Clinical trial NCT03631732
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences
Start date: 2018-08-28; Completion date: 2020-08-19
Enrollment: 496 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of switching from a regimen of 2 nucleos(t)Ide reverse transcriptase inhibitors (NRTIs) and a third agent to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing their baseline regimen in HIV-1 infected, virologically suppressed African American participants.

Detailed description:

Arms: arm 1: Participants will receive B/F/TAF (50/200/25 mg) FDC tablet orally once daily for 48 weeks, without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first. arm 2: Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.
Interventions: intervention 1: B/F/TAF intervention 2: NRTIs intervention 3: Third Agent
Intervention descriptions: intervention 1: 50/200/25 mg FDC tablets administered orally once daily without regard to food intervention 2: The following NRTIs will be administered as prescribed until Week 24 without regard to food:

abacavir (ABC), emtricitabine (FTC), lamivudine (3TC), tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), zidovudine (ZDV or AZT) intervention 3: Any one of the following third agents will be administered as prescribed. Protease inhibitors and EVG will be administered with the appropriate pharmacologic booster cobicistat or ritonavir. :

* Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

  * delavirdine (DLV)
  * efavirenz (EFV)
  * nevirapine (NVP)
  * rilpivirine (RPV)
  * doravirine (DOR)
* Integrase inhibitors

  * dolutegravir (DTG)
  * elvitegravir (EVG)
  * raltegravir (RAL)
* Protease inhibitors (PIs)

  * atazanavir (ATV)
  * darunavir (DRV)
  * lopinavir (LPV)
  * nelfinavir NFV)
  * saquinavir (SQV)
  * tipranavir (TPV)
* Chemokine co-recptor 5 (CCR5) antagonist --maraviroc (MVC)

Protocol documents:
SAP_002.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3b, Multicenter, Open-Label Study to Evaluate 
Switching From a Regimen of Two Nucleos(t)ide Transcriptase
Reverse Inhibitors (NRTI) plus a Third Agent to a Fixed Dose 
Combination (FDC) of Bictegravir/ Emtricitabine/Tenofovir 
Alafenamide (B/F/TAF) in Virologically-Suppressed, HIV-1 
Infected African American Participants
Name of Test Drug:
Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF; GS-9883/F/TAF)
Study Number:
GS-US-380-4580
Protocol Version (Date):
Original (27 June 2018)
Analysis Type:
Final
Analysis Plan Version:
Version 1.0 Final
Analysis Plan Date:
16 November 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(rJ GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF IN-TEXT FIGURES ......................................................................................................................................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
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................12
2.1.
Interim Analyses ....................................................................................................................................12
2.1.1.
Week 24 Analysis.................................................................................................................12
2.1.2.
Week 48 Analysis.................................................................................................................12
2.2.
Final Analysis ........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................13
3.1.
Analysis Sets..........................................................................................................................................13
3.1.1.
All Randomized Analysis Set...............................................................................................13
3.1.2.
B/F/TAF Full Analysis Set...................................................................................................13
3.1.3.
B/F/TAF Safety Analysis Set...............................................................................................14
3.2.
Subject Grouping ...................................................................................................................................14
3.3.
Strata and Covariates..............................................................................................................................14
3.4.
Examination of Subject Subgroups........................................................................................................14
3.4.1.
Subject Subgroups for Efficacy Analyses ............................................................................14
3.4.2.
Subject Subgroups for Safety Analyses ...............................................................................14
3.5.
Multiple Comparisons............................................................................................................................15
3.6.
Missing Data and Outliers......................................................................................................................15
3.6.1.
Missing Data ........................................................................................................................15
3.6.2.
Outliers.................................................................................................................................16
3.7.
Data Handling Conventions and Transformations .................................................................................16
3.8.
Analysis Windows .................................................................................................................................16
3.8.1.
Definition of Study Day .......................................................................................................16
3.8.2.
Analysis Windows................................................................................................................17
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window................................................................................................................................18
4.
SUBJECT DISPOSITION ..................................................................................................................................20
4.1.
Subject Enrollment and Disposition.......................................................................................................20
4.1.1.
Subject Enrollment...............................................................................................................20
4.1.2.
Subject Disposition ..............................................................................................................20
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................21
4.2.1.
Duration of Exposure to Study Drug....................................................................................21
4.2.2.
Adherence to Study Drug Regimen......................................................................................21
4.3.
Protocol Deviations................................................................................................................................22
4.4.
Assessment of COVID-19 Impact..........................................................................................................22
5.
BASELINE CHARACTERISTICS....................................................................................................................23
5.1.
Demographics and Baseline Characteristics ..........................................................................................23
5.2.
Baseline Disease Characteristics............................................................................................................23


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5.3. 
Medical History ...................................................................................................................................... 24 
6. 
EFFICACY ANALYSES ................................................................................................................................... 25 
6.1. 
Primary Efficacy Endpoint ..................................................................................................................... 25 
6.1.1. 
Definition of the Primary Efficacy Endpoint ....................................................................... 25 
6.2. 
Secondary Efficacy Endpoints ............................................................................................................... 25 
6.2.1. 
Definition of the Seconda 
Efficac End oints .................................................................. 25 
6.4. 
7. 
SAFETY ANALYSES ........................................................................................................................................ 27 
7.1. 
Adverse Events and Deaths .................................................................................................................... 27 
7.1.1. 
Adverse Event Dictionary .................................................................................................... 27 
7.1.2. 
Adverse Event Severity ........................................................................................................ 27 
7.1.3. 
Relationship of Adverse Events to Study Drug .................................................................... 27 
7 .1.4. 
Serious Adverse Events ........................................................................................................ 27 
7.1.5. 
Treatment-Emergent Adverse Events ................................................................................... 27 
7 .1.6. 
Summaries of Adverse Events and Death ............................................................................ 28 
7.1.7. 
Additional Analysis of Adverse Events ............................................................................... 29 
7 .2. 
Laboratory Evaluations .......................................................................................................................... 30 
7.2.1. 
Summaries ofNumeric Laboratory Results ......................................................................... 30 
7.2.2. 
Graded Laboratory Values ................................................................................................... 31 
7.2.3. 
Metabolic Laboratory Evaluations ....................................................................................... 32 
7.2.4. 
Liver-Related Laboratory Evaluations ................................................................................. 33 
7.2.5. 
Renal-Related Laboratory Evaluations ................................................................................. 34 
7.3. 
Body Weight, Height, and Yitai Signs ................................................................................................... 34 
7.4. 
Prior and Concomitant Medications ....................................................................................................... 35 
7.4.1. 
Nonstudy Dmg Antiretroviral Medications .......................................................................... 35 
7.4.2. 
Concomitant Non-ARV Medications ................................................................................... 35 
7.5. 
Electrocardiogram Results ..................................................................................................................... 36 
7 .6. 
Other Safety Measures ........................................................................................................................... 36 
7.7. 
Subject Subgroup for Safety Endpoints ................................................................................................. 36 
7 .8. 
Changes from Protocol-Specified Safety Analyses ................................................................................ 36 
8. 
SPECIAL POPULATION ANALYSES ............................................................................................................. 37 
8.1. 
Analyses for HIV/HBV Coinfected Participants .................................................................................... 37 
8.2. 
Analyses for HIV/HCV Coinfected Participants .................................................................................... 38 
9. 
PATIENT REPORTED OUTCOMES ................................................................................................................ 39 
10. REFERENCES ................................................................................................................................................... 40 
11 . SOFTWARE ....................................................................................................................................................... 41 
12. SAP REYISION .................................................................................................................................................. 42 
13. APPENDICES .................................................................................................................................................... 43 
Appendix I. 
Appendix 2. 
Appendix 3. 
Appendix 4. 
Appendix 5. 
Appendix 6. 
CONFIDENTIAL 
Study Procedures Table .......................................................................................................... 44 
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial) ................................. 47 
Cardiovascular or Cerebrovascular Events ............................................................................. 48 
Hepatic Events ........................................................................................................................ 49 
Determining Missing and Virtual visits due to COYID-19 .................................................... 50 
Programming Specifications ................................................................................................... 53 
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LIST OF IN-TEXT TABLES
Table 1-1.
Power for Various Proportions and Noninferiority Margins ..................................................11
Table 3-1.
Analysis Windows for HIV-1 RNA, Hematology, Chemistry, Urinalysis, Urine 
Pregnancy Laboratory Tests, eGFRCG, Vital Signs and Weight.............................................17
Table 3-2.
Analysis Windows for CD4+ cell count, CD4 %, and Metabolic Assessments.....................18
Table 3-3.
Analysis Windows for Plasma HBV DNA.............................................................................18
LIST OF IN-TEXT FIGURES
Figure 1-1.
Study Schema..........................................................................................................................8


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LIST OF ABBREVIATIONS
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ARV
antiretroviral
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
CG
Cockcroft-Gault
CI
confidence interval
CRF
case report form
DNA
deoxyribonucleic acid
DTG
dolutegravir
ECG
electrocardiogram
EFV
efavirenz
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
full analysis set
FDA
Food and Drug Administration
FDC
fixed dose combination
GFR
glomerular filtration rate
Gilead
Gilead Sciences, Inc.
GLPS
global patient safety 
GS-9883
bictegravir
HBcAb
hepatitis B core antibody 
HBeAb
hepatitis B e-antibody 
HBeAg
hepatitis B e-antigen
HBsAb
hepatitis B surface antibody 
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb
hepatitis C antibody
HDL
high density lipoprotein
HIV-1
human immunodeficiency virus (Type 1) 
HLGT
high level group term
HLT
high level term


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ID
identification
INSTI
integrase strand-transfer inhibitor
IWRS
interactive web response system
LDL
low density lipoprotein
LLT
lowest level term
MedDRA
Medical Dictionary for Regulatory Activities
NRTI
nucleos(t)ide reverse transcriptase inhibitors
PP
per protocol
PT
preferred term
Q
quartile
Q1
first quartile
Q3
third quartile
RNA
ribonucleic acid
RPV
rilpivirine
RT
reverse transcriptase
RTV
ritonavir
SAE
serious adverse event
SAP
statistical analysis plan
SBR
stay on baseline regimen
SD
standard deviation
SMQ
Standardised MedDRA Query
SOC
system organ class
TAF
tenofovir alafenamide 
TAM
thymidine analogue mutation
TDF
tenofovir disoproxil fumarate
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 the final analysis for 
Version 1.0 
Study GS-US-380-4580, which will be perfonned when all participants have completed the 
study or prematurely discontinued from the study. This SAP is based on the study protocol dated 
27 June 2018 and the electronic case report fonn ( 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 2 nucleos(t)ide reverse transcriptase 
inhibitors (NRTls) and a third agent to a fixed dose combination (FDC) of 
bictegravir/emtricitabine/tenofovir alafenamide (B/F IT AF) versus continuing their baseline 
regimen in HIV -1 infected, virologically suppressed African American participants as 
detennined by the proportion of participants with HIV-1 RNA~ 50 copies/mL at Week 24. 
The secondary objectives of this study are: 
• 
To evaluate the efficacy of switching to a FDC of B/F/TAF from a regimen of 2 NRTls and a 
third agent as detennined by the proportion of participants with HIV-1 RNA 
50 copies/mL 
at Week 48 
• 
To evaluate the efficacy, safety, and tolerability of switching to a FDC ofB/F/TAF from a 
regimen of 2 NR Tis and a third agent in HIV -1 infected, virologically suppressed 
African American participants through Week 48 
1.2. 
Study Design 
The study schema is provided in Figure 1-1. 
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Figure 1-1.
Study Schema
a
Following the Day 1 visit, participants will be required to return for study visits at Weeks 4 and 12, and then every 12 weeks 
through the Week 48 visit. The Primary Endpoint will be assessed when the last enrolled participant completes the Week 24 
visit.
b
At Week 24, participants randomized to continue on their baseline regimen who complete 24 weeks of treatment on their 
baseline regimen will switch to B/F/TAF FDC.
c
At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an 
additional 24 weeks or until they have access to B/F/TAF, whichever occurs first, and attend study visits every 12 weeks 
followed by a 30 Day Follow up Visit.
Design Configuration and Subject Population
GS-US-380-4580 is a randomized, open-label, multicenter, active-controlled study of HIV-1
infected, virologically suppressed African American participants.
Treatment Groups
Participants who provide written consent and meet all eligibility criteria will be randomized in a 
2:1 ratio to one of the following 2 treatment groups:

Treatment Group 1: FDC of B/F/TAF (50 mg/ 200 mg/ 25 mg) administered orally, 
once daily, without regard to food (n 320 planned)

Treatment Group 2: Stay on baseline regimen (SBR) consisting of 2 NRTIs and a 
third agent (each taken as prescribed) from Day 1 until Week 24, with a delayed switch to a 
FDC of B/F/TAF (50 mg/ 200 mg/ 25 mg) administered orally, once daily, without regard to 
food (n 160 planned)
Key Eligibility Criteria
Medically stable HIV-infected participants who meet the following criteria:

Self-describes as Black, African American, or mixed race, including Black

Currently receiving an antiretroviral (ARV) regimen other than FDC of B/F/TAF that 
consists of any two NRTIs + allowed third agent for ≥ 6 months (see Protocol Section 4.2 for 
allowed agents)
Screening 
30 da~'S prior 
to Day I 
Day 1' 
Treatment 
rou 
. 
G 
D 1 • (N=320) 
BIFITAF FDC QD 
Treatment 
rou 
. 
G 
D 2· (N=J60) 
2 NRT!s + 3rd agent QD 
Week 24" 
Week 48' 
Week 72 
Primary Endpoint 
Secondary Endpoint 


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
Have no documented or suspected resistance to integrase strand transfer inhibitors (INSTIs) 
and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 
RNA ≥ 50 copies/mL after achieving < 50 copies/mL while on an INSTI-containing 
regimen)

History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other reverse 
transcriptase (RT) substitutions are allowed, with the following exceptions: History of 3 or 
more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, 
or K65R/E/N in RT will be excluded.

Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen 
for a minimum period of 6 months, and at least the last two HIV-1 RNA measurements prior 
to the Screening visit

HIV-1 RNA levels < 50 copies/mL at Screening Visit

Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance

Eligible participants with chronic hepatitis C virus (HCV) infection are permitted to enroll. In 
addition, eligible participants with chronic hepatitis B virus (HBV) infection are permitted to 
enroll if their baseline regimen contains either TAF or TDF.
Study Phases
Participants will be treated for at least 48 weeks after randomization (Randomization Phase).
Following the Screening and Day 1 visits, participants will be required to return for study visits 
at Weeks 4, 12, 24, 36, and 48. Participants randomized to SBR will have, after their delayed 
switch at Week 24, an additional visit at Week 28.
Participants who complete the study through the Week 48 visit and wish to continue on 
B/F/TAF, will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks 
or until they have access to FDC of B/F/TAF, whichever occurs first, and will attend study visits
every 12 weeks followed by a 30-Day Follow-Up Visit. This is the Extension Phase.
Participants who complete the study through the Week 48 Visit and do not continue their 
participation in the study will be required to return to the clinic 30 days after their Week 48 Visit 
for a 30-Day Follow-Up Visit.
Schedule of Assessments
After screening procedures, eligible participants will be randomized 2:1 to Treatment Group 1 or 
Treatment Group 2 and treated for at least 48 weeks. Following the Day 1 visit, participants will 
return for study visits at Weeks 4, 8, 12, 24, 36 and 48. Participants randomized to SBR will 
have, after their delayed switch at Week 24, an additional visit at Week 28.


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Laboratory analyses (chemistry, hematology, and urinalysis), HIV-1 RNA, CD4+ cell count, 
assessment of adverse events (AEs) and concomitant medications, and complete or symptom 
directed physical examinations will be performed at Screening, Day 1 and subsequent study 
visits. Whole blood for HIV-1 deoxyribonucleic acid (DNA) archive testing will be collected at 
Day 1 for all participants and at Week 24 for all participants in Treatment Group 2.
Historical HIV-1 RNA genotypes (from resistance testing) will be collected, if available.
More details for study procedures can be found in Appendix 1.
Randomization
Participants will be randomized in a 2:1 allocation ratio to 1 of 2 treatment groups: 
Treatment Group 1 (B/F/TAF); Treatment Group 2 (SBR)]. Randomization will be stratified by
the baseline 3rd agent ARV class at entry (integrase strand transfer inhibitor (INSTI), 
non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI) or CCR5 
antagonist).
Site and/or Stratum Enrollment Limits
Approximately 84 study sites in the United States participated. In order to provide all sites the 
opportunity to enroll participants, the initial enrollment limit for individual sites was initially set 
to 6 participants. Additional enrollment slots at an individual site were allocated on a 
case-by-case basis.
Study Duration
Study duration for each participant will be at least 48 weeks. 
1.3.
Sample Size and Power
A total of 480 HIV-1 infected participants, randomized in a 2:1 ratio to 2 treatment groups, 
achieves approximately 89% power to detect a noninferiority margin difference between the 
group proportions of 6% for HIV-1 RNA ≥50 copies/mL at Week 24.
For sample size and power computation, it is assumed that the reference group proportion is 4%. 
The treatment group proportion is assumed to be 10% under the hypothesis of inferiority. The 
power is computed for the case when the actual treatment group difference is zero 
(treatment
reference). The test statistic used is the one-sided Score test (Farrington & 
Manning) with the significance level of 0.025. Sample size and power calculations were 
performed using the statistical software package PASS (Version 14).
In general, a failure rate of 1% to 3% is assumed for switch studies in virologically suppressed 
participants, and the noninferiority margin for treatment difference is typically set at 4%. The 
failure rate of 4% and noninferiority margin of 6% used for this study was based on the 
observation that African Americans have lower rates of virological suppression compared to 
other cohorts {DeJesus 2019}. In the United States (US), not all communities have had equitable 
access to advancements in HIV treatment. African Americans remain disproportionately affected 
by HIV but have less access to HIV treatment and generally worse health outcomes compared to 
other racial groups.


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Table 1-1 provides approximate power for SBR proportions ranging from 2% to 4% with 
noninferiority margin ranging from 4% to 6%. A total of 480 HIV-1 infected participants, 
randomized in a 2:1 ratio to 2 treatment groups, achieves approximately 87% power to detect a 
noninferiority margin difference between the group proportions of 4%.
Table 1-1.
Power for Various Proportions and Noninferiority Margins
SBR Proportion
Noninferiority Margin
Approximate Power
Actual Alpha
4%
6%
91%
0.026
3%
5%
88%
0.026
2%
4%
87%
0.024
SBR N 160; B/F/TAF N 320; alpha targeted at 0.025. The test statistic used is the one sided Score test (Farrington &Manning). 
Power and actual alpha were computed using binomial enumeration of all possible outcomes.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Week 24 Analysis
The Week 24 (primary endpoint) analysis was conducted after all participants either completed
their Week 24 visit or prematurely discontinued from the study prior to Week 24 and was 
repeated for the Week 48 analysis.
2.1.2.
Week 48 Analysis
The Week 48 analysis was conducted after all participants either completed their Week 48 visit 
or prematurely discontinued from the study.
2.2.
Final Analysis
The final statistical analysis will be conducted after all participants either complete the study or 
prematurely discontinue from the study.
This SAP describes the analysis plan for the final analysis. This final analysis will include all data 
from the participants randomized to FDC of B/F/TAF and post Week 24 (delayed switch) data for 
participants randomized to SBR. Data for the first 24 weeks for the SBR group were presented in 
the Week 24 and Week 48 analyses and will not be summarized in the final analysis. However, all 
data (other than patient-reported outcomes) will be included in the listings.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of participants in each category will be presented; for continuous 
variables, the number of participants (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all participants in the All Randomized Analysis Set
unless otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). 
Data collected on log forms, such as AEs, will be presented in chronological order within a 
participants. The treatment group to which participants were randomized will be used in the 
listings. 
For randomized participants, age (in years) collected on the Day 1 visit will be used for analyses 
and presentation in listings. For screen failures, age calculated on the date of the informed 
consent was signed will be used. Because only birth year is collected on the eCRF, “01 July” will 
be used for the unknown birth day and month for the purpose of age calculation.
In general, permanent discontinuation of study drug refers to premature discontinuation of study 
drug or completion of study drug.
3.1.
Analysis Sets
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. Participants included in each analysis set will be 
determined before database finalization. The analysis set will be included as a subtitle of each 
table, figure, and listing. A summary of the number and percentage of participants in each 
analysis set will be provided by treatment group and in total.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set will include all participants who were randomized into the 
study. This is the primary analysis set for by-subject listings.
3.1.2.
B/F/TAF Full Analysis Set
The B/F/TAF Full Analysis Set (FAS) will include all participants who (1) are randomized into 
the study, (2) have received at least 1 dose of B/F/TAF study drug, and (3) do not have 
pre-existing INSTI resistance-associated mutations (based on historical data). Participants will be 
grouped according to the treatment to which they were randomized. For the B/F/TAF FAS, all 
efficacy data, including data collected after the last dose of study drug, will be included, unless 
specified otherwise. 
This is the primary analysis set for efficacy analyses. 


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3.1.3.
B/F/TAF Safety Analysis Set
The B/F/TAF Safety Analysis Set will include all participants who (1) are randomized into the 
study and (2) have received at least 1 dose of B/F/TAF study drug. All data collected up to 
30 days after participants permanently discontinue study drug will be included in safety 
summaries, unless specified otherwise.
This is the primary analysis set for safety analyses.
3.2.
Subject Grouping
Participants will be grouped into the following 3 groups:

B/F/TAF: this group includes all participants randomized to the B/F/TAF group and who 
received at least 1 dose of B/F/TAF

Delayed Switch to B/F/TAF: this group includes all participants randomized to the SBR 
group who switched to B/F/TAF at Week 24 and received at least 1 dose of B/F/TAF

All B/F/TAF: all participants who received at least one dose of study assigned B/F/TAF 
(both immediate and delayed switch to B/F/TAF).
3.3.
Strata and Covariates
Randomization was stratified by the baseline third agent ARV class at study entry (INSTI, 
NNRTI, PI or CCR5 antagonist).
If there are discrepancies in stratification factor values between the interactive web response 
system (IWRS) and the clinical database, the values recorded in the clinical database will be used 
to group participants for analyses.
3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Efficacy Analyses
No subgroup analyses for efficacy are planned for the final analysis.
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 at birth: (a) male and (b) female 
2) Renal-related laboratory tests (ie, serum creatinine and eGFRCG) will be analyzed for the 
following subgroups: 

Baseline ARV Medication containing any of the following: rilpivirine (RPV), 
dolutegravir (DTG), ritonavir (RTV), cobicistat

Baseline ARV Medication not containing any of the following: RPV, DTG, RTV,
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3) Fasting metabolic laboratory tests will be analyzed for the following subgroups: 

Baseline ARV Medication containing TAF

Baseline ARV Medication containing TDF

Baseline ARV Medication not containing any of the following: TAF, TDF

Baseline ARV Medication containing efavirenz (EFV)

Baseline ARV Medication not containing EFV
4) Selected safety endpoints may be analyzed for the following subject subgroups 
(see Section 8.1 for details):

Participants with HIV/HBV coinfection at baseline

Participants with incident HIV/HBV coinfection while on study drug (if any)
5) Selected safety endpoints will be analyzed for the following subject subgroups 
(see Section 8.2 for details):

Participants with HIV/HCV coinfection at baseline

Participants with incident HIV/HCV coinfection while on study drug (if any)
3.5.
Multiple Comparisons
No prespecified multiplicity adjustments are planned for confidence intervals (CIs) or statistical 
tests.
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 participant 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 adverse event 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:

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 data for efficacy analyses. 
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “<20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purposes.
3.8.
Analysis Windows
3.8.1.
Definition of Study Day
Study Day 1/First Dose Date is defined as the day when the first dose of B/F/TAF was taken. 
The first dose date is the earliest nonmissing start date of B/F/TAF study drug recorded on the 
Study Drug Administration eCRF.
Study Days are calculated relative to Study Day 1. For events that occur on or after the 
Study Day 1 date, study days are calculated as (visit date minus Study Day 1 date plus 1). For 
events that occurred prior to Study Day 1, study days are calculated as (visit date minus Study 
Day 1 date).
Last Dose Date is defined as the maximum, nonmissing end date of B/F/TAF recorded on the 
Study Drug Administration eCRF and “Study Drug Permanently Discontinued” box checked for 
participants who prematurely discontinued study drug or completed study drug according to the 
Study Drug Completion eCRF.
For partial or missing last dose dates, please refer to the programming specifications for 
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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 participants who 
prematurely discontinued study according to the Study Completion eCRF.
Baseline value is defined as the last value obtained on or prior to Study Day 1 for all 
assessments. 
Note: for first dose date for SBR treatment group for listings, refer to the Week 48 SAP.
3.8.2.
Analysis Windows
Participant visits might not occur on protocol specified days. Therefore, for the purpose of 
analysis, observations will be assigned to analysis windows.
The analysis windows for HIV-1 RNA, hematology, chemistry, urinalysis, urine pregnancy
laboratory tests, eGFRCG, vital signs, and weight are presented in Table 3-1.
Table 3-1.
Analysis Windows for HIV-1 RNA, Hematology, Chemistry, 
Urinalysis, Urine Pregnancy Laboratory Tests, eGFRCG, Vital Signs
and Weight
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 4
28
2
56
Week 12
84
57
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
The analysis windows for CD4+ cell count, CD4 %, and metabolic assessments (including 
fasting glucose and lipid panel: total cholesterol, high density lipoprotein [HDL], direct low 
density lipoprotein [LDL], triglycerides, and total cholesterol to HDL ratio are presented in
Table 3-2.


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Table 3-2.
Analysis Windows for CD4+ cell count, CD4 %, and Metabolic 
Assessments
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 24
168
2
252
Week 48
336
253
420
The analysis windows for plasma HBV DNA are presented in Table 3-3.
Table 3-3.
Analysis Windows for Plasma HBV DNA
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 24
168
2
252
Week 48
336
253
420
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Window
Depending on the statistical analysis method, single values are required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time to event analysis would not require one value per analysis window. When a single value is 
needed, the following rule(s) will be used. 
If multiple nonmissing numeric observations exist in a window, then records will be chosen as 
follows:

For baseline, the latest available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, average will be used for the baseline value, except for HIV-1 RNA (see below).

For postbaseline visits:
For CD4+ cell count, CD4%, and 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.
CCI


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
For baseline and postbaseline HIV-1 RNA, the latest (considering both date and time) 
record(s) in the window will be selected. If both “HIV RNA Taqman 2.0” and “HIV RNA 
Repeat” (ie, the HIV-1 RNA result obtained from an additional aliquot of the original 
sample) are available with the same collection time, the results from the “HIV RNA Repeat” 
will be selected for analysis purposes; otherwise, if there are multiple “HIV RNA Taqman 
2.0” records with the same collection time, the geometric mean will be taken for analysis 
purposes.
If multiple valid nonmissing categorical observations exist in a window, records will be chosen 
as follows:

For baseline, the last available record on or prior to the first dose date of study drug will be
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected.

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 participants randomized at each investigator site will be 
summarized by treatment group (B/F/TAF and Delayed Switch to B/F/TAF) and overall using 
the B/F/TAF safety analysis set. The denominator for this calculation will be the number of 
participants in the B/F/TAF safety analysis set. Similarly, the number and percentage of 
participants enrolled in each randomization stratum will be summarized based on reclassified 
strata using the baseline third agent ARV class based on the Non-Study ARV Medication eCRF.
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 (B/F/TAF and Delayed 
Switch to B/F/TAF) and overall for all screened participants. This summary will include the 
number of participants screened, screen failure participants who were not randomized, 
participants who met all eligibility criteria and were not randomized, participants randomized, 
participants randomized but never treated, participants with delayed switch to B/F/TAF, 
participants in the B/F/TAF safety analysis set, and the number of participants in the B/F/TAF 
FAS.
In addition, the number and percentage of the participants in the following categories will be 
summarized:

Completed study drug

Prematurely discontinuing study drug (with summary of reasons for discontinuing study 
drug)

Treated in the Extension phase

Completed study

Prematurely discontinuing from study (with summary of reasons for discontinuing study).
The denominator for the percentages of participants in each category will be the number of 
participants in the B/F/TAF safety analysis set.
No inferential statistics will be generated. A data listing of reasons for study drug/study 
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4.2.
Extent of Study Drug Exposure and Adherence
4.2.1.
Duration of Exposure to Study Drug
Duration of exposure will be calculated for the B/F/TAF and Delayed Switch to B/F/TAF
groups. Duration of exposure to study drug will be defined as (last dose date - 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 participants
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).
Summaries will be provided for participants in the B/F/TAF safety analysis set. No inferential 
statistics will be provided. 
4.2.2.
Adherence to Study Drug Regimen
Study drug regimen adherence will be computed based on pill counts. The numbers of pills of 
study drug dispensed and returned are captured on study drug accountability eCRF.
Adherence (%) of study drug regimen will be calculated as follows:




]
2
[
]
1[
period
dispensing
each 
at 
prescribed
pills
of
No.
period
dispensing
each 
at 
 taken 
pills
of
No.
100
prescribed
pills
of
No.
Total
 taken
pills
of
No.
Total
100
(%)
Adherence
[1] Number of pills taken at a distinct dispensing period for a study drug is calculated as the minimum of (a) the daily number of 
pills prescribed for the study drug multiplied by the duration of treatment at the dispensing period, and (b) the number of pills 
taken for the study drug (number of pills dispensed minus the number of pills returned). Total number of pills taken is determined 
by summing the number of pills taken 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.
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 
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For a record where the number of pills returned was missing (with “Yes” answered for 
“Was Bottle returned?” question), it is assumed the number of pills returned was zero. If the 
number of pills dispensed was missing or any study drug bottle was not returned or the bottle 
return status was unknown, then all records in that dispensing period for that study drug will be 
excluded from both denominator and numerator calculation.
Adherence will be calculated using all data from the entire dosing period up to the date of 
permanent discontinuation of the study drug for participants who prematurely discontinued study 
drug or completed study drug. 
Descriptive statistics for adherence (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
along with the number and percentage of participants belonging to adherence categories 
(eg, < 80%, ≥ 80% to < 90%, ≥ 90% to < 95%, ≥ 95%) will be provided for participants who 
return at least 1 bottle and have calculable adherence during the study in the B/F/TAF safety 
analysis set. No inferential statistics will be provided.
4.3.
Protocol Deviations
A listing will be provided for all participants who violated at least 1 inclusion or exclusion 
criterion. The listing will include the criteria not met.
Protocol deviations occurring after participants entered the study are documented during routine 
monitoring. The number and percentage of participants with important protocol deviations by 
deviation reason and the total number of important protocol deviations by deviation reason
(eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) will be 
summarized by treatment group (B/F/TAF and Delayed Switch to B/F/TAF) for the B/F/TAF 
FAS. A by-subject listing will be provided for those participants with important protocol 
deviations. 
4.4.
Assessment of COVID-19 Impact
This study was ongoing during the novel coronavirus (2019 nCOV [COVID-19]) pandemic 
which caused a disruption in the regular visit schedules for this study. Some participants were 
unable to attend onsite visits due to shelter in place guidelines, site closures or other reasons. 
Visits related to the primary and secondary endpoints of the study were not impacted.
4.4.3. Missed and Virtual Visits due to COVID-19
An overall summary of the number and percentage of participants with missed or virtual visits 
(e.g., at least 1, with 1, 2, 3 or more visits) due to the COVID-19 pandemic will be provided. The 
denominator for the percentage calculation will be the total number of participants in the 
B/F/TAF safety population.
A by-subject listing will be provided presenting participants who missed or had virtual visits due 
to COVID-19. The determination of missing or virtual visits due to COVID-19 was done using 
Natural Language Processing (NLP) to search the CRF comment fields. A detailed explanation 
of the algorithm is given in Appendix 5.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, gender identity, sexual orientation, race, and 
ethnicity) and baseline characteristics (eg, body weight, height, and body mass index [BMI]) will 
be summarized by treatment group (B/F/TAF and Delayed Switch to B/F/TAF) and overall using 
descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) for continuous 
data and by the number and percentage of participants for categorical data. The summaries of 
demographic data and baseline subject characteristics will be provided for the B/F/TAF safety 
analysis set.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized by treatment group (B/F/TAF 
and Delayed Switch to B/F/TAF) and overall using descriptive statistics:

HIV-1 RNA categories (copies/mL): (a) < 50, (b) ≥50

CD4+ cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥50 to < 200, (c) ≥200 to < 350, 
(d) ≥350 to < 500, and (e) ≥500

CD4 percentage (%)

Mode of infection (HIV risk factors)

HIV disease status

eGFRCG (mL/min)

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)

Duration of HIV Diagnosis (years) (calculated as years prior to year from First Dose/Day 1 
date; see programming specifications)

Duration of HIV Treatment (Years) (calculated as years prior to year from First Dose/Day 1 
date; see programming specifications)

Duration of baseline ARV medication prior to randomization (based on the Non-Study ARV 
Medication eCRF, see programming specifications)


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
Baseline ARV Regimen (based on the Non-Study ARV Medication eCRF, see programming 
specifications)
Baseline ARV Medication Backbone (FTC+TAF, FTC+TDF, TDF+3TC, ABC+3TC, 
AZT+3TC)
Baseline 3rd agent (INSTI, NNRTI, PI, CCR5), and further broken down by ingredient
Baseline ARV Medication (Backbone+3rd agent)
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. 
Primary Efficacy Endpoint 
6.1.1. 
Definition of the Primary Efficacy Endpoint 
Version 1.0 
The primary efficacy endpoint is the proportion of participants with HIV-1 RNA ~ 50 copies/mL 
at Week 24 as detennined by the US FDA-defined snapshot algorithm {U.S. Department of 
Health and Human Services 2015}. 
The analyses of the primary efficacy endpoint were perfonned in the Week 24 analysis, and will 
not be repeated here. 
6.2. 
Secondary Efficacy Endpoints 
6.2.1. 
Definition of the Secondary Efficacy Endpoints 
The secondary efficacy endpoints include: 
• 
The proportion of participants with HIV-1 RNA ~ 50 copies/mL at Week 48 as detennined 
by the US FDA-defined snapshot algorithm 
• 
The proportion of participants with HIV-1 RNA < 50 copies/mL at Week 24 and Week 48 as 
detennined by the US FDA-defined snapshot algorithm 
• 
The change from baseline in CD4+ cell com1t at Week 24 and Week 48 
The analyses of the secondary efficacy endpoints were perfonned in the Week 24 and Week 48 
analyses and will not be repeated here. 
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6.4. 
Changes from Protocol-Specified Efficacy Analyses 
No change from the protocol-specified efficacy analyses are planned. 
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7.
SAFETY ANALYSES
Safety data will be summarized for the participants in the B/F/TAF safety analysis set. All safety 
data collected up to 30 days after permanent discontinuation of B/F/TAF study will be 
summarized by treatment group, unless specified otherwise. All safety data will be included in 
data listings.
7.1.
Adverse Events and Deaths
Summaries of AEs by treatment group (B/F/TAF, Delayed Switch to B/F/TAF, All B/F/TAF) 
will include data collected up to 30 days after permanent discontinuation of study drug.
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 Gilead Global Patient Safety (GLPS) 
Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the B/F/TAF study drug start date and no later than 
30 days after permanent discontinuation of the B/F/TAF study drug, or 

Any AEs leading to premature discontinuation of B/F/TAF study drug.


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


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Treatment-emergent death refers to deaths that occurred between the first dose date and the 
last dose date plus 30 days (inclusive).
Multiple events will be counted only once per participant 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 participant 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.
By-participant listings will be provided for all AEs, study drug-related AEs, grade 3 and 4 AEs, 
serious AEs, study drug-related SAEs, and AEs leading to premature study drug discontinuation.
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Stage 3 Opportunistic Illnesses in HIV
On an ongoing basis, AEs will be reviewed for events that might meet the definition of stage 3 
opportunistic illnesses in HIV that are indicative of an AIDS-defining diagnoses (see Protocol
Appendix 6). The Gilead medical monitor will review the possible stage 3 opportunistic illnesses
and approve the events that meet the definition. Events that meet the stage 3 opportunistic illness
definition of an AIDS-Defining Diagnosis will be listed.
7.1.7.2.
Cardiovascular or Cerebrovascular Events
Preferred terms for cardiovascular or cerebrovascular events are from relevant Standardised 
MedDRA Query (SMQ). The selected PT listing was provided by Gilead GLPS and reviewed by 
Gilead medical monitors (see details in Appendix 3).
The number and percentage of participants with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
summarized by treatment group (B/F/TAF, Delayed Switch to B/F/TAF, and All B/F/TAF) 
based on the B/F/TAF safety analysis set. A by-subject 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 4).


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The number and percentage of participants with treatment-emergent hepatic events and serious 
hepatic events by PT will be summarized by treatment group (B/F/TAF, Delayed Switch to 
B/F/TAF, and All B/F/TAF) based on the B/F/TAF safety analysis set. A by-subject data listing 
of hepatic events will be provided.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
B/F/TAF safety analysis set and will include data collected up to the last dose of B/F/TAF study 
drug plus 30 days.
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7.
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the reference range and/or having a severity grade of 1 or higher on the Gilead 
Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be flagged in 
the data listings, as appropriate.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group (B/F/TAF, Delayed Switch to 
B/F/TAF) 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
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.


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Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 

Calcium corrected for albumin (mg/dL)  serum calcium (mg/dL) + 0.8 
× (4.0 - albumin (g/dL)). 
Toxicity grading for calcium will be applied based on the corrected values.
Estimated GFR
The Cockcroft-Gault (CG) formula will be used to calculate eGFRCG: 

eGFRCG (mL/min)  [(140 age (yrs)) × weight (kg) × (0.85 if female)] / 
(SCr (mg/dL) × 72), where weight is total body mass in kilograms, and SCr is serum 
creatinine.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used for assigning toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction 
(ie, increased, decreased) will be presented separately.
If there is any laboratory toxicity grading scale overlapping with the normal reference ranges 
(eg, grade 1 scale overlaps with normal reference ranges), laboratory values that are within the 
normal range will be grade 0 except for lipid tests.
For triglycerides, LDL, and cholesterol, the protocol specified toxicity grading scale is for fasting 
test values, so 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 the cutoffs specified at the 
start of Section 7.2.
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.


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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. Most participants 
had a nonfasting glucose at the Screening visit and a fasting glucose at the Day 1 visit; therefore, 
both a baseline nonfasting glucose and a baseline fasting glucose are available for most 
participants, and treatment-emergent laboratory abnormalities will be summarized for both 
nonfasting glucose and fasting glucose.
Both urine 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.
7.2.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of participants) for treatment-emergent 
laboratory abnormalities will be provided by lab test and treatment group (B/F/TAF, Delayed 
Switch to B/F/TAF, and All B/F/TAF); participants will be categorized according to the most 
severe postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities 
For all summaries of laboratory abnormalities, the denominator is the number of participants 
with any nonmissing postbaseline values for the particular laboratory test.
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 for the B/F/TAF and Delayed Switch to B/F/TAF groups.
In addition, the number and percentage of participants who took lipid modifying medications at 
baseline and initiated the medications during the study will be provided for the B/F/TAF and 
Delayed Switch to B/F/TAF treatment groups.
A lipid modifying medication is defined as a medication with drug class (based on World Health 
Organization [WHO] Drug ATC2 term)
 “LIPID MODIFYING AGENTS” and WHO Drug
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A sensitivity analysis of fasting lipid tests will be performed by excluding participants who took 
lipid modifying medications at baseline or initiated the medications during the study: baseline 
values, Week 72 values, and changes from baseline at Week 72 will be summarized for the 
B/F/TAF group using descriptive statistics. Only participants with both baseline and Week 72
values will be included in the analysis. A similar summary at Week 48 will be produced for the 
Delayed Switch to B/F/TAF group.
Summary of baseline, postbaseline, and change from baseline in fasting metabolic laboratory 
tests will be repeated within each subgroup of baseline ARV medication (see Section 3.4.2).
Median (Q1, Q3) of change from baseline in fasting metabolic assessments over time will be 
plotted by treatment group (B/F/TAF and Delayed Switch to B/F/TAF). 
7.2.4.
Liver-Related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized for 
the B/F/TAF, Delayed Switch to B/F/TAF, and All B/F/TAF groups using the number and 
percentage of participants who were reported to have the following laboratory test values for post 
baseline measurements:

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
For individual laboratory tests, participants 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, participants will be counted once 
when the criteria are met at the same postbaseline visit date. The denominator is the number of 
participants in the B/F/TAF safety analysis set with nonmissing postbaseline value of the tests in 
evaluation at the same postbaseline visit date.
Participants with AST or ALT > 3 × ULN, total bilirubin > 1 x ULN, or ALP > 1.5 x ULN while 
on-treatment 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 (B/F/TAF and Delayed Switch to B/F/TAF) and 
visit using descriptive statistics.
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 
participants with HIV/HBV coinfection at baseline. 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 (B/F/TAF and Delayed Switch to B/F/TAF) and visit using 
descriptive statistics. 
Median (Q1, Q3) of change from baseline in serum creatinine and eGFRCG over time will be 
plotted by treatment group.
Summary of baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG
will be repeated within each subgroup of baseline ARV medication (see Section 3.4.2).
7.2.5.2.
Proteinuria by Urinalysis (Dipstick)
The proteinuria by urinalysis (dipstick) toxicity grade (Grade 0 to Grade 3) will be summarized 
by baseline proteinuria toxicity grade and treatment group (B/F/TAF and Delayed Switch to 
B/F/TAF) by visit. In addition, the last on-treatment proteinuria toxicity grade will be 
summarized by baseline proteinuria toxicity grade and treatment group. On-treatment data is as 
all data collected up to 1 day after permanent discontinuation of study drug. 
7.3.
Body Weight, Height, and Vital Signs
Descriptive statistics will be provided by treatment group (B/F/TAF and Delayed Switch to 
B/F/TAF) for vital signs and body weight as follows:

Baseline values

Values at each postbaseline analysis window

Change from baseline to each postbaseline analysis window 
A baseline value will be defined as the last nonmissing value obtained on or prior to the date of 
first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
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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 antiretroviral (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. 
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 the date of first dose of study treatment up to the date of last dose of study 
treatment will be summarized (number and percentage of participants) by treatment group
(B/F/TAF and Delayed Switch to B/F/TAF) and preferred drug name. Multiple drug use will be 
counted only once per participant 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.
Summaries of non-ARV concomitant medications will be provided for the B/F/TAF safety 
analysis set. Participants with any non-ARV concomitant medications will be listed. No 
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7.5.
Electrocardiogram Results
A by-subject listing for electrocardiogram (ECG) assessment results will be provided. 
7.6.
Other Safety Measures
A data listing will be provided for participants 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 B/F/TAF safety analysis set.
7.8.
Changes from Protocol-Specified Safety Analyses
No changes from the protocol-specified safety analyses are planned.


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8.
SPECIAL POPULATION ANALYSES
8.1.
Analyses for HIV/HBV Coinfected Participants
Participants with HIV/HBV coinfection at baseline are defined as participants who meet any of 
the following two criteria: 

Positive HBsAg on or prior to the first dose date, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) on or prior to the first dose date.
The following analyses will be conducted by treatment (B/F/TAF, and Delayed Switch to 
B/F/TAF) for participants with HIV/HBV coinfection at baseline: 

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.
Listings will be provided for:

adverse events

liver-related laboratory tests and HBV DNA results

ALT elevation (ie, ALT > 2 x Baseline and ALT > 10 x ULN) and ALT flare 
(see section 7.2.4)
Participants with incident HIV/HBV coinfection while on study drug are defined as participants 
who are not HIV/HBV coinfected at baseline and meet any of the following criteria:

Positive HBsAg after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
date, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA (ie, HBV 
DNA ≥20 IU/mL) after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
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
Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first B/F/TAF dose date and on or prior to the 
last B/F/TAF dose date: Acute hepatitis B, Chronic hepatitis B, Congenital hepatitis B 
infection, Hepatitis B, Hepatitis B core antibody positive, Hepatitis B DNA assay positive, 
Hepatitis B surface antigen positive, Hepatitis B virus test positive.
The following listings will be provided for participants with incident HIV/HBV coinfection 
while on study drug: 

Listing of adverse events

Listing of liver-related laboratory tests and HBV DNA results
8.2.
Analyses for HIV/HCV Coinfected Participants
Participants with HIV/HCV coinfection at baseline are defined as participants with positive 
HCVAb and quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) on or prior to the first dose 
date. The following listings will be provided for participants with HIV/HCV coinfection at 
baseline: 

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results
Participants with incident HIV/HCV coinfection while on study drug are defined as participants 
who are not HIV/HCV coinfected at baseline and meet any of the following criteria:

Positive HCVAb after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
date, or

Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the first B/F/TAF dose date and 
on or prior to the last B/F/TAF dose date, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first B/F/TAF dose date and on or prior to the 
last B/F/TAF dose date: Acute hepatitis C, Chronic hepatitis C, Hepatitis C, Hepatitis C 
antibody positive, Hepatitis C RNA positive, Hepatitis C virus test positive.
The following listings will be provided for participants with incident HIV/HCV coinfection 
while on study drug: 

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results


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9.
PATIENT REPORTED OUTCOMES
The patient-reported outcomes were analyzed for the Week 48 analysis, and the analyses will not 
be repeated for the final analysis.


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10.
REFERENCES
DeJesus E, Villanueva J, Lopez J, Brinson C, Crofoot G, Daar ES, et al. Tenofovir Alafenamide 
vs Tenofovir Disoproxil Fumarate in Hispanic/Latinx and Black Participants: 
Efficacy, Bone and Renal Safety Results From a Pooled Analysis of 7 Clinical 
Trials [Poster 318]. IDWeek; 2019 2-6 October; Washington, DC. 
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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11.
SOFTWARE
SASVersion 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
PASS Version 14 (NCSS, LLC, Kaysville, Utah) was used for planned sample size and power 
calculation.


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


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13.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial)
Appendix 3.
Cardiovascular or Cerebrovascular Events
Appendix 4.
Hepatic Events
Appendix 5.
Determining Missing and Virtual visits due to COVID-19
Appendix 6.
Programming Specifications


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Appendix 1.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48e
30 Day 
Follow-Upf
ESDDg
4
12
24
28d
36
48
Every 12 Weekscc
Informed Consent
X
HIV Symptoms Distress Module
X
X
X
X
X
HIV-TSQh
X
X
X
VAS Adherence Questionnairei
X
X
X
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete/Symptom-Directed Physical Examj
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG 
(performed supine)
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
Vital Signsk
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Pregnancy Testl
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testl
X
FSH Testm
X
Chemistry Profilen
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentso
X
X
X
X
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X


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Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48e
30 Day 
Follow-Upf
ESDDg
4
12
24
28d
36
48
Every 12 Weekscc
Hematology Profilep
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAq
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Panels
Xt
Xt
Plasma HBV DNAu
X
X
X
X
HCV Serologyv
X
X
X
HIV-1 Genotype/Phenotypeq
Xq
Plasma, Serum, and Urine Sample Storagew
X
X
X
X
X
X
X
X
X
Whole Blood for HIV-1 DNA archive testing
X
Xx
Obtain Screening Number
X
Randomizationz
X
Study Drug Dispensation 
Xbb
Xbb
Xbb
Xaa
X
X
X
X
Study Drug Accountability
Xbb
Xbb
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Participants should initiate dosing of study drug on the same day as the Day 1 visit.
c
All study visits are to be completed ± 6 days of the protocol specified visit date (based on the Day 1 visit), unless otherwise specified. 
d
Participants randomized to continue their baseline regimen will have an additional visit at Week 28.
e
At the study Week 48 Visit, participants who wish to continue on B/F/TAF will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks or until they 
have access to FDC of B/F/TAF, whichever occurs first, and attend study visits every 12 weeks (± 6 days of the protocol specified visit date) followed by a 30 Day Follow Up 
Visit.
f
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30 Day Follow Up Visit, a ± 6 days window may be used. Required for 
participants who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Participants 
who participate post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30 Day Follow Up Visit.
g
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Participants will be asked to continue attending the scheduled study visits through 
the Week 48 Visit even if the participant discontinues study drug. Participants on Treatment 2 (SBR) who discontinue their baseline regimen due to an AE prior to Week 24 
will be asked to continue attending the scheduled study visits through the Week 24 visit.
CCI
CCI


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HIV TSQs is to be completed at Day I. The HIV TSQc is to be completed at Week 4 and Week 24. Participant is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires. 
VAS Adherence Questionnaire will be administered at Day I and at all visits up to (and including) Week 24 for participants in Treatment Group 2 (SBR) only. 
Complete physical exam is re.quired at Screening, Day I, Week 24, 48, 72, and ESDD. Urogenital/anorectal exams will be perforn1ed at the discretion of the Investigator. 
Symptom directed physical examination, as needed. 
k 
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature. 
I 
All female participants will have a semm test perforn1ed at Screening. Urine pregnancy test will only be done for persons of childbearing potential. Positive urine pregnancy 
tests will be confirn1ed with a semm test. 
m 
FSJ-1 test is re.quired for female participants who are <54 years old and have stopped menstmating for 2:: 12 months but do not have documentation of ovarian horn10nal failure. 
n 
Chemistry profile: alkaline phosphatase, AST, ALT, total bilimbin, direct and indirect bilimbin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphoms, magnesium, potassium, sodium, amylase, and Cystatin C. After Day I, calcium, phosphorous, magnesium, and amylase (reflex lipase testing is 
perforn1ed in participants with total amylase > 1.5 x ULN) 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 I, Weeks 24, 48, and 72. Cystatin C will only be collected at Day I. 
o 
Metabolic Assessments will be perforn1ed at Day I, Weeks 24, 48, and 72. 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 participant has not fasted prior to the visit, the visit may proceed, but the participant must return within 
72 hours in a fasted state to draw blood for the metabolic assessments. 
p 
CBC with differential and platelet count. 
q 
HIV I genotype and phenotype testing for participants with confirn1ed virologic failure and HIV I RNA >200 copies/mL. Following virologic rebound, participants 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 I RNA and HIV I resistance analysis (reverse 
transcriptase, protease, and integrase genotype and phenotype) blood draw. Based on the results of this testing, participants should be managed according to the Virologic 
Rebound Schema. 
r 
ti 
V 
w 
X I' 
z 
oo panel will be perforn1ed at Screening and Week 48: HBsAg, 1-IBsAb, HBcAb. 
For participants who are HBV co-infected (defined in Protocol Section 6.9.1): The following 1-IBV Blood panel will be conducted by the central laboratory: HBsAb, 
1-IBsAg (qualitative and quantitative), and HBeAg (if negative, reflex HBeAb). 
For participants who are NOT HBV co-infected: The following 1-IBV Blood panel will be conducted by the central laboratory: HBsAb, 1-IBcAb, and HBsAg. 
Participants who are HBsAg or HBcAb positive will have a reflex test for HBV DNA (viral load). 
For participants who are HBV co-infected: Plasma 1-IBV DNA will be collected at Day I, Week 24, Week 48 and ESDD. 
Hepatitis C vims serology will be perforn1ed at Screening, Week 48, and Week 72. Participants who are HCV Ab positive will have an I-ICY RNA test perforn1ed. 
Plasma, semm, and urine storage samples will be collected for safety, virology, or PK testing. 
Collect whole blood sam le for artici ants randomized to SBR only at Week 24. 
ic Day I visit provided that all screening procedures have been completed and participant eligibility has 
been confirn1ed. 
aa 
At Week 24, participants randomized to continue their baseline regimen and complete 24 weeks of treatment on their baseline regimen will switch to FDC of B/F/T AF. 
bb 
FDC of B/F/T AF will be dispensed to Treatment Group I only. Study dmg accountability will be perforn1ed accordingly. 
cc 
Participants will receive study dmg for dosing until Week 72. 
CONFIDENTIAL 
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16 November 2020 


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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}.
Is there at least l un-
treatment* HlV-1 RNA data 
Yes____ col lected in the 11apshot 
t------,.,o 
Is the last available on-tnr.itment* 
HIV-I RNA in the Snapshot 
window < 50 copies/rnL? 
Yes 
HlV-1 Rl\ 
< 
50 copics/m L 
lllV-1 Rl A~ 
50 copie /m 
window? 
Js study drug prematurely 
di ·continued on or prior to the 
upper limit of the Snapshot 
·window? 
Yes 
[s discontinuation of the study 
drug due to Lack or Efficacy'! 
No 
ls discontinuation of the study 
drug due to AE/Dcath? 
Yes 
[s the last available on-
Is the last available on-
treatment* HJV-I RNA < treatment* HfV-1 RNA < 
50 copies/mL 
50 copies/mL 
o Virologic Data: 
Discontinued Study 
Drug Due to Other 
Reason and Last HIV-1 
R~A < 50 copks/mL 
. o Vi.rologic Data: 
Discontinued Study 
Drug Due to AE/Death 
a11d Last HJV-1 RNA < 
50 copics/mL 
0 
No Virologic Data: 
Missing Oat.a du.ring 
Window but on Study 
Drug 
* On-Treatment HIV-I RNA data inchide all HIV-I RNA data for subjects who are on-going and .H IV-I RNA data up to I 
day after the last do ·e date of study drug for subjects w ho prematurely discontinue or complete study drug. 


