAb
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed

Review of adverse events and concomitant medications
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30 days after screening for the Day 1 visit. Subjects must continue to take their 
current study treatment regimen up until their scheduled Day 1 visit. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. 
See Section 7 Adverse Events and Toxicity Management for additional details.


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6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
confirmed eligibility before proceeding with the Day 1 visit. The subject must complete all 
study procedures before being administered the study drug:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

12-lead ECG performed supine

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
phosphorus, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing 
is performed in subjects with total amylase > 1.5 × ULN), and TSH
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, 
and triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, 
but the subject must return within 72 hours in a fasted state to draw blood for the 
metabolic assessments.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count


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• 
• 
• 
• 
-
Plasma HIV-1 RNA 
-
CD4+ cell cmmt 
-
Plasma storage samples for safety, virology, or PK testing 
-
Whole blood sample for potential virologic resistance testing and/or HIV DNA 
genotyping 
-
Subjects who meet the definition ofHBV infection at Screening Visit (positive semm 
HBsAg or positive HBcAb with quantifiable HBV DNA), will have plasma HBV DNA 
tested 
PD 
Provide subject dosing diaty to all subjects in Treatment Group 1 
Dispense study dmg 
Subjects in treatment group 1 should be instructed to take study dmgs without regard to food . 
Subjects in treatinent group 2 should be instmcted to take study dmg with food. Subjects are 
required to initiate dosing of study dm gs the day of the Day 1 visit. The subject should be 
counseled regarding the impoliance of adherence and taking their study medications at 
approximately the same time each day as directed by the Investigator. 
6.3. 
Randomization 
Once eligibility has been confinned and prior to or dming the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be perfmmed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedmes have been completed and subject 
eligibility has been confi1med. 
6.4. 
Treatment Assessments (Weeks 4-48) 
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, and 48 unless 
othetwise specified. 
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within± 6 days at Week 24 and Week 36, unless 
othetwise specified. The visit window at Week 48 will be ± 6 weeks of the protocol-specified 
visit date, and these clinical visit windows coincide with the Week 48 statistical analysis window 
for HIV-1 RNA. 
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Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study dmg. 
• 
Review of AEs and changes in concomitant medications 
• 
Complete physical examination (Weeks 24 and 48) (urogenital/anorectal 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 perf01med supine (Weeks 24 and 48) 
• 
Urine collection for the following laborat01y procedures: 
-
Urinalysis 
-
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin (Weeks 24 and 48) 
-
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confnmed with a se1um test. If the test is positive, subjects may opt to 
remain on study dmg and an additional infonned consent would be required. 
• 
PPD 
-
Urine storage sample for possible additional clinical testing 
• 
Blood sample collection for the following laboratory analyses: 
-
Chemi.stly profile: alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and 
indirect bililubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphoms, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is perf01med in subjects with total amylase > 1.5 x ULN). At 
Weeks 12, 24 and 48, analyses of glucose will be done as pati of the fasting metabolic 
assessments and not as pa1i of the chemishy profile. At Weeks 24 and 48, TSH will also 
be analyzed. 
-
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must retmn within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24, and 48) 
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Estimated glomerular filtration rate according to the Cockcroft-Gault formula 
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

For subjects who meet the definition of HBV infection, the following will be 
conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) 
and HBeAg (if negative, reflex HBeAb) (Weeks 12, 24, and 48)
HCV RNA for subjects with positive HCVAb at screening. (Weeks 24 and 48)
Plasma storage sample for safety, virology, or PK testing

Pharmacokinetic Blood Collection for all subjects on GS-9883/F/TAF only 
(Treatment Group 1). Details of pharmacokinetic blood sampling procedures and sample 
management will be documented in the study’s laboratory manual.
Single Anytime, Trough and Post-Dose PK Samples: (GS-9883/F/TAF –
Treatment Group 1 only)
■
Subjects will have a single anytime pre or post-dose PK blood sample at 
Weeks 8, 24, and 36
■
Observed dosing at the clinic: If possible, subjects will have a trough PK blood 
sample collected between 20-28 hours following the last dose at Weeks 4 and 12.
Subjects must be instructed to not take their study drugs on the morning of their visit 
for the trough sample collection.  Subjects will then take an observed dose of study 
drug at the clinic. If the subject has taken their dose of study drugs prior to the visit, 
the visit may proceed, but the subject must return within 72 hours for the single 
trough PK blood sample collection. In the event a subject routinely takes their study 
drug in the evening, a single anytime sample may be drawn at Weeks 4 and 12 as the 
subject will not be instructed to change their dosing time to accommodate this trough 
PK draw. A single PK blood sample will be collected between 1 and 4 hours post 
dose.  
■
Dosing diaries will be collected from subjects for the single anytime PK and trough 
PK collection. If a dosing diary is not returned the site may ask the subject for the 
time of the last dose and if it was taken with or without food.

Provide subject dosing diary to all subjects in Treatment Group 1 (Weeks 4, 8, 12, and 24)

Document study drug dispensation and accountability for all study drugs dispensed


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Amendment 1 
• 
Subjects who meet the criteria for virologic rebmmd will be managed according to the 
Management ofVirologic Rebmmd Section 6.14.1. 
• 
HIV-1 genotype/phenotype testing for subjects with virologic failme (Week 48) 
6.5. 
Treatment Assessments (Post Week 48) 
6.5.1. 
Post Week 48 Assessments 
At the Week 48 Visit, subjects who completed 48 weeks of study dmg treatment and are in a 
country where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for an additional48 weeks and attend study visits eve1y 12 weeks or 1mtil 
the product becomes accessible to subject through an access program, or 1mtil Gilead Sciences 
elects to discontinue the study in that cmmtry, whichever occms first. 
Subjects who continue pruticipation in the study and receive GS-9883/F/TAF will renm1 for 
study visits eve1y 12 weeks. Study visits are to be completed within± 6 days of the 
protocol-specified visit date unless othe1wise specified. 
Subjects pali.icipating in the study post Week 48 will be required to return for study visits 
according to the schedule presented in Appendix 2 Study Procedmes Table and described in the 
text below: 
• 
Review of AEs and changes in concomitant medications 
• 
Symptom-directed physical examination as needed 
• 
Vital signs measurement (blood pressme, pulse, respiration rate, and temperature), 
including weight 
• 
Urine collection for the following laboratmy procedmes: 
-
Urinalysis 
-
Urine albumin, mine creatinine, mine protein, retinol binding protein and 
beta-2 microglobulin. (Every 24 weeks) 
-
Urine pregnancy test (females of childbearing potential only); positive mine pregnancy 
tests will be confnmed with a semm test. If the test is positive, subjects may opt to 
remain on study dmg and an additional infmmed consent would be required. 
• 
PD 
-
Urine storage sample for possible additional clinical testing 
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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN) TSH will 
be analyzed every 24 weeks.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 Weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
■
For subjects who meet the definition of HBV infection, the following will be 
conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) 
and HBeAg (if negative, reflex HBeAb) (Every 24 Weeks)
HCV RNA for subjects with positive HCVAb at screening. (Every 24 Weeks)
Plasma storage samples for safety, virology, or PK testing

Subjects who meet the criteria for virologic rebound will be managed according to the 
Management of Virologic Rebound Section 6.14.1

Document study drug dispensation and accountability for all study drugs dispensed.
6.6.
Post-Treatment Assessments
6.6.1.
Early Study Drugs Discontinuation (ESDD) Assessments
If the subject discontinues study drug prior to the Week 48 Visit, the subject will be asked to 
return to the clinic within 72 hours of stopping study drug for the Early Study Drugs 
Discontinuation Visit. The subject will be asked to continue attending the scheduled study visits 
through the Week 48 Visit.


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At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will 
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drugs Discontinuation Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN), and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage samples for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability


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6.6.2.
30 Day Follow Up
Subjects who complete the study through the Week 48 visit and do not continue participation in
the study will be required to return to the clinic 30 days after the completion of study drug for the 
30-Day Follow-Up Visit. 
Subjects who permanently discontinue study drug and refuse to continue in the study through the 
Week 48 visit will be asked to return to the clinic 30 days after the completion of the 
Early Study Drugs Discontinuation Visit for the 30-Day Follow-Up Visit.
Those subjects who permanently discontinue study drug and continue in the study through 
at least one subsequent visit after the Early Study Drug Discontinuation Visit will not be 
required to complete the 30-Day Follow-Up Visit.
Subjects who participate post Week 48 will complete a 30-Day Follow-Up Visit 30 days after 
last dose of study drug.   
For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight 

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count


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Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly 
(or as often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained. 
6.7.
Criteria for Discontinuation of Study Treatment
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator.

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Lack of efficacy 

Subject request to discontinue for any reason

Subject noncompliance

Breastfeeding

Development of active tuberculosis infection

Discontinuation of the study at the request of Gilead, a regulatory agency or an 
institutional review board or independent ethics committee (IRB/IEC)
6.8.
Other Evaluations
6.8.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include but are not limited to urine albumin, urine creatinine, urine protein, retinol binding 
protein and beta-2-microglobulin at the Day 1 Visit, Weeks 24, 48, and every 24 weeks post 
Week 48. At the conclusion of this study, these samples may be retained in storage by 
Gilead Sciences for a period up to 15 years.


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6.9. 
p 
6.10. 
Blood and Urine Storage 
Final 
Amendment 1 
A portion of the blood and urine samples drawn at all visits (except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its research partners to help answer questions about the 
study dmg, about the disease and its associated conditions and/or to provide additional safety 
data. No human genetic testing will be perf01med 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), eve1y attempt should 
be made to keep the subject in the study and continue to perf01m 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/te1minated their patticipation in the study, long-te1m care for the 
subject will remain the responsibility of their primruy treating physician. 
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6.14.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation or Week 48.  
6.14.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any post Day 1 visit, a rebound in HIV-1 RNA ≥50 copies/mL, which is subsequently
confirmed at the following scheduled or unscheduled visit; 
OR

Any subject with HIV RNA ≥ 50 copies/mL at study drug discontinuation
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing. Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-Day 1 resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.
If no resistance is detected from the genotype or phenotype, the subject may remain on study
drugs and a repeat HIV-1 RNA should be repeated (2 to 3 weeks after date of test with 
HIV-1 RNA ≥ 50 copies/mL). Investigators should carefully evaluate the benefits and risks of 
remaining on study drug for each individual subject and document this assessment in the on-site 
medical record. 
Subjects who are noncompliant on an ongoing basis will be considered for discontinuation per 
the Investigator’s discretion or local treatment guidelines. Investigators who opt to discontinue 
study drugs for an individual subject must discuss with the Medical Monitor prior to study drug 
discontinuation. 
For subjects who are off study drug but remain on study, it will be the Investigator’s discretion to 
manage virologic rebound.
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
rebound.


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


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


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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to IMP interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 7.5.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to IMP
therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg, venipuncture)
7.2.2.
Assessment of Severity
AE severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events.
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): 

All SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30 days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of study IMP, regardless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period; 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of Study IMP, he/she should promptly document and 
report the event to Gilead DSPH.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
form and submit within 24 hours to:
Gilead DSPH 
contact information:
Fax:
E-mail:
+1 (650) 522-5477
Safety_FC@gilead.com

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.

Additional information may be requested to ensure the timely completion of accurate safety 
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
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax only when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA 
Code of Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant 
updates, and other country-specific legislation or regulations, Gilead may be required to expedite 
to worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU 
Clinical Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide 
regulatory agencies and the relevant IEC in concerned Member States of applicable SUSARs as 
outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.5.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 4). 

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results and before investigational medicinal 
product discontinuation, unless such a delay is not consistent with good medical practice

Any questions regarding toxicity management should be directed to the 
Gilead Medical Monitor.
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.


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7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, investigational 
medicinal product may be continued if the event is considered to be unrelated t 
investigational medicinal product.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to investigational medicinal product, 
investigational medicinal product should be withheld until the toxicity returns to 
≤Grade 2.When restarting investigational medicinal product following resolution of the 
adverse event, the investigational medicinal product should be restarted at full dose upon 
discussion with the Gilead Sciences Medical Monitor.

If a laboratory abnormality recurs to ≥Grade 3 following rechallenge with investigational 
medicinal product and is considered related to investigational medicinal product, then 
investigational medicinal product should be permanently discontinued and the subject 
managed according to local practice. Recurrence of laboratory abnormalities considered 
unrelated to investigational medicinal product may not require permanent discontinuation but 
requires discussion with the Gilead Sciences Medical Monitor.
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event

For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to investigational medicinal product, 
investigational medicinal product 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 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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7.5.5.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management
An On-Treatment ALT Flare is defined as:

Confirmed (within 3 days of receipt of initial laboratory results) serum ALT > 2 × Day 1 value 
and >10 × ULN, with or without associated symptoms
7.5.5.1.
Management of ALT Flare in Subjects Receiving Study Medication
If laboratory results indicate elevation of ALT > 2 × Day 1 value and > 10 × ULN, the following 
is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally within 3 days after 
initial laboratory results were drawn). During the visit, a clinical assessment of the subject 
will be performed. The assessment should include a physical examination and evaluation of 
the subject’s mental status.

If the ALT elevation is confirmed, request the central clinical laboratory to conduct reflex 
testing for plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM, and 
HCV serology
Check the following laboratory parameters: serum ALT and AST, total bilirubin, INR, and serum 
albumin. Based on the results of the confirmatory tests, the following treatment modifications are 
recommended:
Elevated Liver Enzymes, Normal or Stable Relative to Day 1 Liver Function Tests
If ALT levels are elevated (ie, 2 × Day 1 and 10 × ULN) with normal or stable total bilirubin 
and INR relative to Day 1, the subject may remain on study medication and should be monitored 
weekly as long as ALT levels return to normal or Day 1 level. During monitoring, if the ALT 
values remain persistently elevated, the Investigator should discuss with the Gilead Medical 
Monitor whether the study drug should be discontinued.
Elevated Liver Enzymes, Elevated Liver Function Tests
If ALT values are elevated (ie, > 2 × Day 1 and > 10 × ULN), and total bilirubin is confirmed to 
be 2 x Day 1 value, and INR is 0.5 above Day 1, provided both are > ULN, the investigator 
should consider discontinuing study medication (upon discussion with the 
Gilead Medical Monitor, unless the safety of the patient is of immediate concern). The subject 
should be monitored weekly as long as ALT, total bilirubin, and INR values remain elevated or 
above Day 1 values.
During monitoring, if the ALT values and the liver function tests remain persistently elevated, 
the Investigator should discuss with the Gilead Medical Monitor whether the study drug should 
be discontinued.


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7.5.5.2.
Management of Exacerbation of Hepatitis B in Subjects Who Have Discontinued 
Study Medication
If laboratory results indicate (1) an ALT elevation > 2 × Day 1 and > 10 × ULN alone OR 
associated with (2) abnormal laboratory parameters suggestive of worsening hepatic function 
(total bilirubin 2 × Day 1, INR 0.5 above Day 1, provided both are > ULN) and the subject is on 
no post-study therapy for HBV, the following is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally no later than 3 days 
after the initial laboratory values were drawn). During the visit, perform a clinical assessment 
of the subject.

Check the following laboratory parameters: serum ALT and AST, bilirubin, INR, and 
albumin.

If the ALT elevation is confirmed, request the clinical laboratory to conduct reflex testing for 
plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM and HCV. If 
serum HBV DNA is increasing, the investigator should consider immediate initiation of 
approved therapy.

The subject should be followed until laboratory parameters (ALT, total bilirubin, INR) return 
to normal or Day 1 up to a maximum of 6 months after the initial occurrence of the event.
7.5.6.
Management of Hyperbilirubinemia
Most patients taking atazanavir sulfate experience asymptomatic elevations in indirect 
(unconjugated) bilirubin related to inhibition of UDP-glucuronyl transferase (UGT). Hepatic 
transaminase elevations that occur with hyperbilirubinemia should be evaluated for alternative 
etiologies. Dose modification of atazanavir sulfate is not permitted. Subjects who experience 
unacceptable jaundice/scleral icterus can be discontinued from study at the discretion of the 
Investigator.

Subjects with bilirubin levels of 5-10 × ULN, if isolated and not accompanied by 
unacceptable clinical jaundice (scleral icterus or cutaneous jaundice) may continue on study, 
if agreed upon by the subject and the Investigator. All subjects with serum bilirubin levels 
5-10 × ULN must have bilirubin, AST and ALT repeated at least once within 7 days of the 
Investigator being notified of the elevated bilirubin level. Thereafter, serum bilirubin levels 
5-10 × ULN without clinically significant elevation in AST or ALT should be followed 
according to the clinical judgment of the Investigator.

Subjects whose hyperbilirubinemia (5-10 × ULN) is accompanied by ≥ Grade 2 ALT or AST 
elevation or who experience a one Grade worsening in ALT or AST do not qualify as having 
isolated hyperbilirubinemia and will be discontinued.


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
Confirmed hyperbilirubinemia > 10 × ULN will require discontinuation.

Elevation of conjugated (direct) bilirubin > 2 mg/dL in association with Grade 2 ALT or 
AST elevation will require discontinuation.
7.5.7.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose interruption. 
Should the Investigator decide to initiate Hepatitis C treatment the Investigator must contact the 
Gilead Medical Monitor to confirm that no drug-drug interactions are expected. Subjects should 
return to the clinic for scheduled or unscheduled follow up visit(s) according to local medical 
practice for laboratory evaluations. If Hepatitis C treatment is initiated, Investigators should use 
the Gilead provided retest laboratory kits to manage the active Hepatitis C.
7.5.8.
Management of Potential Nephrotoxicity
Estimated glomerular filtration rate according to the Cockcroft-Gault formula (eGFRC-G), will be 
followed post-baseline during the study. All subjects with estimated GFR < 50 mL/min 
(0.83 mL/sec) must have serum creatinine and subject’s weight measured again within 
3 calendar days of receipt of results.
If a subject has confirmed eGFRC-G < 50 mL/min, the Medical Monitor should be notified and 
discontinuation of the study drug should be discussed. For subjects with confirmed eGFRC-G
< 50 mL/min who are not discontinued based on toxicity management procedures above and are 
considered to have stable renal function per Principal Investigator and Medical Monitor, it is not 
mandatory to repeat eGFR assessments within 3 days.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, pregnancy reports regardless of an 
associated AE, occupational exposure with an adverse event and adverse event in an infant 
following exposure from breastfeeding.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.


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


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7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.6 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is to evaluate the efficacy of switching to a GS-9883/F/TAF
FDC versus staying on baseline regimen (SBR) in virologically suppressed HIV-1 infected 
women as determined by the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48.
The secondary objective of this study is to evaluate the safety, and tolerability of the 
two treatment groups through Week 48.
8.1.2.
Primary Endpoint
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as determined by the US FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
Secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined by 
the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.
8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study (2) have received at least 1 dose of 
study drug. Subjects will be grouped according to the treatment to which they were randomized.


