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
Phase: PHASE3
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences

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The info1mation contained in this document, paiiiculai·ly unpublished data, is the prope1iy or 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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 4
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 5
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 6
27 June 2018
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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 7
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 8
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 9
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 10
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 11
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 12
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 13
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 14
27 June 2018
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}.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 15
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 16
27 June 2018
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.

BIFITAF 
Protocol GS-US-380-4580 
Gilead Sciences, Inc. 
Final 
Original 
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. 
CONFIDENTIAL 
Page 17 
27 June 2018 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 18
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 19
27 June 2018
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%).

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 20
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 21
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 22
27 June 2018
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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 23
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 24
27 June 2018
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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 25
27 June 2018
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. 

BIFITAF 
Protocol GS-US-380-4580 
Gilead Sciences, Inc. 
Final 
Original 
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. 
CONFIDENTIAL 
Page 26 
27 June 2018 

BIFITAF 
Protocol GS-US-380-4580 
Gilead Sciences, Inc. 
CONFIDENTIAL 
Page 27 
Final 
Original 
27 June 2018 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 28
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 29
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 30
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 31
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 32
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 33
27 June 2018
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. 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 34
27 June 2018
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. 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 35
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 36
27 June 2018
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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 37
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 38
27 June 2018

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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 39
27 June 2018
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)

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 40
27 June 2018

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.  

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 41
27 June 2018
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)

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 42
27 June 2018
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 

BIFITAF 
Protocol GS-US-380-4580 
Gilead Sciences, Inc. 
Final 
Original 
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. 
CONFIDENTIAL 
Page43 
27 June 2018 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 44
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 45
27 June 2018
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 
/ 
Remain in Study 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 46
27 June 2018
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. 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 47
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 48
27 June 2018

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)

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 49
27 June 2018
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.

BIFITAF 
Protocol GS-US-380-4580 
Gilead Sciences, Inc. 
Final 
Original 
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 
CONFIDENTIAL 
Page 50 
27 June 2018 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 51
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 52
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 53
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 54
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 55
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 56
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 57
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 58
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 59
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 60
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 61
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 62
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 63
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 64
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 65
27 June 2018
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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 66
27 June 2018
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);

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 67
27 June 2018

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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 68
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 69
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 70
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 71
27 June 2018
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. 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 72
27 June 2018
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.
Joint United Nations Programme on HIV/AIDS (UNAIDS). Global Aids Update 2016. Available 
at: http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-
2016. 31 May.  2016.
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. 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 73
27 June 2018
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.
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice 
guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10 
(1):1-98.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 74
27 June 2018
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.
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84.
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported adherence supports 
patient preference for the single tablet regimen (STR) in the current cART era. 
Patient preference and adherence 2012;6:427-33.
Stone VE, Jordan J, Tolson J, Pilon T. Potential impact of once daily regimens on adherence to 
HAART [abstract]. . 40th Annual Meeting of the Infectious Disease Society of 
America; 2002 Oct 24-27; Chicago. pp. p.129, Abstract 486.
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines 
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 75
27 June 2018
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

B/F/TAF 
Protocol GS-US-380-4580 
Final 
Gilead Sciences, Inc. 
Original 
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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 77
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 78
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 79
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 80
27 June 2018
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 

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 81
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 82
27 June 2018
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0%
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric 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)

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 92
27 June 2018
SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by 
study participant or  
caregiver (for disabled 
adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or morbilliform 
rash with vesicles or limited 
number of bullae OR 
Superficial ulcerations of 
mucous membrane limited to 
one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson syndrome 
OR Ulceration of mucous 
membrane involving two 
or more distinct mucosal 
sites OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 93
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 94
27 June 2018
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, 
Dysphagia-Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal bleeding 
OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 24–48 
hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening consequences 
(eg, hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening consequences 
(eg, sepsis, circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ 
Stomatitis for Clinical 
Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater than 
minimal interference with usual 
social & functional activities OR 
Medical intervention indicated 
Symptoms causing inability to 
perform usual social/
functional activities OR 
Operative intervention 
indicated 
Life-threatening consequences 
(eg, perforation)
Vomiting
Transient or intermittent 
vomiting with no or 
minimal interference with 
oral intake
Frequent episodes of vomiting 
with no or mild dehydration
Persistent vomiting resulting 
in orthostatic hypotension OR 
Aggressive rehydration 
indicated
Life-threatening consequences 
(eg, hypotensive shock)