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Appendix 3.
Cardiovascular or Cerebrovascular Events
An adverse event record will be flagged as a cardiovascular or cerebrovascular event if its 
MedDRA PT is included in the pre-specified PT list, which includes all PTs from the narrow 
search of the following 3 SMQs under MedDRA v23.0 provided by Gilead GLPS (search name: 
Ischemic cardiac and cerebral events narrow) and reviewed by Gilead medical monitors.
SMQ Source
Cardiovascular or Cerebrovascular 
Events
Ischaemic central nervous system vascular conditions (SMQ) – Narrow 
Scope Term
Myocardial infarction (SMQ) - Narrow Scope Term
Other ischaemic heart disease (SMQ) - Narrow Scope Term


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Appendix 4.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT is included in this
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA v23.0 provided by Gilead GLPS (search name: Non-infectious, non-congenital 
hepatobiliary disorders) and reviewed by Gilead medical monitors.
SMQ Source
Hepatic Events (HEP)
Biliary neoplasms benign (incl cysts and polyps) (SMQ)
Biliary malignant tumours (SMQ)
Biliary tumours of unspecified malignancy (SMQ)
Biliary system related investigations, signs and symptoms (SMQ)
Biliary tract disorders (SMQ)
Gallbladder related disorders (SMQ)
Gallstone related disorders (SMQ)
Cholestasis and jaundice of hepatic origin (SMQ)
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ)
Hepatitis, non-infectious (SMQ)
Liver neoplasms, benign (incl cysts and polyps) (SMQ)
Liver malignant tumours (SMQ)
Liver tumours of unspecified malignancy (SMQ)
Liver related investigations, signs and symptoms (SMQ)
Liver-related coagulation and bleeding disturbances (SMQ)


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Appendix 5.
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
SHELTER
PHONE
HOME VISIT
ZOOM
SKYPE


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


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Appendix 6.
Programming Specifications
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
AGE (years) is calculated from the number of days between the DOB and Study Day 1,
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),
Divide the result in (b) by 12,
AGE  the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened participants refer to all participants who are screened (ie, with non-missing 
screening date) and have a screening number. For summaries the same participant is counted 
only once. DOB and other demographic information such as sex, race, and ethnicity will be 
used to identify unique screened participants.
3) Screen failure participants are the participants who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the participant was consent to.
4) Participants in the randomized analysis set are defined as participants randomized into the 
study. IXRSRAND is the source to determine whether the participant is randomized 
(ie, participant 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) is derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if 
participant took at least 1 dose of study drug and assigned as blank if the participant was 
never dosed.
6) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.
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.


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8) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded from 
percentage calculation. Except for Mode of infection (HIV Risk Factors), where “Unknown” 
will be included for percentage calculation, since a participant may fit more than 1 HIV risk 
factors, therefore percentage may add to more than 100% and no p-value will be generated. 
9) Defining Baseline ARV Medication
Baseline ARV Medication
All participants are expected to enter the study on an ARV regimen other than FDC of 
B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months (see Protocol 
Section 4.2 for allowed agents)
Using the ARV raw dataset, for the B/F/TAF treatment group, include all prior and/or current 
ARVs (ARV.INGRED where ARV.CMSCAT ”Prior ARV” or “Current ARV”), taken on 
or up to 4 days prior to first dose date as defined in Section 3.8.1 (or randomization date if 
not treated). For the SBR treatment group, include all prior and/or current ARVs
(ARV.INGRED where ARV.CMSCAT ”Prior ARV” or “Current ARV”) taken on Study 
Day 1.
Use the following rules to determine if the ARV medication is taken on Day 1:

If ARV end date is before B/F/TAF first dose date -4 for B/F/TAF participants or Day 1 date 
for SBR participants then exclude. If “Ongoing” is not marked and the end date is completely 
missing, then exclude. See below for imputation rules for any partial dates of uncertainty.

If ARV start date is after B/F/TAF first dose date for B/F/TAF participants (or Day 1 visit 
date for SBR participants) then exclude. See below for imputation rules for any partial dates 
of uncertainty.
The different categories used for the baseline ARV medication are (1) backbone, 
(2) third agent, and (3) third agent class.

For participants with more than one baseline ARV medication record, concatenate the 
records together using “+” to get one record for each participant. For all ingredients, replace 
“_” or “+” with “/”.

For each participant, search for the NRTIs: FTC, TAD, TDF, ABC, AZT, and 3TC. There 
should be 2 NRTIs for each participant. Create the backbone variable by concatenating the 
2 NRTIs listed in the order above and separate by a “/” as per the backbone column in the 
table below. 


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
For each participant, identify the Third Agent. These will fall into 4 categories (PI, NNRTI, 
INSTI, and CCR5 antagonist). Each participant should have only 1 category of third agent 
unless they have a protocol deviation. For each participant, create the third agent variable by 
selecting on the ingredients listed:
PIs and boosted PIs include ATV, ATV/RTV, ATV/COBI, DRV/RTV, DRV/COBI, 
LPV/RTV, and NFV. Create the third agent variable by concatenating the ingredients 
(ATV, DRV, LPV, NFV, RTV, COBI) with a “/”. Change “ATV/RTV” to “ATV/r”, 
“ATV/COBI” to “ATV/co”, “DRV/RTV” to “DRV/r”, “DRV/COBI” to “DRV/co”, and 
“LPV/RTV” to “LPV/r”, as per the Third Agent column in the table below.
NNRTIs include DOR, EFV, NVP, and RPV. ETR is not allowed but is to be included 
for participants who were not on a protocol-approved baseline ARV medication.
INSTIs include DTG, EVG/COBI, and RAL. Create the third agent variable by 
concatenating the ingredients (DTG, EVG, COBI, RAL). Change “EVG/COBI” to 
“EVG/co” as per the Third Agent column in the table below. RAL/RTV is a protocol 
violation and should be changed to “RAL/r”.
CCR5 antagonists include MVC.
Each participant should have PI or NNRTI or INSTI or CCR5. If a participant has more 
than one, then it is a protocol violation. The third agent can be listed as “DTG/RPV” and
should be counted in both categories for summary purposes.
The final Baseline ARV Medication will be presented as third agent + backbone as per 
the last column in the table below.
The table below provides example records for each participant with the backbone, 
third agent, third agent class, and final baseline ARV Medication variables.
Baseline ARV Medications 
from the data
Backbone
Third Agent
Third Agent 
Class
Baseline ARV 
Medication
ABC/NVP/FTC/TAF*
ABC/FTC/TAF
NVP
NNRTI
NVP+ABC/FTC/TAF
ATV/ABC/3TC
ABC/3TC
ATV
PI
ATV + ABC/3TC
ATV/RTV/ABC/3TC
ABC/3TC
ATV/r
PI
ATV/r + ABC/3TC
ATV/RTV/FTC/TAF
FTC/TAF
ATV/r
PI
ATV/r + FTC/TAF
ATV/RTV/FTC/TDF
FTC/TDF
ATV/r
PI
ATV/r + FTC/TDF
ATV/COBI/FTC/TAF
FTC/TAF
ATV/co
PI
ATV/co + FTC/TAF
DOR/FTC/TDF
FTC/TDF
DOR
NNRTI
DOR + FTC/TDF
DRV/COBI/ABC/3TC
ABC/3TC
DRV/co
PI
DRV + ABC/3TC
DRV/COBI/FTC/TAF
FTC/TAF
DRV/co
PI
DRV/co + FTC/TAF
DRV/COBI/FTC/TDF
FTC/TDF
DRV/co
PI
DRV/co + FTC/TDF


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Baseline ARV Medications 
from the data
Backbone
Third Agent
Third Agent 
Class
Baseline ARV 
Medication
DRV/DTG/RTV/FTC/TAF*
FTC/TAF
DRV/r and 
DTG
DRV/r is PI
DTG is INSTI
DRV/r and DTG + 
FTC/TAF
DTG/ABC/3TC
ABC/3TC
DTG
INSTI
DTG + ABC/3TC
DTG/FTC/TAF
FTC/TAF
DTG
INSTI
DTG + FTC/TAF
DTG/FTC/TDF
FTC/TDF
DTG
INSTI
DTG + FTC/TDF
DTG/RPV*
-
DTG and 
RPV
DTG is INSTI
RPV is NNRTI
DTG and RPV
EFV/3TC/TDF
TDF/3TC
EFV
NNRTI
EFV + TDF/3TC
EFV/ABC/3TC
ABC/3TC
EFV
NNRTI
EFV + ABC/3TC
EFV/AZT/3TC
AZT/3TC
EFV
NNRTI
EFV + AZT/3TC
EFV/FTC/TAF
FTC/TAF
EFV
NNRTI
EFV + FTC/TAF
EFV FTC/TDF
FTC/TDF
EFV
NNRTI
EFV + FTC/TDF
ETR/ABC/3TC*
ABC/3TC
ETR
NNRTI
ETR + ABC/3TC
EVG/COBI/FTC/TAF
FTC/TAF
EVG/co
INSTI
EVG/co + FTC/TAF
EVG/COBI/FTC/TDF
FTC/TDF
EVG/co
INSTI
EVG/co + FTC/TDF
FTC/RPV/TAF
FTC/TAF
RPV
NNRTI
RPV + FTC/TAF
FTC/RPV/TDF
FTC/TDF
RPV
NNRTI
RPV + FTC/TDF
LPV/RTV/FTC/TDF
FTC/TDF
LPV/RTV
PI
LPV/r + FTC/TDF
MVC/FTC/TDF
FTC/TDF
MVC
CCR5
MVC + FTC/TDF
NFV/FTC/TAF
FTC/TAF
NFV
PI
NFV + FTC/TAF
NVP/AZT/3TC
AZT/3TC
NVP
NNRTI
NVP + AZT/3TC
NVP/FTC/TDF
FTC/TDF
NVP
NNRTI
NVP + FTC/TDF
NVP/FTC/TAF
FTC/TAF
NVP
NNRTI
NVP + FTC/TAF
RAL/ABC/3TC
ABC/3TC
RAL
INSTI
RAL + ABC/3TC
RAL/FTC/TAF
FTC/TAF
RAL
INSTI
RAL + FTC/TAF
RAL/FTC/TDF
FTC/TDF
RAL
INSTI
RAL + FTC/TDF
RTV/DRV/ABC/3TC
ABC/3TC
DRV/r
PI
DRV/r + ABC/3TC
RTV/DRV/FTC/TAF
FTC/TAF
DRV/r
PI
DRV/r + FTC/TAF
RTV/DRV/FTC/TDF
FTC/TDF
DRV/r
PI
DRV/r + FTC/TDF
RTV/RAL*
-
RAL/r
INSTI
RAL/r
TAF/COBI/DRV/FTC
FTC/TAF
DRV/co
PI
DRV/co + FTC/TAF
TAF/DTG/FTC
FTC/TAF
DTG
INSTI
DTG + FTC/TAF
*Protocol Violation


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Duration of Baseline ARV Medication
Duration of the baseline ARV medication (defined above) prior/ to the first dose date is defined 
as (End Date Start Date+1). Duration will be expressed in years so that duration in days will be 
divided by 365.25 days.
End date is defined as the first dose date -1 or randomization date if randomized but not dosed.
Start Date: The start date of the baseline ARV medication is the latest start date of all the 
individual baseline ARV medications selected above
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 the 
minimum of (the start date of the ARV, first dose date-1, the stop date of the same ARV)

If only year is available, month and day will be first imputed as July 1st of the year, then 
imputed as the minimum of (the start date of the ARV, first 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 only month and year are available, day will be first imputed as 15th, then imputed as 
minimum of (the first dose date-1, the stop date of the ARV)

If only year is available, month and day will be first imputed July 1st of the year, then 
imputed as minimum of (first dose date-1, the stop date of the ARV) 

No imputation applied for date missing completely
10) Efficacy analyses:
The 95% CI for percentage estimate of HIV-1 RNA < 50 copies/mL or >
50 copies/mL for 
each treatment is calculated based on the Clopper-Pearson exact method.
proc freq;
by trt;
tables event/ binomial;
exact binomial;
run;
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:
HIV-1 RNA >  50 copies/mL - Discontinued Study Drug Due to AE or Death and 
Last Available HIV-1 RNA >  50 copies/mL
HIV-1 RNA >  50 copies/mL - Discontinued Study Drug Due to Other reason* and 
Last Available HIV-1 RNA >  50 copies/mL


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No virologic Data Discontinued Study Drug Due to AE or Death and Last Available HIV-1 
RNA < 50 copies/mL
No virologic Data Discontinued Study Drug Due to Other reason* and Last Available 
HIV-1 RNA < 50 copies/mL
Note:*
Other reasons include participants 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.
11) TEAE
Events with Missing Onset Day and/or Month
An event is considered treatment emergent if the following 3 criteria are met:
i.
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
ii. 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
iii. End date is as follows: 
The (complete) end date is on or after the first dose date, or
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
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.
12) Toxicity Grades:
For toxicity grade summaries, include post-baseline graded results as defined in 
Section 7.2.2.1, not just those used in by-visit summaries.


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13) Graded Laboratory Abnormalities Summary
The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label 
Used in l-labtox Listing
Toxicity Direction
Lab Test Label
Used in t-labtox Table
Hematology
Hemoglobin
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Chemistry
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Fasting)
Decrease
Serum Glucose (Fasting, Hypoglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Decrease
Serum Glucose (Nonfasting, Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Total Cholesterol (Fasting)
Increase
Total Cholesterol (Fasting, Hypercholesterolemia)
Triglycerides (Fasting)
Increase
Triglycerides (Fasting, Increased)
LDL (Fasting)
Increase
LDL (Fasting, Increased)
Urea Nitrogen (BUN)
Increase
Urea Nitrogen (Increased)
Urinalysis
Urine Blood (Dipstick)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
Note: Prothrombin Intl. Normalized Ratio (INR) and Prothrombin Time (PT) were graded based on the protocol defined toxicity 
grade scale. The results and toxicity grade will be listed in listing, but not be summarized in lab toxicity summary table.


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Due to the reflexive nature of the quantitative urine RBC test, results will be combined with the 
dipstick test of urine blood as described below. General rule is that urine RBC (Quantitative) 
should always be used first (if available), no matter if it is collected at the same time of Urine 
Blood (Dipstick) or not. The combined Urine RBC (hematuria, Quantitative or Dipstick) toxicity 
grade will be used for “Maximum treatment-emergent toxicity grade” summary.
Is Post-BL Urine 
RBC (Quant.) 
Result Available?
Is BL Urine RBC 
(Quant.) Result 
Available?
Is Post-BL 
Urine Blood 
(Dipstick) 
Result 
Available?
Is BL Urine 
Blood (Dipstick) 
Result 
Available?
How to Determine 
Treatment-Emergent Toxicity for “
Urine RBC (Hematuria, 
Quantitative or Dipstick)”
Yes
Yes
Compare post BL Urine RBC (Quant.) 
toxicity grade to BL Urine RBC 
(Quant.) toxicity grade. If post BL 
toxicity is greater than BL toxicity, 
then treatment emergent
Yes
No
Treatment emergent. Use post BL 
Urine RBC (Quant.) toxicity grade.
No
Yes
Yes
Compare post BL Urine Blood 
(Dipstick) toxicity grade to BL Urine 
Blood (Dipstick) toxicity grade. If 
post BL toxicity is greater than BL 
toxicity, then treatment emergent
No
Yes
No
Treatment emergent. Use post BL 
Urine Blood (Dipstick) toxicity grade.
No
No
Do not count participant in the 
denominator for “Urine RBC 
(Hematuria, Quantitative or Dipstick)”
BL  Baseline. Quant  Quantitative. “ ” means any value can be present (or it can be missing), as it does not affect the 
classification
14) 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)
15) 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.

Participants who took lipid modifying medications at baseline refer to the participants who 
have any use of the lipid modifying agents at Study Day 1.
a) More specifically, participants with “Lipid Modifying Agent Use at Baseline” include 
those participants in the B/F/TAF safety analysis set meeting both of the following 
criteria: 1) any selected CM record with the start date ≤ the first dose date, 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 


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b) For lipid modifying medications with the start date completely unknown, assume the start 
date is on or before the first dose date; lipid modifying medication is considered as being 
taken at baseline 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 and the end 
date unknown (completely missing) are considered as being taken at baseline
(the unknown end date is assumed to be on or after the first dose date).

Participants who initiated lipid modifying medications during the study are defined as the 
participants in the B/F/TAF safety analysis set who did not take lipid modifying medications 
at baseline and met the following criteria: any selected CM record with start date after the 
first B/F/TAF dose date and on and prior to the last B/F/TAF dose date.
16) 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 that visit in the figure, but all data will be included in 
the corresponding table summary.
17) Vital signs and weight, height, BMI will be in the same listing.
18) 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) results  “Repeat reactive, confirmed”, “Repeat Reactive Unconfirmed”.


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


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
For incident coinfection, all laboratory tests must share the same accession number and if any 
set of values meets the criteria, then the participant is considered to have incident coinfection
The incident coinfection status will be one of two values: Yes/Null
The following tables provide combinations of HBV and HCV tests that are considered 
“Y” for incident coinfection status (all others are considered Null)
HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
Y
Negative
Negative
Positive
Quantifiable
Y
Missing
Negative
Positive
Quantifiable
Y
HCVAb
HCV RNA
Coinfection Status
Positive*
Y
Quantifiable
Y
*
Participants 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
19) HBV DNA test codes: If the result of the lab test code GET1883 (HBV DNA CAP/CTM
2.0-EDTA-CL) is listed as “>170000000”, then a reflexive test code GET1884 (HBV DNA 
CAP/CTM 2.0Dil-EDTA-CL) should be performed and will share the same accession 
number as the original GET1883 test. In this instance, use the result from GET1884 instead 
of GET1883 when determining HBV DNA.
20) In this study, only 3rd generation LDL is collected.
21) For nonstudy drug ARV listing, ARVs which were dosed between the first dose date and the
last dose date (inclusive) will be flagged (eg, ^). However, please note, if CM end date is 
completely missing and the medication is not marked “Ongoing” and the CRF indicates
‘Prior ARV’, the ARV will not be flagged.
22) Last Dose Date and Last Study Date
a) Last Dose Date for participants who permanently discontinued study drug was defined in 
Section 3.8.1.
If last dose date 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 study drug start dates and end 
dates, the clinic visit dates, and the laboratory visit dates, excluding the date of 30-day 
follow-up visit, will be used to impute the last dose date.
If the last dose date is a partial 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 the dispensing date’s month is after the last dose date’s month, a data 
query is needed.


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If the participant died and the death date is complete (ie, not partial date) and before the 
imputed last dose date, the complete death date should be used as the imputed last dose 
date. 
Last 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 
participants 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 the participant 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. 
23) The precision in reporting numerical values should be as follows:
Raw measurements will be reported the same as the data captured electronically or on the
CRF.
Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement.
Mean, median, minimum, Q1, Q3, maximum, 95% CIs will be reported to the same number 
of decimal places of the raw measurements. 
Exceptions may be considered; for example, if more than 4 significant digits are provided for 
the measurement. 
24) Duration of HIV Diagnosis (years) is defined as the year from the First Dose Date/Study 
Day 1 Date minus the year of HIV diagnosis from Disease Under Study (HIV) CRF page.
25) Duration of HIV Treatment (Years) is defined as the year from the First Dose Date/Study 
Day1 Date minus the year first started HIV treatment from Disease Under Study (HIV) CRF 
page.


SAP-Final-GS-US-380-4580
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Project Team
Leader eSigned
17-Nov-2020
00:48:44
Biostatistics eSigned
17-Nov-2020
21:06:18
PPD
PPD-

SAP_003.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching 
From a Regimen of Two Nucleos(t)ide Transcriptase Inhibitors 
(NRTI) plus a Third Agent to a Fixed Dose Combination (FDC) of 
Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in 
Virologically-Suppressed, HIV-1 Infected African American 
Participants
Name of Test Drug:
Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF; GS-9883/F/TAF)
Study Number:
GS-US-380-4580
Protocol Version (Date):
Original (27 June 2018)
Analysis Type:
Week 48
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
03 March 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF IN-TEXT FIGURES ......................................................................................................................................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
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................12
2.1.
Interim Analyses ....................................................................................................................................12
2.1.1.
Week 24 Analysis.................................................................................................................12
2.1.2.
Week 48 Analysis.................................................................................................................12
2.2.
Final Analysis ........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................13
3.1.
Analysis Sets..........................................................................................................................................13
3.1.1.
All Randomized Analysis Set...............................................................................................13
3.1.2.
Full Analysis Set ..................................................................................................................14
3.1.3.
Per Protocol Analysis Set.....................................................................................................14
3.1.4.
Safety Analysis Set...............................................................................................................15
3.2.
Subject Grouping ...................................................................................................................................15
3.3.
Strata and Covariates..............................................................................................................................16
3.4.
Examination of Subject Subgroups........................................................................................................16
3.4.1.
Subject Subgroups for Efficacy Analyses ............................................................................16
3.4.2.
Subject Subgroups for Safety Analyses ...............................................................................16
3.5.
Multiple Comparisons............................................................................................................................17
3.6.
Missing Data and Outliers......................................................................................................................18
3.6.1.
Missing Data ........................................................................................................................18
3.6.2.
Outliers.................................................................................................................................18
3.7.
Data Handling Conventions and Transformations .................................................................................18
3.8.
Analysis Windows .................................................................................................................................19
3.8.1.
Definition of Study Day .......................................................................................................19
3.8.2.
Analysis Windows................................................................................................................21
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window................................................................................................................................22
4.
SUBJECT DISPOSITION ..................................................................................................................................24
4.1.
Subject Enrollment and Disposition.......................................................................................................24
4.1.1.
Subject Enrollment...............................................................................................................24
4.1.2.
Subject Disposition ..............................................................................................................24
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................25
4.2.1.
Duration of Exposure to Study Drug....................................................................................25
4.2.2.
Adherence to Study Drug Regimen......................................................................................25
4.3.
Protocol Deviations................................................................................................................................27
5.
BASELINE CHARACTERISTICS....................................................................................................................28
5.1.
Demographics and Baseline Characteristics ..........................................................................................28
5.2.
Baseline Disease Characteristics............................................................................................................28


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5.3. 
Medical History ...................................................................................................................................... 29 
6. 
EFFICACY ANALYSES ................................................................................................................................... 30 
6.1. 
Primary Efficacy Endpoint ..................................................................................................................... 30 
6.1.1. 
Definition of the Primary Efficacy Endpoint ....................................................................... 30 
6.1.2. 
US FDA-Defined Snapshot Algorithm ................................................................................ 30 
6.1.3. 
Statistical Hypothesis for the Primary Efficacy Endpoint .................................................... 31 
6.1 .4. 
Primary Analysis of the Primary Efficacy Endpoint ............................................................ 31 
6.1.5. 
Secondary Analysis of the Primmy Efficacy Endpoint ........................................................ 32 
6.2. 
Secondary Efficacy Endpoints ............................................................................................................... 32 
6.2.1. 
Definition of the Secondary Efficacy Endpoints .................................................................. 32 
6.2.2. 
Anal sis ofthe Seconda 
Efficac End oints .................................................................... 32 
6.4. 
7. 
SAFETY ANALYSES ........................................................................................................................................ 37 
7.1. 
Adverse Events and Deaths .................................................................................................................... 37 
7.1.1. 
Adverse Event Dictionary .................................................................................................... 37 
7.1.2. 
Adverse Event Severity ........................................................................................................ 37 
7.1.3. 
Relationship of Adverse Events to Study Drug .................................................................... 38 
7 .1 .4. 
Serious Adverse Events ........................................................................................................ 38 
7.1.5. 
Treatment-Emergent Adverse Events ................................................................................... 38 
7 .1.6. 
Summaries of Adverse Events and Death ............................................................................ 39 
7.1.7. 
Additional Analysis of Adverse Events ............................................................................... 40 
7 .2. 
Laboratory Evaluations .......................................................................................................................... 4 1 
7.2.1. 
Summaries of Numeric Laboratory Results ......................................................................... 42 
7.2.2. 
Graded Laboratory Values ................................................................................................... 42 
7.2.3. 
Metabolic Laboratory Evaluations ....................................................................................... 44 
7.2.4. 
Liver-Related Laboratory Evaluations ................................................................................. 45 
7.2.5. 
Renal-Related Laboratory Evaluations ................................................................................. 46 
7.3. 
Body Weight, Height, and Yitai Signs ................................................................................................... 46 
7.4. 
Prior and Concomitant Medications ....................................................................................................... 47 
7.4.1. 
Nonstudy Dmg Antiretroviral Medications .......................................................................... 47 
7.4.2. 
Concomitant Non-ARV Medications ................................................................................... 47 
7.5. 
Electrocardiogram Results ..................................................................................................................... 48 
7.6. 
Other Safety Measures ........................................................................................................................... 48 
7.7. 
Subject Subgroup for Safety Endpoints ................................................................................................. 48 
7.8. 
Changes From Protocol-Specified Safety Analyses ............................................................................... 48 
8. 
SPECIAL POPULATION ANALYSES ............................................................................................................. 49 
8.1. 
Analyses for HIV/HBV Coinfected Subjects ......................................................................................... 49 
8.2. 
Analyses for HIV/HCV Coinfected Subjects ......................................................................................... 51 
9. 
PATIENT REPORTED OUTCOMES ................................................................................................................ 53 
9.1. 
HIV Symptoms Distress Module ........................................................................................................... 53 
9 .2. 
Medication Adherence Questionnaire .................................................................................................... 54 
9 .3. 
HIV Treatment Satisfaction Questionnaires ........................................................................................... 54 
9.4. 
Change from Protocol Specified Analysis for Patient-Reported Outcomes ........................................... 56 
10. REFERENCES ................................................................................................................................................... 57 
11. SOFTWARE ....................................................................................................................................................... 58 
CONFIDENTIAL 
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12.
SAP REVISION..................................................................................................................................................59
13.
APPENDICES ....................................................................................................................................................60
Appendix 1.
Study Procedures Table..........................................................................................................61
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial).................................64
Appendix 3.
Cardiovascular or Cerebrovascular Events.............................................................................65
Appendix 4.
Hepatic Events........................................................................................................................66
Appendix 5.
Programming Specifications...................................................................................................67
LIST OF IN-TEXT TABLES
Table 3-1.
Subjects Excluded from Week 24 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA Assessment in Week 24 
Analysis Window ...................................................................................................................14
Table 3-2.
Analysis Windows for HIV-1 RNA, Hematology, Chemistry, Urinalysis, Urine 
Pregnancy Laboratory Tests, eGFRCG, Vital Signs, Weight, and VAS..................................21
Table 3-3.
Analysis Windows for HIV Symptoms Distress Module, HIVTSQs (at Day 1 only), 
and HIVTSQc (Week 4 and Week 24 only)...........................................................................22
Table 3-4.
Analysis Windows for CD4+ cell count, 
 Metabolic Assessments, and 
Plasma HBV DNA .................................................................................................................22
Table 9-1.
List of Items on the HIVTSQ .................................................................................................55
LIST OF IN-TEXT FIGURES
Figure 1-1.
Study Schema..........................................................................................................................8
CCI-


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LIST OF ABBREVIATIONS
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARV
antiretroviral
AST
aspartate aminotransferase
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
CG
Cockcroft-Gault
CI
confidence interval
CMH
Cochran-Mantel-Haenszel 
CRF
case report form
CSR
clinical study report 
DNA
deoxyribonucleic acid
DTG
dolutegravir
ECG
electrocardiogram
EFV
efavirenz
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
full analysis set
FDA
Food and Drug Administration
FDC
fixed dose combination
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
ID
identification
IWRS
interactive web response system
LDL
low density lipoprotein
LLT
lowest level term
MedDRA
Medical Dictionary for Regulatory Activities
MH
Mantel-Haenszel 
NRTI
Nucleos(t)ide Transcriptase Inhibitors
PP
per protocol
PT
preferred term
PVE
pharmacovigilance and epidemiology (formerly Drug Safety and Public Health)
Q
quartile
Q1
first quartile
Q3
third quartile
RNA
ribonucleic acid
RPV
rilpivirine
RTV
ritonavir
SAE
serious adverse event
SAP
statistical analysis plan
SBR
stay on baseline regimen
SD
standard deviation
SMQ
Standardised MedDRA Query
SOC
system organ class
TAF
tenofovir alafenamide 
TDF
tenofovir disoproxil fumarate
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 the Week 48 analysis for 
Study GS-US-380-4580, which will be performed when all subjects have completed their 
Week 48 visit or prematurely discontinued from the study. This SAP is based on the study 
protocol dated 27 June 2018 and the electronic case report form (eCRF). The SAP will be 
finalized before database finalization for the Week 48 analysis. 
The Week 24 analysis was performed based on the Week 24 SAP dated 30 August 2019 and the 
database finalization date of 06 September 2019. In the Week 24 analysis, the baseline resistance 
data used in the definition of the Per Protocol population and the subgroup analyses were based 
on pre-existing mutations identified through 05 September 2019. The Week 48 analysis will 
include all Week 24 endpoints in order to incorporate the final resistance mutation data and in 
order to present the data from the first 24 weeks for the delayed switch group and the data from 
the first 24 weeks of the study in the same displays.
1.1.
Study Objectives
The primary objective of this study is:

To evaluate the efficacy of switching from a regimen of 2 NRTIs and a third agent to a fixed 
dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 
versus continuing their baseline regimen in HIV-1 infected, virologically suppressed 
African American participants as determined by the proportion of participants with HIV-1 
RNA ≥50 copies/mL at Week 24.
The secondary objectives of this study are:

To evaluate the efficacy of switching to a FDC of B/F/TAF from a regimen of 2 NRTIs and a 
third agent as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL 
at Week 48

To evaluate the efficacy, safety, and tolerability of switching to a FDC of B/F/TAF from a 
regimen of 2 NRTIs and a third agent in HIV-1 infected, virologically suppressed African 
American participants through Week 48
1.2.
Study Design
The study schema is provided in Figure 1-1..


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Figure 1-1.
Study Schema
a
Following the Day 1 visit, participants will be required to return for study visits at Weeks 4 and 12, and then every 12 weeks 
through the Week 48 visit. The Primary Endpoint will be assessed when the last enrolled participant completes the Week 24 
visit.
b
At Week 24, participants randomized to continue on their baseline regimen who complete 24 weeks of treatment on their 
baseline regimen will switch to B/F/TAF FDC.
c
At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an 
additional 24 weeks or until they have access to B/F/TAF, whichever occurs first, and attend study visits every 12 weeks 
followed by a 30-Day Follow-up Visit.
Design Configuration and Subject Population
GS-US-380-4580 is a randomized, open-label, multicenter, active-controlled study of HIV-1
infected, virologically suppressed African American participants.
Treatment Groups
Participants who provide written consent and meet all eligibility criteria will be randomized in a 
2:1 ratio to one of the following 2 treatment groups:

Treatment Group 1: FDC of B/F/TAF (50 mg/ 200 mg/ 25 mg) administered orally, once 
daily, without regard to food (n=320 planned)

Treatment Group 2: Stay on baseline regimen (SBR) consisting of 2 NRTIs and a third 
agent (each taken as prescribed) from Day 1 until Week 24, with a delayed switch to a FDC 
of B/F/TAF (50 mg/ 200 mg/ 25 mg) administered orally, once daily, without regard to food
(n=160 planned)
Key Eligibility Criteria
Medically stable HIV-infected participants who meet the following criteria:

Self-describes as Black, African American, or mixed race, including Black

Currently receiving an ARV regimen other than FDC of B/F/TAF that consists of any 
two NRTIs + allowed third agent for ≥ 6 months (see Protocol Section 4.2 for allowed 
agents)
Screening 
30 da~-s prior 
to Dar 1 
Day 1' 
Treatment Group 1: (N=3lO) 
B/FffJ;F FDC QD 
Treatment Group 2: (N=l60) 
2 NRT!s + 3rd agent QD 
Week 24b 
Week 48' 
Week 72 
PrimaryI.adpoi.al 
Secoadary EadpoiDt 


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
Have no documented or suspected resistance to integrase stand transfer inhibitors (INSTIs) 
and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 
RNA ≥ 50 copies/mL after achieving < 50 copies/mL while on an INSTI-containing 
regimen)

History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT 
substitutions are allowed, with the following exceptions: History of 3 or more TAMs 
(M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or 
K65R/E/N in RT will be excluded.

Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen 
for a minimum period of 6 months, and at least the last two HIV-1 RNA measurements prior 
to the Screening visit

HIV-1 RNA levels < 50 copies/mL at Screening Visit

Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance

Eligible participants with chronic hepatitis C virus (HCV) infection are permitted to enroll. In 
addition, eligible participants with chronic hepatitis B virus (HBV) infection are permitted to 
enroll if their baseline regimen contains either TAF or TDF.
Study Phases
Participants will be treated for at least 48 weeks after randomization (Randomization Phase).
Following the Screening and Day 1 visits, participants will be required to return for study visits 
at Weeks 4, 12, 24, 36, and 48. Participants randomized to SBR will have, after their delayed 
switch at Week 24, an additional visit at Week 28.
Participants who complete the study through the Week 48 visit and wish to continue on 
B/F/TAF, will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks 
or until they have access to FDC of B/F/TAF, whichever occurs first, and will attend study visits
every 12 weeks followed by a 30-Day Follow-Up Visit. This is the Open-label Extension Phase.
Participants who complete the study through the Week 48 Visit and do not continue their 
participation in the study will be required to return to the clinic 30 days after their Week 48 Visit 
for a 30-Day Follow-Up Visit.
Schedule of Assessments
After screening procedures, eligible subjects will be randomized 2:1 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, 12, 24, 36 and 48. Participants randomized to SBR will 
have, after their delayed switch at Week 24, an additional visit at Week 28.


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Laboratory analyses (chemistry, hematology, and urinalysis), HIV-1 RNA, CD4+ cell count, 
assessment of adverse events (AEs) and concomitant medications, and complete or symptom 
directed physical examinations will be performed at Screening, Day 1 and subsequent study 
visits. Whole blood for HIV-1 DNA archive testing will be collected at Day 1 for all participants 
and at Week 24 for all participants in Treatment Group 2.
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
Participants will be randomized in a 2:1 allocation ratio to 1 of 2 Treatment Groups
[Treatment Group 1 (B/F/TAF): Treatment Group 2 (SBR)]. Randomization will be stratified by 
the baseline 3rd agent ARV class at entry (integrase strand transfer inhibitor (INSTI), non-
nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI) or CCR5 antagonist).
Site and/or Stratum Enrollment Limits
Approximately 84 study sites in the United States participated. In order to provide all sites the 
opportunity to enroll subjects, the initial enrollment limit for individual sites was initially set to 
6 subjects. Additional enrollment slots at an individual site were allocated on a case-by-case 
basis.
Study Duration
Study duration for each participant will be at least 48 weeks. 
1.3.
Sample Size and Power
A total of 480 HIV-1 infected subjects, randomized in a 2:1 ratio to 2 treatment groups, achieves 
approximately 89% power to detect a noninferiority margin difference between the group 
proportions of 6% for HIV-1 RNA ≥50 copies/mL at Week 24.
For sample size and power computation, it is assumed that the reference group proportion is 4%. 
The treatment group proportion is assumed to be 10% under the hypothesis of inferiority. The 
power is computed for the case when the actual treatment group difference is zero 
(treatment = reference). The test statistic used is the one-sided Score test (Farrington & 
Manning) with the significance level of 0.025. Sample size and power calculations were 
performed using the statistical software package PASS (Version 14).
In general, a failure rate of 1% to 3% is assumed for switch studies in virologically suppressed 
subjects, and the noninferiority margin for treatment difference is typically set at 4%. The failure
rate of 4% and noninferiority margin of 6% used for this study was based on the observation that 
African Americans have lower rates of virological suppression compared to other cohorts
{DeJesus 2019}. In the US, not all communities have had equitable access to advancements in 
HIV treatment. African Americans remain disproportionately affected by HIV but have less 
access to HIV treatment and generally worse health outcomes compared to other racial groups.


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The table below provides approximate power for SBR proportions ranging from 2% to 4% with 
noninferiority margin ranging from 4% to 6%. A total of 480 HIV-1 infected subjects, 
randomized in a 2:1 ratio to 2 treatment groups, achieves approximately 87% power to detect a 
noninferiority margin difference between the group proportions of 4%.
SBR Proportion
Noninferiority Margin
Approximate Power
Actual Alpha
4%
6%
91%
0.026
3%
5%
88%
0.026
2%
4%
87%
0.024
SBR N=160; B/F/TAF N=320; alpha targeted at 0.025. The test statistic used is the one-sided Score test (Farrington &Manning). 
Power and actual alpha were computed using binomial enumeration of all possible outcomes.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Week 24 Analysis
The Week 24, primary endpoint, analysis was conducted after all subjects either completed their 
Week 24 visit or prematurely discontinued from the study prior to Week 24. These analyses will 
be rerun for the Week 48 analysis using data through Week 48.
2.1.2.
Week 48 Analysis
The Week 48 analysis will be conducted after all subjects either complete their Week 48 visit or 
prematurely discontinue from the study.
This SAP describes the analysis plan for the Week 48 analysis. The Week 24 analysis is also 
included in this SAP because of updated resistance data and the inclusion of the first 24 weeks 
on Delayed Switch to B/F/TAF for the SBR group (Week 24 data for the SBR group that moved 
to B/F/TAF, that is, CRF Week 48 but 24 weeks on B/F/TAF), which was not included in the 
Week 24 SAP.
2.2.
Final Analysis
The final statistical analysis will be conducted after all subjects either complete the study or 
prematurely discontinue from the study.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, 
first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set unless 
otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). Data 
collected on log forms, such as AEs, will be presented in chronological order within a subject. 
The treatment group to which subjects were randomized will be used in the listings. 
For randomized subjects, age (in years) collected on the Day 1 visit will be used for analyses and
presentation in listings. For screen failures, age calculated on the date of the informed consent 
was signed will be used. Because only birth year is collected on the eCRF, “01 July” will be used 
for the unknown birth day and month for the purpose of age calculation.
In general, permanent discontinuation of study drug refers to premature discontinuation of study 
drug or completion of study drug. Study drug refers to B/F/TAF for subjects randomized to the 
B/F/TAF treatment group. For subjects randomized to the SBR group, study drug refers to the 
baseline ARV regimen through Week 24 and to B/F/TAF after Week 24. For the SBR group, if 
the subject did not switch to B/F/TAF, the date of permanent discontinuation of study drug prior 
to Week 24 is defined as the earliest stop date for all components of the baseline ARV 
medication.
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 
database finalization for the Week 48 analysis. The analysis set will be included as a subtitle of 
each table, figure, and listing. A summary of the number and percentage of subjects in each 
analysis set will be provided by treatment group and in total.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set will include all subjects who are randomized into the study.
This is the primary analysis set for by-subject listings.


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3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) will include all subjects who (1) are randomized into the study,
(2) have received at least 1 dose of study treatment (either B/F/TAF or baseline regimen on or 
after Day 1), and (3) do not have pre-existing INSTI resistance-associated mutations (based on 
historical data). Subjects will be grouped according to the treatment to which they were 
randomized. For the FAS, all efficacy data, including data collected after the last dose of study 
drug, will be included, unless specified otherwise. This is the primary analysis set for efficacy 
analyses.
3.1.3.
Per Protocol Analysis Set
The Week 24 Per Protocol (PP) Analysis Set will include all subjects who (1) are randomized 
into the study, (2) have received at least 1 dose of study treatment (either B/F/TAF or baseline 
regimen on or after Day 1), 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. The Week 24 PP analysis set is the secondary analysis set for efficacy 
analysis.  
Subjects meeting any of the following criteria will be excluded from the Week 24 PP analysis
set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 24 analysis window, except 
when missing due to discontinuation of study treatment for lack of efficacy. (Note: lack of 
efficacy is defined as having the check-box for Lack of Efficacy marked as the reason for 
premature study drug discontinuation in the “Randomized Treatment” study phase on the 
study drug completion eCRF page; Table 3-1). 
Table 3-1.
Subjects Excluded from Week 24 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA 
Assessment in Week 24 Analysis Window
Discontinuation from Study Treatment prior to or on 
the Upper Bound of Week 24 Analysis Window
HIV-1 RNA Data on Randomized Treatment 
Available in Week 24 Analysis Window
Yes
No
Yes
Due to Lack of Efficacy
+
+
Due to Other Reasons
+
-
No
+
-
+ = Inclusion of Subjects in Week 24 PP analysis set; - = Exclusion of Subjects from Week 24 PP analysis set.


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
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 
bictegravir

Subjects who do not meet the inclusion criteria for baseline ARV regimen of any two NRTIs 
+ allowed 3rd agent (Protocol Section 4.2)

Subjects who meet the exclusion criterion for history of 3 or more TAMs (M41L, D67N, 
K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT, including
pre-existing mutations that are detected post-baseline

Subjects who have INSTI resistance-associated mutations, including pre-existing mutations 
that are detected post-baseline
3.1.4.
Safety Analysis Set
The Safety Analysis Set will include all subjects who (1) are randomized into the study and 
(2) have received at least 1 dose of study treatment (either B/F/TAF or baseline regimen on or 
after Day 1). For subjects in Treatment Group 1 and in Treatment Group 2 while on B/F/TAF, all 
data collected up to 30 days after subjects permanently discontinue study drug will be included 
in safety summaries, unless specified otherwise. For subjects in Treatment Group 2 while on the 
baseline ARV medications, all data collected up to the minimum of (1) 30 days after subjects 
permanently discontinue the baseline ARV medications and (2) 1 day prior to the start of 
B/F/TAF will be included in safety summaries, unless specified otherwise.
Subjects will be grouped according to the treatment they actually received. This is the primary
analysis set for safety analyses.
3.2.
Subject Grouping
For analyses based on the All Randomized Analysis Set or the FAS, subjects will be grouped by 
randomized treatment. For other analyses, subjects will be grouped by actual treatment received. 
The actual treatment received will differ from the randomized treatment only when the actual 
treatment received differs from randomized treatment for the entire treatment duration.
Treatment groups include B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF.
For analysis by treatment group, subjects will be grouped using the following terminology:

Treatment Group 1: B/F/TAF

Treatment Group 2:
Up to Week 24: SBR
Post-Week 24: delayed switch to B/F/TAF

All B/F/TAF: all subjects who received at least one dose of study assigned B/F/TAF (both 
immediate and delayed switch to B/F/TAF).


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For the purposes of the Week 24 comparisons, there will be 2 treatment groups (B/F/TAF and 
SBR) used for statistical testing. For the tables, the 3 groups (B/F/TAF, SBR, and delayed switch
to B/F/TAF) or 4 groups (B/F/TAF, SBR, delayed switch to B/F/TAF and all B/F/TAF) will be 
presented. For the listings, observations that occur after a subject in the SBR group switches to 
B/F/TAF will be flagged.
3.3.
Strata and Covariates
Randomization was stratified by the baseline third agent ARV class at entry (integrase strand 
transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease 
inhibitor (PI) or CCR5 antagonist).
If there are discrepancies in stratification factor values between the IWRS and the clinical
database, the values recorded in the clinical database will be used to group subjects for analyses.
3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Efficacy Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 24 and Week 48 as 
determined by the US FDA-defined snapshot algorithm {U. S. Department of Health and Human 
Services 2015} will be analyzed for the following subject subgroups (also see Section 6.2.2.2 for 
details): 

Age (years): (a) < 50 and (b) ≥ 50 

Sex at birth: (a) male and (b) female 

Baseline NRTI Resistance (determined based on virology data): (a) Any NRTI Mutation 
(b) No NRTI Mutation

Baseline M184 Resistance (determined based on virology data): (a) M184 Mutation 
(b) No M184 Mutation
The proportion of subjects with hepatitis B virus (HBV) Deoxyribonucleic Acid (DNA) 
< 29 IU/mL at baseline, Week 24 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 at birth: (a) male and (b) female 


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2) Renal-related laboratory tests (ie, serum creatinine and eGFRCG) will be analyzed for the 
following subgroups: 

Baseline ARV Medication containing any of the following: rilpivirine (RPV), dolutegravir 
(DTG), ritonavir (RTV), cobicistat

Baseline ARV Medication not containing any of the following: RPV, DTG, RTV, cobicistat
3)
Fasting metabolic laboratory tests will be analyzed for the following subgroups: 

Baseline ARV Medication containing TAF

Baseline ARV Medication containing TDF

Baseline ARV Medication not containing any of the following: TAF, TDF

Baseline ARV Medication containing efavirenz (EFV)

Baseline ARV Medication not containing EFV
4) Selected safety endpoints may be analyzed for the following subject subgroups 
(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)
5) Selected safety endpoints will be analyzed for the following subject subgroups 
(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
Efficacy will be evaluated using the primary efficacy endpoint at the significance level of 0.05. 
The primary analysis will consist of a non-inferiority test of switching to FDC of B/F/TAF 
versus SBR, with respect to the proportion of participants with HIV-1 RNA ≥50 copies/mL at 
Week 24, as defined by the US FDA-defined snapshot algorithm. If non-inferiority of B/F/TAF
to SBR is established, the upper bound of the 95% confidence interval (CI) will be compared 
to 0; if the upper bound of the 95% CI is less than 0, superiority of B/F/TAF over SBR will be 
established
No prespecified multiplicity adjustments are planned for confidence intervals or statistical tests.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
A missing datum for a given study analysis window may be due to any of the following reasons:

A visit occurring in the window but data were not collected or were unusable 

A visit not occurring in the window

A subject prematurely discontinuing from the study before reaching the window
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.
For missing last dosing date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for adverse event onset is described in Section 7.1.5.2, 
and for concomitant non-ARV medications in Section 7.4.2.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety 
outcomes, unless specified otherwise. All data will be included in the analyses.
3.7.
Data Handling Conventions and Transformations
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed as follows except for urine creatinine:

A value that is 1 unit less than the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “< x” (where x is considered the 
limit of quantitation). For example, if the values are reported as < 50 and < 5.0, values of 
49 and 4.9, respectively, will be used for calculation of summary statistics. An exception to 
this rule is any value reported as < 1 or < 0.1, etc. For values reported as < 1 or < 0.1, a value 
of 0.9 or 0.09, respectively, will be used for calculation of summary statistics.

A value that is 1 unit above the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “> x” (where x is considered the 
limit of quantitation). Values with decimal points will follow the same logic as above.

The limit of quantitation will be used for calculation of descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the limit of quantitation).
Logarithmic (base 10) transformations will be applied to HIV-1 RNA and HBV 
Deoxyribonucleic Acid (DNA) data for efficacy analyses. HIV-1 RNA results of ‘No HIV-1 
RNA detected’ and “<20 cp/mL HIV-1 RNA Detected” will be imputed as 19 copies/mL for 
analysis purposes. HBV DNA results of “<20 IU/mL HBV DNA detected” or “No HBV DNA 
detected” will be imputed as 19 IU/mL for analysis purposes. HCV RNA results of “<15 IU/mL 
HCV RNA detected” or “No HCV RNA detected” will be imputed as 14 IU/mL for analysis 
purposes.


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3.8.
Analysis Windows
3.8.1.
Definition of Study Day
For the purposes of the SBR treatment group, there are 2 study periods: (1) up to the Week 24
visit, SBR and (2) Post-Week 24 visit, Delayed Switch to B/F/TAF.
Study Day 1/First Dose Date is defined as follows:

Subjects randomized to the B/F/TAF treatment group: Study Day 1/First Dose Date is 
defined as the day when the first dose of B/F/TAF was taken, as recorded on the Study Drug 
Administration eCRF form.

