Conditions: HIV-1-infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 567
Healthy volunteers: no

Brief summary:
The primary objective of this study is to evaluate the efficacy of switching from a regimen of either dolutegravir (DTG) and emtricitabine /tenofovir alafenamide (F/TAF) or DTG and emtricitabine/tenofovir disoproxil fumarate (F/TDF) to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus DTG+F/TAF in virologically suppressed HIV-1 infected adults with or without antiretroviral (ARV) resistance.

Detailed description:

Arms:
arm 1: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) tablet + dolutegravir (DTG) placebo tablet + emtricitabine/tenofovir alafenamide (F/TAF) placebo tablet administered without regard to food for at least 48 weeks. arm 2: DTG 50 mg tablet + F/TAF FDC tablet + B/F/TAF placebo tablet administered without regard to food for at least 48 weeks. arm 3: Participants who received B/F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. arm 4: Participants who received DTG + F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase.

Interventions: intervention 1: B/F/TAF intervention 2: F/TAF intervention 3: DTG intervention 4: DTG Placebo intervention 5: F/TAF Placebo intervention 6: B/F/TAF Placebo
Intervention descriptions: intervention 1: 50/200/25 mg FDC tablet(s) administered orally once daily intervention 2: 200/25 mg FDC tablet(s) administered orally once daily intervention 3: 50 mg tablet(s) administered orally once daily intervention 4: Tablet(s) administered orally once daily intervention 5: Tablet(s) administered orally once daily intervention 6: Tablet(s) administered orally once daily

Protocol document:
SAP_002.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the 
Safety and Efficacy of Switching from a Regimen of Dolutegravir 
and Either Emtricitabine/Tenofovir Alafenamide or 
Emtricitabine/Tenofovir Disoproxil Fumarate to a Fixed Dose 
Combination of Bictegravir/ Emtricitabine/Tenofovir Alafenamide 
in HIV-1 Infected Subjects who are Virologically Suppressed
Name of Test Drug:
Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF; GS-9883/F/TAF)
Study Number:
GS-US-380-4030
Protocol Version (Date):
Amendment 2 (28 June 2018)
Analysis Type:
Final Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
30 April 2021
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
 
 
PPD


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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 ...........................................................................................................................10
1.4.
Actual Sample Size and Power................................................................................................................10
2.
TYPE OF PLANNED ANALYSIS......................................................................................................................11
2.1.
Data Monitoring Committee Analyses....................................................................................................11
2.2.
Interim Analyses......................................................................................................................................11
2.2.1.
Week 48 Analysis..................................................................................................................11
2.3.
Final Analysis..........................................................................................................................................11
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................12
3.1.
Analysis Sets ...........................................................................................................................................13
3.1.1.
Analysis Sets Used for the Randomized Phase Analysis ......................................................13
3.1.2.
Analysis Set Used for the All B/F/TAF Analysis .................................................................15
3.2.
Subject Grouping.....................................................................................................................................16
3.3.
Strata and Covariates...............................................................................................................................16
3.4.
Examination of Subject Subgroups .........................................................................................................17
3.4.1.
Subject Subgroups for Efficacy Analyses .............................................................................17
3.4.2.
Subject Subgroups for Safety Analyses ................................................................................17
3.5.
Multiple Comparisons .............................................................................................................................18
3.6.
Missing Data and Outliers.......................................................................................................................18
3.6.1.
Missing Data..........................................................................................................................18
3.6.2.
Outliers ..................................................................................................................................19
3.7.
Data Handling Conventions and Transformations ..................................................................................19
3.8.
Analysis Windows...................................................................................................................................19
3.8.1.
Definition of Study Day ........................................................................................................19
3.8.2.
Analysis Windows.................................................................................................................20
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window .................................................................................................................................23
4.
SUBJECT DISPOSITION ...................................................................................................................................25
4.1.
Subject Enrollment and Disposition........................................................................................................25
4.1.1.
Subject Enrollment ................................................................................................................25
4.1.2.
Subject Disposition................................................................................................................25
4.2.
Extent of Study Drug Exposure and Adherence......................................................................................26
4.2.1.
Duration of Exposure to Study Drug.....................................................................................26
4.2.2.
Adherence to Study Drug Regimen.......................................................................................27
4.3.
Protocol Deviations .................................................................................................................................28
4.4.
Missing Protocol-Specified Information due to COVID-19 ...................................................................28
5.
BASELINE CHARACTERISTICS .....................................................................................................................29
5.1.
Demographics and Baseline Characteristics ...........................................................................................29
5.2.
Baseline Disease Characteristics .............................................................................................................29
5.3.
Medical History.......................................................................................................................................30


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6.
EFFICACY ANALYSES.....................................................................................................................................31
6.1.
Efficacy Analysis for Randomized Phase Analysis ................................................................................31
6.1.1.
Primary Efficacy Endpoint....................................................................................................31
6.1.2.
Secondary Efficacy Endpoints ..............................................................................................33
6.2.
Efficacy Analysis for All B/F/TAF Analysis ..........................................................................................37
6.2.1.
Definition of the Efficacy Endpoint ......................................................................................37
6.2.2.
Analysis of the Efficacy Endpoints for All B/F/TAF Analysis.............................................37
6.3.
Changes From Protocol-Specified Efficacy Analyses ............................................................................38
7.
SAFETY ANALYSES.........................................................................................................................................39
7.1.
Adverse Events and Deaths.....................................................................................................................39
7.1.1.
Adverse Event Dictionary .....................................................................................................39
7.1.2.
Adverse Event Severity .........................................................................................................39
7.1.3.
Relationship of Adverse Events to Study Drug.....................................................................39
7.1.4.
Serious Adverse Events.........................................................................................................39
7.1.5.
Treatment-Emergent Adverse Events....................................................................................40
7.1.6.
Summaries of Adverse Events and Death .............................................................................40
7.1.7.
Additional Analysis of Adverse Events ................................................................................42
7.2.
Laboratory Evaluations ...........................................................................................................................43
7.2.1.
Summaries of Numeric Laboratory Results ..........................................................................43
7.2.2.
Graded Laboratory Values ....................................................................................................44
7.2.3.
Metabolic Laboratory Evaluations ........................................................................................45
7.2.4.
Liver-Related Laboratory Evaluations ..................................................................................46
7.2.5.
Renal-Related Laboratory Evaluations..................................................................................47
7.3.
Body Weight, Height, and Vital Signs ....................................................................................................47
7.4.
Prior and Concomitant Medications........................................................................................................48
7.4.1.
Nonstudy Drug Antiretroviral Medications...........................................................................48
7.4.2.
Concomitant Non-ARV Medications....................................................................................48
7.5.
Electrocardiogram Results.......................................................................................................................49
7.6.
Other Safety Measures ............................................................................................................................49
7.7.
Subject Subgroup for Safety Endpoints ..................................................................................................49
7.8.
Changes From Protocol-Specified Safety Analyses................................................................................49
8.
SPECIAL POPULATION ANALYSES..............................................................................................................50
8.1.
Analyses for HIV/HBV Coinfected Subjects..........................................................................................50
8.2.
Analyses for HIV/HCV Coinfected Subjects..........................................................................................51
9.
REFERENCES.....................................................................................................................................................53
10.
SOFTWARE.........................................................................................................................................................54
11.
SAP REVISION...................................................................................................................................................55
12.
APPENDICES......................................................................................................................................................56
Appendix 1.
Study Procedures Table...........................................................................................................57
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial)..................................60
Appendix 3.
Region Definition ....................................................................................................................61
Appendix 4.
COVID-19 related Adverse Events .........................................................................................62
Appendix 5.
Cardiovascular or Cerebrovascular Events..............................................................................63
Appendix 6.
Hepatic Events.........................................................................................................................64
Appendix 7.
Determining Missing and Virtual Visits Due to COVID-19...................................................65
Appendix 8.
Programming Specification .....................................................................................................68
CCI


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LIST OF IN-TEXT TABLES
Table 1.
Subjects Excluded from Week 48 Per Protocol Analysis Set Due to Premature 
Discontinuation of blinded Study Drug and/or Missing HIV-1 RNA Assessment in 
Week 48 Analysis Window .....................................................................................................14
Table 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 for Randomized Phase Analysis .......................................21
Table 3.
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 for All B/F/TAF Analysis .................................................21
Table 4.
Analysis Windows for Metabolic Assessments for Randomized Phase Analysis ..................22
Table5.
Analysis Windows for Metabolic Assessments for all B/F/TAF Analysis .............................22
Table 6.
Analysis Windows for HBV and HCV Serology and HCV RNA Assessments for 
Randomized Phase Analysis....................................................................................................23
Table 7.
Analysis Windows for HBV and HCV Serology, and HCV RNA Assessments for 
all B/F/TAF Analysis...............................................................................................................23


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LIST OF ABBREVIATIONS
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARV
antiretroviral
ART
antiretroviral treatment
AST
aspartate aminotransferase
BIC
bictegravir
B/F/TAF
fixed dose combination of bictegravir (BIC; B) 50 mg / emtricitabine (FTC; F) 200 mg / 
tenofovir alafenamide (TAF) 25 mg
BMI
body mass index
CDER
Center for Drug Evaluation and Research
CI
confidence interval
CMH
Cochran-Mantel-Haenszel 
CRF
case report form
DC
premature study drug discontinuation
DNA
deoxyribonucleic acid
DTG
dolutegravir, tivicay
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
F/TAF
fixed dose combination of emtricitabine (FTC; F)/ tenofovir alafenamide (TAF)
FTC, F
emtricitabine
GFR
glomerular filtration rate
Gilead
Gilead Sciences, Inc.
GS-9883
bictegravir
HBcAb
hepatitis B core antibody 
HBeAb
hepatitis B e-antibody 
HBeAg
hepatitis B e-antigen
HBsAb
hepatitis B surface antibody 
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb
hepatitis C antibody
HDL
high density lipoprotein


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HIV-1
human immunodeficiency virus (Type 1) 
HLGT
high level group term
HLT
high level term
ICH
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use
ID
identification
IDMC
independent data monitoring committee
INSTI
integrase strand-transfer inhibitor
IWRS
interactive web response system
LDL
low density lipoprotein
LLT
lowest level term
MedDRA
Medical Dictionary for Regulatory Activities
MH
Mantel-Haenszel 
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
OL
open label
PP
per protocol
PT
preferred term
GLPS
global patient safety
Q
quartile
Q1
first quartile
Q3
third quartile
QD
once daily
RNA
ribonucleic acid
SAE
serious adverse events
SAP
statistical analysis plan
SD
standard deviation
SE
standard error 
SMQ
Standardized MedDRA Query
SOC
system organ class
TAF
tenofovir alafenamide 
TFL
tables, figures, and listings
ULN
upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) of final analysis for Study 
GS-US-380-4030, 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 28 June 2018 and the electronic case report form (eCRF). The SAP will be finalized before 
database finalization. Any changes made after the finalization of the SAP will be documented in 
the clinical study report.
1.1.
Study Objectives
The primary objective of this study is:

To evaluate the efficacy of switching from a regimen of dolutegravir (DTG) and 
emtricitabine (FTC; F) / tenofovir alafenamide (TAF) or DTG + FTC/tenofovir disoproxil 
fumarate (TDF) to a fixed dose combination (FDC) of bictegravir (B)/F/TAF versus 
DTG + F/TAF in virologically suppressed HIV-1 infected subjects with or without 
antiretroviral (ARV) resistance 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
1.2.
Study Design
Design Configuration and Subject Population
GS-US-380-4030 is a randomized, double-blinded, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to a FDC of B/F/TAF tablet versus DTG + F/TAF 
in HIV-1 infected subjects who are virologically suppressed.
Treatment Groups
Subjects who provide written consent and meet all eligibility criteria will be randomized in a 
1:1 ratio to one of the following 2 treatment groups:

Treatment Group 1: FDC of B/F/TAF (50/200/25 mg) + placebo to match DTG 50 mg + 
placebo to match FDC of F/TAF (200/25 mg) administered orally, once daily (QD), without 
regard to food (total of 3 tablets) (n=260)

Treatment Group 2: DTG 50 mg + FDC of F/TAF (200/25 mg) + placebo to match FDC of 
B/F/TAF (50/200/25 mg) administered orally, QD, without regard to food (total of 3 tablets) 
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Key Eligibility Criteria
Medically stable HIV-infected subjects who meet the following criteria:

Currently receiving an ARV regimen of DTG+F/TAF or DTG+F/TDF for the following 
minimum time periods: 
≥ 6 months (if there is documented or suspected nucleoside/nucleotide reverse 
transcriptase inhibitor (NRTI) resistance prior to the screening visit),
≥ 3 months (if there is no documented or suspected NRTI resistance prior to the 
screening visit)

Documented plasma HIV-1 RNA < 50 copies/mL during treatment with DTG+F/TAF or 
DTG+F/TDF (for a minimum period of ≥ 6 or ≥ 3 months, as applicable) preceding the 
screening visit (or undetectable HIV-1 RNA level according to the local assay being used if 
the limit of detection is ≥ 50 copies/mL) 
The last two HIV-1 RNA measurements prior to screening must be < 50 copies/mL; 
however, unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable 
viremia, or “blip”) in the past are acceptable.
If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL 
(eg, < 20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on 
2 consecutive HIV-1 RNA tests after < 50 copies/mL has been achieved.

HIV-1 RNA levels < 50 copies/mL at screening visit.

Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance (eGFRCG)

No documented resistance to integrase stand-transfer inhibitors (INSTIs) or confirmed 
virologic failure (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving < 50 copies/mL 
while on an INSTI-containing regimen)
Eligible subjects with the following historical ARV resistance are permitted to enroll:
■
Any NRTI resistance mutations
■
Any non-nucleoside reverse transcriptase mutations
■
Any protease inhibitor mutations
■
Subjects with resistance to 2 or more classes of antiretrovirals must be reviewed by 
the Gilead medical monitor to confirm eligibility

Eligible subjects with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) 
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Study Periods / Phases
Subjects will be treated for at least 48 weeks during the blinded treatment phase.
After Week 48, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the Week 48 
Visit and Week 48 analysis is completed, all subjects will return to the clinic (preferably within 
30 days) for an End of Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety 
and efficacy of B/F/TAF FDC is demonstrated following review of unblinded data, subjects in a 
country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC 
in an open-label (OL) extension phase for up to 96 weeks, or until the product becomes 
accessible to subjects through an access program, or until Gilead Sciences elects to discontinue 
the study in that country, whichever occurs first.
All subjects participating in the OL extension phase, without regard to their blinded treatment 
regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for up to 
96 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open-label B/F/TAF FDC extension phase, will be required to return to the clinic 
30 days after the End of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
Schedule of Assessments
After screening procedures, eligible subjects will be randomized 1:1 to Treatment Group 1 or 
Treatment Group 2 and treated for at least 48 weeks. Following the Day 1 Visit, subjects will 
return for study visits at Weeks 4, 8, and 12, and then every 12 weeks through the End of 
Blinded Treatment 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 End of Blinded Treatment Visit. Laboratory analyses (hematology, 
chemistry, and urinalysis), HIV-1 RNA, CD4+ cell count and percentage, 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.
Historical HIV-1 RNA genotypes (from resistance testing) will be collected, if available.
More details for study procedure could be found in Appendix 1.
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 prior NRTI use 
(F/TAF vs. F/TDF) and documented or suspected history of NRTI resistance.


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NRTI resistance will be stratified by the following categories:
1) K65R/E/N, or 3 or more thymidine analogue mutations (TAMs) that include M41L or 
L210W, or T69 insertions (TAMs are: M41L, D67N, K70R, L210W, T215F/Y, and 
K219Q/E/R/N) 
2) Any other pattern of NRTI resistance of M41L, D67N, K70R, L74I/V, Y115F, Q151M, 
M184I/V, L210W, T215F/Y, K219Q/E/R/N, T69D, K70E/G/M/Q/S/T, V75A/S/M/T
3) None of these mutations/no NRTI resistance
Site and/or Stratum Enrollment Limits
Approximately 100 study sites in North America and Europe. There was no enrollment limit for 
individual sites.
Study Duration
The randomized, double-blind phase of this study is at least 48 weeks in duration. At the End of 
Blinded Treatment Visit, if safety and efficacy of B/F/TAF FDC is demonstrated following 
review of unblinded data, subjects in a country where B/F/TAF FDC is not available will be 
given the option to receive B/F/TAF FDC in an open-label (OL) extension phase for up to 
96 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. 
1.3.
Sample Size and Power
A total of approximately 520 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (260 subjects per treatment group), achieves at least 90% power to detect a 
non-inferiority margin of 4% in difference in 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® 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).
1.4.
Actual Sample Size and Power
It was noted that the unconditional exact method using 2 inverted 1-sided tests is more 
appropriate than normal approximation method that was used for the sample size calculation in 
the protocol due to the fact that the proportion of participants with HIV-1 RNA ≥ 50 copies/mL 
was very low. Using PASS 14 software, the actual power calculated based on the actual sample 
size of 565 was 85% power, instead of 90% power, to detect a non-inferiority margin of 4% at a 
one-sided alpha of 0.025 when we change the analysis from normal approximation method to 
exact method.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee Analyses
The Week 12 Independent Data Monitoring Committee (IDMC) analysis was conducted after all 
subjects enrolled completed their Week 12 Visit 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 results or to consider 
early termination of the study even if there is early evidence of favorable efficacy for B/F/TAF. 
2.2.
Interim Analyses
2.2.1.
Week 48 Analysis
The Week 48 analysis was conducted after all subjects either completed their Week 48 Visit or 
prematurely discontinued from the blinded study drug. This is 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. This analysis will include all data collected from the 
randomized and the extension phases of the study.
This statistical analysis plan describes the analysis plan for the final analysis.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
The final analysis will include two sets of analyses: randomized phase analysis and all B/F/TAF 
analysis.
Randomized Phase Analysis:

For subjects who are never treated in the extension phase of the study including those who 
prematurely discontinue the blinded study drug or who complete the randomized phase and 
do not receive any dose of B/F/TAF in the extension phase, all available data will be 
included in the randomized phase analysis.

For subjects who complete the randomized phase and receive at least 1 dose of B/F/TAF in 
the extension phase, the randomized phase analysis will include (1) all available adverse 
event (AE), concomitant medication, pregnancy, and death data collected prior to the 
extension phase first dose date; (2) all available other data, such as laboratory, vital sign, and 
electrocardiogram (ECG), collected on or prior to the extension phase first dose date.
All B/F/TAF Analysis:

For subjects who receive B/F/TAF in the randomized phase, all available data collected from 
both randomized phase and OL extension phase (if applicable) will be included in the all 
B/F/TAF analysis. 

For subjects who receive DTG + F/TAF in the randomized phase and receive at least 1 dose 
of B/F/TAF in the extension phase, (1) all available AE, concomitant medication, pregnancy, 
and death data with start date on or after the first dose date of B/F/TAF in the extension 
phase and (2) all available other data, such as laboratory, vital sign, and ECG data, collected 
after the first dose date of B/F/TAF in the extension phase will be included, except that the 
data collected on or prior to the first dose date of B/F/TAF will be used to derive the 
baseline value for the all B/F/TAF analysis. 
Note that all data for subjects who receive DTG + F/TAF in the randomized phase and do not 
receive any dose of B/F/TAF in the extension phase will be excluded from all B/F/TAF analysis. 
The actual treatment received will differ from the randomized treatment only when the actual 
treatment received differs from randomized treatment for the entire treatment duration. 
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.


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By-subject listings will be presented for all subjects in the All Randomized analysis set unless 
otherwise specified, and sorted by subject identification (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 for each analysis 
(see Appendix 7 for details) will be used for analyses and presentation in listings. For 
randomized but never dosed subjects, age on the date of randomization will be used. For screen 
failures, age on the date of the informed consent was signed will be used. If only birth year is 
collected on the eCRF, “01 January” will be used for the unknown birth day and month for the 
purpose of age calculation, similarly, if only birth year and month are collected on the eCRF, 
“01” will be used for the unknown birth day for the purpose of age calculation. 
In general, permanent discontinuation of the blinded study drug refers to premature 
discontinuation of the blinded study drug or completion of the blinded study drug. Similarly, 
permanent discontinuation of the extension phase study drug refers to premature discontinuation 
of the extension phase study drug or completion of the extension phase study drug. More 
specifically, for the randomized phase analysis, study drug refers to the blinded study drugs 
(B/F/TAF or DTG + F/TAF); for all B/F/TAF analysis, study drug refers to B/F/TAF.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. Subjects included in each analysis set will be determined before 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.
Analysis Sets Used for the Randomized Phase Analysis
3.1.1.1.
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.
3.1.1.2.
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 blinded randomized study drug. Subjects will be grouped 
according to the treatment to which they were randomized. For the FAS, all efficacy data 
collected in the randomized phase, including data collected after the last dose of blinded study 
drug and on or prior to the first dose date of the OL study drug (if applicable), will be included, 
unless specified otherwise. This is the primary analysis set for efficacy analyses. 


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3.1.1.3.
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 blinded 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, 
efficacy data up to 1 day after permanent discontinuation of blinded study drug 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 on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing is due to discontinuation of blinded 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 (DC) in the “Blinded Treatment” study phase on the 
study drug completion eCRF page; (Table 1). 
Table 1.
Subjects Excluded from Week 48 Per Protocol Analysis Set Due to 
Premature Discontinuation of blinded Study Drug and/or Missing 
HIV-1 RNA Assessment in Week 48 Analysis Window
HIV-1 RNA Data on Randomized Treatment Available 
in Week 48 Analysis Window
Discontinuation from blinded Study Drug prior to or on the 
Upper Bound of Week 48 Analysis Window
Yes
No
Due to Lack of Efficacy
+
+
Yes
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 criterion of receiving a stable antiretroviral regimen 
of DTG + F/TAF or DTG + F/TDF for the following duration prior to the screening visit:1) 
≥ 6 months (if there is documented or suspected NRTI resistance), or 2) ≥ 3 months (if there 
is no documented or suspected NRTI resistance) 

Subjects who do not meet the inclusion criterion of having documented plasma HIV-1 RNA 
< 50 copies/mL during treatment with DTG+F/TAF or DTG+F/TDF (for a minimum period 
of ≥ 6 or ≥ 3 months, as applicable) preceding the screening visit (or undetectable HIV-1 
RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL)

Subjects who do not meet the inclusion criterion of having HIV RNA-1 < 50 copies/mL at 
the screening visit

Subjects who do not meet the inclusion criterion of having no documented resistance to 
INSTIs or confirmed virologic failure (2 consecutive HIV-1 RNA ≥ 50 copies/mL after 
achieving < 50 copies/mL while on an INSTI-containing regimen)


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
Subjects who do not meet the inclusion criterion of only having the following permitted 
historical ARV resistance:
1) Any NRTI resistance mutations
2) Any non-nucleoside reverse transcriptase mutations
3) Any protease inhibitor mutations
4) Subjects with resistance to 2 or more classes of antiretrovirals must be reviewed by the 
Gilead medical monitor to confirm eligibility

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in Section 4.3 of the protocol including drugs not to be used 
with BIC, FTC, TAF and DTG

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile
3.1.1.4.
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 blinded randomized study drug. Subjects will be grouped 
according to the treatment they actually received. This is the primary analysis set for safety 
analyses.
Adverse event, concomitant medication, pregnancy, and death data collected up to 30 days after 
permanent discontinuation of the blinded randomized study drug and prior to the first dose date 
of OL study drug (if applicable) will be included in the safety summaries, unless specified 
otherwise.
Laboratory data (eg, hematology, chemistry, and urine analysis), vital sign, ECG data collected 
up to 30 days after permanent discontinuation of the blinded randomized study drug and on or 
prior to the first dose date of OL study drug (if applicable) will be included in the safety 
summaries, unless specified otherwise.
3.1.2.
Analysis Set Used for the All B/F/TAF Analysis
3.1.2.1.
All B/F/TAF Analysis Set
The All B/F/TAF Analysis Set will include all subjects who (1) are randomized into the 
randomized phase of the study and (2) have received at least 1 dose of the B/F/TAF in the 
randomized phase or at least 1 dose of the B/F/TAF in the extension phase. This is the primary 
analysis set for the all B/F/TAF efficacy and safety analyses. 
For efficacy analyses, all efficacy data collected for the all B/F/TAF analysis will be included.
For safety analyses, all safety data collected up to 30 days after permanent discontinuation of the 
last B/F/TAF (including randomized and open label phases) will be included in the safety 
summaries, unless specified otherwise.


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3.2.
Subject Grouping
For the randomized phase analyses using the All Randomized Analysis Set or the FAS, subjects 
will be grouped by the randomized treatment (labeled as B/F/TAF vs. DTG + F/TAF). For all 
other randomized phase analyses, subjects will be grouped by the 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.
For all B/F/TAF analyses, subjects will be grouped into the following 3 groups:

B/F/TAF group: This group includes all subjects who actually received B/F/TAF in the 
randomized phase of this study, regardless whether subjects receive any B/F/TAF in the 
extension phase or not.