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8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug (3) have not committed any major protocol violation, including the violation 
of key entry criteria. Subjects will be grouped according to the treatment they actually received.
Subjects meeting any of the following criteria will be excluded from the Week 48 
PP analysis set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing is due to discontinuation of study drug for lack of efficacy. 

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 5 including drugs not to be used with 
GS-9883, FTC, TAF, EVG, COBI, ATV, and RTV.

Non adherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile.
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose of 
GS-9883/F/TAF, and (3) have at least 1 non missing PK concentration data for the analyte under 
evaluation reported by the PK lab. 
8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose. Laboratory data that are continuous in nature 
but are less than the lower limit of quantitation or above the upper limit of quantitation will be 
imputed to the value of the lower or upper limit plus or minus one significant digit, respectively 
(eg, if the result of a continuous laboratory test is < 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (ie, no toxicity grade) for the laboratory abnormality summary.
All available data for subjects that do not complete the study will be included in data listings.


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8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include race, ethnicity, and age. 
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline 
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects with 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 include subjects 
a) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window, or 
b) Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and 
1) Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or 
2) Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than lack of efficacy and have the last available on-treatment 
HIV-1 RNA ≥ 50 copies/mL  


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
No Virologic Data in the Week 48 Analysis Window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following: 
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL or,
b) Missing data during the window but on study drug 
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 in the GS-9883/F/TAF group is at least 4% higher than that in the SBR group; the 
alternative hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 copies/mL in the 
GS-9883/F/TAF group is less than 4% higher than that in the SBR group.
Non-inferiority will be assessed using the conventional confidence interval (CI) approach. The 
point estimate of treatment difference (GS-9883/F/TAF – SBR) and the associated 2-sided 
95% CI will be constructed based on the exact method.  
It will be concluded that GS-9883/F/TAF is non-inferior to E/C/F/TAF if the upper bound of the 
2-sided 95% CI of the difference between treatment groups (GS-9883/F/TAF – SBR) in the 
percentage of subjects with HIV-1 RNA ≥50 copies/mL is less than 4% (ie, a margin of 4% is 
applied to non-inferiority assessment).
If non-inferiority of GS-9883/F/TAF to SBRis established, the upper bound of the 95% CI will 
be compared to 0; if the upper bound of the 95% CI is less than 0, superiority of GS-9883/F/TAF
over SBR will be established.
8.5.2.
Secondary Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined by the
US FDA-defined snapshot algorithm will also be evaluated. The 95% CIs will be constructed in 
the same manner as for the primary efficacy endpoint. However, non-inferiority will be assessed 
using a margin of 10%. It will be concluded that GS-9883/F/TAF is non- inferior to SBRif the 
lower bound of the 2-sided 95% CI of the difference between treatment groups (GS-9883/F/TAF -
SBR) in the response rate is greater than −10%.
The changes from baseline in CD4+ cell count at Week 48 will be summarized by treatment 
using descriptive statistics. The differences in changes from baseline in CD4+ cell count between 
the 2 treatment groups and the associated 95% CIs will be constructed using ANOVA models, 
including treatment (GS-9883/F/TAF vs. SBR) as a fixed effect in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.


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8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise, will be summarized 
for subjects in the safety analysis set according to the study drug received.
Data for the pretreatment period and the period post the date of last dose of study drug plus 
30 days will be included in data listings for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug
administration page in eCRF. Exposure data will be summarized by treatment.
Duration of exposure to study drug will be expressed as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration and summarized by treatment.
Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study drug start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illnesses definition of 
an AIDS-Defining Diagnosis will be listed.  
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.


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8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum post baseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the PK analyses, the pharmacokinetics of GS-9883 may be evaluated using descriptive 
statistics or population approaches.
TAF and FTC concentrations may be analyzed as applicable.  
8.8.
Sample Size
A total of approximately 400 HIV-1 infected subjects, randomized in a 1:1 ratio to 
2 treatment groups (200 subjects per treatment group), achieves at least 80% power to detect a 
non-inferiority margin of 4% difference in percentage of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 between the 2 treatment groups. For the sample size and power 
computation, it is assumed that both treatment groups have 2% of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 (based on the historical Gilead Genvoya® and STB studies), that the
non-inferiority margin is 4%, and that the significance level of the test is at a one-sided 
0.025 level.
8.9.
Independent Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after all 
subjects enrolled complete Week 24 of the study or prematurely discontinue the study drug. 
However, Gilead will defer to the IDMC for any decision to convene earlier or more frequently. 
The IDMC will examine the safety results of the trial and also focus on logistical issues such as 
accrual, retention, quality of clinical and laboratory data, and implications of results of external 
studies.


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No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
An analysis for the Week 24 IDMC meeting will be conducted after the last subjects enrolled 
completes Week 24 of the study. For each IDMC analysis performed prior to analysis for the 
primary efficacy endpoint, an alpha penalty of 0.00001 will be applied for the primary analysis 
of the primary efficacy endpoint.
8.10.
Analysis Schedule
The week 48 analysis will be conducted after all subjects either complete their Week 48 visit or 
prematurely discontinue from the study drug. 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. 


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


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


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responding to the queries in a timely manner, within the system, either by confirming the data as 
correct or updating the original entry, and providing the reason for the update 
(e.g. data entry error). Original entries as well as any changes to data fields will be stored in the 
audit trail of the system. Prior to any interim time points or database lock (as instructed by 
Gilead), the investigator will use his/her log in credentials to confirm that the forms have been 
reviewed, and that the entries accurately reflect the information in the source documents. At the 
conclusion of the trial, Gilead will provide the site with a read-only archive copy of the data 
entered by that site. This archive must be stored in accordance with the records retention 
requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files. 
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP 
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs/IECs or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.


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


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


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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.
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of 
mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. 
Lancet 1998;352 (9142):1725-30.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised 
surveillance case definitions for HIV infection among adults, adolescents, and 
children aged <18 months and for HIV infection and AIDS among children aged 
18 months to <13 years--United States, 2008. MMWR Recomm Rep 2008;57 
(RR-10):1-12.
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84.
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported adherence supports 
patient preference for the single tablet regimen (STR) in the current cART era. 
Patient preference and adherence 2012;6:427-33.
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
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/Ffr AF 
Protocol GS-US-380-1961 
Final 
Gilead Sciences, Inc. 
Amendment 1 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, lNC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Switching to a 
Fixed Dose Combination (FDC) of OS-9883/Emtricitabine!fenofovir Alafenamide 
(GS-9883/FfrAF) from Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/CIF!T AF), Elvitegravir/Cobicistat!Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) 
or Atazanavir + Ritonavir + Emtricitabine!fenofovir Disoproxil Fumarate 
(ATV+RTV+FTC/TDF) in Virologically Suppressed HIV-1 Infected Women 
GS-US-380-1961, Amendment I, 30 June 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
""P""'P""'Do----------. 
Huyen Cao, MD (Printed) 
Author 
Date 
~ 
~~----------------~ 
INVESTIGATOR STATEMENT 
T 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 wiH conduct this study as out! ined herein 
and wiU 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. 1 will discuss this material with 1hem to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 89 
30 June 2016 


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Appendix 2.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48d,v
30 Day 
Follow-Upe
ESDDf
4
8
12
24
36
48
Every 12 Weeks
Informed Consent
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam 
X
X
X
X
X
Symptom-Directed Physical Exam
X
X
X
X
X
X
12-Lead ECG 
X
X
X
X
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Chemistryh
X
X
X
Xw
Urine Pregnancy Testi
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testi
X
Chemistry Profilej
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentsk
X
X
X
X
Xw
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilel
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAm
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Planeln
X


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Study Procedure 
Plasma HBV DNA
0 
HCVAbP 
HCVRNAP 
HIV -1 Genotype/Phenotype q 
Single PK Draw 
Trough PK Dravl 
PK Sample (post-dose)• 
Observed In-Clinic Dose• 
Provide Dosing Diaryu 
Collect Dosing Diaryx 
Plasma Sample Storage' 
t 
Urine Sample Storage 
Whole Blood Storage Sample
1 
~PD 
n 
I 
I 
!rPD 
I 
Randomization 
Study Drug Dispensation 
Study Drug Accountability 
Sc.reening• 
X 
X 
I 
a 
Evaluations to be completed within 30 days prior to Day 1. 
Day l b 
4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b 
Subjects should initiate dosing of study dmg on the same day as the Day 1 visit. 
End ofWeE'kc 
8 
12 
24 
36 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Post Week 48d,v 
48 
Every 12 Weeks 
X 
xw 
X 
xw 
~ 
X 
X 
X 
X 
xv 
xv 
X 
X 
30Day 
Final 
Amendment 1 
Follow-u p• 
ESDDr 
X 
~ 
X 
X 
X 
c 
All study visits should be± 2 days of the protocol-spe.cified visit date based on the Day 1 visit through Week 12 and completed within± 6 days at Week 24 and Week 36, 
tmless otherwise specified. The visit window at Week 48 will be± 6 weeks of the protocol-specified visit da.te. 
d 
At the Week 48 Visit, subjects in a cotmtry where GS-9883/F/TAF FDC is not available wiii be given the option to receive GS-9883/F/TAF FDC for an additional 48 weeks, 
or until the product becomes accessible to subjects tlu·ough an access program, or tmtil Gilead Sciences elects to discontinue the study in that cotmtry, whichever occms first. 
Study visits are to be completed every 12 weeks, witlun ± 6 days of tl1e protocol-specified visit date tmless otherwise specified. 
CONFIDENTIAL 
Page 91 
30 Jtme 2016 


GS-9883/F/T AF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Final 
Amendment 1 
e 
f 
g 
h 
k 
lll 
n 
0 
p 
q 
r 
l1 
v 
w 
X 
y 
Must be completed 30 days after discontinuing study drug. For d1e pmpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. Required for subjects 
who permanently discontinue study drug prior to Week 48 and do not continue in ilie study tlu·ough at least one subsequent visit after ilie ESDD visit. Subjects who participate 
post Week 48 will be required to rettu11 to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit. 
Early Study Drug Discontinuation visit to occur ,,.-jthin 72 hom'S of last dose of study drug. Subjects will be asked to continue attending d1e scheduled study visits du·ough the 
Week 48 Visit even if the subject discontinues study drug. 
Vital signs measurements including blood pressm·e, pulse, respirat01y rate, and temperature 
Urine Chemistty includes urine albmnin, m-ine creatinine, urine protein, retinol binding protein, and beta-2 microglobulin 
Women of childbeatmg potential only. Positive m-ine pregnancy tests will be confumed with a senun test. 
Chemistty profile: alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and indirect bilimbin, total protein, albmnin, bicarbonate, BUN, calcimn, clu01-ide, creatinine, 
glucose, phosphorus, magnesitml, potassimn, soditml, ut-ic acid, and amylase (reflex lipase testing is perfonned in subjects with total amylase > 1.5 x ULN). At Day 1, 
Weeks 24, and 48 and evety 24 weeks during tl1e post Week 48 pet-iod, analyses of gluc.ose will be done as part of ilie fasting metabolic assessments and not as part of ilie 
chemistty profile. TSH will be collected at Screening, Day 1, Weeks 24, and 48, as well as evety 24 weeks post Week 48, and ESDD if applicable. 
Fasting glucose and lipid panel (total cholesterol, HDL, direct LDL, tt-iglycet-ides). If d1e subject has not fasted pt-ior to the visit, ilie visit may proceed, but ilie subject must 
retm11 within 72 hom'S in a fasted state to draw blood for the metabolic assessments. 
CBC with differential and platelet coutlt. 
Ifilie HIV-1 RNA value is :;::: 50 copies/mL at Week 48, a retest HIV-1 RNA value must be collected wiiliin two to tlu·ee weeks of ilie initial test. 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus smface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb). 
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex HBeAb ), and quantitative HBsAg. If positive HBcAb with negative HBsAg and negative 
HBsAb, reflex testing for plasma HBV DNA (if positive, reflex HBeAg). IfHBeAg is performed and fotmd to be negative, reflex HBeAb. 
For subjects who meet the defmition ofHBV infection, the following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) and HBeAg 
(if negative, reflex HBeAb) at Days 1, I2, 24 and ilien evety24 weeks. 
Subjects who are HCV Ab positive will have a HCV RNA test perfonned at screening and every 24 weeks. 
HIV-I genotype/phenotype testing for subjects with HIV-I RNA :;::: 200 copies/mL and virologic rebom1d, at early study dmg discontinuation or Week 48. Following 
tmconfumed virologic rebotmd, subjects will be asked to rettun to the clinic (2-3 weeks later) prior to the next sche.duled visit or at d1e next scheduled study visit, for a 
HIV -I RNA and HIV -I genotype/phenotype (reverse tt·anscriptase, protease and i.ntegrase) blood draw. Based on ilie results of this testing, subjects should be managed 
according to the Virologic Rebotmd Schema (Section 6.I4.I). 
All subjects on GS-9883/F/TAF (Treattnent Group I only) will have a single anytime PK blood san1ple collected at Weeks 8, 24 and 36. 
Subjects on GS-9883/F/TAF (Trea.ttnent Group I only) will have a Trough PK blood sample collected between 20-28 hours following ilieir last dose at Weeks 4 and I2. 
Subjects must be instmcted to not take their study dmgs on the moming of d1eir visit for the tt·ough sample collection. If the subject has taken ilieir dose of study drugs prior 
to the visit, ilie visit may proceed, but the subject must return wiiliin 72 hours for the single trough PK blood sample c.ollection. In the event a subject routinely takes their 
study dmg in ilie evening, a single anytin1e sample may be drawn at Weeks 4 and I2 as the subject will not be instt1.1cted to change their dosing time to acco=odate this 
trough PK draw. A post-dose PK blood sample will be collected betwe·en I and 4 hom·s post dose following an observed, in-clinic dose. 
Plasma storage san1ples banked for possible fi.Jttu·e protocol-related testing (safety, virology, phannacokinetic analysis). Urine storage samples banked for possible fi.1ttu·e 
E
tocol-related safety testing including urine chemistty. Whole blood sampl; for r tential virologic resistance testing and/or HIV DNA genotyping . ._P_P_n ______ ... 
A dostllg""diaty wtlf be CftspensectfOfaii Treattnent Group I subjects to comp ete pnor to each of the PK sample visits. 
Open-label GS-9883/F/TAF FDC will be dispensed to subjects patticipating in the study post Week 48 starting at the Week 48 Visit. 
Evety 24 weeks only. 
Dosing diat-ies will be collected from subjects for the single anytin1e PK and tt·ough PK collection (Treattnent Group I only). If a dosing diary is not returned the site may ask 
the subject for the time of tl1e last dose and if it was taken wiili or wiiliout food. 
PPD 
CONFIDENTIAL 
Page 92 
30 Jtme 2016 


GS-9883/F/TAF 
Protocol GS-US-380-1961 
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------~~ 
~~ __________ a_m_d_e_4--------~ 
! 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
If confirmed and possibly and/or probably related to investigational 
medicinal products: 
1. 
Withhold investigational medicinal products until ::; Grade 2 
2. 
Restart all investigational medicinal products at full dose 
l 
If Grade 3 or 4 recurrence that is con tinned and possibly or probably 
related to investigational medicinal products, discontinue a11 
investigational medicinal products dosing permanently 
Repeat lab to 
confirm toxicity 
grade 
1 
1 
lfc 
elated to 
inve 
dicinal products, 
onfrrmed and unr 
stigationalme 
ng may contin 
he investigator 
dosi 
ue at the discretion 
oft 
If confirmed and 
possibly or probably 
I-+ related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
Page 93 
30 Jw1e 2016 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 94
30 June 2016
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count  
(ANC)
Adult and Pediatric, 
≥ 7 Months#
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 95
30 June 2016
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects. Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.  


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 96
30 June 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 97
30 June 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL                       
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL              
1.74 to <1.94 mmolL
6.1 to  <7.0 mg/dL                   
1.51 to < 1.74 mmolL
< 6.1 mg/dL                           
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 98
30 June 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (corrected for 
albumin if appropriate*)
Adult and Pediatric 7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to  <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63  to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to <LLN mg/dL
1.12 to <LLN mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 99
30 June 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyperbilirubinemia 
Adult and Pediatric > 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 100
30 June 2016
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-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 101
30 June 2016
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 102
30 June 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-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 103
30 June 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-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 104
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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV block 
OR Ventricular pause 3.0 
sec
Complete AV block 
Pediatric 16 Years
1st degree AV block
(PR > normal for age and
rate)
Type I 2nd degree AV block 
Type II 2nd degree AV block 
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc interval 
0.50 sec OR Increase in 
interval 0.06 sec above 
baseline
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Pediatric 16 Years
Asymptomatic, QTc interval 
0.450 to 0.464 sec 
Asymptomatic, QTc interval 
0.465 to 0.479 sec 
Asymptomatic, QTc interval 
0.480 sec 
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated 
(eg, anticoagulation, lysis 
filter, invasive procedure) 
Deep vein thrombosis AND 
Intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Embolic event (eg, 
pulmonary embolism, life-
threatening thrombus) 
Vasovagal Episode (associated 
with a procedure of any kind)
Present without loss of 
consciousness 
Present with transient loss of 
consciousness
NA 
NA
Ventricular Dysfunction 
(congestive heart failure, CHF)
NA
Asymptomatic diagnostic 
finding AND intervention 
indicated
New onset with symptoms 
OR Worsening symptomatic 
CHF
Life-threatening CHF


GS-9883/F/TAF
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Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 105
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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-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 106
30 June 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-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 107
30 June 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 108
30 June 2016
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Dysphagia-Odynophagia 
Symptomatic but able to eat 
usual diet
Symptoms causing altered 
dietary intake without 
medical intervention 
indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention 
indicated
Life-threatening reduction in 
oral intake
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, Dysphagia-
Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal 
bleeding OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 24–
48 hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening 
consequences (eg, 
hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening 
consequences (eg, sepsis, 
circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ Stomatitis 
for Clinical Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities OR 
Medical intervention 
indicated 
Symptoms causing inability 
to perform usual social/ 
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences (eg, 
perforation)
Vomiting
Transient or intermittent 
vomiting with no or minimal 
interference with oral intake
Frequent episodes of 
vomiting with no or mild 
dehydration
Persistent vomiting resulting 
in orthostatic hypotension 
OR Aggressive rehydration 
indicated
Life-threatening 
consequences (eg, 
hypotensive shock)


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 109
30 June 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 110
30 June 2016
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
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 111
30 June 2016
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Seizure: (pre-existing) 
For Worsening of Existing 
Epilepsy the Grades Should Be 
Based on an Increase from 
Previous Level of Control to 
Any of These Levels
NA
Increased frequency of pre-
existing seizures (non-
repetitive) without change in 
seizure character OR 
infrequent breakthrough 
seizures while on stable 
meds in a previously 
controlled seizure disorder
Change in seizure character 
from baseline either in 
duration or quality (eg, 
severity or focality) 
Seizures of any kind that are 
prolonged, repetitive (eg, 
status epilepticus), or 
difficult to control (eg, 
refractory epilepsy)
Seizure 
– Pediatric 18 Years
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
< 5 minutes with < 24 hours 
post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 5–20 
minutes with 
< 24 hours post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
> 20 minutes 
Seizure, generalized onset 
with or without secondary 
generalization, requiring 
intubation and sedation
Syncope (not associated with a 
procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no or 
minimal interference with 
usual social & functional 
activities
Vertigo causing greater than 
minimal interference with 
usual social & functional 
activities 
Vertigo causing inability to 
perform usual social & 
functional activities
Disabling vertigo causing 
inability to perform basic 
self-care functions