Subjects randomized to the SBR treatment group: Study Day 1/First Dose Date is defined as
the Day 1 visit date recorded on the Visit Date eCRF. 
Period 1 Study Day 1/First Dose Date is the same as the Study Day 1/First Dose Date.
Period 2 Study Day 1/First Dose Date is defined as follows:

Subjects randomized to the B/F/TAF treatment group: Not Applicable 

Subjects randomized to the SBR treatment group who do not switch to B/F/TAF at Week 24: 
Not Applicable.

Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24:  
Period 2 Study Day 1/First Dose Date is defined as the day when the first dose of B/F/TAF 
was taken, as recorded on the Study Drug Administration eCRF form. 
Study Days are calculated relative to Study Day 1 (B/F/TAF and SBR using Period 1 Study 
Day 1; delayed switch to B/F/TAF using Period 2 Study Day1). For events that occurred on or 
after the Study Day 1 date, study days are calculated as (visit date minus Study Day 1 plus 1). 
For events that occurred prior to Study Day 1, study days are calculated as (visit date minus 
Study Day 1).

Treatment Group 1: B/F/TAF, study day is calculated based on Study Day 1

Treatment Group 2:
Up to Week 24: SBR, study day is calculated based on Period 1 Study Day 1
Post-Week 24: delayed switch to B/F/TAF, study day is calculated based on Period 2 
Study Day 1

All B/F/TAF: all subjects who received at least one dose of study assigned B/F/TAF (both 
immediate and delayed switch to B/F/TAF). Study day is calculated based on the first dose of 
B/F/TAF; Study Day 1 for the B/F/TAF treatment group and Period 2 Study Day 1 for the 
SBR group who switched to B/F/TAF.


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Last Dose Date is defined as follows:

Subjects randomized to the B/F/TAF treatment group who are not treated in the Extension 
Phase : Last Dose Date is defined as the maximum, nonmissing end date of B/F/TAF
recorded on the Study Drug Administration eCRF form with phase of “Randomization 
Treatment” and “Study Drug Permanently Discontinued” box checked for subjects who 
prematurely discontinued or completed study drug in the “Randomized Treatment Phase” 
according to the Study Drug Completion eCRF.

Subjects randomized to the B/F/TAF treatment group who enter the Extension Phase
(continue treatment with B/F/TAF post-Week 48 visit): Last Dose Date is defined as the 
maximum, nonmissing end date of B/F/TAF recorded on the Study Drug Administration 
eCRF form with phase of “Extension Treatment” and “Study Drug Permanently 
Discontinued” box checked for subjects who prematurely discontinued or completed study 
drug in the “Extension Treatment Phase” according to the Study Drug Completion eCRF.  

Subjects randomized to the SBR treatment group who do not switch to B/F/TAF at Week 24: 
Last Dose Date is defined as the earliest stop date of the baseline ARV medications.

Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24 and 
who are not treated in the Extension phase: Last Dose Date is defined as the maximum, 
nonmissing end date of B/F/TAF recorded on the Study Drug Administration eCRF form
with phase of “Randomized Treatment” and “Study Drug Permanently Discontinued” box 
checked for subjects who prematurely discontinued study drug in the “Randomized 
Treatment Phase” according to the Study Drug Completion eCRF.

Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24 and 
who continue treatment in the Extension phase: Last Dose Date is defined as the maximum, 
nonmissing end date of B/F/TAF recorded on the Study Drug Administration eCRF form
with phase of “Extension Treatment” and “Study Drug Permanently Discontinued” box 
checked for subjects who prematurely discontinued study drug in the “Extension Treatment 
Phase” according to the Study Drug Completion eCRF.
Period 1 Last Dose Date is defined as follows:

Subjects randomized to the B/F/TAF treatment group: the same as Last Dose Date 

Subjects randomized to the SBR treatment group who do not switch to B/F/TAF at Week 24: 
Period 1 Last Dose Date is defined as the earliest stop date of the baseline ARV medications.

Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24: Period 
1 Last Dose Date is defined as the day prior to the first dose date of B/F/TAF, as recorded on 
the Study Drug Administration eCRF form.


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Period 2 Last Dose Date (where applicable) is the same as Last Dose Date.
For partial or missing last dose dates, please refer to the programming specifications for 
imputation rule details.
Last Study Date is the latest of the study drug start dates and end dates, the clinic visit dates, 
and the laboratory visit dates, including the 30-day follow-up visit date, for subjects who 
prematurely discontinued study according to the Study Completion eCRF.
Baseline value is defined as the last value obtained on or prior to Study Day 1 for all 
assessments for subjects randomized to the B/F/TAF treatment group and subjects randomized to 
the SBR treatment group who do not switch to B/F/TAF. For subjects who switch to B/F/TAF at 
Week 24, the baseline value is defined as the last value obtained on prior to the Period 2 Study
Day 1. 
3.8.2.
Analysis Windows
Subject visits might not occur on protocol specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
In the description that follows, the column labelled “B/F/TAF” refers to subjects in the 
immediate (B/F/TAF group) and delayed switch group (SBR group) who have switched to 
B/F/TAF. The baseline for delayed switch subjects will be reset based on the date of first dose of
B/F/TAF and the study day will be calculated relative to that date. Data collected after the date of 
switch to B/F/TAF will be excluded from the analysis of the SBR group.
The analysis windows for HIV-1 RNA, hematology, chemistry, urinalysis, urine pregnancy
laboratory tests, eGFRCG, vital signs, and weight are presented in Table 3-2.
Table 3-2.
Analysis Windows for HIV-1 RNA, Hematology, Chemistry, 
Urinalysis, Urine Pregnancy Laboratory Tests, eGFRCG, Vital Signs, 
Weight, and VAS
B/F/TAF
or 
Delayed Switch to B/F/TAF
SBR
Visit ID
Nominal Day
Lower Limit
Upper Limit
Lower Limit
Upper Limit
Baseline
1
1
Week 4
28
2
56
2
56
Week 12
84
57
126
57
126
Week 24^
168
127
210
127
210*
Week 36
252
211
294
Week 48
336
295
378
Week 60
420
379
462
Week 72
504
463
546
^ VAS is collected for SBR group only and only through Week 24
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The analysis windows for the HIV Symptoms Distress Module, HIVTSQs (at Day 1 only) and 
HIVTSQc (Week 4 and Week 24 only) are presented in Table 3-3.
Table 3-3.
Analysis Windows for HIV Symptoms Distress Module, HIVTSQs 
(at Day 1 only), and HIVTSQc (Week 4 and Week 24 only)
B/F/TAF or 
Delayed Switch to B/F/TAF
SBR
Visit ID
Nominal Day
Lower Limit
Upper Limit
Lower Limit
Upper Limit
Baseline
1
1
1
Week 4
28
2
98
2
98
Week 24
168
99
252
99
252*
Week 48
336
253
420
*For SBR group, values after the first day of B/F/TAF will be excluded.
The analysis windows for CD4+ cell count, 
 metabolic assessments (including fasting 
glucose and lipid panel: total cholesterol, high density lipoprotein [HDL], direct low density 
lipoprotein [LDL], triglycerides, and total cholesterol to HDL ratio), and plasma HBV DNA are 
presented in Table 3-4.
Table 3-4.
Analysis Windows for CD4+ cell count, 
 Metabolic 
Assessments, and Plasma HBV DNA
B/F/TAF or 
Delayed Switch to B/F/TAF
SBR
Visit ID
Nominal Day
Lower Limit
Upper Limit
Lower Limit
Upper Limit
Baseline
1
1
1
Week 24
168
2
252
2
252*
Week 48
336
253
420
*For SBR group, values after the first day of B/F/TAF will be excluded.
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. 
CCI
CCI
CCI
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-


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If multiple nonmissing numeric observations exist in a window, then records will be chosen as 
follows:

For baseline, the latest available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, average will be used for the baseline value, except for HIV-1 RNA (see below).

For postbaseline visits:
For CD4+ cell count, 
, 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, 
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 record on or prior to the first dose date of study drug will be
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected.

For postbaseline visits, the most conservative value within the window will be selected.
CCI
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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 investigator site will be summarized 
by treatment group (B/F/TAF and SBR) and overall using the safety analysis set. The 
denominator for this calculation will be the number of subjects in the safety analysis set. 
Similarly, the number and percentage of subjects enrolled in each randomization stratum will be 
summarized based on reclassified strata using the baseline 3rd agent ARV class based on the 
Non-Study ARV Medication eCRF.
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 (B/F/TAF and SBR) 
and overall for all screened subjects. This summary will include the number of subjects screened, 
screen failure subjects who were not randomized, subjects who met all eligibility criteria and 
were not randomized, subjects randomized, subjects randomized but never treated, subjects in 
the safety analysis set, and subjects in the FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:

Completed 24 weeks on randomized drug (see programming specifications)

Prematurely discontinuing study drug prior to 24 weeks on randomized drug (with summary 
of reasons for discontinuing study drug) (see programming specifications)

Delayed Switch to B/F/TAF (only for Treatment Group 2 [SBR] subjects)

Still on study drug up to the data cut date

Completed study drug

Prematurely discontinuing study drug prior to the data cut date (with summary of reasons for 
discontinuing study drug)

Still on study up to the data cut date

Treated in the Extension phase


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
Completed study

Prematurely discontinuing from study prior to Week 24 (with summary of reasons for 
discontinuing study) (see programming specifications)

Prematurely discontinuing from study prior to the data cut date (with summary of reasons for 
discontinuing study).
The denominator for the percentages of subjects in each category will be the number of subjects 
in the safety analysis set.
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
4.2.
Extent of Study Drug Exposure and Adherence
4.2.1.
Duration of Exposure to Study Drug
Duration of exposure will be calculated for the following groups: B/F/TAF, SBR, and Delayed 
Switch to B/F/TAF). Duration of exposure to study drug will be defined as (the last dose 
date - the first dose date + 1), regardless of temporary interruptions in study drug administration, 
and will be expressed in weeks using up to 1 decimal place (eg, 4.5 weeks). For the calculation 
of the duration of exposure to study drug, the data cut date will be used to impute the last dose 
date for subjects who have not permanently discontinued study drug at the time of the data cut 
date. See Section 3.8.1 for description of first dose and last dose for SBR and Delayed Switch to 
B/F/TAF.
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).
Summaries will be provided for subjects in the safety analysis set. No inferential statistics will be 
provided. 
4.2.2.
Adherence to Study Drug Regimen
Study drug regimen adherence will be computed based on pill counts for B/F/TAF study drug 
only (ie, B/F/TAF and Delayed Switch to B/F/TAF). The numbers of pills of study drug 
dispensed and returned are captured on study drug accountability eCRF.


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Adherence (%) of study drug regimen will be calculated as follows:






]
2
[
]
1[
period
dispensing
each 
at 
prescribed
pills
of
No.
period
dispensing
each 
at 
 taken 
pills
of
No.
100
prescribed
pills
of
No.
Total
 taken
pills
of
No.
Total
100
(%)
Adherence
[1] Number of pills taken at a distinct dispensing period for a study drug is calculated as the minimum of (a) the daily number of 
pills prescribed for the study drug multiplied by the duration of treatment at the dispensing period, and (b) the number of pills 
taken for the study drug (number of pills dispensed minus the number of pills returned). Total number of pills taken is determined 
by summing the number of pills taken 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.
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.
Adherence up to the data cut date will be calculated using all data from the entire dosing period 
up to the date of permanent discontinuation of the study drug for subjects who prematurely 
discontinued study drug or completed study drug, or using all data available for subjects who are 
ongoing on study drug. 
Adherence up to the Week 24 visit will be calculated for the B/F/TAF treatment group using all 
data from the entire dosing period up to the date of permanent discontinuation of the study drug 
for subjects who prematurely discontinued study drug or completed study drug, or the Week 24
study drug dispensing date, whichever occurs earliest.
For the Delayed Switch to B/F/TAF treatment group, adherence up to Week 24 on B/F/TAF will 
be calculated using all data from the entire dosing period up to the date of permanent 
discontinuation of the study drug for subjects who prematurely discontinued study drug or 
completed study drug, or the Week 48 study drug dispensing date, whichever occurs earliest.


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Descriptive statistics for adherence up to the data cut date and adherence up to Week 24 visit for 
a study drug regimen (n, mean, SD, median, Q1, Q3, minimum, and maximum) along with the 
number and percentage of subjects belonging to adherence categories (eg, < 80%, ≥ 80% to 
< 90%, ≥ 90% to < 95%, ≥ 95%) will be provided for Treatment Group 1 for subjects who return 
at least 1 bottle and have calculable adherence during the study in the safety analysis set. No 
inferential statistics will be provided.
Additionally, adherence up to the Week 48 visit will be calculated for the B/F/TAF treatment 
group in a similar manner to adherence up to the Week 24 visit.
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.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason and the total number of important protocol deviations by deviation reason
(eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) will be 
summarized by treatment group (B/F/TAF, SBR) for the Full Analysis Set. A by-subject listing 
will be provided for those subjects with important protocol deviations. 


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, gender identity, sexual orientation, race, and 
ethnicity) and baseline characteristics (eg, body weight, height, and body mass index [BMI]) will 
be summarized by treatment group (B/F/TAF and SBR) and overall using descriptive statistics 
(n, mean, SD, median, Q1, Q3, minimum, and maximum) for continuous data and by the number 
and percentage of subjects for categorical data. The summaries of demographic data and baseline 
subject characteristics will be provided for the safety analysis set.
For categorical data, the Cochran-Mantel-Haenszel (CMH) test (ie, general association statistic 
for nominal data) will be used to compare the 2 treatment groups. For continuous data, the 
2-sided Wilcoxon rank sum test will be used to compare the 2 treatment groups.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics:

HIV-1 RNA 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


Mode of infection (HIV risk factors)

HIV disease status

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)

Duration of HIV Diagnosis (years) (calculated as years prior to year from First Dose/Day 1 
date; see programming specifications)

Duration of  HIV Treatment (Years) (calculated as years prior to year from First Dose/Day 1 
date; see programming specifications)
CCI


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
Duration of baseline ARV medication prior to randomization (based on the Non-Study ARV 
Medication eCRF, see programming specifications)

Baseline ARV Regimen (based on the Non-Study ARV Medication eCRF, see programming 
specifications)
Baseline ARV Medication Backbone (FTC+TAF, FTC+TDF, TDF+3TC, ABC+3TC, 
AZT+3TC)
Baseline 3rd agent (INSTI, NNRTI, PI, CCR5), and further broken down by ingredient
Baseline ARV Medication (Backbone+3rd agent)
For categorical data, the CMH test (general association statistic for nominal data, and row means 
scores differ statistic for ordinal data) will be used to compare the 2 treatment groups. For 
continuous data, the 2-sided Wilcoxon rank sum test will be used to compare the 2 treatment 
groups.  
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will not be coded.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
6.1.1.
Definition of the Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 24 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.
6.1.2.
US FDA-Defined Snapshot Algorithm
The analysis window at Week 24 is defined as from Study Day 127 to Study Day 210, inclusive.
All HIV-1 RNA data collected on-treatment will be used in the US FDA-defined snapshot 
algorithm. On-treatment is defined for B/F/TAF and the Delayed Switch to B/F/TAF treatment 
groups as all data collected up to 1 day after permanent discontinuation of study drug or all 
available data for subjects who were still on study drug. On-treatment is defined for the SBR 
treatment group as all data collected up to 1 day after permanent discontinuation of baseline 
ARV medication or all available data on or before the date of the first B/F/TAF dose for subjects 
who switched to B/F/TAF. 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 24 analysis window

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 24 analysis 
window, or
Who do not have on-treatment HIV-1 RNA data in the Week 24 analysis window and 
i)
Who discontinue study drug prior to or in the Week 24 analysis window due to lack 
of efficacy, or
ii) Who discontinue study drug prior to or in the Week 24 analysis window due to AE or 
death and have the last available on-treatment HIV-1 RNA ≥50 copies/mL, or 
iii) Who discontinue study drug prior to or in the Week 24 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.


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
No Virologic Data in the Week 24 Window: this includes subjects who do not have 
on-treatment HIV-1 RNA data in the Week 24 analysis window because of the following: 
a) Discontinuation of study drug prior to or in the Week 24 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 24 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA
< 50 copies/mL or,
c) Missing data during the window but on study drug.
The flowchart of the US FDA-defined snapshot algorithm is provided in Appendix 2.
The Week 24 virologic outcomes for the US FDA-defined snapshot algorithm will be 
summarized for the B/F/TAF, SBR and Delayed Switch to B/F/TAF groups. 
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 are classified in the “No Virologic Data in the Week 24 Window” 
category.
6.1.3.
Statistical Hypothesis for the Primary Efficacy Endpoint
Null hypothesis: The B/F/TAF group (Treatment Group 1) is at least 6% higher than the SBR
group (Treatment Group 2) with respect to the proportion of subjects with HIV-1 RNA 
≥50 copies/mL as determined by the US FDA-defined snapshot algorithm) at Week 24.
Alternative hypothesis: The B/F/TAF group (Treatment Group 1) is less than 6% higher than
the SBR group (Treatment Group 2) with respect to the proportion of subjects with HIV-1 RNA 
≥50 copies/mL at Week 24.
6.1.4.
Primary Analysis of the Primary Efficacy Endpoint
The analysis purpose of the primary efficacy endpoint is to assess the noninferiority of switching 
to B/F/TAF relative to a regimen of 2 NRTIs and a third agent (SBR). Noninferiority will be 
assessed using a conventional 95% CI approach, with a noninferiority margin of 6%.
The point estimate of treatment difference (B/F/TAF group – SBR group) in the percentage of 
subjects with HIV-1 RNA ≥50 copies/mL and the associated 2-sided 95% CI will be constructed 
based on an unconditional exact method using 2 inverted 1-sided tests.
It will be concluded that B/F/TAF is noninferior to SBR if the upper bound of the 2-sided 95% CI 
of the difference between treatment groups (B/F/TAF group – SBR group) in the percentage of 
subjects with HIV-1 RNA ≥50 copies/mL is less than 6%. 


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If noninferiority of B/F/TAF versus SBR is established, the same 95% CI used in evaluating 
noninferiority at Week 24 will be used to evaluate superiority. If the upper bound of the 95% CI 
is less than 0, then superiority of B/F/TAF over SBR is established. The 2-sided Fisher’s exact 
test will also be used to assess superiority as a secondary assessment.
The 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 24 will be summarized. The 95% CIs 
for percentages of subjects with HIV-1 RNA < 50 copies/mL and HIV-1 RNA ≥ 50 copies/mL 
will be constructed using the exact method.
The FAS will be used for the primary efficacy endpoint analysis and the superiority evaluation.
6.1.5.
Secondary Analysis of the Primary Efficacy Endpoint
A secondary analysis based on the Week 24 PP analysis set will be performed to evaluate the 
robustness of the primary analysis of the primary endpoint. For this secondary analysis, 95% CI 
for the treatment difference in the primary efficacy endpoint will be calculated based on an 
unconditional exact method using 2 inverted 1-sided tests.
6.2.
Secondary Efficacy Endpoints
6.2.1.
Definition of the Secondary Efficacy Endpoints
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 as determined by 
the US FDA-defined snapshot algorithm

The proportion of subjects with HIV-1 RNA 50 copies/mL at Week 24 and Week 48 as 
determined by the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 24 and Week 48 
The analyses for the Week 24 secondary efficacy endpoints will be conducted using both the 
FAS and the Week 24 PP analysis set. The Week 48 analysis will be performed using the FAS 
only.
6.2.2.
Analysis of the Secondary Efficacy Endpoints
6.2.2.1.
Analysis of the Proportion of Subjects with HIV-1 RNA < 50 copies/mL at Week 
24 as Determined by US FDA-defined Snapshot Algorithm 
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 24 will also be analyzed 
by the US FDA-defined snapshot algorithm based on both the FAS and Week 24 PP analysis set.
Proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 24 as determined by US
FDA-defined snapshot algorithm will be analyzed similarly to the primary efficacy endpoint.


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However, the noninferiority margin used for the proportion of subjects with HIV-1 RNA 
< 50 copies/mL will be -10%.
Similar to the primary efficacy endpoint, noninferiority will be assessed using the conventional
CI approach. The point estimate of treatment difference (B/F/TAF group – SBR group) in the 
percentage of subjects with HIV-1 RNA < 50 copies/mL and the associated 2-sided 95% CI will 
be constructed based on an unconditional exact method using 2 inverted 1-sided tests.
It will be concluded that B/F/TAF is noninferior to SBR if the lower bound of the 2-sided 95% CI 
of the difference between treatment groups (B/F/TAF group – SBR group) in the percentage of 
subjects with HIV-1 RNA < 50 copies/mL is greater than −10%.
6.2.2.2.
Subgroup Analysis of the Proportion of Subjects with HIV-1 RNA 
< 50 copies/mL at Week 24 as Determined by US FDA-defined Snapshot 
Algorithm
Because the proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 24 as determined by 
the US FDA-defined snapshot algorithm (primary endpoint) is expected to be very low (around 
4%), 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 24 (a secondary efficacy endpoint) within each subgroup specified in Section 3.4.1 based 
on the FAS.
For each level of subgroup factors, the proportion difference between treatment groups and the 
associated 2-sided 95% CIs will be computed based on an unconditional exact method using 
2 inverted 1-sided tests. 
Additionally, a logistic regression model will be performed which will 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 24 and their associated 95% CIs for each subgroup will be 
generated.
6.2.2.3.
Analysis of Proportion of Subjects with HIV-1 RNA < 50 copies/mL and
≥50 copies/mL as Defined by the US FDA-Defined Snapshot Algorithm at
Week 48
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 as determined by US FDA-defined 
snapshot algorithm will be summarized for B/F/TAF subjects only, using the FAS. The 95% CIs 
for percentages of subjects with HIV-1 RNA < 50 copies/mL and HIV-1 RNA ≥ 50 copies/mL 
will be constructed using the exact method.


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Analysis of CD4+ Cell Count 
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All CD4+ cell com1t will be smmnarized for B/F/TAF, SBR and Delayed Switch to BIFITAF 
treatment groups using observed, on-treatment data. On-treatment data is defined for B/F IT AF 
and Delayed Switch to B/F IT AF as all data collected up to 1 day after pennanent discontinuation 
of study drug or all available data for subjects who were still on study drug. On-treatment data is 
defined for SBR as all data collected up to 1 day after pennanent discontinuation of baseline 
ARV medication or all available data on or before the date of the first B/F/TAF dose for subjects 
who switched to B/F/TAF. 
The changes from baseline in CD4+ cell count at Week 24 will be smmnarized by treatment 
group (BIFITAF, SBR, and Delayed Switch to B/F/TAF) using descriptive statistics. The 
differences in changes from baseline in CD4+ cell count between the B/F/T AF and SBR 
treatment groups and the associated 95% CI will be constructed using analysis of variance 
(ANO VA) models, including treatment group as a fixed effect in the model. 
The change from baseline in CD4+ cell com1ts will also be analyzed based on the Week 24 
PP analysis set. 
In addition, the change from baseline in CD4+ cell counts with missing values imputed using the 
last observation carried forward (LOCF) method will be summarized at Week 24 based on the 
FAS. The algorithm for LOCF is as follows: 
• 
If a value is missing in an analysis visit window, the missing value will be replaced with the 
last on-treatment value. 
• 
Baseline values will be carried forward to impute the postbaseline value at a specific visit, if 
there is no non-missing postbaseline observation collected prior to that visit. 
The changes from baseline in CD4+ cell count at Week 48 will be smmnarized for the B/F IT AF 
group using descriptive statistics with observed data (ie, missing will be excluded) for subjects in 
the FAS. 
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Changes from Protocol-Specified Efficacy Analyses 
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The protocol specified a fourth criterion for the FAS (at least 1 post baseline HIV-1 RNA result 
while on study treatment); however this criterion was removed to eliminate potential bias. 
The Week 24 PP analysis set definition was updated to exclude subjects who do not meet the 
inclusion criteria for baseline ARV regimen (Protocol Section 3.2) and to exclude subjects who 
have INSTI resistance-associated mutations, including pre-existing mutations that are detected 
post-baseline. The exclusion for adherence rate below the 2.5th percentile was removed because 
adherence cannot be calculated for the SBR group. 
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7.
SAFETY ANALYSES
Safety data will be summarized for the subjects in the safety analysis set. All safety data 
collected up to 30 days after permanent discontinuation of study drug and all available data for 
subjects who were still on study drug will be summarized by treatment group, unless specified 
otherwise. All safety data will be included in data listings.
7.1.
Adverse Events and Deaths
Summaries of AEs by treatment group (B/F/TAF, SBR, Delayed Switch to B/F/TAF, All 
B/F/TAF) will include data collected up to:

For subjects in the B/F/TAF, Delayed Switch to B/F/TAF, and All B/F/TAF treatment 
groups, AEs with onset date on or before 30 days after permanent discontinuation of study 
drug, or all AEs if the subject is receiving study drug

For subjects in the SBR treatment group, AEs with onset date on or before the minimum of 
(1) 30 days after permanent discontinuation of baseline ARV medication, or (2) the day prior 
to the first dose date of B/F/TAF
Summaries of AEs up to Week 24 by treatment group (B/F/TAF, SBR) will include data 
collected up to:

For subjects in the B/F/TAF treatment group, AEs with onset date on or before the minimum 
of (1) 30 days after permanent discontinuation of study drug or (2) the day of the Week 24 
visit

For subjects in the SBR treatment group, AEs with onset date on or before the minimum of 
(1) 30 days after permanent discontinuation of baseline ARV medication, or (2) the day prior 
to the first dose date of B/F/TAF
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. 


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7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Pharmacovigilance and 
Epidemiology (PVE) Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:
For subjects who received B/F/TAF:

Any AEs with an onset date on or after the B/F/TAF study drug start date and no later than 
30 days after permanent discontinuation of the B/F/TAF study drug, or 

Any AEs leading to premature discontinuation of B/F/TAF study drug.
For subjects in SBR treatment group:

Any AEs with an onset date on or after Study Day 1 and on or before the minimum of 
(1) 30 days after permanent discontinuation of baseline ARV medication or (2) the day prior 
to the first dose date of B/F/TAF study drug

Any AEs leading to premature discontinuation of baseline ARV medication.
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 
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An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date marked as ongoing or on or after the first dosing date of study drug, will be considered to be 
treatment emergent. In addition, an AE with the onset date missing and incomplete stop date 
with the same or later month and year (or year alone if month is not recorded) as the first dosing 
date of study drug will be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Death
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group (B/F/TAF, SBR, Delayed Switch to 
B/F/TAF, and All B/F/TAF). For other AEs described below, summaries will be provided by 
SOC, PT, and treatment group (B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF) 
using the safety analysis set:

Any Grade 2, 3, or 4 treatment-emergent AEs

Any Grade 3 or 4 treatment-emergent AEs

All treatment-emergent study drug-related AEs

Any Grade 2, 3, or 4 treatment-emergent study drug-related AEs

Any Grade 3 or 4 treatment-emergent study drug-related AEs

All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs

All treatment-emergent AEs that caused premature discontinuation from study drug
A brief, high-level summary of AEs described above will be provided by treatment group
(B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF) 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.


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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.
A second set of summaries will be provided that summarize only B/F/TAF and SBR through the 
Week 24 visit.
Data listings will be provided for the following:

All AEs

All AEs through Week 24

Study-Drug-Related AEs

Grade 3 and 4 AEs

SAEs

Study-Drug-Related SAEs

Deaths report

AEs leading to premature discontinuation of study drug
Listings will include all AEs, and AEs up to Week 24 will be flagged.
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Stage 3 Opportunistic Illnesses in HIV
On an ongoing basis, AEs will be reviewed for events that might meet the definition of stage 3 
opportunistic illnesses in HIV that are indicative of an AIDS-defining diagnoses (see Protocol
Appendix 6). The Gilead medical monitor will review the possible stage 3 opportunistic illnesses
and approve the events that meet the definition. Events that meet the stage 3 opportunistic illness
definition of an AIDS-Defining Diagnosis will be listed.
7.1.7.2.
Cardiovascular or Cerebrovascular Events
Preferred terms for cardiovascular or cerebrovascular events are from relevant Standardised 
MedDRA Query (SMQ). The selected PT listing was provided by Gilead PVE and reviewed by 
Gilead medical monitors (see details in Appendix 3).


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The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
summarized by treatment group (B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF) 
based on the safety analysis set. A second summary will be prepared that only includes B/F/TAF 
and SBR treatment groups (up to Week 24). The second summary will include a statistical 
comparison of the subject incidence rates (up to Week 24) between the B/F/TAF and SBR
treatment groups using Fisher’s exact test. A by-subject 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 PVE and reviewed by Gilead medical monitors (see details in Appendix 4).
The number and percentage of subjects with treatment-emergent hepatic events and serious 
hepatic events by PT will be summarized by treatment group (B/F/TAF, SBR, Delayed Switch to 
B/F/TAF, and All B/F/TAF) based on the safety analysis set. A second summary will be 
prepared that only includes B/F/TAF and SBR treatment groups (up to Week 24). The second 
summary will include a statistical comparison of the subject incidence rates (up to Week 24) 
between the B/F/TAF and SBR treatment groups using Fisher’s exact test. A by-subject data 
listing of hepatic events will be provided.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to:

For subjects in the B/F/TAF or Delayed Switch to B/F/TAF treatment groups who have 
permanently discontinued B/F/TAF study drug, the last dose of B/F/TAF study drug plus 
30 days.

For subjects in the B/F/TAF or Delayed Switch to B/F/TAF treatment groups who are still on 
study drug, data through the data cut date

For subjects in the SBR treatment group, the minimum of (1) 30 days after permanent 
discontinuation of baseline ARV medication, or (2) the first dose date of B/F/TAF
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 
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7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group (B/F/TAF, SBR, and Delayed Switch 
to B/F/TAF) 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)). 
Toxicity grading for calcium will be applied based on the corrected values.
Estimated GFR
The following formula will be used to calculate eGFRCG: 

eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / 
(SCr (mg/dL) × 72), where weight is total body mass in kilograms, and SCr is serum 
creatinine.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used for assigning toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction 
(ie, increased, decreased) will be presented separately.


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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 the cutoffs specified at the 
start of Section 7.2.
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. Most subjects 
had a nonfasting glucose at the Screening visit and a fasting glucose at the Day 1 visit; therefore, 
both a baseline nonfasting glucose and a baseline fasting glucose are available for most subjects, 
and treatment-emergent laboratory abnormalities will be summarized for both nonfasting glucose 
and fasting glucose.
Both urine 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.
7.2.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group (B/F/TAF, SBR, Delayed Switch 
to B/F/TAF, and All B/F/TAF); subjects will be categorized according to the most severe 
postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities 
A second set of summaries will be produced that only includes the B/F/TAF and SBR treatment 
groups through the upper bound of the Week 24 analysis window.
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
any nonmissing postbaseline values for the particular laboratory test.


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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. Results that are within the upper bound of the Week 24 analysis window 
will be flagged.
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 for the B/F/TAF, SBR, and Delayed Switch to B/F/TAF groups. 
P-values comparing the difference between the B/F/TAF and SBR groups in baseline values and 
the change from baseline in metabolic assessment will be estimated from a 2-sided Wilcoxon 
rank sum test.
In addition, the number and percentage of subjects who took lipid modifying medications at 
baseline and initiated the medications during the study (up to Week 24) will be provided for the 
B/F/TAF, SBR and Delayed Switch to B/F/TAF treatment groups (see Appendix 5). Statistical 
comparisons of the subject incidence rates between the B/F/TAF and SBR treatment groups will 
be performed using Fisher’s exact test. 
In addition, the number and percentage of subjects who initiated lipid modifying medications 
during the study (up to Week 48) will be provided for the B/F/TAF treatment group.
A lipid modifying medication is defined as a medication with drug class (based on World Health 
Organization [WHO] Drug ATC2 term) = “LIPID MODIFYING AGENTS” and WHO Drug
preferred drug name containing the wording of “STATIN”.
A sensitivity analysis of fasting lipid tests will be performed by excluding subjects who took 
lipid modifying medications at baseline or initiated the medications during the study (up to Week 
24): baseline values, Week 24 values, and changes from baseline at Week 24 will be summarized 
by treatment group (B/F/TAF, SBR, and Delayed Switch to B/F/TAF) using descriptive 
statistics. Baseline and change from baseline at Week 24 will be compared between the B/F/TAF 
and SBR treatment groups using a 2-sided Wilcoxon rank sum test. Only subjects with both 
baseline and Week 24 values will be included in the analysis. Additionally, baseline, Week 48, 
and change from baseline to Week 48 values will be summarized for subjects in the B/F/TAF 
treatment group, excluding those subjects who took lipid modifying medications at baseline or 
initiated the medications during the study (up to Week 48).
Summary of baseline, postbaseline, and change from baseline in fasting metabolic laboratory 
tests will be repeated within each subgroup of baseline ARV medication (see Section 3.4.2).
P-values comparing the difference between the B/F/TAF and SBR treatment groups in baseline 
values and the change from baseline in metabolic assessment will be generated from a 2-sided 
Wilcoxon rank sum test.
Median (Q1, Q3) of change from baseline in fasting metabolic assessments over time will be 
plotted by treatment group (B/F/TAF, SBR, and Delayed Switch to B/F/TAF). 


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7.2.4.
Liver-Related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized for 
the B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF groups using the number and 
percentage of subjects who were reported to have the following laboratory test values for post 
baseline measurements:

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
For individual laboratory tests, subjects will be counted once based on the most severe 
postbaseline value. For both the composite endpoint of AST or ALT and total bilirubin, and the 
composite endpoint of AST or ALT, total bilirubin, and ALP, subjects will be counted once 
when the criteria are met at the same postbaseline visit date. The denominator is the number of 
subjects in the safety analysis set with nonmissing postbaseline value of the tests in evaluation at 
the same postbaseline visit date.
A second summary will be produced that only summarizes B/F/TAF and SBR through the upper 
bound of the Week 24 analysis visit window.
Subjects with AST or ALT > 3 × ULN will also be listed.
In addition, baseline, postbaseline, and change from baseline in AST, ALT, ALP, and total 
bilirubin will be summarized by treatment group (B/F/TAF, SBR, and Delayed Switch to 
B/F/TAF) and visit using descriptive statistics. Baseline and change from baseline will be 
compared between the B/F/TAF and SBR treatment groups using a 2-sided Wilcoxon rank sum 
test.
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. The first occurrence of two or more consecutive 
ALT elevations will be identified as the ALT flare.


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7.2.5.
Renal-Related Laboratory Evaluations
7.2.5.1.
Serum Creatinine and eGFRCG
Baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG will be 
summarized by treatment group (B/F/TAF, SBR, and Delayed Switch to B/F/TAF) and visit 
using descriptive statistics. Baseline and change from baseline will be compared between the 
B/F/TAF and SBR treatment groups using a 2-sided Wilcoxon rank sum test. 
Median (Q1, Q3) of change from baseline in serum creatinine and eGFRCG over time will be 
plotted by treatment group.
Summary of baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG
will be repeated within each subgroup of baseline ARV medication (see Section 3.4.2). P-values 
comparing the difference between the B/F/TAF and SBR treatment groups in baseline values and 
the change from baseline in metabolic assessment will be generated from a 2-sided Wilcoxon 
rank sum test.
7.2.5.2.
Proteinuria by Urinalysis (Dipstick)
The proteinuria by urinalysis (dipstick) toxicity grade (Grade 0 to Grade 3) at Week 12 and 
Week 24 will be summarized by baseline proteinuria toxicity grade and treatment group 
(B/F/TAF, SBR and Delayed Switch to B/F/TAF), and at Week 36 and Week 48 for the 
B/F/TAF group. In addition, the last on-treatment proteinuria toxicity grade will be summarized 
by baseline proteinuria toxicity grade and treatment group. On-treatment data is defined for the 
B/F/TAF and Delayed Switch to B/F/TAF treatment groups as all data collected up to 1 day after 
permanent discontinuation of study drug or all available data for subjects who were still on study 
drug.  On-treatment data is defined for the SBR treatment group as all data collected up to 1 day 
after permanent discontinuation of baseline ARV medication or all available data on or before 
the date of the first B/F/TAF dose for subjects who switched to B/F/TAF.
The distribution of proteinuria toxicity grade at Weeks 12 and 24 and at the last on treatment 
value will be compared between B/F/TAF and SBR groups adjusting for baseline proteinuria 
toxicity grade using rank analysis of covariance {LaVange 2008}.
7.3.
Body Weight, Height, and Vital Signs
Descriptive statistics will be provided by treatment group (B/F/TAF, SBR, and Delayed Switch 
to B/F/TAF) for vital signs and body weight as follows:

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 antiretroviral (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. 
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 the date of first dose of study treatment up to the date of last dose of study 
treatment (as defined in Section 3.8.1) will be summarized (number and percentage of subjects) 
by treatment group (B/F/TAF, SBR, and Delayed Switch to B/F/TAF) and preferred drug name. 
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. 
A second summary will be produced that summarizes concomitant medications with onset up to 
Week 24 for the B/F/TAF and SBR treatment groups only. Use of concomitant medications from 
the date of first dose of study treatment up through the earliest of (1) date of last dose of study 
treatment (as defined in Section 3.8.1) and (2) date of Week 24 visit will be summarized.
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


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If the start and stop date of non-ARV medications are complete, the start date is not after last 
dose date and the stop date is not before first dose date, or the non-ARV medications are marked 
as ongoing and start date is on or before last dose date, the non-ARV medications are 
concomitant.
Summaries of non-ARV concomitant medications will be provided for the safety analysis set. 
Subjects with any non-ARV concomitant medications will be listed. No inferential statistics will 
be provided.
7.5.
Electrocardiogram Results
A by-subject listing for electrocardiogram (ECG) assessment results will be provided. 
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.
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
8.1.
Analyses for HIV/HBV Coinfected Subjects
Subjects with HIV/HBV coinfection at baseline are defined as subjects who meet any of the 
following two criteria: 

Positive HBsAg on or prior to the first dose date, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 20 IU/mL) on or prior to the first dose date.
The following analyses will be conducted by treatment (B/F/TAF and SBR) for subjects with 
HIV/HBV coinfection at baseline: 

The proportion of subjects with HBV DNA < 29 IU/mL at baseline and Week 24 by missing 
= excluded approach. 

The change from baseline in log10 HBV DNA (log10 IU/mL) at Week 24

Treatment-emergent adverse events overall summary through Week 24

Treatment-emergent adverse events by SOC, HLT, and PT through Week 24

Treatment-emergent laboratory abnormalities through Week 24
The following analyses will be conducted by treatment (B/F/TAF, SBR, and Delayed Switch to 
B/F/TAF) for subjects with HIV/HBV coinfection at baseline: 

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.
The following analyses will be conducted for subjects with HIV/HBV coinfection at baseline in 
the B/F/TAF group: 

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) at Week 48


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Listings will be provided for:

adverse events

liver-related laboratory tests and HBV DNA results

ALT elevation (ie, ALT > 2 x Baseline and ALT > 10 x ULN) and ALT flare (see section 
7.2.4)
HBV DNA will be analyzed using observed, on-treatment data for subjects in the FAS with 
HIV/HBV coinfection at baseline. On-treatment is defined for Treatment Group 1 (B/F/TAF) as 
all data collected up to 1 day after permanent discontinuation of study drug or all available data 
for subjects who were still on study drug.  On-treatment is defined for Treatment Group 2 (SBR) 
as all data collected up to 1 day after permanent discontinuation of baseline ARV medication or 
all available data on or before the date of the first B/F/TAF dose for subjects who switched to 
B/F/TAF.
Subjects with incident HIV/HBV coinfection while on study drug are defined as subjects who are 
not HIV/HBV coinfected at baseline and meet any of the following criteria:
For subjects in Treatment Group 1 (B/F/TAF) or subjects in Treatment Group 2 who switched to 
B/F/TAF:

Positive HBsAg after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
date, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA (ie, HBV 
DNA ≥ 20 IU/mL) after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
date, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first B/F/TAF dose date and on or prior to the 
last B/F/TAF dose date: Acute hepatitis B, Chronic hepatitis B, Congenital hepatitis B 
infection, Hepatitis B, Hepatitis B core antibody positive, Hepatitis B DNA assay positive, 
Hepatitis B surface antigen positive, Hepatitis B virus test positive.
For subjects in Treatment Group 2 (SBR):

Positive HBsAg after the first dose date and on or prior to the minimum of (1) the date of 
permanent discontinuation of baseline ARV medication, or  (2) the day prior to the first dose 
date of B/F/TAF, 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 minimum of (1) the date of 
permanent discontinuation of baseline ARV medication, or  (2) the day prior to the first dose 
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
Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first dose date and on or prior to the minimum of 
(1) the date of permanent discontinuation of baseline ARV medication, or  (2) the day prior 
to the first dose date of B/F/TAF: 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: 

Listing of adverse events

Listing of liver-related laboratory tests and HBV DNA results
Adverse events with onset date after Week 24 and test results collected after Week 24 will be 
flagged. 
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 listings will be provided for subjects with HIV/HCV coinfection at baseline: 

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results  
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:
For subjects in Treatment Group 1 (B/F/TAF) or subjects in Treatment Group 2 who switched to 
B/F/TAF:

Positive HCVAb after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
date, or

Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the first B/F/TAF dose date and 
on or prior to the last B/F/TAF dose date, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first B/F/TAF dose date and on or prior to the 
last B/F/TAF dose date: 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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For subjects in Treatment Group 2 (SBR):

Positive HCVAb after the first dose date and on or prior to the minimum of (1) the date of 
permanent discontinuation of baseline ARV medication, or (2) the day prior to the first dose 
date of B/F/TAF, 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 minimum of (1) the date of permanent discontinuation of baseline ARV medication, or 
(2) the day prior to the first dose date of B/F/TAF, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first dose date and on or prior to the minimum of 
(1) the date of permanent discontinuation of baseline ARV medication, or (2) the day prior to 
the first dose date of B/F/TAF: Acute hepatitis C, Chronic hepatitis C, Hepatitis C, 
Hepatitis C antibody positive, Hepatitis C RNA positive, Hepatitis C virus test positive.
The following listings will be provided for subjects with incident HIV/HCV coinfection while on 
study drug: 

Listing of adverse events

Listing of liver-related laboratory tests and HCV RNA results


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9.
PATIENT REPORTED OUTCOMES
The patient-reported outcomes (PROs) include the following assessments:

HIV Symptoms Distress Module [assessed at Day 1, Week 4, Week 24, Week 28 
(SBR treatment group only), and Week 48]

HIV Treatment Satisfaction Questionnaire Status (HIV-TSQs, assessed at Day 1)

HIV Treatment Satisfaction Questionnaire Change (HIV-TSQc, assessed at Week 4 and 
Week 24)

VAS Adherence Questionnaire (assessed at Day 1, Week 4, Week 12, and Week 24 for SBR 
group only)
Summaries will be provided for the Safety Analysis Set and will include data collected up to:

For subjects in the B/F/TAF treatment group who have permanently discontinued B/F/TAF 
study drug, the last dose of B/F/TAF study drug plus 30 days.

For subjects in the B/F/TAF group who are still on study drug, data through the data cut date

For subjects in the SBR treatment group, the minimum of (1) 30 days after permanent 
discontinuation of baseline ARV medication, or (2) the first dose date of B/F/TAF
Assessments will be listed using the Randomized Analysis set. 
9.1.
HIV Symptoms Distress Module
The Symptoms Distress Module is a self-completed questionnaire to evaluate symptoms and 
measure the presence and bothersomeness of side effects commonly seen with HIV and ARV
treatment over the last 4 weeks (20 questions about all symptoms which the patient might have 
had during the past four weeks). Higher scores indicate the presence of more symptoms and/or a 
greater degree of distress related to the 20 symptoms. 
There are 5 possible responses for each HIV symptom. These responses will be analyzed as both 
categorical response and numerical response.  The mapping between the categorical response and 
the numerical response is listed in below.
Categorical Response
Numerical Response
I do not have this symptom
0
Doesn’t bother
1
Bothers a little
2
Bothers
3
Bothers a lot
4


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If multiple responses are provided for a single question, then the largest (worst) value will be 
chosen (eg, (4) bothers a lot will be chosen over (3) bothers). This applies regardless of how 
many responses are provided. That is, if (1) doesn’t bother, (2) bothers a little, and (3) bothers 
are all marked, then (3) bothers will be used in the analysis.
Missing values will not be imputed.
For each question, the number and percentage of subjects in each category of the categorical 
responses will be summarized by treatment group (B/F/TAF, SBR, and Delayed Switch to 
B/F/TAF) and visit. No inferential statistics will be generated.
For each question, the numerical responses will be summarized by treatment group at baseline 
using descriptive statistics (sample size, mean, SD, median, Q1, Q3, minimum, and maximum). 
The baseline and change from baseline at Week 4 and Week 24 will be compared between the 
B/F/TAF and SBR treatment groups using a Wilcoxon rank-sum test.
9.2.
Medication Adherence Questionnaire
Adherence will be assessed by the medication adherence questionnaire that includes a VAS and 
2 additional questions.
For the VAS, the subject is asked to describe their adherence to their ARV regimen by using a 
linear scale (0% – 100%) to indicate what percent of medications was taken in the last 30 days 
(0% = taken none of prescribed anti-HIV medication, and 100% = taken all doses of prescribed 
anti-HIV medication). A value of “999” indicates a missing, ambiguous, or illegible response, 
and will be treated as a missing value for summaries. The 2 additional questions ask how many 
days the subject has missed medications in the last 30 days and how many days the subject has 
missed medications in the last 4 days. A value of “99” indicates a missing, ambiguous, or 
illegible response, and will be treated as a missing value for summaries.
The VAS (%) absolute value and change from baseline at each study visit will be summarized 
for the SBR group using descriptive statistics.
Number of days with missed doses in the past 30 days and past 4 days will be summarized 
categorically (< 2, 2 to < 4, 4 to < 6, ≥ 6 for the past 30 days; 0 and > 0 for the past 4 days) 
for each study visit.
9.3.
HIV Treatment Satisfaction Questionnaires
The HIV Treatment Satisfaction Questionnaire (HIVTSQ) has 10 questions regarding current 
treatment regimen. The Status form HIVTSQs is used at Baseline, and the change form 
HIVTSQc is used at postbaseline visits. 
At baseline, a treatment satisfaction scale total will be calculated as the sum of the responses to 
the 10 question items on the HIVTSQs form (range from 0 to 60). At postbaseline visits, a 
treatment satisfaction scale total in change will be calculated as the sum of the responses to the 
10 question items on the HIVTSQc form (range from -30 to 30).


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Additionally, two subscale scores, one for general satisfaction/clinical and another for 
lifestyle/ease will be computed. Each subscale ranges from 0 to 30 on the HIVTSQs form and 
from -15 to 15 on the HIVTSQc form.
Table 9-1 lists the questions, possible responses for both the status and change questionnaires, as 
well as the subscale each question belongs to.
Table 9-1.
List of Items on the HIVTSQ
Question
Response Options for 
Status Form
Response Options for 
Change Form
Subscale
How satisfied are you 
with your current 
treatment?
Very satisfied 6 to 0 very 
dissatisfied
Much more satisfied now 
3 to −3 much less satisfied 
now
General 
Satisfaction/Clinical
How well controlled do 
you feel your HIV has 
been recently?
Very well controlled 6 to 0 
very poorly controlled
Much better controlled now 
3 to −3 much worse 
controlled now
General 
Satisfaction/Clinical
How satisfied are you 
with any side effects of 
your present treatment?
Very satisfied 6 to 0 very 
dissatisfied
Much more satisfied now 
3 to −3 much less satisfied 
now
General 
Satisfaction/Clinical
How satisfied are you 
with the demands made by 
your current treatment?
Very satisfied 6 to 0 very 
dissatisfied
Much more satisfied now 
3 to −3 much less satisfied 
now
Lifestyle/Ease
How convenient have you 
been finding your 
treatment to be recently?
Very convenient 6 to 0 very 
inconvenient
Much more convenient now 
3 to −3 much less convenient 
now
Lifestyle/Ease
How flexible have you 
been finding your 
treatment to be recently?
Very flexible 6 to 0 very 
inflexible
Much more flexible now 
3 to −3 much less flexible 
now
Lifestyle/Ease
How satisfied are you 
with your understanding 
of your HIV?
Very satisfied 6 to 0 very 
dissatisfied
Much more satisfied now 
3 to −3 much less satisfied 
now
Lifestyle/Ease
How satisfied are you 
with the extent to which 
the treatment fits in with 
your lifestyle?
Very satisfied 6 to 0 very 
dissatisfied
Much more satisfied now 
3 to −3 much less satisfied 
now
Lifestyle/Ease
Would you recommend
your present treatment to 
someone else with HIV?
Yes I would definitely 
recommend the treatment 
6 to 0 No I would definitely 
not recommend the treatment
Much more likely to 
recommend the treatment 
now 3 to −3 much less likely 
to recommend the treatment 
now
General 
Satisfaction/Clinical
How satisfied would you 
be to continue with your 
present form of treatment?
Very satisfied 6 to 0 very 
dissatisfied
Much more satisfied now 
3 to −3 much less satisfied 
now
General 
Satisfaction/Clinical


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The HIVTSQs scale and subscale totals at baseline, and the HIVTSQc scale and subscale totals 
at each visit will be summarized by treatment group (B/F/TAF and SBR) using descriptive 
statistics. 
Comparison between treatment groups (B/F/TAF and SBR) in HIVTSQc scale total scores will 
use an analysis of covariance model adjusting for HIVTSQs scale total at Baseline. A similar 
analysis will be performed on the two subscale scores as well.
For each subscale, if more than 1 question is missing, then the subscale total or subscale total in 
change will be set to missing. Otherwise, the missing total will be imputed by taking the average 
of non-missing responses from the other questions in that subscale.
For the scale total or scale total in change, if more than 5 questions are missing, then the value 
will be set to missing. Otherwise, the missing total will be imputed by taking the average of 
nonmissing responses from the other questions.
If two responses are provided for a single question, and the scores are next to each other, then the 
midpoint will be used. If two responses are provided for a single question, and the scores are not 
immediately next to each other, then the response will be considered missing. 
9.4.
Change from Protocol Specified Analysis for Patient-Reported Outcomes
There are no changes from the protocol-specified patient-reported outcomes analyses.