DTG + F/TAF to B/F/TAF group: This group includes all subjects who actually received 
DTG + F/TAF regimen in the randomized phase of this study and then receive at least 1 dose 
of B/F/TAF in the extension phase

All B/F/TAF group: This group includes all subjects who actually received at least 1 dose of 
B/F/TAF in either phase. This group includes the B/F/TAF group and the DTG + F/TAF to 
B/F/TAF group. Only data collected on and after the first dose date of B/F/TAF may be 
included.
Treatment comparisons will only be made between B/F/TAF and DTG + F/TAF for the 
randomized phase analysis.
3.3.
Strata and Covariates
Randomization was stratified by prior NRTI backbone use (F/TAF vs. F/TDF) and documented 
or suspected history of NRTI resistance. For analysis, the baseline NRTI resistance stratum was 
re-classified based on virology data collected at both screening and/or baseline:
Baseline NRTI resistance stratum are as follows:
1) No NRTI mutation:
None of these following mutations/no NRTI resistance
2) K65R/E/N or ≥ 3 TAMs:
K65R/E/N or ≥ 3 TAMs that include M41L, L210W, or T69 insertions: K65R/E/N, or 3 or 
more thymidine analogue mutations (TAMs) that include M41L or L210W, or 
T69 insertions, (TAMs are: M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/R/N) 
3) Any other pattern of NRTI mutation: 
Any other pattern of NRTI resistance of M41L, D67N, K70R, L74I/V, Y115F, Q151M, 
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3.4.
Examination of Subject Subgroups
Subject subgroup analysis will only be performed for randomized phase analysis unless specified 
below.
3.4.1.
Subject Subgroups for Efficacy Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 will be analyzed for the 
following subject subgroups (also see Section 6.1.2.2.2 for details): 

Age (years): (a) < 50 and (b) ≥ 50 

Sex: (a) male and (b) female 

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) 

Baseline NRTI resistance (determined based on virology data): (a) No NRTI mutation 
(b) any NRTI mutation

Baseline NRTI resistance (determined based on virology data): (a) No NRTI mutation, 
(b) K65R/E/N or ≥ 3 TAMs (c) any other pattern of NRTI mutation 

Baseline M184I/V resistance (determined based on virology data): (a) No M184I/V mutation 
(b) any M184I/V mutation
The proportion of subjects with 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
1) Incidence of all treatment-emergent AEs (TEAEs) will be analyzed for the following subject 
subgroups (also see Section 7.1.6): 

Age (years): (a) < 50 and (b) ≥ 50 

Sex: (a) male and (b) female 

Race: (a) black and (b) nonblack 

Region: (a) US and (b) Ex-US 
2) Renal-related laboratory tests (ie, serum creatinine and eGFRCG) and fasting metabolic 
laboratory tests will be analyzed for each subgroup of baseline NRTI backbone: (a) F/TAF 
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3) Selected safety endpoints may be analyzed for the following subject subgroups for 
randomized phase analysis and for all B/F/TAF analyses (see Section 8.1 for details): 

Subjects with HIV/HBV coinfection at baseline

Subjects with incident HIV/HBV coinfection while on study drug (if any)
4) Selected safety endpoints will be analyzed for the following subject subgroups for 
randomized phase analysis and for all B/F/TAF analyses (see Section 8.2 for details):

Subjects with HIV/HCV coinfection at baseline

Subjects with incident HIV/HCV coinfection while on study drug (if any)
3.5.
Multiple Comparisons
The noninferiority evaluation of the proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at 
Week 48 was the prespecified primary comparison. However, 1 interim IDMC analysis was 
performed prior to the analysis for the primary endpoint and an alpha penalty of 0.00001 was 
applied. Therefore, the alpha level for the primary endpoint (ie, the proportion of subjects with 
HIV-1 RNA ≥ 50 copies/mL at Week 48) 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, will be also adjusted to 0.04999 (corresponding to 95.001% CI) to 
be conservative. 
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-ARV medications in Section 7.4.2.


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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).
Logarithmic (base 10) transformations will be applied to HIV-1 RNA and HBV DNA data for 
efficacy analyses. HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “<20 copies/mL HIV-1 
RNA Detected” will be imputed as 19 copies/mL for analysis purposes. HBV DNA results of 
“<20 IU/mL HBV DNA detected” or “No HBV DNA detected” will be imputed as 19 IU/mL for 
analysis purposes. HCV RNA results of “<15 IU/mL HCV RNA detected” or “No HCV RNA 
detected” will be imputed as 14 IU/mL for analysis purposes. 
3.8.
Analysis Windows
3.8.1.
Definition of Study Day
Study Day 1 for the Randomized Phase analysis is defined as the day when the first dose of 
blinded randomized study drug (ie, B/F/TAF or Placebo, or DTG or Placebo, or F/TAF or 
Placebo) was taken, as recorded on the Study Drug Administration eCRF for “Randomized 
Phase”.
Last Dose Date for the Randomized Phase analysis is the latest of the blinded randomized 
study drug (ie, B/F/TAF or Placebo, or DTG or Placebo, or F/TAF or Placebo) end dates 
recorded on the Study Drug Administration eCRF for “Randomized Phase”.
If the last dose date for the randomized phase analysis is missing (eg, only year of last dose is 
known or completely missing due to lost to follow-up), the latest of the blinded study drug start 
dates and end dates, or the latest of clinical and the laboratory visit dates prior to the first dose 
date of B/F/TAF in the extension phase (if applicable), excluding the 30-day follow-up visit date, 
will be used to impute the last dose date. For other partial missing last dose date, please see the 
Appendix 7 for imputation rule details. 


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Study Day 1 for the all B/F/TAF analysis is defined as 

For subjects who actually received B/F/TAF in the randomized phase of this study 
(ie, B/F/TAF group), Study Day 1 for the all B/F/TAF analysis is defined as the day when 
the first dose of B/F/TAF in the randomized phase was taken, as recorded on the Study Drug 
Administration eCRF form.

For subjects who actually received DTG + F/TAF in the randomized phase of this study and 
then receive at least 1 dose of B/F/TAF in the extension phase (ie, DTG + F/TAF to B/F/TAF 
group), Study Day 1 for the all B/F/TAF analysis is defined as the day when the first dose of 
B/F/TAF in the extension phase was taken (ie, OL B/F/TAF), as recorded on the Study Drug 
Administration eCRF form. 
Last Dose Date for the All B/F/TAF Analysis is the latest of B/F/TAF (including both 
randomized phase and open label phase) end dates recorded on the Study Drug Administration 
eCRF form.
If the last dose date for the all B/F/TAF analysis is missing (eg, only year of last dose date is 
known or completely missing due to lost to follow-up), the latest of the B/F/TAF (including both 
randomized phase and open label phase) start dates and end dates, the latest clinical and 
laboratory visit dates, excluding the 30-day follow-up visit date, will be used to impute the 
last dose date. 
Study Days are calculated relative to Study Day 1 for the randomized phase analysis. For events 
that occurred on or after the Study Day 1 date, study days are calculated as (visit date minus 
Study Day 1 plus 1). For events that occurred prior to Study Day 1 for either analysis, study days 
are calculated as (visit date minus Study Day 1). 
Last Study Date is the latest of the study drug (including DTG + F/TAF, and B/F/TAF in both 
randomized phase and open label phase) start dates and end dates, the clinic visit dates, and the 
laboratory visit dates, including the 30-day follow-up visit date. 
Baseline Value is defined as the last nonmissing value obtained on or prior to Study Day 1 for 
the randomized phase analysis or the all B/F/TAF analysis, as appropriate. Subjects who actually 
received DTG + F/TAF in the randomized phase and received at least 1 dose of B/F/TAF in 
extension phase will have a baseline for Randomized Phase Analysis and a new baseline value 
for the all B/F/TAF analysis. 
3.8.2.
Analysis Windows
Subject visits might not occur on protocol specified days. Therefore, for the purpose of analysis, 
observations will be assigned to two different analysis windows based on the following tables: 
the analysis windows for the randomized phase analysis are derived relative to the Study Day 1 
for the randomized phase analysis, while the analysis windows for the all B/F/TAF analysis are 
derived relative to the Study Day 1 for the all B/F/TAF analysis.


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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 2 and Table 3 for randomized phase analysis and all B/F/TAF analysis separately.
Table 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 for Randomized 
Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 4
28
2
42
Week 8
56
43
70
Week 12
84
71
126
Week 24
168
127
210
Week 36
252
211
294
Week 48
336
295
378
Week 60
420
379
462
Week 72
504
463
546
Week 84
588
547
630
Week K 
K*7
(K-6)*7+1
(K+6)*7
Note: Week K is every 12 weeks after previous visit.
Table 3.
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 for All B/F/TAF 
Analysis
B/F/TAF Group
DTG+F/TAF to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 4
28
2
42
NA
NA
NA
Week 8
56
43
70
NA
NA
NA
Week 12
84
71
126
84
2
126
Week 24
168
127
210
168
127
210
Week 36
252
211
294
252
211
294
Week 48
336
295
378
336
295
378
Week 60
420
379
462
420
379
462
Week 72
504
463
546
504
463
546
Week 84
588
547
630
588
547
630
Week 96
672
631
714
672
631
714
Week k
K*7
(K-6)*7+1
(K+6)*7
K*7
(K-6)*7+1
(K+6)*7
NA = Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; For the DTG 
+ F/TAF to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension phase.
Note: Week K is every 12 weeks after previous visit.


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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) are presented in Table 4 and Table5 for randomized phase 
analysis and all B/F/TAF analysis separately.
Table 4.
Analysis Windows for Metabolic Assessments for Randomized Phase 
Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 12
84
2
126
Week 24
168
127
252
Week 48
336
253
420
Week 72
504
421
588
Week K
K*7
(K-12)*7+1
(K+12)*7
Note: Week K is every 24 weeks after previous visit.
Table5.
Analysis Windows for Metabolic Assessments for all B/F/TAF 
Analysis
B/F/TAF Group
DTG + F/TAF to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 12
84
2
126
NA
NA
NA
Week 24
168
127
252
168
2
252
Week 48
336
253
420
336
253
420
Week 72
504
421
588
504
421
588
Week 96
672
589
756
672
589
756
Week K
K*7
(K-12)*7+1
(K+12)*7
K*7
(K-12)*7+1
(K+12)*7
NA = Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; For the DTG 
+ F/TAF to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension phase. 
Note: Week K is every 24 weeks after previous visit.
The analysis windows for HBV Serology (including HBsAb, HBsAg, hepatitis B e-antigen 
[HBeAg], hepatitis B e-antibody [HBeAb], HBcAb) and HCV Serology (including HCV 
antibody [HCVAb]), and HCV RNA assessments are presented in Table 6 and Table 7.


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Table 6.
Analysis Windows for HBV and HCV Serology and HCV RNA 
Assessments for Randomized Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 48
336
2
504
Week K
K*7
(K-24)*7+1
(K+24)*7
Note: Week K is every 48 weeks after previous visit.
Table 7.
Analysis Windows for HBV and HCV Serology, and HCV RNA Assessments 
for all B/F/TAF Analysis
B/F/TAF Group
DTG + F/TAF to B/F/TAF
Visit ID
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 48
336
2
504
336
2
504
Week 96
672
505
840
672
505
840
Week K 
K*7
(K-24)*7+1
(K+24)*7
K*7
(K-24)*7+1
(K+24)*7
NA = Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; For the DTG 
+ F/TAF to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension phase. 
Note: Week k is every 48 weeks after previous visit.
Analysis window is not defined for ECG, since there is no related summary analysis. 
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Window
Depending on the statistical analysis method, single values are required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time to event analysis would not require one value per analysis window. When a single value is 
needed, the following rule(s) will be used. 
If multiple nonmissing numeric observations exist in a window, then records will be chosen as 
follows:

For baseline, the latest available record on or prior to the first dose date of study drug for 
randomized phase analysis or B/F/TAF phase analysis will be selected. If there are multiple 
records with the same time or no time recorded on the same day, average will be used for the 
baseline value, except for HIV-1 RNA (see below). 


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


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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 region, country, and investigator will 
be summarized by treatment group and overall using the safety analysis set. The region 
definition is provided in Appendix 2. 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 based on reclassified strata using baseline NRTI 
backbone based on the Non-Study ARV Medication eCRF, and baseline NRTI resistance data as 
determined by Gilead Virology based on virology data instead of using interactive web response 
system (IWRS) data.
If there are discrepancies between IWRS and collected 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, subjects in the FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:

Subjects completing study drug in the double-blinded randomized phase

Subjects prematurely discontinuing study drug in the double-blinded randomized phase 
(with summary of reasons for discontinuing study drug in the randomized phase)

Subjects completing study in the double-blinded randomized phase

Subjects prematurely discontinuing from study in the double-blinded randomized phase 
(with summary of reasons for discontinuing from study in the randomized phase)

Subjects entering the OL extension phase

Subjects treated in the OL extension phase

Subjects completing study drug in the OL extension phase


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
Prematurely discontinuing study drug in the OL extension phase (with summary of reasons 
for discontinuing study drug in the OL extension phase)

Subjects completing study in the OL extension phase

Prematurely discontinuing from study in the OL extension phase (with summary of reasons 
for discontinuing from study in the OL extension phase)
The denominator for the percentages of subjects in each category in the randomized phase, 
including “Subjects entering the OL extension phase”, will be the number of subjects 
randomized and treated in the randomized phase. The denominator for the percentages of 
subjects in each category in the OL extension phase will be the number of subjects who were 
treated in OL extension phase.
No inferential statistics will be generated. Reasons for premature study drug/study 
discontinuation will be provided in by-subject listings by subject ID number in ascending order. 
Reasons for premature study drug/study discontinuation due to COVID-19 will also be provided 
in a separate listing.
4.2.
Extent of Study Drug Exposure and Adherence
4.2.1.
Duration of Exposure to Study Drug
Duration of exposure to study drug will be defined for both the randomized phase analysis and 
the all B/F/TAF analysis. For the randomized phase analysis, the terms “first dose date” and “last 
dose date” in the text below refer to the first dose date and last dose date defined for the 
randomized phase analysis. For the all B/F/TAF analysis, the terms “first dose date” and “last 
dose date” in the text below refer to the first dose date and last dose date defined for the all 
B/F/TAF analysis. Duration of exposure to study drug will be defined as (the last dose date – the 
first dose date + 1), regardless of temporary interruptions in study drug administration, and will be 
expressed in weeks using up to 1 decimal place (eg, 4.5 weeks). 
Duration of exposure to study drug will be summarized using descriptive statistics (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 
(756days), ≥ 120 weeks (840 days), ≥ 132 weeks (924 days), ≥ 144 weeks (1008 days), 
≥ 156 weeks (1092 days), ≥ 168 weeks (1176 days), etc.
Summaries will be provided by treatment group for subjects in Safety Analysis Set for the 
randomized phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively. 
No inferential statistics will be provided. 
For the randomized phase analysis, time to permanent discontinuation of blinded study drug will 
be analyzed using the Kaplan-Meier (KM) method by treatment group based on the safety 
analysis set. The log rank test will be used to compare the difference in study drug exposure 
between the 2 treatment groups. Subjects who completed blinded randomized study drug will be 
censored on last blinded randomized study drug dose date. A plot of KM estimates for the time 
to premature discontinuation of blinded study drug by treatment group will be generated.


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For all B/F/TAF analysis, time to premature discontinuation of study drug (B/F/TAF) will be 
analyzed by treatment group using the KM method based on the All B/F/TAF Analysis Set. No 
statistical comparisons will be made for the all B/F/TAF analysis. A plot of KM estimates for the 
time to permanent discontinuation of study drug by treatment group (B/F/TAF vs DTG + F/TAF 
to B/F/TAF) will be generated for the all B/F/TAF analysis. Subjects who completed study drug 
(B/F/TAF) will be censored at the last study drug dose date of B/F/TAF.
4.2.2.
Adherence to Study Drug Regimen
Adherence to study drug regimen will be defined for both the randomized phase analysis and the 
all B/F/TAF analysis. For randomized phase analysis, adherence will be computed for both 
treatment groups, including B/F/TAF and DTG + F/TAF. For all B/F/TAF analysis, study drug 
adherence (B/F/TAF) will be computed for both treatment groups and overall as defined in 
Section 3.2. Study drug regimen adherence will be computed based on pill counts for active drug 
only. The numbers of pills of study drug dispensed and returned are captured on study drug 
accountability eCRF.
Adherence (%) of study drug regimen will be calculated as follows:
[1] Number of pills taken at a distinct dispensing period for a study drug is calculated as the minimum of (a) the daily number of 
pills prescribed for the study drug multiplied by the duration of treatment at the dispensing period, and (b) the number of pills 
taken for the study drug (number of pills dispensed minus the number of pills returned). Total number of pills taken is determined 
by summing the number of pills taken 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. 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.






]
2
[
]1[
period
dispensing
each 
at 
prescribed
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of
No.
period
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each 
at 
 taken 
pills
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100
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pills
of
No.
Total
 taken
pills
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100
(%)
Adherence






]
2
[
]1[
period
dispensing
each 
at 
prescribed
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of
No.
period
dispensing
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at 
 taken 
pills
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pills
of
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 taken
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of
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100
(%)
Adherence


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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 study drug at a dispensing period, (b) date of premature 
discontinuation of the study drug, and (c) next pill dispensing date of the study drug, minus 
dispensing date of the study drug.
The next pill dispensing date is the following dispensing date of the study drug regardless of the 
bottle return date. 
For a record where the number of pills returned was missing (with “Yes” answered for 
“Was Bottle returned?” question), it is assumed the number of pills returned was zero. If the 
number of pills dispensed was missing or any study drug bottle was not returned or the bottle 
return status was unknown, then all records in that dispensing period for that study drug will be 
excluded from both denominator and numerator calculation.
Overall adherence will be calculated for both the randomized phase analysis and the all B/F/TAF 
analysis. For the randomized analysis, overall adherence will use all data from the entire dosing 
period up to the last dose date of the randomized study drug. For the all B/F/TAF analysis, 
overall adherence will use all available data collected from both randomized phase and OL phase 
for subjects who actually received B/F/TAF in the randomized phase, and data on or after the 
first dose date of extension B/F/TAF for subjects who actually received DTG + F/TAF in the 
randomized phase and received at least 1 dose of B/F/TAF in the extension phase.
Descriptive statistics for adherence to study drug regimen (n, mean, SD, median, Q1, Q3, 
minimum, and maximum) along with the number and percentage of subjects belonging to 
adherence categories (eg, < 80%, ≥ 80% to < 90%, ≥ 90% to < 95%, ≥ 95%) will be provided by 
treatment group for subjects who return at least 1 bottle of randomized study drug, and who have 
calculable adherence for the randomized phase analysis and for All B/F/TAF analysis, 
respectively. 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.
4.4.
Missing Protocol-Specified Information due to COVID-19
A by-subject listing of subjects with missed or virtual visits due to COVID-19 will be provided 
by subject ID number in ascending order. 
The determination of missing or virtual Visits due to COVID-19 was done using Natural 
Language Processing (NLP) to search the CRF comment fields. A detailed explanation of the 
algorithm is given in Appendix 7. 


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, race, and ethnicity) and baseline characteristics 
(eg, body weight, height, and body mass index [BMI]) will be summarized by treatment group 
and overall using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
for continuous data and by the number and percentage of subjects for categorical data. The 
summaries of demographic data and baseline subject characteristics will be provided for subjects 
in Safety Analysis Set for the randomized phase analysis and All B/F/TAF Analysis Set for all 
B/F/TAF analysis, respectively (noticing that the baseline for all B/F/TAF analysis will be 
adjusted based on first dose of B/F/TAF), respectively.
For the randomized phase analysis using Safety Analysis Set, the Cochran-Mantel-Haenszel 
(CMH) test (ie, general association statistic for nominal data) will be used to compare the 2 
treatment groups for categorical data, and the 2-sided Wilcoxon rank sum test will be used to 
compare the 2 treatment groups for continuous data. No statistical comparisons will be made for 
the all B/F/TAF analysis.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics for subjects in Safety Analysis Set for the randomized phase 
analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively:

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) (randomized phase analysis only)

HIV disease status (randomized phase analysis only)

eGFRCG (mL/min)

HIV/HBV co-infection status (Yes/No/Missing, see Section 8.1 for definition) 

HIV/HCV co-infection status (Yes/No/Missing, see Section 8.2 for definition) 


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
Duration of baseline ARV regimen (based on the Non-Study ARV Medication eCRF): 
(a) DTG + F/TAF; (b) DTG + F/TDF (randomized phase analysis only)

Baseline NRTI backbone stratum (F/TAF vs F/TDF, based on the Non-Study ARV 
Medication eCRF) (randomized phase analysis only)

Baseline NRTI resistance stratum (based virology data) (a) No NRTI mutation (b) K65R/E/N 
or ≥ 3 TAMs (c) any other pattern of NRTI mutation (randomized phase analysis only)
For the randomized phase analysis using Safety Analysis Set, the CMH test (general association 
statistic for nominal data, and row means scores differ statistic for ordinal data) will be used to 
compare the 2 treatment groups for categorical data and the 2-sided Wilcoxon rank sum test will 
be used to compare the 2 treatment groups for continuous data.
No statistical comparisons will be made for the all B/F/TAF analysis.
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will not be coded.


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6.
EFFICACY ANALYSES
6.1.
Efficacy Analysis for Randomized Phase Analysis 
6.1.1.
Primary Efficacy Endpoint
6.1.1.1.
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 purpose.
6.1.1.2.
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 to 1 day after permanent 
discontinuation of study drug) will be used in the US FDA-defined snapshot algorithm. Virologic 
outcome will be defined as the following categories:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 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
b) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
c) Missing data during the window but on study drug.


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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.
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 naïve study 
population, these subjects will be classified in the “No Virologic Data in the Week 48 Window” 
category.
6.1.1.3.
Statistical Hypothesis for the Primary Efficacy Endpoint
Null hypothesis: The B/F/TAF group (Treatment Group 1) is at least 4% higher than the 
DTG + F/TAF 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 DTG + F/TAF group (Treatment Group 2) with respect to the proportion of subjects with 
HIV-1 RNA ≥ 50 copies/mL at Week 48.
6.1.1.4.
 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 DTG + F/TAF. 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 12, 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 – DTG+F/TAF 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 DTG+F/TAF if the upper bound of the 2-sided 
95.001% CI of the difference between treatment groups (B/F/TAF group – DTG+F/TAF 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.
If noninferiority of B/F/TAF versus DTG+F/TAF 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, then superiority of B/F/TAF over DTG+F/TAF 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.


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6.1.1.5.
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 calculated 
based on an unconditional exact method using 2 inverted 1-sided tests.
6.1.2.
Secondary Efficacy Endpoints
6.1.2.1.
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 
The analyses for the secondary efficacy endpoints will be conducted using the FAS and the 
Week 48 PP analysis set, respectively.
6.1.2.2.
Analysis of the Secondary Efficacy Endpoints
6.1.2.2.1.
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 will also be analyzed 
by the US FDA-defined snapshot algorithm based on the FAS and Week 48 PP analysis set, 
respectively.
Proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as determined by 
US FDA-defined snapshot algorithm will be analyzed similarly to the primary efficacy endpoint. 
However, the noninferiority margin used for the proportion of subjects with HIV-1 RNA 
< 50 copies/mL 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 – DTG+F/TAF 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 DTG+F/TAF if the lower bound of the 2-sided 
95.001% CI of the difference between treatment groups (B/F/TAF group – DTG+F/TAF 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 region and treatment to assess homogeneity of treatment effect across different regions.
A region is defined as multiple sites combined based on geographical locations (see Appendix 2 
for region definition).
For each region, the difference in the proportion of subjects with HIV-1 RNA < 50 copies/mL 
between treatment groups and its 95% CI will be calculated based 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 
region and overall. The homogeneity of the odds ratios across different regions will be tested 
using a Breslow-Day test and a corresponding p value will be reported. 
6.1.2.2.2.
Subgroup Analysis of the Proportion of Subjects with HIV-1 RNA 
< 50 copies/mL at Week 48 as Determined by US FDA-defined Snapshot 
Algorithm
Since 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 randomized phase analysis.
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, treatment, 
and treatment by subgroup interaction. 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.
6.1.2.2.3
Analysis of CD4+ Cell Count
All CD4+ cell count will be summarized by visit using observed, on-treatment data (ie, data 
collected up to 1 day after permanent discontinuation of blinded study drug) for subjects in the 
FAS for randomized phase analysis and for subjects in all B/F/TAF Analysis Set for all B/F/TAF 
analysis. 








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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 copies/mL Not Detectable
■
< 20 copies/mL 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 for the proportion of subjects with HIV-1 RNA < 50 copies/mL for a treatment 
group will be constructed using the Clopper-Pearson exact method. No statistical comparisons 
will be made for the all B/F/TAF analysis.
6.2.2.2.
Analysis of CD4+ Cell Count and CD4%
The analysis of CD4 cell count will be based on on-treatment data (ie, up to 1 day after the last 
dose date of study drug) using the All B/F/TAF Analysis Set for the all B/F/TAF analysis.
The changes from baseline in CD4+ cell count at each visit will be summarized by treatment group 
using descriptive statistics. No statistical comparisons will be made for the all B/F/TAF analysis.
Similar analysis will be conducted for CD4% using the All B/F/TAF Analysis Set for the all 
B/F/TAF analysis.
In addition, the mean and 95% CI of change from baseline in CD4+ cell count over time will be 
plotted for the all B/F/TAF analysis.
6.3.
Changes From Protocol-Specified Efficacy Analyses
No change from the protocol-specified efficacy analysis is planned. 


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7.
SAFETY ANALYSES
Safety data will be summarized by treatment group for the subjects in the Safety Analysis Set for 
the randomized phase analysis, and the subjects in the All B/F/TAF Analysis Set for the all 
B/F/TAF analysis, unless specified otherwise. All safety data from both phases of the study will 
be included in data listings.
For the randomized phase analysis, the terms “study drug start date (ie, the first dose date)”, 
“study drug stop date (ie, the last dose date)”, and “baseline” in the text below refer to the first 
dose date, the last dose date, and baseline defined for the randomized phase analysis; the term 
“study drug” in the text below refer to the randomized study drugs.
For the all B/F/TAF analysis, the terms “study drug start date (ie, the first dose date)”, “study 
drug stop date (ie, the last dose date)”, and “baseline” in the text below refer to the first dose 
date, the last dose date, and baseline defined for the all B/F/TAF analysis; the term “study drug” 
in the text below refer to B/F/TAF.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of MedDRA. System organ 
class (SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and 
lowest-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe) or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will be left as 
“missing” for data listings. 
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAE database from the Global Patient Safety (GLPS) 
Department before data finalization.