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Amendment 1
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SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Acute Systemic Allergic 
Reaction 
Localized urticaria (wheals) 
with no medical intervention 
indicated
Localized urticaria with 
medical intervention 
indicated OR Mild 
angioedema with no medical 
intervention indicated
Generalized urticaria OR 
Angioedema with medical 
intervention indicated OR 
Symptomatic mild 
bronchospasm
Acute anaphylaxis OR Life-
threatening bronchospasm 
OR laryngeal edema
Chills
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities 
Symptoms causing inability 
to perform usual social & 
functional activities
NA
Fatigue
Malaise
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities
Symptoms causing inability 
to perform usual social & 
functional activities
Incapacitating 
fatigue/malaise symptoms 
causing inability to perform 
basic self-care functions
Fever (nonaxillary)
37.7C to 38.6C
99.8F to 101.5F
38.7C to 39.3C
101.6F to 102.8F
39.4C to 40.5C
102.9F to 104.9F
40.5C 
104.9F
Pain- Indicate Body Site
See also Injection Site Pain, 
Headache, Arthralgia, and 
Myalgia
Pain causing no or minimal 
interference with usual social 
& functional activities
Pain causing greater than 
minimal interference with 
usual social & functional 
activities
Pain causing inability to 
perform usual social & 
functional activities
Disabling pain causing 
inability to perform basic 
self-care functions OR 
Hospitalization (other than 
ER visit) indicated
Unintentional Weight Loss
NA
5% to 9% loss in body 
weight from baseline
10% to 19% loss in body 
weight from baseline
20% loss in body weight 
from baseline OR  
Aggressive intervention 
indicated [eg, tube feeding or 
total parenteral nutrition]


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


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


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


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


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


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Amendment 1
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Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Females are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, females of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
2) Contraception Requirements for Women
a. Study Drug Effects on Pregnancy and Hormonal Contraception
The data on GS-9883/F/TAF in pregnant women is limited or not available. There is no 
suspicion of human teratogenicity based on class effects or genotoxic potential. Relevant 
non-clinical reproductive studies for human pregnancy do not indicate a strong suspicion of 
human teratogenicity/fetotoxicity. Data from clinical pharmacokinetic interaction studies of 
GS-9883 and F/TAF have demonstrated that there is no reduction in the clinical efficacy of 
hormonal contraception or that the effect on hormonal contraception is insignificant. Please refer 
to the latest version of the GS-9883/F/TAF investigator’s brochure and the latest versions of the 
E/C/F/TAF, E/C/F/TDF, ATV, RTV and FTC/TDF package inserts or investigator’s brochures
for additional information.  
b. Contraception Requirements for Women of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Day 1 visit prior to randomization. At a minimum a pregnancy 
test will be performed at the end of relevant systemic exposure. In the event of a delayed 
menstrual period (over one month between menstruations), a pregnancy test must be performed 
to rule out pregnancy. This is true even for women of childbearing potential with infrequent or 
irregular periods. Female subjects must agree to one of the following from Screening until 
30 days following the end of relevant systemic exposure.


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
Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle. 
Or

Consistent and correct use of 1 of the following methods of birth control listed below. 
Intrauterine device (IUD) with a failure rate of < 1% per year
Intrauterine hormone-releasing system (IUS) with a failure rate of < 1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Or

Consistent and correct use of one hormonal method and one barrier method
Barrier methods

Diaphragm with spermicide

Cervical cap with spermicide

Male condom (with or without spermicide)
Hormonal methods

Oral contraceptives (either combined or progesterone only)

Injectable progesterone

Implants of levonorgestrel

Transdermal contraceptive patch

Contraceptive vaginal ring
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 30 days after the end of relevant systemic exposure.  


GS-9883/F/T AF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
3) Unacceptable Birth Control Methods 
Final 
Amendment 1 
Biith control methods that aTe unacceptable include periodic abstinence (e.g., calendar, ovulation, 
symptothetmal, post-ovulation methods), withdrawal (coitus intem1ptus), spennicides only, and 
lactational amenonhea method (LAM). Female condom and male condom should not be used 
together. 
4) Procedures to be Followed in the Event of Pregnancy 
Subjects will be instmcted to notify the investigator if they become pregnant at any time dming 
the study, or if they become pregnant within 30 days oflast study dmg dose. Subjects who 
become pregnant or who suspect that they are pregnant dming the study must report the 
inf01mation to the investigator immediately. The iilVestigator will counsel the subject regarding 
pregnancy management options. Counseling will be provided regarding altemative anti-HIV 
treatment. Information on the risks and benefits of antii·etrovii·al therapies will be discussed, 
including the risk of ongoing fetal exposme to the study dmg versus the new altemative therapy 
and the risk of discontinuing matemal therapy. 
If a subject becomes pregnant dming the study, sh~ ma)'_2£t to remain on study dmo and an 
additional inf01med consent would be re uii·ed. PPD 
If the subject elects to discontinue study dmgs but remain in the study, a new ARV regimen will 
be constmcted at the fu.vestigator's discretion. 
The fu.vestigator should counsel the subject on the need to inf01m the study site of the outcome 
of the pregnancy. fuf01mation collected will include gestational dating, ultrasound rep01t, records 
of matemal, fetal complications and pregnancy outcome. 
fu.stmctions for reporting pregnancy and pregnancy outcome are outlined in Section 7.6. 
CONFIDENTIAL 
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Prot_000.pdf: 
(fJ GILEAiJ 
CLINICAL STUDY PROTOCOL 
Study Title: 
A Phase 3, Randomized, Open Label Study to Evaluate the 
Safety and Efficacy of Switching to a Fixed Dose Combination 
(FDC) of GS-9883/Emtricitabine/Tenofovir Alafenamide 
(GS-9883/F IT AF) from Elvitegravir/Cobicistat/Emtricitabine/ 
Tenofovir Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/ 
Emtricitabine/T enofovir Disoproxil Fmnarate (E/C/F /TDF) or 
Atazanavir + Ritonavir + Emti·icitabine/Tenofovir Disoproxil 
Fmnarate (ATV+RTV+FTC/TDF) in Virologically Suppressed 
HIV -1 Infected Women 
Sponsor: 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
IND Number: 
125589 
EudraCT Number: 
Not Applicable 
Clinical Trials.gov Identifier: 
Not Available 
Indication: 
HIV -1 Infection 
Protocol ID: 
GS-US-380-1961 
Gilead Clinical Program 
Manager: 
Gilead Medical Monitor: 
Protocol Version/Date: 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Mobile: 
Original: 
PPD 
Huyen Cao, MD 
PD 
PPD 
PPD 
20 November 2015 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this docmnent, particularly m1published data, is the prope1iy or 
under conti·ol of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Board or Independent Ethics Committee. The info1mation is only to be used 
by you in connection with authorized clinical studies of the investigational dmg described in the 
protocol. You will not disclose any of the info1mation to others without written authorization 
from Gilead Sciences, Inc., except to the extent necessruy to obtain infmm ed consent from those 
persons to whom the dmg may be administered. 


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Protocol GS-US-380-1961
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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....................................................................11
1.
INTRODUCTION ..............................................................................................................................................14
1.1.
Background ............................................................................................................................................14
1.2.
GS-9883 .................................................................................................................................................15
1.2.1.
General Information .............................................................................................................15
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................15
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................17
1.3.
Information About Emtricitabine (Emtriva®, FTC) ...............................................................................26
1.4.
Information About Tenofovir Alafenamide (TAF, GS-7340)................................................................26
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide 
(FTC/TAF)...........................................................................................................................26
1.4.2.
Clinical Trials of FTC/TAF as Part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF).........................................................................................................................28
1.5.
Information About GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) .......................29
1.5.1.
GS-US-141-1233: Relative Bioavailability of GS-9883, FTC, and TAF 
Between GS-9883/F/TAF and GS-9883 + F/TAF ...............................................................30
1.6.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)...................................................................................31
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®) ..................................................31
1.8.
Ritonavir (RTV, /r, Norvir®)..................................................................................................................31
1.9.
Atazanavir (ATV, Reyataz®)..................................................................................................................31
1.10.
Rationale for This Study ........................................................................................................................31
1.11.
Risk/Benefit Assessment for the Study..................................................................................................32
1.12.
Rationale for Dose Selection..................................................................................................................33
1.13.
Compliance ............................................................................................................................................35
2.
OBJECTIVES.....................................................................................................................................................36
3.
STUDY DESIGN................................................................................................................................................37
3.1.
Endpoints ...............................................................................................................................................37
3.2.
Study Design..........................................................................................................................................37
3.3.
Study Treatments ...................................................................................................................................37
3.4.
Duration of Treatment............................................................................................................................38
3.5.
Biomarker Testing..................................................................................................................................38
3.5.1.
Biomarker Samples for Optional Future Research...............................................................38
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................43
5.1.
Randomization .......................................................................................................................................43
5.2.
Description and Handling.......................................................................................................................43


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


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


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Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................93
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............94
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................117
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................119
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........19
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................20
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................20
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following GS-9883 
Administration Under Fasting Conditions and Corresponding Protein-Adjusted IQ95
Values (GS-9883 PK Analysis Set)........................................................................................21
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................33
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)..........................................47
Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens) .........................................................................................48
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................22
Figure 3-1.
Study Schema.........................................................................................................................38
Figure 6-1.
Virologic Rebound Schema....................................................................................................62


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


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Study Design:
Randomized, open label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to an FDC of 
GS-9883/F/TAF in HIV-1 infected women who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting 
of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir 
Disoproxil Fumarate (E/C/F/TDF), or ATV+RTV+FTC/TDF for 
≥12 consecutive weeks prior to screening.    
All subjects will be HIV positive women drawn from pre-defined 
Gilead clinical studies and must be virologically suppressed. 
Women in Gilead study GS-US-236-0128 who completed the 
Week 48 open-label extension (OLE) visit or any post Week 48 
OLE visits or women in study GS-US-292-0109 who completed the 
Week 96 visit or any post Week 96 visits may be eligible to enroll. 
Subjects who provide written consent and meet all eligibility 
criteria will be randomized in a 1:1 ratio to receive open label 
medication as follows: 

Treatment Group 1: FDC of GS-9883 50 mg/
emtricitabine 200 mg/tenofovir alafenamide 25 mg 
(GS-9883/F/TAF) administered orally, once daily, without 
regard to food (n = 200) 

Treatment Group 2: Stay on baseline regimen (SBR), 
including E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF
administered orally, once daily, with food (n = 200) 
Randomization will be stratified by the prior treatment regimen 
group (ie, E/C/F/TAF, E/C/F/TDF and ATV+RTV+FTC/TDF).
Number of Subjects 
Planned:
Approximately 400 subjects total
Target Population:
HIV-1 infected women who are virologically suppressed 
(HIV-1 RNA < 50 copies/mL) on a stable regimen of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF for ≥12 weeks prior to 
screening
Duration of Treatment:
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, 
subjects in a country where GS-9883/F/TAF FDC is not available 
will be given the option to receive GS-9883/F/TAF FDC for an 
additional 48 weeks, or until the product becomes accessible to 
subjects through an access program, or until Gilead Sciences elects 
to discontinue the study in that country, whichever occurs first.


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Subjects who complete the study through the Week 48 Visit and 
do not continue participation in the study will be required to return 
to the clinic 30 days after the Week 48 Visit for a 30 Day 
Follow-Up Visit.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected women who meet the following 
criteria:

Currently on a stable antiretroviral regimen consisting of 
E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF continuously 
for ≥12 consecutive weeks preceding the screening visit

Documented plasma HIV-1 RNA levels < 50 copies/mL for 
≥12 weeks preceding the Screening visit. After reaching 
HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by re-suppression to < 50 copies/mL 
is allowed

HIV-1 RNA <50 copies/mL at screening

Estimated glomerular filtration rate (eGFR) ≥50 mL/min 
according to the Cockcroft-Gault (C-G) formula at the 
screening visit
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 
48 weeks. Following the Screening and Day 1 visits, subjects will 
return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
until the Week 48 visit. 
For all eligible subjects, blood and urine will be collected at Day 1, 
Weeks 4, 8, 12, and then every 12 weeks through the Week 48 visit. 
Laboratory analyses (including hematology, chemistry, 
and urinalysis), HIV-1 RNA, CD4+ cell count, and complete or 
symptom directed physical examinations will be performed at the 
Screening, Day 1, and all subsequent study visits. 
Adverse events and concomitant medications will be assessed at 
each visit.
Test Product, Dose, and 
Mode of Administration:
FDC of GS-9883 50 mg/emtricitabine 200 mg/
tenofovir alafenamide 25 mg (GS-9883/F/TAF) administered 
orally, once daily, without regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Current antiretroviral drug regimen consisting of E/C/F/TAF, 
E/C/F/TDF, or ATV+RTV+FTC/TDF administered orally,
once daily, with food.


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Criteria for Evaluation:
Safety:
Adverse events and clinical laboratory tests to evaluate the safety 
and tolerability of the treatment regimens.  
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects with virologic failure (HIV-1 RNA 
≥50 copies/mL at Week 48, as defined by the modified 
United States (US) Food and Drug Administration (FDA) 
snapshot algorithm).
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
Pharmacokinetics:
For all subjects on GS-9883/F/TAF (Treatment Group 1), a single 
anytime pre or post-dose PK blood sample will be collected at 
Weeks 8, 24, and 36. 
For all subjects on GS-9883/F/TAF (Treatment Group 1), a trough 
PK blood sample will be obtained 20-28 hours following the last 
dose at Weeks 4 and 12. Following an observed dose, one PK blood 
sample will be collected between 1 and 4 hours post-dose. 
The concentration of GS-9883 may be summarized using 
descriptive statistics. 
Statistical Methods:
The primary analysis will consist of a non-inferiority test of 
switching to GS-9883/F/TAF FDC versus staying on baseline 
regimen (SBR) with respect to the proportion of subjects with 
virologic failure (HIV-1 RNA ≥ 50 copies/mL) at Week 48 as 
defined by the modified US FDA snapshot algorithm. It will be 
concluded that GS-9883/F/TAF is non-inferior to SBR if the upper 
bound of the 2-sided 95% confidence interval (CI) of the difference 
between treatment groups (GS-9883/F/TAF – SBR) in the virologic 
failure rate is less than 4%; ie, a margin of 4% is applied to 
non-inferiority assessment. The 2-sided 95% CIs will be 
constructed based on the exact method.
The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the FDA snapshot algorithm will also be 
summarized. The 95% CIs will be constructed in the same manner 
as described for the primary efficacy endpoint. 


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The change from baseline in CD4+ cell count at Week 48 will be 
summarized by treatment using descriptive statistics. The 
differences and the associated 95% CIs will be constructed using 
Analysis of Variance (ANOVA) model, including treatment 
(GS-9883/F/TAF vs. SBR) as a fixed effect in the model. 
Adverse events and clinical laboratory assessments will be 
summarized using descriptive statistics.
A total of approximately 400 HIV-1 infected women, randomized 
in a 1:1 ratio to 2 treatment groups (200 subjects per treatment 
group), achieves at least 80% power to detect a non-inferiority 
margin of 4% in Week 48 virologic failure rate (HIV-1 RNA 
≥50 copies/mL) difference between the 2 treatment groups. 
For sample size and power computation, it is assumed that both 
treatment groups have a virologic failure rate of 2% (based on the 
historical Gilead E/C/F/TAF and Stribild® (STB) studies), that a 
non-inferiority margin is 4%, and that the significance level of the 
test is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
ABC/DTG/3TC
abacavir/dolutegravir/lamivudine, Triumeq®
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir, Reyataz®
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration versus 
time curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, C, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
DTG
dolutegravir, Tivicay®
EC50
50% effective inhibitory concentration
ECG
electrocardiogram
eCRF
electronic case report form(s)
EVG, E
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild®
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination


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FSH
follicle-stimulating hormone
FTC, F
emtricitabine, Emtriva®
FTC/TAF 
emtricitabine/tenofovir alafenamide 
FTC/TDF
emtricitabine/tenofovir disoproxil fumarate, Truvada®
GCP
Good Clinical Practice (Guidelines)
GGT
gamma glutamyl transferase
GSI
Gilead Sciences, Inc.
GS-9883/F/TAF
GS-9883/emtricitabine/tenofovir alafenamide
HAART
highly active antiretroviral therapy
HBV
hepatitis B virus
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDPE
high-density polyethylene
hERG
human Ether-à-go-go-Related Gene
HIV
Human Immunodeficiency Virus
HIV Sx
HIV Symptoms Distress Module
HLA
human leukocyte antigen
IB
investigator’s brochure
IC50
50% maximal inhibitory concentration
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
institutional ethics committee
IND
Investigational New Drug (Application)
INSTI
integrase strand-transfer inhibitors
IRB
institutional review board
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LDH
lactate dehydrogenase
LLN
lower limit of the normal range
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
MH
Mantel-Haenszel
min
minute
mmHg
millimeters mercury
MT4
human t cell leukemia cell line
nM
nanoMolar
NNRTI
non-nucleoside reverse transcriptase inhibitor
NOAEL
no observed adverse effect level


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NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
OCT2
organic cation transporter 2
PI
protease inhibitor
PK
pharmacokinetic
PT
preferred term 
PT
prothrombin time 
QD
once daily 
RAL
raltegravir
RNA
ribonucleic acid
RTV
ritonavir, Norvir®
SAE
serious adverse event
STB
Stribild®, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide, GS-7340
TDF
tenofovir disoproxil fumarate, Viread®
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase 
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {36201}. The infection, if left untreated or suboptimally treated, is characterized by 
deterioration in immune function, ultimately resulting in death. Therapeutic strategies for the 
treatment of HIV-1 disease have been significantly advanced by the availability of highly active 
antiretroviral therapy (HAART); the introduction of HAART was associated with a dramatic 
decrease in acquired immune deficiency syndrome (AIDS)-related morbidity and mortality 
{27881}, {5125}, {8284}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {29705}. In addition, there remains a significant medical need 
for new, effective therapies that take into consideration HIV genetic variability, the aging 
HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {34898}. 
Virologically suppressed, HIV-infected patients may switch from their current regimen because 
of safety or tolerability concerns or for regimen simplification. All patient populations may 
benefit from once-daily fixed-dose combination (FDC) regimens as these have been shown to 
provide increased adherence and improved clinical and virologic outcomes {21053}, {29702}.
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other NRTIs. Tenofovir alafenamide (TAF) is also an 
oral prodrug of TFV. TAF is more stable in plasma than TDF, provides higher intracellular 
levels of the active phosphorylated metabolite tenofovir diphosphate (TFV-DP), and
approximately 90% lower circulating levels of TFV relative to TDF at the clinical doses. 
The distinct metabolism of TAF offers the potential for an improved clinical profile compared 
with TDF.
GS-9883 is a potent inhibitor of HIV-1 integrase that is being evaluated for the treatment of 
HIV-1 infection. Antiviral testing has shown that GS-9883 is active against a broad panel of 
HIV-1 viral lab strains and clinical isolates. GS-9883 is fully active against a panel of mutant 
viruses with resistance to NRTI’s, non-nucleoside reverse-transcriptase inhibitors (NNRTIs), and 
protease inhibitors (PIs). Integrase mutant viruses that are resistant to the INSTIs raltegravir 
(RAL) and elvitegravir (EVG) remain largely sensitive to GS-9883.