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10.
REFERENCES
DeJesus E, Villanueva J, Lopez J, Brinson C, Crofoot G, Daar ES, et al. Tenofovir Alafenamide 
vs Tenofovir Disoproxil Fumarate in Hispanic/Latinx and Black Participants: 
Efficacy, Bone and Renal Safety Results From a Pooled Analysis of 7 Clinical 
Trials [Poster 318]. IDWeek; 2019 2-6 October; Washington, DC. 
LaVange LM, Koch GG. Randomization-Based Nonparametric (ANCOVA). In: D'Agostino Sr. 
RB, Sullivan LM, Massaro JM, eds.  Wiley Encyclopedia of Clinical Trials. John 
Wiley & Sons, Inc.; 2008: 31-8. vol 4).
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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11.
SOFTWARE
SASVersion 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
PASS Version 14 (NCSS, LLC, Kaysville, Utah) was used for planned sample size and power 
calculation.


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


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13.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial)
Appendix 3.
Cardiovascular or Cerebrovascular Events
Appendix 4.
Hepatic Events
Appendix 5.
Programming Specifications


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Appendix 1.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48e
30 Day 
Follow-Upf
ESDDg
4
12
24
28d
36
48
Every 12 Weekscc
Informed Consent
X
HIV Symptoms Distress Module
X
X
X
X
X
HIV-TSQh
X
X
X
VAS Adherence Questionnairei
X
X
X
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete/Symptom-Directed Physical Examj
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG 
(performed supine)
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsk
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Pregnancy Testl
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testl
X
FSH Testm
X
Chemistry Profilen
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentso
X
X
X
X
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X


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Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48e
30 Day 
Follow-Upf
ESDDg
4
12
24
28d
36
48
Every 12 Weekscc
Hematology Profilep
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAq
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Panels
Xt
Xt
Plasma HBV DNAu
X
X
X
X
HCV Serologyv
X
X
X
HIV-1 Genotype/Phenotypeq
Xq
Plasma, Serum, and Urine Sample Storagew
X
X
X
X
X
X
X
X
X
Whole Blood for HIV-1 DNA archive testing
X
Xx
Obtain Screening Number
X
Randomizationz
X
Study Drug Dispensation 
Xbb
Xbb
Xbb
Xaa
X
X
X
X
Study Drug Accountability
Xbb
Xbb
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Participants should initiate dosing of study drug on the same day as the Day 1 visit.
c
All study visits are to be completed ± 6 days of the protocol-specified visit date (based on the Day 1 visit), unless otherwise specified. 
d
Participants randomized to continue their baseline regimen will have an additional visit at Week 28.
e
At the study Week 48 Visit, participants who wish to continue on B/F/TAF will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks or until they 
have access to FDC of B/F/TAF, whichever occurs first, and attend study visits every 12 weeks (± 6 days of the protocol specified visit date) followed by a 30 Day Follow-Up 
Visit.
f
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. Required for 
participants who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Participants 
who participate post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit.  
g
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Participants will be asked to continue attending the scheduled study visits through 
the Week 48 Visit even if the participant discontinues study drug. Participants on Treatment 2 (SBR) who discontinue their baseline regimen due to an AE prior to Week 24 
will be asked to continue attending the scheduled study visits through the Week 24 visit.
CCI
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1-IIV-TSQs is to be completed at Day I. The 1-IIV-TSQc is to be completed at Week 4 and Week 24. Participant is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires. 
VAS Adherence Questionnaire will be administered at Day I and at all visits up to (and including) Week 24 for participants in Treatment Group 2 (SBR) only. 
Complete physical exam is re.quired at Screening, Day I, Week 24, 48, 72, and ESDD. Urogenital/anorectal exams will be perforn1ed at the discretion of the Investigator. 
Symptom-directed physical examination, as needed. 
k. 
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature. 
I 
All female participants will have a semm test perforn1ed at Screening. Urine pregnancy test will only be done for persons of childbearing potential. Positive urine pregnancy 
tests will be confirn1ed with a semm test. 
m 
FSJ-1 test is re.quired for female participants who are <54 years old and have stopped menstmating for 2:: 12 months but do not have documentation of ovarian horn10nal failure. 
n 
Chemistry profile: alkaline phosphatase, AST, ALT, total bilimbin, direct and indirect bilimbin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphoms, magnesium, potassium, sodium, amylase, and Cystatin C. After Day I, calcium, phosphorous, magnesium, and amylase (reflex lipase testing is 
perforn1ed in participants with total amylase > 1.5 x ULN) 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 I, Weeks 24, 48, and 72. Cystatin C will only be collected at Day I. 
o 
Metabolic Assessments will be perforn1ed at Day I, Weeks 24, 48, and 72. 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 participant has not fasted prior to the visit, the visit may proceed, but the participant must return within 
72 hours in a fasted state to draw blood for the metabolic assessments. 
p 
CBC with differential and platelet count. 
q 
I-IIV- 1 genotype and phenotype testing for participants with confirn1ed virologic failure and HIV- I RNA >200 copies/mL. Following virologic rebound, participants 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- I RNA and I-IIV- 1 resistance analysis (reverse 
transcriptase, protease, and integrase genotype and phenotype) blood draw. Based on the results of this testing, participants should be managed according to the Virologic 
Rebound Schema. 
r 
ti 
V 
w 
X r 
z 
oo panel will be perforn1ed at Screening and Week 48: HBsAg, 1-IBsAb, HBcAb. 
For participants who are HBV co-infected (defined in Protocol Section 6.9.1): The following 1-IBV Blood panel will be conducted by the central laboratory: HBsAb, 
1-IBsAg (qualitative and quantitative), and 1-IBeAg (if negative, reflex HBeAb). 
For participants who are NOT HBV co-infected: The following 1-IBV Blood panel will be conducted by the central laboratory: HBsAb, 1-IBcAb, and HBsAg. 
Participants who are HBsAg or HBcAb positive will have a reflex test for HBV DNA (viral load). 
For participants who are HBV co-infected: Plasma 1-IBV DNA will be collected at Day I, Week 24, Week 48 and ESDD. 
Hepatitis C vims serology will be perforn1ed at Screening, Week 48, and Week 72. Participants who are 1-ICV Ab positive will have a HCV RNA test perforn1ed. 
Plasma, semm, and urine storage samples will be collected for safety, virology, or PK testing. 
Collect whole blood sam le for artici ants randomized to SBR only at Week 24. 
ic Day I visit provided that all screening procedures have been completed and participant eligibility has 
been confirn1ed. 
aa 
At Week 24, participants randomized to continue their baseline regimen and complete 24 weeks of treatment on their baseline regimen will switch to FDC of B/F/T AF. 
bb 
FDC of B/F/T AF will be dispensed to Treatment Group I only. Study dmg accountability will be perforn1ed accordingly. 
cc 
Subjects will receive study dmg for dosing until Week 72. 
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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}.
Is there at least l un-
treatment* HIV-] RNA data 
Yes ___ __, 
col lected in the Snapshot 1------. o 
Is the last available on-treatment* 
HIV-I RNA in the Snapshot 
window < 50 copies/mL? 
Yes 
HJV-lRN < 
50 c.opics/m L 
IUV-1 Rl A~ 
50 copies/mL 
window? 
,., 
Is study drug prematurely 
discontinued on or prior to the 
upper limit of the Snapshot 
window? 
.I 
Yes .. 
[s discontinuation of the study 
drug due to Lack of Efficacy'! 
I 
No 
ls discontinuation of the study 
drug due to AE/Dcath? 
Yes 
[s the last available on-
ls the last available on-
treatment* HIV-] RNA < treatment* HIV-1 RNA < 
50 copies/ml 
o Virologic Data: 
Discontinued Study 
Drug Due to Other 
Reason and Last mv-1 
R. A < 50 copks/m L 
50 copies/ml 
o Vi.rologic Data: 
Discontinued Study 
Drug Due to AE/Death 
and Last HJV-1 RNA < 
SC) copics/mL 
0 
No Virologic Data: 
Missing Oat~ duri.ng 
Window but OD Study 
Drug 
* On-Treatment HIV-I RNA data inchide all HIV-I RNA data for subjects who are on-going and.HIV-I RNA data up to I 
day after the last dose date of study drug for subjects who prematurely discontinue or complete study drug. 


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Appendix 3.
Cardiovascular or Cerebrovascular Events
An adverse event record will be flagged as a cardiovascular or cerebrovascular event if its 
MedDRA PT is included in the pre-specified PT list, which includes all PTs from the narrow 
search of the following 3 SMQs under MedDRA v22.1 provided by Gilead PVE (search name: 
Ischemic cardiac and cerebral events narrow) and reviewed by Gilead medical monitors.
SMQ Source
Cardiovascular or Cerebrovascular 
Events
Ischaemic central nervous system vascular conditions (SMQ) – Narrow 
Scope Term
Myocardial infarction (SMQ) - Narrow Scope Term
Other ischaemic heart disease (SMQ) - Narrow Scope Term


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Appendix 4.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT is included in this
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA v22.1 provided by Gilead PVE (search name: Non-infectious, non-congenital 
hepatobiliary disorders) and reviewed by Gilead medical monitors.
SMQ Source
Hepatic Events (HEP)
Biliary neoplasms benign (incl cysts and polyps) (SMQ)
Biliary malignant tumours (SMQ)
Biliary tumours of unspecified malignancy (SMQ)
Biliary system related investigations, signs and symptoms (SMQ)
Biliary tract disorders (SMQ)
Gallbladder related disorders (SMQ)
Gallstone related disorders (SMQ)
Cholestasis and jaundice of hepatic origin (SMQ)
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ)
Hepatitis, non-infectious (SMQ)
Liver neoplasms, benign (incl cysts and polyps) (SMQ)
Liver malignant tumours (SMQ)
Liver tumours of unspecified malignancy (SMQ)
Liver related investigations, signs and symptoms (SMQ)
Liver-related coagulation and bleeding disturbances (SMQ)


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Appendix 5.
Programming Specifications
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
AGE (years) is calculated from the number of days between the DOB and Study Day 1,
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),
Divide the result in (b) by 12,
AGE = the integer of the result in (c),
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, and ethnicity 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) is 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 the subject was never dosed.
6) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.
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.


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8) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
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;
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;
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 from 
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. 
10) Defining Baseline ARV Medication
Baseline ARV Medication
All subjects are expected to enter the study on an ARV regimen other than FDC of 
B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months
(see Protocol Section 4.2 for allowed agents)
Using the ARV raw dataset, for the B/F/TAF treatment group, include all prior and/or 
current ARVs (ARV.INGRED where ARV.CMSCAT =”Prior ARV” or “Current 
ARV”), taken on or up to 4 days prior to first dose date as defined in Section 3.8.1
(or randomization date if not treated). For the SBR treatment group, include all prior 
and/or current ARVs (ARV.INGRED where ARV.CMSCAT =”Prior ARV” or 
“Current ARV”) taken on Study Day 1.


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Use the following rules to determine if the ARV medication is taken on Day 1:

If ARV end date is before B/F/TAF first dose date -4 for B/F/TAF subjects or Day 1 
date for SBR subjects then exclude. If “Ongoing” is not marked and the end date is 
completely missing, then exclude. See below for imputation rules for any partial 
dates of uncertainty.

If ARV start date is after B/F/TAF first dose date for B/F/TAF subjects (or Day 1 
visit date for SBR subjects) then exclude. See below for imputation rules for any 
partial dates of uncertainty.
The different categories used for the baseline ARV medication are (1) backbone, 
(2) third agent, and (3) third agent class.

For subjects with more than one baseline ARV medication record, concatenate the records 
together using “+” to get one record for each subject. For all ingredients, replace “_” or “+”
with “/”.

For each subject, search for the NRTIs: FTC, TAD, TDF, ABC, AZT, and 3TC. There should 
be 2 NRTIs for each subject.  Create the backbone variable by concatenating the 2 NRTIs 
listed in the order above, and separate by a “/” as per the backbone column in the table 
below. 

For each subject, identify the Third Agent. These will fall into 4 categories (PI, NNRTI, 
INSTI, and CCR5 antagonist). Each subject should have only 1 category of third agent unless 
they have a protocol deviation. For each subject, create the third agent variable by selecting 
on the ingredients listed:
PIs and boosted PIs include ATV, ATV/RTV, ATV/COBI, DRV/RTV, DRV/COBI, 
LPV/RTV, and NFV. Create the third agent variable by concatenating the ingredients 
(ATV, DRV, LPV, NFV, RTV, COBI) with a “/”. Change “ATV/RTV” to “ATV/r”, 
“ATV/COBI” to “ATV/co”,  “DRV/RTV” to “DRV/r”, “DRV/COBI” to “DRV/co”, and 
“LPV/RTV” to “LPV/r”, as per the Third Agent column in the table below.
NNRTIs include DOR, EFV, NVP, and RPV. ETR is not allowed, but is to be included 
for subjects who were not on a protocol-approved baseline ARV medication.
INSTIs include DTG, EVG/COBI, and RAL. Create the third agent variable by 
concatenating the ingredients (DTG, EVG, COBI, RAL). Change “EVG/COBI” to 
“EVG/co” as per the Third Agent column in the table below. RAL/RTV is a protocol 
violation and should be changed to “RAL/r”.
CCR5 antagonists include MVC.


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Each subject should have PI or NNRTI or INSTI or CCR5. If a subject has more than 
one, then it is a protocol violation. The third agent can be listed as “DTG/RPV”, and 
should be counted in both categories for summary purposes.
The final Baseline ARV Medication will be presented as third agent + backbone as per 
the last column in the table below.
The table below provides example records for each subject with the backbone, 
third agent, third agent class, and final baseline ARV Medication variables.
Baseline ARV Medications 
from the data
Backbone
Third Agent
Third Agent 
Class
Baseline ARV 
Medication
ABC/NVP/FTC/TAF*
ABC/FTC/TAF
NVP
NNRTI
NVP+ABC/FTC/TAF
ATV/ABC/3TC
ABC/3TC
ATV
PI
ATV + ABC/3TC
ATV/RTV/ABC/3TC
ABC/3TC
ATV/r
PI
ATV/r + ABC/3TC
ATV/RTV/FTC/TAF
FTC/TAF
ATV/r
PI
ATV/r + FTC/TAF
ATV/RTV/FTC/TDF
FTC/TDF
ATV/r
PI
ATV/r + FTC/TDF
ATV/COBI/FTC/TAF
FTC/TAF
ATV/co
PI
ATV/co + FTC/TAF
DOR/FTC/TDF
FTC/TDF
DOR
NNRTI
DOR + FTC/TDF
DRV/COBI/ABC/3TC
ABC/3TC
DRV/co
PI
DRV + ABC/3TC
DRV/COBI/FTC/TAF
FTC/TAF
DRV/co
PI
DRV/co + FTC/TAF
DRV/COBI/FTC/TDF
FTC/TDF
DRV/co
PI
DRV/co + FTC/TDF
DRV/DTG/RTV/FTC/TAF*
FTC/TAF
DRV/r and 
DTG
DRV/r is PI
DTG is INSTI
DRV/r and DTG + 
FTC/TAF
DTG/ABC/3TC
ABC/3TC
DTG
INSTI
DTG + ABC/3TC
DTG/FTC/TAF
FTC/TAF
DTG
INSTI
DTG + FTC/TAF
DTG/FTC/TDF
FTC/TDF
DTG
INSTI
DTG + FTC/TDF
DTG/RPV*
-
DTG and 
RPV
DTG is INSTI
RPV is NNRTI
DTG and RPV
EFV/3TC/TDF
TDF/3TC
EFV
NNRTI
EFV + TDF/3TC
EFV/ABC/3TC
ABC/3TC
EFV
NNRTI
EFV + ABC/3TC
EFV/AZT/3TC
AZT/3TC
EFV
NNRTI
EFV + AZT/3TC
EFV/FTC/TAF
FTC/TAF
EFV
NNRTI
EFV + FTC/TAF
EFV_FTC/TDF
FTC/TDF
EFV
NNRTI
EFV + FTC/TDF
ETR/ABC/3TC*
ABC/3TC
ETR
NNRTI
ETR + ABC/3TC
EVG/COBI/FTC/TAF
FTC/TAF
EVG/co
INSTI
EVG/co + FTC/TAF
EVG/COBI/FTC/TDF
FTC/TDF
EVG/co
INSTI
EVG/co + FTC/TDF
FTC/RPV/TAF
FTC/TAF
RPV
NNRTI
RPV + FTC/TAF
FTC/RPV/TDF
FTC/TDF
RPV
NNRTI
RPV + FTC/TDF
LPV/RTV/FTC/TDF
FTC/TDF
LPV/RTV
PI
LPV/r + FTC/TDF
MVC/FTC/TDF
FTC/TDF
MVC
CCR5
MVC + FTC/TDF
NFV/FTC/TAF
FTC/TAF
NFV
PI
NFV + FTC/TAF
NVP/AZT/3TC
AZT/3TC
NVP
NNRTI
NVP + AZT/3TC
NVP/FTC/TDF
FTC/TDF
NVP
NNRTI
NVP + FTC/TDF


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Baseline ARV Medications 
from the data
Backbone
Third Agent
Third Agent 
Class
Baseline ARV 
Medication
NVP/FTC/TAF
FTC/TAF
NVP
NNRTI
NVP + FTC/TAF
RAL/ABC/3TC
ABC/3TC
RAL
INSTI
RAL + ABC/3TC
RAL/FTC/TAF
FTC/TAF
RAL
INSTI
RAL + FTC/TAF
RAL/FTC/TDF
FTC/TDF
RAL
INSTI
RAL + FTC/TDF
RTV/DRV/ABC/3TC
ABC/3TC
DRV/r
PI
DRV/r + ABC/3TC
RTV/DRV/FTC/TAF
FTC/TAF
DRV/r
PI
DRV/r + FTC/TAF
RTV/DRV/FTC/TDF
FTC/TDF
DRV/r
PI
DRV/r + FTC/TDF
RTV/RAL*
-
RAL/r
INSTI
RAL/r
TAF/COBI/DRV/FTC
FTC/TAF
DRV/co
PI
DRV/co + FTC/TAF
TAF/DTG/FTC
FTC/TAF
DTG
INSTI
DTG + FTC/TAF
*Protocol Violation
Duration of Baseline ARV Medication
Duration of the baseline ARV medication (defined above) prior/ to the first dose date is defined 
as (End Date – Start Date+1). Duration will be expressed in years so that duration in days will be 
divided by 365.25 days.
End date is defined as the first dose date -1 or randomization date if randomized but not dosed.
Start Date: The start date of the baseline ARV medication is the latest start date of all the 
individual baseline ARV medications selected above
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 the 
minimum of (the start date of the ARV, first dose date-1, the stop date of the same ARV)

If only year is available, month and day will be first imputed as July 1st of the year, then 
imputed as the minimum of (the start date of the ARV, first 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 only month and year are available, day will be first imputed as 15th, then imputed as 
minimum of (the first dose date-1, the stop date of the ARV)

If only year is available, month and day will be first imputed July 1st of the year, then 
imputed as  minimum of (first dose date-1, the stop date of the ARV) 

No imputation applied for date missing completely


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11) Efficacy analyses:
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% CIs (for HIV-1 RNA < 50 at wk24 by snapshot algorithm for FAS or Week 24 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. 
The following SAS code will be used to compute cell counts and p-values. 
data example;
input  grp trt01a $  outcome $ count ;
datalines;
1       Treat-A        2-Fail        x     
1       Treat-A        1-Succ      xxx     
1       Treat-B        2-Fail        x     
1       Treat-B        1-Succ      xxx     
run;
proc freq data = example;
table trt01a*outcome /riskdiff(CL=(exact)) alpha=0.05;
weight count; exact RISKDIFF(METHOD=SCORE);
output out=ciexact(keep=_RDIF1_ XL_RDIF1 XU_RDIF1 _RSK11_  _RSK21) riskdiff;
run;
data final(keep=A1 B1 Estimate LowerCL UpperCL ocharc1);
set ciexact;
label Estimate ="Percentage Difference"
LowerCL = "95% Lower Confidence Limit"
UpperCL = "95% Upper Confidence Limit"
A1 = "Percentage of Success in Treat-A"
B1 = "Percentage of Success in Treat-B";
Estimate=100*_RDIF1_;
LowerCL = 100*XL_RDIF1;
UpperCL = 100*XU_RDIF1;
A1 = 100*_RSK11_;
B1 = 100*_RSK21_;
ocharc1 = right(compress(put(Estimate,8.1)) || '% (' || compress(put(LowerCL,8.1)) || '% 
to ' || compress(put(UpperCL,8.1)) || '%)');
run;
The 95% CI for percentage estimate of HIV-1 RNA < 50 copies/mL or >= 50 copies/mL for 
each treatment is calculated based on the Clopper-Pearson exact method.
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. 


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proc freq data=adeff;
tables trtgrp*response/fisher; /*p value from Fisher’s exact test*/
run;
Subgroup analyses for HIV-1 RNA < 50 copies/mL by US FDA-defined snapshot algorithm
For the subgroups, 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, similar to that for the primary efficacy endpoint.
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 24 (Snapshot Algorithm)
For the subgroups, 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. 
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).
(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.)
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.


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proc glm data=adeff;
class trtgrp;
model CD4=trtgrp;
lsmeans trtgrp /alpha=0.05 cl pdiff;
run;
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:
HIV-1 RNA >= 50 copies/mL - Discontinued Study Drug Due to AE or Death and Last 
Available HIV-1 RNA >= 50 copies/mL
HIV-1 RNA >= 50 copies/mL - Discontinued Study Drug Due to Other reason* and Last 
Available HIV-1 RNA >= 50 copies/mL
No virologic Data – Discontinued Study Drug Due to AE or Death and Last Available 
HIV-1 RNA < 50 copies/mL
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.
12) 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.
13) TEAE
Events with Missing Onset Day and/or Month
An event is considered treatment emergent if the following 3 criteria are met:
i.  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
ii.  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
iii.  End date is as follows: 
The (complete) end date is on or after the first dose date, or


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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
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.
14) Toxicity Grades:
For toxicity grade summaries, include post-baseline graded results as defined in Section 
7.2.2.1, not just those used in by-visit summaries.
15) Graded Laboratory Abnormalities Summary
The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label 
Used in l-labtox Listing
Toxicity Direction
Lab Test Label
Used in t-labtox Table
Hematology
Hemoglobin
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Chemistry
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Fasting)
Decrease
Serum Glucose (Fasting, Hypoglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Decrease
Serum Glucose (Nonfasting, Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)


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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)
Urinalysis
Urine Blood (Dipstick)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative or Dipstick)*
Note: Prothrombin Intl. Normalized Ratio (INR) and Prothrombin Time (PT) were graded based on the protocol defined toxicity 
grade scale. The results and toxicity grade will be listed in listing, but not be summarized in lab toxicity summary table.
Due to the reflexive nature of the quantitative urine RBC test, results will be combined with the 
dipstick test of urine blood as described below. General rule is that urine RBC (Quantitative) 
should always be used first (if available), no matter if it is collected at the same time of Urine 
Blood (Dipstick) or not. The combined Urine RBC (hematuria, Quantitative or Dipstick) toxicity 
grade will be used for “Maximum treatment-emergent toxicity grade” summary.
Is Post-BL Urine 
RBC (Quant.) 
Result Available?
Is BL Urine RBC 
(Quant.) Result 
Available?
Is Post-BL Urine 
Blood (Dipstick) 
Result 
Available?
Is BL Urine 
Blood (Dipstick) 
Result 
Available?
How to Determine 
Treatment-Emergent Toxicity for “
Urine RBC (Hematuria, Quantitative 
or Dipstick)”
Yes
Yes
-
-
Compare post-BL Urine RBC (Quant.) 
toxicity grade to BL Urine RBC 
(Quant.) toxicity grade. If post-BL 
toxicity is greater than BL toxicity, then 
treatment-emergent
Yes
No
-
-
Treatment-emergent. Use post-BL 
Urine RBC (Quant.) toxicity grade.
No
-
Yes
Yes
Compare post-BL Urine Blood 
(Dipstick) toxicity grade to BL Urine 
Blood (Dipstick) toxicity grade. If post-
BL toxicity is greater than BL toxicity, 
then treatment-emergent
No
-
Yes
No
Treatment-emergent. Use post-BL 
Urine Blood (Dipstick) toxicity grade.
No
-
No
-
Do not count subject in the denominator 
for “Urine RBC (Hematuria, 
Quantitative or Dipstick)”
BL = Baseline. Quant = Quantitative. “-” means any value can be present (or it can be missing), as it does not affect the 
classification
16) Rank analysis of covariance for proteinuria shift table


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Rank analysis of covariance:
proc rank data=up nplus1 ties=mean out=ranks1;
var upbase upwk48;
run;
proc reg data=ranks1;
model upwk48=upbase;
output out=residual1 r=resid;
run;
proc freq data=residual1;
tables trtgrp*resid/noprint cmh2;
run;
17) 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)
18) 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 baseline refer to the subjects who have any 
use of the lipid modifying agents at Period 1 Study Day 1 for B/F/TAF and SBR groups and 
Period 2 Study Day 1 for the Delayed Switch to B/F/TAF group.
a) More specifically, subjects with “Lipid Modifying Agent Use at Baseline” include those 
subjects in the safety analysis set meeting both of the following criteria: 1) any selected 
CM record with the start date ≤ the first dose date, 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, assume the start 
date is on or before the first dose date; lipid modifying medication is considered as being 
taken at baseline 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 and the end 
date unknown (completely missing) are considered as being taken at baseline (the 
unknown end date is assumed to be on or after the first dose date).

Subjects who initiated lipid modifying medications during the study (up to Week 24) are
defined as the subjects in the safety analysis set who did not take lipid modifying 
medications at baseline and met the following criteria: 1) for subjects who permanently 
discontinued study treatment with any selected CM record with start date after the first dose 
date and on and prior to the minimum of (a) last dose date, or (b) Week 24 visit date; 2) for 


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subjects who are still on study treatment with any selected CM records first started after the 
first dose date and on or prior to the Week 24 visit date. Note for the Delayed Switch to 
B/F/TAF group, the Week 24 visit date refers to the nominal Week 48 visit date.

Subjects in the B/F/TAF group who initiated lipid modifying medications during the study 
(up to Week 48) are defined as the subjects in the safety analysis set who did not take lipid 
modifying medications at baseline and met the following criteria: 1) for subjects who 
permanently discontinued study treatment with any selected CM record with start date after 
the first dose date and on and prior to the minimum of (a) last dose date, or (b) Week 48 visit 
date; 2) for subjects who are still on study treatment with any selected CM records first 
started after the first dose date and on or prior to the Week 48 visit date.
19) Analysis of covariance for HIVTSQc scores
proc mixed;
class trtgrp;
   model change = trtgrp baseline;
  lsmeans trtgrp;
run;
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 that visit in the 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.
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) results = “Repeat reactive, confirmed”, “Repeat Reactive Unconfirmed”.


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


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HCVAb
HCV RNA
Coinfection Status
Positive
Quantifiable
Y
Not Quantifiable
N
Missing
Null
Negative
-
N
Missing
Quantifiable
Null
Not Quantifiable
N
Missing
Null
“-” means any value can be present, as it does not affect the classification

For incident coinfection, all laboratory tests must share the same accession number and if any 
set of values meets the criteria, then the subject is considered to have incident coinfection
The incident coinfection status will be one of two values: Yes/Null
The following tables provide combinations of HBV and HCV tests that are considered 
“Y” for incident coinfection status (all others are considered Null)
HBsAg
HBsAb
HBcAb
HBV DNA
Coinfection Status
Positive
-
-
-
Y
Negative
Negative
Positive
Quantifiable
Y
Missing
Negative
Positive
Quantifiable
Y
HCVAb
HCV RNA
Coinfection Status
Positive*
-
Y
-
Quantifiable
Y
*
Subjects with positive HCVAb postbaseline must also have negative or missing HCVAb at baseline in order to be 
considered as having incident HIV/HCV coinfection.
“-” means any value can be present, as it does not affect the classification
23) HBV DNA test codes: If the result of the lab test code GET1883 (HBV DNA CAP/CTM
2.0-EDTA-CL) is listed as “>170000000”, then a reflexive test code GET1884 (HBV DNA 
CAP/CTM 2.0Dil-EDTA-CL) should be performed and will share the same accession 
number as the original GET1883 test. In this instance, use the result from GET1884 instead 
of GET1883 when determining HBV DNA.
24) Reasons for Subjects who excluded from Week 24 PP Analysis Set will be summarized as
follows in the table: 


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a) Had Pre-existing INSTI Resistance-associated Mutations, including pre-existing 
mutations that were detected post-baseline
b) Did Not Have On-Treatment HIV-1 RNA in Week 24 Window Unless due to 
Discontinuation of Study Drug for Lack of Efficacy
c) Met the Exclusion Criteria for 3 or more TAMs (M41L,D67N, K70R, L210W, T215F/Y, 
and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT, including pre-existing 
mutations that were detected post-baseline
d) Did not Meet the Inclusion Criteria for Baseline ARV Regimen
e) Took Protocol Prohibited Medications
25) The number of decimal places in reporting p-values should be as follows:
a) values less than 0.001 < 0.001
b) values 0.001 to less than 1.000 4 decimal places (no rounding)
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) will be flagged (eg, ^).  However, please note, if CM end date is 
completely missing and the medication is not marked “Ongoing” and the CRF indicates
‘Prior ARV’, the ARV will not be flagged.
28) Last Dose Date and Last Study Date
a) Last Dose Date for subjects who permanently discontinued study drug was defined in 
Section 3.8.1.
For subjects in the B/F/TAF or Delayed Switch to B/F/TAF groups who permanently 
discontinued study drug at the data cut date:
If last dose date 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 study drug start dates and end 
dates, the clinic visit dates, and the laboratory visit dates, excluding the date of 30-day 
follow-up visit, will be used to impute the last dose date.
If the last dose date is a partial 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 the dispensing date’s month is after the last dose date’s month, a data 
query is needed.


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If the 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. 
For subjects in the SBR group who permanently discontinued study drug at the data cut 
date:
If the last dose date (as defined in Section 3.8.1) is missing (eg, only year of last dose 
date is known or completely missing due to lost to follow-up) for subjects who did not 
switch to B/F/TAF at the data cut date, the latest of the ARV baseline medication end
dates, the clinic visit dates, and the laboratory visit dates, excluding the date of 30-day 
follow-up visit, will be used to impute the last dose date.
If the last dose date is a partial date (ie, month and year of last dose are known), the latest 
of the ARV baseline medication end dates and the imputed last dose date [day imputed as 
15] will be used as the final imputed last dose date.
If the subject died and the death date is complete (ie, not partial date) and before the 
imputed last dose date, the complete death date should be used as the imputed last dose 
date. 
Last dose date is not defined for subjects still on study drug in this SAP. However, for the 
calculation of the duration of exposure to study drug, the data cut date will be used to 
impute the last dose date for subjects who have not permanently discontinued study drug 
at the time of the data cut date.
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 the subject died and the death date is complete (ie, not partial date) and before the 
imputed last study date, the complete death date should be used as the imputed last study 
date. 
Last study date is not defined for subjects still on study in this SAP. However, for 
programing purposes, the latest of data cut date, the clinic visit dates, and the laboratory 
visit dates, including the 30-day follow-up visit date, will be used to impute the last study 
date for subjects still on study.
29) The precision in reporting numerical values should be as follows:
Raw measurements will be reported the same as the data captured electronically or on the
CRF.


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Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement.
Mean, median, minimum, Q1, Q3, maximum, 95% CIs will be reported to the same number 
of decimal places of the raw measurements. 
Exceptions may be considered; for example if more than 4 significant digits are provided for 
the measurement. 
30) Duration of HIV Diagnosis (years) is defined as the year from the First Dose Date/Study Day 
1 Date minus the year of HIV diagnosis from Disease Under Study (HIV) CRF page.
31) Duration of  HIV Treatment (Years) is defined as the year from the First Dose Date/Study 
Day1 Date minus the year first started HIV treatment from Disease Under Study (HIV) CRF 
page.
32) Premature study drug discontinuation prior to Week 24 is defined as

For SBR group: subjects with Study Drug Completion form marked “No” for “Did subject 
complete study drug dosing as specified per protocol?” and subject did not switch to 
B/F/TAF

B/F/TAF group: subjects with Study Drug Completion eCRF marked “No” for “Did subject 
complete study drug dosing as specified per protocol?”, permanently discontinued study drug 
per the Study Drug Administration eCRF, and last dose was less than the latest of 168 days 
or the Week 24 visit date (if non-missing).
33) Completed 24 weeks on randomized drug is defined as “Yes” if subjects did not prematurely 
discontinue study drug prior to Week 24 
34) Premature study discontinuation prior to Week 24 is defined as

For SBR group: subjects with Study Completion form marked “No” for “Did subject 
complete the protocol-planned duration of the study?” and subject did not switch to B/F/TAF

B/F/TAF group: subjects with Study Completion eCRF marked “No” for “Did subject 
complete the protocol-planned duration of the study?” and there are no scheduled visit dates 
on or after Week 24.


SAP-Week48-GS-US-380-4580-v1
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
04-Mar-2020
00:29:00
Project Team
Leader eSigned
04-Mar-2020
18:48:00
PPD
PPD--

Prot_000.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Clinical Program 
Manager: 
Gilead Medical Monitor: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching 
From a Regimen of Two Nucleos(t)ide Reverse Transcriptase 
Inhibitors (NRTI) plus a Third Agent to a Fixed Dose Combination 
(FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF), in Virologically-Suppressed, HIV-1 Infected 
African American Paiiicipants 
Gilead Sciences, Inc. 
333 Lakeside drive 
Foster City, CA 94404 
125,589 
Not Applicable 
Not Available 
HIV-1 Infection 
GS-US-380-4580 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Original: 
IPIPD 
IPIPD 
IPIPD 
IPIPD 
IPIPD 
IPIPD 
27 June 2018 
CONFIDENTIALITY STATEMENT 
The info1mation contained in this document, paiiiculai·ly unpublished data, is the prope1iy or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The infonnation is only to be used by you in 
connection with authorized clinical studies of the investigational dmg described in the protocol. 
You will not disclose any of the info1mation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessaiy to obtain infonned consent from those 
persons to whom the dmg may be administered. 


BIFITAF 
Protocol GS-US-380-4580 
Gilead Sciences, Inc. 
Final 
Original 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ 5 
LIST OF IN-TEXT FIGURES ...................................................................................................................................... 5 
PROTOCOL SYNOPSIS .............................................................................................................................................. 6 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 11 
1. 
INTRODUCTION .............................................................................................................................................. 14 
1.1. 
Backgrowid ............................................................................................................................................ 14 
1.2. 
Bictegravir (GS-9883, B) ....................................................................................................................... 15 
1. 2 .1. 
General Infonnation ............................................................................................................. 15 
1.2.2. 
Preclinical Phannacology and Toxicology ........................................................................... 15 
1.2.3. 
Clinical Trials ofBictegravir ................................................................................................ 16 
1.3. 
Rationale for This Study ........................................................................................................................ 22 
1.4. 
Risk/Benefit Assessment for the Study .................................................................................................. 22 
1.5. 
Rationale for Dose Selection .................................................................................................................. 23 
1.6. 
Compliance ............................................................................................................................................ 23 
2. 
OBJECTIVES ..................................................................................................................................................... 24 
3. 
STUDY DESIGN ................................................................................................................................................ 25 
3 .1. 
Endpoints ............................................................................................................................................... 25 
3.2. 
Study Design .......................................................................................................................................... 25 
3.3. 
Study Treatments ................................................................................................................................... 25 
3.4. 
Duration of Treatment and End of Study ............................................................................................... 25 
3.5. 
Biomarker Testin .................................................................................................................................. 26 
3.5.1. 
. .............................................................. 26 
3.5.2. 
.. .......................................... 26 
4. 
PARTICIPANT POPULATION ......................................................................................................................... 28 
4.1. 
Number of Participants and Participant Selection .................................................................................. 28 
4.2. 
Inclusion Criteria .................................................................................................................................... 28 
4.3. 
Exclusion Criteria ................................................................................................................................... 30 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS ........................................................................................... 32 
5.1. 
Randomization ....................................................................................................................................... 32 
5.2. 
Description and Handling of B/F/T AF ................................................................................................... 32 
5.2.1. 
Foimulation .......................................................................................................................... 32 
5.2.2. 
Packaging and Labeling ....................................................................................................... 33 
5.2.3. 
Storage and Handling ........................................................................................................... 33 
5.3. 
Dosage and Ad1ninist1·ation ofB/F/TAF ................................................................................................ 33 
5 .4. 
Prior and Concomitant Medications ....................................................................................................... 34 
5.5. 
Accowitability for B/F/TAF ................................................................................................................... 35 
5.5.1. 
Investigational Medicinal Product Retuin or Disposal. ....................................................... 35 
6. 
STUDY PROCEDURES ...................................................................................................................... .............. 36 
6.1. 
Participant Enrollment and Treatment Assignment.. .............................................................................. 36 
6.2. 
Preti·eatinent Assessments ...................................................................................................................... 36 
6.2.1. 
Screening Visit ..................................................................................................................... 36 
6.3. 
Randomization ....................................................................................................................................... 37 
6.4. 
Day 1 Assessments ................................................................................................................................. 37 
CONFIDENTIAL 
Page2 
27 Jwie 2018 


B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 3
27 June 2018
6.5.
Treatment Assessments (Week 4-48).....................................................................................................38
6.6.
Treatment Assessments (Post Week 48) ................................................................................................39
6.6.1.
Post Week 48 Assessments ..................................................................................................39
6.7.
Post-Treatment Assessments..................................................................................................................39
6.7.1.
Early Study Drug Discontinuation Assessments..................................................................39
6.7.2.
30-Day Follow-up Visit........................................................................................................40
6.8.
Criteria for Discontinuation of Study Treatment....................................................................................41
6.9.
Clinical Laboratory Assessments ...........................................................................................................41
6.9.1.
Blood Samples......................................................................................................................41
6.9.2.
Urine Samples ......................................................................................................................43
6.9.3.
Blood Storage Samples ........................................................................................................43
6.10.
Assessments for Premature Discontinuation from Study.......................................................................44
6.11.
End of Study...........................................................................................................................................44
6.12.
Post Study Care......................................................................................................................................44
6.13.
Virologic Failure....................................................................................................................................44
6.13.1.
Management of Virologic Rebound .....................................................................................44
6.13.2.
Participants with HIV-1 RNA ≥50 copies/mL at Study Drug 
Discontinuation, Week 24, or Week 48................................................................................46
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................47
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................47
7.1.1.
Adverse Events.....................................................................................................................47
7.1.2.
Serious Adverse Events........................................................................................................47
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................48
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................48
7.2.2.
Assessment of Severity ........................................................................................................49
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................49
7.3.1.
Adverse Events.....................................................................................................................49
7.3.2.
Serious Adverse Events........................................................................................................49
7.4.
Gilead Reporting Requirements.............................................................................................................50
7.5.
Clinical Laboratory Abnormalities.........................................................................................................51
7.6.
Toxicity Management ............................................................................................................................51
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................52
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................52
7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................52
7.6.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................52
7.6.5.
Management of Potential Nephrotoxicity.............................................................................54
7.7.
Special Situations Reports......................................................................................................................55
7.7.1.
Definitions of Special Situations..........................................................................................55
7.7.2.
Instructions for Reporting Special Situations.......................................................................56
8.
STATISTICAL CONSIDERATIONS................................................................................................................58
8.1.
Analysis Objectives and Endpoints........................................................................................................58
8.1.1.
Analysis Objectives..............................................................................................................58
8.1.2.
Primary Endpoint .................................................................................................................58
8.1.3.
Secondary Endpoint .............................................................................................................58
8.2.
Analysis Conventions.............................................................................................................................59
8.2.1.
Analysis Sets ........................................................................................................................59
8.3.
Data Handling Conventions ...................................................................................................................60
8.4.
Demographic Data and Baseline Characteristics ...................................................................................60
8.5.
Efficacy Analysis ...................................................................................................................................60
8.5.1.
Primary Analysis..................................................................................................................60


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8.5.2.
Secondary Analyses .............................................................................................................62
8.6.
Safety Analysis.......................................................................................................................................62
8.6.1.
Extent of Exposure...............................................................................................................62
8.6.2.
Adverse Events.....................................................................................................................62
8.6.3.
Laboratory Evaluations ........................................................................................................63
8.6.4.
Other Safety Evaluations......................................................................................................63
8.7.
Patient Reported Outcomes (PRO).........................................................................................................63
8.8.
Sample Size............................................................................................................................................64
8.9.
Analysis Schedule ..................................................................................................................................64
9.
RESPONSIBILITIES..........................................................................................................................................65
9.1.
Investigator Responsibilities ..................................................................................................................65
9.1.1.
Good Clinical Practice..........................................................................................................65
9.1.2.
Institutional Review Board (IRB) ........................................................................................65
9.1.3.
Informed Consent.................................................................................................................65
9.1.4.
Confidentiality......................................................................................................................66
9.1.5.
Study Files and Retention of Records ..................................................................................66
9.1.6.
Case Report Forms...............................................................................................................67
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................68
9.1.8.
Inspections............................................................................................................................68
9.1.9.
Protocol Compliance............................................................................................................68
9.2.
Sponsor Responsibilities ........................................................................................................................69
9.2.1.
Protocol Modifications.........................................................................................................69
9.2.2.
Study Report and Publications .............................................................................................69
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................69
9.3.1.
Payment Reporting...............................................................................................................69
9.3.2.
Access to Information for Monitoring..................................................................................70
9.3.3.
Access to Information for Auditing or Inspections ..............................................................70
9.3.4.
Study Discontinuation..........................................................................................................70
10.
REFERENCES ...................................................................................................................................................71
11.
APPENDICES ....................................................................................................................................................75
Appendix 1.
Investigator Signature Page....................................................................................................76
Appendix 2.
Study Procedures Table..........................................................................................................77
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................80
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............81
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................103
Appendix 6.
Pregnancy Precautions, Definition for Persons of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................105


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LIST OF IN-TEXT TABLES
Table 1-1.
Pooled Virologic Outcomes of Studies 1489 and 1490 at Week 48 in 
Treatment-Naïve Patientsa......................................................................................................19
Table 1-2.
Virologic Outcomes of Studies 1844 and 1878 at Week 48a..................................................21
Table 5-1.
Prior and Concomitant Medications.......................................................................................34
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).......................................................................................17
Figure 3-1.
Study Schema.........................................................................................................................26
Figure 6-1.
Virologic Rebound Schema....................................................................................................45


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside drive
Foster City, CA 94404
Study Title: 
A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching
From a Regimen of Two Nucleos(t)ide Reverse Transcriptase 
Inhibitors (NRTI) plus a Third Agent to a Fixed Dose Combination 
(FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide
(B/F/TAF), in Virologically-Suppressed, HIV-1 Infected 
African American Participants
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125,589
NA
TBD
Study Centers 
Planned:
Multiple centers in the United States
Objectives:
The primary objective of this study is:

To evaluate the efficacy of switching from a regimen of 2 NRTIs 
and a third agent to a fixed dose combination (FDC) of 
bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus 
continuing their baseline regimen in HIV-1 infected, virologically 
suppressed African American participants as determined by the 
proportion of participants with HIV-1 RNA ≥50 copies/mL at 
Week 24
The secondary objectives of this study are:

To evaluate the efficacy of switching to a FDC of B/F/TAF from 
a regimen of 2 NRTIs and a third agent as determined by the 
proportion of participants with HIV-1 RNA ≥50 copies/mL at 
Week 48

To evaluate the efficacy, safety, and tolerability of switching to 
FDC of B/F/TAF from a regimen of 2 NRTIs and a third agent in 
HIV-1 infected, virologically suppressed African American 
participants through Week 48 


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Study Design:
Randomized, open-label, multicenter, active-controlled study of 
HIV-1 infected, virologically suppressed African American 
participants.  
Participants who provide written consent and meet all eligibility 
criteria will be randomized in a 2:1 ratio to one of the following 
2 treatment groups:
Treatment Group 1 (n=320): FDC of B/F/TAF (50 mg/ 200 mg/
25 mg) administered orally, once daily (QD), without regard to food.
Treatment Group 2 (n=160): Stay on baseline regimen (SBR) 
consisting of 2 NRTIs and a third agent (each taken as prescribed) 
from Day 1 until Week 24, with a delayed switch to a FDC of 
B/F/TAF (50 mg/200 mg/25 mg) administered orally, QD, without 
regard to food at Week 24.
Randomization will be stratified by the baseline 3rd agent ARV class 
at entry (integrase strand transfer inhibitor (INSTI), non-nucleoside 
reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI) or 
CCR5 antagonist).
Study duration will be at least 48 weeks in this study.
Number of 
Participants Planned:
Approximately 480 participants
Target Population:
HIV-1 infected adult participants that self-describe as Black, 
African American, or mixed race, including Black, who are 
virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable 
regimen of two NRTIs and a 3rd agent for ≥6 months prior to 
screening
Duration of 
Treatment:
After screening, eligible participants will be treated for at least 
48 weeks. Following the Screening and Day 1 visits, participants will 
be required to return for study visits at Weeks 4, 12, 24, 36, and 48. 
Participants randomized to SBR will have, after their delayed switch,
an additional visit at Week 28. 
Participants who complete the study through the Week 48 visit and 
wish to continue on FDC of B/F/TAF, will be given the option to 
receive FDC of B/F/TAF for up to an additional 24 weeks or until 
they have access to FDC of B/F/TAF, whichever occurs first, and will 
attend study visits every 12 weeks followed by a 30-Day Follow-Up 
Visit. Participants who complete the study through the Week 48 Visit 
and do not continue their participation in the study, will be required to 
return to the clinic 30 days after their Week 48 Visit for a 30-Day 
Follow-Up Visit.


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Diagnosis and Main 
Eligibility Criteria:
Participants must meet all of the following inclusion criteria to be 
eligible to participate in the study. Eligible participants with chronic 
hepatitis C virus (HCV) infection are permitted to enroll. In addition, 
eligible participants with chronic hepatitis B virus (HBV) infection 
are permitted to enroll if their baseline regimen contains either TAF 
or TDF.
Medically stable HIV-1 infected participants who meet the following
criteria:

Self-describes as Black, African American, or mixed race, 
including Black

Currently receiving an ARV regimen other than FDC of B/F/TAF 
that consists of any two NRTIs + allowed 3rd agent for ≥6 months
Allowed 3rd agents include any FDA-approved INSTI, with 
the exception of bictegravir, any FDA-approved NNRTI with 
the exception of etravirine, PI or the CCR5 antagonist, 
maraviroc.
If the baseline 3rd agent is dolutegravir, dosing other than 
50 mg once daily is excluded.
Baseline regimens containing investigational drugs or 
> 2 classes of ARVs are not permitted, with the exception of 
the pharmacologic enhancers cobicistat (taken with 
elvitegravir or a PI), or ritonavir (taken with a PI).

Have no documented or suspected resistance to INSTIs and no 
history of virologic failure on an INSTI containing regimen
(2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving 
<50 copies/mL while on an INSTI-containing regimen).

History of 1-2 thymidine analogue mutations (TAMs), M184V/I, 
and any other RT substitutions are allowed, with the following 
exceptions: History of 3 or more TAMs (M41L, D67N, K70R, 
L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or 
K65R/E/N in RT will be excluded.

Documented plasma HIV-1 RNA < 50 copies/mL during 
treatment with the baseline regimen for a minimum period of 
6 months and at least the last two HIV-1 RNA measurements 
prior to the Screening visit

HIV-1 RNA levels < 50 copies/mL at Screening 

Estimated glomerular filtration rate (eGFR) ≥50 mL/min 
according to the Cockcroft-Gault formula for creatinine clearance


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Study Procedures/
Frequency:
After Screening procedures, eligible participants will be randomized 
2:1 to Treatment Group 1 or Treatment Group 2 and treated for 
48 weeks.  Following the Day 1 visit, participants will be required to 
return for study visits at Weeks 4, 12, 24, 36, and 48. Participants
randomized to SBR will have an additional visit at Week 28. 
Laboratory analyses (chemistry, hematology, and urinalysis), HIV-1 
RNA, CD4+ cell count, assessment of adverse events and 
concomitant medications, and complete or symptom directed physical 
examinations will be performed at Screening, Day 1 and subsequent 
study visits. Whole blood for HIV-1 DNA archive testing will be 
collected at Day 1 for all participants and at Week 24 for all 
participants in Treatment Group 2.
Historical HIV-1 RNA genotypes 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:
Baseline regimen consisting of 2 NRTIs and an allowed 3rd agent 
taken as prescribed
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests, and tolerability of treatment 
regimens
Efficacy:
The primary efficacy endpoint is:

The proportion of participants with HIV-1 RNA ≥50 copies/mL 
at Week 24 as defined by the US FDA-defined snapshot algorithm 
The secondary efficacy endpoints are:

The proportion of participants with HIV-1 RNA ≥50 copies/mL 
at Week 48 as defined by the US FDA-defined snapshot algorithm

The proportion of participants with HIV-1 RNA < 50 copies/mL 
at Week 24 and 48 as defined by the US FDA-defined snapshot 
algorithm

The change from baseline in CD4+ cell count at Weeks 24 
and 48.