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


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
Any Grade 2, 3, or 4 treatment-emergent study drug-related AEs

Any Grade 3 or 4 treatment-emergent study drug-related AEs

All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs

All treatment-emergent AEs that caused premature discontinuation from study drug
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs. Treatment-emergent 
deaths observed in the study will be also included in this summary.
Treatment-emergent death refers to deaths that occurred between the first dose date and the last 
dose date plus 30 days (inclusive).
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study. 
In addition to the above summary tables, all treatment-emergent AEs, Grade 3 or 4 
treatment-emergent AEs, treatment-emergent study drug-related AEs, Grade 2, 3, or 4 
treatment-emergent study drug-related AEs, and treatment-emergent SAEs will be summarized 
by PT only, in descending order of total frequency.
Summary of treatment-emergent AEs by SOC and PT will also be conducted for all subgroups 
listed in Section 3.4.2 for randomized phase analysis.
In addition, data listings will be provided for the following:

All AEs

Grade 3 and 4 AEs

SAEs

Study-Drug-Related SAEs

Deaths report

AEs leading to premature discontinuation of study drug


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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 Appendix 6 
of the protocol). 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 cardiovascular or cerebrovascular events are from relevant Standardized 
MedDRA Query (SMQ). The selected PT listing was provided by GLPS and reviewed by Gilead 
medical monitors (see details in Appendix 5).
The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
summarized by treatment group based on the safety analysis set for randomized phase analysis 
and All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively. Statistical comparisons of 
the subject incidence rates between the 2 treatment groups will be performed using the Fisher’s 
exact test for randomized phase analysis. No statistical comparisons of the subject incidence 
rates between the 2 treatment groups will be performed for all B/F/TAF analysis. A data listing 
of cardiovascular or cerebrovascular events will be provided.
7.1.7.3.
Hepatic Events
Preferred terms for hepatic events are from 15 relevant SMQs, which are identified as 
non-infectious and non-congenital hepatobiliary disorders. The selected PT listing was provided 
by Gilead GLPS and reviewed by Gilead medical monitors (see details in Appendix 6).
The number and percentage of subjects with treatment-emergent hepatic events and serious 
hepatic events by PT will be summarized by treatment group based on the safety analysis set for 
randomized phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively. 
Statistical comparisons of the subject incidence rates between the 2 treatment groups will be 
performed using the Fisher’s exact test for randomized phase analysis. No statistical comparisons 
of the subject incidence rates between the 2 treatment groups will be performed for all B/F/TAF 
analysis. A data listing of hepatic events will be provided.
7.1.7.4.
COVID-19
A data listing of TEAEs for COVID-19 and Suspected COVID-19 infection (see definition in 
Appendix 4) will be provided.


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7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided based on the 
Safety Analysis Set for randomized phase analysis and All B/F/TAF Analysis Set for all 
B/F/TAF analysis, respectively. The analysis will be based on values reported in conventional 
units. When values are below the LOQ, they will be listed as such, and the imputed value will be 
used for the purpose of calculating summary statistics as specified in Section 3.7.
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the reference range and/or having a severity grade of 1 or higher on the Gilead 
Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be flagged in 
the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group based on the safety analysis set for 
randomized phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis 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 study drug. Change from baseline to a postbaseline visit will be defined 
as the postbaseline value minus the baseline value. The mean, median, Q1, Q3, minimum, and 
maximum values will be displayed to the reported number of digits; SD values will be displayed 
to the reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 

Calcium corrected for albumin (mg/dL) = serum calcium (mg/dL) + 0.8 × (4.0 – albumin (g/dL)). 
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Estimated GFR
The following formula will be used to calculate eGFRCG: 

eGFR(CG) (mL/min) = [(140 – age (years)) × weight (kg) × (0.85 if female)] / 
(SCr (mg/dL) × 72), where weight is total body mass in kilograms, and SCr is serum 
creatinine.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used for assigning toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction 
(ie, increased, decreased) will be presented separately. 
If there is any laboratory toxicity grading scale overlapping with the normal reference ranges 
(eg, grade 1 scale overlaps with normal reference ranges), laboratory values that are within the 
normal range will be grade 0 except for lipid tests. 
For triglycerides, LDL, and cholesterol, the protocol specified toxicity grading scale is for fasting 
test values, so non-fasting lipid results (or lipid results without known fasting status) will not be 
graded or summarized by toxicity grades. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to 30 days after permanent 
discontinuation of study drug. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment emergent.
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.
Both urine red blood cell (RBC) based on microscopic examination, labeled as Hematuria 
(Quantitative), and urine blood based on a dipstick, labeled as Hematuria (Dipstick), are assessed 
and assigned a toxicity grade in this study. Hematuria (Quantitative) is a reflex test. Urine RBC 
based on microscopic examination or dipstick will be presented in laboratory toxicity summary 
tables and listings.


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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 laboratory test and treatment group based on Safety Analysis 
Set for randomized phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, 
respectively; subjects will be categorized according to the most severe postbaseline abnormality 
grade for a given laboratory test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities

Treatment-emergent Grade 2, 3 and 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
any nonmissing postbaseline values up to 30 days after last dosing date.
A by-subject listing of all treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities will be provided by subject ID number and visit in 
chronological order. 
7.2.3.
Metabolic Laboratory Evaluations
For metabolic assessments, including fasting glucose and the lipid panel (ie, total cholesterol, 
triglycerides, LDL, HDL, total cholesterol to HDL ratio), only those measurements under fasting 
status will be summarized based on the Safety Analysis Set for randomized phase analysis and 
All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively. P-values comparing the 
difference between the 2 treatment groups in baseline values and the change from baseline in 
metabolic assessment will be estimated from a 2-sided Wilcoxon rank sum test for randomized 
phase analysis. No formal statistical testing is planned for all B/F/TAF analysis.
For randomized phase analysis, the number and percentage of subjects who took lipid modifying 
medications at study entry and initiated the medications during the randomized phase of study 
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 Fisher’s exact 
test. For all B/F/TAF analysis, the number and percentage of subjects who took lipid modifying 
medications at the First Dose of B/F/TAF and While Receiving B/F/TAF will be provided by 
treatment group based on the All B/F/TAF Analysis Set. No formal statistical testing is planned 
for all B/F/TAF analysis.
A lipid modifying medication is defined as a medication with drug class (based on the World 
Health Organization [WHO] Drug ATC2 term) = “LIPID MODIFYING AGENTS” and WHO 
Drug preferred drug name containing the wording of “STATIN”.
For randomized phase analysis, a sensitivity analysis of fasting lipid tests will be performed by 
excluding subjects who took lipid modifying medications at study entry or initiated the 
medications during the study: baseline values, Week 48 values, and changes from baseline at 
Week 48 will be summarized by treatment group using descriptive statistics for randomized 
phase analysis. Baseline and change from baseline at Week 48 will be compared between the 2 
treatment groups using a 2-sided Wilcoxon rank sum test for randomized phase analysis. Only 
subjects with both baseline and Week 48 postbaseline values will be included in the analysis. 


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Summary of baseline, postbaseline, and change from baseline in fasting metabolic laboratory 
tests will be repeated within each subgroup of baseline NRTI backbone (F/TAF vs. F/TDF) 
based on the Non-Study ARV Medication eCRF based on the Safety Analysis Set for 
randomized phase analysis. P-values comparing the difference between the 2 treatment groups in 
baseline values and the change from baseline in metabolic assessment will be generated from a 
2-sided Wilcoxon rank sum test for randomized phase analysis. 
Median (Q1, Q3) of change from baseline in fasting metabolic assessments over time will be 
plotted by treatment group based on the Safety Analysis Set for randomized phase analysis and 
All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively. 
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 based on the Safety Analysis Set for randomized 
phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively:

Aspartate aminotransferase (AST): (a) > 3 × Upper limit of normal (ULN), (b) > 5 × ULN, 
(c) > 10 × ULN, (d) > 20 × ULN

Alanine aminotransferase (ALT): (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, 
(d) > 20 × ULN

AST or ALT: (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, (d) > 20 × ULN

Total bilirubin: (a) > 1 × ULN, (b) > 2 × ULN

Alkaline phosphatase (ALP) > 1.5 × ULN

AST or ALT > 3 × ULN and total bilirubin: (a) > 1.5 × ULN, (b) > 2 × ULN

AST or ALT > 3 × ULN and total bilirubin > 2 × ULN and ALP < 2 × ULN
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
study drug. For individual laboratory tests, subjects will be counted once based on the most 
severe postbaseline value. For both the composite endpoint of AST or ALT and total bilirubin, 
and the composite endpoint of AST or ALT, total bilirubin, and ALP, subjects will be counted 
once when the criteria are met at the same postbaseline visit date. For randomized phase 
analysis, 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. For all B/F/TAF 
analysis, 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.


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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 based on 
the Safety Analysis Set for randomized phase analysis and All B/F/TAF Analysis Set for all 
B/F/TAF analysis, respectively. Baseline and change from baseline will be compared between 
the 2 treatment groups using a 2-sided Wilcoxon rank sum test for randomized phase analysis. 
No formal statistical testing is planned for all B/F/TAF analysis.
In addition, ALT elevation (ie, ALT > 2 x Baseline and ALT > 10 x ULN) and ALT flare, 
defined as ALT elevations confirmed at two consecutive visits, will be evaluated and listed for 
subjects with HIV/HBV coinfection at baseline for randomized phase analysis and B/F/TAF 
phase analysis. The first occurrence of two or more consecutive ALT elevations will be 
identified as the ALT flare.
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 based on the Safety Analysis 
Set for randomized phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, 
respectively. Baseline and change from baseline will be compared between the 2 treatment 
groups using a 2-sided Wilcoxon rank sum test for randomized phase analysis. No formal 
statistical testing is planned for all B/F/TAF analysis.
Median (Q1, Q3) of change from baseline in serum creatinine and eGFRCG over time will be 
plotted by treatment group based on the Safety Analysis Set for randomized phase analysis and 
All B/F/TAF Analysis Set for all B/F/TAF analysis, respectively. 
Summary of baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG 
will be repeated within each subgroup of baseline NRTI backbone based on the Non-Study ARV 
Medication eCRF (F/TAF vs. F/TDF) based on the Safety Analysis Set for randomized phase 
analysis. P-values comparing the difference between the 2 treatment groups in baseline values 
and the change from baseline in metabolic assessment will be generated from a 2-sided 
Wilcoxon rank sum test for randomized phase analysis. 
7.3.
Body Weight, Height, and Vital Signs
Descriptive statistics will be provided by treatment group for vital signs and body weight as 
follows based on the Safety Analysis Set for randomized phase analysis and All B/F/TAF 
Analysis Set for all B/F/TAF analysis, respectively:

Baseline values

Values at each postbaseline analysis window

Change from baseline to each postbaseline analysis window 


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A baseline value will be defined as the last nonmissing value obtained on or prior to the date of 
first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. In the same listing, a by-subject listing of body weight, height, and BMI 
will be provided. 
7.4.
Prior and Concomitant Medications
7.4.1.
Nonstudy Drug Antiretroviral Medications
Any nonstudy drug ARV medications used prior to, during, or after the study (if collected) will 
be coded using the Gilead-modified WHO Drug Dictionary for ARV medications. The WHO 
preferred drug name and drug code will be attached to the clinical database. All nonstudy drug 
ARV medications will be listed. No inferential statistics will be provided.
7.4.2.
Concomitant Non-ARV Medications
Concomitant non-ARV medications (ie, medications other than study drug that are taken while 
receiving study drug) will be coded using the WHO Drug Dictionary. The WHO Drug preferred 
drug name and drug code will be attached to the clinical database. Use of concomitant 
medications from Study Day 1 up to the last dose date will be summarized (number and 
percentage of subjects) by treatment group and preferred drug name based on the Safety Analysis 
Set for randomized phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, 
respectively. Multiple drug use will be counted only once per subject for each preferred drug 
name. The summary will be sorted by decreasing total frequency. For drugs with the same 
frequency, sorting will be done alphabetically. 
If the start or stop date of non-ARV medications is incomplete, the month and year (or year alone 
if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARVs are concomitant or not. The medication is concomitant if the month and year of the 
start or stop (or year of the start or stop, if month is not recorded) of the medication does not 
meet either of the following criteria:

The month and year of start of the medication is after the date of the last dose of study drug

The month and year of stop of the medication is before the date of the first dose of study drug
If the start and stop date of non-ARV medications are complete, the start date is not after last dose 
date and the stop date is not before first dose date, or the non-ARV medications are marked as 
ongoing and start date is on or before last dose date, the non-ARV medications are concomitant. 
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Day 1, the first dose date and the last dose date defined for the randomized phase analysis. For 
the all B/F/TAF analysis, Study Day 1, the first and last dose dates refer to Study Day 1, the first 
dose date and the last dose date defined for the All B/F/TAF analysis.
Summaries of non-ARV concomitant medications will be provided based on the Safety Analysis 
Set for randomized phase analysis and All B/F/TAF Analysis Set for all B/F/TAF analysis, 
respectively. Subjects with any non-ARV concomitant medications will be listed. No inferential 
statistics will be provided.
7.5.
Electrocardiogram Results
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 data 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 for randomized phase analysis.
7.8.
Changes From Protocol-Specified Safety Analyses
No change from the protocol-specified safety analysis is planned.


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8.
SPECIAL POPULATION ANALYSES
Special population analyses will be performed by treatment group based on the Safety Analysis 
Set for randomized phase analysis and all B/F/TAF analyses (if applicable). Study Day 1, the 
first and last dose dates refer to Study Day 1, the first dose date and the last dose date defined for 
the randomized phase analysis and all B/F/TAF analyses (if applicable). 
8.1.
Analyses for HIV/HBV Coinfected Subjects
Subjects with HIV/HBV coinfection at baseline for randomized phase analysis and for all 
B/F/TAF analyses are defined as subjects meet any of the following two criteria for each 
analysis:

Positive HBsAg on or prior to the first dose date, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) on or prior to the first dose date.
The following summary analyses will be conducted by treatment group and overall for subjects 
with HIV/HBV coinfection at baseline for randomized phase analysis and for all B/F/TAF 
analyses: 

The proportion of subjects with HBV DNA < 29 IU/mL at baseline and Week 48 by missing 
= excluded approach. 

The change from baseline in log10 HBV DNA (log10 IU/mL)

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. 
For summary, HBV DNA will be analyzed for all visits using observed, on-treatment data 
(ie, data collected up to 1 day after permanent discontinuation of study drug) for subjects with 
HIV/HBV coinfection at baseline for randomized phase analysis using FAS and for all B/F/TAF 
analyses using all B/F/TAF set.
The following listings will be provided for subjects with HIV/HBV coinfection at baseline for 
safety analysis set and for all B/F/TAF analysis set.

Listing of adverse events

Listing of liver-related laboratory tests and HBV DNA results

Listing of ALT elevation (ie, ALT > 2 x Baseline and ALT > 10 x ULN) and ALT flare 
(see Section 7.2.4)


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Subjects with incident HIV/HBV coinfection while on study drug for randomized phase analysis 
and for all B/F/TAF analyses are defined as subjects who are not HIV/HBV coinfected at 
baseline and meet any of the following criteria for each analysis:

Positive HBsAg after the first dose date and on or prior to the date of permanent 
discontinuation of study drug, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) after the first dose date and on or prior to the date of permanent 
discontinuation of study drug, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the first dose date and on or prior to the date of permanent 
discontinuation of study drug: Acute hepatitis B, Chronic hepatitis B, Congenital hepatitis B 
infection, Hepatitis B, Hepatitis B core antibody positive, Hepatitis B DNA assay positive, 
Hepatitis B surface antigen positive, Hepatitis B virus test positive.
The following listings will be provided for subjects with incident HIV/HBV coinfection while on 
study drug (if any) for safety analysis set and for all B/F/TAF analysis set.

Listing of adverse events

Listing of liver-related laboratory tests and HBV DNA results
8.2.
Analyses for HIV/HCV Coinfected Subjects
Subjects with HIV/HCV coinfection at baseline are defined as subjects with positive HCVAb 
and quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) on or prior to the first dose date. The 
following analyses will be provided for subjects with HIV/HCV coinfection at baseline for 
randomized phase analysis and for all B/F/TAF analysis: 

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 first dose date and on or prior to the date of permanent 
discontinuation of study drug with baseline HCVAb Negative or missing, or

Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the first dose date and on or prior 
to the date of permanent discontinuation of study drug, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the first dose date for randomized phase analysis and on or prior to 
the date of permanent discontinuation of study drug: Acute hepatitis C, Chronic hepatitis C, 
Hepatitis C, Hepatitis C antibody positive, Hepatitis C RNA positive, Hepatitis C virus test 
positive.


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The following listings will be provided for subjects with incident HIV/HCV coinfection while on 
study drug for randomized phase analysis and for all B/F/TAF analysis: 

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results


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9.
REFERENCES
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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10.
SOFTWARE
SAS Version 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
nQuery Advisor® Version 6.0 (Statistical Solutions, Cork, Ireland.) was used for planned sample 
size and power calculation.
PASS Version 14 (NCSS, LLC, Kaysville, Utah) was used for actual 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.
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial)
Appendix 3.
Region Definition
Appendix 4.
COVID-19 related Adverse Events
Appendix 5.
Cardiovascular or Cerebrovascular Events
Appendix 6.
Hepatic Events
Appendix 7.
Determining Missing and Virtual Visits Due to COVID-19
Appendix 8.
Programming Specification


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Appendix 1.
Study Procedures Table
Weekb,c
Post-Week 48
Open Label Extension (OL) Weeksc,f
Study Procedures
Screeninga
Day 1
4
8
12
24
36
48
Every 
12 Weeksc,d
End of 
Blinded 
Treatment 
Visite
12
OL
24
OL
36
OL
48
OL
60
OL
72
OL
84
OL
96
OL
30 Day 
Follow upg
ESDDh
Informed Consent
X
Questionnairesi
X
X
X
X
Medical History
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj
Complete/ Symptom-
Directedk Physical 
Exam
X
X
X
X
X
X
X
X
Xl
X
X
X
X
X
X
X
X
X
Xj
Xj
12-Lead ECG
(performed supine)
X
Height
X
Vital signsm and 
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj
Serum Pregnancy 
Testn
X
Urine Pregnancy 
Testn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry Profileo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj,o
eGFR
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
X
Hematology Profilep
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj
Metabolic 
Assessmentsq
X
X
X
X
Xr
X
X
X
X
X
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CCI
CCI


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Weekb,c
Post-Week 48
Open Label Extension (OL) Weeksc,f
Study Procedures
Screeninga
Day 1
4
8
12
24
36
48
Every 
12 Weeksc,d
End of 
Blinded 
Treatment 
Visite
12
OL
24
OL
36
OL
48
OL
60
OL
72
OL
84
OL
96
OL
30 Day 
Follow upg
ESDDh
CD4+ Cell Count and 
Percentage
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HCV Serologys
X
X
Xl
X
X
HBV blood panelt
Xu
Xu
Xu
Xu
Xu
Plasma HBV DNAv
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomizationw
X
Study Drug 
Dispensation
Xx
X
X
X
X
X
X
X
Xy
X
X
X
X
X
X
X
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV-1 Genotype/ 
Phenotypec
Xc
a.
Evaluations to be completed within 30 days prior to Day 1.
b.
Study visits are to be completed within ± 2 days of the protocol specified visit date (based on the Day 1) through Week 12 and within ± 6 days through to Week 36, unless 
otherwise specified. The visit window for Week 48 will be ± 6 weeks of the protocol specified visit date.
c.
HIV-1 genotype and phenotype testing for subjects with confirmed virologic failure and HIV-1 RNA >200 copies/mL. Following virologic rebound, subjects will be asked to 
return to the clinic (2-3 weeks later) prior to the next scheduled visit or at the next scheduled study visit for a HIV-1 RNA and HIV-1 resistance analysis (reverse transcriptase, 
protease, and integrase genotype and phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema 
(Protocol Section 6.11). 
d.
After Week 48, all subjects will continue to take their blinded study drug and attend visits every 12 weeks (± 6 days of the protocol specified visit date) until the End of 
Blinded Treatment Visit.
e.
Once the last subject completes the Week 48 visit and Gilead completes the Week 48 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety and efficacy of B/F/TAF is demonstrated following review of unblinded data, subjects in a country 
where B/F/TAF FDC is not available, will be given the option to receive B/F/TAF FDC in an OL extension phase for up to 96 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. Treatment assignments will be provided to the 
investigators within 30 days of the last subject completing the End of Blinded Treatment Visit.
f.
Study visits are to be completed within ± 6 days of the protocol specified visit date based on the End of Blinded Treatment Visit date, unless otherwise specified. 
CCI
CCI




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Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial)
The following flowchart 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 Human Services 2015}.
 
  
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix 3.
Region Definition
Region
Country Name
State
No. of Subjects in Safety 
Analysis Set or FAS 
(N=565)
Total No. of Subjects by 
Region in Safety 
Analysis Set or FAS Set
(N=565)
Region 1
CANADA (CAN)
49
49
AUSTRIA (AUT)
3
85
FRANCE (FRA)
26
Region 2
GERMANY (DEU)
56
United States (USA)
CA
63
83
United States
HI
4
Region 3
United States
WA
16
United States
AZ
3
64
United States
CO
2
United States
NM
6
Region 4
United States
TX
53
United States
KY
6
33
United States
MI
3
United States
MN
12
Region 5
United States
MO
12
United States
DC
28
82
United States
MA
35
United States
NJ
4
Region 6
United States
NY
15
United States
GA
31
67
United States
LA
0
United States
NC
33
Region 7
United States
SC
3
United States
FL
70
102
Region 8
United States
PR*
32
*
PR = Puerto Rico.
Note: In general, a region is defined as multiple sites combined based on geographical locations. For example, for international 
studies, sites from each country or multiple neighboring counties were combined; and for US studies, sites from each state or 
multiple neighboring states were combined.


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Appendix 4.
COVID-19 related Adverse Events
An adverse event record will be flagged as a COVID-19 related adverse event if its MedDRA PT 
is included in the pre-specified PT list, which includes all PTs from the narrow search of the 
following SMQs under MedDRA v23.1 provided by Gilead GLPS (search name: COVID-19 
(SMQ) – Narrow ) and reviewed by Gilead medical monitors.
SMQ Source
COVID-19 related Events
COVID-19 (SMQ) (Narrow Scope)


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Appendix 5.
Cardiovascular or Cerebrovascular Events 
An adverse event record will be flagged as a cardiovascular or cerebrovascular event if its 
MedDRA PT is included in the pre-specified PT list, which includes all PTs from the narrow 
search of the following 3 SMQs under MedDRA v23.1 provided by Gilead GLPS (search name: 
Essential ischaemic cardiac and cerebral events without supportive tests and conditions) and 
reviewed by Gilead medical monitors and GLPS safety physician.
SMQ Source
Ischaemic central nervous system vascular conditions (SMQ) – Narrow 
Scope Term
Myocardial infarction (SMQ) - Narrow Scope Term
Cardiovascular or Cerebrovascular 
Events 
Other ischaemic heart disease (SMQ) - Narrow Scope Term


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Appendix 6.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT is included in this 
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA v23.1 provided by Gilead GLPS (search name: Non-infectious, non-congenital 
hepatobiliary disorders in Final_MST_Global_v23.1_05Nov2020) and reviewed by Gilead 
medical monitors and GLPS safety physician.
SMQ Source
Biliary neoplasms benign (incl cysts and polyps) (SMQ)
Biliary malignant tumours (SMQ)
Biliary tumours of unspecified malignancy (SMQ)
Biliary system related investigations, signs and symptoms (SMQ)
Biliary tract disorders (SMQ)
Gallbladder related disorders (SMQ)
Gallstone related disorders (SMQ)
Cholestasis and jaundice of hepatic origin (SMQ)
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ)
Hepatitis, non-infectious (SMQ)
Liver neoplasms, benign (incl cysts and polyps) (SMQ)
Liver malignant tumours (SMQ)
Liver tumours of unspecified malignancy (SMQ)
Liver related investigations, signs and symptoms (SMQ)
Hepatic Events (HEP)
Liver-related coagulation and bleeding disturbances (SMQ)


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Appendix 7.
Determining Missing and Virtual Visits Due to COVID-19
This appendix describes the site collection of COVID-19 data as pertains to missed/virtual visits 
and the data processing algorithm used to determine which visits were missing and which visits 
were virtual.
Data collection
A COVID-19 supplement to the eCRF Completion Guidelines (CCG) was provided by data 
management to instruct clinical trial sites with respect to data entry expectations pertaining to 
scenarios related to the COVID-19 pandemic. If a visit was missed, sites should enter “Visit 
missed due to COVID-19.” If a visit which was to be conducted in-person was conducted 
virtually, sites should enter “Virtual visit due to COVID-19.”
Determination of Missed and Virtual visits
Natural Language Processing (NLP) was used to search the CRF comment fields to identify 
instances of “COVID-19” (or synonyms, see Table X 1) and “Virtual” (or synonyms, see 
Table X 1). The search terms are maintained in a global lookup and can be modified and/or 
corrected to tune the NLP model. For each comment field the following algorithm was applied:
STEP 1: Eliminate extraneous text from each comment field, e.g. “and”, “or”, “for”, etc. This is 
done using the list of extraneous terms given in Table X 2.
STEP 2: Check each of the remaining comment text strings against the “COVID-19” terms and 
“Virtual” terms with the Levenshtein distance, using SAS function COMPGED (Computes a 
generalized edit distance using the Levenshtein operations to compute/summarize the degree of 
difference between two text strings): 
i.
If Levenshtein distance < 149 for any of the “COVID-19” terms then COVIDFL = 1, 
else COVIDFL = 0
ii. If Levenshtein distance < 149 for any of the “Virtual” terms then VIRTFL = 1, 
else VIRTFL = 0
STEP 3: For any comments with COVIDFL = 1, assign “Missed visit” or “Virtual visit as 
follows
i.
IF COVIDFL =1 and the visit date is missing then result is ‘Missed Visit’
ii. IF COVIDFL =1 and VIRTFL = 1 then result is = ‘Virtual Visit’
iii. Otherwise result is missing


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Table X 1.
Examples of search terms for “COVID-19” and “Virtual” used to 
identify missed and virtual visits.
Search terms for “COVID-19”
Search terms for “Virtual”
COVID19
VIRTUAL
CORONA
TELEMED
CORONAVIRUS
TELEHEALTH
PANDEMIC
TELEPHONE
OUTBREAK
REMOTE
CRISIS
TELEMEDICINE
LOCKDOWN
TELECONSULTATION
QUARANTINE
TELEPHONICALLY
PHONE
HOME VISIT
ZOOM
SHELTER
SKYPE


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


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Appendix 8.
Programming Specification
1) AGE calculated as follows
a) AGE (years) is calculated from the number of days between the date of birth (DOB) and 
Day 1 (first dose date) defined for both randomized phase analysis and all B/F/TAF 
analysis. For subjects randomized to DTG + F/TAF group, AGE (years) is calculated for 
both randomized phase analysis and all B/F/TAF analysis.
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
d) AGE = the integer of the result in (c),
e) If the DOB and Day 1 have the month in common and the birthday is later in the month 
than the date of Study Day 1, then subtract one from the AGE result above.
For subjects randomized and never dosed with study drug, age will be calculated from the 
date of randomization.
Age for laboratory test reference range will be based on the age at the sample collection date.
2) All screened subjects refer to all subjects who are screened (ie, with non-missing 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 were 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 
non-missing RGMNDTN in the IXRSRAND dataset), and confirmed by the eCRF ENROLL 
dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) are derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if subject 
took at least 1 dose of study drug and assigned as blank if subject never dosed.
6) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.