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Gilead Sciences (Gilead) has coformulated GS-9883 with the NRTI emtricitabine (FTC; F) and 
the NtRTI tenofovir alafenamide (TAF) into an FDC tablet that is suitable for once-daily use. 
This GS-9883/F/TAF FDC may provide a potent, convenient, tolerable, and practical regimen 
for the long-term treatment of patients with HIV infection.
1.2.
GS-9883
1.2.1.
General Information
GS-9883, a potent inhibitor of HIV-1 integrase is being evaluated for the treatment of HIV 
infection. Antiviral testing has shown that GS-9883 is active against a broad panel of HIV-1 viral 
lab strains and clinical isolates. GS-9883 is fully active against a panel of mutant viruses with 
resistance to NRTIs, NNRTIs, and PIs. Integrase mutant viruses that are resistant to the INSTIs
RAL and EVG remain largely sensitive to GS-9883.
1.2.2.
Preclinical Pharmacology and Toxicology
A core battery of safety pharmacology studies have been conducted with GS-9883. These 
include assessments of cytotoxicity, off-target receptor and ion-channel binding, effects on 
human Ether-à-go-go-Related Gene (hERG) potassium current and papillary muscle action 
potential, and in vivo studies in rats and dogs that evaluated effects of GS-9883 on all major 
organ systems. The volume of distribution of GS-9883 ranged between 0.09 and 0.22 L/kg in the 
preclinical species, which indicates that the distribution of GS-9883 is limited to the extracellular 
compartment due to its high binding to plasma proteins. The projected half-life of GS-9883 in 
humans is approximately 20 hours based upon the estimates of clearance and volume of 
distribution.
1.2.2.1.
Pharmacology
GS-9883 has half maximal inhibitory concentration (IC50)values ranging from 1.5 to 2.4 nM, 
similar to the inhibitory effect of DTG and EVG. GS-9883 is highly potent against HIV 
replication in the human T cell leukemia MT4 cell line with an EC50 (50% effective inhibitory 
concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. GS-9883 does not 
show significant cytotoxicity against dividing and non-dividing human PBMCs, primary human 
hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 μM. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter organic cation transporter 2 (OCT2)
(IC50 = 0.42 μM). As a result, GS-9883 is not expected to significantly interfere with the key 
transporter responsible for creatinine tubular elimination at the clinically projected Cmax. 
Additionally, the risk that GS-9883 will affect the OCT2-mediated excretion of co-administered 
drugs is considered to be low.


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GS-9883 does not activate AhR and only weakly activates PXR at concentrations up to 50 μM 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.
1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 μg•h/mL and 1931 μg•h/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 μg•h/mL and 1078 μg•h/mL, 
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day. At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal 
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males. The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy.
No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL). The estimated margin of exposure at the NOEL 
was approximately 4.7-fold based on expected human exposure with the once daily dosing of the 
GS-9883/F/TAF (50/200/25 mg) tablet.


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A standard battery of in vitro and in vivo studies was performed to assess the genotoxic potential 
of GS-9883. There was no evidence of mutagenic or clastogenic activity in an in vitro bacterial 
reverse mutation assay (Study TX-141-2026), a chromosomal aberration assay in human 
lymphocytes (Study TX-141-2027), or in a rat micronucleus test (Study TX-141-2029).
1.2.3.
Clinical Trials of GS-9883
Clinical trials entailing the use of GS-9883 include:

GS-US-141-1218, a Phase 1 double blind, randomized, placebo-controlled, first-in-human, 
single- and multiple-ascending dose study evaluating the safety, tolerability, and PK of oral 
GS-9883 in healthy subjects and a randomized, open-label, 2-cohort, 3-period, crossover, PK 
study evaluating the drug interaction potential between F/TAF FDC tablet and GS-9883 in 
healthy subjects (completed)

GS-US-141-1219, a Phase 1b randomized, double-blinded, sequential cohort
placebo-controlled study of the safety, PK, and antiviral activity of GS-9883 in HIV-1 
infected subjects (5 mg, 25 mg, 50 mg, 100 mg) (completed)

GS-US-141-1233, a Phase 1,Open-label, Two-Cohort, Multiple-Period, Fixed-Sequence, 
Crossover Study to Evaluate 1) the Relative Bioavailability of Two 
GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg) 
Fixed-Dose Combination Tablets Versus a GS-9883 (75 mg) Tablet and a 
Emtricitabine/Tenofovir Alafenamide (200/25 mg) Fixed-Dose Combination Tablet 
Administered Simultaneously and 2) the Effect of Food on the Pharmacokinetics of 
GS-9883, Emtricitabine and Tenofovir Alafenamide When Administered as 
GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg) 
Fixed-Dose Combination Tablets (ongoing)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (ongoing)

GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled Phase 1 Study 
Evaluating the Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular 
Filtration Rate (ongoing)


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 18
20 November 2015

GS-US-311-1790, a Phase 1 Randomized, Open Label, Drug Interaction Study Evaluating 
the Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (ongoing)

GS-US-380-1761, a Phase 1 Study to Evaluate Pharmacokinetic Drug-Drug Interaction 
Potential between GS-9883/Emtricitabine/Tenofovir Alafenamide Fumarate 
(GS-9883/F/TAF) and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-Dose Combination (FDC) 
Tablets (ongoing)

GS-US-141-1475, a Phase 2 Randomized, Double-Blinded Study of the Safety and Efficacy 
of GS-9883 + Emtricitabine/Tenofovir Alafenamide Versus 
Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral 
Treatment-Naive Adults (ongoing).
Please refer to the GS-9883/F/TAF Investigators’ Brochure for further information about these 
studies.
1.2.3.1.
Phase 1 Safety and Pharmacokinetics
Study GS-US-141-1218 was a four part, first-in-human study.  Parts A and B were randomized, 
double-blind, placebo-controlled, single and multiple ascending dose studies of GS-9883 in 
healthy male and female subjects.  Part C was an open label, fixed sequence food effect study 
evaluating the effect of food on the PK of GS-9883.  Part D was a randomized, open-label, 
2-cohort, 3-period, crossover PK study evaluating the drug interaction potential between 
FTC/TAF FDC tablet and GS-9883 in healthy subjects.
There was no difference in the overall incidence or type of AEs when GS-9883 was administered 
in the fasted and fed states. There was no difference in the overall incidence of AEs when 
GS-9883 or FTC/TAF was each administered alone or in combination.
No deaths or pregnancies were reported. No Grade 3 or 4 AEs or SAEs, were reported in any 
cohort.
Increases in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2. In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort. In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF. All 
changes returned to baseline after discontinuation of GS-9883.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood. All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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20 November 2015
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).


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by 
GS-9883 Dose Following Multiple-Dose Administration of GS-9883 
(Analysis Set: GS-9883 PK Part B: Multiple-Dose)
GS-9883 PK Parameter Mean
(%CV)a
Multiple-Dose GS-9883
5 mg
(N = 6)
25 mg
(N = 6)
50 mg
(N = 6)
100 mg
(N = 6)
300 mg
(N = 6)
Day 1
AUC0-24 (hr•ng/mL)
9033.6
(8.2)
27,775.1
(28.3)
58,371.4
(18.9)
79,773.8
(18.9)
180,714.3
(17.6)
Cmax (ng/mL)
709.7
(9.5)
2220.0
(35.6)
4648.3
(18.7)
6248.3
(26.8)
13,716.7
(19.1)
Tmax (hr)
1.50
(1.50, 1.50)
1.75
(1.00, 3.00)
1.50
(1.00, 2.00)
2.50
(2.00, 3.00)
2.50
(2.00, 4.00)
Day 7
AUCtau (hr•ng/mL)
14,392.0
(16.7)
50,008.2
(26.6)
89,710.1
(22.7)
126,785.8 
(23.7)
277,200.2 
(16.7)
Cmax (ng/mL)
982.5
(7.9)
3455.0
(24.1)
6538.3
(17.6)
9396.7
(20.8)
19,900.0 
(21.2)
Ctau (ng/mL)
400.83
(26.9)
1322.00
(27.8)
2241.67
(28.2)
3145.00 
(26.1)
6758.33 
(21.6)
Tmax (hr)
1.50
(1.00, 2.00)
3.00
(2.00, 3.00)
1.75
(1.50, 2.00)
1.75
(1.50, 3.00)
4.00
(2.00, 4.00)
Accumulation Ratio of AUC (%)
160.5
(19.0)
182.2
(17.1)
154.0
(15.9)
158.5
(12.1)
157.5
(22.6)
a
Data are presented as mean (%CV), except for Tmax, and t½, which are presented as median (Q1, Q3)
Table 1-3 presents the geometric least squares mean (GLSM) ratios and associated 90% CIs for 
the test (fed) versus reference (fasted) treatments for the primary plasma PK parameters of 
GS-9883. Administration of a single dose of GS-9883 100 mg with food 
(high-calorie/high-fat breakfast) increased the GLSM values of Cmax and AUCinf 101% 
(90% CI of GLSM ratio 165.93% to 242.74%) and 84% (90% CI of GLSM ratio 
152.05% to 222.59%), respectively. There were no apparent changes in clearance and t1/2
following administration with food, indicating that food enhanced the bioavailability of 
GS-9883 by improving its solubility and/or absorption.
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic 
Parameters Following Single-Dose Administration of GS-9883 in the 
Fasted and Fed States (GS-9883 PK Analysis Set)
GS-9883 PK Parameter 
Mean (%CV)
% GLSM Ratio 
(90% CI)
Test
GS-9883 100 mg Fed
(n = 8)
Reference
GS-9883 100 mg Fasted
(n = 8)
AUCinf (hr•ng/mL)
214,146.3 (15.9)
117,777.1 (23.3)
183.97 (152.05, 222.59)
AUClast (hr•ng/mL)
209,259.9 (15.1)
115,681.7 (24.0)
183.58 (151.91, 221.86)
Cmax (ng/mL)
11,268.8 (15.1)
5885.0 (34.9)
200.69 (165.93, 242.74)
CI = confidence interval; GLSM = geometric least squares mean


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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1.2.3.2.
Phase 1 b Proof of Concept
The first HIV-1 positive human subjects were dosed in the fasted state with 10 days of GS-9883 
in study (GS-US-141-1219). Four cohorts of 5 subjects each were randomized 4:1 to receive 
GS-9883 or placebo to match at doses of 5 mg, 25 mg, 50 mg, and 100 mg once daily for 
10 days.
GS-9883 was generally well tolerated at the doses evaluated. A total of 9 of 20 subjects had an 
AE in this study. The most frequently reported AEs across all subjects were diarrhea (2 subjects), 
and headache (3 subjects). No other AE was reported in more than 1 subject. There was no 
increase in the incidence of AEs with increasing doses of GS-9883.
The majority of AEs were considered by the investigator to be not related to study drug. A total 
of 2 subjects experienced mild diarrhea that was considered related to study drug 
(1 in the 5 mg cohort, 1 in the 100 mg cohort).
No deaths or pregnancies were reported. No Grade 3 or 4 AEs, SAEs, or AEs leading to 
discontinuation of study drug were reported in any cohort.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. No Grade 3 
treatment emergent laboratory abnormalities were observed. Median serum creatinine changes at 
Day 10 were: 0.05 mg/dL (5 mg), 0.04 mg/dL (25 mg), 0.06 mg/dL (50 mg), and 0.15 mg/dL 
(100 mg). These changes in serum creatinine appeared to be transient and returned close to 
baseline values on discontinuation of study drug. One Grade 4 new onset laboratory abnormality 
was seen in 1 subject who received 5 mg GS-9883. This was a Grade 4 CPK seen on Day 17, 
7 days following his last dose of study medication. The subject was asymptomatic. The 
Investigator felt that this was unrelated to study medication and was due to resumption of crystal 
methamphetamine use by the subject. An adverse event of elevated CK was reported unrelated to
study medication.
Based on PK information collected in study GS-US-141-1219, which was in line with PK 
observed in study GS-US-141-1218, the median IQ for each dose were calculated and are 
presented in the table below.
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ95 Values
(GS-9883 PK Analysis Set)
GS-9883 Dose
N
Median (range) Ctau, SS (ng/mL)
Median (range) paIQ95
a
5 mg
4
206.5 (146.0 to 342.0)
1.3 (0.9 to 2.1)
25 mg
4
797.5 (714.0 to 1900.0)
4.9 (4.4 to 11.7)
50 mg
4
2170.0 (852.0 to 3020.0)
13.4 (5.3 to 18.6)
100 mg
4
4190.0 (3730.0 to 5970.0)
25.9(23.0 to 36.9)
a
The protein adjusted IQ95 (paIQ95) value is estimated based on steady-state Ctau values and the in vitro paIC95 value for 
wild-type HIV-1 (162 ng/ml).


GS-9883/F/T AF 
Protocol GS-US-380-1961 
Gilead Sciences, Inc. 
Final 
Original 
The mean and 95% Cis of change from baseline in HIV -1 RNA (log10 copieslmL) are presented 
in Figure 1-1. 
Figure 1-1. 
<( 
z 
n:: 
-1 
~ 
J: 
c 
-2 
-~ 
8i 
~ -3 
E 
,g 
~ -4 
~ 
(.) 
GS-9883 5 mg <~ ): 
GS-9883 25 mg (~): 
GS-9883 50 mg (~): 
GS-9883 100 mg (~): 
Placebo(~): 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
e = GS-9883 5 mg 
0 = GS-9883 25 mg 
b. = GS-9883 50 mg 
0 = GS-9883 100 mg 
0 = Placebo 
BL 
2 
3 
4 
3 
3 
3 
3 
4 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
3 
4 
4 
4 
4 
7 
8 
9 
Day 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
------
--
10 
11 
14 
17 
3 
3 
3 
3 
4 
4 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study drug. 
2 
0 
-1 
-2 
-3 
-4 
-5 
Mean viral load change on Day 11 was - 2.08log10 in the 25 mg cohort, - 2.06 log10 in the 50 mg 
cohott, and - 2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVGll) was - 0.92log10 in the 5 mg cohot1~ - 1.33log10 in the 25 mg cohort, 
- 1.37log10 in the 50 mg cohort and - 1.61 log10 in the 100 mg cohmt. Viral suppression 
(HIV-1 RNA < 50 copieslmL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group. 
1.2.3.3. 
Summaty of Phase 2 Study (GS-US-141-1475) 
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing 
GS-9883+F IT AF versus dolutegravir (DTG)+F IT AF in HIV -infected, antiretroviral therapy 
(ART)-naive adult subjects. 
CONFIDENTIAL 
Page22 
20 November 2015 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 23
20 November 2015
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, > 100,000 copies/mL to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 
50 mg once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 
75 mg once daily
Week 24 interim data are summarized below. 
1.2.3.4.
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24
data analysis, 2 subjects (2.0%) had prematurely discontinued study treatment, one in each 
treatment group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and estimated glomerular 
filtration rate [eGFR] using the Cockcroft-Gault method [eGFRCG]) were similar between the 
2 treatment groups.
Median (Q1, Q3) baseline HIV-1 RNA was 4.45 (3.96, 4.79) log10 copies/mL, with 
82.7% of subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had > 400,000 copies/mL 
at baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 1 subject was 
randomized to DTG+F/TAF.

Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 
41.8% of subjects having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 
125.3 (105.7, 147.0) mL/min.
1.2.3.5.
Efficacy Results
Virologic success at Week 12 and 24 was assessed using the US FDA snapshot algorithm, 
defined as plasma HIV-1 RNA < 50 copies/mL. At Weeks 12 and 24, virologic success was high 
and similar between the 2 treatment groups as follows: Week 12 GS-9883+F/TAF 93.8%; 
DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: −1.3%; 95% CI: 
−12.9% to 10.2%; p = 0.79); Week 24 GS-9883/F/TAF 95.4%, DTG+F/TAF 93.9% 
(1.0%; 95%CI: -10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 was considered a virologic failure by US FDA snapshot 
algorithm with HIV-1 RNA of 60 copies/mL.


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 24
20 November 2015
Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF +170 (150.0) cells/μL; DTG+F/TAF +173 (220.5) cells/μL 
(difference in LSM: 0; 95% CI: −76 to 76; p = 1.00). There were similar increases in the mean 
(SD) CD4 cell count in both treatment groups Week 24: GS-9883/F/TAF, +189 (177.8) cells/µL 
(difference in LSM: 39; 95% CI: -35 to 113; p = 0.30
Interim Virology Resistance Data
Through Week 24, no emergent drug resistance was detected.
1.2.3.6.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 58.5%, 38 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common TEAEs (occurring in > 1 subject) by treatment group were as follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883/F/TAF group; this event was also 
reported as an SAE, and 1 other SAE (appendicitis), also in the GS-9883/F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator, resulted in study 
drug discontinuation, or required interruption of study drug, and both SAEs resolved.
The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883/F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs that were considered related to study 
drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation 
were reported in either treatment group.
Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least
1 grade level increase from baseline in graded abnormality) was similar between treatment groups 
as follows: GS-9883+F/TAF 76.6%, 49 subjects; DTG+F/TAF 78.1%, 25 subjects. The majority 


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 25
20 November 2015
of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The percentage of 
subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality was similar 
between treatment groups as follows: GS-9883+F/TAF 17.2%, 11 subjects; DTG+F/TAF 12.5%, 
4 subjects. Grade 3 or 4 treatment-emergent laboratory abnormalities occurring in at least 
2 subjects in either treatment group were as follows: creatine kinase (GS-9883+F/TAF, 3.1% 
[2 subjects]), and fasting low-density lipoprotein (LDL) (GS-9883+F/TAF, 3.1% [2 subjects]). 
The only Grade 4 laboratory abnormalities were for creatine kinase, reported in 2 subjects (3.1%) 
in the GS-9883+F/TAF group. All increased creatine kinase values appeared to be transient, and 
none were associated with AEs. Of the 2 subjects with increased AST, 1 subject had Grade 3 AST 
and Grade 3 ALT at Week 24 in the setting of alcohol abuse; the other subject had Grade 3 AST 
at Week 8 that returned to normal by Week 24.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. There were 
similar increases from baseline in median (Q1, Q3) serum creatinine in both treatment groups at 
Week 24: GS-9883+F/TAF 0.12 (0.06, 0.18) mg/dL; DTG+F/TAF 0.13 (0.05, 0.21) mg/dL. 
There were decreases in median (Q1, Q3) eGFRCG at Week 24, which were smaller in the 
GS-9883+F/TAF compared with the DTG+F/TAF group: GS-9883+F/TAF 
−13.3 (−19.9, −4.0) mL/min; DTG+F/TAF −17.2 (−25.7, −6.9) mL/min.
Conclusions
Key Week 24 conclusions from Study GS-US-141-1475 include the following:

Virologic success at Week 24 when assessed using the FDA-defined snapshot algorithm, 
defined as plasma HIV-1 RNA < 50 copies/mL, was similar between the 2 treatment groups 
as follows: GS-9883+F/TAF 95.4%; DTG+F/TAF 93.9%; stratum-adjusted difference in 
percentages: 1.0%; 95% CI: -10.7% to 12.7%; p = 0.84. There was a similar increase in the 
mean (SD) CD4 cell count between the 2 treatment groups, GS-9883+F/TAF,
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).