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Patient reported 
outcomes:
HIV Symptoms Distress Module Index will be administered at Day 1, 
Weeks 4, 24, 28 (SBR only) and 48. HIV Treatment Satisfaction 
Questionnaire Status (HIV-TSQs) will be administered at Day 1 and 
HIV Treatment Satisfaction Questionnaire Change (HIV-TSQc) will 
be administered at Week 4 and Week 24. Visual Analogue Scale 
(VAS) Adherence Questionnaire will be administered at Day 1 and at 
all visits up to (and including) Week 24 for participants in Treatment 
Group 2 (SBR) only. 
Statistical Methods:
The primary analysis will consist of a non-inferiority test of switching 
to FDC of B/F/TAF versus SBR, with respect to the proportion of 
participants with HIV-1 RNA ≥ 50 copies/mL at Week 24, as defined 
by the US FDA-defined snapshot algorithm. It will be concluded that 
FDC of B/F/TAF is non-inferior to SBR if the upper bound of the 
2-sided 95% confidence interval (CI) of the difference between 
treatment groups [B/F/TAF – SBR] in the percentage of participants
with HIV-1 RNA ≥ 50 copies/mL is less than 6% (i.e., a margin of 
6% is applied to non-inferiority assessment). The 2-sided 95% CIs 
will be constructed based on the exact method.
The proportion of participants with HIV-1 RNA < 50 copies/mL at 
Weeks 24 and 48, and the proportion of participants 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 at 
Week 24 will be constructed in the same manner as described for the 
primary efficacy endpoint.
The change from baseline in CD4+ cell count at Weeks 24 and 48 
will be summarized by treatment using descriptive statistics. The 
differences and the associated 95% CIs at Week 24 will be 
constructed using an Analysis of Variance (ANOVA) model, 
including treatment (B/F/TAF vs. SBR).  
Adverse events and clinical laboratory assessments will be 
summarized using descriptive statistics. 
Sample sizes of 320 in B/F/TAF FDC and 160 in SBR Group achieve 
approximately 89% power to detect a non-inferiority margin 
difference between the group proportions of 0.06 for HIV-1 RNA 
≥50 copies/mL at Week 24. The assumed reference group proportion 
is 0.04. The treatment group proportion is assumed to be 0.10 under 
the hypothesis of inferiority. The power is computed for the case 
when the actual treatment group difference is zero (treatment = 
reference). The test statistic used is the one-sided Score test 
(Farrington & Manning) with the significance level of 0.025. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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


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F/TAF 
emtricitabine/tenofovir alafenamide , Descovy
F/TDF
emtricitabine/tenofovir disoproxil fumarate, Truvada
FSH
follicle-stimulating hormone
FTC, F
emtricitabine, Emtriva
GCP
Good Clinical Practice (Guidelines)
GGT
gamma glutamyl transferase
GLSM
geometric least squares mean
GSI
Gilead Sciences, Inc.
GS-9883
bictegravir, B
GS-9883/F/TAF
GS-9883/emtricitabine/tenofovir alafenamide
HAART
highly active antiretroviral therapy
HBV
hepatitis B virus
HBcAb
hepatitis B core antibody
HBeAb
hepatitis B e-antibody
HBeAg
hepatitis B e-antigen
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDPE
high-density polyethylene
HCC
hepatocellular carcinoma
hERG
human Ether-à-go-go-Related Gene
HIV
human immunodeficiency virus
HIV Sx
HIV Symptoms  Distress Module
HIV
HIV Treatment Satisfaction Questionnaire
HIV-TSQs
HIV Treatment Satisfaction Questionnaire Status
HIV-TSQc
HIV Treatment Satisfaction Questionnaire Change
HLA
human leukocyte antigen
IB
investigator’s brochure
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IMP
Investigational Medicinal Product
IND
Investigational New Drug (Application)
INSTI
integrase strand-transfer inhibitors
IRB
institutional review board
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LDH
lactate dehydrogenase
LLN
lower limit of the normal range
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram


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MH
Mantel-Haenszel
min
Minute
mmHg
millimeters mercury
nM
nanoMolar
NNRTI
non-nucleoside reverse transcriptase inhibitor
NOEL
no observed effect level
OL
Open Label
NOAEL
no observed adverse effect level
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
PEP
post-exposure prophxylaxis
P-gp
P-glycoprotein
PI
protease inhibitor
PK
Pharmacokinetic
PT
preferred term 
PT
prothrombin time 
PTM
placebo-to-match
PVE
Pharmacovigilance and Epidemiology
QD
once daily 
RAL
Raltegravir
RNA
ribonucleic acid
SA
single agent
SAE
serious adverse event
SmPC
Summary of Product Characteristics
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide 
TAM
thymidine analogue mutation
TDF
tenofovir disoproxil fumarate, Viread
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase 
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 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}.
With the success of potent and well-tolerated antiretroviral therapy (ART) clinical attention has 
become more focused on the optimization of tolerability, long-term safety, and adherence of 
potent ART regimens {Costagliola 2014}.
For ART-naive HIV-infected patients, current treatment guidelines recommend that initial 
therapy for most people consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and 
an integrase strand-transfer inhibitor (INSTI) {Panel on Antiretroviral Guidelines for Adults and 
Adolescents 2018}. 
Bictegravir (BIC) (previously referred to as GS-9883) is a potent inhibitor of HIV-1 integrase.  
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 a fixed dose combination (FDC) tablet that is suitable for once daily use. This 
bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC provides a potent, convenient, 
tolerable, and practical regimen for the long term treatment of patients with HIV infection. 
B/F/TAF (Biktarvy®) was approved for the treatment of adults with HIV-1 infection by the FDA 
and is recommended in DHHS treatment guidelines.
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 FDC regimens as these have been shown to provide increased adherence 
and improved clinical and virologic outcomes {Sterrantino 2012}, {Aldir 2014}. Virologically 
suppressive ART has also contributed to a decline in HIV incidence in communities with high 
rates of virologic suppression, by reducing the transmissibility of infected individuals on 
treatment {Grabowski 2017}, {Kurth 2011}.


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In the US, not all communities have benefitted equally from advancements in HIV treatment. 
African Americans remain disproportionately affected by the epidemic. The prevalence of HIV 
is 8 fold higher in African Americans compared to whites and disparities in the risk for HIV 
acquisition are magnified in African American women whose risk is 16 times that of white 
women. The prognosis of living with HIV is also worse for African Americans for whom the risk 
of death from HIV disease is approximately nine times that of their white counterparts {Centers 
for Disease Control and Prevention (CDC) 2018}.
Racial inequities in access to medical care, medical insurance and in trust in the medical system 
are well documented in US healthcare, as are racial differences in clinical outcomes {Bailey 
2017}. Structural and interpersonal discrimination influence not only who has access to the 
medical system, but also determine the care they receive from physicians. Amongst persons 
living with HIV who are engaged in medical care, race, gender, and geographic differences 
influence physician prescribing patterns for ARVs and prophylactic medications {Lemly 2009}, 
{King 2008}, {Meditz 2011}, {Oramasionwu 2011}, {Oramasionwu 2012}. Since the US social 
factors and structural inequalities confounding health disparities are poorly measured, even large 
sophisticated studies may not rule out the possibility that biological differences contribute to 
these disparities in clinical outcomes {Ribaudo 2013}. This has complicated clinical decision 
making despite evidence that race and ethnic origin play no major role in outcomes associated 
with HAART where access to health care is more equitably distributed {Jensen-Fangel 2002}.
1.2.
Bictegravir (GS-9883, B)
1.2.1.
General Information
Bictegravir, a potent inhibitor of HIV-1 integrase is now approved for the treatment of HIV 
infection. 
1.2.2.
Preclinical Pharmacology and Toxicology
A core battery of safety pharmacology studies have been conducted with bictegravir. 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 bictegravir on all major 
organ systems. Please refer to the Investigator Brochure for details. 
1.2.2.1.
Pharmacology
Bictegravir is absorbed following oral administration with peak plasma concentrations occurring 
at 2-4 hours after administration. The multiple dose pharmacokinetics of BIC are dose 
proportional over the dose range of 25 to 100 mg Relative to fasting conditions, administration 
with either a moderate fat (~600 kcal, 27% fat) or high fat meal (~800 kcal, 50% fat) resulted in 
an increase in BIC AUC (24%). This modest change is not considered clinically meaningful and 
BIC can be administered with or without food.


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Bictegravir is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) 
and CYP3A. Bictegravir does not inhibit major human CYP isoforms or UGT1A1 at 
concentrations up to 25 M. Consequently, bictegravir 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. Bictegravir only modestly inhibits renal transporter OCT2 
(IC50 = 0.42 M). As a result, bictegravir is not expected to significantly interfere with the key 
transporter responsible for creatinine tubular elimination at the clinically projected Cmax. 
Additionally, the risk that bictegravir will affect the OCT2-mediated excretion of 
co-administered drugs is considered to be low.
BIC is primarily eliminated by hepatic metabolism. Renal excretion of intact BIC is a minor 
pathway (~1% of dose). The plasma BIC half-life was 17.3 hours.
1.2.2.2.
Toxicology
The nonclinical safety profile of BIC has been well characterized in genetic toxicology, safety
pharmacology (central nervous system [CNS], cardiovascular [CV], respiratory),
carcinogenicity, repeat-dose toxicity, and developmental toxicity studies. Bictegravir is not
genotoxic and did not have adverse effects on the CNS, CV, or respiratory systems. Bictegravir
demonstrated no carcinogenic potential in 6-month transgenic mouse or 2-year rat
carcinogenicity studies at exposures 15- or 31-fold higher, respectively, than the estimated
clinical exposure of BIC when administered as B/F/TAF (50/200/25 mg), hereafter referred to as
exposure margins. The no-observed-adverse-effects levels (NOAELs) in chronic 26-week rat and
39-week monkey toxicity studies were at exposure margins of 18-/46-fold (males/females) and
7.0-fold, respectively. Administration of BIC to cynomolgus monkeys at a high dose of
1000 mg/kg/day for 39 weeks resulted in microscopic liver changes that persisted through the
recovery phase; observed increased alanine aminotransferase (ALT) activities at 1000 mg/kg/day
exhibited reversibility. In offspring from rat and rabbit dams treated with BIC during pregnancy,
there were no toxicologically significant effects on developmental endpoints, and studies in
animals administered BIC have shown no evidence of teratogenicity or an effect on reproductive
function.
1.2.3.
Clinical Trials of Bictegravir
Please refer to the B/F/TAF Investigators’ Brochure for a list of clinical studies of BIC and 
B/F/TAF as well as further information about these studies.
1.2.3.1.
Phase 1 Safety and Pharmacokinetics
Study GS-US-141-1218 was a four part, first-in-human study.  Parts A and B were randomized, 
double-blind, placebo-controlled, single and multiple ascending dose studies of bictegravir in 
healthy male and female participants which helped establish the PK of BIC and evaluated the 
drug-drug interaction potential with F/TAF FDC. Please see the Investigator Brochure for 
additional details.


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1.2.3.2. 
Phase 1 b Proof of Concept 
The first HIV-1 positive human participants were dosed in the fasted state with 10 days of 
bictegravir in study (GS-US-141-1219). Four coho1ts of 5 pa1ticipants each were randomized 
4: 1 to receive bictegravir or placebo to match at doses of 5 mg, 25 mg, 50 mg, and 100 mg once 
daily for 10 days. 
There was no increase in the incidence of AEs with increasing doses ofbictegravir. 
The mean and 95% Cls of change from baseline in HIV-1 RNA (log10 copies/mL) ar·e presented 
in Figure 1-1. 
Figure 1-1. 
GS-9883 5 mg (n= ): 
GS-9883 25 mg (n=J: 
GS-9883 50 mg (n=J: 
GS-9883 100 mg (n=): 
Placebo (n=): 
GS-US-141-1219: Mean and 95% Cls of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set) 
• = GS-9883 5 mg 
0 = GS-9883 25 mg 
!:,. = GS-9883 50 mg 
= GS-9883 100 mg 
= Placebo 
BL 
2 
3 
4 
3 
3 
3 
3 
4 
3 
4 
3 
4 
4 
4 
4 
4 
4 
4 
3 
4 
4 
4 
4 
7 
8 
9 
10 
11 
Day 
3 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
4 
---
--
-----
----
-- --
14 
17 
3 
3 
4 
3 
4 
4 
4 
4 
4 
4 
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study drug. 
2 
-1 
-2 
-3 
-4 
Mean viral load change on Day 11 was -2.08 log10 in the 25 mg coho1t, -2.06 logio in the 50 mg 
coho1t, and -2.43 log10 in the 100 mg coho1t. Time weighted average change from baseline at 
Day 11 (DA VG 11) was -0.92 log10 in the 5 mg coho1t, -1.33 log10 in the 25 mg 
coho1t, -1.37 logioin the 50 mg cohort and-l.6l log1o in the 100 mg coho1t . Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 
1 participant (25.0%) in the bictegravir 50 mg group and 2 pa1ticipants (50%) in the bictegravir 
100 mg group. 
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1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing B+F/TAF versus 
dolutegravir (DTG)+F/TAF in HIV-infected, ART-naive adult participants.
Eligible participants were randomized in a 2:1 ratio to receive BIC 75 mg + F/TAF (200/25 mg) 
+ placebo-to-match DTG 50 mg once daily or DTG 50 mg + F/TAF (200/25 mg) + 
placebo-to-match bictegravir 75 mg once daily.
The primary efficacy endpoint was the proportion of participants 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 participants 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 (B+F/TAF – DTG+F/TAF) was 
greater than the prespecified −12% margin, B+F/TAF was determined to be noninferior to 
DTG+F/TAF.
HIV-1 RNA levels decreased rapidly in the first 4 weeks following initiation of study drug in 
both treatment groups. No resistance to any INSTIs, NRTIs, NNRTIs, or PIs was detected 
through Week 48 in the B+F/TAF group. Both B+F/TAF and DTG+F/TAF were generally well 
tolerated through 48 weeks of treatment with similar proportions of adverse events reported in 
each treatment group. Participants in both groups were switched to open-label B/F/TAF after all 
participants completed 48 Weeks of blinded treatment. 
1.2.3.4.
Summary of Phase 3 Studies
Treatment-Naïve Patients
In Study 1489, patients were randomized in a 1:1 ratio to receive either fixed-dose combination 
B/F/TAF (50/200/25 mg) (N = 314) or ABC/DTG/3TC (600/50/300 mg) (N = 315) once daily. 
In Study 1490, patients were randomized in a 1:1 ratio to receive either fixed-dose combination 
B/F/TAF (50/200/25 mg) (N = 320) or DTG + FTC/TAF (50+200/25 mg) (N = 325) once daily.
In Studies 1489 and 1490, the mean age was 35 years (range 18-77), 89% were male, 58% were
White, 33% were Black, and 3% were Asian. 24% percent of patients identified as
Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.4 log10 copies/mL
(range 1.3-6.6). The mean baseline CD4+ cell count was 460 cells/mm3 (range 0-1636) and 11%
had CD4+ cell counts less than 200 cells/mm3. 18% of patients had baseline viral loads greater
than 100,000 copies/mL. In both studies, patients were stratified by baseline HIV-1 RNA (less 
than or equal to 100,000 copies/mL, greater than 100,000 copies/mL to less than or equal to
400,000 copies/mL, or greater than 400,000 copies/mL), by CD4 count (less than 50 cells/μL,
50-199 cells/μL, or greater than or equal to 200 cells/μL), and by region (US or ex-US).
Treatment outcomes of Studies 1489 and 1490 through Week 48 are presented in Table 1-1.


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Table 1-1.
Pooled Virologic Outcomes of Studies 1489 and 1490 at Week 48 in 
Treatment-Naïve Patientsa
B/F/TAF FDC 
(N = 634)b
ABC/DTG/3TC
(N = 315)c
DTG + FTC/TAF
(N = 325)d
HIV-1RNA < 50 copies/mL
91%
93%
93%
Treatment Difference (95% CI) 
B/F/TAF FDC vs. Comparator
-
-2.1%
(-5.9% to 1.6%)
-1.9%
(-5.6% to 1.8%)
HIV-1 RNA ≥50 copies/mLe
3%
3%
1%
No Virologic Data at Week 48 Window
6%
4%
6%
Discontinued Study Drug Due to AE or Deathf
<1%
1%
1%
Discontinued Study Drug Due to Other Reasons 
and Last Available HIV-1 RNA < 50 copies/mLg
4%
3%
4%
Missing Data During Window but on Study Drug
2%
<1%
1%
a.
Week 48 window was between Day 295 and 378 (inclusive).
b.
Pooled from Study 1489 (N = 314) and Study 1490 (N = 320).
c.
Study 1489
d.
Study 1490
e.
Includes patients who had ≥ 50 copies/mL in the Week 48 window; patients who discontinued early due to lack or loss of 
efficacy; patients who discontinued for reasons other than an adverse event (AE), death or lack or loss of efficacy and at the 
time of discontinuation had a viral value of ≥ 50 copies/mL.
f.
Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.
g.
Includes patients who discontinued for reasons other than an AE, death or lack or loss of efficacy, e.g., withdrew consent, 
loss to follow-up, etc.
B/F/TAF FDC was noninferior in achieving HIV-1 RNA < 50 copies/mL at Week 48 when
compared to ABC/DTG/3TC and DTG+FTC/TAF, respectively. Treatment outcomes were
similar across subgroups by age, sex, race, baseline viral load, and baseline CD4+ cell count.
In Studies 1489 and 1490, the mean increase from baseline in CD4+ count at Week 48 was 207, 
229, and 201 cells per mm3 in the pooled B/F/TAF FDC, ABC/DTG/3TC, and DTG+FTC/TAF 
groups, respectively.
Bone Mineral Density:
In Study 1489, bone mineral density (BMD) change from baseline to Week 48 was assessed by
dual-energy X-ray absorptiometry (DXA). In patients who had both baseline and Week 48 hip
and lumbar spine BMD measurements (N = 257 and 267 in the B/F/TAF FDC group and
N = 270 and 274 in the ABC/DTG/3TC group, for hip and lumbar spine, respectively), mean
percentage changes in BMD were similar in the B/F/TAF FDC group compared to the
ABC/DTG/3TC group for hip (−0.8% vs. −1.0%) and lumbar spine (−0.8% vs.−0.6%).


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Virologically Suppressed Patients
In Study 1844, the efficacy and safety of switching from a regimen of DTG + ABC/3TC or
ABC/DTG/3TC to B/F/TAF FDC were evaluated in a randomized, double-blind study of
virologically-suppressed (HIV-1 RNA < 50 copies/mL) HIV-1 infected adults (N = 563).
Patients must have been stably suppressed (HIV-1 RNA < 50 copies/mL) on their baseline
regimen for at least 3 months prior to study entry. Patients were randomized in a 1:1 ratio to
either switch to B/F/TAF FDC at baseline (N = 282), or stay on their baseline antiretroviral
regimen (N = 281). Patients had a mean age of 45 years (range 20-71), 89% were male, 73%
were White, and 22% were Black. 17% of patients identified as Hispanic/Latino. The mean
baseline CD4+ cell count was 723 cells/mm3 (range 124-2444).
In Study 1878, the efficacy and safety of switching from either ABC/3TC or FTC/TDF
(200/300 mg) plus ATV or DRV (boosted by either COBI or RTV) to B/F/TAF FDC were
evaluated in a randomized, open-label study of virologically-suppressed HIV-1 infected adults
(N = 577). Patients must have been stably suppressed on their baseline regimen for at least
6 months and INSTI naïve prior to study entry. Patients were randomized in a 1:1 ratio to either
switch to B/F/TAF FDC (N = 290), or stay on their baseline antiretroviral regimen (N = 287).
Patients had a mean age of 46 years (range 20-79), 83% were male, 66% were White, and 26%
were Black. 19% of patients identified as Hispanic/Latino. The mean baseline CD4+ cell count
was 663 cells/mm3 (range 62-2582). Patients were stratified by prior treatment regimen. At
screening, 15% of patients were receiving ABC/3TC plus ATV or DRV (boosted by either COBI
or RTV) and 85% of patients were receiving FTC/TDF plus ATV or DRV (boosted by either
COBI or RTV).
Treatment outcomes of Studies 1844 and 1878 through Week 48 are presented in Table 1-2.


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Table 1-2.
Virologic Outcomes of Studies 1844 and 1878 at Week 48a
Study 1844
Study 1878
B/F/TAF 
FDC 
(N = 282)
ABC/DTG/3TC
(N = 281)
B/F/TAF 
FDC
(N = 290)
Baseline ATV- or 
DRV-based 
regimen
(N = 287)
HIV RNA < 50 copies/mL
94%
95%
92%
89%
Treatment Difference (95% CI)
-1.4% (-5.5% to 2.6%)
3.2% (-1.6% to 8.2%)
HIV-1 RNA ≥ 50 copies/mLb
1%
<1%
2%
2%
Treatment Difference (95% CI)
0.7% (-1.0% to 2.8%)
0.0% (-2.5% to 2.5%)
No Virologic Data at Week 48 Window
5%
5%
6%
9%
Discontinued Study Drug Due to AE or 
Death and Last Available HIV-1 RNA 
< 50 copies/mL
2%
1%
1%
1%
Discontinued Study Drug Due to Other 
Reasons and Last Available HIV-1 RNA 
<50 copies/mLc
2%
3%
3%
7%
Missing Data During Window but on Study 
Drug
2%
1%
2%
2%
a.
Week 48 window was between Day 295 and 378 (inclusive).
b.
Includes patients who had ≥ 50 copies/mL in the Week 48 window; patients who discontinued early due to lack or loss of
efficacy; patients who discontinued for reasons other than lack or loss of efficacy and at the time of discontinuation had a
viral value of ≥ 50 copies/mL.
c.
Includes patients who discontinued for reasons other than an AE, death or lack or loss of efficacy, e.g., withdrew consent
loss to follow-up, etc.
In Study 1844, at Week 48, switching to B/F/TAF FDC was noninferior to remaining on
ABC/DTG/3TC. The percentages of patients with HIV-1 RNA ≥50 copies/mL and who
maintained HIV-1 RNA < 50 copies/mL were similar between the B/F/TAF FDC and
ABC/DTG/3TC groups. The mean change from baseline in CD4+ count at Week 48 was
−31 cells per mm3 in patients who switched to B/F/TAF FDC and 4 cells per mm3 in patients
who stayed on ABC/DTG/3TC.
In Study 1878, at Week 48, switching to B/F/TAF FDC was noninferior to remaining on an
ATV- or DRV-based regimen. The percentages of patients with HIV-1 RNA ≥50 copies/mL and
who maintained HIV-1 RNA < 50 copies/mL were similar between the B/F/TAF FDC and ATV-
or DRV-based regimen groups. The mean change from baseline in CD4+ count at Week 48 was 
25 cells per mm3 in patients who switched to B/F/TAF FDC and 0 cells per mm3 in patients who 
stayed on their baseline regimen.


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Bone Mineral Density:
In Study 1844, BMD change from baseline to Week 48 was assessed by DXA. In patients who
had both baseline and Week 48 hip and lumbar spine BMD measurements (N = 229 and 233 in
the B/F/TAF FDC group and N = 242 and 244 in the ABC/DTG/3TC group, for hip and lumbar 
spine, respectively), mean percentage increases in BMD were similar in the B/F/TAF FDC group 
compared to the ABC/DTG/3TC group for hip (0.2% vs. 0.3%) and lumbar spine (0.7% 
vs.0.4%).
1.3.
Rationale for This Study
Despite the racial composition of the US HIV epidemic, African Americans have less access to 
and engagement with clinical studies of new antiretroviral therapy. Most phase 3 studies of 
INSTIs have only enrolled between 10 and 25% of participants who identified as Black or 
African American {Lennox 2009}, {Walmsley 2013}, {Arribas 2017}. The most recently FDA 
approved INSTI, BIC, included ~30-36% of participants who identified as Black or 
African Americans, a level of engagement that under-represents African Americans compared to 
the demographics of the US HIV epidemic {Gallant 2017}, {Sax 2017}. 
Despite progress, these studies have not overcome racial disparities in the distribution of access 
to medical research opportunities. The resulting subgroup analyses have limited precision, and 
comparisons between racial groups fail to adequately control for unmeasured social 
circumstances or structural systems of discrimination in America that may impact healthcare 
outcomes. As a result, there is a need for further study of B/F/TAF in African Americans 
infected with HIV-1.
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 
is a primary barrier to successful long-term treatment. {Maggiolo 2001}, {Felizarta 2004}, 
{Arribas 2004}, {Willig 2008}.
Regimen simplification of an established therapy may reduce pill burden and potentially enhance 
long-term safety and tolerability. B/F/TAF combines potent and sustained efficacy, favorable 
tolerability, minimal long-term toxicity, and practical, convenient dosing. This study will 
evaluate switching to B/F/TAF in African American participants who are virologically 
suppressed on their current regimen. The goal of this study is to assess whether switching to a 
single tablet regimen of B/F/TAF from a regimen of two NRTIs plus a third agent will provide 
comparable virologic control along with improved safety and tolerability.
1.4.
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 {Department of Health and Human Services (DHHS) 2018}.  The 
risk of class effects is considered to be low. Potential benefits may include provision of a new 


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ARV therapy which may have fewer side effects than alternative therapies resulting in improved 
adherence and long-term virologic suppression. 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 in African American patients. In phase 3 studies of 
B/F/TAF, the subgroup of participants self-identified as Black or African American had similar 
outcomes for efficacy and safety compared with the study population as a whole.  
The overall benefit-risk assessment for B/F/TAF is favorable at this time. 
1.5.
Rationale for Dose Selection
B/F/TAF
The B/F/TAF FDC containing B (50 mg), F (200 mg), and TAF (25 mg), has been approved by 
the US-FDA for use once daily for the treatment of human immunodeficiency virus type 1 
(HIV-1) infection in adults. B/F/TAF contains 25 mg of TAF, the approved and recommended 
dosage for the treatment of HBV infection with other ARVs for treatment of HIV/HBV 
coinfection {Gunthard 2016}, {Panel on Antiretroviral Guidelines for Adults and Adolescents 
2016}, {Terrault 2016}, {European Association for the Study of the Liver 2017}, {European 
AIDS Clinical Society (EACS) 2016}, and {Sarin 2016}.
1.6.
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 2 NRTIs and a third agent to a fixed 
dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)
versus continuing their baseline regimen in HIV-1 infected, virologically suppressed 
African American participants as determined by the proportion of participants with HIV-1 
RNA ≥50 copies/mL at Week 24
The secondary objectives of this study are:

To evaluate the efficacy of switching to a FDC of B/F/TAF from a regimen of 2 NRTIs and a 
third agent as determined by the proportion of participants with HIV-1 RNA ≥50 copies/mL 
at Week 48

To evaluate the efficacy, safety, and tolerability of switching to FDC of B/F/TAF from a
regimen of 2 NRTIs and a third agent in HIV-1 infected, virologically suppressed 
African American participants through Week 48 


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3.
STUDY DESIGN
3.1.
Endpoints
The primary efficacy endpoint is:

The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 as defined by 
the US FDA-defined snapshot algorithm 
The secondary efficacy endpoints are:

The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as defined by 
the US FDA-defined snapshot algorithm

The proportion of participants with HIV-1 RNA < 50 copies/mL at Week 24 and 48 as 
defined by the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Weeks 24 and 48.
3.2.
Study Design
This protocol describes a randomized, open-label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to a FDC of B/F/TAF versus continuing a regimen 
of 2 NRTIs and a third agent in HIV-1 infected African American participants who are
virologically suppressed (HIV-1 RNA < 50 copies/mL) for ≥6 months.
3.3.
Study Treatments
Participants who provide written consent and meet all eligibility criteria will be randomized in a 
2:1 ratio to one of the following 2 treatment groups:
Treatment Group 1 (n=320): FDC of B/F/TAF (50 mg/200 mg/25 mg) administered orally, 
once daily (QD), without regard to food.
Treatment Group 2 (n=160): Stay on baseline regimen (SBR) consisting of 2 NRTIs and a 
third agent (each taken as prescribed) from Day 1 until Week 24, with a delayed switch to a FDC 
of B/F/TAF (50 mg/200 mg/25 mg) administered orally, QD, without regard to food at Week 24.
Randomization will be stratified as defined in Section 5.1.
3.4.
Duration of Treatment and End of Study
Participants who meet eligibility criteria will be treated for at least 48 weeks. Following the 
Screening and Day 1 visits, participants will be required to return for study visits at Weeks 4, 12, 
24, 36, and 48. Participants randomized to SBR will have, after their delayed switch, an 
additional visit at Week 28. 


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Paiiicipants who complete the study through the Week 48 visit and wish to continue on 
B/FffAF, will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks 
or until they have access to FDC of B/FffAF, whichever occurs first, and will attend study visits 
every 12 weeks followed by a 30-Day Follow-Up Visit. Paiticipants who complete the study 
through the Week 48 Visit and do not continue their paiiicipation in the study, will be required to 
return to the clinic 30 days after their Week 48 Visit for a 30-Day Follow-Up Visit. 
Figure 3-1. 
Screening 
:S 30 days prior 
to Dar 1 
Study Schema 
Day 1' 
Trealment G ro u,> 1: (N=320) 
B/F/ JAF FDC QO 
Tt·eatment Group 2: (N= I60) 
2 l:s'RTis + 3rd agent QO 
Weck 24 " 
Primary £odpo1nt 
Weck 48' 
Weck 72 
s~cona.ry £11dpolnc 
"Y-28,7:f-~ 
zzz'ff'/;Zt/~z 
·I 
½ 
~&/ 
§: 
go ~ 
D'elav<'d,Swlkh,fu:, :.. 
¥fl'l'~FDO QD 
8' 
a 
Following the Day 1 visit, participants will be required to retum for study visits at Weeks 4 and 12, and then eve1y 12 weeks 
through the Week 48 visit. TI1e Primary Endpoint will be assessed when the last enrolled pa1t icipant completes the Week 24 
visit. 
b 
At Week 24, pa1t icipants randomized to continue on their baseline regimen who complete 24 weeks of treatment on their 
baseline regimen will switch to FDC ofB/F/TAF. 
c 
At Week 48, pa1t icipants who wish to continue on FDC of B/F/TAF will be given the option to receive FDC ofB/F/TAF for 
up to an additional 24 weeks or until they have access to FDC of B/F/TAF, whichever occurs first, and attend study visits 
eve1y 12 weeks followed by a 30-Day Follow-up Visit. 
3.5. 
Bio marker Testing 
3.5.1. 
3.5.2. 
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4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection
Approximately 480 participants who meet the eligibility criteria will be enrolled. Eligible 
participants with chronic hepatitis C virus (HCV) infection are permitted to enroll. In addition, 
eligible participants with chronic hepatitis B virus (HBV) infection are permitted to enroll if their 
baseline regimen contains either TAF or TDF.
4.2.
Inclusion Criteria
Participants 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) Self-describes as Black, African American, or mixed race including Black
4) Currently receiving an ARV regimen other than FDC of B/F/TAF that consists of any two 
NRTIs + allowed 3rd agent for ≥6 months
a) Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, 
any FDA-approved NNRTI with the exception of etravirine, and FDA-approved PI or the 
CCR5 antagonist, maraviroc
b) If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded
c) Baseline regimens containing investigational drugs or > 2 classes of ARVs are not 
permitted, with the exception of the pharmacologic enhancers cobicistat (taken with 
elvitegravir or a PI), or ritonavir (taken with a PI)
5) Have no documented or suspected resistance to INSTIs and no history of virologic failure on 
an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving 
<50 copies/mL while on an INSTI-containing regimen)
6) History of 1-2 thymidine analogue mutations (TAMs; M41L, D67N, K70R, L210W, 
T215F/Y, and K219Q/E/N/R), M184V/I, and RT substitutions not described in exclusion 
criterion 1 are allowed. Any NNRTI or PI resistance mutations are allowed.
7) Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen 
for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior 
to the Screening visit
a) Must include one or more HIV-1RNA tests within the 12 months prior to screening


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8) Willingness to wait approximately 6 months before switching from current ARVs
9) HIV-1 RNA levels < 50 copies/mL at Screening
10) Estimated glomerular filtration rate (eGFR) 50 mL/min according to the Cockcroft-Gault 
(C-G) formula  {Cockcroft 1976}:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
         (140 – age in years) (wt in kg)         CLcr (mL/sec)
            72 (serum creatinine in umol/L) 0.6786  
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
         (140 – age in years) (wt in kg)          0.85  CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
11) Normal ECG (or if abnormal, determined by the investigator not to be clinically significant)
12) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
13) Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin
14) 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))
15) Serum amylase ≤ 5 × ULN (participants with serum amylase > 5 × ULN will remain eligible 
if serum lipase is ≤5 × ULN)
16) Persons of childbearing potential (as defined in Appendix 6) must have a negative serum 
pregnancy test at screening and clinic admission.
17) Male participants and persons of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol specified method(s) of contraception as described in 
Appendix 6
18) Participants must agree to refrain from egg donation from first dose of FDC of B/F/TAF and 
throughout the study period as described in Appendix 6.
19) Life expectancy ≥ 1 year


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4.3.
Exclusion Criteria
Participants who meet any of the following exclusion criteria are not to be enrolled in this study.
1) History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), 
T69-insertions, or K65R/E/N in RT will be excluded
2) No desire to switch from current ARVs
3) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
4) Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal 
bleeding)
5) 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)
6) Malignancy within 5 years of screening other than cutaneous Kaposi’s sarcoma, completely 
resected non-melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous 
squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus 
(AIN 3). A prior malignancy treated with curative therapy and for which there has been no 
evidence of disease for at least five years prior to screening is allowed.
7) Current alcohol or substance use judged by the Investigator to potentially interfere with 
participant study compliance
8) Active, serious infections (other than HIV-1 infection) requiring antibiotic or antifungal 
therapy within 30 days prior to Day 1
9) Participation in any other clinical trial, including observational studies,  without prior 
approval from the sponsor is prohibited while participating in this trial
10) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the participant unsuitable for the study or unable to comply with the dosing 
requirements
11) Known hypersensitivity to FDC of B/F/TAF tablets, their metabolites, or formulation 
excipient
12) Females who are pregnant (as confirmed by positive serum pregnancy test)
13) Females who are breastfeeding
14) Participants receiving ongoing therapy with any of the following medications in the table 
below, including drugs not to be used with FDC of B/F/TAF


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


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Participants will be assigned a screening number in the Interactive Web Response System 
(IWRS) at the time of consent. Randomization and Day 1 visits cannot occur until 
participant 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 participant using IWRS. Once a participant number has been 
assigned to a participant, it will not be reassigned to any other participant. The participant
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 participant eligibility 
has been confirmed.
Participants will be randomized in a 2:1 ratio to Treatment Group 1 or Treatment Group 2.
Treatment Group 1 (n=320): FDC of B/F/TAF (50 mg/200 mg/25 mg) administered orally, 
once daily (QD), without regard to food.
Treatment Group 2 (n=160): Stay on baseline regimen (SBR) consisting of 2 NRTIs and a 
third agent (each taken as prescribed) from Day 1 until Week 24, with a delayed switch to a FDC 
of B/F/TAF (50 mg/200 mg/25 mg) administered orally, QD, without regard to food at Week 24.
The IWRS will assign study drug bottle numbers of open label FDC of B/F/TAF at each study 
visit for participants in Treatment Group 1 and at each study visit starting at Week 24 for 
participants in Treatment Group 2.
Randomization will be stratified by the baseline 3rd agent ARV class at entry (integrase strand 
transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease 
inhibitor (PI) or CCR5 antagonist).
5.2.
Description and Handling of B/F/TAF
5.2.1.
Formulation
5.2.1.1.
B/F/TAF (50/200/25 mg)
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.


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5.2.2.
Packaging and Labeling
5.2.2.1.
B/F/TAF (50/200/25 mg) 
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.
B/F/TAF 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
B/F/TAF 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 participants, all bottles of B/F/TAF should be stored in a securely locked 
area, accessible only to authorized site personnel.
To ensure the stability and proper identification, B/F/TAF should not be stored in a container 
other than the container in which it was 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
B/F/TAF FDC tablets will be provided by Gilead Sciences. 
Treatment Group 1 (n=320): FDC of B/F/TAF (50 mg/200 mg/25 mg) administered orally, 
once daily (QD), without regard to food.
Treatment Group 2 (n=160): Stay on baseline regimen (SBR) consisting of 2 NRTIs and a 
third agent (each taken as prescribed) from Day 1 until Week 24, with a delayed switch to a FDC 
of B/F/TAF (50 mg/200 mg/25 mg) administered orally, QD, without regard to food at Week 24.
After Week 48, all participants who wish to continue on B/F/TAF, will receive B/F/TAF once 
daily for up to an additional 24 weeks. 
Participants will be instructed to bring all study medication in the original container to each 
clinic visit for drug accountability.  The Investigator will be responsible for maintaining accurate 
records for all B/F/TAF dispensed and tablets returned. The inventory and dispensing logs must 
be available for inspection by the study monitor. Study medication supplies, including partially 
used or empty bottles, must be accounted for by the study monitor prior to destruction or return. 


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5.4.
Prior and Concomitant Medications
Treatment Group 1 (B/F/TAF) and Treatment Group 2 (SBR) After Switch to B/F/TAF at 
Week 24
The use of medications for the treatment of HIV, other than B/F/TAF, is prohibited.
Medications listed in the following table and use of herbal/natural supplements are excluded or 
should be used with caution while participants are participating in the study.  
Table 5-1.
Prior and Concomitant Medications
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With 
Caution
Medications or oral
supplements containing
polyvalent cations (e.g.,
Mg, Al, Ca, Fe):
Calcium or iron
supplements
Cation-containing antacids
or laxatives
Buffered medications
Antacids containing Al/Mg or Calcium:
B/F/TAF can be taken under fasting conditions 2 
hours before antacids containing Al/Mg or 
calcium.
Routine administration of B/F/TAF
simultaneously with, or 2 hours after, antacids 
containing Al/Mg or calcium is not
recommended.
Supplements containing Calcium or Iron:
B/F/TAF and supplements containing calcium or 
iron can be taken together with food. Routine 
administration of B/F/TAF under fasting 
conditions simultaneously with, or 2 hours after, 
supplements containing calcium or iron is not 
recommended.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine, Rifabutin
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
Hypoglycemic agent
Metformin:
Refer to the prescribing information of
metformin for assessing the benefit and risk of 
concomitant use of BIKTARVY and metformin.
Herbal/Natural 
Supplements
St. John’s Wort
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study. 
In jurisdictions in which B/F/TAF has been approved, consult the local prescribing information 
for B/F/TAF dose recommendations with concomitant medications. 


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Should participants have a need to initiate treatment with any excluded concomitant medication, 
the Gilead Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead as soon as he/she is aware of the use of the excluded medication.
Treatment Group 2 (SBR) Prior to Week 24
Investigators should refer to the current product/package inserts of the antiretroviral medications 
for contraindications and dose recommendations with concomitant medications related to their 
use.
5.5.
Accountability for B/F/TAF
The investigator is responsible for ensuring adequate accountability of all used and unused 
B/F/TAF. This includes acknowledgement of receipt of each shipment of B/F/TAF (quantity and 
condition). All used and unused B/F/TAF dispensed to participants must be returned to the site.
B/F/TAF accountability records will be provided to each study site to:

Record the date received and quantity of B/F/TAF kits

Record the date, participant number, participant initials, the B/F/TAF kit number dispensed

Record the date, quantity of used and unused B/F/TAF returned, along with the initials of the 
person recording the information.
5.5.1.
Investigational Medicinal Product Return or Disposal
Return and disposal of B/F/TAF 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 participant 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.
Participant Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that participants are eligible for study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Participants 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 demographic information, including gender at birth, sexual orientation, and gender 
identity

Obtain screening number in IWRS

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 6.9.1 and 6.9.2

Review concomitant medications

Record any SAEs and all AEs related to protocol mandated procedures occurring after 
signing of the consent form 


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Participants 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. Participants randomized to
Treatment Group 1 must continue to take their prior treatment regimen up until the day before 
their scheduled Day 1 visit. Participants randomized to Treatment Group 2 will continue to take 
their prior treatment regimen until they switch to FDC of B/F/TAF at Week 24.
From the time of obtaining informed consent through the first administration of study treatment,
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.
6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the participant using the Interactive Web Response System (IWRS). 
Once a participant number has been assigned to a participant, it will not be reassigned to any 
other participant. The participant 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 participant eligibility has been confirmed.
6.4.
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. Participants in Treatment Group 
1 must complete all study procedures before being administered FDC of B/F/TAF:

HIV Symptoms Distress Module Index and HIV Treatment Satisfaction Status (HIV-TSQs)
are to be completed by the participant. Visual Analogue Scale (VAS) Adherence 
Questionnaire is to be completed by participants in Treatment Group 2 only. Participant 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 6.9.1 and 6.9.2.

Dispense FDC of B/F/TAF for participants in Treatment Group 1


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
Observed first dose administration of FDC of B/F/TAF in Treatment Group 1 as described in 
Section 5.3. If the participant has taken their prior regimen on Day 1, prior to the Study Visit, 
they should be instructed to take their first dose of B/F/TAF the following day and dosing 
can be confirmed by phone.

Participants should be instructed to take FDC of B/F/TAF without regard to food. The 
participant should be counseled regarding the importance of adherence and taking their study 
medication at approximately the same time each day as directed by the Investigator.
6.5.
Treatment Assessments (Week 4-48)
The following evaluations are to be completed at Weeks 4, 12, 24, 36, and 48 unless otherwise 
specified. Participants randomized to SBR will have, after their delayed switch, an additional 
visit at Week 28. 
All study visits are to be completed within ± 6 days of the protocol specified visit date (based on 
the Day 1 visit), unless otherwise specified.  
Regularly scheduled evaluations will be made on all participants whether or not they continue to 
receive their study treatment regimen.

HIV Symptoms Distress Module Index is to be completed by the participant at Weeks 4, 24, 
28 (SBR only) and 48. HIV Treatment Satisfaction Change (HIV-TSQc) is to be completed 
at Weeks 4 and 24 only. VAS Adherence Questionnaire is to be completed by the participant
at Weeks 4, 12, and 24 in Treatment Group 2 only. Participant 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 6.9.1 and 6.9.2

Document dispensation and accountability for FDC of B/F/TAF dispensed for Treatment 
Group 1 for all visits and starting at Week 24 for Treatment Group 2.

Participants who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.13.1 and 6.13.2


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6.6.
Treatment Assessments (Post Week 48)
6.6.1.
Post Week 48 Assessments
At the Week 48 visit, participants who wish to continue on FDC of B/F/TAF, will be given the 
option to receive FDC of B/F/TAF for up to an additional 24 weeks or until they have access to 
FDC of B/F/TAF, whichever occurs first, and will attend study visits every 12 weeks followed 
by a 30-Day Follow-Up 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 (Week 72) (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 6.9.1 and 6.9.2

Document dispensation and accountability for FDC of B/F/TAF dispensed

Participants who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.13.1 and 6.13.2
6.7.
Post-Treatment Assessments
6.7.1.
Early Study Drug Discontinuation Assessments 
If the participant discontinues their study regimen prior to the Week 48 visit, the participant will 
be asked to return to the clinic within 72 hours of stopping study treatment for the Early Study 
Drug Discontinuation Visit. The participant will be asked to continue attending the scheduled 
study visits through the Week 48 visit. Participants on Treatment 2 (SBR) who discontinue their 
baseline regimen due to an AE prior to Week 24 will be asked to continue attending the 
scheduled study visits through the Week 24 visit.
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 treatment 
regimen, 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)


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
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Obtain blood and urine samples as described in Sections 6.9.1 and 6.9.2

Document study drug accountability for FDC of B/F/TAF dispensed
6.7.2.
30-Day Follow-up Visit
Participants who complete the study through the Week 48 Visit and do not continue their 
participation in the study, will be required to return to the clinic 30 days after their Week 48 Visit 
for a 30-Day Follow-Up Visit.
Participants who prematurely discontinue study treatment and refuse to continue in the study 
through the Week 48 visit will be asked to return to the clinic 30 days after the completion of the 
Early Study Drugs Discontinuation Visit for the 30-Day Follow-up Visit.
Those participants who prematurely discontinue study treatment 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, as long as the visit is > 30 days 
after last dose.
Participants who participate post Week 48 will complete a 30-Day Follow-up Visit 30 days after 
the last dose of B/F/TAF.
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 6.9.1 and 6.9.2
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with study treatment 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.  


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6.8.
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 participant’s 
best interest

Participant request to discontinue for any reason

Pregnancy during the study; refer to Appendix 6
Note: Female participants who become pregnant during the study will be discontinued from 
the study.

Development of active tuberculosis infection

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board (IRB)
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 
participant may resume study dosing at the discretion of the investigator.

Lack of efficacy

Participant noncompliance
6.9.
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.
6.9.1.
Blood Samples

Blood sample collection for the following laboratory analyses will be performed at every 
study visit, unless otherwise specified:
Serum pregnancy test (all female participants). If the test is positive, the participant will 
not be enrolled (Screening only). 
FSH test:  Required for female participants who are <54 years old and have stopped 
menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure 
(Screening only)


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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, and Cystatin C
■
Calcium, phosphorus, magnesium, amylase (reflex lipase testing is performed in 
participants with total amylase 1.5 ULN) (Screening and Day 1 only)
■
Cystatin C (Day 1 only)
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 24, 48, and 72.
■
If the participant has not fasted prior to the visit, the visit may proceed, but the 
participant 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 (Screening, Day 1, Weeks 24, 48, and 72, 30 Day 
Follow-up and ESDD)
Plasma HIV-1 RNA. Any subsequent HIV-1 genotype and phenotype testing will be 
performed as described in Sections 6.13.1 and 6.13.2. 
HBV blood panel (Screening and Week 48): 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 


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If positive HBcAb with negative HBsAg and negative HBsAb: reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). IfHBeAg is perfonned and found to 
be negative, reflex HBeAb 
-
Plasma HBV DNA for patients who are HBV co-infected (Day 1, Week 24, Week 48, 
and ESDD) 
HBV coinfection, for the pmposes of this study, is defined as any one of the following 
two criteria on or prior to Day 1: 
1. Positive HBsAg 
2. Negative HBsAg, negative HBsAb, positive HBcAb and quantifiable HBV DNA 
(HBV DNA ~20 IU/mL) 
-
HCV antibody (Ab) serology (Screening, Week 48, and Week 72). Paiiicipants who ai·e 
HCV Ab positive will have a HCV RNA test perfo1med. 
-
Mandato1y Whole blood for HIV-1 DNA ai·chive testing (Day 1 for all participants, 
and at Week 24 for participants randomized to SBR only) 
-
Plasma and sernm storage sample for safety, virology, or PK testing (Not collected at 
Screening and 30-day Follow-up Visits) 
6.9.2. 
Urine Samples 
Urine samples will be collected for the following laborato1y analyses will be perfo1med at eve1y 
study visit, unless othe1w ise specified: 
• 
Urinalysis 
• 
Urine pregnancy testing (Not collected at Screening) for persons of childbeai·ing potential. If 
result is positive, a sennn pregnancy test will be perfo1med. 
• 
Urine storage sample (Not collected at Screening and 30-day Follow-up Visits) 
6.9.3. 
Blood Storage Samples 
A po1iion of the blood and urine samples drawn at all visits ( except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its reseai·ch partners to help answer questions about 
B/F/TAF, about the disease and its associated conditions and/or to provide additional safety data. 
No human genetic testing will be perfo1med without expressed consent of study paiiicipants. At 
the conclusion of this study, these samples may be retained in storage by Gilead Sciences for a 
period up to 15 yeai·s. 
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6.10.
Assessments for Premature Discontinuation from Study
If a participant discontinues study dosing (for example, as a result of an AE), every attempt 
should be made to keep the participant in the study, and continue to perform the required study-
related follow-up and procedures (See Section 6.8, Criteria for Discontinuation of Study 
Treatment). If this is not possible or acceptable to the participant or investigator, the participant
may be withdrawn from the study.
6.11.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.12.
Post Study Care
After a participant has completed/terminated their participation in the study, long-term care for 
the participant will remain the responsibility of their primary treating physician.
6.13.
Virologic Failure
Virologic failure is defined as confirmed virologic rebound of HIV-1 RNA ≥50 copies/mL at 
2 consecutive visits or having HIV-1 RNA ≥50 copies/mL at study drug discontinuation,
Week 24, or Week 48.
6.13.1.
Management of Virologic Rebound
Participants 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
Following the virologic rebound, participants will be asked to return to the clinic for a scheduled 
or unscheduled blood draw (within 2 to 3 weeks after the date of the original test that resulted in
HIV-1 RNA ≥50 copies/mL). Participants with HIV-1 RNA values between 50-200 copies/mL 
should follow the algorithm in Figure 6-1. If virologic rebound is confirmed at the scheduled or 
unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the plasma sample from the 
confirmation visit will be the primary sample used for HIV-1 genotypic and phenotypic testing.  
After a participant’s first post-Day 1 resistance test, additional testing will be conducted on a 
case-by-case basis. Any participant may be discontinued at Investigator’s discretion or per local 
treatment guidelines.
If no resistance to study treatment is detected from the genotype or phenotype, the participant
may remain on study treatment and HIV-1 RNA should be analyzed at a new visit (within 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 treatment for each individual participant
and document this assessment in the on-site medical record.


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Participants 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 treatment for an individual participant must discuss with the Medical Monitor 
prior to study drug discontinuation.
For participants who are off study treatment 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 participants who meet the criteria for virologic 
rebound.
Figure 6-1.
Virologic Rebound Schema
a.
If the HIV-1 RNA is between 50 and 200 copies/mL, a reflex HIV-1 RNA repeat test will be conducted on stored plasma if 
available. If the repeat result is < 50 copies/mL, then no further action is required. If the repeat result is ≥ 50 copies/mL then 
proceed to the scheduled or unscheduled visit 2 – 3 weeks later.
I 
Screening 
Treatment Period 
30 Day Follow-Up I 
t 
At Any Post-Day 1 Visit, HIV-1 RNA 2::: 
50 copies/mL' 
t 
Return for scheduled or unscheduled visit (2-3 weeks after 
preceding visit) for HIV-1 RNA and collect sample for 
potential genotyping/phenotypingb 
i 
HIV-1 RNA 2::: 200 copies/mL 
Confirmed Viral Load Rebound 
Genotype and Phenotype Test Orderedc 
II 
+ 
+ 
If no new resistance to 
If new resistance to study 
study treatment detected, 
treatment detected, may 
may eontinue on study 
discontinue study 
treatment<! 
treatment and construct 
new ARV regimena 
/ 
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b.
If the HIV-1 RNA is < 50 copies/mL then no further action is required. If the HIV-1 RNA is between 50 and 200 copies/mL, 
a reflex HIV-1 RNA repeat test will be conducted on stored plasma if available. If the repeat result is < 50 copies/mL, then
no further action is required. If the repeat result is between 50 and 200 copies/mL this is protocol defined confirmed
virologic failure and the Medical Monitor should be consulted. If the repeat result is ≥ 200 copies/mL, then a Genotype and
Phenotype test will be ordered.
c.
If virologic rebound is confirmed and the last HIV-1 RNA is ≥ 200 copies/mL, the HIV-1 genotype and phenotype (reverse 
transcriptase, protease and integrase) will be analyzed. If the genotype and phenotype assay fails, Investigator reviews study 
treatment continuation/discontinuation options and discuss with the Medical Monitor prior to study treatment
discontinuation.   
d.
If no new resistance to study treatment is detected, HIV-1 RNA will be repeated 2 – 3 weeks later. Investigator reviews 
study treatment continuation/discontinuation options and discuss with the Medical Monitor prior to study treatment
discontinuation. The participant will remain in the study.
e.
A new ARV regimen may be configured, at the Investigator’s discretion and the participant will remain in the study.
6.13.2.
Participants with HIV-1 RNA ≥50 copies/mL at Study Drug 
Discontinuation, Week 24, or Week 48
Participants with HIV-1 RNA ≥50 copies/mL at study drug discontinuation, last visit, or last 
Week 24 or Week 48 result will be considered virologic failures. Participants with HIV-1 RNA 
≥50 copies/mL at Week 24 or Week 48 will be asked to return for an unscheduled visit within 
the visit window for a retest. 
Participants with HIV-1 RNA ≥200 copies/mL at study drug discontinuation, last visit, or 
Week 24 or Week 48 visit, will also have resistance testing conducted. 