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7) Body mass index (BMI) and Body Surface Area (BSA)
BMI and BSA will be calculated only at baseline as follows:

BMI = (weight [kg]) / (height [meters]2)

BSA (m2) = SQRT( [Height(cm) × Weight(kg) ] / 3600 )
Baseline height and weight will be used for this calculation.
8) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
a) CMH test for nominal variable (Y), the p-value from general association test should be 
used for nominal variable:
proc freq order=adsl;
tables trtgrp * Y /cmh /*general association test*/
run;
b) CMH test for ordinal variable (Y), the p-value from row mean score test should be used 
for ordinal variable:
proc freq order=adsl;
tables trtgrp * Y / cmh2 ; /*row mean score test*/
run;
c) Wilcoxon rank sum test for continuous variable (Y), the p-value from the normal 
approximation two-sided test should be used for continuous variable:
proc npar1way wilcoxon data=adsl;
class trtgrp; 
var Y;  
run;
9) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded percentage 
calculation and also excluded for p value generation for categorical data analysis (eg, CMH 
test or Fisher exact test). Except for Mode of infection (HIV Risk Factors), where 
“Unknown” will be included for percentage calculation, since a subject may fit more than 
1 HIV risk factors, therefore percentage may add to more than 100% and no p-value will be 
generated. 
Subjects with Race = “Not Permitted” will also be excluded to define Race subgroup 
(ie, black vs. nonblack) for efficacy subgroup analysis. 
10) SAS code for treatment comparison for duration of exposure. The p-value from log rank test 
should be used. 
proc lifetest data=ADSL method=km; 
time TRTDURD*ESDD(0); /*Derive ESDD from COMT01FL, where ESDD = 0 
indicates censored observation (ie, subjects completed study drug)*/
Strata TRT01AN;
label TRTDURD = "Duration of Exposure (Days)";
run;


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11) Last Dose Date and Last Study Date
a) Last Dose Date (ie, TRTEDTC, TRTEDT, TR01EDT or TR01EDTC) in ADSL for 
randomized phase analysis and all B/F/TAF analysis was defined in SAP Section 3.8.1.
For subjects with a partial last dosing date (ie, month and year of last dose are known), 
the latest of the dispensing dates of study drug bottles, study drug start dates and end 
dates, and the imputed last dose date [day imputed as 15] will be used as the final 
imputed last dose date. However if dispensing date’s month is after last dose date’s 
month, data query is needed.
If subject died and the death date is complete (ie, not partial date) and before the imputed 
last dose date, the complete death date should be used as the imputed last dose date. 
b) Last Study Date is the latest of the study drug start dates and end dates, the clinic visit 
dates, and the laboratory visit dates, including the 30-day follow-up visit date, for 
subjects who prematurely discontinued study or who completed study according to the 
Study Completion eCRF. If study drug start date or end date is partially missing 
(ie, only year and month are known), the day will be imputed as 15 for the purpose of this 
analysis.
If subject died and the death date is complete (ie, not partial date) and before the imputed 
last study date, the complete death date should be used as the imputed last study date. 
12) Duration of baseline ARV regimen
a) Defining ARV Regimen at Baseline:
All subjects are expected to enter the study on DTG + F/TAF or DTG + F/TDF. Using the 
ARV raw dataset, include all prior and/or current ARVs (ARV.INGRED where 
ARV.CMSCAT =’Prior ARV” or “Current ARV”), taken on or up to 2 day prior to first dose 
date (or randomization date if not treated) for randomized phase analysis:
Select only ARV with the start date on or prior to first dose date of randomized study drug, 
and the end date ongoing or >= the first dosed date of randomized study drug, (For the same 
ARV, if the stop date of 1 record is on the same date or 1 day before the start date of another 
record, please combine it as one record)
When determining the baseline ARV regimen, look at the ingredient of drugs, replacing “_” 
with “/” (for FTC_TAF and FTC_TDF), respectively. Moreover, replace “FTC/” with “F/”. 
Assign an order priority of 1 to “DTG” and 2 to “F/TAF” or “F/TDF” for each subject. 
Once the ingredients have been updated and assigned an appropriate priority, transpose the 
ingredients by subject (using the ingredient as the variable and priority as the id) and 
concatenate each column with a “+” following the priority specified above. To illustrate this, 
if a subject is on DTG and FTC_TAF, then their regimen would be presented as 
“DTG+F/TAF”.


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b) Calculation of the duration of baseline ARV regimen
Duration of baseline regimen DTG + FTC/TAF or DTG + FTC/TDF prior to the randomized 
phase 1st dose date (or B/F/TAF first dose date) is defined as (End Date – Start Date+1) 
(ie, equal to [randomized first dose date (or B/F/TAF first dose date)-1 – start date of prior 
ARV +1)]. Duration will be expressed in years so that duration in days will be divided by 
365.25 days. 
End date is defined as randomized phase first dose date (or B/F/TAF first dose date) -1 or 
randomized date if randomized but not dosed,
Start Date: The use of baseline ARV regimen: DTG + DESCOVY (FTC/TAF) or DTG + 
TRUVADA
Step 1: Use the following rules to handle any incomplete start dates 

If only month and year are available, day will be first imputed as 15th, then imputed as 
minimum of (the start date of the ARV, randomized phase 1st dose date-1, the stop date of 
the same ARV)

If only year is available, month and day will be first imputed July 1st of the year, then 
imputed as minimum of (the start date of the ARV, randomized phase 1st dose date-1, the 
stop date of the same ARV) 

No imputation applied for date missing completely 
(Use the following rules to handle any incomplete stop dates, if needed

If only month and year are available, day will be first imputed as 15th, then imputed as 
minimum of (the randomized phase 1st dose date-1, the stop date of the same ARV)

If only year is available, month and day will be first imputed July 1st of the year, then 
imputed as minimum of (randomized phase 1st dose date-1, the stop date of the same ARV) 

No imputation applied for date missing completely)
Step 2: Select ARVs with start date on or prior to the randomized phase 1st dose date (or 
B/F/TAF first dose date for all B/F/TAF analysis)
Step 3: For each subject, find the first dose date and last dose date for each study drug 
component: 
For the same ARV, if the stop date of 1 record is on the same date or 1 day before the start date 
of another record, please combine it as one record.

Select all ARVs containing the wording of ‘DTG’ in ARV.INGRED and select the latest start 
date (D1_DTG)


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
Select all ARVs containing the wording of ‘FTC_TAF’ in ARV.INGRED and select the 
latest start date (D1_DESCOVY)

Select all ARVs containing the wording of ‘FTC_TDF’ in ARV.INGRED and select the 
latest start date (D1_TRUVADA)
Step 4: Determine of the start date of ARV regimen

The start date of DTG+DESCOVY (D1_DTG+DESCOVY) after taking into account all 
2 components of DTG, DESCOVY is the latest start date of D1_DTG, D1_DESCOVY

The start date of DTG+ TRUVADA (D1_DTG+TRUVADA)after taking into account all 
2 components of DTG, DESCOVY is the latest start date of D1_DTG, D1_TRUVADA 
13) Toxicity Grades:
a) For toxicity grade summaries, include all post-baseline graded results up to 30 days after 
the last dose of study drug, not just those used in by-visit summaries.
b) For glucose grading, as specified in SAP Section 7.2.2.1, the treatment-emergent flag 
cannot be determined for nonfasting glucose (including glucose results without a known 
fasting status). As a result, these records will be excluded from the “Maximum 
Treatment-emergent Toxicity Grade” summary in the “Treatment-emergent Laboratory 
Abnormalities” or “Treatment-emergent Grade 3 or 4 Laboratory Abnormalities” 
summary tables. In addition, fasting glucose and 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.
14) Efficacy analyses:
a) 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 two treatment 
groups and its 95.002% CIs (for HIV-1 RNA < 50 at wk48 by snapshot algorithm for 
FAS or Week 48 PP set) or 95% CIs are calculated based on the an unconditional exact 
method using 2 inverted 1-sided tests in SAS v9.3 or above. 
b) The following SAS code will be used to compute difference in percentage, its 95.001%CI 
and p-value. 
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     


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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 _RSK11_  _RSK21) riskdiff;
run;
c
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;
c) Please note, alpha=0.04999 is only used for the primary efficacy endpoint (HIV-1 RNA 
>= 50 c/mL by snapshot algorithm at Week 48) to obtain 95.001% CIs and the endpoint 
of subjects with HIV-1 RNA < 50 c/mL by snapshot algorithm at Week 48 in FAS and 
Week48 PP analysis set; otherwise, for the efficacy endpoints with proportions, the 
alpha=0.05 is used to obtain 95% CIs.
d) The 95% CI for percentage estimate of HIV-1 RNA < 50 copies/mL for each treatment is 
calculated based on the Clopper-Pearson exact method.
e) Fisher’s exact test for categorical efficacy response (eg, HIV-1 RNA < 50 copies/mL by 
US FDA-defined snapshot algorithm), where trtgrp is the treatment, and response is the 
categorical efficacy response. P-value from 2-sided Fisher’s exact test should be used to 
test superiority. 
proc freq data=adeff;
tables trtgrp*response/fisher; /*p value from Fisher’s exact test*/
run;
f)
Homogeneity test: Homogeneity Test of Treatment Effect (HIV-1 RNA < 50 copies/mL 
by US FDA-defined snapshot algorithm) Across Region in HIV-1 RNA < 50 copies/mL 
at Week 48 (Snapshot Algorithm). For each region, the odds ratio and its 95% CI are 
calculated from the CMH test. For overall, the odds ratio and its 95% CI are calculated 
based on the common odds ratio estimate from the CMH test. The p-value for the 
homogeneity test is based on the Breslow-Day test of the interaction between region and 
treatment group as follows. 


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proc freq data=xxx;
tables region*trtgrp* response /all; /*p value from Breslow Day test,
(trtgrp: 1, 2; response: 1: < 50, 2: >=50)*/
run; 
g) Subgroup analyses for HIV-1 RNA < 50 copies/mL by US FDA-defined snapshot 
algorithm 
For the subgroups of age, sex, race, baseline CD4 cell count, and study drug adherence, 
the proportion difference between two treatment groups and its 95% CIs are calculated 
based on an unconditional exact method using 2 inverted 1-sided tests, similarly to that 
for the primary efficacy endpoint.
h) Homogeneity test: Homogeneity Test of Treatment Effect (HIV-1 RNA < 50 copies/mL 
by US FDA-defined snapshot algorithm) between Subgroups in HIV-1 RNA 
< 50 copies/mL at Week 48 (Snapshot Algorithm)
a.
For the subgroups of age, sex, race, region and study drug adherence, the odds ratio 
and the associated 95% CIs are estimated for the response variable (response; coded 
as 1 for success and 0 for non-success) using a logistic regression model including 
subgroup factor (coded as 1 for the first subgroup and 2 for the second subgroup), 
treatment (trtgrp; coded as 1 for active [ie, B/F/TAF] and 2 for control), and treatment 
by subgroup factor. 
eg. region stratum (region; coded as 1 for “US” and 2 for “Ex-US”)
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. 
e.g. for the age subgroup, the following codes will be used to get Odds Ratio and 
95% CI within subgroup:
proc genmod data=data descending;     /*model for success*/
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: trtgrpn is the numeric treatment group variable, response is the response 
outcome variable (1 vs 0 (’<50’ vs’>=50’)), agegrp is the subgroup variable for age 
(1:< 50 vs 2: >= 50).


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(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.)
i)
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 effect in the model.
proc glm data=adeff;
class trtgrp;
model CD4=trtgrp;
lsmeans trtgrp /alpha=0.05 cl pdiff;
run;
j)
Listing for US FDA-defined snapshot outcome:
In addition to flagging the values of HIV-1 RNA < 50 or ≥ 50 copies/mL for virologic 
outcomes, flag the last available HIV-1 RNA value while on treatment for the following 
categories:
i)
HIV-1 RNA >= 50 copies/mL - Discontinued Study Drug Due to AE or Death and 
Last Available HIV-1 RNA >= 50 copies/mL
ii) HIV-1 RNA >= 50 copies/mL - Discontinued Study Drug Due to Other reason* and 
Last Available HIV-1 RNA >= 50 copies/mL
iii) No virologic Data – Discontinued Study Drug Due to AE or Death and Last Available 
HIV-1 RNA < 50 copies/mL
iv) 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.
15) Clarification of the following LOCF algorithms:

Baseline values will be carried forward.

For CD4:
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.
16) TEAE
Events with Missing Onset Day and/or Month


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An event is treatment emergent if the following 3 criteria are met:
1) The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
2) The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
3) End date is as follows: 
a) The (complete) end date is on or after the first dose date, or
b) The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
c) End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
criteria specified in 3) above.
17) Graded Laboratory Abnormalities Summary
The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label 
Used in l-labtox Listing
Toxicity Direction
Lab Test Label
Used in t-labtox Table
Hemoglobin
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
Hematology
WBC
Decrease
WBC (Decreased)
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
Lipase
Increase
Lipase (Increased)
Chemistry
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)
Urine Blood (Dipstick)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urinalysis
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
*
Due to the reflexive nature of the quantitative urine RBC test, results will be combined with the dipstick test of urine blood 
as described below:
Is Post-BL Urine 
RBC (Quant.) 
Result Available?
Is BL Urine RBC 
(Quant.) Result 
Available?
Is Post-BL 
Urine Blood 
(Dipstick) 
Result 
Available?
Is BL Urine 
Blood (Dipstick) 
Result 
Available?
How to Determine Treatment-
Emergent Toxicity for “Urine RBC 
(Hematuria, Quantitative or 
Dipstick)”
Yes
Yes
-
-
Compare post-BL Urine RBC 
(Quant.) toxicity grade to BL Urine 
RBC (Quant.) toxicity grade. If 
post-BL toxicity is greater than BL 
toxicity, then treatment-emergent
Yes
No
-
-
Treatment-emergent. Use post-BL 
Urine RBC (Quant.) toxicity grade.
No
-
Yes
Yes
Compare post-BL Urine Blood 
(Dipstick) toxicity grade to BL Urine 
Blood (Dipstick) toxicity grade. If 
post-BL toxicity is greater than BL 
toxicity, then treatment-emergent
No
-
Yes
No
Treatment-emergent. Use post-BL 
Urine Blood (Dipstick) toxicity 
grade.
No
-
No
-
Do not count subject in the 
denominator for “Urine RBC 


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(Hematuria, Quantitative or 
Dipstick)”
BL = Baseline. Quant = Quantitative. “-” means any value can be present (or it can be missing), as it does not affect the 
classification
18) Concomitant nonstudy-drug ARV medications (ie, ARV medications other than study drug 
that are taken while receiving study drug) will be flagged in “Nonstudy-Drug Antiviral 
Medication” listing. The logic to define concomitant nonstudy-drug ARV is similar to 
concomitant non-ARV Medications (see details in Section 7.4.2)
19) Lipid modifying medication analyses:

Lipid modifying medication is defined to be the concomitant medication with WHO Drug 
ATC2 term (drug class) = “LIPID MODIFYING AGENTS” and WHO Drug preferred 
drug name (CMDECOD) contains wording of “STATIN” in the ADCM dataset.

Subjects who took lipid modifying medications at study entry refer to the subjects who 
have any use of the lipid modifying agents at study day 1 (ie, the first dose date) for 
randomized phase analysis.
a) More specifically, subjects with “Lipid Modifying Agent Use at Study Entry” include 
those subjects in safety analysis set for randomized phase analysis with meeting both 
the following criteria: 1) any selected CM record with the start date ≤ the first dose 
date for randomized phase analysis, and 2) the end date of the selected CM 
record ≥ the first dose date or the end date of the selected CM record is ongoing 
b) For lipid modifying medications with the start date completely unknown, we assume 
the start date is on or before the first dose date, lipid modifying medication was 
considered as being taken at study entry if the end date is not prior to the first dose 
date (ie, the end date is on or after the first dose date, completely unknown, or 
ongoing). 
c) Lipid modifying medications with the start date prior to the first dose date for 
randomized phase analysis and the end date unknown (completely missing) were 
considered as being taken at study entry (the unknown end date is assumed on or after 
the first dose date).

Subjects who initiated lipid modifying medications during the study for randomized 
phase analysis refer to the subjects in the safety analysis set who didn’t take lipid 
modifying medications at study entry and with any selected CM record started after the 
first blinded study drug dose date and on and prior to the last blinded study drug dose 
date. 

Subjects who took lipid modifying medications at first dose of B/F/TAF (including both 
phases) refer to the subjects who use of the lipid modifying agents at study day 1 of all 
B/F/TAF analysis. More specifically, subjects with “Lipid Modifying Agent Use at 


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First Dose of B/F/TAF” include those subjects in All B/F/TAF Analysis Set with: 1) any 
selected CM record with the start date ≤ the first dose date of B/F/TAF (including both 
phases), and 2) the end date of the selected CM record is ongoing or the end date of the 
selected CM record ≥ the first dose date of B/F/TAF (including both phases).
a) For lipid modifying medications with start date completely unknown, we assume the start 
date is on or before the first dose date of B/F/TAF (including both phases), lipid 
modifying medication was considered as being taken at first dose of B/F/TAF (including 
both phases) if the end date is not prior to the first dose date of B/F/TAF (including both 
phases) (ie, the end date is on or after the first dose date of B/F/TAF (including both 
phases), completely unknown, or ongoing).
b) Lipid modifying medications with the start date on or prior to the first dose date of 
B/F/TAF (including both phases) and the end date completely unknown were considered 
as being taken at first dose of B/F/TAF (including both phases).

Subjects who initiated lipid modifying medications while subject receiving B/F/TAF 
includes the following subjects in the All B/F/TAF Analysis Set: (1) for subjects who 
permanently discontinued study drug with any selected CM record started after the first 
dose date of B/F/TAF (including both phases) and on or prior to last dose of B/F/TAF 
(including both phases). (2) for subjects who meet criteria (1) above, if they took lipid 
modification medications at first dose of B/F/TAF (including both phases), or if they took 
lipid modifying medications on or after randomized phase first dose and before first dose 
of B/F/TAF, they will NOT be considered initiated lipid modifications while receiving 
B/F/TAF for the all B/F/TAF analysis.
20) 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.
21) Vital signs and weight, height, BMI will be in the same listing.


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22) HIV/HBV and HIV/HCV Coinfection:

The following table presents the HBV and HCV tests with all possible values. Values that 
have an asterisk after them denote a “positive” (or “quantifiable” for HBV DNA and 
HCV RNA) result while all others denote a “negative” result.
Label
LBTESTCD
LBTEST
Possible Values
HBsAg
ATT1
Hep.B Surf.Ag Quant(-70)CL
 NUMERICAL VALUE or “<0.05” or 
“>124925.00” (IU/mL)
HBsAg
ATT2
Hep. B Surf. Ag Qual(-70)-CL
“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 (IU/mL)*
HBV DNA
GET1884
HBV DNA CAP/CTM 2.0Dil-
EDTA-CL
NUMERICAL VALUE (IU/mL)*
HCVAb
CNT350
Hepatitis C Virus Antibody
“Positive”*, “Indeterminate”, “Negative”
HCV RNA
GET1881
HCV RNA CAP/CTM 
2.0EDTA-CL
“No HCV RNA detected”, “<15 IU/mL HCV RNA 
detected”, NUMERICAL VALUE (IU/mL)* 
Note: HBVDNA AMPLIPREPTAQMAN 2.0 DIL(GET1884) is for HBV DNA CAP/CTM 2.0 >170,000,000 IU/mL.
HBsAg(ATT1) test is conducted when HBsAg(ATT2) when ATT2 results = “Repeat reactive, confirmed”, “Repeat Reactive 
Unconfirmed”.Only HBsAg (ATT2) results will be summarized for HBV surface antigen.

For baseline coinfection, when considering the different laboratory tests, take the latest, 
non-missing record on or prior to the first dose date defined for randomized phase 
analysis or all B/F/TAF analysis for each test (eg, HBsAg, HBsAb, HBcAb, and HBV 
DNA)
The baseline coinfection status will be one of the three values: Yes/No/Null
The following tables provide combinations of HBV and HCV tests and the 
corresponding baseline coinfection status


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HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
-
-
-
Y
Positive
-
-
N
Quantifiable
Y
Not Quantifiable
N
Positive
Missing
Null
Negative
-
N
Quantifiable
Null
Not Quantifiable
N
Negative
Missing
Missing
Null
Quantifiable
Null
Not Quantifiable
N
Positive
Missing
Null
Negative
-
N
Quantifiable
Null
Not Quantifiable
N
Negative
Missing
Missing
Missing
Null
Positive
-
-
Null
Quantifiable
Y
Not Quantifiable
Null
Positive
Missing
Null
Negative
-
Null
Negative
Missing
-
Null
Missing
Missing
-
-
Null
HCVAb
HCV RNA
Coinfection Status
Quantifiable
Y
Not Quantifiable
N
Positive
Missing
Null
Negative
-
N
Quantifiable
Null
Not Quantifiable
N
Missing
Missing
Null
 “-” means any value can be present, as it does not affect the classification

For incident coinfection, all laboratory tests must share the same accession number and if 
any set of values meets the criteria, then the subject is considered to have incident 
coinfection
The incident coinfection status will be one of two values: Yes/Null
The following tables provide combinations of HBV and HCV tests that are 
considered “Y” for incident coinfection status (all others are considered Null)


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HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
-
-
-
Y
Negative
Negative
Positive
Quantifiable
Y
Missing
Negative
Positive
Quantifiable
Y
HCVAb
HCV RNA
Coinfection Status
Positive*
-
Y
-
Quantifiable
Y
*
Subjects with positive HCVAb postbaseline must also have negative or missing HCVAb at baseline in order to be 
considered as having incident HIV/HCV coinfection.
“-” means any value can be present, as it does not affect the classification
For adverse events, the start date must be after the first dose date and on or prior to 
the last dose date for randomized phase analysis.
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 for randomized phase analysis”.
23) HBV DNA test codes: If the result of the laboratory test code GET1883 (HBV DNA 
CAP/CTM 2.0-EDTA-CL) is listed as “>170000000”, then a reflexive test code GET1884 
(HBV DNA CAP/CTM 2.0Dil-EDTA-CL) should be performed and will share the same 
accession number as the original GET1883 test. In this instance, use the result from 
GET1884 instead of GET1883 when determining HBV DNA.
24) Reasons for Subjects who excluded from Week 48 PP Analysis Set will be summarized as 
follows in table: 
a) Did Not Have On-Treatment HIV-1 RNA in Week 48 Window Unless due to 
Discontinuation of Study Drug for Lack of Efficacy
b) Did Not Meet the Criteria of Taking DTG + F/TAF, or DTG + F/TDF for the 
Protocol-defined Duration Before the screening visit 
c) Did Not Meet the Criterion of HIV-1 RNA < 50 copies/mL for the Protocol-defined 
Duration Before screening visit
d) Did Not Meet the Criteria of HIV-1 RNA < 50 copies/mL at screening visit
e) Did Not Meet the Criteria of Having no Resistance to INSTIs or Confirmed Virologic 
Failure


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f)
Did Not Meet the Criteria of Having only the Protocol Permitted Historical ARV 
resistance
g) Took Protocol Prohibited Medications
h) Adherence Rate for Active Study Drug up to Week 48 Visit Below the 2.5th Percentile
25) The number of decimal places in reporting p-values should be as follows:
a) values less than 0.0001  < 0.0001
b) values greater than 0.0001  round to 4 decimal places
26) In this study, only 3rd generation LDL is collected.
27) For nonstudy-drug ARV listing, ARVs which were dosed between the first dose date and the 
last dose date (inclusive) of study will be flagged (eg, ^). However, please note, if CM end 
date is completely missing and it’s not ongoing and CRF said it’s a ‘Prior ARV’, the ARV 
will not be flagged.
28) Study and/or study drug discontinuations due to COVID-19
a) Study Drug Discontinuation

Run NLP algorithm on the comment field from Study Drug Completion eCRF, 
checking for “COVID-19” text

In COCOVID19 data set if COFORM = “Study Drug Completion” , then subject 
discontinued study drug due to COVID-19

If study drug discontinued due to an AE, check if corresponding AE flagged as a 
COVID-19
b) Study Discontinuation

Run NLP algorithm on the comment field from general comments for “COVID-19” 
text

In COCOVID19 data set if COFORM = “Study Completion”, then subject 
discontinued study due to COVID-19

If study discontinued due to an AE, check if corresponding AE flagged as a 
COVID-19


B/F/TAF
GS-US-380-4030
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 84
30 April 2021
29) Serum Creatinine and eGFR correction
a) Serum creatinine (corrected)
For serum creatinine, the calibrator lot used in the quantitative assay for the measurement 
of serum creatinine was changed globally on 01JUL2018 local time. Each regional lab 
center conducted its own alternate (quantitative) method comparison, comparable results 
as noted in the table below.

For test results reported (RPTDTM) on or after 01JUL2018, use the inverse 
conversion formula in the below table as Calibration lot changed on 01JUL2018 local 
time.