No resistance to any INSTIs, NRTIs, NNRTIs or PIs was detected through Week 24.

No AEs led to study drug discontinuation in either treatment group.

Both GS-9883+F/TAF and DTG+F/TAF were generally well tolerated through 24 weeks of 
treatment. The most commonly reported treatment-emergent AEs were diarrhea and 
headache (7.7% each) in the GS-9883+F/TAF group and nausea (12.1%) and diarrhea (9.1%) 
in the DTG+F/TAF group. There were 2 SAEs, 1 of which was also a Grade 3 AE; neither of 
these events was considered related to study drug by the investigator, or led to study drug 
discontinuation. There were no other Grade 3 or 4 AEs, and no deaths, pregnancies, or AEs 
leading to premature study drug discontinuation reported. The percentage of subjects with at 
least 1 treatment-emergent laboratory abnormality was similar between treatment groups. 
The majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. 
There were similar increases from baseline in serum creatinine in both treatment groups at 
Week 24.


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1.3.
Information About Emtricitabine (Emtriva®, FTC)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US Food and Drug Administration (FDA) for 
marketing on 2 July 2003 and is available under the name Emtriva®. In the European Union 
(EU), marketing authorization was granted for both the 200 mg Emtriva® capsule formulation 
and a 10 mg/mL Emtriva® oral Solution formulation on 24 October 2003, with indications for the 
treatment of HIV infection concurrently with other antiretroviral drugs in both adult and 
pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information About Tenofovir Alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) or 
Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide (FTC/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected subjects (completed)

GS-US-120-0104, a Phase 1b study of the pharmacokinetics and antiviral activity of 
GS-7340 (8 mg, 25 mg, 40 mg) in HIV infected subjects (completed)

GS-US-120-0107, a Phase 1, partially-blinded, randomized, placebo- and positive controlled 
study to evaluate the effect of GS-7340 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-120-0108, a Phase 1, open-label, parallel-design study to evaluate the 
pharmacokinetics of GS-7340 in subjects with severe renal impairment (completed)

GS-US-120-0109, a Phase 1 study to evaluate the pharmacokinetics, metabolism and 
excretion of GS-7340 (completed)


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
GS-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the 
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic 
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug 
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of 
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in 
healthy subjects (completed)

GS-US-311-1386, a Phase 1 study to determine the effect of food on the pharmacokinetics of 
tenofovir alafenamide when administered as F/TAF FDC in healthy volunteers (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential 
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz (EFV) or 
COBI-boosted darunavir (DRV) (completed)

GS-US-311-1088, a Phase 1, relative bioavailability study of 
Emtricitabine/Tenofovir Alafenamide fixed dose combination tablet to evaluate the 
formulation performance of emtricitabine (FTC) and tenofovir alafenamide (TAF) fixed dose 
combination tablets relative to co-administration of individual agents (completed)

GS-US-311-1089, a Phase 3 study of the safety and efficacy of FTC/TAF in HIV infected, 
virologically suppressed patients (ongoing)
In Study GS-US-311-1386, the effect of food (high-calorie, high-fat meal) on the PK of the TAF 
component of the F/TAF FDC was evaluated. The GLSM ratio of the AUClast of TAF when 
administered with a high-fat meal was 177% (90% CI: 166% to 188%), and the TAF Cmax
GLSM ratio was 84.5% (90% CI: 74.9% to 95.4%). This ~75% increase in TAF plasma 
exposure and ~15% decrease in TAF plasma Cmax when administered with food was 
accompanied by a delay in Tmax (increase from 1.00 hour under fasted conditions to 2.00 hours 
under fed conditions). The exposures of TAF observed under fed or fasted conditions in this 
study are within the range of exposures observed in the E/C/F/TAF clinical development 
program and are commensurate with safe and effective plasma levels of TAF 
(see investigator brochure for further details). Therefore, the changes in TAF exposures when 
F/TAF is administered with food should not result in differences in efficacy and thus are not 
clinically relevant. TAF can be administered without regard for food and these findings can be 
extrapolated to F/TAF (as FTC can be taken without regard to food). 


GS-9883/F/TAF
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Final
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1.4.2.
Clinical Trials of FTC/TAF as Part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF)
Clinical trials using tenofovir alafenamide, coformulated into the E/C/F/TAF STR include: 

GS-US-292-0101, a Phase 1 healthy volunteer study evaluating the relative bioavailability of 
EVG, FTC, TFV, and COBI administered as E/C/F/TAF STR relative to E/C/F/TDF or TAF 
(completed)

GS-US-292-0103, a Phase 1 healthy volunteer study to evaluate the pharmacokinetics and 
relative bioavailability of the E/C/F/TAF STR relative to the individual components at 
GS-7340 doses of 10 mg (STR) or 25 mg Single Agent (SA) (completed)

GS-US-292-0102, a Phase 2 randomized, double-blinded study of the safety and efficacy of 
E/C/F/TAF STR versus E/C/F/TDF STR in HIV-1 infected, antiretroviral treatment-naive 
adults (ongoing)

GS-US-292-0104 and GS-US-292-0111, Phase 3 randomized, double-blinded study of the 
safety and efficacy of E/C/F/TAF STR versus E/C/F/TDF STR in HIV-1 infected, 
antiretroviral treatment-naive adults (ongoing)

GS-US-292-0109, a Phase 3 open-label study to evaluate switching from a TDF-containing 
combination regimen to a TAF-containing combination single tablet regimen (STR) in 
virologically-suppressed, HIV-1 positive subjects (ongoing)

GS-US-292-0112, a Phase 3 Open-label Safety Study of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide single-tablet Regimen in HIV-1 
positive patients with mild to moderate renal impairment (ongoing)

GS-US-292-0117, a Phase 3, two-part study to evaluate the efficacy of Tenofovir 
Alafenamide versus placebo added to a failing regimen followed by treatment with 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in HIV-1 positive, 
antiretroviral treatment-experienced adults (ongoing)

GS-US-292-0119, a Phase 3 open-label study to evaluate switching from optimized stable 
antiretroviral regimens containing darunavir to 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) single tablet 
regimen (STR) plus darunavir (DRV) in treatment experienced HIV-1 positive adults 
(ongoing)

GS-US-292-0106, a Phase 2/3, open-label study of the pharmacokinetics, safety, and 
antiviral activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected antiretroviral treatment-naive 
adolescents (ongoing)


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Study GS-US-292-0101 is a Phase 1 study of 40 subjects evaluating the relative bioavailability 
of two different formulations of E/C/F/TAF STR, each with TAF dose of 25 mg or 40 mg, versus 
E/C/F/TDF STR or TAF 25 mg alone. Exposures of EVG, COBI, and FTC were comparable 
between E/C/F/TAF vs E/C/F/TDF regardless of formulation (monolayer or bi-layer). In 
contrast, TAF exposures were ~2.2-fold higher (and corresponding tenofovir exposures 
~3-fold higher) when administered as E/C/F/TAF (25 mg) vs TAF single agent (SA) 25 mg for 
both formulations of the E/C/F/TAF, likely mediated by inhibition of P-gp-mediated intestinal 
secretion of TAF by COBI.
Study GS-US-292-0103 is a completed Phase 1 healthy volunteer study which evaluated the PK 
and relative bioavailability of the E/C/F/TAF STR relative to the individual components at TAF 
doses of 10 (STR) or 25 mg SA. Results indicate that when dosed as the E/C/F/TAF 10 mg STR, 
TAF and TFV exposures were comparable to those observed with TAF 25 mg dosed alone. 
Exposures of EVG, COBI, and FTC were also comparable between the STR and individually 
dosed formulations. 
Study GS-US-292-0102 is an ongoing, randomized, active-controlled Phase 2 study, compares 
E/C/F/TAF (10 mg) versus Stribild® (STB, E/C/F/TDF) in treatment-naïve, HIV-1 infected 
subjects. At Week 48, the E/C/F/TAF demonstrated potent antiviral efficacy 
(HIV-1 RNA < 50 copies/mL) similar to STB (88.4% [99/112] vs 87.9% [51/58] using the 
snapshot algorithm); in the E/C/F/TAF group, no patient had emergent resistance to 
1 or more components of the E/C/F/TAF. Importantly, E/C/F/TAF demonstrated a potential 
benefit over E/C/F/TDF in terms of renal and bone safety: smaller median decreases in eGFR 
(mL/min) (at Week 48, E/C/F/TAF −5.5 vs E/C/F/TDF −10.0 [P < 0.001) and smaller median 
percentage decreases in BMD (at Week 48, spine E/C/F/TAF −1.00 vs E/C/F/TDF −3.37 
[p < 0.001], hip −0.62 vs −2.39 [p < 0.001]).
Studies GS-US-292-0104 and GS-US-292-0111 are ongoing, Phase 3 randomized, 
double-blinded studies of the safety and efficacy of E/C/F/TAF versus E/C/F/TDF in HIV-1 
infected, antiretroviral treatment-naive adults. The interim Week 48 key conclusions from pooled 
data showed that E/C/F/TAF once daily was noninferior to STB once daily when administered 
for 48 weeks to HIV-infected, ART-naive adults, as assessed using the US Food and Drug 
Administration (FDA)-defined snapshot algorithm with HIV-1 RNA < 50 copies/mL 
(E/C/F/TAF 92.4%; STB 90.4%; difference in percentages: 2.0%, 95% CI: −0.7% to 4.7%). 
Administration of E/C/F/TAF resulted in > 90% lower plasma TFV and higher intracellular 
TFV-DP relative to STB. E/C/F/TAF showed an improved renal and bone safety profile with 
significantly less decline in hip and spine BMD, less increase in serum creatinine and reduction 
in estimated glomerular filtration rate (eGFR).
1.5.
Information About GS-9883/Emtricitabine/Tenofovir Alafenamide 
(GS-9883/F/TAF)
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.


GS-9883/F/TAF
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1.5.1.
GS-US-141-1233: Relative Bioavailability of GS-9883, FTC, and TAF 
Between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is an ongoing Phase 1, open-label, 2-cohort, multiple-period,
fixed-sequence, crossover study conducted at a single center in the US to evaluate 1) the relative 
bioavailability (BA) of 2 GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets 
compared with the GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered 
simultaneously and 2) the effect of food on the PK of GS-9883, FTC, and TAF when 
administered as GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets. 
Cohort 1 evaluated the relative BA and food effect of GS-9883/F/TAF (75/200/25 mg) FDC 
tablet in a 3-period sequence. Following review of preliminary data from Cohort 1, Cohort 2 was 
added to the study via protocol amendment. Cohort 2 will evaluate the relative BA and food 
effect of GS-9883/F/TAF (50/200/25 mg) FDC tablet in a 4-period sequence. 
The in-life portion of Cohort 1 is complete; preliminary results are summarized below. The 
in-life portion of Cohort 2 is ongoing.
Cohort 1 Results:
Pharmacokinetic Results
Under fasted conditions, GS-9883 AUCinf and Cmax were 27% and 31% higher, respectively, 
following GS-9883/F/TAF (75/200/25 mg) FDC administration than following administration of 
single-agent GS-9883 (75 mg) with the F/TAF (200/25 mg) FDC. FTC and TAF exposure was 
similar following administration of GS-9883/F/TAF (75/200/25 mg) or single-agent GS-9883 
(75 mg) with the F/TAF (200/25 mg) FDC. Compared with administration under fasted 
conditions, administration of the GS-9883/F/TAF (75/200/25 mg) FDC with a high-fat meal 
resulted in a 46% higher GS-9883 AUCinf and a 27% higher GS-9883 Cmax. The impact of food 
on TAF and FTC exposure was similar to that previously observed for F/TAF 
(Study GS-US-311-1386). GS-9883/F/TAF may be taken without regard to food. Based on these 
results, Cohort 2 was added to the study via protocol amendment to evaluate the relative BA of 
the GS-9883/F/TAF (50/200/25 mg) FDC tablet compared with the single-agent GS-9883 
(75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered simultaneously.
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 1, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.


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Cohort 2 Results:
Pharmacokinetic Results
Preliminary data of Cohort 2 showed that GS-9883 and Cmax and AUCinf following 
GS-9883/F/TAF FDC (50/200/25 mg) administration under fasted conditions were 
78% and 79%, respectively as the exposures following administration of single-agent GS-9883 
(75 mg) with the F/TAF FDC (200/25 mg). FTC and TAF exposure was similar following 
administration of GS-9883/F/TAF (50/200/25 mg) or single-agent GS-9883 (75 mg) with the 
F/TAF FDC (200/25 mg). 
Food had a small effect on GS-9883 exposure following GS 9883/F/TAF (50/200/25 mg) single 
dose. A high fat meal increased GS-9883 Cmax and AUCinf by 13% and 24%, respectively 
compared to exposure under fasted conditions. Similarly, a moderate fat meal increased GS-9883 
Cmax and AUCinf by 20% and 24%, respectively. The impact of food on TAF and FTC exposure 
was similar to that previously observed for F/TAF (Study GS-US-311-1386).
GS-9883 exposures following administration of the GS-9883/F/TAF (75/200/25 mg and 
50/200/25 mg) FDC tablets are approximately dose proportional under fasted and fed conditions. 
GS 9883/F/TAF may be taken without regard to food.
1.6.
EVG/COBI/FTC/TDF (E/C/F/TDF or Stribild®)
Further information is available in the US Prescribing Information and Investigator’s Brochure 
for E/C/F/TDF.
1.7.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®)
Further information is available in the Prescribing Information for Truvada®.
1.8.
Ritonavir (RTV, /r, Norvir®)
Further information is available in the Prescribing Information for Norvir®.
1.9.
Atazanavir (ATV, Reyataz®)
Further information is available in the Prescribing Information for Reyataz®.
1.10.
Rationale for This Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 
HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.


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The GS-9883/F/TAF FDC has the potential to offer a simple, once-daily regimen containing a 
second generation INSTI that provides a high barrier to resistance, does not require a boosting 
agent, and offers an effective and safer alternative to standard nucleos(t)ide based regimens, 
without the need for HLA testing or close monitoring of renal or bone toxicities. It could provide 
an FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute to an 
increased risk of cardiovascular events, could be used in patients with chronic hepatitis B or C 
infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities.Approximately 50% of the global population of HIV-infected 
persons are women, however they remain under-represented in most clinical HIV studies. In 
general, studies to date have not shown gender differences in virologic responses to antiretroviral 
therapy (ART), but a number of studies have suggested that gender may influence the frequency, 
presentation, and severity of selected ARV-related adverse events. Although data are limited, the
pharmacokinetics for some ARV drugs may differ between men and women, possibly because of 
variations in factors such as body weight, plasma volume, gastric emptying time, plasma protein 
levels, CYP450 activity, drug transporter function, and excretion activity. It is important to 
understand potential gender-specific safety and efficacy issues in women when assessing 
virologic response, tolerability, and adherence. This study will ensure that there is adequate 
safety data in HIV-1-infected women in the Phase 3 program for GS-9883/F/TAF.
The objective of this study is to evaluate the safety and efficacy of an FDC containing 
GS-9883/F/TAF versus continuing on a regimen consisting of E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF in women who are virologically suppressed. Switching to 
GS-9883/F/TAF offers the advantages of a single-tablet FDC containing the unboosted, 
next-generation INSTI, GS-9883, combined with a TAF-based nucleotide backbone.
GS-9883/F/TAF FDC which includes TAF, has the potential to offer an effective and safer 
alternative to standard nucleos(t)ide based regimens, without the need for close monitoring of 
renal or bone toxicities or increase risk of cardiovascular complications as patients age and 
confront non HIV-related comorbidities.
1.11.
Risk/Benefit Assessment for the Study
All patients with HIV-1 infection should receive effective anti-retroviral therapy. Potential risks
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and
lactic acidosis with steatosis. The risk of class effects is considered to be low. Important
identified risks appropriately managed by study inclusion/exclusion criteria as well as through
close clinical and laboratory monitoring during the study are as follows: allergy to any 
components of the tablets. Protease inhibitors may be associated with increased lipid levels and 
gastrointestinal side effects. If patients are currently infected with hepatitis B and discontinue 
their existing or new therapy, there is a risk of severe acute exacerbations of hepatitis B.
Potential benefits may include provision of a new antiretroviral therapy that is not currently
available and which may have fewer side effects than alternative therapies. Other potential
benefits include provisions of fixed dose combination therapy, and the knowledge that patient
participation will contribute to the body of knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF is favorable at this time.