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


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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 treatment 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.
7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occur after the participant 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.


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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 pa1ticipation has concluded 
and the event is deemed relevant to the use of IMP, he/she should promptly document and repo1t 
the event to Gilead PVE. 
Electronic Serious Adverse Event Reporting Process 
• 
Site personnel record all SAE data in the eCRF database and from there tr·ansmit the SAE 
infonnation 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 info1mation electr·onically, because the 
eCRF database cannot be accessed or is not available (including at study strut), record the 
SAE on the paper serious adverse event repo1t fo1m and submit by e-mail or fax within 
24 hours of the investigator's knowledge of the event to: 
Gilead PVE contact information: 
• 
As soon as it is possible to do so, any SAE repo1ted via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines. 
• If an SAE has been repo1ted via a paper fonn because the eCRF database has been locked, no 
finther action is necessa1y. 
• 
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
repo1ts. 
• 
Any medications necessmy for tr·eatinent of the SAE must be recorded onto the concomitant 
medication section of the pmticipant's eCRF and the event description section of the SAE 
fo1m 
• 
For fatal or life-threatening events, copies of hospital case repo1ts, autopsy repo1ts, and other 
documents m·e also to be submitted by e-mail or fax only when requested and applicable. 
Transmission of such documents should occur without personal pmticipant identification, 
maintaining the tr·aceability of a document to the pmticipant 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 
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worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB 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.
Clinical Laboratory Abnormalities
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).
Severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4). 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.
7.6.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 4). 

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results and before 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.


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7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.
7.6.2.
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.

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 
participant 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.
7.6.3.
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 participant managed according to local practice. The 
participant 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.
7.6.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management
For participants defined as having HBV infection, an On-Treatment ALT Flare is classified as:

Confirmed (within 3 days of receipt of initial laboratory results) serum ALT > 2 × Day 1 
value and >10 × ULN, with or without associated symptoms.


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7.6.4.1.
Management of ALT Flare in Participants Receiving Study Medication
If laboratory results indicate elevation of ALT 2 × Day 1 value and 10 × ULN, the following 
is recommended:

Schedule the participant 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 
participant will be performed. The assessment should include a physical examination and 
evaluation of the participant’s mental status.

If the ALT elevation is confirmed, request the central clinical laboratory to conduct reflex 
testing for PT/INR, plasma HBV DNA, HBV serology (HBsAg, HbsAb, HbeAg and 
HbeAb), HDV, HAV IgM, and HCV serology

Check the following laboratory parameters: serum ALT and AST, total bilirubin, INR, and 
serum albumin. Based on the results of the confirmatory tests, the following treatment 
modifications are recommended.
Elevated Liver Enzymes, Normal or Stable relative to Day 1 Liver Function Tests 
If ALT levels are elevated (ie, 2 × Day 1 and 10 × ULN) with normal or stable total bilirubin 
and INR relative to Day 1, the participant may remain on study medication and should be 
monitored weekly as long as ALT levels return to normal or Day 1 level.  During monitoring, if 
the ALT values remain persistently elevated, the Investigator should discuss with the Gilead 
Medical Monitor whether the study drug should be discontinued.  
Elevated Liver Enzymes, Elevated Liver Function Tests
If ALT values are elevated (ie, 2 × Day 1 and 10 × ULN), and total bilirubin is confirmed to 
be 2 x Day 1 value, and INR is 0.5 above Day 1, provided both are > ULN,  the investigator 
should consider discontinuing study medication (upon discussion with the Gilead Medical 
Monitor, unless the safety of the patient is of immediate concern).  The participant should be 
monitored weekly as long as ALT, total bilirubin, and INR values remain elevated or above 
Day 1 values.
During monitoring, if the ALT values and the liver function tests remain persistently elevated, 
the Investigator should discuss with the Gilead Medical Monitor whether the study drug should 
be discontinued.


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7.6.4.2.
Management of Exacerbation of Hepatitis B in Participants who have 
Discontinued Study Medication
If laboratory results indicate (1) an ALT elevation 2 × Day 1 and 10 × ULN alone OR 
associated with (2) abnormal laboratory parameters suggestive of worsening hepatic function 
(total bilirubin 2 × Day 1, INR 0.5 above Day 1, provided both are > ULN) and the participant is 
on no post-study therapy for HBV, the following is recommended:

Schedule the participant to return to the clinic as soon as possible (ideally no later than 
3 days after the initial laboratory values were drawn). During the visit, perform a clinical 
assessment of the participant.

Check the following laboratory parameters: serum ALT and AST, bilirubin, INR, and 
albumin.

If the ALT elevation is confirmed, request the clinical laboratory to conduct reflex testing for 
plasma HBV DNA, HBV serology (HBsAg,HbsAb, HbeAg, HbeAb), HDV, HAV IgM and 
HCV. If plasma HBV DNA is increasing, the investigator should consider immediate 
initiation of approved therapy.

The participant should be followed until laboratory parameters (ALT, total bilirubin, INR) 
return to normal or Day 1 up to a maximum of 6 months after the initial occurrence of the 
event.
7.6.5.
Management of Potential Nephrotoxicity
Estimated glomerular filtration rate (eGFR), according to the Cockcroft-Gault formula for 
creatinine clearance, will be followed post-baseline during the study. All participants with 
estimated eGFR < 50 mL/min must have serum creatinine measured again within 3 calendar days 
of receipt of results.
At the time of this repeat serum creatinine assessment, Cystatin C will also be measured and the 
eGFR by CKD-EPI (cystatin C) will be calculated and compared with the baseline 
measurement. 
Any participants who have an eGFR < 50 mL/min that also experience > 20% reduction in eGFR 
by CKD-EPI (cystatin C) from baseline or who have other clinical and/or laboratory evidence of 
acute renal failure will be discussed with the Medical Monitor and potentially discontinue from 
study drug.
For participants with eGFR < 50 mL/min who are not discontinued based on toxicity 
management procedures above and considered to have stable renal function per Principal 
Investigator and Medical Monitor, it is not mandatory to repeat eGFR assessments within 3 days.
Participants in Treatment Group 2 (SBR) should have dose adjustments made to their ARVs as 
clinically appropriate.


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CKD-EPI (cystatin C) formula adjusted for age and sex: 
eGFR (mL/min/1.73m2) = 133 x min(Scys/0.8,1)-0.499 × max(Scys/0.8,1)-1.328 ×
0.996Age [× 0.932 if female] 
Where Scys is serum cystatin C (mg/L), min (Scys/0.8,1) indicates the minimum of 
Scys/0.8 or 1, and max (Scys/0.8,1) indicates the maximum of Scys/0.8 or 1.
Once an individual participant has developed any of these renal changes and followed the 
management guidelines above, it is not necessary to have repeat evaluations if it is determined 
that it is safe for that participant to continue on treatment with standard follow-up visits as 
described in the protocol
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, participant, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
participant.
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 participant in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the participant has taken the excess dose(s). Overdose cannot be established 
when the participant cannot account for the discrepancy except in cases in which the investigator 
has reason to suspect that the participant 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.


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7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study participants 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.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE 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.
Any complications during pregnancy and the outcome should be reported to Gilead PVE using 
the pregnancy outcome report form. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead PVE. Gilead PVE contact 
information is as follows: 
Email: 
 and Fax: 
 
Refer to Appendix 6 for Pregnancy Precautions, Definition for Persons of Childbearing Potential, 
and Contraceptive Requirements.
7.7.2.2.
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 do 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.
PPD
PPD


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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.


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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 2 NRTIs and a third agent to fixed 
dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)
versus continuing their baseline regimen in HIV-infected, virologically suppressed 
African American participants as determined by the proportion of participants with HIV-1 
RNA ≥50 copies/mL at Week 24
The secondary objectives of this study are:

To evaluate the efficacy of switching to FDC of B/F/TAF from a regimen of 2 NRTIs and a 
third agent as determined by the proportion of participants with HIV-1 RNA ≥50 copies/mL 
at Week 48

To evaluate the efficacy, safety, and tolerability of switching to FDC of B/F/TAF from a
regimen of 2 NRTIs and a third agent in HIV-infected, virologically suppressed 
African American participants through Week 48 
8.1.2.
Primary Endpoint
The primary efficacy endpoint is:

The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 as defined by 
the US FDA-defined snapshot algorithm 
8.1.3.
Secondary Endpoint
The secondary efficacy endpoints are:

The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as defined by 
the US FDA-defined snapshot algorithm

The proportion of participants with HIV-1 RNA <50 copies/mL at Week 24 and 48 as 
defined by the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Weeks 24 and 48.


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8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all participants who are randomized into the study. This is 
the primary analysis set for by-participant listings.
8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set 
The primary analysis set for efficacy analyses is defined as the full analysis set (FAS), which 
will include all participants who (1) are randomized into the study, (2) have received at least 
1 dose of study treatment, (3) have at least 1 post baseline HIV-1 RNA result while on study 
treatment, and (4) do not have pre-existing resistance-associated mutations. Participants will be 
grouped according to the treatment to which they were randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set for anti-HIV Efficacy Analysis
The secondary analysis set for anti-HIV efficacy analyses is defined as the per-protocol (PP) 
analysis set for anti-HIV efficacy analysis, which will include all participants who (1) are 
randomized into the study, (2) have received at least 1 dose of study treatment, and (3) have not 
committed any major protocol violation, including the violation of key entry criteria. Participants
will be grouped according to the treatment they actually received.
Participants meeting any of the following criteria will be excluded from the Week 24 PP analysis 
set for anti-HIV efficacy analysis:

Participants who do not have on-treatment HIV-1 RNA in the Week 24 analysis window, 
except when missing due to discontinuation of study treatment for lack of efficacy. 

Participants 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 
bictegravir.

Nonadherence to study treatment: participants with adherence rate for active study treatment
up to the Week 24 Visit below the 2.5th percentile

Participants who do not meet the inclusion criteria for history of 3 or more TAMs (M41L, 
D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT, 
including pre-existing mutations that are detected post-baseline


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8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as the safety analysis set, which will 
include all participants who (1) are randomized into the study and (2) have received at least 
1 dose of study treatment. All data collected up to 30 days after participants permanently 
discontinue their study treatment will be included in the safety summaries, unless specified 
otherwise. Participants 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 purposes. 
Laboratory data that are continuous in nature, but are less than the lower limit of quantitation or 
above the upper limit of quantitation, will be imputed to the value of the lower or upper limit 
plus or minus one significant digit, respectively (eg, if the result of a continuous laboratory test is 
< 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (ie, no toxicity grade) for the laboratory abnormality summary.
All available data for participants 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, age, sexual orientation and gender identity.
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 of B/F/TAF 
versus SBR, with respect to the proportion of participants with HIV-1 RNA ≥50 copies/mL at 
Week 24, as defined by the US FDA-defined snapshot algorithm. The primary analysis of the 
efficacy endpoint will be based on the FAS.


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8.5.1.1.
US FDA-defined Snapshot Algorithm
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 participants who have the last available 
on-treatment HIV-1 RNA < 50 copies/mL in the Week 24 analysis window 

HIV-1 RNA ≥ 50 copies/mL: this includes participants
a) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 24
analysis window, or
b) Who do not have on-treatment HIV-1 RNA data in the Week 24 analysis window and
1. Who discontinue study treatment prior to or in the Week 24 analysis window due to 
lack of efficacy, or
2. Who discontinue study treatment prior to or in the Week 24 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 24 Analysis Window: this includes participants who do not 
have on-treatment HIV-1 RNA data in the Week 24 analysis window because of the 
following:
a) Discontinuation of study treatment prior to or in the Week 24 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 treatment
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of participants achieving HIV-1 RNA < 50 copies/mL
(as defined by the US FDA-defined snapshot algorithm) at Week 24 in B/F/TAF is at least 6% 
lower than the response rate in SBR; the alternative hypothesis is that the response rate in 
B/F/TAF is less than 6% lower than that in SBR.
Non-inferiority will be assessed using the conventional confidence interval (CI) approach. The 
point estimate of treatment difference (B/F/TAF – SBR) and the associated 2-sided 95% CI will 
be constructed based on the exact method.


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It will be concluded that FDC of B/F/TAF is non-inferior to SBR if the upper bound of the 
2-sided 95% CI of the difference between treatment groups [B/F/TAF – SBR] in the percentage 
of participants with HIV-1 RNA ≥ 50 copies/mL is less than 6% (i.e., a margin of 6% is applied 
to non-inferiority assessment).
If non-inferiority of B/F/TAF to SBR is established, the upper bound of the 95% CI will be 
compared to 0; if the upper bound of the 95% CI is less than 0, superiority of B/F/TAF over SBR 
will be established.
8.5.2.
Secondary Analyses
The proportion of participants with HIV-1 RNA < 50 copies/mL at Weeks 24 and 48, and the 
proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as defined by the US 
FDA-defined snapshot algorithm will also be summarized.
The changes from baseline in CD4+ cell count at Weeks 24 and 48 will be summarized by 
treatment using descriptive statistics. The differences between treatment groups at Week 24 and 
the associated 95% CIs will be constructed using an Analysis of Variance (ANOVA) model, 
including treatment (B/F/TAF vs. SBR) as a fixed effect 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 treatment was first administered up to 
the date of the last dose of study treatment plus 30 days, unless specified otherwise, will be 
summarized for participants in the safety analysis set according to the study treatment received.
Data for the pretreatment period and the period post the date of last dose of study treatment plus 
30 days will be included in data listings for all enrolled participants.
8.6.1.
Extent of Exposure
A participant’s extent of exposure to study treatment will be generated from the study drug 
administration page in eCRF. Exposure data will be summarized by treatment.
Duration of exposure to study treatment will be expressed as the number of weeks between the 
first and last dose of the study treatment, inclusive, regardless of temporary interruptions in study 
drug administration and summarized by treatment.
Dosing information for individual participants 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.


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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 treatment
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 participants) 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 
treatment, and effect on study dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 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 treatment 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 post baseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study treatment or after the last dose 
of study treatment 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 will be summarized by treatment and visit using 
descriptive statistics.


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8.8.
Sample Size
Sample sizes of 320 in B/F/TAF FDC and 160 in SBR Group achieve approximately 89% power 
to detect a non-inferiority margin difference between the group proportions of 0.06 for HIV-1 
RNA ≥ 50 copies/mL at Week 24. The assumed reference group proportion is 0.04. The 
treatment group proportion is assumed to be 0.10 under the hypothesis of inferiority. The power 
is computed for the case when the actual treatment group difference is zero (treatment = 
reference). The test statistic used is the one-sided Score test (Farrington & Manning) with the 
significance level of 0.025. 
8.9.
Analysis Schedule
The Week 24 and 48 analyses will be conducted after all participants either complete their 
Week 24 and 48 visits or prematurely discontinue from the study treatment, respectively. Final 
analysis will be performed after all participants 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 participant. These standards are consistent with the European Union 
Clinical Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last participant completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)
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 
participant (such as advertisements, participant information sheets, or descriptions of the study 
used to obtain informed consent) to an IRB. The investigator will not begin any study participant
activities until approval from the IRB 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 any modifications made to the protocol or any accompanying material to be provided to 
the participant after initial approval, with the exception of those necessary to reduce immediate 
risk to study participants.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IRB-approved consent form for documenting written 


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informed consent. Each informed consent (or assent as applicable) will be appropriately signed 
and dated by the participant or the participant’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB or local 
requirements. The consent form will inform participants 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 participants’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties. Only participant initials, date of birth, 
another unique identifier (as allowed by local law) and an identification code will be recorded on 
any form or biological sample submitted to the Sponsor, or laboratory. Laboratory specimens 
must be labeled in such a way as to protect participant identity while allowing the results to be 
recorded to the proper participant. Refer to specific laboratory instructions. NOTE: The 
investigator must keep a screening log showing codes, names, and addresses for all participants
screened and for all participants enrolled in the trial. Participant 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) participant clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, IRB 
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 participant:

Participant identification (name, date of birth, gender);

Documentation that participant 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 participant 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 
participant, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each participant 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, 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, 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 participants, 
may be made only by Gilead. The investigator must submit all protocol modifications to the IRB 
in accordance with local requirements and receive documented IRB approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency. Gilead will 
ensure that the report meets the standards set out in the ICH Guideline for Structure and Content 
of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:
The results of the study in their entirety have been publicly disclosed by or with the consent of 
Gilead in an abstract, manuscript, or presentation form or the study has been completed at all 
study sites for at least 2 years.
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, e.g. attendance at Investigator’s Meetings.  If required under the applicable statutory 
and regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any participant 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 and IRBs. In terminating the study, Gilead and the investigator will assure 
that adequate consideration is given to the protection of the participants’ 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. 
Arribas JR, Thompson M, Sax PE, Haas B, McDonald C, Wohl DA, et al. Brief Report: 
Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs 
Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, 
Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 
Results. J Acquir Immune Defic Syndr 2017;75 (2):211-8.
Bailey ZD, Krieger N, Agenor M, Graves J, Linos N, Bassett MT. Structural racism and health 
inequities in the USA: evidence and interventions. Lancet 2017;389:1453-63.
Centers for Disease Control and Prevention (CDC). HIV and African Americans: HIV Diagnoses 
In 2016. Fact Sheet.  2018:
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.
Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in Adults and Adolescents Living with HIV.  2018:298. 
European AIDS Clinical Society (EACS). Guidelines Version 8.1 English.  October, 2016.
European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the 
Management of Hepatitis B Virus Infection. J Hepatol 2017;67 (2):370-98.
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. 


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Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, et al. Bictegravir, 
Emtricitabine, and Tenofovir Alafenamide Versus Dolutegravir, Abacavir, and 
Lamivudine for Initial Treatment of HIV-1 Infection (GS-US-380-1489): A 
Double-Blind, Multicentre, Phase 3, Randomised Controlled Non-Inferiority 
Trial. Lancet 2017;390:2063-72.
Grabowski MK, Serwadda DM, Gray RH, Nakigozi G, Kigozi G, Kagaayi J, et al. HIV 
Prevention Efforts and Incidence of HIV in Uganda. N Engl J Med 2017;377 
(22):2154-66.
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.
Jensen-Fangel S, Pedersen L, Pedersen C, Larsen CS, Tauris P, Moller A, et al. The effect of 
race/ethnicity on the outcome of highly active antiretroviral therapy for human 
immunodeficiency virus type 1-infected patients. Clin Infect Dis 2002;35 
(12):1541-8.
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at: http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-
2016. 31 May.  2016.
King WD, Minor P, Ramirez Kitchen C, Ore LE, Shoptaw S, Victorianne GD, et al. Racial, 
gender and geographic disparities of antiretroviral treatment among US Medicaid 
enrolees in 1998 [Author Manuscript]. J Epidemiol Community Health 2008;62 
(9):798-803.
Kurth AE, Celum C, Baeten JM, Vermund SH, Wasserheit JN. Combination HIV prevention: 
significance, challenges, and opportunities [Author Manuscript]. Current 
HIV/AIDS reports 2011;8 (1):62-72.
Lemly DC, Shepherd BE, Hulgan T, Rebeiro P, Stinnette S, Blackwell RB, et al. Race and sex 
differences in antiretroviral therapy use and mortality among HIV-infected 
persons in care. J Infect Dis 2009;199 (7):991-8.
Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, et al. Safety and 
efficacy of raltegravir-based versus efavirenz-based combination therapy in 
treatment-naive patients with HIV-1 infection: a multicentre, double-blind 
randomised controlled trial. Lancet 2009;374 (9692):796-806.
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. 


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Meditz AL, MaWhinney S, Allshouse A, Feser W, Markowitz M, Little S, et al. Sex, race, and 
geographic region influence clinical outcomes following primary HIV-1 infection. 
J Infect Dis 2011;203 (4):442-51.
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.
Oramasionwu CU, Brown CM, Lawson KA, Ryan L, Skinner J, Frei CR. Differences in national 
antiretroviral prescribing patterns between black and white patients with 
HIV/AIDS, 1996-2006 [Author Manuscript]. South Med J 2011;104 (12):794-
800.
Oramasionwu CU, Koeller JM, Lawson KA, Brown CM, Morse GD, Frei CR. The state of 
disparities in opportunistic infection prophylaxis for blacks with HIV/AIDS. 
[Author Manuscript]. Medical care 2012;50 (11):920-7.
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. Developed by 
the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A 
Working Group of the Office of AIDS Research Advisory Council (OARAC) 
Available at: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. 
Last Updated 14 July.  2016.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of 
Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of 
Health and Human Services. Available at 
http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Last 
Updated : 27 March.  2018.
Ribaudo HJ, Smith KY, Robbins GK, Flexner C, Haubrich R, Chen Y, et al. Racial differences 
in response to antiretroviral therapy for HIV infection: an AIDS clinical trials 
group (ACTG) study analysis. Clin Infect Dis 2013;57 (11):1607-17.
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Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, et al. Coformulated 
Bictegravir, Emtricitabine, and Tenofovir Alafenamide Versus Dolutegravir With 
Emtricitabine and Tenofovir Alafenamide, For Initial Treatment of HIV-1 
Infection (GS-US-380-1490): A Randomised, Double-Blind, Multicentre, Phase 
3, Non-Inferiority Trial. Lancet 2017;390:2073-82.
Selik RM, Mokotoff ED, Branson B, Owen SM, Whitmore S, Hall HI. Morbidity and Mortality 
Weekly Report (MMWR). Revised Surveillance Case Definition for HIV 
Infection - United States 2014. Centers for Disease Control and Prevention,  2014.
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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.
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for treatment of chronic hepatitis B. Hepatology 2016;63 (1):261-83.
Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutierrez F, et al. Dolutegravir 
plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med 
2013;369 (19):1807-18.
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.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)
Appendix 6.
Pregnancy Precautions, Definition for Persons of Childbearing Potential, and 
Contraceptive Requirements


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Appendi,'l( 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From a Regimen of Two 
Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) plus a Third Agent to a Fixed Dose 
Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/T AF), in 
Virologically-Suppressed, HIV-1 Infected African American Participants 
GS-US-380-4580 Original Protocol, 27 June 2018 
ature documents 
1gna ure 
Author 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I wilJ discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 76 
27 June 2018 


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Appendix 2.
Study Procedures Table
Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48e
30 Day 
Follow-Upf
ESDDg
4
12
24
28d
36
48
Every 12 Weekscc
Informed Consent
X
HIV Symptoms Distress Module
X
X
X
X
X
HIV-TSQh
X
X
X
VAS Adherence Questionnairei
X
X
X
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Complete/Symptom-Directed Physical Examj
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG 
(performed supine)
X
Height
X
Weight  
X
X
X
X
X
X
X
X
X
X
X
Vital Signsk
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
Urine Pregnancy Testl
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Testl
X
FSH Testm
X
Chemistry Profilen
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentso
X
X
X
X
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilep
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAq
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count and Percentager
X
X
X
X
X
X
X


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Study Procedure
Screeninga
Day 1b
End of Weekc
Post Week 48e
30 Day 
Follow-Upf
ESDDg
4
12
24
28d
36
48
Every 12 Weekscc
HBV Blood Panels
Xt
Xt
Plasma HBV DNAu
X
X
X
X
HCV Serologyv
X
X
X
HIV-1 Genotype/Phenotypeq
Xq
Plasma, Serum, and Urine Sample Storagew
X
X
X
X
X
X
X
X
X
Whole Blood for HIV-1 DNA archive testing
X
Xx
Obtain Screening Number
X
Randomizationz
X
Study Drug Dispensation 
Xbb
Xbb
Xbb
Xaa
X
X
X
X
Study Drug Accountability
Xbb
Xbb
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Participants should initiate dosing of study drug on the same day as the Day 1 visit.
c
All study visits are to be completed ± 6 days of the protocol-specified visit date (based on the Day 1 visit), unless otherwise specified. 
d
Participants randomized to continue their baseline regimen will have an additional visit at Week 28.
e
At the study Week 48 Visit, participants who wish to continue on B/F/TAF will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks or until they 
have access to FDC of B/F/TAF, whichever occurs first, and attend study visits every 12 weeks (± 6 days of the protocol specified visit date) followed by a 30 Day Follow-Up 
Visit.
f
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. Required for 
participants who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Participants
who participate post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit.  
g
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Participants will be asked to continue attending the scheduled study visits through 
the Week 48 Visit even if the participant discontinues study drug. Participants on Treatment 2 (SBR) who discontinue their baseline regimen due to an AE prior to Week 24 
will be asked to continue attending the scheduled study visits through the Week 24 visit.
h
HIV-TSQs is to be completed at Day 1. The HIV-TSQc is to be completed at Week 4 and Week 24. Participant is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires.
i
VAS Adherence Questionnaire will be administered at Day 1 and at all visits up to (and including) Week 24 for participants in Treatment Group 2 (SBR) only.
j
Complete physical exam is required at Screening, Day 1, Week 24, 48, 72, and ESDD. Urogenital/anorectal exams will be performed at the discretion of the Investigator. 
Symptom-directed physical examination, as needed. 
k.
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature.
l
All female participants will have a serum test performed at Screening. Urine pregnancy test will only be done for persons of childbearing potential. Positive urine pregnancy 
tests will be confirmed with a serum test.  
CCI


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m
FSH test is required for female participants who are <54 years old and have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure.
n
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, amylase, and Cystatin C. After Day 1, calcium, phosphorous, magnesium, and amylase (reflex lipase testing is 
performed in participants with total amylase > 1.5 x ULN) 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 24, 48, and 72. Cystatin C will only be collected at Day 1.
o
Metabolic Assessments will be performed at Day 1, Weeks 24, 48, and 72. 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 participant has not fasted prior to the visit, the visit may proceed, but the participant must return within 72 
hours in a fasted state to draw blood for the metabolic assessments.
p
CBC with differential and platelet count.
q
HIV-1 genotype and phenotype testing for participants with confirmed virologic failure and HIV-1 RNA >200 copies/mL. Following virologic rebound, participants 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, participants should be managed according to the Virologic
Rebound Schema.
r
CD4+ Cell Count and Percentage to be collected at Screening and Day 1, and every 24 weeks thereafter, at Weeks 24, 48, and 72, in addition to the 30 Day Follow-up Visit 
and ESDD.
s
HBV blood panel will be performed at Screening and Week 48: HBsAg, HBsAb, HBcAb.
t
For participants who are HBV co-infected (defined in Section 6.9.1): The following HBV Blood panel will be conducted by the central laboratory: HBsAb, HBsAg 
(qualitative and quantitative), and HBeAg (if negative, reflex HBeAb).
For participants who are NOT HBV co-infected: The following HBV Blood panel will be conducted by the central laboratory: HBsAb, HBcAb, and HBsAg.
Participants who are HBsAg or HBcAb positive will have a reflex test for HBV DNA (viral load).
u
For participants who are HBV co-infected: Plasma HBV DNA will be collected at Day 1, Week 24, Week 48 and ESDD.
v
Hepatitis C virus serology will be performed at Screening, Week 48, and Week 72. Participants who are HCVAb positive will have a HCV RNA test performed.
w
Plasma,  serum ,and urine storage samples will be collected for safety, virology, or PK testing. 
x
Collect whole blood sample for participants randomized to SBR only at Week 24.
y
z
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 participant eligibility has 
been confirmed.
aa
At Week 24, participants randomized to continue their baseline regimen and complete 24 weeks of treatment on their baseline regimen will switch to FDC of B/F/TAF.
bb
FDC of B/F/TAF will be dispensed to Treatment Group 1 only. Study drug accountability will be performed accordingly.
cc
Subjects will receive study drug for dosing until Week 72.
CCI


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Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grade 1 
Grade 2 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
I 
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 
Grade 3 
! 
Repeat lab to 
confirm toxicity 
grade 
l 
I 
d, and unrelated to 
f confirme 
nvestigatio 
roducts, do 
t the disco 
iscretion o 
i 
n medicinal 
p 
sing may continue 
a 
ntinue at the 
d 
f the investigator 
Grade 4 
If confirmed, and 
I---+ 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 


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Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count 
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


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0%
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric participants.  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
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 83
27 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
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 84
27 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
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 85
27 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


B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 86
27 June 2018
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
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 87
27 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 participants >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
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 88
27 June 2018
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
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 89
27 June 2018
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
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 90
27 June 2018
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


B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 91
27 June 2018
RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced to 
70% to 80%
FEV1 or peak flow 50% to 69%
FEV1 or peak flow 25% to 
49% 
Cyanosis OR FEV1 or peak flow 
25% OR Intubation
Dyspnea or Respiratory 
Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities 
Dyspnea on exertion causing 
greater than minimal interference 
with usual social & functional 
activities 
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate for 
age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 
90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional activities 
OR Pulse oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis OR 
Medical intervention indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in affected 
eye(s) 
Visual Changes (from 
baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing greater 
than minimal interference with 
usual social & functional 
activities
Visual changes causing 
inability to perform usual 
social & functional activities
Disabling visual loss in affected 
eye(s)


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


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


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


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


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Headache 
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference with 
usual social & functional 
activities
Symptoms causing inability to 
perform usual social & 
functional activities
Symptoms causing inability to 
perform basic self-care 
functions OR Hospitalization 
indicated (other than ER visit) 
OR Headache with significant 
impairment of alertness or 
other neurologic function 
Insomnia
NA
Difficulty sleeping causing 
greater than minimal 
interference with usual 
social/functional activities
Difficulty sleeping causing 
inability to perform usual 
social & functional activities
Disabling insomnia causing 
inability to perform basic self-
care functions
Neuromuscular Weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength on exam 
OR Minimal muscle weak-
ness causing no or minimal 
interference with usual 
social & functional activities
Muscle weakness causing 
greater than minimal 
interference with usual social 
& functional activities
Muscle weakness causing 
inability to perform usual 
social & functional activities 
Disabling muscle weakness 
causing inability to perform 
basic self-care functions OR 
Respiratory muscle weakness 
impairing ventilation
Neurosensory Alteration 
(including paresthesia and 
painful neuropathy)
Asymptomatic with sensory 
alteration on exam or 
minimal paresthesia causing 
no or minimal interference 
with usual social & 
functional activities 
Sensory alteration or 
paresthesia causing greater 
than minimal interference with 
usual social & functional 
activities 
Sensory alteration or 
paresthesia causing inability to 
perform usual social & 
functional activities
Disabling sensory alteration or 
paresthesia causing inability to 
perform basic self-care 
functions
Seizure: (new onset) 
NA
1 seizure 
2–4 seizures 
Seizures of any kind that are 
prolonged, repetitive (eg, 
status epilepticus), or difficult 
to control (eg, refractory 
epilepsy)


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


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


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


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


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


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


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


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


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Appendix 6.
Pregnancy Precautions, Definition for Persons of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born participant is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women < 54 years of age with amenorrhea of ≥ 12 months may also be considered 
postmenopausal if their FSH level is in the postmenopausal range, and they are not using 
hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female participant of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born participant is considered to be fertile after the
initiation of puberty unless permanently sterile by bilateral orchiectomy or medical 
documentation.
2) Contraception Requirements for Persons of Childbearing Potential
a.
Study Drug Effects on Pregnancy and Hormonal Contraception
The data on B/F/TAF in pregnancy 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.
Some anti-retroviral agents allowed under this protocol in the SBR arm are contraindicated in 
pregnancy as a malformation effect has been demonstrated/suspected or is unknown, taking into 
consideration class effects, or a strong suspicion of human teratogenicity/fetotoxicity in early 
pregnancy is based on non-clinical data.  Some ARVs allowed in the SBR arm in this protocol 
have demonstrated/suspected or have insufficient data to exclude the possibility of a clinically 
relevant interaction with hormonal contraception that results in reduced contraception efficacy.  
Please refer to the latest prescribing information for comparator ARVs allowed under this 
protocol for additional information and for product-specific contraceptive recommendations.


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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 Persons of Childbearing Potential
The inclusion of persons 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 
menstrual period (over one month between menstruations), a pregnancy test must be performed 
to rule out pregnancy.  This is true even for persons of childbearing potential with infrequent or 
irregular periods.  Female participants 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 participant’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)
Persons of childbearing potential who wish to use a hormonally-based contraceptive method 
must use it in conjunction with a barrier method, preferably a male condom.  Persons of 
childbearing potential 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:


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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)
■
Injectable progesterone
■
Subdermal contraceptive implant
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring
Persons of childbearing potential 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 Participants
During the study, male participants with persons of childbearing potential should use condoms 
when engaging in intercourse of reproductive potential.
4) Unacceptable Contraceptive Methods
Contraceptive methods that are unacceptable include periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM).  Female condom and male condom should not 
be used together.
5) Procedures to be Followed in the Event of Pregnancy
Participants 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. Participants who become pregnant or who suspect that they are 
pregnant during the study must report the information to the investigator and discontinue study 
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Participants 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 7.7.2.1.
CC

SAP_001.pdf: 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
Study Title: 
A Phase 3, Multicenter, Open-Label Study to Evaluate Switching 
From a Regimen of Two Nucleos(t)ide Transcriptase Inhibitors 
(NRTI) plus a Third Agent to a Fixed Dose Combination (FDC) of 
Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in 
Virologically-Suppressed, HIV-1 Infected African American 
Participants 
 
 
Name of Test Drug: 
Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF; GS-9883/F/TAF) 
 
 
Study Number: 
GS-US-380-4580 
 
 
Protocol Version (Date): 
Original (27 June 2018) 
 
 
Analysis Type: 
Week 24 
 
 
Analysis Plan Version: 
Version 1 
 
 
Analysis Plan Date: 
30 August 2019 
 
 
Analysis Plan Author(s): 
 
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION 
PPD
(r) GILEAU 


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TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ 4 
LIST OF ABBREVIATIONS ........................................................................................................................................ 5 
1. 
INTRODUCTION ................................................................................................................................................ 7 
1.1. 
Study Objectives ...................................................................................................................................... 7 
1.2. 
Study Design ............................................................................................................................................ 7 
1.3. 
Sample Size and Power ............................................................................................................................ 9 
2. 
TYPE OF PLANNED ANALYSIS .................................................................................................................... 11 
2.1. 
Interim Analyses .................................................................................................................................... 11 
2.1.1. 
Week 24 Analysis ................................................................................................................. 11 
2.2. 
Final Analysis ........................................................................................................................................ 11 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................ 12 
3.1. 
Analysis Sets .......................................................................................................................................... 12 
3.1.1. 
All Randomized Analysis Set ............................................................................................... 13 
3.1.2. 
Full Analysis Set .................................................................................................................. 13 
3.1.3. 
Per Protocol Analysis Set ..................................................................................................... 13 
3.1.4. 
Safety Analysis Set ............................................................................................................... 14 
3.2. 
Subject Grouping ................................................................................................................................... 14 
3.3. 
Strata and Covariates .............................................................................................................................. 14 
3.4. 
Examination of Subject Subgroups ........................................................................................................ 15 
3.4.1. 
Subject Subgroups for Efficacy Analyses ............................................................................ 15 
3.4.2. 
Subject Subgroups for Safety Analyses ............................................................................... 15 
3.5. 
Multiple Comparisons ............................................................................................................................ 16 
3.6. 
Missing Data and Outliers ...................................................................................................................... 16 
3.6.1. 
Missing Data ........................................................................................................................ 16 
3.6.2. 
Outliers ................................................................................................................................. 17 
3.7. 
Data Handling Conventions and Transformations ................................................................................. 17 
3.8. 
Analysis Windows ................................................................................................................................. 17 
3.8.1. 
Definition of Study Day ....................................................................................................... 17 
3.8.2. 
Analysis Windows ................................................................................................................ 19 
3.8.3. 
Selection of Data in the Event of Multiple Records in an Analysis 
Window ................................................................................................................................ 21 
4. 
SUBJECT DISPOSITION .................................................................................................................................. 23 
4.1. 
Subject Enrollment and Disposition ....................................................................................................... 23 
4.1.1. 
Subject Enrollment ............................................................................................................... 23 
4.1.2. 
Subject Disposition .............................................................................................................. 23 
4.2. 
Extent of Study Drug Exposure and Adherence ..................................................................................... 24 
4.2.1. 
Duration of Exposure to Study Drug .................................................................................... 24 
4.2.2. 
Adherence to Study Drug Regimen ...................................................................................... 24 
4.3. 
Protocol Deviations ................................................................................................................................ 25 
5. 
BASELINE CHARACTERISTICS .................................................................................................................... 26 
5.1. 
Demographics and Baseline Characteristics .......................................................................................... 26 
5.2. 
Baseline Disease Characteristics ............................................................................................................ 26 
5.3. 
Medical History ...................................................................................................................................... 27 
6. 
EFFICACY ANALYSES ................................................................................................................................... 28 


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6.1. 
Primary Efficacy Endpoint ..................................................................................................................... 28 
6.1.1. 
Definition of the Primary Efficacy Endpoint ....................................................................... 28 
6.1.2. 
US FDA-Defined Snapshot Algorithm ................................................................................ 28 
6.1.3. 
Statistical Hypothesis for the Primary Efficacy Endpoint .................................................... 29 
6.1.4. 
Primary Analysis of the Primary Efficacy Endpoint ............................................................ 29 
6.1.5. 
Secondary Analysis of the Primary Efficacy Endpoint ........................................................ 30 
6.2. 
Secondary Efficacy Endpoints ............................................................................................................... 30 
6.2.1. 
Definition of the Secondary Efficacy Endpoints .................................................................. 30 
6.2.2. 
Analysis of the Secondary Efficacy Endpoints .................................................................... 30 
6.3. 
Tertiary Efficacy Endpoints ................................................................................................................... 32 
6.3.1. 
Definition of the Tertiary Efficacy Endpoints ...................................................................... 32 
6.3.2. 
Analysis of the Tertiary Efficacy Endpoints ........................................................................ 32 
6.4. 
Changes From Protocol-Specified Efficacy Analyses ............................................................................ 34 
7. 
SAFETY ANALYSES ........................................................................................................................................ 35 
7.1. 
Adverse Events and Deaths .................................................................................................................... 35 
7.1.1. 
Adverse Event Dictionary .................................................................................................... 35 
7.1.2. 
Adverse Event Severity ........................................................................................................ 35 
7.1.3. 
Relationship of Adverse Events to Study Drug .................................................................... 36 
7.1.4. 
Serious Adverse Events ........................................................................................................ 36 
7.1.5. 
Treatment-Emergent Adverse Events ................................................................................... 36 
7.1.6. 
Summaries of Adverse Events and Death ............................................................................ 37 
7.1.7. 
Additional Analysis of Adverse Events................................................................................ 38 
7.2. 
Laboratory Evaluations .......................................................................................................................... 39 
7.2.1. 
Summaries of Numeric Laboratory Results ......................................................................... 40 
7.2.2. 
Graded Laboratory Values ................................................................................................... 40 
7.2.3. 
Metabolic Laboratory Evaluations ....................................................................................... 42 
7.2.4. 
Liver-Related Laboratory Evaluations ................................................................................. 43 
7.2.5. 
Renal-Related Laboratory Evaluations ................................................................................. 44 
7.3. 
Body Weight, Height, and Vital Signs ................................................................................................... 44 
7.4. 
Prior and Concomitant Medications ....................................................................................................... 45 
7.4.1. 
Nonstudy Drug Antiretroviral Medications .......................................................................... 45 
7.4.2. 
Concomitant Non-ARV Medications ................................................................................... 45 
7.5. 
Electrocardiogram Results ..................................................................................................................... 46 
7.6. 
Other Safety Measures ........................................................................................................................... 46 
7.7. 
Subject Subgroup for Safety Endpoints ................................................................................................. 46 
7.8. 
Changes From Protocol-Specified Safety Analyses ............................................................................... 46 
8. 
SPECIAL POPULATION ANALYSES ............................................................................................................. 47 
8.1. 
Analyses for HIV/HBV Coinfected Subjects ......................................................................................... 47 
8.2. 
Analyses for HIV/HCV Coinfected Subjects ......................................................................................... 49 
9. 
PATIENT REPORTED OUTCOMES................................................................................................................ 51 
9.1. 
HIV Symptoms Distress Module ........................................................................................................... 51 
9.2. 
Medication Adherence Questionnaire .................................................................................................... 52 
9.3. 
HIV Treatment Satisfaction Questionnaires ........................................................................................... 52 
9.4. 
Change from Protocol Specified Analysis for Patient-Reported Outcomes ........................................... 54 
10. REFERENCES ................................................................................................................................................... 55 
11. SOFTWARE ....................................................................................................................................................... 56 
12. SAP REVISION .................................................................................................................................................. 57 
13. APPENDICES .................................................................................................................................................... 58 


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Appendix 1. 
Study Procedures Table .......................................................................................................... 59 
Appendix 2. 
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial) ................................. 62 
Appendix 3. 
Cardiovascular or Cerebrovascular Events ............................................................................. 63 
Appendix 4. 
Hepatic Events ........................................................................................................................ 64 
Appendix 5. 
Programming Specifications................................................................................................... 65 
 
 
LIST OF IN-TEXT TABLES 
 
Table 3-1. 
Subjects Excluded from Week 24 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA Assessment in Week 24 
Analysis Window ................................................................................................................... 13 
Table 3-2. 
Analysis Windows for HIV-1 RNA, Hematology, Chemistry, Urinalysis, Urine 
Pregnancy Laboratory Tests, eGFRCG, Vital Signs, Weight, and VAS .................................. 20 
Table 3-3. 
Analysis Windows for HIV Symptoms Distress Module, HIVTSQs (at Day 1 only), 
and HIVTSQc (Week 4 and Week 24 only) ........................................................................... 20 
Table 3-4. 
Analysis Windows for CD4+ cell count, CD4 %, Metabolic Assessments, and 
Plasma HBV DNA ................................................................................................................. 21 
Table 9-1. 
List of Items on the HIVTSQ ................................................................................................. 53 
 


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LIST OF ABBREVIATIONS 
 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANOVA 
analysis of variance 
ARV 
antiretroviral 
AST 
aspartate aminotransferase 
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 
CG 
Cockcroft-Gault 
CI 
confidence interval 
CMH 
Cochran-Mantel-Haenszel  
CRF 
case report form 
CSR 
clinical study report  
DNA 
deoxyribonucleic acid 
DTG 
dolutegravir 
ECG 
electrocardiogram 
EFV 
efavirenz 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
eGFRCG 
estimated glomerular filtration rate using Cockcroft-Gault formula 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FDC 
fixed dose combination 
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 
ID 
identification 
IWRS 
interactive web response system 
LDL 
low density lipoprotein 
LLT 
lowest level term 
MedDRA 
Medical Dictionary for Regulatory Activities 
MH 
Mantel-Haenszel  
NRTI 
Nucleos(t)ide Transcriptase Inhibitors 
PP 
per protocol 
PT 
preferred term 
PVE 
pharmacovigilance and epidemiology (formerly Drug Safety and Public Health) 
Q 
quartile 
Q1 
first quartile 
Q3 
third quartile 
RNA 
ribonucleic acid 
RPV 
rilpivirine 
RTV 
ritonavir 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SBR 
stay on baseline regimen 
SD 
standard deviation 
SMQ 
Standardised MedDRA Query 
SOC 
system organ class 
TAF 
tenofovir alafenamide  
TDF 
tenofovir disoproxil fumarate 
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 the Week 24 analysis for 
Study GS-US-380-4580, which will be performed when all subjects have completed their 
Week 24 visit or prematurely discontinued from the study. This SAP is based on the study 
protocol dated 27 June 2018 and the electronic case report form (eCRF). The SAP will be 
finalized before database finalization for the Week 24 analysis.  
1.1. 
Study Objectives 
The primary objective of this study is: 
• To evaluate the efficacy of switching from a regimen of 2 NRTIs and a third agent to a fixed 
dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 
versus continuing their baseline regimen in HIV-1 infected, virologically suppressed 
African American participants as determined by the proportion of participants with HIV-1 
RNA ≥ 50 copies/mL at Week 24. 
The secondary objectives of this study are: 
• To evaluate the efficacy of switching to a FDC of B/F/TAF from a regimen of 2 NRTIs and a 
third agent as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL 
at Week 48 
• To evaluate the efficacy, safety, and tolerability of switching to FDC of B/F/TAF from a 
regimen of 2 NRTIs and a third agent in HIV-1 infected, virologically suppressed African 
American participants through Week 48 
1.2. 
Study Design 
Design Configuration and Subject Population 
GS-US-380-4580 is a randomized, open-label, multicenter, active-controlled study of HIV-1 
infected, virologically suppressed African American participants. 
Treatment Groups 
Participants who provide written consent and meet all eligibility criteria will be randomized in a 
2:1 ratio to one of the following 2 treatment groups: 
• Treatment Group 1: FDC of B/F/TAF (50 mg/ 200 mg/ 25 mg) administered orally, once 
daily, without regard to food  (n=320 planned) 
• Treatment Group 2: Stay on baseline regimen (SBR) consisting of 2 NRTIs and a third 
agent (each taken as prescribed) from Day 1 until Week 24, with a delayed switch to a FDC 
of B/F/TAF (50 mg/ 200 mg/ 25 mg) administered orally, once daily, without regard to food 
(n=160 planned) 


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Key Eligibility Criteria 
Medically stable HIV-infected participants who meet the following criteria: 
• Self-describes as Black, African American, or mixed race, including Black 
• Currently receiving an ARV regimen other than FDC of B/F/TAF that consists of any 
two NRTIs + allowed third agent for ≥ 6 months (see Protocol Section 4.2 for allowed 
agents) 
• Have no documented or suspected resistance to integrase stand transfer inhibitors (INSTIs) 
and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 
RNA ≥ 50 copies/mL after achieving < 50 copies/mL while on an INSTI-containing 
regimen) 
• History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT 
substitutions are allowed, with the following exceptions: History of 3 or more TAMs 
(M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N 
in RT will be excluded. 
• Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen 
for a minimum period of 6 months, and at least the last two HIV-1 RNA measurements prior 
to the Screening visit 
• HIV-1 RNA levels < 50 copies/mL at Screening Visit 
• Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance 
• Eligible participants with chronic hepatitis C virus (HCV) infection are permitted to enroll. In 
addition, eligible participants with chronic hepatitis B virus (HBV) infection are permitted to 
enroll if their baseline regimen contains either TAF or TDF. 
Study Periods / Phases 
Participants will be treated for at least 48 weeks after randomization.  
Following the Screening and Day 1 visits, participants will be required to return for study visits 
at Weeks 4, 12, 24, 36, and 48. Participants randomized to SBR will have, after their delayed 
switch at Week 24, an additional visit at Week 28. 
Participants who complete the study through the Week 48 visit and wish to continue on 
B/F/TAF, will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks 
or until they have access to FDC of B/F/TAF, whichever occurs first, and will attend study visits 
every 12 weeks followed by a 30-Day Follow-Up Visit.  
Participants who complete the study through the Week 48 Visit and do not continue their 
participation in the study will be required to return to the clinic 30 days after their Week 48 Visit 
for a 30-Day Follow-Up Visit. 


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Schedule of Assessments 
After screening procedures, eligible subjects will be randomized 2:1 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, 12, 24, 36 and 48. Participants randomized to SBR will 
have, after their delayed switch at Week 24, an additional visit at Week 28. 
Laboratory analyses (chemistry, hematology, and urinalysis), HIV-1 RNA, CD4+ cell count, 
assessment of adverse events (AEs) and concomitant medications, and complete or symptom 
directed physical examinations will be performed at Screening, Day 1 and subsequent study 
visits. Whole blood for HIV-1 DNA archive testing will be collected at Day 1 for all participants 
and at Week 24 for all participants in Treatment Group 2. 
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 
Participants will be randomized in a 2:1 allocation ratio to 1 of 2 Treatment Groups 
[Treatment Group 1 (B/F/TAF): Treatment Group 2 (SBR)]. Randomization will be stratified by 
the baseline 3rd agent ARV class at entry (integrase strand transfer inhibitor (INSTI), non-
nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI) or CCR5 antagonist). 
Site and/or Stratum Enrollment Limits 
Approximately 84 study sites in the United States participated. In order to provide all sites the 
opportunity to enroll subjects, the initial enrollment limit for individual sites was initially set to 
6 subjects. Additional enrollment slots at an individual site were allocated on a case-by-case 
basis. 
Study Duration 
Study duration for each participant will be at least 48 weeks.  
1.3. 
Sample Size and Power 
A total of 480 HIV-1 infected subjects, randomized in a 2:1 ratio to 2 treatment groups, achieves 
approximately 89% power to detect a noninferiority margin difference between the group 
proportions of 0.06 for HIV-1 RNA ≥ 50 copies/mL at Week 24. 
For sample size and power computation, it is assumed that the reference group proportion is 
0.04. The treatment group proportion is assumed to be 0.10 under the hypothesis of inferiority. 
The power is computed for the case when the actual treatment group difference is zero (treatment 
= reference). The test statistic used is the one-sided Score test (Farrington & Manning) with the 
significance level of 0.025. Sample size and power calculations were performed using the 
statistical software package PASS (Version 14). 


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In general, a failure rate of 1% to 3% is assumed for switch studies in virologically suppressed 
subjects, and the noninferiority margin for treatment difference is typically set at 4%. The failure 
rate of 4% and noninferiority margin of 6% used for this study was based on the observation that 
African Americans have lower rates of virological suppression compared to other cohorts. In the 
US, not all communities have had equitable access to advancements in HIV treatment. African 
Americans remain disproportionately affected by HIV but have less access to HIV treatment and 
generally worse health outcomes compared to other racial groups. 
The table below provides approximate power for SBR proportions ranging from 2% to 4% with 
noninferiority margin ranging from 0.04 to 0.06. A total of 480 HIV-1 infected subjects, 
randomized in a 2:1 ratio to 2 treatment groups, achieves approximately 87% power to detect a 
noninferiority margin difference between the group proportions of 0.04. 
SBR Proportion 
Noninferiority Margin 
Approximate Power 
Actual Alpha 
4% 
0.06 
91% 
0.026 
3% 
0.05 
88% 
0.026 
2% 
0.04 
87% 
0.024 
SBR N=160; B/F/TAF N=320; alpha targeted at 0.025. The test statistic used is the one-sided Score test (Farrington &Manning). 
Power and actual alpha were computed using binomial enumeration of all possible outcomes. 