The correction is based on unit of umol/L, after correction by regular regression, 
covert to mg/dL by multiplying 0.0113.
Regional Lab Center
Accession Number
Regular Regression for 
Correction (umol/L)
Inverse Conversion 
Formula (umol/L)
Indianapolis
start with 65
Y=1.002*X+1.77
Y=(X-1.77)/1.002
Geneva
start with 62 or 63
Y=1.025*X+2.62
Y=(X-2.62)/1.025
Shanghai
start with 67
Y=0.971*X+5.42
Y=(X-5.42)/0.971
Singapore 
start with 64 or 66
Y=1.009*X-1.42
Y=(X+1.42)/1.009
Japan
start with 68
Y=1.033*X+7.25
Y=(X-7.25)/1.033
Accession numbers specified which regional lab center tested the sample. For example, samples with accession number
started with 65 were tested in Indianapolis Auto Chemistry Center.
b) eGFR (corrected)
Recalculate eGFR using the corrected serum creatinine, using the following formula: 
eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / (SCr (mg/dL) 
× 72), where weight is total body mass in kilograms, and SCr is serum creatinine, age 
refers to the age at the sample collection date.
30) After Day 1, calcium, phosphorous, and magnesium tests were not performed unless a retest 
was needed so there is no summary table provided for these laboratory tests.


GS-US-380-4030 Final Analysis SAP V1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
30-Apr-2021
21:44:20
Clinical Research eSigned 04-May-2021
04:00:46
PPD
PPD

Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of Switching from a Regimen of Dolutegravir and 
Either Emtricitabine/Tenofovir Alafenamide or 
Emtricitabine/Tenofovir Disoproxil Fumarate to a Fixed Dose 
Combination of Bictegravir/ Emtricitabine/Tenofovir Alafenamide in 
HIV-1 Infected Subjects who are Virologically Suppressed
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2017-000308-17
TBD
Indication:
HIV-1 Infection
Protocol ID:
GS-US-380-4030
Gilead Study Clinical 
Program Manager:
Name:
Telephone:
Fax:
Gilead Medical 
Monitor:
Name:
Telephone:
Fax:
Protocol Version/Date:
Original:
06 February 2017
Amendment 1:
20 March 2017
Amendment 2:
28 June 2018
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The information is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol. 
You will not disclose any of the information to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered.
PPD
PPD
PPD
PPD
PPD
PPD


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Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 2
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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................13
1.
INTRODUCTION ..............................................................................................................................................16
1.1.
Background ............................................................................................................................................16
1.2.
Bictegravir..............................................................................................................................................17
1.2.1.
General Information .............................................................................................................17
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................17
1.2.3.
Clinical Studies of BIC.........................................................................................................19
1.3.
Information About Emtricitabine/Tenofovir Alafenamide (Descovy®, F/TAF) ....................................31
1.4.
Information about B/F/TAF ...................................................................................................................31
1.4.1.
GS-US-141-1233: Relative Bioavailability of BIC, FTC, and TAF 
between B/F/TAF and BIC+F/TAF .....................................................................................31
1.5.
Information about Dolutegravir (DTG, Tivicay®)..................................................................................32
1.6.
Rationale for this Study..........................................................................................................................32
1.7.
Risk/Benefit Assessment for the Study..................................................................................................33
1.8.
Rationale for Dose Selection..................................................................................................................33
1.9.
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............................................................................................................................37
3.5.
Biomarker Testing..................................................................................................................................39
3.5.1.
39
3.5.2.
Additional Sample Storage...................................................................................................39
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................42
5.
INVESTIGATIONAL MEDICINAL PRODUCTS (IMP).................................................................................44
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................44
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................44
5.2.
Description and Handling.......................................................................................................................45
5.2.1.
Formulation..........................................................................................................................45
5.2.2.
Packaging and Labeling .......................................................................................................46
5.2.3.
Storage and Handling...........................................................................................................47
5.3.
Dosage and Administration of B/F/TAF and DTG+F/TAF ...................................................................47
5.4.
Prior and Concomitant Medications.......................................................................................................47
5.5.
Accountability for IMP ..........................................................................................................................48
5.5.1.
IMP Return or Disposal........................................................................................................49
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6.
STUDY PROCEDURES ....................................................................................................................................50
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................50
6.2.
Pretreatment Assessments......................................................................................................................50
6.2.1.
Screening Visit .....................................................................................................................50
6.2.2.
Day 1 Assessments...............................................................................................................51
6.3.
Randomization .......................................................................................................................................51
6.4.
Treatment Assessments (Week 4 - 48)...................................................................................................52
6.5.
Treatment Assessments (Post Week 48 until the End of Blinded Treatment Visit)...............................53
6.5.1.
Post Week 48 Assessments ..................................................................................................53
6.5.2.
End of Blinded Treatment Visit Assessments ......................................................................53
6.5.3.
OL Extension Assessments ..................................................................................................54
6.6.
Post-treatment Assessments ...................................................................................................................55
6.6.1.
Early Study Drug Discontinuation Assessments..................................................................55
6.6.2.
30-Day Follow-Up Visit.......................................................................................................56
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................56
6.8.
End of Study...........................................................................................................................................57
6.9.
Post Study Care......................................................................................................................................57
6.10.
Clinical Laboratory Assessments ...........................................................................................................57
6.10.1.
Blood Samples......................................................................................................................57
6.10.2.
Urine Samples ......................................................................................................................59
6.10.3.
59
6.11.
Virologic Failure....................................................................................................................................59
6.11.1.
Management of Virologic Rebound .....................................................................................59
6.11.2.
Subjects with HIV-1 RNA ≥50 copies/mL at Study Drug 
Discontinuation, or Week 48................................................................................................61
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................62
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................62
7.1.1.
Adverse Events.....................................................................................................................62
7.1.2.
Serious Adverse Events........................................................................................................62
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................63
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................63
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................63
7.2.2.
Assessment of Severity ........................................................................................................64
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................64
7.3.1.
Adverse Events.....................................................................................................................64
7.3.2.
Serious Adverse Events........................................................................................................65
7.4.
Gilead Reporting Requirements.............................................................................................................66
7.5.
Toxicity Management ............................................................................................................................66
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................66
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................66
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................67
7.5.4.
On-Treatment ALT Flare .....................................................................................................67
7.5.5.
Management of Potential Hepatobiliary Toxicity ................................................................68
7.5.6.
On-Treatment Hepatitis C Management...............................................................................68
7.6.
Special Situations Reports......................................................................................................................69
7.6.1.
Definitions of Special Situations..........................................................................................69
7.6.2.
Instructions for Reporting Special Situations.......................................................................69
8.
STATISTICAL CONSIDERATIONS................................................................................................................71
8.1.
Analysis Objectives and Endpoints........................................................................................................71
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8.1.1.
Analysis Objectives..............................................................................................................71
8.1.2.
Primary Endpoint .................................................................................................................71
8.1.3.
Secondary Endpoint .............................................................................................................71
8.2.
Analysis Conventions.............................................................................................................................71
8.2.1.
Analysis Sets ........................................................................................................................71
8.3.
Data Handling Conventions ...................................................................................................................72
8.4.
Demographic Data and Baseline Characteristics ...................................................................................73
8.5.
Efficacy Analysis ...................................................................................................................................73
8.5.1.
Primary Analysis..................................................................................................................73
8.5.2.
Secondary Analyses .............................................................................................................74
8.6.
Safety Analysis.......................................................................................................................................75
8.6.1.
Extent of Exposure...............................................................................................................75
8.6.2.
Adverse Events.....................................................................................................................75
8.6.3.
Laboratory Evaluations ........................................................................................................76
8.6.4.
Other Safety Evaluations......................................................................................................76
8.7.
Patient Reported Outcomes (PRO).........................................................................................................76
8.8.
Sample Size............................................................................................................................................76
8.9.
Data Monitoring Committee ..................................................................................................................77
8.10.
Analysis Schedule ..................................................................................................................................77
9.
RESPONSIBILITIES..........................................................................................................................................78
9.1.
Investigator Responsibilities ..................................................................................................................78
9.1.1.
Good Clinical Practice..........................................................................................................78
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................78
9.1.3.
Informed Consent.................................................................................................................78
9.1.4.
Confidentiality......................................................................................................................79
9.1.5.
Study Files and Retention of Records ..................................................................................79
9.1.6.
Case Report Forms...............................................................................................................80
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................81
9.1.8.
Inspections............................................................................................................................81
9.1.9.
Protocol Compliance............................................................................................................81
9.2.
Sponsor Responsibilities ........................................................................................................................82
9.2.1.
Protocol Modifications.........................................................................................................82
9.2.2.
Study Report and Publications .............................................................................................82
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................82
9.3.1.
Payment Reporting...............................................................................................................82
9.3.2.
Access to Information for Monitoring..................................................................................83
9.3.3.
Access to Information for Auditing or Inspections ..............................................................83
9.3.4.
Study Discontinuation..........................................................................................................83
10.
REFERENCES ...................................................................................................................................................84
11.
APPENDICES ....................................................................................................................................................86
Appendix 1.
Investigator Signature Page....................................................................................................87
Appendix 2.
Study Procedures Table..........................................................................................................88
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................92
Appendix 4.
Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities ..........93
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................115
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................117


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LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: BIC Mean (%CV) PK Parameters Following Single Doses of 
BIC in Healthy Subjects (BIC PK Analysis Set; Part A: Single Dosing)...............................22
Table 1-2.
GS-US-141-1218: BIC Plasma Pharmacokinetic Parameters by BIC Dose 
Following Multiple-Dose Administration of BIC (Analysis Set: BIC PK Part B: 
Multiple-Dose) .......................................................................................................................23
Table 1-3.
GS-US-141-1218: Statistical Comparison of BIC Pharmacokinetic Parameters 
Following Single-Dose Administration of BIC in the Fasted and Fed States (BIC PK 
Analysis Set)...........................................................................................................................24
Table 1-4.
Trough BIC Plasma Concentrations at Steady State Following BIC Administration 
Under Fasting Conditions and Corresponding Protein-Adjusted IQ95 Values (BIC
PK Analysis Set) ....................................................................................................................25
Table 1-5.
GS-US-141-1475: Virologic Outcome at Week 48 Using the US FDA-Defined 
Snapshot Algorithm and HIV-1 RNA < 50 copies/mL (FAS) ...............................................28
Table 1-6.
GS-US-141-1219: Trough BIC Plasma Concentrations at Steady State Following 
BIC Administration Under Fasting Conditions and Corresponding Protein-Adjusted 
IQ95 Values.............................................................................................................................34
Table 5-1.
Prior and Concomitant Medications.......................................................................................48
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................25
Figure 3-1.
Study Schema.........................................................................................................................38
Figure 6-1.
Virologic Rebound Schema....................................................................................................60


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Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of Switching from a Regimen of Dolutegravir and 
Either Emtricitabine/Tenofovir Alafenamide or 
Emtricitabine/Tenofovir Disoproxil Fumarate to a Fixed Dose 
Combination of Bictegravir/ Emtricitabine/Tenofovir Alafenamide 
in HIV-1 Infected Subjects who are Virologically Suppressed
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2017-000308-17
TBD
Study Centers Planned:
Approximately 100 centers in North America and Europe
Objectives:
The primary objective of this study is:

To evaluate the efficacy of switching from a regimen of either 
dolutegravir (DTG) and emtricitabine/tenofovir alafenamide 
(F/TAF) or DTG and emtricitabine/tenofovir disoproxil fumarate
(F/TDF) to a fixed dose combination (FDC) of 
bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)
versus DTG+F/TAF in virologically suppressed HIV-1 infected 
subjects with or without antiretroviral (ARV) resistance 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
Study Design:
Randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to a FDC of B/F/TAF 
versus DTG+F/TAF in HIV-1 infected subjects who are 
virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable 
regimen of DTG+F/TAF or DTG+F/TDF for ≥6 months prior to 
screening (if there is documented or suspected nucleos(t)ide reverse 
transcriptase inhibitor [NRTI] resistance), or ≥3 months prior to 
screening (if there is no documented or suspected NRTI resistance).


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Subjects who provide written consent and meet all eligibility criteria 
will be randomized in a 1:1 ratio to switch to one of the following 
2 treatment groups:
Treatment Group 1 (n=260): FDC of B/F/TAF (50/200/25 mg) 
+ placebo to match DTG 50 mg + placebo to match FDC of F/TAF 
(200/25 mg) administered orally, once daily (QD), without regard to 
food (total of 3 tablets)
Treatment Group 2 (n=260): DTG 50 mg + FDC of F/TAF 
(200/25 mg) + placebo to match FDC of B/F/TAF (50/200/25 mg)
administered orally, QD, without regard to food (total of 3 tablets)
Randomization will be stratified by prior NRTI use (F/TAF vs. 
F/TDF) and documented or suspected history of NRTI resistance. 
The following NRTI-associated mutations will be considered as 
having NRTI resistance: M41L, K65R/E/N, D67N, T69 insertions, 
K70R, L74I/V, Y115F, Q151M, M184I/V, L210W, T215F/Y, 
K219Q/E/R/N, T69D, K70E/G/M/Q/S/T, V75A/S/M/T. NRTI 
resistance will be stratified by the following categories:
1) K65R/E/N, or 3 or more thymidine analogue mutations (TAMs)
that include M41L or L210W , or T69 insertions, (TAMs are: 
M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/R/N)
2) Any other pattern of NRTI resistance of M41L, D67N, K70R, 
L74I/V, Y115F, Q151M, M184I/V, L210W, T215F/Y, 
K219Q/E/R/N, T69D, K70E/G/M/Q/S/T, V75A/S/M/T
3) None of these mutations/No NRTI resistance
For subjects that qualify for more than one resistance category, 
stratification will be prioritized by category 1, then 2, then 3 above. 
Subjects taking F/TDF prior to study entry will discontinue F/TDF 
and will switch to an F/TAF-containing regimen (blinded B/F/TAF
or DTG+F/TAF). Subjects taking F/TAF prior to study entry will 
remain on an F/TAF-containing regimen (blinded B/F/TAF or 
DTG+F/TAF).
Number of Subjects 
Planned:
Approximately 520 subjects in total.
260 subjects in each Treatment Group 1 and Treatment Group 2
Target Population:
HIV-1 infected adult subjects who are virologically suppressed 
(HIV-1 RNA < 50 copies/mL) for ≥6 months (if there is 
documented or suspected NRTI resistance), or ≥3 months (if there 
is no documented or suspected NRTI resistance) prior to screening,
on a stable regimen of DTG+F/TAF or DTG+F/TDF.


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Duration of 
Treatment:
Subjects will be treated for at least 48 weeks during the blinded 
treatment phase. 
After Week 48, all subjects will continue to take their blinded study 
drug and attend visits every 12 weeks until the End of Blinded 
Treatment Visit. Once the last subject completes the Week 48 visit 
and Week 48 analysis is completed, all subjects will return to the 
clinic (preferably within 30 days) for an End of Blinded Treatment 
Visit. At the End of Blinded Treatment Visit, if safety and efficacy 
of B/F/TAF FDC is demonstrated following review of unblinded 
data, subjects in a country where B/F/TAF FDC is not available will 
be given the option to receive B/F/TAF FDC in an open-label (OL) 
extension phase for up to 96 weeks, or until the product becomes 
accessible to subjects through an access program, or until Gilead 
Sciences elects to discontinue the study in that country, whichever 
occurs first.
All subjects participating in the OL extension phase, without regard 
to their blinded treatment regimen, will return for study visits at 
Week 12 OL and every 12 weeks thereafter for up to 96 weeks. 
Subjects who complete the study through the End of Blinded 
Treatment Visit and do not continue on the open-label B/F/TAF
FDC extension phase, will be required to return to the clinic 30 days 
after the End of Blinded Treatment Visit for a 30-Day Follow-Up 
Visit.
Treatment assignments will be provided to the investigators within 
30 days of the last subject completing the End of Blinded Treatment 
Visit.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Currently receiving an ARV regimen of DTG+F/TAF or 
DTG+F/TDF for the following minimum time periods:
≥6 months (if there is documented or suspected NRTI 
resistance prior to the screening visit), 
≥3 months (if there is no documented or suspected NRTI 
resistance prior to the screening visit)


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Amendment 2
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
Documented plasma HIV-1 RNA < 50 copies/mL during 
treatment with DTG+F/TAF or DTG+F/TDF (for a minimum 
period of ≥ 6 or ≥3 months, as applicable) preceding the 
Screening Visit (or undetectable HIV-1 RNA level according to 
the local assay being used if the limit of detection is 
≥50 copies/mL)
The last two HIV-1 RNA measurements prior to screening 
must be < 50 copies/mL; however, unconfirmed virologic 
elevations of ≥ 50 copies/mL (transient detectable viremia, 
or “blip”) in the past are acceptable.
If the lower limit of detection of the local HIV-1 RNA assay 
is < 50 copies/mL (eg, < 20 copies/mL), the plasma HIV-1 
RNA level cannot exceed 50 copies/mL on two consecutive 
HIV-1 RNA tests after < 50 copies/mL has been achieved.

HIV-1 RNA levels < 50 copies/mL at Screening Visit. 

Estimated Glomerular Filtration Rate (eGFR) 30 mL/min 
according to the Cockcroft-Gault formula for creatinine 
clearance

No documented resistance to integrase stand transfer inhibitors 
(INSTIs) or confirmed virologic failure (2 consecutive HIV-1 
RNA ≥ 50 copies/mL after achieving < 50 copies/mL while on 
an INSTI-containing regimen)
Eligible subjects with the following historical ARV 
resistance are permitted to enroll:
■
Any NRTI resistance mutations
■
Any non-nucleoside reverse transcriptase mutations
■
Any protease inhibitor mutations
■
Subjects with resistance to 2 or more classes of 
antiretrovirals must be reviewed by the Gilead Medical 
Monitor to confirm eligibility

Eligible subjects with chronic HBV and/or HCV infection are 
permitted to enroll
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2, and treated for at least 
48 weeks. Following the Day 1 visit, subjects will return for study 
visits at Weeks 4, 8, and 12, and then every 12 weeks through the 
End of Blinded Treatment Visit.


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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 End of Blinded 
Treatment Visit. Laboratory analyses (hematology, chemistry, and 
urinalysis), HIV-1 RNA, CD4+ cell count and percentage, 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.  
Historical HIV-1 RNA genotypes (from resistance testing) will be 
collected, if available.
Test Product, Dose, and 
Mode of 
Administration:
FDC of bictegravir 50 mg/emtricitabine 200 mg/tenofovir 
alafenamide 25 mg (B/F/TAF) administered orally, once daily 
without regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Dolutegravir 50 mg (DTG) plus an FDC of emtricitabine 
200 mg/tenofovir alafenamide 25 mg (F/TAF) administered orally, 
once daily without regard to food.
Criteria for Evaluation:
Safety:
Adverse events, clinical laboratory tests, and tolerability of 
treatment regimens 
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as defined 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 defined by the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
 
 
 
 
 
 
 
PPD


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Patient Reported 
Outcome:
Short Form 36 Health Survey (SF-36), HIV Symptoms Distress 
Module, Work Productivity and Activity Impairment Questionnaire 
(WPAI), and Pittsburgh Sleep Quality Index (PSQI) will be 
administered at Day 1, Weeks 4, 12, and 48.
 
Statistical Methods:
The primary analysis will consist of a non-inferiority test of 
switching to B/F/TAF FDC versus DTG+F/TAF, with respect to the 
proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48, as defined by the US FDA-defined snapshot algorithm. It 
will be concluded that B/F/TAF FDC is non-inferior to 
DTG+F/TAF if the upper bound of the 2-sided 95% confidence 
interval (CI) of the difference between treatment groups [B/F/TAF –
(DTG+F/TAF)] 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). 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 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 an 
Analysis of Variance (ANOVA) model, including treatment 
(B/F/TAF vs. DTG+F/TAF), prior NRTI use (F/TAF vs. F/TDF),
and documented or suspected history of NRTI resistance  as fixed 
effects in the model.
Adverse events and clinical laboratory assessment will be 
summarized using descriptive statistics.
Patient reported outcome instrument assessments may be 
summarized using descriptive statistics.
A total of approximately 520 HIV-1 infected subjects, randomized 
in a 1:1 ratio to 2 treatment groups (260 subjects per treatment 
group), achieves at least 90% power to detect a non-inferiority 
margin of 4% in difference in percentage of subjects with HIV-1 
RNA ≥50 copies/mL at Week 48 between the 2 treatment groups.
PPD


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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® 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
AE
adverse event
AhR
aryl hydrocarbon receptor
AIDS
acquired immune deficiency syndrome
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration 
versus time curve
BA
bioavailability
BIC, B
bictegravir
B/F/TAF
bictegravir/emtricitabine/tenofovir alafenamide
BMD
bone mineral density
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CK
creatine kinase
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRO
contract (or clinical) research organization 
CSR
clinical study report
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DTG
dolutegravir, Tivicay
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
EVG
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, Genvoya®
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination
F/TAF 
emtricitabine/tenofovir alafenamide, Descovy®


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F/TDF 
emtricitabine/tenofovir disoproxil fumarate 
FTC, F
emtricitabine, Emtriva
GCP
Good Clinical Practice (Guidelines)
GGT
gamma glutamyl transferase
GLSM
geometric least squares mean
GSI, Gilead
Gilead Sciences, Inc.
HAART
highly active antiretroviral therapy
HBV
hepatitis B virus
HBcAb
hepatitis B core antibody
HBeAB
hepatitis B virus e-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
HLA
human leukocyte antigen
HLGT
high-level group term
HLT
high-level term
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IMP, study drug
investigational medicinal products
IND
Investigational New Drug (Application)
INSTI
integrase strand-transfer inhibitor
IRB
institutional review board
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LLN
lower limit of the normal range
LLT
lower level term
LSM
least-squares mean
MAD
multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
min
minute
mmHg
millimeters mercury
NNRTI
non-nucleoside reverse transcriptase inhibitor
NOEL
no observed effect level
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
N(t)RTI
nucleos(t)ide reverse transcriptase inhibitor


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OCT2
organic cation transporter 2
OL
open label
PBMC
peripheral blood mononuclear cell
PI
protease inhibitor
PK
pharmacokinetic
PP
per-protocol
PRO
patient reported outcomes
PSQI
Pittsburgh Sleep Quality Index
PT
preferred term 
PTM
placebo-to-match
PVE
Pharmacovigilance and Epidemiology
PXR
pregnane X receptor
RAL
raltegravir
rBA
relative bioavailability
RNA
ribonucleic acid
SAD
single ascending dose
SADR
serious adverse drug reaction
SAE
serious adverse event
SF-36
Short Form 36 Health Survey
SmPC
Summary of Product Characteristics
SOC
system organ class
SOP
standard operating procedures
STR
single tablet regimen
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide 
TAM
thymidine analogue mutations
TDF
tenofovir disoproxil fumarate, Viread
TFV
tenofovir
TFV-DP
tenofovir diphosphate (TFVpp)
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase 
ULN
upper limit of the normal range
US
United States
WPAI
Work Productivity and Activity Impairment Questionnaire


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 37 million people 
worldwide {Joint United Nations Programme on HIV/AIDS (UNAIDS) 2016}. 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 1998}, {Mocroft 1998}, {Sterne 
2005}.
The success of potent and well-tolerated antiretroviral therapy (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, antiretroviral (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 {Panel on 
Antiretroviral Guidelines for Adults and Adolescents 2016}. 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 2012}, {Aldir 2014}
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other nucleoside/nucleotide reverse transcriptase 
inhibitor (NRTIs). Tenofovir alafenamide (TAF) is also an oral prodrug of TFV. TAF is more 
stable in plasma than TDF, provides higher intracellular levels of the active phosphorylated 
metabolite tenofovir diphosphate (TFV-DP), and approximately 90% lower circulating levels of 
TFV relative to TDF at the clinical doses. The distinct metabolism of TAF offers the potential 
for an improved clinical profile compared with TDF.


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Bictegravir (BIC) (previously referred to as 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 
BIC is active against a broad panel of HIV-1 viral lab strains and clinical isolates. BIC is fully 
active against a panel of mutant viruses with resistance to NRTIs, non-nucleoside 
reverse-transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). Integrase mutant viruses 
that are resistant to the INSTIs raltegravir (RAL) and elvitegravir (EVG) remain largely sensitive 
to BIC.
Gilead Sciences (Gilead) has coformulated BIC with the NRTI emtricitabine (FTC; F) and the 
NtRTI TAF into an FDC tablet that is suitable for once-daily use. This 
bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC may provide a potent, 
convenient, tolerable, and practical regimen for the long-term treatment of patients with HIV 
infection.
1.2.
Bictegravir
1.2.1.
General Information
BIC, a potent inhibitor of HIV-1 integrase is being evaluated for the treatment of HIV infection. 
1.2.2.
Preclinical Pharmacology and Toxicology
A core battery of safety pharmacology studies have been conducted with BIC. 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 BIC on all major organ systems. The 
volume of distribution of BIC ranged between 0.09 and 0.22 L/kg in the preclinical species, 
which indicates that the distribution of BIC is limited to the extracellular compartment due to its 
high binding to plasma proteins. The projected half-life of BIC in humans is approximately 
20 hours based upon the estimates of clearance and volume of distribution.
1.2.2.1.
Pharmacology
BIC has IC50 values ranging from 1.5 to 2.4 nM, similar to the inhibitory effect of dolutegravir 
(DTG) and EVG. BIC is highly potent against HIV replication in MT4 cells with an EC50 (50% 
effective inhibitory concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. 
BIC does not show significant cytotoxicity against dividing and non-dividing human peripheral 
blood mononuclear cell (PBMCs), primary human hepatocytes and various non-target human 
cell lines.
BIC is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
cytochrome P450 enzyme (CYP)3A. BIC does not inhibit major human CYP isoforms or
UGT1A1 at concentrations up to 25 M. Consequently, BIC 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. BIC only modestly inhibits renal transporter organic cation 
transporter 2 (OCT2) (IC50 = 0.42 M). As a result, BIC is not expected to significantly interfere


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with the key transporter responsible for creatinine tubular elimination at the clinically projected 
Cmax. Additionally, the risk that BIC will affect the OCT2-mediated excretion of co-administered 
drugs is considered to be low.
BIC does not activate aryl hydrocarbon receptor (AhR) and only weakly activates pregnane X 
receptor (PXR) at concentrations up to 50 M (less than 5% and 40% of activation, respectively,
compared to positive control compound). Therefore, BIC 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 BIC up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of BIC
up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was limited 
(< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL, respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, BIC was well-tolerated with no BIC-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, BIC exposures in the rat were considered to be 
approximately 12-/31-fold higher (males/females) than the projected steady state human 
exposure of BIC following administration of B/F/TAF (50/200/25 mg) once daily under fed 
conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of BIC 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, BIC-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 alanine aminotransferase (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 BIC-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the 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 B/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 BIC. 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 Studies of BIC
Clinical studies entailing the use of BIC 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 emtricitabine/tenofovir alafenamide 
(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 (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)


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
GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)

GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled Phase 1 Study 
Evaluating the Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular 
Filtration Rate (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 (B/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 (completed)

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 B/F/TAF Investigators’ Brochure for further information about these studies.
1.2.3.1.
Phase 1 Safety and Pharmacokinetics (PK)
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 BIC in healthy 
male and female subjects.  Part C was an open label, fixed sequence food effect study evaluating 


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the effect of food on the PK of BIC.  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 
BIC in healthy subjects.
There was no difference in the overall incidence or type of adverse events (AEs) when BIC was 
administered in the fasted and fed states. There was no difference in the overall incidence of AEs 
when BIC or FTC/TAF was each administered alone or in combination.
No deaths or pregnancies were reported. No Grade 3 or 4 AEs or serious adverse events (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 multiple ascending dose (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 BIC
monotherapy for 7 days and 100 mg BIC with FTC/TAF for 7 days, the mean serum creatinine 
change at Day 7 was 0.14 mg/dL following BIC and 0.17 mg/dL following BIC + FTC/TAF. All 
changes returned to baseline after discontinuation of BIC.
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 BIC 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. BIC exposures were 
appropriately dose proportional following single dose 25-100 mg dose administration, with 
decreasing dose proportional at higher doses. The half-life of BIC 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 BIC with average accumulation ratios for AUC24hr of 1.6.