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1.12.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady 
State Following GS-9883 Administration Under Fasting Conditions 
and Corresponding Protein-Adjusted IQ95 Values
GS-9883 Dose
n
Median (range) Ctau,SS (ng/mL)
Median (range) paIQ95
a
5 mg
4
206.5 (146.0 – 342.0)
1.3 (0.9 – 2.1)
25 mg
4
797.5 (714.0 – 1900.0)
4.9 (4.4 – 11.7)
50 mg
4
2170.0 (852.0 – 3020.0)
13.4 (5.3 – 18.6)
100 mg
4
4190.0 (3730.0 – 5970.0)
25.9 (23 – 36.9)
a
The paIQ95 value is estimated based on steady-state Ctau values and the in vitro paIC95 value for wild-type HIV-1 
(162 ng/mL).
Source: Data on File


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Single-agent GS-9883 was well tolerated at all doses administered. The range of GS-9883 
plasma exposure at steady state (Ctau,SS) observed in the 50-mg cohort correlated with protein 
adjusted 95% inhibitory quotient (paIQ95) values ranging from 5.3 to 19, while the range of 
GS-9883 plasma exposure at steady state (Ctau,SS) observed in the 100-mg cohort correlated with
paIQ95 values ranging from 23 to 37 (Table 1-5).
Based on PK/PD analyses, exposure following a 75-mg dose of single-agent GS-9883 is 
expected to provide near-maximal virologic response, with a predicted paIQ95 of approximately 
20, providing considerable coverage above the target concentration of 162 ng/mL (paIC95).
GS-9883 (75 mg) single agent coadministered with F/TAF (200/25 mg) is currently being 
evaluated in a Phase 2 study, GS-US-141-1475 (GS-9883+F/TAF vs DTG+F/TAF). The 
Week 24 interim data from this study, support the safety and efficacy of GS-9883 exposures 
obtained with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF is being developed for use in Phase 3 studies. 
Preliminary results from the relative bioavailability (rBA) study (GS-US-141-1233) of 
GS-9883/F/TAF (75/200/25 mg) showed that GS-9883 plasma exposure was higher (with Cmax
and AUCinf increase of 31% and 27%, respectively) following administration of the FDC as 
compared with exposure following administration of GS-9883 (75 mg) + F/TAF (200/25 mg) 
under fasted conditions. The increase in GS-9883 exposures associated with the FDC 
formulation results in an estimated mean paIQ95 of 24.3, compared to an estimated mean paIQ95
of 19.2 for the GS-9883 (75 mg) single agent coadministered with F/TAF, in the fasted state.
In order to bridge exposures of GS-9883 in the FDC to the exposure observed with GS-9883 
75 mg administered as a single agent, and to bridge to the safe and effective exposures observed 
in the Phase 2 study GS-US-141-1475, a lower strength GS-9883/F/TAF FDC is being 
developed for use in the Phase 3 studies. Comparability of GS-9883 exposures will be confirmed 
in an rBA study of GS-9883/F/TAF (50/200/25 mg) and GS-9883 (75 mg) + F/TAF prior to 
initiation of dosing in the Phase 3 studies.  
E/C/F/TAF
EVG/COBI/FTC/TAF (200/25/25 mg) is a fixed dose combination, with only one dose 
combination available; and has been approved by the United States Food and Drug Administration 
(FDA) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and 
pediatric patients 12 years of age and older with no ARV treatment history or to replace the current 
ARV regimen in those who are virologically suppressed on a stable ARV regimen with no history 
of treatment failure and no known substitutions associated with resistance. This FDC contains the 
equivalent doses of EVG, COBI and FTC in the marketed product, Stribild® (STB).


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E/C/F/TDF (STB)
EVG/COBI/FTC/TDF (150/150/200/300 mg) is a fixed dose combination, with only one dose 
combination available; and is approved for use (Stribild®) in the United States by the 
Food and Drug Administration (FDA), for the treatment of HIV-1 infection in treatment-naïve 
adults.
ATV+RTV+FTC/TDF
ATV (300 mg), RTV (100 mg) and FTC/TDF (200/300 mg) represent the current marketed 
doses of these products.
1.13.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.  


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of switching to an FDC of GS-9883/F/TAF versus continuing on a 
regimen consisting of E/C/F/TAF, E/C/F/TDF or ATV+RTV+FTC/TDF in virologically 
suppressed HIV-1 infected women as determined by the proportion of subjects with virologic 
failure (HIV-1 RNA ≥ 50 copies/mL) at Week 48. 
The secondary objective of this study is:

To evaluate the safety and tolerability of the treatment groups through Week 48.  


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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

The proportion of subjects with virologic failure (HIV-1 RNA ≥ 50 copies/mL at Week 48, 
as defined by the modified United States (US) Food and Drug Administration (FDA) 
snapshot algorithm). 
The secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA snapshot algorithm.

The change from baseline in CD4+ cell count at Week 48. 
3.2.
Study Design
This protocol describes a randomized, open label, multicenter, active-controlled study to evaluate 
the safety and efficacy of switching to a GS-9883/F/TAF FDC in HIV-1 infected women who 
are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF), 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF), or 
ATV+RTV+FTC/TDF for ≥ 12 consecutive weeks prior to screening.
3.3.
Study Treatments
Subjects who complete the following criteria will be given the option to participate in this study:

Completion of the Week 48 OLE visit or any post Week 48 OLE visits in study
GS-US-236-0128, or

Completion of the Week 96 visit or any post Week 96 visits in study GS-US-292-0109 
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to receive open label medication:

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food (n = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)


GS-9883/F/T AF 
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3.4. 
Duration of Treatment 
Final 
Original 
Subjects will be treated for at least 48 weeks. At the Week 48 Visit, subjects in a colliltly where 
GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/TAF FDC 
for an additional48 weeks and attend study visits evety 12 weeks, or lliltil the product becomes 
accessible to subjects through an access program, or lliltil Gilead Sciences elects to discontinue 
the study in that colliltty, whichever occurs first. 
Subjects who complete the study through the Week 48 Visit and do not continue post Week 48 
will be required to retum to the clinic 30 days after the Week 48 Visit for a 30 Day Follow-Up 
Visit. 
Figure 3-1. 
Screening 
~ 30 days pl'iot· 
to Day 1 
Study Schema 
Dayl 
a 
Treatment Group 1: GS-9883/F/TAF FDC 
N=200 
Treatment Group 2: Stay on baseline 
regimen (E/C/F/TAF, EICIFITDF or 
ATV+RTV+FTCITDF) N=200 
b 
Wet>k48 
30 
Day 
Ftu' 
a 
Following the Day 1 visit, subje.cts will be required to return for study visits at Weeks 4, 8, 12 and then every 12 weeks 
tlu·ough Week 48 
b 
Aftet· Week 48, subjects in a cmmtry where GS-9883/F!TAF FDC is not available will be given the option to receive 
GS-9883/F!TAF for an additional48 weeks, or tmtil the product becomes accessible to subjects through an access program, 
or tmtil Gilead Sciences elects to discontinue the study in that cotmtry, whichever occurs fu·st 
c 
Subjects who complete the study tlu·ough Week 48 and do not wish to receive GS-9883/F!TAF FDC will be required to 
rettun to the clinic 30 days after the completion of study dmg for a 30-day follow-up visit 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Future Research 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 400 subjects who meet the eligibility criteria will be enrolled. 
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Female, (at birth), Age ≥18 years
3) Currently on a stable antiretroviral regimen of E/C/F/TAF, E/C/F/TDF, or 
ATV+RTV+FTC/TDF continuously for ≥12 consecutive weeks preceding the screening 
visit
4) Completion of the Week 48 OLE visit or any post Week 48 OLE visits in 
study GS-US-236-0128 or completion of the Week 96 visit or any post Week 96 visits in 
study GS-US-292-0109
5) Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥ 12 weeks preceding the 
Screening Visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA 
≥50 copies/mL followed by resuppression to < 50 copies/mL are allowed
6)
HIV-1 RNA < 50 copies/mL at screening
7) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) 
8) Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min according to the Cockcroft-Gault formula 
{2202}:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg)
72 (serum creatinine in μmol/L)
0.85
0. 6786
CrCL (mL/sec)
9) Hepatic transaminases (AST and ALT) ≤5 × upper limit of normal (ULN).
10) Total bilirubin 1.5 mg/dL (26 μmol/L), or normal direct bilirubin.


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11) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L)).
12) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN).
13) Women of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Women who utilize hormonal contraceptive as one of their birth control methods must 
have used the same method for at least 3 months prior to study drug dosing. 
b) Female subjects who have stopped menstruating for ≥12 months but do not have 
documentation of ovarian hormonal failure must have a serum follicle stimulating 
hormone (FSH) level at screening within the post-menopausal range based on the 
Central Laboratory reference range.
14) Have no documented or suspected resistance to FTC, TFV, ATV or EVG including, but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
2) Subjects experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or 
variceal bleeding)
3) Have been treated with immunosuppressant therapies or chemotherapeutic agents within 
3 months of study screening, or expected to receive these agents or systemic steroids 
during the study (eg, corticosteroids, immunoglobulins, and other immune- or 
cytokine-based therapies)  
4) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance  
5) A history of or ongoing malignancy (including untreated carcinoma in-situ) other than 
cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous 
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must 
not have received any systemic therapy for KS within 30 days of Day 1 and are not 
anticipated to require systemic therapy during the study


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6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1 
7) Participation in any clinical trial other than GS-US-236-0128 or GS-US-292-0109, including 
observational studies, without prior approval from the sponsor is prohibited while 
participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC, E/C/F/TAF, E/C/F/TDF, 
ATV, RTV, or FTC/TDF
10) Women who are pregnant (as confirmed by positive serum pregnancy test)
11) Women who are breastfeeding  
12) Subjects receiving ongoing therapy with any of the medications in Table 5-1 or Table 5-2.
Administration of any disallowed agent must be discontinued at least 30 days prior to the 
Day 1 visit and for the duration of the study
13) Acute hepatitis in the 30 days prior to study entry
14) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visit cannot occur until subject eligibility has been confirmed.  
Once eligibility has been confirmed and prior to or during the Day 1 visit the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2. 

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food (n = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)
The IWRS will assign study drug bottle numbers of open label FDC of GS-9883/F/TAF, 
open label E/C/F/TAF, open label E/C/F/TDF or open label ATV+RTV+FTC/TDF at each study 
visit for each subject.  
Randomization will be stratified by the prior treatment regimen group (ie, E/C/F/TAF, E/C/F/TDF 
and ATV+RTV+FTC/TDF).
5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Tablets
GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.


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


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg
(GS-9883/F/TAF) Tablets
GS-9883/F/TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each 
bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.2.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Alafenamide 10 mg (E/C/F/TAF) Tablets
E/C/F/TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.3.
Elvitegravir 150 mg/Cobicistat 150 mg/Emtricitabine 200 mg/
Tenofovir Disoproxil Fumarate 300 mg (E/C/F/TDF, Stribild®) Tablets
E/C/F/TDF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets and a silica gel desiccant with or without polyester coil fiber. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
5.2.2.4.
Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg 
(FTC/TDF, Truvada®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.5.
Ritonavir (RTV, Norvir®) Tablets
Refer to commercially available Prescribing Information.
5.2.2.6.
Atazanavir (ATV, Reyataz®) Capsules
Refer to commercially available Prescribing Information.
All study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice −Annex 13 
(Investigational Medicinal Products), and/or other local regulations.


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5.2.3.
Storage and Handling
Study drugs GS-9883/F/TAF FDC, E/C/F/TAF and E/C/F/TDF should be stored at controlled 
room temperature of 25 °C (77 °F); excursions are permitted between 15 °C and 30 °C 
(59 °F and 86 °F). Storage conditions are specified on the label. Until dispensed to the subjects, 
all bottles of study drugs should be stored in a securely locked area, accessible only to authorized 
site personnel.
Commercial product of Norvir® (RTV), Reyataz® (ATV), and Truvada® (FTC/TDF) will be used 
for the study. Further information regarding storage and handling are available in the 
Prescribing Information for commercial products.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/F/TAF, E/C/F/TAF, E/C/F/TDF and 
ATV+RTV+FTC/TDF
Study drugs GS-9883/F/TAF FDC, E/C/F/TAF, E/C/F/TDF, and ATV+RTV+FTC/TDF will be 
provided by Gilead Sciences.

Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food (n = 200)

Treatment Group 2: Stay on baseline regimen (SBR), including E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF administered orally, once daily, with food (n = 200)
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability. The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return. 
5.4.
Prior and Concomitant Medications
The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following tables and use of herbal/natural supplements are excluded or 
should be used with caution while subjects are participating in the study. Subjects will refrain 
from consumption of grapefruit juice and Seville orange juice throughout participation in the 
study. 


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Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids 
(eg, Tums or Rolaids); the ulcer medication 
sucralfate (Carafate); or vitamin or mineral 
supplements that contain calcium, iron or zinc for 
a minimum of 2 hours before and 6 hours after any 
dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinaccea
Oral Hypoglycemic Agent
Metformin: close monitoring is recommended. 
A dose adjustment of Metformin may be 
necessary. Limit total daily doses of Metformin to 
1000mg either when starting or at study entry.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study. 


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Table 5-2.
Prior and Concomitant Medications (E/C/F/TAF, E/C/F/TDF, and 
ATV+RTV+FTC/TDF Regimens)
Drug Class
Agents Disallowed*
Alpha-1 Adrenoreceptor Antagonist 
Alfuzosin
Antiarrhythmic Agent 
Amiodarone, Dronedarone
Anticonvulsants 
Phenytoin, Carbamazepine and Phenytoin
Antimycobacterials 
Rifampin
Antipsychotics
Lurasidone, Pimozide
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements 
St. John’s Wort
Anticancer drugs
Irinotecana
Ergot Derivatives
Ergotamine, Ergonovine, Dihydroergotamine, Methylergonovine, Ergometrine
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Phosphodiesterase-5 Inhibitors
Sildenafil (for PAH)
Sedatives/Hypnotics 
Midazolam (PO), Triazolam
Calcium Channel Blockers 
Bepridil
Chronic angina 
Ranolazine
a
Applied to ATV regimen only
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Sciences Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead Sciences as soon as he/she is aware of the use of the excluded 
medication.
5.5.
Accountability for Investigational Medicinal Product (IMP)
The investigator is responsible for ensuring adequate accountability of all used and unused IMP. 
This includes acknowledgement of receipt of each shipment of IMP (quantity and condition). All 
used and unused IMP dispensed to subjects must be returned to the site.
Study Drug accountability records will be provided to each study site to:

Record the date received and quantity of IMP kits 

Record the date, subject number, subject initials, the IMP kit number dispensed

Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
Study drug return and disposal will be performed as outlined in Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that subjects are eligible for the study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30 days before Day 1 to determine eligibility for participation in 
the study. The screening visit may coincide with the Week 48 OLE visit or any post-Week 48
OLE visits in study GS-US-236-0128 or the Week 96 visit or any post-Week 96 visits in 
study GS-US-292-0109. The following will be performed and documented at screening: 

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events and prior 
medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (women of childbearing potential only). If the test is positive, the 
subject will not be enrolled
FSH test is required for women who have stopped menstruating for ≥ 12 months but do 
not have documentation of ovarian hormonal failure


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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, amylase (reflex lipase 
testing is performed in subjects with total amylase > 1.5 × ULN), and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
(140 – age in years) (wt in kg)
72 (serum creatinine in mg/dL)
0.85
= CrCL (mL/min)
(140 – age in years) (wt in kg)
72 (serum creatinine in μmol/L)
0.85
0. 6786
CrCL (mL/sec)
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
Plasma HIV-1 RNA 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), 
Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)
The following will be conducted by the central laboratory if the following criteria are met:

If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, 
reflex HBeAb), and quantitative HBsAg

If positive HBcAb with negative HBsAg and negative HBsAb, reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to 
be negative, reflex HBeAb
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed

Review of adverse events and concomitant medications
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30 days after screening for the Day 1 visit. Subjects must continue to take their 
current study treatment regimen up until their scheduled Day 1 visit. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. 
See Section 7 Adverse Events and Toxicity Management for additional details.


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6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
confirmed eligibility before proceeding with the Day 1 visit. The subject must complete all 
study procedures before being administered the study drug:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

12-lead ECG performed supine

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
phosphorus, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing 
is performed in subjects with total amylase > 1.5 × ULN), and TSH
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, 
and triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, 
but the subject must return within 72 hours in a fasted state to draw blood for the 
metabolic assessments.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count


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• 
• 
• 
• 
-
Plasma HIV-1 RNA 
-
CD4+ cell cmmt 
-
Plasma storage samples for safety, virology, or PK testing 
-
Whole blood sample for potential virologic resistance testing and/or HIV DNA 
genotyping 
-
Subjects who meet the definition ofHBV infection at Screening Visit (positive semm 
HBsAg or positive HBcAb with quantifiable HBV DNA), will have plasma HBV DNA 
tested 
PD 
Provide subject dosing diaty to all subjects in Treatment Group 1 
Dispense study dmg 
Subjects in treatment group 1 should be instructed to take study dmgs without regard to food . 
Subjects in treatinent group 2 should be instmcted to take study dmg with food. Subjects are 
required to initiate dosing of study dmgs the day of the Day 1 visit. The subject should be 
counseled regarding the impoliance of adherence and taking their study medications at 
approximately the same time each day as directed by the Investigator. 
6.3. 
Randomization 
Once eligibility has been confinned and prior to or dming the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be perfmmed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedmes have been completed and subject 
eligibility has been confi1med. 
6.4. 
Treatment Assessments (Weeks 4-48) 
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, and 48 unless 
othetwise specified. 
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within± 6 days at Week 24 and Week 36, unless 
othetwise specified. The visit window at Week 48 will be ± 6 weeks of the protocol-specified 
visit date, and these clinical visit windows coincide with the Week 48 statistical analysis window 
for HIV-1 RNA. 
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Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24 and 48) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

12-lead ECG performed supine (Weeks 24 and 48)

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2 microglobulin (Weeks 24 and 48)
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, subjects on 
GS-9883/F/TAF will be discontinued.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN). At 
Weeks 12, 24 and 48, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. At Weeks 24 and 48, TSH will also 
be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24 and 48)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula 
Hematology profile: complete blood count (CBC) with differential and platelet count


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Plasma HIV-1 RNA
CD4+ cell count
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

For subjects who meet the definition of HBV infection, the following will be 
conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) 
and HBeAg (if negative, reflex HBeAb) (Weeks 12, 24 and 48)
HCV RNA for subjects with positive HCVAb at screening. (Weeks 24 and 48)
Plasma storage sample for safety, virology, or PK testing

Pharmacokinetic Blood Collection for all subjects on GS-9883/F/TAF only 
(Treatment Group 1). Details of pharmacokinetic blood sampling procedures and sample 
management will be documented in the study’s laboratory manual.
Single Anytime, Trough and Post-Dose PK Samples: (GS-9883/F/TAF –
Treatment Group 1 only)

Subjects will have a single anytime pre or post-dose PK blood sample at 
Weeks 8, 24 and 36

Observed dosing at the clinic: If possible, subjects will have a trough PK blood 
sample collected between 20-28 hours following the last dose at Weeks 4 and 12.
Subjects must be instructed to not take their study drugs on the morning of their visit 
for the trough sample collection.  Subjects will then take an observed dose of study 
drug at the clinic. If the subject has taken their dose of study drugs prior to the visit, 
the visit may proceed, but the subject must return within 72 hours for the single 
trough PK blood sample collection. In the event a subject routinely takes their study 
drug in the evening, a single anytime sample may be drawn at Weeks 4 and 12 as the 
subject will not be instructed to change their dosing time to accommodate this trough 
PK draw. A single PK blood sample will be collected between 1 and 4 hours post 
dose.  

Dosing diaries will be collected from subjects for the single anytime PK and trough 
PK collection. If a dosing diary is not returned the site may ask the subject for the 
time of the last dose and if it was taken with or without food.

Provide subject dosing diary to all subjects in Treatment Group 1 (Weeks 4, 8, 12 and 24)

Document study drug dispensation and accountability for all study drugs dispensed


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


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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN) TSH will 
be analyzed every 24 weeks.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 Weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

For subjects who meet the definition of HBV infection, the following will be 
conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) 
and HBeAg (if negative, reflex HBeAb) (Every 24 Weeks)
HCV RNA for subjects with positive HCVAb at screening. (Every 24 Weeks)
Plasma storage samples for safety, virology, or PK testing

Subjects who meet the criteria for virologic rebound will be managed according to the 
Management of Virologic Rebound Section 6.13.1

Document study drug dispensation and accountability for all study drugs dispensed.
6.6.
Post-Treatment Assessments
6.6.1.
Early Study Drugs Discontinuation (ESDD) Assessments
If the subject discontinues study drug prior to the Week 48 Visit, the subject will be asked to 
return to the clinic within 72 hours of stopping study drug for the Early Study Drugs 
Discontinuation Visit. The subject will be asked to continue attending the scheduled study visits 
through the Week 48 Visit.