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2. 
TYPE OF PLANNED ANALYSIS 
2.1. 
Interim Analyses 
2.1.1. 
Week 24 Analysis 
The Week 24 analysis will be conducted after all subjects either complete their Week 24 visit or 
prematurely discontinue from the study. 
This statistical analysis plan describes the analysis plan for the Week 24 analysis, the primary 
analysis of this study.  
2.2. 
Final Analysis 
The final statistical analysis will be conducted after all subjects either complete the study or 
prematurely discontinue from the study. 


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3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, 
first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented. 
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified. 
By-subject listings will be presented for all subjects in the All Randomized Analysis Set unless 
otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). Data 
collected on log forms, such as AEs, will be presented in chronological order within a subject. 
The treatment group to which subjects were randomized will be used in the listings.  
For randomized subjects, age (in years) collected on the Day 1 visit will be used for analyses and 
presentation in listings. For screen failures, age calculated on the date of the informed consent 
was signed will be used. Because only birth year is collected on the eCRF, “01 July” will be used 
for the unknown birth day and month for the purpose of age calculation.  
In general, permanent discontinuation of study drug refers to premature discontinuation of study 
drug or completion of study drug. Study drug refers to B/F/TAF for subjects randomized to the 
B/F/TAF treatment group. For subjects randomized to the SBR group, study drug refers to the 
baseline ARV regimen through Week 24 and to B/F/TAF after Week 24. For the SBR group, if 
the subject did not switch to B/F/TAF, the date of permanent discontinuation of study drug prior 
to Week 24 is defined as the earliest stop date for all components of the baseline ARV 
medication. 
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 
database finalization for the Week 24 analysis. The analysis set will be included as a subtitle of 
each table, figure, and listing. A summary of the number and percentage of subjects in each 
analysis set will be provided by treatment group and in total. 
For analysis by treatment group, subjects will be grouped using the following terminology: 
• Treatment Group 1: B/F/TAF 
• Treatment Group 2: 
 Up to Week 24: SBR 
 Post-Week 24: delayed switch to B/F/TAF 
• All B/F/TAF: all subjects who received at least one dose of study assigned B/F/TAF (both 
immediate and delayed switch to B/F/TAF). 


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For comparative summaries of safety data, only data through the Week 24 visit will be 
summarized and presented by treatment group (B/F/TAF and SBR). 
3.1.1. 
All Randomized Analysis Set 
The All Randomized Analysis Set will include all subjects who are randomized into the study. 
This is the primary analysis set for by-subject listings. 
3.1.2. 
Full Analysis Set 
The Full Analysis Set (FAS) will include all subjects who (1) are randomized into the study, 
(2) have received at least 1 dose of study treatment (either B/F/TAF or baseline regimen on or 
after Day 1), and (3) do not have pre-existing INSTI resistance-associated mutations (based on 
historical data). Subjects will be grouped according to the treatment to which they were 
randomized. For the FAS, all efficacy data, including data collected after the last dose of study 
drug, will be included, unless specified otherwise. This is the primary analysis set for efficacy 
analyses.  
3.1.3. 
Per Protocol Analysis Set 
The Week 24 Per Protocol (PP) Analysis Set will include all subjects who (1) are randomized 
into the study, (2) have received at least 1 dose of study treatment  (either B/F/TAF or baseline 
regimen on or after Day 1), 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. The Week 24 PP analysis set is the secondary analysis set for efficacy 
analysis.   
Subjects meeting any of the following criteria will be excluded from the Week 24 PP analysis 
set: 
• Subjects who do not have on-treatment HIV-1 RNA in the Week 24 analysis window, except 
when missing due to discontinuation of study treatment for lack of efficacy. (Note: lack of 
efficacy is defined as having the check-box for Lack of Efficacy marked as the reason for 
premature study drug discontinuation in the “Randomized Treatment” study phase on the 
study drug completion eCRF page; Table 3-1).  
Table 3-1. 
Subjects Excluded from Week 24 PP Analysis Set Due to Premature 
Discontinuation of Study Drug and/or Missing HIV-1 RNA 
Assessment in Week 24 Analysis Window 
Discontinuation from Study Treatment prior to or on 
the Upper Bound of Week 24 Analysis Window 
HIV-1 RNA Data on Randomized Treatment 
Available in Week 24 Analysis Window 
Yes 
No 
Yes 
Due to Lack of Efficacy 
+ 
+ 
Due to Other Reasons 
+ 
- 
No 
+ 
- 
+ = Inclusion of Subjects in Week 24 PP analysis set; - = Exclusion of Subjects from Week 24 PP analysis set. 


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• 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 
bictegravir 
• Subjects who do not meet the inclusion criteria for baseline ARV regimen of any two NRTIs 
+ allowed 3rd agent (Protocol Section 4.2) 
• Subjects who meet the exclusion criterion for history of 3 or more TAMs (M41L, D67N, 
K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT, including 
pre-existing mutations that are detected post-baseline 
• Subjects who have INSTI resistance-associated mutations, including pre-existing mutations 
that are detected post-baseline) 
3.1.4. 
Safety Analysis Set 
The Safety Analysis Set will include all subjects who (1) are randomized into the study and 
(2) have received at least 1 dose of study treatment (either B/F/TAF or baseline regimen on or 
after Day 1). For subjects in Treatment Group 1 and in Treatment Group 2 while on B/F/TAF, all 
data collected up to 30 days after subjects permanently discontinue study drug will be included 
in safety summaries, unless specified otherwise. For subjects in Treatment Group 2 while on the 
baseline ARV medications, all data collected up to the minimum of (1) 30 days after subjects 
permanently discontinue the baseline ARV medications and (2) 1 day prior to the start of 
B/F/TAF will be included in safety summaries, unless specified otherwise.  
Subjects will be grouped according to the treatment they actually received. This is the primary 
analysis set for safety analyses. 
3.2. 
Subject Grouping 
For analyses based on the All Randomized Analysis Set or the FAS, subjects will be grouped by 
randomized treatment. For other analyses, subjects will be grouped by actual treatment received. 
The actual treatment received will differ from the randomized treatment only when the actual 
treatment received differs from randomized treatment for the entire treatment duration. 
Treatment groups include B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF. 
For the purposes of the Week 24 comparisons, there will be 2 treatment groups (B/F/TAF and 
SBR). For the listings, observations that occur after a subject in the SBR group switches to 
B/F/TAF will be flagged. 
3.3. 
Strata and Covariates 
Randomization was stratified by the baseline third agent ARV class at entry (integrase strand 
transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease 
inhibitor (PI) or CCR5 antagonist). 
If there are discrepancies in stratification factor values between the IWRS and the clinical 
database, the values recorded in the clinical database will be used to group subjects for analyses. 


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3.4. 
Examination of Subject Subgroups 
3.4.1. 
Subject Subgroups for Efficacy Analyses 
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 24 as determined by the 
US FDA-defined snapshot algorithm {U. S. Department of Health and Human Services 2015} 
will be analyzed for the following subject subgroups (also see Section 6.2.2.2 for details):  
• Age (years): (a) < 50 and (b) ≥ 50  
• Sex at birth: (a) male and (b) female  
• Baseline NRTI Resistance (determined based on virology data): (a) Any NRTI Mutation 
(b) No NRTI Mutation 
• Baseline M184 Resistance (determined based on virology data): (a) M184 Mutation (b) No 
M184 Mutation 
The proportion of subjects with hepatitis B virus (HBV) Deoxyribonucleic Acid (DNA) 
< 29 IU/mL at baseline and Week 24 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 at birth: (a) male and (b) female  
2) Renal-related laboratory tests (ie, serum creatinine and eGFRCG) will be analyzed for the 
following subgroups:  
• Baseline ARV Medication containing any of the following: rilpivirine (RPV), dolutegravir 
(DTG), ritonavir (RTV), cobicistat 
• Baseline ARV Medication not containing any of the following: RPV, DTG, RTV, cobicistat 
3)  Fasting metabolic laboratory tests will be analyzed for the following subgroups:  
• Baseline ARV Medication containing TAF 
• Baseline ARV Medication containing TDF 


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• Baseline ARV Medication not containing any of the following: TAF, TDF 
• Baseline ARV Medication containing efavirenz (EFV) 
• Baseline ARV Medication not containing EFV 
4) Selected safety endpoints may be analyzed for the following subject subgroups 
(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) 
5) Selected safety endpoints will be analyzed for the following subject subgroups 
(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 
Efficacy will be evaluated using the primary efficacy endpoint at the significance level of 0.05. 
The primary analysis will consist of a non-inferiority test of switching to FDC of B/F/TAF 
versus SBR, with respect to the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at 
Week 24, as defined by the US FDA-defined snapshot algorithm. If non-inferiority of B/F/TAF 
to SBR is established, the upper bound of the 95% confidence interval (CI) will be compared 
to 0; if the upper bound of the 95% CI is less than 0, superiority of B/F/TAF over SBR will be 
established 
No prespecified multiplicity adjustments are planned for confidence intervals or statistical tests. 
3.6. 
Missing Data and Outliers 
3.6.1. 
Missing Data 
A missing datum for a given study analysis window may be due to any of the following reasons: 
• A visit occurring in the window but data were not collected or were unusable  
• A visit not occurring in the window 
• A subject prematurely discontinuing from the study before reaching the window 
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified. 


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For missing last dosing date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for adverse event onset is described in Section 7.1.5.2, 
and for concomitant non-ARV medications in Section 7.4.2. 
3.6.2. 
Outliers 
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety 
outcomes, unless specified otherwise. All data will be included in the analyses.  
3.7. 
Data Handling Conventions and Transformations 
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed as follows except for urine creatinine: 
• A value that is 1 unit less than the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “< x” (where x is considered the 
limit of quantitation). For example, if the values are reported as < 50 and < 5.0, values of 
49 and 4.9, respectively, will be used for calculation of summary statistics. An exception to 
this rule is any value reported as < 1 or < 0.1, etc. For values reported as < 1 or < 0.1, a value 
of 0.9 or 0.09, respectively, will be used for calculation of summary statistics. 
• A value that is 1 unit above the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “> x” (where x is considered the 
limit of quantitation). Values with decimal points will follow the same logic as above. 
• The limit of quantitation will be used for calculation of descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the limit of quantitation). 
Logarithmic (base 10) transformations will be applied to HIV-1 RNA and HBV 
Deoxyribonucleic Acid (DNA) data for efficacy analyses. HIV-1 RNA results of ‘No HIV-1 
RNA detected’ and “<20 cp/mL HIV-1 RNA Detected” will be imputed as 19 copies/mL for 
analysis purposes. HBV DNA results of “<20 IU/mL HBV DNA detected” or “No HBV DNA 
detected” will be imputed as 19 IU/mL for analysis purposes. HCV RNA results of “<15 IU/mL 
HCV RNA detected” or “No HCV RNA detected” will be imputed as 14 IU/mL for analysis 
purposes.  
3.8. 
Analysis Windows 
3.8.1. 
Definition of Study Day 
For the purposes of the SBR treatment group, there are 2 study periods: (1) up to Week 24, SBR 
and (2) Post-Week 24, Delayed Switch to B/F/TAF. 


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Study Day 1/First Dose Date is defined as follows: 
• Subjects randomized to the B/F/TAF treatment group: Study Day 1/First Dose Date is 
defined as the day when the first dose of B/F/TAF was taken, as recorded on the Study Drug 
Administration eCRF form.  
• Subjects randomized to the SBR treatment group:  Study Day 1/First Dose Date is defined as 
the Day 1 visit date recorded on the Visit Date eCRF.  
Period 1 Study Day 1/First Dose Date is the same as the Study Day 1/First Dose Date. 
Period 2 Study Day 1/First Dose Date is defined as follows: 
• Subjects randomized to the B/F/TAF treatment group: Not Applicable  
• Subjects randomized to the SBR treatment group who do not switch to B/F/TAF at Week 24: 
Not Applicable. 
• Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24:  
Period 2 Study Day 1/First Dose Date is defined as the day when the first dose of B/F/TAF 
was taken, as recorded on the Study Drug Administration eCRF form.  
Study Days are calculated relative to Study Day 1. For events that occurred on or after the 
Study Day 1 date, study days are calculated as (visit date minus Study Day 1 plus 1). For events 
that occurred prior to Study Day 1, study days are calculated as (visit date minus Study Day 1). 
• Treatment Group 1: B/F/TAF, study day is calculated based on Study Day 1 
• Treatment Group 2: 
 Up to Week 24: SBR, study day is calculated based on Period 1 Study Day 1 
 Post-Week 24: delayed switch to B/F/TAF, study day is calculated based on Period 2 
Study Day 1 
• All B/F/TAF: all subjects who received at least one dose of study assigned B/F/TAF (both 
immediate and delayed switch to B/F/TAF). Study day is calculated based on the first dose of 
B/F/TAF; Study Day 1 for the B/F/TAF treatment group and Period 2 Study Day 1 for the 
SBR group who switched to B/F/TAF. 
Last Dose Date is defined as follows: 
• Subjects randomized to the B/F/TAF treatment group: Last Dose Date is defined as the 
maximum, nonmissing end date of B/F/TAF recorded on the Study Drug Administration 
eCRF form with “Study Drug Permanently Discontinued” box checked for subjects who 
prematurely discontinued study drug according to the Study Drug Completion eCRF.   


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• Subjects randomized to the SBR treatment group who do not switch to B/F/TAF at Week 24: 
Last Dose Date is defined as the earliest stop date of the baseline ARV medications. 
• Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24: Last 
Dose Date is defined as the maximum, nonmissing end date of B/F/TAF recorded on the 
Study Drug Administration eCRF form with “Study Drug Permanently Discontinued” box 
checked for subjects who prematurely discontinued study drug according to the Study Drug 
Completion eCRF. 
Period 1 Last Dose Date is defined as follows: 
• Subjects randomized to the B/F/TAF treatment group: the same as Last Dose Date  
• Subjects randomized to the SBR treatment group who do not switch to B/F/TAF at Week 24: 
Period 1 Last Dose Date is defined as the earliest stop date of the baseline ARV medications. 
• Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24: Period 
1 Last Dose Date is defined as the day prior to the first dose date of B/F/TAF, as recorded on 
the Study Drug Administration eCRF form. 
Period 2 Last Dose Date is defined as follows: 
• Subjects randomized to the B/F/TAF treatment group: Not applicable 
• Subjects randomized to the SBR treatment group who do not switch to B/F/TAF at Week 24: 
Not applicable 
• Subjects randomized to the SBR treatment group who switch to B/F/TAF at Week 24: the 
same as Last Dose Date 
For partial or missing last dose dates, please refer to the programming specifications for 
imputation rule details. 
Last Study Date is the latest of the study drug start dates and end dates, the clinic visit dates, 
and the laboratory visit dates, including the 30-day follow-up visit date, for subjects who 
prematurely discontinued study according to the Study Completion eCRF.  
Baseline value is defined as the last value obtained on or prior to Study Day 1 for all 
assessments.  
3.8.2. 
Analysis Windows 
Subject visits might not occur on protocol specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows. 


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In the description that follows, the column labelled “B/F/TAF” refers to subjects in the 
immediate (B/F/TAF group) and delayed switch group (SBR group) who have switched to 
B/F/TAF. The baseline for delayed switch subjects will be reset based on the date of first dose of 
B/F/TAF and the study day will be calculated relative to that date. Data collected after the date of 
switch to B/F/TAF will be excluded from the analysis of the SBR group. 
The analysis windows for HIV-1 RNA, hematology, chemistry, urinalysis, urine pregnancy 
laboratory tests, eGFRCG, vital signs, and weight are presented in Table 3-2. 
Table 3-2. 
Analysis Windows for HIV-1 RNA, Hematology, Chemistry, 
Urinalysis, Urine Pregnancy Laboratory Tests, eGFRCG, Vital Signs, 
Weight, and VAS 
 
 
B/F/TAF 
SBR 
Visit ID 
Nominal Day 
Lower Limit 
Upper Limit 
Lower Limit 
Upper Limit 
Baseline 
 
 
1 
 
1 
Week 4 
28 
2 
56 
2 
56 
Week 12 
84 
57 
126 
57 
126 
Week 24^ 
168 
127 
210 
127 
210* 
Week 36 
252 
211 
294 
 
 
Week 48 
336 
295 
378 
 
 
^ VAS is collected for SBR group only and only through Week 24 
*For SBR group, values after the first day of B/F/TAF will be excluded. 
The analysis windows for the HIV Symptoms Distress Module, HIVTSQs (at Day 1 only) and 
HIVTSQc (Week 4 and Week 24 only) are presented in Table 3-3. 
Table 3-3. 
Analysis Windows for HIV Symptoms Distress Module, HIVTSQs (at 
Day 1 only), and HIVTSQc (Week 4 and Week 24 only) 
 
 
B/F/TAF 
SBR 
Visit ID 
Nominal Day 
Lower Limit 
Upper Limit 
Lower Limit 
Upper Limit 
Baseline 
1 
 
1 
 
1 
Week 4 
28 
2 
98 
2 
98 
Week 24 
168 
99 
252 
99 
252* 
Week 48 
336 
253 
420 
 
 
*For SBR group, values after the first day of B/F/TAF will be excluded. 
The analysis windows for CD4+ cell count, CD4 %, metabolic assessments (including fasting 
glucose and lipid panel: total cholesterol, high density lipoprotein [HDL], direct low density 
lipoprotein [LDL], triglycerides, and total cholesterol to HDL ratio), and plasma HBV DNA are 
presented in Table 3-4. 


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Table 3-4. 
Analysis Windows for CD4+ cell count, CD4 %, Metabolic 
Assessments, and Plasma HBV DNA 
 
 
B/F/TAF 
SBR 
Visit ID 
Nominal Day 
Lower Limit 
Upper Limit 
Lower Limit 
Upper Limit 
Baseline 
1 
 
1 
 
1 
Week 24 
168 
2 
252 
2 
252* 
Week 48 
336 
253 
420 
 
 
*For SBR group, values after the first day of B/F/TAF will be excluded. 
3.8.3. 
Selection of Data in the Event of Multiple Records in an Analysis Window 
Depending on the statistical analysis method, single values are required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time to event analysis would not require one value per analysis window. When a single value is 
needed, the following rule(s) will be used.  
If multiple nonmissing numeric observations exist in a window, then records will be chosen as 
follows: 
• For baseline, the latest available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, average will be used for the baseline value, except for HIV-1 RNA (see below).  
• For postbaseline visits: 
 For CD4+ cell count, CD4%, and 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. 


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If multiple valid nonmissing categorical observations exist in a window, records will be chosen 
as follows: 
• For baseline, the last available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected. 
• 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 investigator site will be summarized 
by treatment group (B/F/TAF and SBR) and overall using the safety analysis set. The 
denominator for this calculation will be the number of subjects in the safety analysis set. 
Similarly, the number and percentage of subjects enrolled in each randomization stratum will be 
summarized based on reclassified strata using the baseline 3rd agent ARV class based on the 
Non-Study ARV Medication eCRF. 
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 (B/F/TAF and SBR) 
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, and subjects in the Week 24 PP. 
In addition, the number and percentage of the subjects in the following categories will be 
summarized: 
• Completed 24 weeks on randomized drug (see programming specifications) 
• Prematurely discontinuing study drug prior to 24 weeks on randomized drug (with summary 
of reasons for discontinuing study drug) (see programming specifications) 
• Delayed Switch to B/F/TAF (only for Treatment Group 2 [SBR] subjects) 
• Still on study drug up to the data cut date 
• Prematurely discontinuing study drug prior to the data cut date (with summary of reasons for 
discontinuing study drug) 
• Still on study up to the data cut date 
• Prematurely discontinuing from study prior to Week 24 (with summary of reasons for 
discontinuing study) (see programming specifications) 
• Prematurely discontinuing from study prior to the data cut date (with summary of reasons for 
discontinuing study). 


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The denominator for the percentages of subjects in each category will be the number of subjects 
in the safety analysis set.  
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided. 
4.2. 
Extent of Study Drug Exposure and Adherence 
4.2.1. 
Duration of Exposure to Study Drug 
Duration of exposure will be calculated for the following groups: B/F/TAF, SBR, and Delayed 
Switch B/F/TAF). Duration of exposure to study drug will be defined as (the last dose date – the 
first dose date + 1), regardless of temporary interruptions in study drug administration, and will 
be expressed in weeks using up to 1 decimal place (eg, 4.5 weeks). For the calculation of the 
duration of exposure to study drug, the data cut date will be used to impute the last dose date for 
subjects who have not permanently discontinued study drug at the time of the data cut date. See 
Section 3.8.1 for description of first dose and last dose for SBR and Delayed Switch B/F/TAF. 
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). 
Summaries will be provided for subjects in the safety analysis set. No inferential statistics will be 
provided.  
4.2.2. 
Adherence to Study Drug Regimen 
Study drug regimen adherence will be computed based on pill counts for B/F/TAF study drug 
only (ie, B/F/TAF and Delayed Switch B/F/TAF). The numbers of pills of study drug dispensed 
and returned are captured on study drug accountability eCRF. 
Adherence (%) of study drug regimen will be calculated as follows: 
∑∑
∑∑
×
=
×
=
]
2
[
]
1
[
period
 
dispensing
each 
at 
 
prescribed
 
pills
 
of
 
No.
period
 
dispensing
each 
at 
 taken 
pills
 
of
 
No.
100
 
prescribed
 
pills
 
of
 
No.
 
Total
 taken
pills
 
of
 
No.
 
Total
100
 
 
(%)
 
Adherence
 
[1] Number of pills taken at a distinct dispensing period for a study drug is calculated as the minimum of (a) the daily number of 
pills prescribed for the study drug multiplied by the duration of treatment at the dispensing period, and (b) the number of pills 
taken for the study drug (number of pills dispensed minus the number of pills returned). Total number of pills taken is determined 
by summing the number of pills taken 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. 


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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. 
Adherence up to the data cut date will be calculated using all data from the entire dosing period 
up to the date of permanent discontinuation of the study drug for subjects who prematurely 
discontinued study drug or completed study drug, or using all data available for subjects who are 
ongoing on study drug.  
Adherence up to the Week 24 visit will be calculated for the B/F/TAF treatment group using all 
data from the entire dosing period up to the date of permanent discontinuation of the study drug 
for subjects who prematurely discontinued study drug or completed study drug, or the Week 24 
study drug dispensing date, whichever occurs earliest. 
For the Delayed Switch B/F/TAF treatment group, adherence up to Week 24 on B/F/TAF will be 
calculated using all data from the entire dosing period up to the date of permanent 
discontinuation of the study drug for subjects who prematurely discontinued study drug or 
completed study drug, or the Week 48 study drug dispensing date, whichever occurs earliest. 
Descriptive statistics for adherence up to the data cut date and adherence up to Week 24 visit for 
a study drug regimen (n, mean, SD, median, Q1, Q3, minimum, and maximum) along with the 
number and percentage of subjects belonging to adherence categories (eg, < 80%, ≥ 80% to 
< 90%, ≥ 90% to < 95%, ≥ 95%) will be provided for Treatment Group 1 for subjects who return 
at least 1 bottle and have calculable adherence during the study in the safety analysis set. No 
inferential statistics will be provided. 
4.3. 
Protocol Deviations 
A listing will be provided for all randomized subjects who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met. A listing of subjects who 
received the wrong study drug will also be provided. 
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason and the total number of important protocol deviations by deviation reason (eg, 
nonadherence to study drug, violation of select inclusion/exclusion criteria) will be summarized 
by treatment group (B/F/TAF, SBR) for the Full Analysis Set. A by-subject listing will be 
provided for those subjects with important protocol deviations.  


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5. 
BASELINE CHARACTERISTICS 
5.1. 
Demographics and Baseline Characteristics 
Subject demographic data (eg, age, sex at birth, gender identity, sexual orientation, race, and 
ethnicity) and baseline characteristics (eg, body weight, height, and body mass index [BMI]) will 
be summarized by treatment group (B/F/TAF and SBR) and overall using descriptive statistics 
(n, mean, SD, median, Q1, Q3, minimum, and maximum) for continuous data and by the number 
and percentage of subjects for categorical data. The summaries of demographic data and baseline 
subject characteristics will be provided for the safety analysis set. 
For categorical data, the Cochran-Mantel-Haenszel (CMH) test (ie, general association statistic 
for nominal data) will be used to compare the 2 treatment groups. For continuous data, the 
2-sided Wilcoxon rank sum test will be used to compare the 2 treatment groups. 
5.2. 
Baseline Disease Characteristics 
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics: 
• HIV-1 RNA categories (copies/mL): (a) < 50, (b) ≥ 50 
• CD4+ cell count (/μL) 
• CD4+ cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, 
(d) ≥ 350 to < 500, and (e) ≥ 500  
• CD4 percentage (%) 
• Mode of infection (HIV risk factors) 
• HIV disease status 
• eGFRCG (mL/min) 
• 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) 
• Duration of HIV Diagnosis (years) (calculated as years prior to year from First Dose/Day 1 
date; see programming specifications) 
• Duration of  HIV Treatment (Years) (calculated as years prior to year from First Dose/Day 1 
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• Duration of baseline ARV medication prior to randomization (based on the Non-Study ARV 
Medication eCRF, see programming specifications) 
• Baseline ARV Regimen (based on the Non-Study ARV Medication eCRF, see programming 
specifications) 
 Baseline ARV Medication Backbone (FTC+TAF, FTC+TDF, TDF+3TC, ABC+3TC, 
AZT+3TC) 
 Baseline 3rd agent (INSTI, NNRTI, PI, CCR5), and further broken down by ingredient 
 Baseline ARV Medication (Backbone+3rd agent) 
For categorical data, the CMH test (general association statistic for nominal data, and row means 
scores differ statistic for ordinal data) will be used to compare the 2 treatment groups. For 
continuous data, the 2-sided Wilcoxon rank sum test will be used to compare the 2 treatment 
groups.   
5.3. 
Medical History 
General medical history data will be collected at screening and listed only. General medical 
history data will not be coded. 


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6. 
EFFICACY ANALYSES 
6.1. 
Primary Efficacy Endpoint 
6.1.1. 
Definition of the Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at 
Week 24 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. 
6.1.2. 
US FDA-Defined Snapshot Algorithm 
The analysis window at Week 24 is defined as from Study Day 127 to Study Day 210, inclusive. 
All HIV-1 RNA data collected on-treatment will be used in the US FDA-defined snapshot 
algorithm. On-treatment is defined for B/F/TAF and the Delayed Switch to B/F/TAF treatment 
groups as all data collected up to 1 day after permanent discontinuation of study drug or all 
available data for subjects who were still on study drug.  On-treatment is defined for the SBR 
treatment group as all data collected up to 1 day after permanent discontinuation of baseline 
ARV medication or all available data on or before the date of the first B/F/TAF dose for subjects 
who switched to B/F/TAF. 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 24 analysis window 
• 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 24 analysis 
window, or 
Who do not have on-treatment HIV-1 RNA data in the Week 24 analysis window and  
i) Who discontinue study drug prior to or in the Week 24 analysis window due to lack 
of efficacy, or 
ii) Who discontinue study drug prior to or in the Week 24 analysis window due to AE or 
death and have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or  
iii) Who discontinue study drug prior to or in the Week 24 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. 


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• No Virologic Data in the Week 24 Window: this includes subjects who do not have 
on-treatment HIV-1 RNA data in the Week 24 analysis window because of the following:  
a) Discontinuation of study drug prior to or in the Week 24 analysis window due to AE or 
death and the last available on-treatment HIV-1 RNA < 50 copies/mL, or 
Discontinuation of study drug prior to or in the Week 24 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, 
Missing data during the window but on study drug. 
The flowchart of the US FDA-defined snapshot algorithm is provided in Appendix 2. 
The Week 24 virologic outcomes for the US FDA-defined snapshot algorithm will be 
summarized for the B/F/TAF and SBR groups. Results will be listed for B/F/TAF, SBR, and 
Delayed Switch to B/F/TAF treatments. 
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 are classified in the “No Virologic Data in the Week 24 Window” 
category. 
6.1.3. 
Statistical Hypothesis for the Primary Efficacy Endpoint 
Null hypothesis: The B/F/TAF group (Treatment Group 1) is at least 6% higher than the SBR 
group (Treatment Group 2) with respect to the proportion of subjects with HIV-1 RNA 
≥ 50 copies/mL as determined by the US FDA-defined snapshot algorithm) at Week 24. 
Alternative hypothesis: The B/F/TAF group (Treatment Group 1) is less than 6% higher than 
the SBR group (Treatment Group 2) with respect to the proportion of subjects with HIV-1 RNA 
≥ 50 copies/mL at Week 24. 
6.1.4. 
Primary Analysis of the Primary Efficacy Endpoint 
The analysis purpose of the primary efficacy endpoint is to assess the noninferiority of switching 
to B/F/TAF relative to a regimen of 2 NRTIs and a third agent (SBR). Noninferiority will be 
assessed using a conventional 95% CI approach, with a noninferiority margin of 6%. 
The point estimate of treatment difference (B/F/TAF group – SBR group) in the percentage of 
subjects with HIV-1 RNA ≥ 50 copies/mL and the associated 2-sided 95% CI will be constructed 
based on an unconditional exact method using 2 inverted 1-sided tests. 
It will be concluded that B/F/TAF is noninferior to SBR if the upper bound of the 2-sided 95% CI 
of the difference between treatment groups (B/F/TAF group – SBR group) in the percentage of 
subjects with HIV-1 RNA ≥ 50 copies/mL is less than 6%.  


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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 24 will be summarized. 
If noninferiority of B/F/TAF versus SBR is established, the same 95% CI used in evaluating 
noninferiority at Week 24 will be used to evaluate superiority. If the upper bound of the 95% CI 
is less than 0, then superiority of B/F/TAF over SBR is established. The 2-sided Fisher’s exact 
test will also be used to assess superiority as a secondary assessment.  
The FAS will be used for the primary efficacy endpoint analysis and the superiority evaluation. 
6.1.5. 
Secondary Analysis of the Primary Efficacy Endpoint 
A secondary analysis based on the Week 24 PP analysis set will be performed to evaluate the 
robustness of the primary analysis of the primary endpoint. For this secondary analysis, 95% CI 
for the treatment difference in the primary efficacy endpoint will be calculated based on an 
unconditional exact method using 2 inverted 1-sided tests. 
6.2. 
Secondary Efficacy Endpoints 
6.2.1. 
Definition of the Secondary Efficacy Endpoints 
The secondary efficacy endpoints include: 
• The proportion of subjects with HIV-1 RNA  ≥ 50 copies/mL at Week 48 as determined by 
the US FDA-defined snapshot algorithm 
• The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 24 and Week 48 as 
determined by the US FDA-defined snapshot algorithm 
• The change from baseline in CD4+ cell count at Week 24 and Week 48  
The analysis of secondary endpoints related to Week 48 will be described in a future SAP. The 
analyses for the Week 24 secondary efficacy endpoints will be conducted using both the FAS 
and the Week 24 PP analysis set. 
6.2.2. 
Analysis of the Secondary Efficacy Endpoints 
6.2.2.1. 
Analysis of the Proportion of Subjects with HIV-1 RNA < 50 copies/mL as 
Determined by US FDA-defined Snapshot Algorithm  
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 24 will also be analyzed 
by the US FDA-defined snapshot algorithm based on both the FAS and Week 24 PP analysis set. 
Proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 24 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%. 


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Similarly to the primary efficacy endpoint, noninferiority will be assessed using the conventional 
CI approach. The point estimate of treatment difference (B/F/TAF group – SBR group) in the 
percentage of subjects with HIV-1 RNA < 50 copies/mL and the associated 2-sided 95% CI will 
be constructed based on an unconditional exact method using 2 inverted 1-sided tests. 
It will be concluded that B/F/TAF is noninferior to SBR if the lower bound of the 2-sided 95% CI 
of the difference between treatment groups (B/F/TAF group – SBR group) in the percentage of 
subjects with HIV-1 RNA < 50 copies/mL is greater than −10%. 
6.2.2.2. 
Subgroup Analysis of the Proportion of Subjects with HIV-1 RNA 
< 50 copies/mL at Week 24 as Determined by US FDA-defined Snapshot 
Algorithm 
Because the proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Week 24 as determined by 
the US FDA-defined snapshot algorithm (primary endpoint) is expected to be very low (around 
4%), 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 24 (a secondary efficacy endpoint) within each subgroup specified in Section 3.4.1 based 
on the FAS. 
For each level of subgroup factors, the proportion difference between treatment groups and the 
associated 2-sided 95% CIs will be computed based on an unconditional exact method using 
2 inverted 1-sided tests.  
Additionally, a logistic regression model will be performed which will 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 24 and their associated 95% CIs for each subgroup will be 
generated. 
6.2.2.3. 
Analysis of CD4+ Cell Count 
All CD4+ cell count will be summarized for B/F/TAF and SBR treatment groups using observed, 
on-treatment data.  On-treatment data is defined for B/F/TAF as all data collected up to 1 day 
after permanent discontinuation of study drug or all available data for subjects who were still on 
study drug.  On-treatment data is defined for SBR as all data collected up to 1 day after 
permanent discontinuation of baseline ARV medication or all available data on or before the date 
of the first B/F/TAF dose for subjects who switched to B/F/TAF. 
The changes from baseline in CD4+ cell count at Week 24 will be summarized by treatment 
group using descriptive statistics. The differences in changes from baseline in CD4+ cell count 
between the 2 treatment groups and the associated 95% CI will be constructed using analysis of 
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The change from baseline in CD4+ cell counts will also be analyzed based on the Week 24 
PP analysis set. 
In addition, the change from baseline in CD4+ cell counts with missing values imputed using the 
last observation caITied fo1ward (LOCF) method will be summarized at Week 24 based on the 
FAS. The algorithm for LOCF is as follows: 
• 
If a value is missing in an analysis visit window, the missing value will be replaced with the 
last on-treatment value. 
• 
Baseline values will be caITied fo1ward to impute the postbaseline value at a specific visit, if 
there is no non-missing postbaseline observation collected prior to that visit. 
6.3. 
6.3.1. 
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Definition of the Tertiary Efficacy Endpoints 
Analysis of the Tertiary Efficacy Endpoints 
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Changes From Protocol-Specified Efficacy Analyses 
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The protocol specified a fourth criterion for the FAS (at least 1 post baseline HIV-1 RNA result 
while on study ti·eatment); however this criterion was removed to eliminate potential bias. 
The Week 24 PP analysis set definition was updated to exclude subjects who do not meet the 
inclusion criteria for baseline ARV regimen (Protocol Section 3.2) and to exclude subjects who 
have INST! resistance-associated mutations, including pre-existing mutations that are detected 
post-baseline. The exclusion for adherence rate below the 2.5th percentile was removed because 
adherence cannot be calculated for the SBR group. 
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7. 
SAFETY ANALYSES 
Safety data will be summarized for the subjects in the safety analysis set. All safety data 
collected up to 30 days after permanent discontinuation of study drug and all available data for 
subjects who were still on study drug will be summarized by treatment group, unless specified 
otherwise. All safety data will be included in data listings. 
7.1. 
Adverse Events and Deaths 
Summaries of AEs by treatment group (B/F/TAF, SBR, Delayed Switch to B/F/TAF, All 
B/F/TAF) will include data collected up to: 
• For subjects in the B/F/TAF, Delayed Switch B/F/TAF, and All B/F/TAF treatment groups, 
AEs with onset date on or before 30 days after permanent discontinuation of study drug, or 
all AEs if the subject is receiving study drug 
• For subjects in the SBR treatment group, AEs with onset date on or before the minimum of 
(1) 30 days after permanent discontinuation of baseline ARV medication, or (2) the day prior 
to the first dose date of B/F/TAF 
Summaries of AEs up to Week 24 by treatment group (B/F/TAF, SBR) will include data 
collected up to: 
• For subjects in the B/F/TAF treatment group, AEs with onset date on or before the minimum 
of (1) 30 days after permanent discontinuation of study drug or (2) the day of the Week 24 
visit 
• For subjects in the SBR treatment group, AEs with onset date on or before the minimum of 
(1) 30 days after permanent discontinuation of baseline ARV medication, or (2) the day prior 
to the first dose date of B/F/TAF 
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.  


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7.1.3. 
Relationship of Adverse Events to Study Drug 
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing. 
7.1.4. 
Serious Adverse Events 
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Pharmacovigilance and 
Epidemiology (PVE) Department before data finalization. 
7.1.5. 
Treatment-Emergent Adverse Events 
7.1.5.1. 
Definition of Treatment-Emergent Adverse Events 
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following: 
For subjects who received B/F/TAF: 
• Any AEs with an onset date on or after the B/F/TAF study drug start date and no later than 
30 days after permanent discontinuation of the B/F/TAF study drug, or  
• Any AEs leading to premature discontinuation of B/F/TAF study drug. 
For subjects in SBR treatment group: 
• Any AEs with an onset date on or after Study Day 1 and on or before the minimum of 
(1) 30 days after permanent discontinuation of baseline ARV medication or (2) the day prior 
to the first dose date of B/F/TAF 
• Any AEs leading to premature discontinuation of baseline ARV medication. 
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 
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An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date marked as ongoing or on or after the first dosing date of study drug, will be considered to be 
treatment emergent. In addition, an AE with the onset date missing and incomplete stop date 
with the same or later month and year (or year alone if month is not recorded) as the first dosing 
date of study drug will be considered treatment emergent. 
7.1.6. 
Summaries of Adverse Events and Death 
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group (B/F/TAF, SBR, Delayed Switch to 
B/F/TAF, and All B/F/TAF). For other AEs described below, summaries will be provided by 
SOC, PT, and treatment group (B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF) 
using the safety analysis set: 
• Any Grade 2, 3, or 4 treatment-emergent AEs 
• Any Grade 3 or 4 treatment-emergent AEs 
• All treatment-emergent study drug-related AEs  
• Any Grade 2, 3, or 4 treatment-emergent study drug-related AEs 
• Any Grade 3 or 4 treatment-emergent study drug-related AEs 
• All treatment-emergent SAEs 
• All treatment-emergent study drug-related SAEs 
• All treatment-emergent AEs that caused premature discontinuation from study drug 
A brief, high-level summary of AEs described above will be provided by treatment group 
(B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF) 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. 


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Summary of treatment-emergent AEs by SOC and PT will also be conducted for all subgroups 
listed in Section 3.4.2. 
A second set of summaries will be provided that summarize only B/F/TAF and SBR through the 
Week 24 visit. 
Data listings will be provided for the following: 
• All AEs 
• All AEs through Week 24 
• Study-Drug-Related AEs 
• Grade 3 and 4 AEs 
• SAEs 
• Study-Drug-Related SAEs 
• Deaths report 
• AEs leading to premature discontinuation of study drug 
Listings will include all AEs, and AEs up to Week 24 will be flagged. 
7.1.7. 
Additional Analysis of Adverse Events 
7.1.7.1. 
Stage 3 Opportunistic Illnesses in HIV 
On an ongoing basis, AEs will be reviewed for events that might meet the definition of stage 3 
opportunistic illnesses in HIV that are indicative of an AIDS-defining diagnoses (see Protocol 
Appendix 6). The Gilead medical monitor will review the possible stage 3 opportunistic illnesses 
and approve the events that meet the definition. Events that meet the stage 3 opportunistic illness 
definition of an AIDS-Defining Diagnosis will be listed. 
7.1.7.2. 
Cardiovascular or Cerebrovascular Events 
Preferred terms for cardiovascular or cerebrovascular events are from relevant Standardised 
MedDRA Query (SMQ). The selected PT listing was provided by Gilead PVE and reviewed by 
Gilead medical monitors (see details in Appendix 3). 
The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
summarized by treatment group (B/F/TAF, SBR, Delayed Switch to B/F/TAF, and All B/F/TAF) 
based on the safety analysis set. A second summary will be prepared that only includes B/F/TAF 
and SBR treatment groups (up to Week 24). The second summary will include a statistical 
comparison of the subject incidence rates (up to Week 24) between the B/F/TAF and SBR 
treatment groups using Fisher’s exact test. A data listing of cardiovascular or cerebrovascular 
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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 PVE and reviewed by Gilead medical monitors (see details in Appendix 4). 
The number and percentage of subjects with treatment-emergent hepatic events and serious 
hepatic events by PT will be summarized by treatment group (B/F/TAF, SBR, Delayed Switch to 
B/F/TAF, and All B/F/TAF) based on the safety analysis set. A second summary will be 
prepared that only includes B/F/TAF and SBR treatment groups (up to Week 24). The second 
summary will include a statistical comparison of the subject incidence rates (up to Week 24) 
between the B/F/TAF and SBR treatment groups using Fisher’s exact test. A data listing of 
hepatic events will be provided. 
7.2. 
Laboratory Evaluations 
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to:  
• For subjects in the B/F/TAF or Delayed Switch to B/F/TAF treatment groups who have 
permanently discontinued B/F/TAF study drug, the last dose of B/F/TAF study drug plus 
30 days. 
• For subjects in the B/F/TAF or Delayed Switch to B/F/TAF treatment groups who are still on 
study drug, data through the data cut date 
• For subjects in the SBR treatment group, the minimum of (1) 30 days after permanent 
discontinuation of baseline ARV medication, or (2) the first dose date of B/F/TAF 
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 
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7.2.1. 
Summaries of Numeric Laboratory Results 
Descriptive statistics will be provided by treatment group (B/F/TAF, SBR, and Delayed Switch 
to B/F/TAF) 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)).  
Toxicity grading for calcium will be applied based on the corrected values. 
Estimated GFR 
The following formula will be used to calculate eGFRCG:  
• eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / 
(SCr (mg/dL) × 72), where weight is total body mass in kilograms, and SCr is serum 
creatinine. 
7.2.2. 
Graded Laboratory Values 
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used for assigning toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction 
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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 the cutoffs specified at the 
start of Section 7.2.  
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. Most subjects 
had a nonfasting glucose at the Screening visit and a fasting glucose at the Day 1 visit; therefore, 
both a baseline nonfasting glucose and a baseline fasting glucose are available for most subjects, 
and treatment-emergent laboratory abnormalities will be summarized for both nonfasting glucose 
and fasting glucose. 
Both urine 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. 
7.2.2.2. 
Summaries of Laboratory Abnormalities 
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group (B/F/TAF, SBR, and Delayed 
Switch to B/F/TAF); subjects will be categorized according to the most severe postbaseline 
abnormality grade for a given lab test: 
• Treatment-emergent laboratory abnormalities 
• Treatment-emergent Grade 3 and 4 laboratory abnormalities  
A second set of summaries will be produced that only includes the B/F/TAF and SBR treatment 
groups through the upper bound of the Week 24 analysis window. 
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
any nonmissing postbaseline values for the particular laboratory test.  


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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. Results that are within the upper bound of the Week 24 analysis window 
will be flagged. 
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 for the B/F/TAF, SBR, and Delayed Switch to B/F/TAF groups. 
P-values comparing the difference between the B/F/TAF and SBR groups in baseline values and 
the change from baseline in metabolic assessment will be estimated from a 2-sided Wilcoxon 
rank sum test. 
In addition, the number and percentage of subjects who took lipid modifying medications at 
study entry and initiated the medications during the study (up to Week 24) will be provided for 
the B/F/TAF and SBR treatment groups. Statistical comparisons of the subject incidence rates 
between the 2 treatment groups will be performed using Fisher’s exact test.  
A lipid modifying medication is defined as a medication with drug class (based on World Health 
Organization [WHO] Drug ATC2 term) = “LIPID MODIFYING AGENTS” and WHO Drug 
preferred drug name containing the wording of “STATIN”. 
A sensitivity analysis of fasting lipid tests will be performed by excluding subjects who took 
lipid modifying medications at study entry or initiated the medications during the study (up to 
Week 24): baseline values, Week 24 values, and changes from baseline at Week 24 will be 
summarized by treatment group (B/F/TAF and SBR) using descriptive statistics. Baseline and 
change from baseline at Week 24 will be compared between the 2 treatment groups using a 
2-sided Wilcoxon rank sum test. Only subjects with both baseline and Week 24 values will be 
included in the analysis.  
Summary of baseline, postbaseline, and change from baseline in fasting metabolic laboratory 
tests will be repeated within each subgroup of baseline ARV medication (see Section 3.4.2). 
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. 
Median (Q1, Q3) of change from baseline in fasting metabolic assessments over time will be 
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7.2.4. 
Liver-Related Laboratory Evaluations 
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of subjects who were reported to have the following laboratory 
test values for postbaseline measurements: 
• 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 
For individual laboratory tests, subjects will be counted once based on the most severe 
postbaseline value. For both the composite endpoint of AST or ALT and total bilirubin, and the 
composite endpoint of AST or ALT, total bilirubin, and ALP, subjects will be counted once 
when the criteria are met at the same postbaseline visit date. The denominator is the number of 
subjects in the safety analysis set with nonmissing postbaseline value of the tests in evaluation at 
the same postbaseline visit date. 
A second summary will be produced that only summarizes B/F/TAF and SBR through the upper 
bound of the Week 24 analysis visit window. 
Subjects with AST or ALT > 3 × ULN will also be listed. 
In addition, baseline, postbaseline, and change from baseline in AST, ALT, ALP, and total 
bilirubin will be summarized by treatment group (B/F/TAF, SBR, and Delayed Switch to 
B/F/TAF and visit using descriptive statistics. Baseline and change from baseline will be 
compared between the B/F/TAF and SBR treatment groups using a 2-sided Wilcoxon rank sum 
test. 
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. The first occurrence of two or more consecutive 
ALT elevations will be identified as the ALT flare. 


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7.2.5. 
Renal-Related Laboratory Evaluations 
7.2.5.1. 
Serum Creatinine and eGFRCG 
Baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG will be 
summarized by treatment group (B/F/TAF, SBR, and Delayed Switch to B/F/TAF) and visit 
using descriptive statistics. Baseline and change from baseline will be compared between the 
B/F/TAF and SBR treatment groups using a 2-sided Wilcoxon rank sum test.  
Median (Q1, Q3) of change from baseline in serum creatinine and eGFRCG over time will be 
plotted by treatment group.  
Summary of baseline, postbaseline, and change from baseline in serum creatinine and eGFRCG 
will be repeated within each subgroup of baseline ARV medication (see Section 3.4.2). P-values 
comparing the difference between the B/F/TAF and SBR treatment groups in baseline values and 
the change from baseline in metabolic assessment will be generated from a 2-sided Wilcoxon 
rank sum test. 
7.2.5.2. 
Proteinuria by Urinalysis (Dipstick) 
The proteinuria by urinalysis (dipstick) toxicity grade (Grade 0 to Grade 3) at Week 12 and 
Week 24 will be summarized by baseline proteinuria toxicity grade and treatment group 
(B/F/TAF and SBR). In addition, the last on-treatment proteinuria toxicity grade will be 
summarized by baseline proteinuria toxicity grade and treatment group. On-treatment data is 
defined for the B/F/TAF treatment group as all data collected up to 1 day after permanent 
discontinuation of study drug or all available data for subjects who were still on study drug.  
On-treatment data is defined for the SBR treatment group as all data collected up to 1 day after 
permanent discontinuation of baseline ARV medication or all available data on or before the date 
of the first B/F/TAF dose for subjects who switched to B/F/TAF.  
The distribution of proteinuria toxicity grade at Weeks 24 and 48 and at the last on treatment 
value, respectively, will be compared between B/F/TAF and SBR adjusting for baseline 
proteinuria toxicity grade using rank analysis of covariance {LaVange 2008}. 
7.3. 
Body Weight, Height, and Vital Signs 
Descriptive statistics will be provided by treatment group (B/F/TAF, SBR, and Delayed Switch 
to B/F/TAF) for vital signs and body weight as follows: 
• 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 antiretroviral (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.  
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 the date of first dose of study treatment up to the date of last dose of study 
treatment (as defined in Section 3.8.1) will be summarized (number and percentage of subjects) 
by treatment group (B/F/TAF, SBR, and Delayed Switch to B/F/TAF) and preferred drug name. 
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.  
A second summary will be produced that summarizes concomitant medications with onset up to 
Week 24 for the B/F/TAF and SBR treatment groups only. Use of concomitant medications from 
the date of first dose of study treatment up through the earliest of (1) date of last dose of study 
treatment (as defined in Section 3.8.1) and (2) date of Week 24 visit will be summarized. 
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 
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If the start and stop date of non-ARV medications are complete, the start date is not after last 
dose date and the stop date is not before first dose date, or the non-ARV medications are marked 
as ongoing and start date is on or before last dose date, the non-ARV medications are 
concomitant. 
Summaries of non-ARV concomitant medications will be provided for the safety analysis set. 
Subjects with any non-ARV concomitant medications will be listed. No inferential statistics will 
be provided. 
7.5. 
Electrocardiogram Results 
A by-subject listing for electrocardiogram (ECG) assessment results will be provided.  
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. 
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 
8.1. 
Analyses for HIV/HBV Coinfected Subjects 
Subjects with HIV/HBV coinfection at baseline are defined as subjects who meet any of the 
following two criteria:  
• Positive HBsAg on or prior to the first dose date, or 
• Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA (ie, HBV 
DNA ≥ 20 IU/mL) on or prior to the first dose date. 
The following analyses will be conducted by treatment (B/F/TAF and SBR) for subjects with 
HIV/HBV coinfection at baseline:  
• The proportion of subjects with HBV DNA < 29 IU/mL at baseline and Week 24 by missing 
= excluded approach.  
• The change from baseline in log10 HBV DNA (log10 IU/mL) at Week 24 
• Treatment-emergent adverse events overall summary through Week 24 
• Treatment-emergent adverse events by SOC, HLT, and PT through Week 24 
• Treatment-emergent laboratory abnormalities through Week 24 
The following analyses will be conducted by treatment (B/F/TAF, SBR, and Delayed Switch to 
B/F/TAF) for subjects with HIV/HBV coinfection at baseline:  
• 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. 
Listings will be provided for:  
• adverse events 
• liver-related laboratory tests and HBV DNA results 
• ALT elevation (ie, ALT > 2 x Baseline and ALT > 10 x ULN) and ALT flare (see section 
7.2.4) 


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HBV DNA will be analyzed using observed, on-treatment data for subjects in the FAS with 
HIV/HBV coinfection at baseline. On-treatment is defined for Treatment Group 1 (B/F/TAF) as 
all data collected up to 1 day after permanent discontinuation of study drug or all available data 
for subjects who were still on study drug.  On-treatment is defined for Treatment Group 2 (SBR) 
as all data collected up to 1 day after permanent discontinuation of baseline ARV medication or 
all available data on or before the date of the first B/F/TAF dose for subjects who switched to 
B/F/TAF. 
Subjects with incident HIV/HBV coinfection while on study drug are defined as subjects who are 
not HIV/HBV coinfected at baseline and meet any of the following criteria: 
For subjects in Treatment Group 1 (B/F/TAF) or subjects in Treatment Group 2 who switched to 
B/F/TAF: 
• Positive HBsAg after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
date, or 
• Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA (ie, HBV 
DNA ≥ 20 IU/mL) after the first B/F/TAF dose date and on or prior to the to the last 
B/F/TAF dose date, or 
• Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first B/F/TAF dose date and on or prior to the 
last B/F/TAF dose date: Acute hepatitis B, Chronic hepatitis B, Congenital hepatitis B 
infection, Hepatitis B, Hepatitis B core antibody positive, Hepatitis B DNA assay positive, 
Hepatitis B surface antigen positive, Hepatitis B virus test positive. 
For subjects in Treatment Group 2 (SBR): 
• Positive HBsAg after the first dose date and on or prior to the minimum of (1) the date of 
permanent discontinuation of baseline ARV medication, or  (2) the day prior to the first dose 
date of B/F/TAF, 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 minimum of (1) the date of 
permanent discontinuation of baseline ARV medication, or  (2) the day prior to the first dose 
date of B/F/TAF, or 
• Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first dose date and on or prior to the minimum of 
(1) the date of permanent discontinuation of baseline ARV medication, or  (2) the day prior 
to the first dose date of B/F/TAF: 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. 