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Table 1-1.
GS-US-141-1218: BIC Mean (%CV) PK Parameters Following 
Single Doses of BIC in Healthy Subjects (BIC PK Analysis Set; 
Part A: Single Dosing)
BIC 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 BIC plasma PK parameters following administration of BIC
(5, 25, 50, 100, and 300 mg) once daily for 7 days. Following administration of either BIC
(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 single ascending dose (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 BIC AUC and Cmax on Days 1 and 7 over the dose range of 25 to 50 mg. 
Steady state levels of BIC 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 BIC (approximately 18 hours).


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Table 1-2.
GS-US-141-1218: BIC Plasma Pharmacokinetic Parameters by BIC
Dose Following Multiple-Dose Administration of BIC
(Analysis Set: BIC PK Part B: Multiple-Dose)
BIC PK Parameter Mean
(%CV)a
Multiple-Dose BIC
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% confidence intervals (CIs) for the test (fed) versus reference (fasted) treatments for the 
primary plasma PK parameters of BIC . Administration of a single dose of BIC 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 BIC by improving 
its solubility and/or absorption.


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Table 1-3.
GS-US-141-1218: Statistical Comparison of BIC Pharmacokinetic 
Parameters Following Single-Dose Administration of BIC in the 
Fasted and Fed States (BIC PK Analysis Set)
BIC PK Parameter 
Mean (%CV)
% GLSM Ratio 
(90% CI)
Test 
BIC 100 mg Fed
(n = 8)
Reference
BIC 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 1b Proof of Concept
The first HIV-1 positive human subjects were dosed in the fasted state with 10 days of BIC in 
Study GS-US-141-1219.  Four cohorts of 5 subjects each were randomized 4:1 to receive BIC or 
placebo to match (PTM) at doses of 5 mg, 25 mg, 50 mg, and 100 mg once daily for 10 days.
BIC 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 BIC.
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 BIC. This was a Grade 4 creatine phosphokinase (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 
creatine kinase (CK) was reported unrelated to study medication.
Based on PK information collected in Study GS-US-141-1219, which was in line with PK 
observed in Study GS-US-141-1218, the median IQ for each dose were calculated and are 
presented in Table 1-4 below.


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Table 1-4. 
Trough BIC Plasma Concentrations at Steady State Following BIC 
Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ9s Values (BIC PK Analysis Set) 
BIC dose 
n 
Median (mnge) Ctau,ss (nglmL) 
Median (range) paiQ9s" 
5mg 
4 
206.5 (146.0 to 342.0) 
1.3 (0.9 to 2.1) 
25mg 
4 
797.5 (714.0 to 1900.0) 
4.9 (4.4 to 11.7) 
50 mg 
4 
2170.0 (852.0 to 3020.0) 
13.4 (5.3 to 18.6) 
lOOmg 
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 (162ng/ml). 
The mean and 95% Cis of change from baseline in HIV -1 ribonucleic acid (RNA) 
(log10 copies/mL) are presented in Figure 1-1. 
Figure 1-1. 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log1o copies/mL) (PP Analysis Set) 
GS-9883 5 mg (~): 
GS-9883 25 mg (~): 
GS-9883 50 mg (~): 
GS-9883 100 mg (~): 
Placebo (n= ): 
• = GS-9883 5 mg 
0 = GS-9883 25 mg 
fl = GS-9883 50 mg 
D = GS-9883100 mg 
<:> =Placebo 
Bl 
2 
3 
3 
3 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
7 
8 
9 
Day 
3 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
3 
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 
----_..... 
--
--
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study drug. 
17 
3 
3 
4 
4 
4 
2 
-1 
-2 
-3 
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Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort.  Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the BIC 50 mg group and 2 subjects (50%) in the BIC 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 BIC+F/TAF
versus DTG+F/TAF in HIV-infected, ART-naive adult subjects.
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to 
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: BIC 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 BIC 75 mg 
once daily
Week 48 interim data are summarized below. 
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the BIC+F/TAF
group and 33 subjects in the DTG+F/TAF group. At the time of the Week 48 data analysis, 
5 subjects (5.1%) had prematurely discontinued study drug, 3 in the BIC+F/TAF group and 2 in 
the DTG+F/TAF group. The reasons for study drug discontinuation were as follows (one subject 
each): AE, withdrawal of consent, and lost to follow-up in the BIC+F/TAF group, and 
noncompliance with study drug and lost to follow up in the DTG+F/TAF group.
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]CG) 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% 
having ≤ 100,000 copies/mL at baseline. Five subjects (5.1%) had > 400,000 copies/mL at 
baseline; of these, 4 subjects were randomized to BIC+F/TAF and 1 subject was randomized to 
DTG+F/TAF. 
Median (Q1, Q3) baseline CD4+ cell count was 444 (316, 595) cells/μL, with 41.8% of subjects 
having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 
125.3 (105.7, 147.0) mL/min.


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Efficacy Results
The primary efficacy endpoint was the proportion of subjects with HIV-1 RNA 50 copies/mL 
at Week 24 as determined by the United States (US) Food and Drug Administration 
(FDA)-defined snapshot algorithm. The percentages of subjects with HIV-1 RNA 
< 50 copies/mL at Week 24 was high in both groups, as follows: BIC+F/TAF 96.9%; 
DTG+F/TAF 93.9%; difference in percentages: 2.9%, 95% CI: −8.5% to 14.2%. Because the 
lower bound of the 95% CI for the difference in response rate (BIC+F/TAF – DTG+F/TAF) was 
greater than the prespecified −12% margin, BIC+F/TAF was determined to be noninferior to 
DTG+F/TAF.
The percentages of subjects with HIV-1 RNA < 50 copies/mL at Week 48 were similar between 
the 2 treatment groups when assessed using the US FDA-defined snapshot algorithm based on 
the full analysis set (FAS) (Table 1-5), as follows: BIC+F/TAF 96.9%; DTG+F/TAF 90.9%; 
difference in percentages: 6.4%, 95% CI: −6.0% to 18.8%.
As expected for an INSTI-containing regimen, HIV-1 RNA levels decreased rapidly in the 
first 4 weeks following initiation of study drug in both treatment groups. After Week 4, HIV-1 
RNA values were stable and similar between the 2 treatment groups through Week 48; mean 
(SD) decreases from baseline at Week 48 using the FAS were as follows: BIC+F/TAF 
−3.09 (0.752) log10copies/mL; DTG+F/TAF −3.11 (0.852) log10copies/mL; difference in 
least-squares mean (LSM): −0.06 log10copies/mL, 95% CI: −0.32 to 0.20 log10copies/mL.
The mean (SD) increases from baseline in CD4+ cell counts were similar between the 
2 treatment groups through Week 48 using the FAS, as follows: BIC+F/TAF 
258 (221.7) cells/μL; DTG+F/TAF 192 (242.0) cells/μL; difference in LSM: 72 cells/μL, 
95% CI: −30 to 174 cells/μL.


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Table 1-5.
GS-US-141-1475: Virologic Outcome at Week 48 Using the US 
FDA-Defined Snapshot Algorithm and HIV-1 RNA < 50 copies/mL 
(FAS)
BIC+F/TAF
(N = 65)
DTG+F/TAF
(N = 33)
BIC+F/TAF vs DTG+F/TAF
p-valuea
Difference in 
Percentages 
(95% CI)b
HIV-1 RNA < 50 copies/mL
63 (96.9%)
30 (90.9%)
0.17
6.4% 
(−6.0% to 18.8%)
HIV-1 RNA ≥ 50 copies/mL
1 (1.5%)
2 (6.1%)
HIV-1 RNA ≥ 50 copies/mL in Week 48 
window
0
1 (3.0%)
Discontinued study drug due to lack of efficacy
0
0
Discontinued study drug due to other reasons 
and last available HIV-1 RNA ≥50 copies/mLc
1 (1.5%)
1 (3.0%)
No virologic data in Week 48 window
1 (1.5%)
1 (3.0%)
Discontinued study drug due to AE/death
1 (1.5%)
0
Discontinued study drug due to other reasons 
and last available HIV-1 RNA < 50 copies/mLc
0
1 (3.0%)
Missing data during window but on study drug
0
0
Week 48 window was between Day 295 and 378 (inclusive).
a
p-value for the superiority test comparing the percentages of subjects with HIV-1 RNA < 50 copies/mL between treatment 
groups was from the Cochran-Mantel-Haenszel test stratified by baseline HIV-1 RNA stratum (≤100,000 vs 
> 100,000 copies/mL).
b
Difference in percentages of subjects with HIV-1 RNA < 50 copies/mL between treatment groups and its 95% CI were 
calculated based on the baseline HIV-1 RNA stratum-adjusted Mantel-Haenszel proportion.
c
Discontinuation due to other reasons included subjects who prematurely discontinued study drug due to investigator’s 
discretion, withdrew consent, lost to follow-up, noncompliance with study drug, protocol violation, pregnancy, and study 
termination by sponsor.
Interim Virology Resistance Data
Through Week 48, no emergent drug resistance was detected in the BIC+F/TAF group.
Safety Results
Adverse Events
Adverse events were reported in 84.6% (55 of 65 subjects) in the BIC+F/TAF group and 66.7% 
(22 of 33 subjects) in the DTG+F/TAF group. The most commonly reported AEs by treatment 
group were as follows:

BIC+F/TAF group—diarrhea (12.3%, 8 of 65 subjects); and headache, nausea, and upper 
respiratory tract infection (each 7.7%, 5 subjects)

DTG+F/TAF group—diarrhea and nausea (each 12.1%, 4 of 33 subjects); and arthralgia, 
fatigue, flatulence, furuncle, gastroenteritis, costochondritis, hemorrhoids, and pruritus 
(each 6.1%, 2 subjects)


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The majority of AEs were Grade 1 in severity, with similar incidence of Grade 2, 3, or 4 AEs 
between the 2 treatment groups. Grade 3 AEs were uncommon, with all Grade 3 AEs reported in 
the BIC+F/TAF group (6.2%, 4 subjects); only 1 Grade 3 AE was considered related to study 
drug by the investigator (urticaria in a BIC+F/TAF subject). No individual Grade 3 AE was 
reported for > 1 subject. No Grade 4 AEs were reported.
Serious AEs were uncommon, with all reported SAEs occurring in the BIC+F/TAF group 
(4.6%, 3 subjects). No SAE was considered related to study drug by the investigator. The SAEs 
reported were appendicitis, psychotic disorder/suicidal ideation, and diabetic ketoacidosis.
The incidence of AEs considered related to study drug by the investigator was similar between 
the 2 treatment groups (BIC+F/TAF 20.0%, 13 subjects; DTG+F/TAF 21.2%, 7 subjects). 
Nearly all study drug-related AEs were Grade 1 in severity, with similar incidence of Grade 2, 3, 
or 4 study drug-related AEs between the 2 treatment groups (BIC+F/TAF 3.1%, 2 subjects; 
DTG+F/TAF 3.0%, 1 subject). The only Grade 3 study drug-related AE reported (urticaria in a 
BIC+F/TAF subject) was also the only AE leading to premature study drug discontinuation; the 
event began on Day 130 and led to discontinuation of study drug on Day 162.
No deaths or pregnancies were reported in either treatment group.
Clinical Laboratory Evaluations
Most subjects in both treatment groups had at least 1 laboratory abnormality (BIC+F/TAF 
84.4%, 54 of 64 subjects; DTG+F/TAF 87.5%, 28 of 32 subjects). Most of the reported 
laboratory abnormalities were Grade 1 or 2 in severity. The incidence of Grade 3 or 4 laboratory 
abnormalities was similar between the 2 treatment groups (BIC+F/TAF 25.0%, 16 subjects; 
DTG+F/TAF 21.9%, 7 subjects). 
Graded laboratory abnormalities in ALT and aspartate aminotransferase (AST) were reported 
more frequently and with greater severity in the BIC+F/TAF group than in the DTG+F/TAF 
group. Graded ALT abnormalities were reported in 23.4% (15 of 64 subjects) in the BIC+F/TAF 
group and 9.4% (3 of 32 subjects) in the DTG+F/TAF group, and graded AST abnormalities 
were reported in 20.3% (13 of 64 subjects) in the BIC+F/TAF group and 9.4% (3 of 32 subjects) 
in the DTG+F/TAF group. Grade 3 ALT elevations occurred in 1 subject in the BIC+F/TAF 
group and none in the DTG+F/TAF group. Grade 3 AST elevations were seen in 3 subjects in 
the BIC+F/TAF group (one of whom also had a Grade 3 ALT elevation) and none in the 
DTG+F/TAF group. Of the 3 subjects who had Grade 3 transaminase elevations, 2 were 
associated with simultaneous Grade 4 CK elevations, were transient, and resolved rapidly 
without any associated AEs. One participant had both Grade 3 AST and ALT persistent 
elevations that were attributed to ongoing alcohol use. No Grade 4 transaminase elevations were 
observed in either treatment group.
Grade 3 or 4 CK elevations were seen in 9.4% (6 of 64 subjects) in the BIC+F/TAF group and in 
3.1% (1 of 32 subjects) in the DTG+F/TAF group. All of the Grade 3 or 4 CK elevations 
occurred in young men (age range, 24 to 31 years), were transient, and resolved without 
treatment interruption, and none of these laboratory abnormalities were associated with AEs.


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There were similar increases from baseline in median (Q1, Q3) serum creatinine in both 
treatment groups at Week 48: BIC+F/TAF 0.08 (0.02, 0.15) mg/dL; DTG+F/TAF 
0.12 (0.02, 0.20) mg/dL. There were decreases in median (Q1, Q3) eGFRCG at Week 48, which 
were smaller in the BIC+F/TAF than in the DTG+F/TAF group: BIC+F/TAF 
−7.0 (−18.7, 1.6) mL/min; DTG+F/TAF −11.3 (−24.5, −0.8) mL/min.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. 
Conclusions
Key conclusions from Study GS-US-141-1475 at Week 48 include the following:

The percentages of subjects with HIV-1 RNA < 50 copies/mL at Week 48 were similar 
between the 2 treatment groups when assessed using the US FDA-defined snapshot algorithm 
based on the FAS, as follows: BIC+F/TAF 96.9%; DTG+F/TAF 90.9%; difference in 
percentages: 6.4%, 95% CI: −6.0% to 18.8%. There was a similar increase in the mean (SD) 
CD4+ cell count between the 2 treatment groups: BIC+F/TAF 258 (221.7) cells/μL; 
DTG+F/TAF 192 (242.0) cells/μL; difference in LSM: 72 cells/μL, 
95% CI: −30 to 174 cells/μL.

No resistance to any INSTIs, NRTIs, NNRTIs, or PIs was detected through Week 48 in the 
BIC+F/TAF group.

Both BIC+F/TAF and DTG+F/TAF were generally well tolerated through 48 weeks of 
treatment. 
The most commonly reported AEs were diarrhea (12.3%, 8 of 65 subjects); and 
headache, nausea, and upper respiratory tract infection (each 7.7%, 5 subjects) in the 
BIC+F/TAF group, and diarrhea and nausea (each 12.1%, 4 of 33 subjects); and 
arthralgia, fatigue, flatulence, furuncle, gastroenteritis, costochondritis, hemorrhoids, and 
pruritus (each 6.1%, 2 subjects) in the DTG+F/TAF group. 
One subject discontinued study drug due to AE: Grade 3 urticaria beginning on Day 130 
in a BIC+F/TAF subject. There were SAEs in 3 subjects, none of which were considered 
related to study drug by the investigator, or led to study drug discontinuation. 
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. Graded laboratory abnormalities in ALT and 
AST were reported more frequently and with greater severity in the BIC+F/TAF group 
than in the DTG+F/TAF group. 
There were similar increases from baseline in serum creatinine in both treatment groups at 
Week 48. The decrease from baseline in eGFRCG was smaller in the BIC+F/TAF group than in 
the DTG+F/TAF group.


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1.3.
Information About Emtricitabine/Tenofovir Alafenamide (Descovy®, F/TAF)
F/TAF is a FDC tablet containing two medications: emtricitabine (FTC) and TAF.  
The safety of F/TAF FDC is based on two year-long clinical studies (GS-US-292-0104 and 
GS-US-292-0111) in which 866 treatment-naïve subjects received 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) FDC. The following 
adverse drug reactions have been identified for F/TAF: 
Very common (more than or equal to 10%): headache, diarrhea, and nausea
Common (≥ 1% and < 10%): vomiting, abdominal pain, dyspepsia , flatulence, rash, and fatigue
Across all Phase 2 and Phase 3 studies in which 2,394 subjects received E/C/F/TAF FDC, eye 
disorders were uncommon, balanced between treatment groups, and most were considered by the 
investigator as unrelated to the study drugs. None were definitive for posterior uveitis, and none 
resulted in permanent discontinuation of study drugs. One subject in Study GS-US-292-0106 had 
an adverse reaction of intermediate uveitis (inflammation in the middle of the eye) that was 
considered related to study drug by the investigator but resolved while the subject continued on 
study drug without interruption.
For further information on F/TAF, refer to the current Prescribing Information for Descovy®™.
1.4.
Information about B/F/TAF
Please refer to the B/F/TAF Investigator’s Brochure for further information.
1.4.1.
GS-US-141-1233: Relative Bioavailability of BIC, FTC, and TAF between 
B/F/TAF and BIC+F/TAF
Study GS-US-141-1233 was a Phase 1, open-label, 2-cohort, multiple-period, fixed-sequence, 
crossover study conducted at a single center in the US to evaluate the relative bioavailability of 
2 B/F/TAF FDC tablets (75/200/25 mg and 50/200/25 mg) compared with the BIC tablet 
(75 mg) and the F/TAF FDC tablet (200/25 mg) administered simultaneously. For more detailed 
information on study design and key findings of this study refer to the Investigators’ Brochure.
For the 75-mg B/F/TAF FDC, BIC AUCinf and Cmax were approximately 27% and 31% higher, 
respectively, than those observed for BIC 75 mg + F/TAF. Emtricitabine and TAF exposures 
were similar between the 75-mg B/F/TAF FDC and BIC 75 mg + F/TAF.
For the 50-mg B/F/TAF FDC, the GLSM ratios and their 90% CIs comparing the primary PK 
parameters for BIC, FTC, and TAF between the 50-mg B/F/TAF FDC and BIC 75 mg + F/TAF 
under fasted conditions were within the protocol-defined boundaries of equivalence, with the 
exception of TAF Cmax, for which the GLSM ratio (90% CI) was 84.17% (67.59%, 104.81%; 
equivalence boundary of 70% to 143%). Emtricitabine exposure was comparable with that 
observed historically {EMTRIVA® 2012}, and TAF exposure was within the wide range of safe 
and efficacious exposure established in the Phase 3 Genvoya studies (predicted individual 


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steady-state mean [95% CI, %CV] AUC 206.4 ng•h/mL [55.6 to 526.1 ng•h/mL, 71.8%]. 
Together, these results demonstrate that the B/F/TAF (50/200/25 mg) FDC will provide 
therapeutic concentrations of BIC, FTC, and TAF. The variability associated with BIC exposure 
following administration of the 50-mg B/F/TAF FDC was lower, irrespective of fasted or fed 
condition, relative to BIC 75 mg + F/TAF administered under fasted conditions.
1.5.
Information about Dolutegravir (DTG, Tivicay®)
An ongoing observational study in Botswana identified neural tube defects (NTDs) in infants 
born to four of 426 women who started DTG prior to pregnancy, and were on it at the time of 
conception. The incidence rate for NTDs in these infants was 0.9%, while the reported rate of 
NTDs for HIV-infected women on non-DTG-containing regimen was 0.1%. These preliminary 
results suggest that women who received DTG at the time of becoming pregnant or early in the 
first trimester appear to be at higher risk for these embryonic defects.
The following guidance has been issued regarding the use of DTG in women who are pregnant, 
who become pregnant, or are of child bearing potential. 

FDA statement: https://www.fda.gov/Drugs/DrugSafety/ucm608112.htm

U.S. DHHS Recommendations Regarding the Use of Dolutegravir in Adults and Adolescents 
with HIV who are Pregnant or of Child-Bearing Potential: 
https://aidsinfo.nih.gov/news/2109/recommendations-regarding-the-use-of-dolutegravir-in-
adults-and-adolescents-with-hiv-who-are-pregnant-or-of-child-bearing-potential

European Medicines Agency (EMA): 
http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2018/05/news_
detail_002956.jsp&mid=WC0b01ac058004d5c1
For more detailed information, refer to the current Prescribing Information and local product 
labeling for DTG.
1.6.
Rationale for this Study
The two tablet regimen of DTG+F/TAF has become a regimen of choice for the initiation of 
treatment of HIV infected adults, as this combination provides the safety and efficacy of a TAF 
based regimen with the benefits of an unboosted INSTI that provides a high barrier to resistance. 
In addition, all patients taking DTG+F/TDF will switch to an F/TAF containing regimen. 
HIV-infected patients are often diagnosed earlier and initiate therapy earlier, and despite the 
availability of single tablet regimen (STRs), a need remains for an STR, particularly an 
INSTI-based STR that combines potent and sustained efficacy, favorable tolerability, minimal 
long-term toxicity, and practical, convenient dosing that does not require human leukocyte 
antigen (HLA) or hepatitis B testing prior to initiation. 
Total pill burden, dosing frequency, and safety concerns are among the greatest obstacles to 
achieving adherence {Stone 2002}, {Chesney 2000}. Incomplete adherence to ARV regimens is 
a critical factor contributing to the development of viral resistance and treatment failure and thus 


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is a primary barrier to successful long-term treatment. This is supported by studies in which 
simple, once-daily HAART regimens demonstrate high levels of adherence and treatment 
satisfaction resulting in durable viral suppression and CD4+ cell recovery {Maggiolo 2001}, 
{Felizarta 2004}, {Arribas 2004}, {Willig 2008}.
Regimen simplification of an established therapy will reduce pill burden and will potentially 
enhance long-term safety and tolerability. This study will provide clinical data in patients who 
are virologically suppressed but who are taking a multi-tablet regimen. The goal of this study is 
to assess whether switching to a single tablet regimen of B/F/TAF from a 2 tablet regimen of 
DTG plus F/TAF or F/TDF will provide comparable virologic control along with improved 
safety and tolerability. DTG+F/TAF was selected as the active comparator for this study as it is a 
recommended INSTI-based, once-daily regimen {Panel on Antiretroviral Guidelines for Adults and 
Adolescents 2016}, {Gunthard 2016}, {European AIDS Clinical Society (EACS) 2016}. Use of 
DTG+F/TAF as a comparator in this study will therefore allow for a direct comparison of DTG 
versus BIC, two second generation, unboosted INSTIs.
1.7.
Risk/Benefit Assessment for the Study
All patients with HIV-1 infection should receive effective antiretroviral therapy. Potential risks 
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and 
lactic acidosis with steatosis.  The risk of class effects is considered to be low. Interim data will 
also be reviewed by an independent data monitoring committee. Potential benefits may include 
provision of a new ARV 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 BIC (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 BIC exposures that were approximately 5-fold 
above human exposures when given the B/F/TAF FDC. No adverse drug reactions associated 
with liver or bile duct problems has been identified in humans treated with BIC. Potential 
hepatobiliary toxicity is appropriately managed by study inclusion/exclusion criteria, close 
clinical and laboratory monitoring, as well as specific toxicity management guidance to 
investigators (Refer to Section 7.5.5).
The overall benefit-risk assessment for B/F/TAF is favorable at this time. 
1.8.
Rationale for Dose Selection
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.