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At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will 
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drugs Discontinuation Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN), and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage samples for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability


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6.6.2.
30 Day Follow Up
Subjects who complete the study through the Week 48 visit and do not continue participation in
the study will be required to return to the clinic 30 days after the completion of study drug for the 
30-Day Follow-Up Visit. 
Subjects who permanently discontinue study drug and refuse to continue in the study through the 
Week 48 visit will be asked to return to the clinic 30 days after the completion of the 
Early Study Drugs Discontinuation Visit for the 30-Day Follow-Up Visit.
Those subjects who permanently discontinue study drug and continue in the study through 
at least one subsequent visit after the Early Study Drug Discontinuation Visit will not be 
required to complete the 30-Day Follow-Up Visit.
Subjects who participate post Week 48 will complete a 30-Day Follow-Up Visit 30 days after 
last dose of study drug.   
For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), 
including weight 

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (women of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count


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Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly 
(or as often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained. 
6.7.
Criteria for Discontinuation of Study Treatment
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator.

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Lack of efficacy 

Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study; refer to Appendix 6

Development of active tuberculosis infection

Discontinuation of the study at the request of Gilead, a regulatory agency or an 
institutional review board or independent ethics committee (IRB/IEC)
6.8.
Other Evaluations
6.8.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include but are not limited to urine albumin, urine creatinine, urine protein, retinol binding 
protein and beta-2-microglobulin at the Day 1 Visit, Weeks 24, 48, and every 24 weeks post 
Week 48. At the conclusion of this study, these samples may be retained in storage by 
Gilead Sciences for a period up to 15 years.


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6.9.
Blood and Urine Storage
A portion of the blood and urine samples drawn at all visits (except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its research partners to help answer questions about the 
study drug, about the disease and its associated conditions and/or to provide additional safety 
data. No human genetic testing will be performed without expressed consent of study subjects. 
At the conclusion of this study, these samples may be retained in storage by Gilead Sciences for 
a period up to 15 years. 
6.10.
Assessments for Premature Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.7, Criteria for Discontinuation of Study Treatment). If 
this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study.
6.11.
End of Study
The end of study will be the last patient’s last observation (or visit). 
6.12.
Post Study Care
After a subject has completed/terminated their participation in the study, long-term care for the 
subject will remain the responsibility of their primary treating physician. 
6.13.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥ 50 copies/mL at study 
drug discontinuation or Week 48.  
6.13.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any post Day 1 visit, a rebound in HIV-1 RNA ≥ 50 copies/mL, which is subsequently
confirmed at the following scheduled or unscheduled visit; 
OR

Any subject with HIV RNA ≥ 50 copies/mL at study drug discontinuation
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥ 200 copies/mL, the 


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


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Figure 6-1.
Virologic Rebound Schema
a
If virologic rebound is not confirmed, the subject will remain on their current regimen.
b
If virologic rebound is confirmed and the HIV-1 RNA is ≥200 copies/mL, the HIV-1 genotype and phenotype 
(reverse transcriptase, protease, and integrase) will be analyzed.
c
Based on the results of the genotype and phenotype assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping fails, a new ARV regimen may be configured at the discretion of the 
Investigator.
d
If no resistance is detected, HIV-1 RNA will be repeated (2-3 weeks later). Investigator reviews study drug 
continuation/discontinuation options and discuss with the Medical Monitor prior to study drug discontinuation.
e
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study. 
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation or 
Week 48
Subjects with HIV-1 RNA ≥ 50 copies/mL at study drug discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 will be 
asked to return for an unscheduled visit within the visit window for a retest. 
Subjects with HIV-1 RNA ≥ 200 copies/mL at study drug discontinuation, last visit or Week 48
will also have resistance testing conducted.  


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


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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to IMP interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 7.5.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to IMP
therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.


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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures, (eg, venipuncture)
7.2.2.
Assessment of Severity
AE severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events.
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): 

All SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30 days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.


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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Drug Safety and Public Health (DSPH) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of study IMP, regardless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period; 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of Study IMP, he/she should promptly document and 
report the event to Gilead DSPH.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
form and submit within 24 hours to:
Gilead DSPH 
contact information:
Fax:
E-mail:
+1 (650) 522-5477
Safety_FC@gilead.com

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.

Additional information may be requested to ensure the timely completion of accurate safety 
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
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax only when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA 
Code of Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant 
updates, and other country-specific legislation or regulations, Gilead may be required to expedite 
to worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU 
Clinical Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide 
regulatory agencies and the relevant IEC in concerned Member States of applicable SUSARs as
outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.5.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 4). 

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results and before investigational medicinal 
product discontinuation, unless such a delay is not consistent with good medical practice

Any questions regarding toxicity management should be directed to the 
Gilead Medical Monitor.
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.


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


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


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7.5.4.2.
Management of Exacerbation of Hepatitis B in Subjects Who Have Discontinued 
Study Medication
If laboratory results indicate (1) an ALT elevation > 2 × Day 1 and > 10 × ULN alone OR 
associated with (2) abnormal laboratory parameters suggestive of worsening hepatic function 
(total bilirubin 2 × Day 1, INR 0.5 above Day 1, provided both are > ULN) and the subject is on 
no post-study therapy for HBV, the following is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally no later than 3 days 
after the initial laboratory values were drawn). During the visit, perform a clinical assessment 
of the subject.

Check the following laboratory parameters: serum ALT and AST, bilirubin, INR, and 
albumin.

If the ALT elevation is confirmed, request the clinical laboratory to conduct reflex testing for 
plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM and HCV. If 
serum HBV DNA is increasing, the investigator should consider immediate initiation of 
approved therapy.

The subject should be followed until laboratory parameters (ALT, total bilirubin, INR) return 
to normal or Day 1 up to a maximum of 6 months after the initial occurrence of the event.
7.5.5.
Management of Hyperbilirubinemia
Most patients taking atazanavir sulfate experience asymptomatic elevations in indirect 
(unconjugated) bilirubin related to inhibition of UDP-glucuronyl transferase (UGT). Hepatic 
transaminase elevations that occur with hyperbilirubinemia should be evaluated for alternative 
etiologies. Dose modification of atazanavir sulfate is not permitted. Subjects who experience 
unacceptable jaundice/scleral icterus can be discontinued from study at the discretion of the 
Investigator.

Subjects with bilirubin levels of 5-10 × ULN, if isolated and not accompanied by 
unacceptable clinical jaundice (scleral icterus or cutaneous jaundice) may continue on study, 
if agreed upon by the subject and the Investigator. All subjects with serum bilirubin levels 
5-10 × ULN must have bilirubin, AST and ALT repeated at least once within 7 days of the 
Investigator being notified of the elevated bilirubin level. Thereafter, serum bilirubin levels 
5-10 × ULN without clinically significant elevation in AST or ALT should be followed 
according to the clinical judgment of the Investigator.

Subjects whose hyperbilirubinemia (5-10 × ULN) is accompanied by ≥ Grade 2 ALT or AST 
elevation or who experience a one Grade worsening in ALT or AST do not qualify as having 
isolated hyperbilirubinemia and will be discontinued.


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
Confirmed hyperbilirubinemia > 10 × ULN will require discontinuation.

Elevation of conjugated (direct) bilirubin > 2 mg/dL in association with Grade 2 ALT or 
AST elevation will require discontinuation.
7.5.6.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose interruption. 
Should the Investigator decide to initiate Hepatitis C treatment the Investigator must contact the 
Gilead Medical Monitor to confirm that no drug-drug interactions are expected. Subjects should 
return to the clinic for scheduled or unscheduled follow up visit(s) according to local medical 
practice for laboratory evaluations. If Hepatitis C treatment is initiated, Investigators should use 
the Gilead provided retest laboratory kits to manage the active Hepatitis C.
7.5.7.
Management of Potential Nephrotoxicity
Estimated glomerular filtration rate according to the Cockcroft-Gault formula (eGFRC-G), will be 
followed post-baseline during the study. All subjects with estimated GFR < 50 mL/min 
(0.83 mL/sec) must have serum creatinine and subject’s weight measured again within 
3 calendar days of receipt of results.
If a subject has confirmed eGFRC-G < 50 mL/min, the Medical Monitor should be notified and 
discontinuation of the study drug should be discussed. For subjects with confirmed eGFRC-G
< 50 mL/min who are not discontinued based on toxicity management procedures above and are 
considered to have stable renal function per Principal Investigator and Medical Monitor, it is not 
mandatory to repeat eGFR assessments within 3 days.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.


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


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7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.6 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is to evaluate the efficacy of switching to a GS-9883/F/TAF
FDC versus staying on baseline regimen (SBR) in virologically suppressed HIV-1 infected 
women as determined by the proportion of subjects with virologic failure 
(HIV-1 RNA ≥50 copies/mL) at Week 48.
The secondary objective of this study is to evaluate the safety, and tolerability of the 
two treatment groups through Week 48.
8.1.2.
Primary Endpoint
The primary efficacy endpoint is the proportion of subjects with virologic failure
(HIV-1 RNA ≥50 copies/mL) at Week 48 as defined by the modified FDA snapshot algorithm.
8.1.3.
Secondary Endpoint
Secondary endpoints include:

The proportion of subjects withHIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.
8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study (2) have received at least 1 dose of 
study drug. Subjects will be grouped according to the treatment to which they were randomized.


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8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug (3) have not committed any major protocol violation, including the violation 
of key entry criteria. Subjects will be grouped according to the treatment they actually received.
Subjects meeting any of the following criteria will be excluded from the Week 48 
PP analysis set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing is due to discontinuation of study drug for lack of efficacy. 

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 5 including drugs not to be used with 
GS-9883, FTC, TAF, EVG, COBI, ATV and RTV.

Non adherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile.
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose of 
GS-9883/F/TAF, and (3) have at least 1 non missing PK concentration data for GS-9883 under 
evaluation reported by the PK lab. 
8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose. Laboratory data that are continuous in nature 
but are less than the lower limit of quantitation or above the upper limit of quantitation will be 
imputed to the value of the lower or upper limit plus or minus one significant digit, respectively 
(e.g., if the result of a continuous laboratory test is < 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (ie, no toxicity grade) for the laboratory abnormality summary.
All available data for subjects that do not complete the study will be included in data listings.


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8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include race, ethnicity, and age. 
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline 
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects with virologic failure 
(HIV-1 RNA ≥50 copies/mL) at Week 48 as defined by the modified FDA snapshot algorithm. 
The primary analysis of the efficacy will be based on the FAS.
8.5.1.1.
Modified FDA Snapshot Algorithm
The modified FDA snapshot algorithm appears below.
The analysis window at Week 48 is defined as from Study Day 294 to Study Day 377, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, including data collected up to 1 day after the last 
dose date of study drug) will be used in the snapshot algorithm. Virologic outcome will be 
defined as the following categories: 

Virologic Success: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window 

Virologic Failure: this include subjects 
a) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window, or 
b) Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and 
1) Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or 
2) Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than lack of efficacy and have the last available on-treatment 
HIV-1 RNA ≥ 50 copies/mL  


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
No Virologic Data in the Week 48 Analysis Window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following: 
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL or,
b) Missing data during the window but on study drug 
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects with virologic failure 
(HIV-1 RNA ≥50 copies/mL) at Week 48 in the GS-9883/F/TAF group is at least 4% higher
than the virologic failure rate in the SBR group; the alternative hypothesis is that the virologic 
failure rate in the GS-9883/F/TAF group is less than 4% higher than that in the SBR group.
Non-inferiority will be assessed using the conventional confidence interval (CI) approach. The 
point estimate of treatment difference (GS-9883/F/TAF – SBR) and the associated 2-sided 
95% CI will be constructed based on the exact method.  
It will be concluded that GS-9883/F/TAF is non-inferior to E/C/F/TAF if the upper bound of the 
2-sided 95% CI of the difference between treatment groups (GS-9883/F/TAF – SBR) in the 
virologic failure rate is less than 4% (ie, a margin of 4% is applied to non-inferiority assessment).
If non-inferiority of GS-9883/F/TAF to SBRis established, the upper bound of the 95% CI will 
be compared to 0; if the upper bound of the 95% CI is less than 0, superiority of GS-9883/F/TAF
over SBR will be established.
8.5.2.
Secondary Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the
US FDA snapshot algorithm will also be evaluated. The 95% CIs will be constructed in the same 
manner as for the primary efficacy endpoint. However, non-inferiority will be assessed using a 
margin of 10%. It will be concluded that GS-9883/F/TAF is non- inferior to SBRif the lower 
bound of the 2-sided 95% CI of the difference between treatment groups (GS-9883/F/TAF - SBR) 
in the response rate is greater than −10%.
The changes from baseline in CD4+ cell count at Week 48 will be summarized by treatment 
using descriptive statistics. The differences in changes from baseline in CD4+ cell count between 
the 2 treatment groups and the associated 95% CIs will be constructed using ANOVA models, 
including treatment (GS-9883/F/TAF vs. SBR) as a fixed effect in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.


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8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise, will be summarized 
for subjects in the safety analysis set according to the study drug received.
Data for the pretreatment period and the period post the date of last dose of study drug plus 
30 days will be included in data listings for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug
administration page in eCRF. Exposure data will be summarized by treatment.
Duration of exposure to study drug will be expressed as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration and summarized by treatment.
Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study drug start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illnesses definition of 
an AIDS-Defining Diagnosis will be listed.  
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.


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8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum post baseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the PK analyses, the pharmacokinetics of GS-9883 may be evaluated using descriptive 
statistics or population approaches.
TAF and FTC concentrations may be analyzed as applicable.  
8.8.
Sample Size
A total of approximately 400 HIV-1 infected subjects, randomized in a 1:1 ratio to 
2 treatment groups (200 subjects per treatment group), achieves at least 80% power to detect a 
non-inferiority margin of 4% in Week 48 virologic failure rate (HIV-1 RNA ≥50 copies/mL) 
difference between the 2 treatment groups. For the sample size and power computation, it is 
assumed that both treatment groups have a virologic failure rate of 2% (based on the historical 
Gilead E/C/F/TAF and STB studies), that the non-inferiority margin is 4%, and that the 
significance level of the test is at a one-sided 0.025 level.
8.9.
Independent Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after all 
subjects enrolled complete Week 24 of the study or prematurely discontinue the study drug. 
However, Gilead will defer to the IDMC for any decision to convene earlier or more frequently. 
The IDMC will examine the safety results of the trial and also focus on logistical issues such as 
accrual, retention, quality of clinical and laboratory data, and implications of results of external 
studies.


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No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
An analysis for the Week 24 IDMC meeting will be conducted after the last subjects enrolled 
completes Week 24 of the study. For each IDMC analysis performed prior to analysis for the 
primary efficacy endpoint, an alpha penalty of 0.00001 will be applied for the primary analysis 
of the primary efficacy endpoint.


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


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


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


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responding to the queries in a timely manner, within the system, either by confirming the data as 
correct or updating the original entry, and providing the reason for the update 
(e.g. data entry error). Original entries as well as any changes to data fields will be stored in the 
audit trail of the system. Prior to any interim time points or database lock (as instructed by 
Gilead), the investigator will use his/her log in credentials to confirm that the forms have been 
reviewed, and that the entries accurately reflect the information in the source documents. At the 
conclusion of the trial, Gilead will provide the site with a read-only archive copy of the data 
entered by that site. This archive must be stored in accordance with the records retention 
requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. If 
return is not possible, the study monitor will evaluate each study center’s IMP disposal
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files. 
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP 
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs/IECs or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.


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


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


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10.
REFERENCES
2202
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum 
creatinine. Nephron 1976;16:31-41.
5125
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. 
Changing patterns of mortality across Europe in patients infected with HIV-1. 
Lancet 1998;352 (9142):1725-30.
8284
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term 
effectiveness of potent antiretroviral therapy in preventing AIDS and death: a 
prospective cohort study. Lancet 2005;366 (9483):378-84.
13585
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. 
Revised surveillance case definitions for HIV infection among adults, 
adolescents, and children aged <18 months and for HIV infection and AIDS 
among children aged 18 months to <13 years--United States, 2008. MMWR 
Recomm Rep 2008;57 (RR-10):1-12.
21053
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported 
adherence supports patient preference for the single tablet regimen (STR) in the 
current cART era. Patient preference and adherence 2012;6:427-33.
27881
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. 
Declining Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
29702
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a 
difference? Curr Med Res Opin 2013;30 (1):89-97.
29705
Costagliola D. Demographics of HIV and aging. Curr Opin HIV AIDS 2014;9 
(4):294-301.
34898
Department for Health and Human Services (DHHS). Guidelines for the Use of 
Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Developed by 
the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A 
Working Group of the Office of AIDS Research Advisory Council (OARAC). 
Downloaded from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 
08 April, 2015.
36201
The Joint United Nations Programme oHAU. Fact Sheet: 2014 Global Statistics. 
Available at: 
http://www.unaids.org/sites/default/files/media_asset/20150714_FS_MDG6_Rep
ort_en.pdf.  2014.