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The following listings will be provided for subjects with incident HIV/HBV coinfection while on 
study drug:  
• Listing of adverse events 
• Listing of liver-related laboratory tests and HBV DNA results 
Adverse events with onset date after Week 24 and test results collected after Week 24 will be 
flagged.  
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 listings will be provided for subjects with HIV/HCV coinfection at baseline:  
• Listing of adverse events 
• Listing of liver-related laboratory tests and HCV RNA results   
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: 
For subjects in Treatment Group 1 (B/F/TAF) or subjects in Treatment Group 2 who switched to 
B/F/TAF: 
• Positive HCVAb after the first B/F/TAF dose date and on or prior to the last B/F/TAF dose 
date, or 
• Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the first B/F/TAF dose date and 
on or prior to the last B/F/TAF dose date, or 
• Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first B/F/TAF dose date and on or prior to the 
last B/F/TAF dose date: 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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For subjects in Treatment Group 2 (SBR): 
• Positive HCVAb after the first dose date and on or prior to the minimum of (1) the date of 
permanent discontinuation of baseline ARV medication, or (2) the day prior to the first dose 
date of B/F/TAF, 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 minimum of (1) the date of permanent discontinuation of baseline ARV medication, or 
(2) the day prior to the first dose date of B/F/TAF, or 
• Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) with onset date after the first dose date and on or prior to the minimum of 
(1) the date of permanent discontinuation of baseline ARV medication, or (2) the day prior to 
the first dose date of B/F/TAF: Acute hepatitis C, Chronic hepatitis C, Hepatitis C, 
Hepatitis C antibody positive, Hepatitis C RNA positive, Hepatitis C virus test positive. 
The following listings will be provided for subjects with incident HIV/HCV coinfection while on 
study drug:  
• Listing of adverse events 
• Listing of liver-related laboratory tests and HCV RNA results 


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9. 
PATIENT REPORTED OUTCOMES 
The patient-reported outcomes (PROs) include the following assessments: 
• HIV Symptoms Distress Module [assessed at Day 1, Week 4, Week 24, Week 28 
(SBR treatment group only, and Week 48)] 
• HIV Treatment Satisfaction Questionnaire Status  (HIV-TSQs, assessed at Day 1) 
• HIV Treatment Satisfaction Questionnaire Change (HIV-TSQc, assessed at Week 4 and 
Week 24) 
• VAS Adherence Questionnaire (assessed at Day 1, Week 4,  Week 12, and Week 24 for SBR 
group only) 
Summaries will be provided for the Safety Analysis Set and will include data collected up to: 
• For subjects in the B/F/TAF treatment group who have permanently discontinued B/F/TAF 
study drug, the last dose of B/F/TAF study drug plus 30 days. 
• For subjects in the B/F/TAF group who are still on study drug, data through the data cut date 
• For subjects in the SBR treatment group, the minimum of (1) 30 days after permanent 
discontinuation of baseline ARV medication, or (2) the first dose date of B/F/TAF 
Assessments will be listed using the Randomized Analysis set.  
9.1. 
HIV Symptoms Distress Module 
The Symptoms Distress Module is a self-completed questionnaire to evaluate symptoms and 
measure the presence and bothersomeness of side effects commonly seen with HIV and ARV 
treatment over the last 4 weeks (20 questions about all symptoms which the patient might have 
had during the past four weeks). Higher scores indicate the presence of more symptoms and/or a 
greater degree of distress related to the 20 symptoms.  
There are 5 possible responses for each HIV symptom. These responses will be analyzed as both 
categorical response and numerical response.  The mapping between the categorical response and 
the numerical response is listed in below. 
Categorical Response 
Numerical Response 
I do not have this symptom 
0 
Doesn’t bother 
1 
Bothers a little 
2 
Bothers 
3 
Bothers a lot 
4 
 


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If multiple responses are provided for a single question, then the largest (worst) value will be 
chosen (eg, (4) bothers a lot will be chosen over (3) bothers). This applies regardless of how 
many responses are provided. That is, if (1) doesn’t bother, (2) bothers a little, and (3) bothers 
are all marked, then (3) bothers will be used in the analysis. 
Missing values will not be imputed. 
For each question, the number and percentage of subjects in each category of the categorical 
responses will be summarized by treatment group (B/F/TAF and SBR) and visit (Baseline, 
Week 4, and Week 24). No inferential statistics will be generated.  
For each question, the numerical responses will be summarized by treatment group at baseline 
using descriptive statistics (sample size, mean, SD, median, Q1, Q3, minimum, and maximum). 
The baseline and change from baseline at Week 4 and Week 24 will be compared between 
treatment groups will be assessed using a Wilcoxon rank-sum test. 
9.2. 
Medication Adherence Questionnaire 
Adherence will be assessed by the medication adherence questionnaire that includes a VAS and 
2 additional questions. 
For the VAS, the subject is asked to describe their adherence to their ARV regimen by using a 
linear scale (0% – 100%) to indicate what percent of medications was taken in the last 30 days 
(0% = taken none of prescribed anti-HIV medication, and 100% = taken all doses of prescribed 
anti-HIV medication).  A value of “999” indicates a missing, ambiguous, or illegible response, 
and will be treated as a missing value for summaries. The 2 additional questions ask how many 
days the subject has missed medications in the last 30 days and how many days the subject has 
missed medications in the last 4 days. A value of “99” indicates a missing, ambiguous, or 
illegible response, and will be treated as a missing value for summaries. 
The VAS (%) absolute value and change from baseline at each study visit will be summarized 
for the SBR group using descriptive statistics. 
Number of days with missed doses in the past 30 days and past 4 days will be summarized 
categorically (< 2, 2 to < 4, 4 to < 6, ≥ 6 for the past 30 days; 0 and > 0 for the past 4 days) 
for each study visit. 
9.3. 
HIV Treatment Satisfaction Questionnaires 
The HIV Treatment Satisfaction Questionnaire (HIVTSQ) has 10 questions regarding current 
treatment regimen. The Status form HIVTSQs is used at Baseline, and the change form 
HIVTSQc is used at postbaseline visits.  
At baseline, a treatment satisfaction scale total will be calculated as the sum of the responses to 
the 10 question items on the HIVTSQs form (range from 0 to 60). At postbaseline visits, a 
treatment satisfaction scale total in change will be calculated as the sum of the responses to the 
10 question items on the HIVTSQc form (range from -30 to 30). 


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Additionally, two subscale scores, one for general satisfaction/clinical and another for 
lifestyle/ease will be computed. Each subscale ranges from 0 to 30 on the HIVTSQs form and 
from -15 to 15 on the HIVTSQc form. 
Table 9-1 lists the questions, possible responses for both the status and change questionnaires, as 
well as the subscale each question belongs to. 
Table 9-1. 
List of Items on the HIVTSQ 
Question 
Response Options for 
Status Form 
Response Options for 
Change Form 
Subscale 
How satisfied are you 
with your current 
treatment? 
Very satisfied 6 to 0 very 
dissatisfied 
Much more satisfied now 
3 to −3 much less satisfied 
now 
General 
Satisfaction/Clinical 
How well controlled do 
you feel your HIV has 
been recently? 
Very well controlled 6 to 0 
very poorly controlled 
Much better controlled now 
3 to −3 much worse 
controlled now 
General 
Satisfaction/Clinical 
How satisfied are you 
with any side effects of 
your present treatment? 
Very satisfied 6 to 0 very 
dissatisfied 
Much more satisfied now 
3 to −3 much less satisfied 
now 
General 
Satisfaction/Clinical 
How satisfied are you 
with the demands made by 
your current treatment? 
Very satisfied 6 to 0 very 
dissatisfied 
Much more satisfied now 
3 to −3 much less satisfied 
now 
Lifestyle/Ease 
How convenient have you 
been finding your 
treatment to be recently? 
Very convenient 6 to 0 very 
inconvenient 
Much more convenient now 
3 to −3 much less convenient 
now 
Lifestyle/Ease 
How flexible have you 
been finding your 
treatment to be recently? 
Very flexible 6 to 0 very 
inflexible 
Much more flexible now 
3 to −3 much less flexible 
now 
Lifestyle/Ease 
How satisfied are you 
with your understanding 
of your HIV? 
Very satisfied 6 to 0 very 
dissatisfied 
Much more satisfied now 
3 to −3 much less satisfied 
now 
Lifestyle/Ease 
How satisfied are you 
with the extent to which 
the treatment fits in with 
your lifestyle? 
Very satisfied 6 to 0 very 
dissatisfied 
Much more satisfied now 
3 to −3 much less satisfied 
now 
Lifestyle/Ease 
Would you recommend 
your present treatment to 
someone else with HIV? 
Yes I would definitely 
recommend the treatment 
6 to 0 No I would definitely 
not recommend the treatment 
Much more likely to 
recommend the treatment 
now 3 to −3 much less likely 
to recommend the treatment 
now 
General 
Satisfaction/Clinical 
How satisfied would you 
be to continue with your 
present form of treatment? 
Very satisfied 6 to 0 very 
dissatisfied 
Much more satisfied now 
3 to −3 much less satisfied 
now 
General 
Satisfaction/Clinical 
 


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The HIVTSQs scale and subscale totals at baseline, and the HIVTSQc scale and subscale totals 
at each visit will be summarized by treatment group (B/F/TAF and SBR) using descriptive 
statistics.  
Comparison between treatment groups in HIVTSQc scale total scores will use an analysis of 
covariance model adjusting for HIVTSQs scale total at Baseline. A similar analysis will be 
performed on the two subscale scores as well. 
For each subscale, if more than 1 question is missing, then the subscale total or subscale total in 
change will be set to missing. Otherwise, the missing total will be imputed by taking the average 
of non-missing responses from the other questions in that subscale. 
For the scale total or scale total in change, if more than 5 questions are missing, then the value 
will be set to missing. Otherwise, the missing total will be imputed by taking the average of 
nonmissing responses from the other questions. 
If two responses are provided for a single question, and the scores are next to each other, then the 
midpoint will be used. If two responses are provided for a single question, and the scores are not 
immediately next to each other, then the response will be considered missing.  
9.4. 
Change from Protocol Specified Analysis for Patient-Reported Outcomes 
There are no changes from the protocol-specified patient-reported outcomes analyses. 


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10. 
REFERENCES 
LaVange LM, Koch GG. Randomization-Based Nonparametric (ANCOVA). In: D'Agostino Sr. 
RB, Sullivan LM, Massaro JM, eds.  Wiley Encyclopedia of Clinical Trials. John 
Wiley & Sons, Inc.; 2008: 31-8. vol 4). 
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015. 
 
 


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11. 
SOFTWARE 
SAS Version 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures. 
PASS Version 14 (NCSS, LLC, Kaysville, Utah) was used for planned sample size and power 
calculation. 
 


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


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13. 
APPENDICES 
Appendix 1. 
Study Procedures Table 
Appendix 2. 
Flowchart of US FDA-defined Snapshot Algorithm (for Switch Trial) 
Appendix 3. 
Cardiovascular or Cerebrovascular Events 
Appendix 4. 
Hepatic Events 
Appendix 5. 
Programming Specifications 
 


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Appendix 1. 
Study Procedures Table 
Study Procedure 
Screeninga 
Day 1b 
End of Weekc 
Post Week 48e 
30 Day 
Follow-Upf 
ESDDg 
4 
12 
24 
28d 
36 
48 
Every 12 Weekscc 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
HIV Symptoms Distress Module 
 
X 
X 
 
X 
X 
 
X 
 
 
 
HIV-TSQh 
 
X 
X 
 
X 
 
 
 
 
 
 
VAS Adherence Questionnairei 
 
X 
X 
X 
X 
 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete/Symptom-Directed Physical Examj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG  
(performed supine) 
X 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Weight   
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signsk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Pregnancy Testl 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum Pregnancy Testl 
X 
 
 
 
 
 
 
 
 
 
 
FSH Testm 
X 
 
 
 
 
 
 
 
 
 
 
Chemistry Profilen 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Metabolic Assessmentso 
 
X 
 
 
X 
 
 
X 
X 
 
 
Estimated GFR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Study Procedure 
Screeninga 
Day 1b 
End of Weekc 
Post Week 48e 
30 Day 
Follow-Upf 
ESDDg 
4 
12 
24 
28d 
36 
48 
Every 12 Weekscc 
 
 
Hematology Profilep 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma HIV-1 RNAq 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CD4+ Cell Count and Percentager 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
HBV Blood Panels 
Xt 
 
 
 
 
 
 
Xt 
 
 
 
Plasma HBV DNAu 
 
X 
 
 
X 
 
 
X 
 
 
X 
HCV Serologyv 
X 
 
 
 
 
 
 
X 
X 
 
 
HIV-1 Genotype/Phenotypeq 
 
 
 
 
 
 
 
 
 
 
Xq 
Plasma, Serum, and Urine Sample Storagew 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Whole Blood for HIV-1 DNA archive testing 
 
X 
 
 
Xx 
 
 
 
 
 
 
Obtain Screening Number 
X 
 
 
 
 
 
 
 
 
 
 
Randomizationz 
 
X 
 
 
 
 
 
 
 
 
 
Study Drug Dispensation  
 
Xbb 
Xbb 
Xbb 
Xaa 
X 
X 
X 
X 
 
 
Study Drug Accountability 
 
 
Xbb 
Xbb 
X 
X 
X 
X 
X 
 
X 
a 
Evaluations to be completed within 30 days prior to Day 1. 
b 
Participants should initiate dosing of study drug on the same day as the Day 1 visit. 
c 
All study visits are to be completed ± 6 days of the protocol-specified visit date (based on the Day 1 visit), unless otherwise specified.  
d 
Participants randomized to continue their baseline regimen will have an additional visit at Week 28. 
e 
At the study Week 48 Visit, participants who wish to continue on B/F/TAF will be given the option to receive FDC of B/F/TAF for up to an additional 24 weeks or until they 
have access to FDC of B/F/TAF, whichever occurs first, and attend study visits every 12 weeks (± 6 days of the protocol specified visit date) followed by a 30 Day Follow-Up 
Visit.  
f 
Must be completed 30 days after discontinuing study drug. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used. Required for 
participants who permanently discontinue study drug prior to Week 48 and do not continue in the study through at least one subsequent visit after the ESDD visit. Participants 
who participate post Week 48 will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit.   
g 
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Participants will be asked to continue attending the scheduled study visits through 
the Week 48 Visit even if the participant discontinues study drug. Participants on Treatment 2 (SBR) who discontinue their baseline regimen due to an AE prior to Week 24 
will be asked to continue attending the scheduled study visits through the Week 24 visit. 
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h 
HIV-TSQs is to be completed at Day 1. The HIV-TSQc is to be completed at Week 4 and Week 24. Participant is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires. 
i 
VAS Adherence Questionnaire will be administered at Day 1 and at all visits up to (and including) Week 24 for participants in Treatment Group 2 (SBR) only. 
j 
Complete physical exam is required at Screening, Day 1, Week 24, 48, 72, and ESDD. Urogenital/anorectal exams will be performed at the discretion of the Investigator. 
Symptom-directed physical examination, as needed.  
k. 
Vital signs measurements including blood pressure, pulse, respiratory rate, and temperature. 
l 
All female participants will have a serum test performed at Screening. Urine pregnancy test will only be done for persons of childbearing potential. Positive urine pregnancy 
tests will be confirmed with a serum test.   
m 
FSH test is required for female participants who are <54 years old and have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure. 
n 
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, amylase, and Cystatin C. After Day 1, calcium, phosphorous, magnesium, and amylase (reflex lipase testing is 
performed in participants with total amylase > 1.5 x ULN) 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 24, 48, and 72. Cystatin C will only be collected at Day 1. 
o 
Metabolic Assessments will be performed at Day 1, Weeks 24, 48, and 72. 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 participant has not fasted prior to the visit, the visit may proceed, but the participant must return within 
72 hours in a fasted state to draw blood for the metabolic assessments. 
p 
CBC with differential and platelet count. 
q 
HIV-1 genotype and phenotype testing for participants with confirmed virologic failure and HIV-1 RNA >200 copies/mL. Following virologic rebound, participants 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, participants should be managed according to the Virologic 
Rebound Schema. 
r 
CD4+ Cell Count and Percentage to be collected at Screening and Day 1, and every 24 weeks thereafter, at Weeks 24, 48, and 72, in addition to the 30 Day Follow-up Visit 
and ESDD. 
s 
HBV blood panel will be performed at Screening and Week 48: HBsAg, HBsAb, HBcAb. 
 
t 
For participants who are HBV co-infected (defined in Protocol Section 6.9.1): The following HBV Blood panel will be conducted by the central laboratory: HBsAb, 
HBsAg (qualitative and quantitative), and HBeAg (if negative, reflex HBeAb). 
 
For participants who are NOT HBV co-infected: The following HBV Blood panel will be conducted by the central laboratory: HBsAb, HBcAb, and HBsAg. 
 
Participants who are HBsAg or HBcAb positive will have a reflex test for HBV DNA (viral load). 
u 
For participants who are HBV co-infected: Plasma HBV DNA will be collected at Day 1, Week 24, Week 48 and ESDD. 
v 
Hepatitis C virus serology will be performed at Screening, Week 48, and Week 72. Participants who are HCVAb positive will have a HCV RNA test performed. 
w 
Plasma, serum, and urine storage samples will be collected for safety, virology, or PK testing.  
x 
Collect whole blood sample for participants randomized to SBR only at Week 24. 
y 
 
z 
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 participant eligibility has 
been confirmed. 
aa 
At Week 24, participants randomized to continue their baseline regimen and complete 24 weeks of treatment on their baseline regimen will switch to FDC of B/F/TAF. 
bb FDC of B/F/TAF will be dispensed to Treatment Group 1 only. Study drug accountability will be performed accordingly. 
cc 
Subjects will receive study drug for dosing until Week 72. 
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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}. 
 
 
Is there at least l on-
treatment* HIV-I RNA data 
Y ----
-----.. 
es 
col lected in the Snapshot 
o 
Is the last available on-treatment* 
HIV-I RNA in the Snapshot 
window < 50 copies/mL? 
Yes 
HIV-1 Rl\A < 
50 copicii/m L 
HIV-I Rl A~ 
SO copie /mL 
window? 
ls study drug prematurely 
discontinued 0 11 or prior to the 
upper limit of the Snapshot 
window? 
Yes 
Is discontinuation of the study 
drng due to Lack of Efficacy'! 
No 
ls discontinuation of the study 
drug due to AE,/Dcath? 
Ye 
ls the last available on-
Is the last available on-
treatment* HIV-I RNA < treatment* HIV- I RNA < 
50 copies/mL 
o Virologie Data: 
Discontinued Study 
Drug Due to Other 
Reason and Last HIV-1 
R A < 50 copiCll/m L 
50 copies/mL 
No Virologic Data: 
Discontinued Study 
Drug Due to AEilleath 
and Last HIV-1 RNA < 
50 copicii/m L 
0 
No Virologic Data: 
Missing Data during 
Window but on Study 
Drug 
* On-Treatment HJV-1 RNA data include all HIV-I RNA data for subjects who are on-going and HIV-I RNA data up to I 
day after the last dose date of study drug for subjects who prematurely discontinue or complete study drug. 


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Appendix 3. 
Cardiovascular or Cerebrovascular Events 
An adverse event record will be flagged as a cardiovascular or cerebrovascular event if its 
MedDRA PT is included in the pre-specified PT list, which includes all PTs from the narrow 
search of the following 3 SMQs under MedDRA v22.0 provided by Gilead PVE (search name: 
Ischemic cardiac and cerebral events narrow) and reviewed by Gilead medical monitors. 
SMQ Source 
Cardiovascular or Cerebrovascular 
Events  
Ischaemic central nervous system vascular conditions (SMQ) – Narrow 
Scope Term 
Myocardial infarction (SMQ) - Narrow Scope Term 
Other ischaemic heart disease (SMQ) - Narrow Scope Term 
 


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Appendix 4. 
Hepatic Events 
An adverse event record will be flagged as a hepatic event if its MedDRA PT is included in this 
pre-specified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA v22.0 provided by Gilead PVE (search name: Non-infectious, non-congenital 
hepatobiliary disorders) and reviewed by Gilead medical monitors. 
SMQ Source 
Hepatic Events (HEP) 
Biliary neoplasms benign (incl cysts and polyps) (SMQ) 
Biliary malignant tumours (SMQ) 
Biliary tumours of unspecified malignancy (SMQ) 
Biliary system related investigations, signs and symptoms (SMQ) 
Biliary tract disorders (SMQ) 
Gallbladder related disorders (SMQ) 
Gallstone related disorders (SMQ) 
Cholestasis and jaundice of hepatic origin (SMQ) 
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ) 
Hepatitis, non-infectious (SMQ) 
Liver neoplasms, benign (incl cysts and polyps) (SMQ) 
Liver malignant tumours (SMQ) 
Liver tumours of unspecified malignancy (SMQ) 
Liver related investigations, signs and symptoms (SMQ) 
Liver-related coagulation and bleeding disturbances (SMQ) 
 


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Appendix 5. 
Programming Specifications 
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows: 
Only year is provided for the date of birth (DOB). Use July 1 for the month and day. 
AGE (years) is calculated from the number of days between the DOB and Study Day 1, 
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), 
Divide the result in (b) by 12, 
AGE = the integer of the result in (c), 
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, and ethnicity 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) is 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 the subject was never dosed. 
6) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF. 
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 ) 


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Baseline height and weight will be used for this calculation.    
8) SAS codes for the treatment comparison for demographics and baseline characteristics tables. 
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; 
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; 
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 from 
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.  
10)  Defining Baseline ARV Medication 
Baseline ARV Medication 
All subjects are expected to enter the study on an ARV regimen other than FDC of 
B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months (see 
Protocol Section 4.2 for allowed agents) 
Using the ARV raw dataset, for the B/F/TAF treatment group, include all prior and/or 
current ARVs (ARV.INGRED where ARV.CMSCAT =”Prior ARV” or “Current 
ARV”), taken on or up to 4 days prior to first dose date as defined in Section 3.8.1 (or 
randomization date if not treated). For the SBR treatment group, include all prior and/or 
current ARVs (ARV.INGRED where ARV.CMSCAT =”Prior ARV” or “Current ARV”) 
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Use the following rules to determine if the ARV medication is taken on Day 1:  
• If ARV end date is before B/F/TAF first dose date -4 for B/F/TAF subjects or Day 1 
date for SBR subjects then exclude. If “Ongoing” is not marked and the end date is 
completely missing, then exclude.  See below for imputation rules for any partial 
dates of uncertainty. 
• If ARV start date is after B/F/TAF first dose date for B/F/TAF subjects (or Day 1 
visit date for SBR subjects) then exclude. See below for imputation rules for any 
partial dates of uncertainty. 
The different categories used for the baseline ARV medication are (1) backbone, 
(2) third agent, and (3) third agent class. 
• For subjects with more than one baseline ARV medication record, concatenate the records 
together using “+” to get one record for each subject. For all ingredients, replace “_” or “+” 
with “/”. 
• For each subject, search for the NRTIs: FTC, TAD, TDF, ABC, AZT, and 3TC. There should 
be 2 NRTIs for each subject.  Create the backbone variable by concatenating the 2 NRTIs 
listed in the order above, and separate by a “/” as per the backbone column in the table 
below.  
• For each subject, identify the Third Agent. These will fall into 4 categories (PI, NNRTI, 
INSTI, and CCR5 antagonist). Each subject should have only 1 category of third agent unless 
they have a protocol deviation. For each subject, create the third agent variable by selecting 
on the ingredients listed: 
  PIs and boosted PIs include ATV, ATV/RTV, ATV/COBI, DRV/RTV, DRV/COBI, 
LPV/RTV, and NFV. Create the third agent variable by concatenating the ingredients 
(ATV, DRV, LPV, NFV, RTV, COBI) with a “/”. Change “ATV/RTV” to “ATV/r”, 
“ATV/COBI” to “ATV/co”,  “DRV/RTV” to “DRV/r”, “DRV/COBI” to “DRV/co”, and 
“LPV/RTV” to “LPV/r”, as per the Third Agent column in the table below. 
 NNRTIs include DOR, EFV, NVP, and RPV. ETR is not allowed, but is to be included 
for subjects who were not on a protocol-approved baseline ARV medication. 
 INSTIs include DTG, EVG/COBI, and RAL. Create the third agent variable by 
concatenating the ingredients (DTG, EVG, COBI, RAL). Change “EVG/COBI” to 
“EVG/co” as per the Third Agent column in the table below. RAL/RTV is a protocol 
violation and should be changed to “RAL/r”. 
 CCR5 antagonists include MVC. 


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 Each subject should have PI or NNRTI or INSTI or CCR5. If a subject has more than 
one, then it is a protocol violation. The third agent can be listed as “DTG/RPV”, and 
should be counted in both categories for summary purposes. 
 The final Baseline ARV Medication will be presented as third agent + backbone as per 
the last column in the table below. 
The table below provides example records for each subject with the backbone, 
third agent, third agent class, and final baseline ARV Medication variables. 
Baseline ARV Medications 
from the data 
Backbone 
Third Agent 
Third Agent 
Class 
Baseline ARV 
Medication 
ABC/NVP/FTC/TAF* 
ABC/FTC/TAF 
NVP 
NNRTI 
NVP+ABC/FTC/TAF 
ATV/ABC/3TC 
ABC/3TC 
ATV 
PI 
ATV + ABC/3TC 
ATV/RTV/ABC/3TC 
ABC/3TC 
ATV/r 
PI 
ATV/r + ABC/3TC 
ATV/RTV/FTC/TAF 
FTC/TAF 
ATV/r 
PI 
ATV/r + FTC/TAF 
ATV/RTV/FTC/TDF 
FTC/TDF 
ATV/r 
PI 
ATV/r + FTC/TDF 
ATV/COBI/FTC/TAF 
FTC/TAF 
ATV/co 
PI 
ATV/co + FTC/TAF 
DOR/FTC/TDF 
FTC/TDF 
DOR 
NNRTI 
DOR + FTC/TDF 
DRV/COBI/ABC/3TC 
ABC/3TC 
DRV/co 
PI 
DRV + ABC/3TC 
DRV/COBI/FTC/TAF 
FTC/TAF 
DRV/co 
PI 
DRV/co + FTC/TAF 
DRV/COBI/FTC/TDF 
FTC/TDF 
DRV/co 
PI 
DRV/co + FTC/TDF 
DRV/DTG/RTV/FTC/TAF* 
FTC/TAF 
DRV/r and 
DTG 
DRV/r is PI 
DTG is INSTI 
DRV/r and DTG + 
FTC/TAF 
DTG/ABC/3TC 
ABC/3TC 
DTG 
INSTI 
DTG + ABC/3TC 
DTG/FTC/TAF 
FTC/TAF 
DTG 
INSTI 
DTG + FTC/TAF 
DTG/FTC/TDF 
FTC/TDF 
DTG 
INSTI 
DTG + FTC/TDF 
DTG/RPV* 
- 
DTG and 
RPV 
DTG is INSTI 
RPV is NNRTI 
DTG and RPV 
EFV/3TC/TDF 
TDF/3TC 
EFV 
NNRTI 
EFV + TDF/3TC 
EFV/ABC/3TC 
ABC/3TC 
EFV 
NNRTI 
EFV + ABC/3TC 
EFV/AZT/3TC 
AZT/3TC 
EFV 
NNRTI 
EFV + AZT/3TC 
EFV/FTC/TAF 
FTC/TAF 
EFV 
NNRTI 
EFV + FTC/TAF 
EFV_FTC/TDF 
FTC/TDF 
EFV 
NNRTI 
EFV + FTC/TDF 
ETR/ABC/3TC* 
ABC/3TC 
ETR 
NNRTI 
ETR + ABC/3TC 
EVG/COBI/FTC/TAF 
FTC/TAF 
EVG/co 
INSTI 
EVG/co + FTC/TAF 
EVG/COBI/FTC/TDF 
FTC/TDF 
EVG/co 
INSTI 
EVG/co + FTC/TDF 


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Baseline ARV Medications 
from the data 
Backbone 
Third Agent 
Third Agent 
Class 
Baseline ARV 
Medication 
FTC/RPV/TAF 
FTC/TAF 
RPV 
NNRTI 
RPV + FTC/TAF 
FTC/RPV/TDF 
FTC/TDF 
RPV 
NNRTI 
RPV + FTC/TDF 
LPV/RTV/FTC/TDF 
FTC/TDF 
LPV/RTV 
PI 
LPV/r + FTC/TDF 
MVC/FTC/TDF 
FTC/TDF 
MVC 
CCR5 
MVC + FTC/TDF 
NFV/FTC/TAF 
FTC/TAF 
NFV 
PI 
NFV + FTC/TAF 
NVP/AZT/3TC 
AZT/3TC 
NVP 
NNRTI 
NVP + AZT/3TC 
NVP/FTC/TDF 
FTC/TDF 
NVP 
NNRTI 
NVP + FTC/TDF 
NVP/FTC/TAF 
FTC/TAF 
NVP 
NNRTI 
NVP + FTC/TAF 
RAL/ABC/3TC 
ABC/3TC 
RAL 
INSTI 
RAL + ABC/3TC 
RAL/FTC/TAF 
FTC/TAF 
RAL 
INSTI 
RAL + FTC/TAF 
RAL/FTC/TDF 
FTC/TDF 
RAL 
INSTI 
RAL + FTC/TDF 
RTV/DRV/ABC/3TC 
ABC/3TC 
DRV/r 
PI 
DRV/r + ABC/3TC 
RTV/DRV/FTC/TAF 
FTC/TAF 
DRV/r 
PI 
DRV/r + FTC/TAF 
RTV/DRV/FTC/TDF 
FTC/TDF 
DRV/r 
PI 
DRV/r + FTC/TDF 
RTV/RAL* 
- 
RAL/r 
INSTI 
RAL/r 
TAF/COBI/DRV/FTC 
FTC/TAF 
DRV/co 
PI 
DRV/co + FTC/TAF 
TAF/DTG/FTC 
FTC/TAF 
DTG 
INSTI 
DTG + FTC/TAF 
*Protocol Violation 
Duration of Baseline ARV Medication 
Duration of the baseline ARV medication (defined above) prior/ to the first dose date is defined 
as (End Date – Start Date+1). Duration will be expressed in years so that duration in days will be 
divided by 365.25 days.  
End date is defined as the first dose date -1 or randomization date if randomized but not dosed. 
Start Date: The start date of the baseline ARV medication is the latest start date of all the 
individual baseline ARV medications selected above 
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 the 
minimum of (the start date of the ARV, first dose date-1, the stop date of the same ARV) 
• If only year is available, month and day will be first imputed as July 1st of the year, then 
imputed as the minimum of (the start date of the ARV, first dose date-1, the stop date of the 
same ARV)  


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• No imputation applied for date missing completely  
Use the following rules to handle any incomplete stop dates 
• If only month and year are available, day will be first imputed as 15th, then imputed as 
minimum of (the first dose date-1, the stop date of the ARV) 
• If only year is available, month and day will be first imputed July 1st of the year, then 
imputed as  minimum of (first dose date-1, the stop date of the ARV)  
• No imputation applied for date missing completely 
11) Efficacy analyses: 
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% CIs (for HIV-1 RNA < 50 at wk24 by snapshot algorithm for FAS or Week 24 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.  
The following SAS code will be used to compute cell counts and p-values.  
data example; 
input  grp trt01a $  outcome $ count ; 
datalines; 
1       Treat-A        2-Fail        x      
1       Treat-A        1-Succ      xxx      
1       Treat-B        2-Fail        x      
1       Treat-B        1-Succ      xxx      
run; 
proc freq data = example; 
table trt01a*outcome /riskdiff(CL=(exact)) alpha=0.05; 
weight count; exact RISKDIFF(METHOD=SCORE); 
output out=ciexact(keep=_RDIF1_ XL_RDIF1 XU_RDIF1 _RSK11_  _RSK21) riskdiff; 
run; 
 
data final(keep=A1 B1 Estimate LowerCL UpperCL ocharc1); 
set ciexact; 
label Estimate ="Percentage Difference" 
LowerCL = "95% Lower Confidence Limit" 
UpperCL = "95% Upper Confidence Limit" 
A1 = "Percentage of Success in Treat-A" 
B1 = "Percentage of Success in Treat-B"; 
Estimate=100*_RDIF1_; 
LowerCL = 100*XL_RDIF1; 
UpperCL = 100*XU_RDIF1; 
A1 = 100*_RSK11_; 


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B1 = 100*_RSK21_; 
ocharc1 = right(compress(put(Estimate,8.1)) || '% (' || compress(put(LowerCL,8.1)) || '% 
to ' || compress(put(UpperCL,8.1)) || '%)'); 
run; 
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. 
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; 
Subgroup analyses for HIV-1 RNA < 50 copies/mL by US FDA-defined snapshot algorithm  
For the subgroups, 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, 
similar to that for the primary efficacy endpoint. 
f) 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 24 (Snapshot Algorithm) 
i) For the subgroups, 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.  
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; 


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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). 
(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.) 
g) 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; 
h) 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. 


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12) 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. 
13) TEAE 
Events with Missing Onset Day and/or Month 
An event is considered 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:  
The (complete) end date is on or after the first dose date, or 
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 
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. 
14) Toxicity Grades: 
For toxicity grade summaries, include post-baseline graded results as defined in Section 
7.2.2.1, not just those used in by-visit summaries. 


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15) Graded Laboratory Abnormalities Summary 
The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings: 
Battery 
Lab Test Label  
Used in l-labtox Listing 
Toxicity Direction 
Lab Test Label 
Used in t-labtox Table 
Hematology 
Hemoglobin 
Decrease 
Hemoglobin (Decreased) 
Neutrophils 
Decrease 
Neutrophils (Decreased) 
Platelets 
Decrease 
Platelets (Decreased) 
WBC 
Decrease 
WBC (Decreased) 
Chemistry 
Albumin 
Decrease 
Albumin (Decreased) 
Alkaline Phosphatase 
Increase 
Alkaline Phosphatase (Increased) 
ALT 
Increase 
ALT (Increased) 
Amylase 
Increase 
Amylase (Increased) 
AST 
Increase 
AST (Increased) 
Bicarbonate 
Decrease 
Bicarbonate (Decreased) 
Corrected Calcium 
Increase 
Corrected Calcium (Hypercalcemia) 
Corrected Calcium 
Decrease 
Corrected Calcium (Hypocalcemia) 
Creatine Kinase (CK) 
Increase 
Creatine Kinase (Increased) 
Creatinine 
Increase 
Creatinine (Increased) 
Lipase 
Increase 
Lipase (Increased) 
Magnesium 
Decrease 
Magnesium (Hypomagnesemia) 
Phosphate 
Decrease 
Phosphate (Hypophosphatemia) 
Serum Glucose (Fasting) 
Increase 
Serum Glucose (Fasting, Hyperglycemia) 
Serum Glucose (Fasting) 
Decrease 
Serum Glucose (Fasting, Hypoglycemia) 
Serum Glucose (Nonfasting) 
Increase 
Serum Glucose (Nonfasting, Hyperglycemia) 
Serum Glucose (Nonfasting) 
Decrease 
Serum Glucose (Nonfasting, Hypoglycemia) 
Serum Potassium 
Increase 
Serum Potassium (Hyperkalemia) 
Serum Potassium 
Decrease 
Serum Potassium (Hypokalemia) 
Serum Sodium 
Increase 
Serum Sodium (Hypernatremia) 
Serum Sodium 
Decrease 
Serum Sodium (Hyponatremia) 
Total Bilirubin 
Increase 
Total Bilirubin (Hyperbilirubinemia) 
Total Cholesterol (Fasting) 
Increase 
Total Cholesterol (Fasting, Hypercholesterolemia) 
Triglycerides (Fasting) 
Increase 
Triglycerides (Fasting, Increased) 
LDL (Fasting) 
Increase 
LDL (Fasting, Increased) 
Urea Nitrogen (BUN) 
Increase 
Urea Nitrogen (Increased) 
Urinalysis 
Urine Blood (Dipstick) 
Increase 
Urine RBC (Hematuria, Quantitative or Dipstick)* 
Urine Glucose 
Increase 
Urine Glucose (Glycosuria) 
Urine RBC (Quantitative) 
Increase 
Urine RBC (Hematuria, Quantitative or Dipstick)* 
Note: Prothrombin Intl. Normalized Ratio (INR) and Prothrombin Time (PT) were graded based on the protocol defined toxicity 
grade scale. The results and toxicity grade will be listed in listing, but not be summarized in lab toxicity summary table. 


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Due to the reflexive nature of the quantitative urine RBC test, results will be combined with the 
dipstick test of urine blood as described below. General rule is that urine RBC (Quantitative) 
should always be used first (if available), no matter if it is collected at the same time of Urine 
Blood (Dipstick) or not. The combined Urine RBC (hematuria, Quantitative or Dipstick) toxicity 
grade will be used for “Maximum treatment-emergent toxicity grade” summary. 
Is Post-BL Urine 
RBC (Quant.) 
Result 
Available? 
Is BL Urine 
RBC (Quant.) 
Result 
Available? 
Is Post-BL 
Urine Blood 
(Dipstick) 
Result 
Available? 
Is BL Urine 
Blood 
(Dipstick) 
Result 
Available? 
How to Determine Treatment-
Emergent Toxicity for “Urine 
RBC (Hematuria, Quantitative or 
Dipstick)” 
Yes 
Yes 
- 
- 
Compare post-BL Urine RBC 
(Quant.) toxicity grade to BL Urine 
RBC (Quant.) toxicity grade. If 
post-BL toxicity is greater than BL 
toxicity, then treatment-emergent 
Yes 
No 
- 
- 
Treatment-emergent. Use post-BL 
Urine RBC (Quant.) toxicity grade. 
No 
- 
Yes 
Yes 
Compare post-BL Urine Blood 
(Dipstick) toxicity grade to BL 
Urine Blood (Dipstick) toxicity 
grade. If post-BL toxicity is greater 
than BL toxicity, then treatment-
emergent 
No 
- 
Yes 
No 
Treatment-emergent. Use post-BL 
Urine Blood (Dipstick) toxicity 
grade. 
No 
- 
No 
- 
Do not count subject in the 
denominator for “Urine RBC 
(Hematuria, Quantitative or 
Dipstick)” 
BL = Baseline. Quant = Quantitative. “-” means any value can be present (or it can be missing), as it does not affect the 
classification 
16) Rank analysis of covariance for proteinuria shift table 
Rank analysis of covariance: 
proc rank data=up nplus1 ties=mean out=ranks1; 
 
var upbase upwk48; 
run; 
proc reg data=ranks1; 
 
model upwk48=upbase; 
 
output out=residual1 r=resid; 
run; 
proc freq data=residual1; 
 
tables trtgrp*resid/noprint cmh2; 
run; 


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17) 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) 
18) 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. 
a) More specifically, subjects with “Lipid Modifying Agent Use at Study Entry” include 
those subjects in the safety analysis set meeting both of the following criteria: 
1) any selected CM record with the start date ≤ the first dose date, 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, assume the start 
date is on or before the first dose date; lipid modifying medication is 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 and the end 
date unknown (completely missing) are considered as being taken at study entry (the 
unknown end date is assumed to be on or after the first dose date). 
• Subjects who initiated lipid modifying medications during the study (up to Week 24) are 
defined as the subjects in the safety analysis set who did not take lipid modifying 
medications at study entry and met the following criteria: 1) for subjects who permanently 
discontinued study treatment with any selected CM record with start date after the first dose 
date and on and prior to the minimum of (a) last dose date, or (b) Week 24 visit date; 2) for 
subjects who are still on study treatment with any selected CM records first started after the 
first dose date and on or prior to the Week 24 visit date. 
• Subjects who initiated lipid modifying medications during the study (at any time) are defined 
as the subjects in the safety analysis set who did not take lipid modifying medications at 
study entry and met the following criteria: 1) for subjects who permanently discontinued 
study treatment with any selected CM record with start date after the first dose date and on 
and prior to the last dose date; 2) for subjects who are still on study treatment with any 
selected CM records first started after the first dose date. 


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19) Analysis of covariance for HIVTSQc scores 
proc mixed; 
 
class trtgrp; 
   model change = trtgrp baseline; 
   lsmeans trtgrp; 
run; 
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 that visit in the 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. 
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)  results = “Repeat reactive, confirmed”, “Repeat Reactive Unconfirmed”. 
• For baseline coinfection, when considering the different laboratory tests, take the latest, 
non-missing record on or prior to the first dose date for each test (eg, HBsAg, HBsAb, 
HBcAb, and HBV DNA) 
 The baseline coinfection status will be one of the three values: Yes/No/Null 
 The following tables provide combinations of HBV and HCV tests and the corresponding 
baseline coinfection status 


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HBsAg 
HBsAb 
HBcAb 
HBV DNA 
Coinfection Status 
Positive 
- 
- 
- 
Y 
Negative 
Positive 
- 
- 
N 
Negative 
Positive 
Quantifiable 
Y 
Not Quantifiable 
N 
Missing 
Null 
Negative 
- 
N 
Missing 
Quantifiable 
Null 
Not Quantifiable 
N 
Missing 
Null 
Missing 
Positive 
Quantifiable 
Null 
Not Quantifiable 
N 
Missing 
Null 
Negative 
- 
N 
Missing 
Quantifiable 
Null 
Not Quantifiable 
N 
Missing 
Null 
Missing 
Positive 
- 
- 
Null 
Negative 
Positive 
Quantifiable 
Y 
Not Quantifiable 
Null 
Missing 
Null 
Negative 
- 
Null 
Missing 
- 
Null 
Missing 
- 
- 
Null 
 


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HCVAb 
HCV RNA 
Coinfection Status 
Positive 
Quantifiable 
Y 
Not Quantifiable 
N 
Missing 
Null 
Negative 
- 
N 
Missing 
Quantifiable 
Null 
Not Quantifiable 
N 
Missing 
Null 
 “-” means any value can be present, as it does not affect the classification 
• For incident coinfection, all laboratory tests must share the same accession number and if any 
set of values meets the criteria, then the subject is considered to have incident coinfection 
 The incident coinfection status will be one of two values: Yes/Null 
 The following tables provide combinations of HBV and HCV tests that are considered 
“Y” for incident coinfection status (all others are considered Null) 
HBsAg 
HBsAb 
HBcAb 
HBV DNA 
Coinfection Status 
Positive 
- 
- 
- 
Y 
Negative 
Negative 
Positive 
Quantifiable 
Y 
Missing 
Negative 
Positive 
Quantifiable 
Y 
 
HCVAb  
HCV RNA 
Coinfection Status 
Positive* 
- 
Y 
- 
Quantifiable 
Y 
* 
Subjects with positive HCVAb postbaseline must also have negative or missing HCVAb at baseline in order to be 
considered as having incident HIV/HCV coinfection. 
“-” means any value can be present, as it does not affect the classification 
• For 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”. 
23) HBV DNA test codes: If the result of the lab test code GET1883 (HBV DNA CAP/CTM 
2.0-EDTA-CL) is listed as “>170000000”, then a reflexive test code GET1884 (HBV DNA 
CAP/CTM 2.0Dil-EDTA-CL) should be performed and will share the same accession 
number as the original GET1883 test. In this instance, use the result from GET1884 instead 
of GET1883 when determining HBV DNA. 


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24) Reasons for Subjects who excluded from Week 24 PP Analysis Set will be summarized as 
follows in the table:  
a) Had Pre-existing INSTI Resistance-associated Mutations, including pre-existing 
mutations that were detected post-baseline 
b) Did Not Have On-Treatment HIV-1 RNA in Week 24 Window Unless due to 
Discontinuation of Study Drug for Lack of Efficacy 
c) Met the Exclusion Criteria for 3 or more TAMs (M41L,D67N, K70R, L210W, T215F/Y, 
and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT, including pre-existing 
mutations that were detected post-baseline 
d) Did not Meet the Inclusion Criteria for Baseline ARV Regimen 
e) Took Protocol Prohibited Medications 
25) The number of decimal places in reporting p-values should be as follows: 
a) values less than 0.001  < 0.001 
b) values 0.001 to less than 1.000  4 decimal places (no rounding) 
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) will be flagged (eg, ^).  However, please note, if CM end date is 
completely missing and the medication is not marked “Ongoing” and the CRF indicates 
‘Prior ARV’, the ARV will not be flagged. 
28) Last Dose Date and Last Study Date 
a) Last Dose Date for subjects who permanently discontinued study drug was defined in 
Section 3.8.1.   
For subjects in the B/F/TAF or Delayed Switch B/F/TAF groups who permanently 
discontinued study drug at the data cut date: 
If last dose date 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 study drug start dates and end 
dates, the clinic visit dates, and the laboratory visit dates, excluding the date of 30-day 
follow-up visit, will be used to impute the last dose date. 
If the last dose date is a partial 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 the dispensing date’s month is after the last dose date’s month, a data 
query is needed. 


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If the subject died and the death date is complete (ie, not paiiial date) and before the 
imputed last dose date, the complete death date should be used as the imputed last dose 
date. 
For subjects in the SBR group who pe1manently discontinued study drng at the data cut 
date: 
If the last dose date (as defined in Section 3.8.1) is missing (eg, only yeai· oflast dose 
date is known or completely missing due to lost to follow-up) for subjects who did not 
switch to B/F/TAF at the data cut date, the latest of the ARV baseline medication end 
dates, the clinic visit dates, and the laborato1y visit dates, excluding the date of 30-day 
follow-up visit, will be used to impute the last dose date. 
If the last dose date is a paiiial date (ie, month and year of last dose are known), the latest 
of the ARV baseline medication end dates and the imputed last dose date [day imputed as 
15] will be used as the final imputed last dose date. 
If the subject died and the death date is complete (ie, not paiiial date) and before the 
imputed last dose date, the complete death date should be used as the imputed last dose 
date. 
Last dose date is not defined for subjects still on study drng in this SAP. However, for the 
calculation of the duration of exposme to study diug, the data cut date will be used to 
impute the last dose date for subjects who have not pe1m anently discontinued study diug 
at the time of the data cut date. 
For the Week 24 analysis, 07 August 2019 (last Week 24 visit date for all subjects
1 
excew 
Subject lPIPD will be used as the data cut date for all subjects except for SubjectlPPD . 
For SubjectPPD PPD 
_ ,_ will be used as the data cut date (con esponding to 
that subject's Week 24 visit aate . 
Last Study Date is the latest of the study diug staii dates and end dates, the clinic visit 
dates, and the laborato1y 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 di11g staii date or end date is paiiially missing 
(ie, only year and month ai·e known), the day will be imputed as 15 for the pm-pose of this 
analysis. 
If the subject died and the death date is complete (ie, not paiiial date) and before the 
imputed last study date, the complete death date should be used as the imputed last study 
date. 
Last study date is not defined for subjects still on study in this SAP. However, for 
programing pmposes, the latest of data cut date, the clinic visit dates, and the laborato1y 
visit dates, including the 30-day follow-up visit date, will be used to impute the last study 
date for subjects still on study. 
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29) The precision in reporting numerical values should be as follows: 
Raw measurements will be reported the same as the data captured electronically or on the 
CRF. 
Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement. 
Mean, median, minimum, Q1, Q3, maximum, 95% CIs will be reported to the same number 
of decimal places of the raw measurements.  
Exceptions may be considered; for example if more than 4 significant digits are provided for 
the measurement.  
30) Duration of HIV Diagnosis (years) is defined as the year from the First Dose Date/Study Day 
1 Date minus the year of HIV diagnosis from Disease Under Study (HIV) CRF page. 
31) Duration of  HIV Treatment (Years) is defined as the year from the First Dose Date/Study 
Day1 Date minus the year first started HIV treatment from Disease Under Study (HIV) CRF 
page. 
32) Premature study drug discontinuation prior to Week 24 is defined as 
• For SBR group: subjects with Study Drug Completion form marked “No” for “Did subject 
complete study drug dosing as specified per protocol?” and subject did not switch to 
B/F/TAF 
• B/F/TAF group: subjects with Study Drug Completion eCRF marked “No” for “Did subject 
complete study drug dosing as specified per protocol?”, permanently discontinued study drug 
per the Study Drug Administration eCRF, and last dose was less than the latest of 168 days 
or the Week 24 visit date (if non-missing). 
33) Completed 24 weeks on randomized drug is defined as “Yes” if subjects did not prematurely 
discontinue study drug prior to Week 24  
34) Premature study discontinuation prior to Week 24 is defined as 
• For SBR group: subjects with Study Completion form marked “No” for “Did subject 
complete the protocol-planned duration of the study?” and subject did not switch to B/F/TAF 
• B/F/TAF group: subjects with Study Completion eCRF marked “No” for “Did subject 
complete the protocol-planned duration of the study??” and there are no scheduled visit dates 
on or after Week 24.