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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 cobicistat 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-141-1218 showed 
that BIC does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the B/F/TAF FDC.
F/TAF
Emtricitabine 200 mg is the marketed dose for the treatment of HIV-1 infection in adults. The 
F/TAF FDC (200/25 mg) is the marketed dose for the treatment of HIV-1 infection in adults in 
combination with DTG.
BIC
The dose of BIC for Phase 2 was selected based upon data from Study GS-US-141-1219
(Table 1-6), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
BIC monotherapy under fasting conditions for 10 days.
Table 1-6.
GS-US-141-1219: Trough BIC Plasma Concentrations at Steady State 
Following BIC Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ95 Values
BIC dose
N
Median (range) Ctau,SS (ng/mL)
Median (range) paIQ95a
5 mg
4
206.5 (146.0 – 342.0)
1.3 (0.9 – 2.1)
25 mg
4
797.5 (714.0 – 1900.0)
4.9 (4.4 – 12)
50 mg
4
2170.0 (852.0 – 3020.0)
13 (5.3 – 19)
100 mg
4
4190.0 (3730.0 – 5970.0)
26 (23 – 37)
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 BIC was well tolerated at all doses administered. The range of BIC 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 BIC plasma 
exposure at steady state (Ctau,SS) observed in the 100-mg cohort correlated with paIQ95 values 
ranging from 23 to 37 (Table 1-6).
Based on PK/pharmacodynamics analyses, exposure following a 75-mg dose of single-agent BIC
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). BIC (75 mg) single agent coadministered with F/TAF (200/25 mg) is currently being 
evaluated in a Phase 2 study, GS-US-141-1475 (BIC +F/TAF vs DTG+F/TAF). The Week 24
data from this study support the safety and efficacy of B/F/TAF exposures obtained with the 
75 mg dose of the single agent.


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B/F/TAF FDC Dose Selection
A fixed dose formulation of B/F/TAF was developed for use in Phase 3 studies. Preliminary 
results from the relative bioavailability (rBA) study (GS-US-141-1233) of B/F/TAF
(75/200/25 mg) showed that BIC 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 BIC (75 mg) + F/TAF (200/25 mg) under fasted conditions. The 
increase in BIC 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 BIC (75 mg) single agent 
coadministered with F/TAF, in the fasted state.
In order to bridge exposures of BIC in the FDC to the exposure observed with BIC 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 B/F/TAF FDC was developed for use in the 
Phase 3 studies. Comparability of BIC exposures was confirmed in an rBA study of B/F/TAF
(50/200/25 mg) and BIC (75 mg) + F/TAF prior to initiation of dosing in the Phase 3 studies.
1.9.
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 from a regimen of either DTG and F/TAF or DTG and 
F/TDF to a FDC of B/F/TAF versus DTG+F/TAF in virologically suppressed HIV-1 infected 
subjects with or without ARV resistance 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


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3.
STUDY DESIGN
3.1.
Endpoints
The primary efficacy endpoint is:

The proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 as defined by the
US FDA-defined snapshot algorithm
The secondary endpoints of this study include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined 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, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to a FDC of B/F/TAF versus DTG+F/TAF in 
HIV-1 infected subjects who are virologically suppressed (HIV-1 RNA < 50 copies/mL) for 
≥6 months (if there is documented or suspected NRTI resistance), or ≥3 months (if there is no 
documented or suspected NRTI resistance), on a stable regimen of DTG+F/TAF or 
DTG+F/TDF.
3.3.
Study Treatments
Subjects who provide written consent and meet all eligibility criteria will be randomized in a 
1:1 ratio to one of the following 2 treatment groups:
Treatment Group 1: FDC of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (B/F/TAF) + placebo to match of dolutegravir 50 mg + placebo to match FDC of 
emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF) administered orally, once daily, 
without regard to food (total of 3 tablets) (n=260)
Treatment Group 2: Dolutegravir 50 mg + FDC of emtricitabine 200 mg/tenofovir alafenamide 
25 mg (F/TAF) + placebo to match FDC of bictegravir 50 mg/emtricitabine 200 mg/tenofovir 
alafenamide 25 mg (B/F/TAF) administered orally, once daily, without regard to food (total of 
3 tablets) (n=260)
Randomization will be stratified as defined in Section 5.1.
3.4.
Duration of Treatment
Subjects who meet eligibility criteria will be treated for at least 48 weeks during the blinded 
treatment phase. The maximum expected duration is approximately 214 weeks (includes the 
Screening period, blinded treatment period, the open-label extension phase and Follow-up 
period).


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After Week 48, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the Week 48 
visit and Week 48 analysis is completed, all subjects will return to the clinic (preferably within 
30 days) for an End of Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety 
and efficacy of B/F/TAF FDC is demonstrated following review of unblinded data, subjects in a 
country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC 
in an open-label (OL) extension phase for up to 96 weeks, or until the product becomes 
accessible to subjects through an access program, or until Gilead elects to discontinue the study 
in that country, whichever occurs first.
All subjects participating in the OL extension phase, without regard to their blinded treatment 
regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for up to 
96 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the OL extension phase, will be required to return to the clinic 30 days after the End 
of Blinded Treatment Visit for a 30-Day Follow-Up Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
Figure 3-1.
Study Schema
a
Following the Day 1 visit, subjects will be required to return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
through the End of Blinded Treatment Visit. The Primary Endpoint will be met when the last enrolled subject completes the 
Week 48 visit.
b
Once the last subject completes the Week 48 visit and Gilead completes the Week 48 analysis, all subjects will return to the 
clinic (preferably within 30 days) for an End of Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety 
and efficacy of B/F/TAF FDC is demonstrated following review of unblinded data, subjects in a country where B/F/TAF
FDC is not available will be given the option to receive B/F/TAF FDC in an OL extension for up to 96 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.
c
Subjects who complete the study through the End of Blinded Treatment Visit and do not continue on the open-label 
B/F/TAF FDC extension phase will be required to return to the clinic 30 days after the last dose of study drugs for a 30-Day 
Follow-Up Visit.


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3.5.
Biomarker Testing
 
 
 
 
 
 
3.5.2.
Additional Sample Storage
 
 
PPD
PPD
• 


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 520 subjects who meet the eligibility criteria will be enrolled. Eligible subjects 
with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection are permitted to 
enroll.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Age 18 years
3) Currently receiving an ARV regimen of DTG+F/TAF or DTG+F/TDF for the following 
minimum time periods:
a) ≥6 months (if there is documented or suspected NRTI resistance prior to the screening 
visit), 
b) ≥3 months (if there is no documented or suspected NRTI resistance prior to the 
screening visit)
4) Documented plasma HIV-1 RNA < 50 copies/mL during treatment with DTG+F/TAF or 
DTG+F/TDF (for a minimum period of ≥ 6 or ≥ 3 months, as applicable) preceding the 
Screening Visit (or undetectable HIV-1 RNA level according to the local assay being used if 
the limit of detection is ≥50 copies/mL)
a) The last two HIV-1 RNA measurements prior to screening must be < 50 copies/mL;
however, unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable 
viremia, or “blip”) in the past are acceptable.
b) If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL 
(eg, < 20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on 
two consecutive HIV-1 RNA tests after < 50 copies/mL has been achieved.
5) Plasma HIV-1 RNA levels < 50 copies/mL at Screening Visit
6) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)


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7) Adequate renal function:
eGFR ≥30 mL/min according to the Cockcroft-Gault formula for creatinine clearance
{Cockcroft 1976}:
a) Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg)          CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
b) Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg)           0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
8) No documented resistance to INSTIs or confirmed virologic failure (2 consecutive HIV-1 
RNA ≥50 copies/mL after achieving < 50 copies/mL while on an INSTI-containing 
regimen)
9) Eligible subjects with the following historical ARV resistance are permitted to enroll:

Any NRTI resistance mutations

Any non-nucleoside reverse transcriptase mutations

Any protease inhibitor mutations

Subjects with resistance to 2 or more classes of antiretrovirals must be reviewed by the 
Gilead Medical Monitor to confirm eligibility
10) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
11) Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin
12) 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))
13) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
14) Male subjects who are fertile and female subjects of childbearing potential who engage in 
heterosexual intercourse must agree to use protocol specified method(s) of contraception as 
described in Appendix 6
15) Male subjects must agree to refrain from sperm donation from first study drug dose and 
throughout the study period
16) Life expectancy ≥ 1 year


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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
6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
7) Participation in any other clinical trial, including observational studies,  without prior 
approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Known hypersensitivity to B/F/TAF FDC or DTG+F/TAF FDC tablets, their metabolites, or 
formulation excipient
10) Females who are pregnant (as confirmed by positive serum pregnancy test)
11) Females who are breastfeeding
12) Subjects receiving ongoing therapy with any of the following medications in the table below, 
including drugs not to be used with BIC, FTC, TAF, and DTG


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Drug Class
Agents Disallowed*
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study.
13) Acute hepatitis in the 30 days prior to randomization
14) Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS (IMP)
5.1.
Randomization, Blinding and Treatment Codes
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Randomization will be stratified by NRTI use (F/TAF vs. F/TDF) and documented or suspected 
history of NRTI resistance. The following NRTI-associated mutations will be considered as 
having NRTI resistance: M41L, K65R/E/N, D67N, T69 insertions, K70R, L74I/V, Y115F, 
Q151M, M184I/V, L210W, T215F/Y, K219Q/E/R/N, T69D, K70E/G/M/Q/S/T, V75A/S/M/T. 
NRTI resistance will be stratified by the following categories:
1. K65R/E/N, or 3 or more thymidine analogue mutations (TAMs) that include M41L or 
L210W, or T69 insertions, (TAMs are: M41L, D67N, K70R, L210W, T215F/Y, and 
K219Q/E/R/N)
2. Any other pattern of NRTI resistance of M41L, D67N, K70R, L74I/V, Y115F, Q151M, 
M184I/V, L210W, T215F/Y, K219Q/E/R/N , T69D, K70E/G/M/Q/S/T, V75A/S/M/T.
3. None of these mutations/No NRTI resistance
For subjects that qualify for more than one resistance category, stratification will be prioritized 
by category 1, then 2, then 3 above. The IWRS will assign study drug bottle numbers of blinded 
B/F/TAF FDC + placebo to match DTG + placebo to match F/TAF FDC, or DTG+F/TAF FDC 
+ placebo to match B/F/TAF FDC, at each study visit for each subject. 
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject or in the case of pregnancy that occurs while on study drug, the investigator may 
obtain treatment assignment for that subject. Gilead recommends but does not require that the 
investigator contact the Gilead medical monitor before breaking the blind. Treatment assignment 
should remain blinded unless that knowledge is necessary to determine subject emergency 
medical care or in the event of a pregnancy that occurs while on study drug. The rationale for 
unblinding must be clearly explained in source documentation and on the electronic case report 
form (eCRF), along with the date on which the treatment assignment was obtained. The 
investigator is requested to contact the Gilead medical monitor promptly in case of any treatment 
unblinding.


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Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Pharmacovigilance and Epidemiology (PVE) (formerly referred to as Drug Safety and 
Public Health may independently unblind cases for expedited reporting of suspected unexpected 
serious adverse reactions (SUSARs).
5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
B/F/TAF (50/200/25 mg) and PTM Tablets
The B/F/TAF (50/200/25 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 bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide. In 
addition to the active ingredients, the B/F/TAF tablets contain croscarmellose sodium, 
magnesium stearate, and microcrystalline cellulose. The tablet cores are film-coated with iron 
oxide red, iron oxide black, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
The PTM B/F/TAF tablets are capsule-shaped, film-coated purplish-brown, debossed with "GSI" 
on one side of the tablet and "9883" on the other side and are identical in physical appearance to 
B/F/TAF tablets. The placebo tablets contain microcrystalline cellulose, lactose monohydrate, 
croscarmellose sodium and magnesium stearate. The tablet cores are film-coated with iron oxide 
red, iron oxide black, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
5.2.1.2.
DTG (50 mg) and PTM Tablets
Dolutegravir 50-mg tablets are round, film-coated yellow, debossed with “50” on one side and 
debossed with “SV 572” on the other side. Each tablet core contains 50 mg of dolutegravir. In 
addition to the active ingredient, DTG tablets contain D-mannitol, microcrystalline cellulose, 
povidone K29/32, sodium starch glycolate and sodium stearyl fumarate. The tablet cores are 
film-coated with iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc and titanium 
dioxide.
The PTM DTG tablets are round, film coated yellow, debossed with “50” on one side and 
debossed with “SV 572” on the other side.  PTM DTG tablets are identical in physical 
appearance to DTG 50-mg tablets. The placebo tablet cores contain microcrystalline cellulose, 
lactose monohydrate, croscarmellose sodium and magnesium stearate. The tablet cores are 
film-coated with iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc and titanium 
dioxide.


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5.2.1.3.
F/TAF (200/25 mg) and PTM Tablets
The F/TAF (200/25 mg) tablets are rectangular-shaped, film-coated blue, debossed with "GSI" 
on one side of the tablet and "225" on the other side of the tablet. Each tablet core contains 
200 mg of emtricitabine and 25 mg of tenofovir alafenamide. In addition to the active 
ingredients, the F/TAF tablets contain croscarmellose sodium, magnesium stearate and 
microcrystalline cellulose. The tablet cores are film-coated with FD&C blue #2/indigo carmine 
aluminum lake, polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide.
The PTM F/TAF tablets are rectangular-shaped, film-coated blue, debossed with "GSI" on 
one side of the tablet and "225" on the other side of the tablet. PTM F/TAF tablets are identical 
in physical appearance to F/TAF (200/25 mg) tablets. The placebo tablet cores contain 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. 
The tablet cores are film-coated with FD&C blue #2/indigo carmine aluminum lake,
polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide.
5.2.2.
Packaging and Labeling
5.2.2.1.
B/F/TAF (50/200/25 mg) and PTM Tablets
B/F/TAF tablets and PTM B/F/TAF tablets are packaged in white, high density polyethylene 
(HDPE) bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester packing 
material.  Each bottle is enclosed with a white, continuous thread, child-resistant polypropylene 
screw cap with an induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.
5.2.2.2.
DTG (50 mg) and PTM Tablets
DTG 50-mg tablets and PTM tablets are packaged in white, HDPE bottles. Each bottle contains 
30 tablets.  Each bottle is enclosed with a white, continuous thread, child-resistant polypropylene 
screw cap with an induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.
5.2.2.3.
F/TAF (200/25 mg) and PTM Tablets
F/TAF (200/25 mg) and PTM tablets are packaged in white, HDPE bottles. Each bottle contains 
30 tablets, silica gel desiccant, and polyester packing material.  Each bottle is enclosed with a 
white, continuous thread, child-resistant polypropylene screw cap with an induction-sealed and 
aluminum-faced liner.


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Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drugs should be stored at controlled room temperature of 25°C (77°F); excursions are 
permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label. 
Until dispensed to the subjects, all bottles of study drugs should be stored in a securely locked 
area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied. Keep the bottle tightly closed to protect 
from moisture.
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 B/F/TAF and DTG+F/TAF
Study drug B/F/TAF FDC, DTG, F/TAF FDC, and PTM tablets will be provided by Gilead .
Treatment Group 1: FDC B/F/TAF (50/200/25 mg) + PTM of DTG (50 mg) + PTM FDC of 
F/TAF (200/25 mg) administered orally, once daily, without regard to food (total of 3 tablets)
Treatment Group 2: DTG (50 mg) + FDC of F/TAF (200/25 mg) + PTM FDC B/F/TAF
(50/200/25 mg) administered orally, once daily, without regard to food (total of 3 tablets)
After the End of Blinded Treatment Visit, all subjects who choose to participate in the open label 
extension will receive B/F/TAF FDC once daily for up to 96 weeks.
5.4.
Prior and Concomitant Medications

The use of medications for the treatment of HIV, other than study drug, is prohibited.

Medications listed in the following table and use of herbal/natural supplements are excluded 
or should be used with caution while subjects are participating in the study.  Subjects will 
refrain from consumption of grapefruit juice and Seville orange juice throughout 
participation in the study.


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Table 5-1.
Prior and Concomitant Medications
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With 
Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids 
(eg, Tums or Rolaids); the ulcer medication 
sucralfate (Carafate); or vitamin or mineral 
supplements that contain calcium, iron or zinc 
for a minimum of 6 hours before and 2 hours 
after any dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not 
part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
Oral Hypoglycemic Agent
Metformin: close monitoring is recommended. 
A dose adjustment of Metformin may be 
necessary. Limit total daily doses of Metformin 
to 1000mg when initiating study medication or 
if initiating metformin while on study drug.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study. 
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Medical Monitor must be consulted prior to initiation of the new medication. In instances 
where an excluded medication is initiated prior to discussion with the Sponsor, the Investigator 
must notify Gilead as soon as he/she is aware of the use of the excluded medication.
5.5.
Accountability for IMP
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.
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.


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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.
IMP Return or Disposal
Study drug return and disposal will be performed as outlined in Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that subjects are eligible for study prior to 
enrollment. Please refer to Section 6.2.2 for details about randomization and treatment 
assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30 days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent(s)

Obtain medical history including history of HIV-1 disease-related events, and prior 
medications within 30 days of the screening visit

If available, obtain documentation of historical genotype(s) (not required for entry to 
study)

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

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2

Review concomitant medications

Record any SAEs and all AEs related to protocol mandated procedures occurring after 
signing of the consent form
 
 
PPD


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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 into the study. Subjects must continue to 
take their prior treatment regimen up until their scheduled Day 1 visit.
From the time of obtaining informed consent through the first administration of study drug, 
record all SAEs, as well as any AEs related to protocol-mandated procedures on the adverse 
events 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:

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject.  Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

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

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2.

Dispense study drug

Observed first dose administration of the assigned study drugs as described in Section 5.3

Subjects should be instructed to take study drugs without regard to food. The subject should 
be counseled regarding the importance of adherence and taking their study medications at 
approximately the same time each day as directed by the Investigator.
6.3.
Randomization
Once eligibility has been confirmed, prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using 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.


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6.4.
Treatment Assessments (Week 4 - 48)
The following evaluations are to be completed at 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 of the protocol specified visit date 
through Week 36, unless otherwise specified.  The visit window at Week 48 will be ± 6 weeks of 
the protocol specified visit date, and this clinical visit window coincides 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.

SF-36, HIV Symptoms Distress Module, WPAI and PSQI to be completed by the subject at 
Weeks 4, 12 and 48. Subject is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires

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

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2

Document study drug dispensation and accountability for all study drugs dispensed.

Subjects who meet the criteria for virologic failure will be managed according to the
Management of Virologic Rebound Section 6.11.1 and 6.11.2
 
 
PPD


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6.5.
Treatment Assessments (Post Week 48 until the End of Blinded Treatment 
Visit)
6.5.1.
Post Week 48 Assessments
After Week 48, all subjects will continue to take their blinded study drugs and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the Week 48
visit, and Gilead completes the Week 48 analysis, all subjects will return to the clinic 
(preferably within 30 days) for the End of Blinded Treatment Visit. Study visits are to be 
completed within 6 days of the protocol specified visit date, unless otherwise specified.

Review of AEs and changes in concomitant medications

Complete physical examination (Every 48 weeks) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2

Document study drug dispensation and accountability for all study drugs dispensed

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.11.1 and 6.11.2
6.5.2.
End of Blinded Treatment Visit Assessments
Once the last subject completes the Week 48 visit, and Gilead completes the Week 48 analysis, 
all subjects will return to the clinic (preferably within 30 days) for an End of Blinded Treatment
Visit. At the End of Blinded Treatment Visit, if safety and efficacy of B/F/TAF FDC is 
demonstrated, following review of unblinded data, subjects in a country where B/F/TAF FDC is 
not available, will be given the option to receive B/F/TAF FDC in an OL extension phase for up 
to 96 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 receive the OL B/F/TAF FDC will return for study visits every 12 weeks.
Subjects who choose to not receive the OL B/F/TAF FDC will be required to return to the clinic 
for a 30-Day Follow-up visit following the End of Blinded Treatment Visit. Subjects who have 
discontinued study drug prior to the End of Blinded Treatment Visit will not be eligible for the 
OL extension. However, these subjects will be asked to continue attending the scheduled study 
visits through to the End of Blinded Treatment Visit, and then discontinue from the study after 
the End of Blinded Treatment Visit.


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Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
The following will be performed at the End of Blinded Treatment Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2

Document study drug dispensation, if applicable, and accountability for all blinded study 
drugs dispensed

Subjects who wish to continue in the OL Extension study will receive OL B/F/TAF
6.5.3.
OL Extension Assessments
For purposes of study visit identification during the OL extension, study visits will be identified 
by the number of weeks that have elapsed between the End of Blinded Treatment Visit and the 
corresponding OL study visit, and labeled with “OL” (eg, Week 12 OL, Week 24 OL, etc.).
All subjects participating in the OL extension phase, without regard to their blinded treatment 
regimen, will return for study visits at Week 12 OL, and every 12 weeks thereafter for up to 
96 weeks.
Study visits are to be completed within ± 6 days of the protocol specified visit date (based on the 
End of Blinded Treatment Visit date) unless otherwise specified.
The following will be performed at the OL Extension Visits:

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 48 and 96 OL) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination, as 
needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2


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
Document study drug dispensation and accountability for all study drugs dispensed

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.11.1 and 6.11.2
6.6.
Post-treatment Assessments
6.6.1.
Early Study Drug Discontinuation Assessments
If the subject discontinues study drug prior to the End of Blinded Treatment Visit, the subject 
will be asked to return to the clinic within 72 hours of stopping study drug for the Early Study 
Drug Discontinuation Visit. Prior to the End of Blinded Treatment Visit, 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 
through to the End of Blinded Treatment Visit (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.
If the subject discontinues study drug during the OL extension, the subject will be asked to return 
to the clinic within 72 hours of stopping the study drug for the Early Study Drug Discontinuation 
Visit, and will be discontinued from both study drug and study.
At the Early Study Drug 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 (Day 1) value, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drug Discontinuation Visit:

Review of AEs and changes in concomitant 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

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2

Document study drug accountability for all study drugs dispensed


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6.6.2.
30-Day Follow-Up Visit
Subjects who prematurely discontinue study drug during the blinded phase, and refuse to 
continue in the study through the End of Blinded Treatment Visit will be asked to return to the 
clinic 30 days after the completion of the Early Study Drug Discontinuation Visit, for the 30-Day 
Follow-Up Visit.
Subjects who complete the study drug through the End of Blinded Treatment Visit, and who do 
not wish to participate in the open-label extension, will be required to return to the clinic 30 days 
after the last dose of study drug, for the 30-Day Follow-Up Visit.
Those subjects who prematurely discontinue study drug during the blinded phase and 
continue in the study through at least one subsequent visit after the Early Study Drug 
Discontinuation Visit will not be required to complete the 30-Day Follow-Up Visit.
Subjects who prematurely discontinue study drug during the OL extension will be asked to return 
to the clinic 30 days after the completion of the Early Study Drug Discontinuation Visit, for the 
30-day Follow-Up Visit. The subject will not continue attending the scheduled OL study visits.
Subjects who complete the OL extension phase will be asked to return to the clinic 30 days after 
the completion of study drug for the 30-day Follow-Up Visit.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Obtain blood and urine samples as described in Sections 6.10.1 and 6.10.2
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
(Day 1) value, or is otherwise explained. 
6.7.
Criteria for Discontinuation of Study Treatment
Study medication will be discontinued in the following instances:

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest


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
Subject request to discontinue for any reason

Pregnancy during the study; refer to Appendix 6
Note: Female subjects who become pregnant during the study will be discontinued from the 
study and their study treatment assignment will be unblinded by the investigator and shared 
with the subject.

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)
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator.

Lack of efficacy

Subject noncompliance
6.8.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.9.
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.
6.10.
Clinical Laboratory Assessments
Blood and urine samples will be collected throughout the study as outlined below, within 
Section 6, and in Appendix 2 Study Procedures Table.
6.10.1.
Blood Samples

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, blood urea nitrogen (BUN), chloride, 
creatinine, glucose, potassium, sodium, amylase (reflex lipase testing is performed in 
subjects with total amylase 1.5 ULN)
■
Calcium, phosphorus, magnesium (Screening and Day 1)


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Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides) collected at Day 1, Weeks 12, 24, and 48, and every 24 weeks thereafter, 
End of Blinded Treatment Visit, and every 24 weeks in the OL extension phase
■
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 
eGFR according to the Cockcroft-Gault formula:
Male:
(140 – age in years) (wt in kg) creatinine clearance (CLcr) (mL/min)
72 (serum creatinine in mg/dL)
         (140 – age in years) (wt in kg)         CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
         (140 – age in years) (wt in kg)        0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count and percentage
Plasma HIV-1 RNA
HBV blood panel (Screening, Week 48,  every 48 weeks through End of Blinded 
Treatment Visit, and Weeks 48OL, 96OL): Hepatitis B virus surface antigen (HBsAg), 
Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)
The following tests will be conducted by the central laboratory if the following criteria 
are met:
■
If positive HBsAg: reflex testing for plasma HBV DNA, Hepatitis B virus e-antigen 
(HBeAg) (if negative, reflex Hepatitis B virus e-Antibody [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 
Plasma HBV DNA for patients who are HBV co-infected


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HCV antibody (Ab) serology. Subjects who are HCVAb positive will have a HCV RNA 
test performed (Screening, Week 48, every 48 weeks through End of Blinded 
Treatment Visit, and Weeks 48OL, 96OL)
 
 
6.10.2.
Urine Samples
Urine samples will be collected for the following laboratory analyses:

Urinalysis

Urine pregnancy testing (Not collected at Screening and 30-day Follow-up Visits)
 
 
 
 
6.11.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study
drug discontinuation, or Week 48.
6.11.1.
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 
PPD
PPD
PPD
PPD
PPD


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


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6.11.2.
Subjects with HIV-1 RNA ≥50 copies/mL at Study Drug Discontinuation, or 
Week 48
Subjects with HIV-1 RNA ≥50 copies/mL at study drug discontinuation, or last visit, or 
Week 48 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 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 (eg, 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 is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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


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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting.
The relationship to study procedures (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 Gilead Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events.
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the eCRF:

all SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30-days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead 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 PVE as instructed. This also includes any SAEs resulting from 
protocol-associated procedures performed after informed consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30-days of the 
last dose of study IMP, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period; 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of IMP, he/she should promptly document and report 
the event to Gilead PVE.
Electronic Serious Adverse Event Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead PVE within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study start), record the 
SAE on the paper serious adverse event report form and submit by e-mail or fax within 
24 hours of the investigator’s knowledge of the event to:
Gilead PVE contact information:
Email: 
Fax: 

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form
PPD
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
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 
SUSARs. In accordance with the EU Clinical Trials Directive (2001/20/EC), Gilead or a 
specified designee will notify worldwide regulatory agencies and the relevant IEC in concerned 
Member States of applicable SUSARs as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure, EU Summary of Product Characteristics 
(SmPC), or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 4 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 5). 