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


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Appendix l. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Switching to a 
Fixed Dose Combination (FDC) ofGS-9883/Emnicitabine/Tenofovir Alafenamide 
(GS-9883/F/T AF) from Elvitegravir/Cobicistat/Emtricitabineffenofovir Alafenamide 
(6/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabinerrenofovir Disoproxi l Fumarate (E/C/F!T DF) 
or Atazanavir + Ritonavir + Emtricitabineffenofovir Disoproxil Fumarate 
(ATV+RTV+FTCffDF) in Virologically Suppressed HIV-1 infected Women 
GS-US-380-1961, Original, 20 Novembea· 2015 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
ppo--------------
Huyen Cao, MD (Printed) 
Author 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary details 
for me and my staff to conduct this study as described. 1 will conduct this study as outlined herein 
and wil1 make a reasonable eff01t to complete the study within the time designated. 
1 will provide aJl study personnel under my supervision copies of the protocol and access to all 
infonnation provided by Gilead Sciences, Inc. 1 will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
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Appendix 2.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48d,v
30 Day 
Follow-Upe
ESDDf
4
8
12
24
36
48
Every 12 Weeks
Informed Consent
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam 
X
X
X
X
X
Symptom-Directed Physical Exam
X
X
X
X
X
X
12-Lead ECG 
X
X
X
X
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Chemistryh
X
X
X
Xw
Urine Pregnancy Testi
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testi
X
Chemistry Profilej
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentsk
X
X
X
X
Xw
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilel
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAm
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Planeln
X


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Study Procedure 
Plasma HBV DNA
0 
HCVAb" 
HCVRNAP 
HIV -1 Genotype/Phenotype q 
Single PK Draw 
Trough PK Draw• 
PK Sample (post-dose)' 
Observed In-Clinic Dose• 
Provide Dosing Diatyu 
Collect Dosing DiarY' 
Plasma Sample Storage
1 
Urine Sample Storage
1 
Whole Blood Storage Sample
1 
~PD 
n 
I 
Randomization 
Study Drug Dispensation 
Study Drug Accountability 
Sc.reening• 
X 
X 
I 
a 
Evaluations to be completed within 30 days prior to Day 1. 
Day lb 
4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b 
Subjects should initiate dosing of study dmg on the same day as the Day 1 visit. 
8 
X 
X 
X 
X 
X 
X 
X 
End ofWeE'kc 
12 
24 
36 
48 
X 
X 
X 
X 
X 
~ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
xv 
X 
X 
X 
X 
Post Week 48d,v 
Every 12 Weeks 
xw 
xw 
X 
X 
xv 
X 
30Day 
Follow-up• 
Final 
Original 
ESDDr 
X 
xq 
X 
X 
X 
c 
All study visits should be± 2 days of the protocol-specified visit date based on the Day 1 visit through We.ek 12 and completed \.,'ithin ± 6 days at We.ek 24 and Week 36, 
lmless othetwise specified. The visit window at Week 48 will be± 6 weeks of the protocol-specified visit date. 
d 
At the Week 48 Visit, subjects in a cmmtry where GS-9883/F/TAF FDC is not available will be given the option to receive GS-9883/F/T AF FDC for an additional48 weeks, 
or until the product becomes accessible to subjects through an access program, or lmtil Gilead Sciences elects to discontinue the study in that cmmtry, whichever occm-s first. 
Study visits are to be completed every 12 weeks, within± 6 days of the protocol-spe.cified visit date lmless otherwise specified. 
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e 
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30-Day Follow-Up Visit, a± 6 days window may be used. Required for subjects 
who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Subjects who participate 
post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit. 
f 
Early Study Drug Discontinuation visit to occur within 72 hours oflast dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Week 48 Visit even if the subject discontinues study drug. 
g 
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature 
h 
Urine Chemistry includes urine albumin, urine creatinine, urine protein, retinol binding protein, and beta-2 microglobulin 
Women of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test. 
Chemistry profile: alkaline phosphatase, AST, AL T, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing is performed in subjects with total amylase > 1.5 x ULN). At Day 1, 
Weeks 24, and 48 and every 24 weeks during the post Week 48 period, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of the 
chemistry profile. TSH will be collected at Screening, Day 1, Weeks 24, and 48, as well as every 24 weeks post Week 48, and ESDD if applicable. 
k 
Fasting glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the subject must 
return within 72 hours in a fasted state to draw blood for the metabolic assessments. 
CBC with differential and platelet count. 
m 
If the HIV-1 RNA value is 2: 50 copies/mL at Week 48, a retest HIV -1 RNA value must be collected within two to three weeks of the initial test. 
n 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb). 
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex HBeAb), and quantitative HBsAg. If positive HBcAb with negative HBsAg and negative 
HBsAb, reflex testing for plasma HB V DNA (if positive, reflex HBeAg). If HBeAg is performed and found to be negative, reflex HBeAb. 
o 
For subjects who meet the definition ofHBV infection, the following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) and HBeAg 
(if negative, reflex HBeAb) at Days 1, 12, 24 and then every 24 weeks. 
p 
Subjects who are HCVAb positive will have a HCV RNA test performed at screening and every 24 weeks. 
q 
HIV-1 genotype/phenotype testing for subjects with HIV-1 RNA 2: 200 copies/mL and virologic rebound, at early study drug discontinuation or Week 48. Following 
unconfirmed virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to the next scheduled visit or at the next scheduled study visit, for a 
HIV-1 RNA and HIV-1 genotype/phenotype (reverse transcriptase, protease and integrase) blood draw. Based on the results of this testing, subjects should be managed 
according to the Virologic Rebound Schema (Section 6.13. 1 ). 
r 
All subjects on GS-9883/FfrAF (Treatment Group 1 only) will have a single anytime PK blood sample collected at Weeks 8, 24 and 36. 
s 
Subjects on GS-9883/FfrAF (Treatment Group 1 only) will have a Trough PK blood sample collected between 20-28 hours following their last dose at Weeks 4 and 12. 
Subjects must be instructed to not take their study drugs on the morning of their visit for the trough sample collection. If the subject has taken their dose of study drugs prior 
to the visit, the visit may proceed, but the subject must return within 72 hours for the single trough PK blood sample collection. In the event a subject routinely takes their 
study drug in the evening, a single anytime sample may be drawn at Weeks 4 and 12 as the subject will not be instructed to change their dosing time to accommodate this 
trough PK draw. A post-dose PK blood sample will be collected between 1 and 4 hours post dose following an observed, in-clinic dose. 
Plasma storage samples banked for possible future protocol-related testing (safety, virology, pharmacokinetic analysis). Urine storage samples banked for ossible future 
IJrotocol-related safety testi11g includi11g urine chernist:ry. Whole blood sampl:::::.Jotential virologic resistance testing and/or HIV DNA genotyping . .__P_D _____ ___. 
u 
A dos1ng diary will be dispensed for all Treatment Group 1 sUDJects to complete pnor to each of the PK sample visits. 
v 
Open-label GS-9883/F/T AF FDC will be dispensed to subjects participating in the study post Week 48 starting at the Week 48 Visit. 
w 
Every 24 weeks only. 
x 
Dosing diaries will be collected from subjects for the single anytime PK and trough PK collection (Treatment Group 1 only). If a dosing diary is not returned the site may ask 
the subject for the time of the last dose and if it was taken with or without food. 
CONFIDENTIAL 
Page 92 
20November 2015 


GS-9883/F/TAF 
Protocol GS-US-380-1961 
Final 
Gilead Sciences, Inc. 
Original 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
Grade I 
~-----G_r_a_d_e_2----~~ 
~
~ ______ G_r_a_de-3------~~ ~
~ __________ G_m_d_e_4--------~ 
! 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
If confirmed and possibly and/or probably related to investigational 
medicinal products: 
1. 
Withhold investigational medicinal products until ::; Grade 2 
2. 
Restart all investigational medicinal products at full dose 
l 
If Grade 3 or 4 recurrence that is con tinned and possibly or probably 
related to investigational medicinal products, discontinue a11 
investigational medicinal products dosing permanently 
Repeat lab to 
confirm toxicity 
grade 
1 
1 
lfc 
elated to 
inve 
dicinal products, 
onfrrmed and unr 
stigationalme 
ng may contin 
he investigator 
dosi 
ue at the discretion 
oft 
If confirmed and 
possibly or probably 
I-+ related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
Page 93 
20 November 2015 


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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 95
20 November 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects. Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.  


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 96
20 November 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 97
20 November 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL                       
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL              
1.74 to <1.94 mmolL
6.1 to  <7.0 mg/dL                    
1.51 to < 1.74 mmolL
< 6.1 mg/dL                           
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 98
20 November 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (corrected for 
albumin if appropriate*)
Adult and Pediatric 7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to  <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63  to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to <LLN mg/dL
1.12 to <LLN mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 99
20 November 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyperbilirubinemia 
Adult and Pediatric > 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 100
20 November 2015
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L
LDL (Fasting)
Adult
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
LDL (Fasting)
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to  4.92 mmol/L
>4.92 mmol/L
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects > 70 yrs. Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.  


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 101
20 November 2015
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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Original
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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.
Original
CONFIDENTIAL
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20 November 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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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20 November 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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Final
Gilead Sciences, Inc.
Original
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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-380-1961
Final
Gilead Sciences, Inc.
Original
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20 November 2015
SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by study 
participant or  caregiver (for 
disabled adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or 
morbilliform rash with 
vesicles or limited number of 
bullae OR Superficial 
ulcerations of mucous 
membrane limited to one site
Extensive or generalized 
bullous lesions OR Stevens-
Johnson syndrome OR 
Ulceration of mucous 
membrane involving two or 
more distinct mucosal sites 
OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 107
20 November 2015
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Anorexia
Loss of appetite without 
decreased oral intake
Loss of appetite associated 
with decreased oral intake 
without significant weight 
loss 
Loss of appetite associated 
with significant weight loss 
Life-threatening 
consequences OR 
Aggressive intervention 
indicated [eg, tube feeding or 
total parenteral nutrition]
Ascites
Asymptomatic
Symptomatic AND 
Intervention indicated (eg, 
diuretics or therapeutic 
paracentesis)
Symptomatic despite 
intervention
Life-threatening 
consequences
Cholecystitis
NA
Symptomatic AND Medical 
intervention indicated
Radiologic, endoscopic, or 
operative intervention 
indicated
Life-threatening 
consequences (eg, sepsis or 
perforation) 
Constipation 
NA
Persistent constipation 
requiring regular use of 
dietary modifications, 
laxatives, or enemas 
Obstipation with manual 
evacuation indicated
Life-threatening 
consequences (eg, 
obstruction)
Diarrhea 
Adult and Pediatric 1 Year
Transient or intermittent 
episodes of unformed stools 
OR Increase of 3 stools 
over baseline/24 hr
Persistent episodes of 
unformed to watery stools 
OR Increase of 4–6 stools 
over baseline per 24 hrs. 
Bloody diarrhea OR Increase 
of 7 stools per 24-hour 
period OR IV fluid 
replacement indicated
Life-threatening 
consequences (eg, 
hypotensive shock)
Pediatric 1 Year
Liquid stools (more 
unformed than usual) but 
usual number of stools
Liquid stools with increased 
number of stools OR Mild 
dehydration
Liquid stools with moderate 
dehydration
Liquid stools resulting in 
severe dehydration with 
aggressive rehydration 
indicated OR Hypotensive 
shock


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 108
20 November 2015
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Dysphagia-Odynophagia 
Symptomatic but able to eat 
usual diet
Symptoms causing altered 
dietary intake without 
medical intervention 
indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention 
indicated
Life-threatening reduction in 
oral intake
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, Dysphagia-
Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal 
bleeding OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 24–
48 hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening 
consequences (eg, 
hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening 
consequences (eg, sepsis, 
circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ Stomatitis 
for Clinical Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities OR 
Medical intervention 
indicated 
Symptoms causing inability 
to perform usual social/ 
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences (eg, 
perforation)
Vomiting
Transient or intermittent 
vomiting with no or minimal 
interference with oral intake
Frequent episodes of 
vomiting with no or mild 
dehydration
Persistent vomiting resulting 
in orthostatic hypotension 
OR Aggressive rehydration 
indicated
Life-threatening 
consequences (eg, 
hypotensive shock)


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Protocol GS-US-380-1961
Final
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Original
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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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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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
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 111
20 November 2015
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Seizure: (pre-existing) 
For Worsening of Existing 
Epilepsy the Grades Should Be 
Based on an Increase from 
Previous Level of Control to 
Any of These Levels
NA
Increased frequency of pre-
existing seizures (non-
repetitive) without change in 
seizure character OR 
infrequent breakthrough 
seizures while on stable 
meds in a previously 
controlled seizure disorder
Change in seizure character 
from baseline either in 
duration or quality (eg, 
severity or focality) 
Seizures of any kind that are 
prolonged, repetitive (eg, 
status epilepticus), or 
difficult to control (eg, 
refractory epilepsy)
Seizure 
– Pediatric 18 Years
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
< 5 minutes with < 24 hours 
post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 5–20 
minutes with 
< 24 hours post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
> 20 minutes 
Seizure, generalized onset 
with or without secondary 
generalization, requiring 
intubation and sedation
Syncope (not associated with a 
procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no or 
minimal interference with 
usual social & functional 
activities
Vertigo causing greater than 
minimal interference with 
usual social & functional 
activities 
Vertigo causing inability to 
perform usual social & 
functional activities
Disabling vertigo causing 
inability to perform basic 
self-care functions


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
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Original
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20 November 2015
MUSCULOSKELETAL
Grade 1
Grade 2
Grade 3
Grade 4
Arthralgia
See also Arthritis
Joint pain causing no or 
minimal interference with 
usual social & functional 
activities
Joint pain causing greater 
than minimal interference 
with usual social & 
functional activities
Joint pain causing inability to 
perform usual social & 
functional activities
Disabling joint pain causing 
inability to perform basic 
self-care functions
Arthritis
See also Arthralgia
Stiffness or joint swelling 
causing no or minimal 
interference with usual social 
& functional activities
Stiffness or joint swelling 
causing greater than minimal 
interference with usual social 
& functional activities
Stiffness or joint swelling 
causing inability to perform 
usual social & functional 
activities
Disabling joint stiffness or 
swelling causing inability to 
perform basic self-care 
functions
Bone Mineral Loss
BMD t-score or z-score
–2.5 to –1.0 
BMD t-score or z-score
–2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening 
consequences 
Pediatric 21 Years
BMD z-score 
–2.5 to –1.0
BMD z-score < –2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening 
consequences 
Myalgia
(non-injection site)
Muscle pain causing no or 
minimal interference with 
usual social & functional 
activities
Muscle pain causing greater 
than minimal interference 
with usual social & 
functional activities
Muscle pain causing inability 
to perform usual social & 
functional activities
Disabling muscle pain 
causing inability to perform 
basic self-care functions
Osteonecrosis
NA
Asymptomatic with 
radiographic findings AND 
No operative intervention 
indicated
Symptomatic bone pain with 
radiographic findings OR 
Operative intervention 
indicated
Disabling bone pain with 
radiographic findings 
causing inability to perform 
basic self-care functions


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 113
20 November 2015
SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Acute Systemic Allergic 
Reaction 
Localized urticaria (wheals) 
with no medical intervention 
indicated
Localized urticaria with 
medical intervention 
indicated OR Mild 
angioedema with no medical 
intervention indicated
Generalized urticaria OR 
Angioedema with medical 
intervention indicated OR 
Symptomatic mild 
bronchospasm
Acute anaphylaxis OR Life-
threatening bronchospasm 
OR laryngeal edema
Chills
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities 
Symptoms causing inability 
to perform usual social & 
functional activities
NA
Fatigue
Malaise
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities
Symptoms causing inability 
to perform usual social & 
functional activities
Incapacitating 
fatigue/malaise symptoms 
causing inability to perform 
basic self-care functions
Fever (nonaxillary)
37.7C to 38.6C
99.8F to 101.5F
38.7C to 39.3C
101.6F to 102.8F
39.4C to 40.5C
102.9F to 104.9F
40.5C 
104.9F
Pain- Indicate Body Site
See also Injection Site Pain, 
Headache, Arthralgia, and 
Myalgia
Pain causing no or minimal 
interference with usual social 
& functional activities
Pain causing greater than 
minimal interference with 
usual social & functional 
activities
Pain causing inability to 
perform usual social & 
functional activities
Disabling pain causing 
inability to perform basic 
self-care functions OR 
Hospitalization (other than 
ER visit) indicated
Unintentional Weight Loss
NA
5% to 9% loss in body 
weight from baseline
10% to 19% loss in body 
weight from baseline
20% loss in body weight 
from baseline OR  
Aggressive intervention 
indicated [eg, tube feeding or 
total parenteral nutrition]


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


GS-9883/F/TAF
Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
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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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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 117
20 November 2015
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV 
(CDC Guidelines)
1) Candidiasis of bronchi, trachea, or lungs
2) Candidiasis of esophagus
3) Cervical cancer, invasive
4) Coccidioidomycosis, disseminated or extrapulmonary
5) Cryptococcosis, extrapulmonary
6) Cryptosporidiosis, chronic intestinal (> 1 month duration)
7) Cytomegalovirus disease (other than liver, spleen or nodes)
8) Cytomegalovirus retinitis (with loss of vision)
9) Encephalopathy, HIV-related
10) Herpes simplex: chronic ulcer(s) (> 1 month duration); or bronchitis, pneumonitis or 
esophagitis
11) Histoplasmosis, disseminated or extrapulmonary
12) Isosporiasis, chronic intestinal (> 1 month duration)
13) Kaposi’s sarcoma
14) Lymphoma, Burkitt’s (or equivalent term)
15) Lymphoma, immunoblastic (or equivalent term)
16) Lymphoma, primary, of brain
17) Mycobacterium avium complex or Myobacterium kansasii, disseminated or extrapulmonary
18) Mycobacterium tuberculosis, of any site,  pulmonary, disseminated or extrapulmonary
19) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
20) Pneumocystis jirovecii (previously known as “Pneumocystis carinii) pneumonia
21) Pneumonia, recurrent
22) Progressive multifocal leukoencephalopathy


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Original
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23) Salmonella septicemia, recurrent
24) Toxoplasmosis of brain
25) Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection −2014 {13585}


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Protocol GS-US-380-1961
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 119
20 November 2015
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Females are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, females of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
2) Contraception Requirements for Women
a. Study Drug Effects on Pregnancy and Hormonal Contraception
The data on GS-9883/F/TAF in pregnant women is limited or not available. There is no 
suspicion of human teratogenicity based on class effects or genotoxic potential. Relevant 
non-clinical reproductive studies for human pregnancy do not indicate a strong suspicion of 
human teratogenicity/fetotoxicity. Data from clinical pharmacokinetic interaction studies of 
GS-9883 and F/TAF have demonstrated that there is no reduction in the clinical efficacy of 
hormonal contraception or that the effect on hormonal contraception is insignificant. Please refer 
to the latest version of the GS-9883/F/TAF investigator’s brochure and the latest versions of the 
E/C/F/TAF, E/C/F/TDF, ATV, RTV and FTC/TDF package inserts or investigator’s brochures
for additional information.  
b. Contraception Requirements for Women of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Day 1 visit prior to randomization. At a minimum a pregnancy 
test will be performed at the end of relevant systemic exposure. In the event of a delayed 
menstrual period (over one month between menstruations), a pregnancy test must be performed 
to rule out pregnancy. This is true even for women of childbearing potential with infrequent or 
irregular periods. Female subjects must agree to one of the following from Screening until 
30 days following the end of relevant systemic exposure.


GS-9883/F/TAF
Protocol GS-US-380-1961
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Gilead Sciences, Inc.
Original
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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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Protocol GS-US-380-1961
Final
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Original
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3) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM). Female condom and male condom should not be used 
together.
4) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator immediately. The investigator will counsel the subject regarding 
pregnancy management options. Counseling will be provided regarding alternative anti-HIV 
treatment. Information on the risks and benefits of antiretroviral therapies will be discussed, 
including the risk of ongoing fetal exposure to the study drug versus the new alternative therapy 
and the risk of discontinuing maternal therapy.
If the subject is on GS-9883/F/TAF, they must discontinue study drug immediately. Subjects 
may be allowed to continue on study drug if they are taking E/C/F/TAF, E/C/F/TDF or 
ATV+RTV+FTC/TDF and an additional informed consent will be required.
If the subject elects to discontinue study drugs but remain in the study, a new ARV regimen will 
be constructed at the Investigator’s discretion. 
The Investigator should counsel the subject on the need to inform the study site of the outcome 
of the pregnancy. Information collected will include gestational dating, ultrasound report, records 
of maternal, fetal complications and pregnancy outcome. 
Instructions for reporting pregnancy and pregnancy outcome are outlined in Section 7.6.