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results and before study drug 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.
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, study drug may be 
continued if the event is considered to be unrelated to study drug.


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
For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to study drug, study drug will be withheld until 
the toxicity returns to Grade 2. When restarting study drug following resolution of the 
adverse event, the study drug should be restarted at full dose upon discussion with the Gilead 
Medical Monitor.

If a laboratory abnormality recurs to Grade 3 following rechallenge with study drug and is 
considered related to study drug, then study drug will be permanently discontinued and the 
subject managed according to local practice. Recurrence of laboratory abnormalities 
considered unrelated to study drug may not require permanent discontinuation but requires 
discussion with the Gilead 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 study drug, study drug 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.

Study drug 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 study drug requires discussion with the Gilead Medical Monitor.
7.5.4.
On-Treatment ALT Flare 
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.
7.5.4.1.
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 
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Check the following laboratory parameters: serum ALT and AST, total bilirubin, 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, 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, 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, and 
total bilirubin 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.
7.5.5.
Management of Potential Hepatobiliary Toxicity
Monkeys given a high dose (1000 mg/kg/day) for 39 weeks had evidence of biliary hyperplasia 
and hepatocyte hypertrophy on histopathologic examination. The risk to humans given the 
clinical dose of BIC (50 mg/day) is unknown. Investigators should be aware of this potential 
toxicity. Any study subject exhibiting signs/symptoms or laboratory abnormalities suggestive of 
possible hepatobiliary toxicity should undergo thorough examination and clinical workup as 
deemed appropriate by the Investigator, and the Investigator must communicate promptly with 
the Gilead Medical Monitor. Consideration should be given to appropriate imaging studies 
(for example, ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. Management of graded 
laboratory and clinical abnormalities will be managed as outlined in Section 7.5.
7.5.6.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Study drug may be continued without dose interruption. Should the 
Investigator decide to initiate Hepatitis C treatment the Investigator must contact the Gilead 
Medical Monitor to confirm that no drug-drug interactions are expected. Subjects should return 
to the clinic for scheduled or unscheduled follow up visit(s) according to local medical practice 
for laboratory evaluations. If Hepatitis C treatment is initiated, Investigators should use the 
Gilead provided retest laboratory kits to manage the active Hepatitis C.


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7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, reports of adverse reactions in infants 
following exposure from breastfeeding, occupational exposure with an adverse event, and 
pregnancy reports regardless of an associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
Occupational exposure 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 female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to Gilead PVE using the pregnancy report form within 24 hours of becoming aware of 
the pregnancy. 
The subject’s treatment assignment will be unblinded by the Investigator as described in Protocol 
Section 5.1.1.
Refer to below and the eCRF completion guidelines for full instructions on the mechanism of 
pregnancy reporting.


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The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead PVE.
The subject should receive appropriate monitoring and care until the conclusion of the pregnancy
. Any complications during pregnancy and the outcome should be reported to Gilead PVE using 
the pregnancy outcome report form. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead PVE. Gilead PVE contact 
information is as follows:
Email: 
 or Fax: 
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications.
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
PPD
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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is:

To evaluate the efficacy of switching from a regimen of either DTG and F/TAF or DTG and 
F/TDF to a FDC of B/F/TAF versus DTG+F/TAF in virologically suppressed HIV-1 infected 
subjects with or without ARV resistance 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 proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 as defined 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 defined 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.


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8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set 
The primary analysis set for efficacy analyses is defined as FAS, which will include all subjects 
who (1) are randomized into the study and (2) have received at least 1 dose of study drug.
Subjects will be grouped according to the treatment to which they were randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as PP analysis set, which will include 
all subjects who (1) are randomized into the study, (2) have received at least 1 dose of study 
drug, and (3) have not committed any major protocol violation, including the violation of key 
entry criteria. Subjects will be grouped according to the treatment they actually received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis
set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing, 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 4.3 including drugs not to be used with 
BIC, FTC, TAF, and DTG.

Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.3.
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).


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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.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods, including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables, and frequency and percentages for categorical variables.
Demographic data will include sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, eGFR, HIV-1 infection, and enrollment 
distribution will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel 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 analysis will consist of a non-inferiority test of switching to FDC B/F/TAF versus 
DTG+F/TAF, with respect to the proportion of subjects with HIV 1 RNA ≥50 copies/mL at 
Week 48, as defined by the US FDA-defined snapshot algorithm. The primary analysis of the 
efficacy endpoint will be based on the FAS.
8.5.1.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, including data collected up to 1 day after the 
last dose date of study drug) will be used in the snapshot algorithm. Virologic outcome will be 
defined as the following categories:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window 

HIV-1 RNA ≥50 copies/mL: this includes subjects
a) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window, or


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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 reason 
other than lack of efficacy and have the last available on-treatment HIV-1 RNA 
≥50 copies/mL

No Virologic Data in the Week 48 Analysis Window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following:
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons
other than lack of efficacy and the last available on-treatment HIV-1 RNA 
< 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 B/F/TAF group is at least 4% higher than that in the DTG+F/TAF group; the 
alternative hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 copies/mL in the 
B/F/TAF group is less than 4% higher than that in the DTG+F/TAF group.
Non-inferiority will be assessed using the conventional CI approach. The point estimate of 
treatment difference (B/F/TAF group – DTG+F/TAF group) and the associated 2-sided 95% CI 
will be constructed based on the exact method.
It will be concluded that B/F/TAF FDC is non-inferior to DTG+F/TAF if the upper bound of the 
2-sided 95% CI of the difference between treatment groups (B/F/TAF group – DTG+F/TAF
group) 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). The 2-sided 95% CIs will be 
constructed based on the exact method.
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-defined snapshot algorithm will also be summarized. The 95% CIs will be constructed 
in the same manner as described for the primary efficacy endpoint. However, non-inferiority will 
be assessed using a margin of 10%. It will be concluded that B/F/TAF FDC is noninferior to 
DTG+F/TAF if the lower bound of the 2-sided 95% CI of the difference between treatment 
groups (B/F/TAF group – DTG+F/TAF group) in the response rate is greater than -10%.


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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 an 
Analysis of Variance (ANOVA) model, including treatment (B/F/TAF group vs. DTG+F/TAF
group), prior NRTI use (F/TAF vs. F/TDF) and history of NRTI resistance as fixed effects in the 
model.
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 group.
Duration of exposure to study drug will be expressed as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration and summarized by treatment.
Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study drug start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.


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On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to, and including, the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (ie, at least a Grade 1) will be considered treatment emergent. The 
maximum postbaseline 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 will be summarized as appropriate.
8.7.
Patient Reported Outcomes (PRO)
The PRO measures based on questionnaires may be summarized by treatment and visit using 
descriptive statistics.
8.8.
Sample Size
A total of approximately 520 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment
groups (260 subjects per treatment group), achieves at least 90% power to detect a 
non-inferiority margin of 4% in difference in 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® 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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8.9.
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 have completed their Week 12 Visit or prematurely discontinued from the study drug. 
However, Gilead will defer to the IDMC for any decision to convene earlier or more frequently. 
The IDMC will examine the safety results of the trial and also focus on logistical issues such as 
accrual, retention, quality of clinical and laboratory data, and implications of results of external 
studies. Blinding will be preserved during the conduct of the study and access to unblinded data 
will be limited to designated parties.
No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
For each IDMC analysis performed prior to the analysis of the primary efficacy endpoint, an 
alpha penalty of 0.00001 will be applied for the analysis of the primary 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, respectively. Final analysis will be performed after 
all subjects complete the study or prematurely discontinue from the study.


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


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


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


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source data verification within the EDC system. System-generated or manual queries will be 
issued to the investigative site staff as data discrepancies are identified by the monitor or internal 
Gilead staff, who routinely review the data for completeness, correctness, and consistency. The 
site coordinator is responsible for responding to the queries in a timely manner, within the 
system, either by confirming the data as correct or updating the original entry, and providing the 
reason for the update (eg, 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 study drug 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 study drug
disposal procedures and provide appropriate instruction for destruction of unused study drug
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 study drug is destroyed on site, the investigator must maintain accurate records for all study 
drug destroyed. Records must show the identification and quantity of each unit destroyed, the 
method of destruction, and the person who disposed of the study drug. Upon study completion, 
copies of the study drug accountability records must be filed at the site. Another copy will be 
returned to Gilead.
The study monitor will review study drug 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.


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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB or IEC 
in accordance with local requirements and receive documented IRB or IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). Gilead 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:
The results of the study in their entirety have been publicly disclosed by or with the consent of 
Gilead in an abstract, manuscript, or presentation form or the study has been completed at all 
study sites for at least 2 years
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation.
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg attendance at Investigator's Meetings.  If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.


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


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10.
REFERENCES
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? 
Curr Med Res Opin 2014;30 (1):89-97.
Arribas JR, Iribarren JA, Knobel H, Ribera E, Rubio R, Viciana P. Adherence, treatment 
satisfaction and effectiveness of once-daily (QD) vs twice-daily (BID) 
antiretroviral therapy (AT), in a large prospective observational cohort (CUVA 
Study).  [Poster WePeB5780]. . XV International AIDS Conference; 2004 July 
11-16; Bangkok, Thailand. 
Chesney M. Factors affecting adherence to antiretroviral therapy. Clin Infect Dis. 2000;30 
(Suppl 2):S-171-S6.
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.
EMTRIVA®, Gilead Sciences Inc. EMTRIVA® (emtricitabine) capsule, for oral use. 
EMTRIVA® (emtricitabine) oral solution. US Prescribing Information. Foster 
City, CA. Revised November.  2012:
European AIDS Clinical Society (EACS). Guidelines Version 8.1 English.  October, 2016.
Felizarta F, Becker S, Bellos N, Jayaweera D, Sands M, Slater L. Adherence and efficacy with a 
once-daily efavirenz-based regimen: 48-week results from the Daily 
Antiretroviral Therapy II (DART II) Study [Poster 5842]. . XV International 
AIDS Conference; 2004 July 11-16; Bangkok, Thailand. 
Gunthard HF, Saag MS, Benson CA, del Rio C, Eron JJ, Gallant JE, et al. Antiretroviral Drugs 
for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations 
of the International Antiviral Society-USA Panel. JAMA 2016;316 (2):191-210.
Joint United Nations Programme on HIV/AIDS (UNAIDS). Global Aids Update 2016. Available 
at: http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-
2016. 31 May.  2016.
Maggiolo F, Migliorino M, Maserati R, Rizzi L, Pan A, Rizzi A. Once-a-day treatment for HIV 
infection: Final 48-week results. [Abstract 320]. 8th Conference on Retroviruses 
and Opportunistic Infections; 2001 February 4-8; Chicago, IL. 
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of 
mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. 
Lancet 1998;352 (9142):1725-30.


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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.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of 
Health and Human Services. Available at 
http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL. Accessed 15 
August.  2016.
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.
Stone VE, Jordan J, Tolson J, Pilon T. Potential impact of once daily regimens on adherence to 
HAART [abstract]. . 40th Annual Meeting of the Infectious Disease Society of 
America; 2002 Oct 24-27; Chicago. pp. p.129, Abstract 486.
Willig JH, Abroms S, Westfall AO, Routman J, Adusumilli S, Varshney M, et al. Increased 
regimen durability in the era of once-daily fixed-dose combination antiretroviral 
therapy. AIDS 2008;22 (15):1951-60.


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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.
Gilead 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, Double-Blind Study to Evaluate tbe Safety and Efficacy of 
Switching from a Regimen of Dolutegravir and Either Emtricitabine/Tenofovir 
AJafenamide or Emtricitabine/Tenofovir Disoproxil Fumarate to a Fixed Dose 
Combination ofBictegravir/Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected 
Subjects wbo are Virologically Suppressed 
GS-US-380-4030 Protocol Amendment 2, 28 June 2018 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
._ _____ 
____. (Printed) 
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 
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Appendix 2.
Study Procedures Table
Study Procedures
Screeninga
Day 
1
Weekb,c
Post-
Week 48
End of 
Blinded 
Treatment 
Visite
Open Label Extension (OL) Weeksc,f
30 Day 
Follow 
upg
ESDDh
4
8
12
24
36
48
Every 12 
Weeksc,d
12
OL
24
OL
36
OL
48
OL
60
OL
72
OL
84
OL
96
OL
Informed Consent
X
Questionnairesi
X
X
X
X
Medical History
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj
Complete/
Symptom-
Directedk Physical 
Exam
X
X
X
X
X
X
X
X
Xl
X
X
X
X
X
X
X
X
X
Xj
Xj
12-Lead ECG
(performed supine)
X
Height
X
Vital signsm and 
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj
Serum Pregnancy 
Testn
X
Urine Pregnancy 
Testn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry Profileo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj,o
eGFR
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
X
PPD


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 89
28 June 2018
Study Procedures
Screeninga
Day 
1
Weekb,c
Post-
Week 48
End of 
Blinded 
Treatment 
Visite
Open Label Extension (OL) Weeksc,f
30 Day 
Follow 
upg
ESDDh
4
8
12
24
36
48
Every 12 
Weeksc,d
12
OL
24
OL
36
OL
48
OL
60
OL
72
OL
84
OL
96
OL
Hematology 
Profilep
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xj
Metabolic 
Assessmentsq
X
X
X
X
Xr
X
X
X
X
X
Plasma HIV-1 
RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
and Percentage
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HCV Serologys
X
X
Xl
X
X
HBV blood panelt
Xu
Xu
Xu
Xu
Xu
Plasma HBV DNAv
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomizationw
X
Study Drug 
Dispensation
Xx
X
X
X
X
X
X
X
Xy
X
X
X
X
X
X
X
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV-1 Genotype/
Phenotypec
Xc
PPD
PPD


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 90
28 June 2018
a.
Evaluations to be completed within 30 days prior to Day 1.
b.
Study visits are to be completed within ± 2 days of the protocol specified visit date (based on the Day 1) through Week 12 and within ± 6 days through to Week 36, unless 
otherwise specified. The visit window for Week 48 will be ± 6 weeks of the protocol specified visit date.
c.
HIV-1 genotype and phenotype testing for subjects with confirmed virologic failure and HIV-1 RNA >200 copies/mL. Following virologic rebound, subjects will be asked to 
return to the clinic (2-3 weeks later) prior to the next scheduled visit or at the next scheduled study visit for a HIV-1 RNA and  HIV-1 resistance analysis (reverse 
transcriptase, protease, and integrase genotype and phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic 
Rebound Schema (Section 6.11). 
d.
After Week 48, all subjects will continue to take their blinded study drug and attend visits every 12 weeks (± 6 days of the protocol specified visit date) until the End of 
Blinded Treatment Visit.
e.
Once the last subject completes the Week 48 visit and Gilead completes the Week 48 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, if safety and efficacy of B/F/TAF is demonstrated following review of unblinded data, subjects in a country 
where B/F/TAF FDC is not available, will be given the option to receive B/F/TAF FDC in an OL extension phase for up to 96 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. Treatment assignments will be provided to the 
investigators within 30 days of the last subject completing the End of Blinded Treatment Visit.
f.
Study visits are to be completed within ± 6 days of the protocol specified visit date based on the End of Blinded Treatment Visit date, unless otherwise specified. 
g.
Before the OL extension period, 30-Day Follow-up is required for subjects not enrolling in the OL extension, or those who prematurely discontinue study drugs and do not 
continue in the study through at least one subsequent visit after the Early Study Drugs Discontinuation Visit. 
During the OL extension period, subjects who complete the OL extension, or who permanently discontinue study drugs during the OL extension, will be required to return 
to the clinic 30 days after the last dose of study drugs, for the 30-Day Follow-Up Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be 
used.
h.
Before the OL extension period, Early Study Drugs Discontinuation visit is to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending 
the scheduled study visits through the End of Blinded Treatment Visit, even if the subject discontinues study drugs. 
During the OL extension period, subjects who discontinue study drug will be asked to return to the clinic within 72 hours of stopping study drugs, for the Early Study Drugs 
Discontinuation Visit, followed by a 30-Day Follow-Up Visit.  The subject will not continue attending the scheduled OL study visits.
i.
SF-36, HIV Symptoms Distress Module, WPAI, PSQI, to be completed by the subject. Subject is to read questionnaire by himself/herself and write/mark answers directly 
onto questionnaires.
j.
Any AE or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often as deemed 
prudent by the Investigator) until the abnormality is resolved, returns to baseline (Day 1) value, or is otherwise explained.
k.
Symptom-directed physical examination, as needed.
l.
Post Week 48, complete physical examination and HCV Serology, are to be performed every 48 weeks
m.
Blood pressure, pulse, respiration rate, and temperature.
n.
Females of childbearing potential only. After the Screening visit, positive urine pregnancy tests will be confirmed with a serum pregnancy test.
o.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, and amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). After Day 1, calcium, 
phosphorous, and magnesium will not be collected. Analyses of glucose will be done as part of the fasting metabolic assessments, and not as part of the chemistry profile at 
Day 1, Weeks 12, 24, 48, post Week 48 (every 24 weeks), and End of Blinded Treatment, Week 24OL, Week 48OL, Week 72OL, Week 96OL.
p.
CBC with differential and platelet count.
q.
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments. 
r.
Metabolic assessments during the post Week 48 will be done every 24 weeks.
s.
Hepatitis C virus serology. Subjects who are HCVAb positive will have a HCV RNA test performed.
t.
HBV blood panel will be performed at Screening, Week 48, every 48 weeks through End of Blinded Treatment Visit, and Weeks 48OL, 96OL: HBsAg, HBsAb, 
HBcAb


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 91
28 June 2018
u.
For subjects who are HBV co-infected at any visit: The following HBV Blood panel will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and 
quantitative), and HBeAg (if negative, reflex HBeAb) 
For subjects who are NOT HBV co-infected at any visit: The following HBV Blood panel will be conducted by the central laboratory: HBsAb, HBcAb, and HBsAg. 
Subjects who are HBsAg or HBcAb positive will have a reflex test for HBV DNA (viral load) 
v.
For subjects who are HBV co-infected at any visit: Plasma HBV DNA at every visit (including OL extension period [not collected at Screening and 30-day Follow-up])
w.
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.
x.
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures at the Day 1 visit.
y.
Open label study drug, B/F/TAF FDC will be dispensed to subjects participating in the OL extension for up to 96 weeks.
 
PPD


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 92
28 June 2018
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grade 1 
Grade 2 
L-~------G_r_a_d_e_3--------~~~ L~-------G--ra_d_e_4 
________ ~ 
I 
l 
r 
r 
May continue dosing 
at the discretion of 
the investigator 
Repeat lab to 
onfirm toxicity 
grade 
c 
If confirmed, and possibly or probably related to investigational 
medicinal products: 
1. Withhold investigational medicinal products until ~ Grade 2 
2. Restart all investigational medicinal products at full dose upon 
discussion with the Gilead Sciences Medical Monitor 
l 
If Grade 3 or 4 recurrence is 
confirmed, and possibly or 
probably related to investigational 
medicinal products, discontinue all 
investigational medicinal products 
dosing permanently, and manage 
the subject according to local 
practice 
l 
If Grade 3 or 4 recurrence is 
confirmed, and unrelated to 
investigational medicinal 
products, continue all 
investigational medicinal 
products at the same dose, at 
the discretion of the 
investigator 
Repeat lab to 
confirm toxicity 
grade 
1 
d, and unrelated to 
If confirme 
investigatio 
products, d 
at the disco 
discretion o 
n medicinal 
osing may continue 
ntinue at the 
f the investigator 
----.. 
If confirmed, and 
possibly or probably 
related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently, 
and manage subject 
according to local 
practice. Subject should 
be followed as 
clinically indicated until 
the laboratory 
abnormality returns to 
baseline, or is otherwise 
explained 


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 93
28 June 2018
Appendix 4.
Gilead 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 
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


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 94
28 June 2018
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 lower limit of the normal range (LLN) and ULN a 0.


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 95
28 June 2018
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L                
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L                 
2.0 to <2.5 mmolL
2.0 mEq/L                         
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant <1 Year
>ULN to 6.0 mEq/L           
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L             
6.5 to 7.0 mmol/L
7.0 mEq/L                  
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 96
28 June 2018
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL                          
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL              
1.74 to <1.94 mmolL
6.1 to  <7.0 mg/dL                      
1.51 to < 1.74 mmolL
< 6.1 mg/dL                           
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia (corrected 
for albumin if appropriate*)
Adult and Pediatric 
7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 97
28 June 2018
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63  to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to <LLN mg/dL
1.12 to <LLN mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia 
Adult and Pediatric 
> 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN


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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 98
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L
LDL (Fasting)
Adult
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
LDL (Fasting)
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to  4.92 mmol/L
>4.92 mmol/L


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 99
28 June 2018
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects >70 yrs. Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 100
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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 (eg, the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.


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


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 102
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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV 
block OR Ventricular pause 
3.0 sec
Complete AV block 
Pediatric 16 Years
1st degree AV block
(PR > normal for age and 
rate)
Type I 2nd degree AV block 
Type II 2nd degree AV 
block 
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc interval 
0.50 sec OR Increase in 
interval 0.06 sec above 
baseline
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Pediatric 16 Years
Asymptomatic, QTc interval 
0.450 to 0.464 sec 
Asymptomatic, QTc interval 
0.465 to 0.479 sec 
Asymptomatic, QTc interval 
0.480 sec 
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Deep vein thrombosis AND
Intervention indicated (eg, 
anticoagulation, lysis filter, 
invasive procedure) 
Embolic event (eg, pulmonary 
embolism, life-threatening 
thrombus) 
Vasovagal Episode (associated 
with a procedure of any kind)
Present without loss of 
consciousness 
Present with transient loss of 
consciousness
NA 
NA
Ventricular Dysfunction 
(congestive heart failure, 
CHF)
NA
Asymptomatic diagnostic 
finding AND intervention 
indicated
New onset with symptoms 
OR Worsening symptomatic 
CHF
Life-threatening CHF


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


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 104
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SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by 
study participant or  
caregiver (for disabled 
adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or morbilliform 
rash with vesicles or limited 
number of bullae OR 
Superficial ulcerations of 
mucous membrane limited to 
one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson syndrome 
OR Ulceration of mucous 
membrane involving two 
or more distinct mucosal 
sites OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA


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


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Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 106
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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, 
Dysphagia-Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal bleeding 
OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 24–48 
hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening consequences 
(eg, hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening consequences 
(eg, sepsis, circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ 
Stomatitis for Clinical 
Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater than 
minimal interference with usual 
social & functional activities OR 
Medical intervention indicated 
Symptoms causing inability to 
perform usual social/
functional activities OR 
Operative intervention 
indicated 
Life-threatening consequences 
(eg, perforation)
Vomiting
Transient or intermittent 
vomiting with no or 
minimal interference with 
oral intake
Frequent episodes of vomiting 
with no or mild dehydration
Persistent vomiting resulting 
in orthostatic hypotension OR 
Aggressive rehydration 
indicated
Life-threatening consequences 
(eg, hypotensive shock)


B/F/TAF FDC
Protocol GS-US-380-4030
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 107
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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
Central nervous system
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


B/F/TAF FDC
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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 108
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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)


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


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


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


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


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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 113
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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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Amendment 2
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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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Amendment 2
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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 2008}


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Amendment 2
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Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1)
Definitions
a.
Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b.
Definition of Male Fertility
For the purposes of this study, a male born subject is considered to be fertile after the initiation 
of puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2)
Contraception Requirements for Female Subjects
a.
Study Drug Effects on Pregnancy and Hormonal Contraception
The data on B/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 BIC 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 B/F/TAF investigator’s brochure and the current Prescribing Information 
and local product labeling.
Serious cases of neural tube birth defects involving the brain, spine, and spinal cord have been 
reported in babies born to women treated with dolutegravir. Preliminary results from an ongoing 
observational study in Botswana found that women who received dolutegravir at the time of 
becoming pregnant or early in the first trimester appear to be at higher risk for these defects.
Please refer to the latest local product labeling for DTG for additional information.
b.
Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures.  They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Baseline/Day 1 visit prior to randomization.  At minimum, a 
pregnancy test will be performed 7 days after the last study drug dose.  In the event of a delayed 


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Amendment 2
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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 also agree to one of the following from Screening until 
30 days after the last dose of study drug.

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 by hysterosalpingogram 
three months after procedure and where permitted and used per local prescribing label)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Female subjects who wish to use a hormonally based method must use it in conjunction with a 
barrier method, preferably a male condom.  Female subjects who utilize a hormonal 
contraceptive as one of their birth control methods must have consistently used the same method 
for at least three months prior to study dosing.   Hormonally-based contraceptives and barrier 
methods permitted for use in this protocol are as follows:
Barrier methods (each method must be used with a hormonal method)
■
Male condom (with or without spermicide)
■
Female condom (with or without spermicide)
■
Diaphragm with spermicide
■
Cervical cap with spermicide
■
Sponge with spermicide
Hormonal methods (each method must be used with a barrier method, preferably male 
condom)
■
Oral contraceptives (either combined or progesterone only)


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■
Injectable progesterone
■
Subdermal contraceptive implant
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 30 days after the end of relevant systemic exposure.
3)
Contraception Requirements for Male Subjects
During the study, male subjects with female partners of childbearing potential should use 
condoms when engaging in intercourse of reproductive potential.
4)
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM).  Female condom and male condom should not be used 
together.
5)
Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant, or are concerned 
they may be pregnant at any time during the study, or if they become pregnant within 30 days of 
last study drug dose. Subjects who become pregnant or who suspect that they are pregnant during 
the study must report the information to the investigator and discontinue study drug immediately.  
Subjects who become pregnant will be discontinued from the study and their study treatment 
assignment will be unblinded by the Investigator and provided to the subject.
Subjects who become pregnant while on study should receive appropriate monitoring and care 
until the conclusion of the pregnancy. Subjects who become pregnant while on study who are not 
engaged in pre-natal care that includes a routine second trimester ultrasound will be referred for 
ultrasonography as part of study follow-up. Instructions for reporting pregnancy and pregnancy 
outcome are outlined in Section 7.6.2.1.


amd-2-prot-GS-US-380-4030_Final
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Erin Quirk
Clinical Research eSigned 28-Jun-2018
23:26:45