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 95
27 June 2018
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Alteration in Personality-
Behavior or in Mood (eg, 
agitation, anxiety, 
depression, mania, 
psychosis)
Alteration causing no or 
minimal interference with 
usual social & functional 
activities 
Alteration causing greater than 
minimal interference with 
usual social & functional 
activities 
Alteration causing inability to 
perform usual social & 
functional activities 
Behavior potentially harmful 
to self or others (eg, 
suicidal/homicidal ideation or 
attempt, acute psychosis) OR 
Causing inability to perform 
basic self-care functions
Altered Mental Status 
For Dementia, see Cognitive 
and Behavioral/Attentional 
Disturbance (including 
dementia and ADD)
Changes causing no or 
minimal interference with 
usual social & functional 
activities
Mild lethargy or somnolence 
causing greater than minimal 
interference with usual social 
& functional activities
Confusion, memory 
impairment, lethargy, or 
somnolence causing inability 
to perform usual social & 
functional activities
Delirium OR obtundation, OR 
coma
Ataxia 
Asymptomatic ataxia 
detectable on exam OR 
Minimal ataxia causing no 
or minimal interference with 
usual social & functional 
activities
Symptomatic ataxia causing 
greater than minimal 
interference with usual social 
& functional activities
Symptomatic ataxia causing 
inability to perform usual 
social & functional activities 
Disabling ataxia causing 
inability to perform basic self-
care functions
Cognitive and 
Behavioral/Attentional 
Disturbance (including 
dementia and Attention 
Deficit Disorder) 
Disability causing no or 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources not indicated
Disability causing greater than 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources on part-time basis 
indicated
Disability causing inability to 
perform usual social & 
functional activities OR 
Specialized resources on a 
full-time basis indicated
Disability causing inability to 
perform basic self-care 
functions OR 
Institutionalization indicated
Central nervous system
Ischemia (acute)
NA
NA
Transient ischemic attack
Cerebral vascular accident 
(CVA, stroke) with 
neurological deficit 
Developmental delay –
Pediatric 16 Years
Mild developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate 
for the setting
Moderate developmental 
delay, either motor or 
cognitive, as determined by 
comparison with a 
developmental screening tool 
appropriate for the setting 
Severe developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting 
Developmental regression, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 96
27 June 2018
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Headache 
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference with 
usual social & functional 
activities
Symptoms causing inability to 
perform usual social & 
functional activities
Symptoms causing inability to 
perform basic self-care 
functions OR Hospitalization 
indicated (other than ER visit) 
OR Headache with significant 
impairment of alertness or 
other neurologic function 
Insomnia
NA
Difficulty sleeping causing 
greater than minimal 
interference with usual 
social/functional activities
Difficulty sleeping causing 
inability to perform usual 
social & functional activities
Disabling insomnia causing 
inability to perform basic self-
care functions
Neuromuscular Weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength on exam 
OR Minimal muscle weak-
ness causing no or minimal 
interference with usual 
social & functional activities
Muscle weakness causing 
greater than minimal 
interference with usual social 
& functional activities
Muscle weakness causing 
inability to perform usual 
social & functional activities 
Disabling muscle weakness 
causing inability to perform 
basic self-care functions OR 
Respiratory muscle weakness 
impairing ventilation
Neurosensory Alteration 
(including paresthesia and 
painful neuropathy)
Asymptomatic with sensory 
alteration on exam or 
minimal paresthesia causing 
no or minimal interference 
with usual social & 
functional activities 
Sensory alteration or 
paresthesia causing greater 
than minimal interference with 
usual social & functional 
activities 
Sensory alteration or 
paresthesia causing inability to 
perform usual social & 
functional activities
Disabling sensory alteration or 
paresthesia causing inability to 
perform basic self-care 
functions
Seizure: (new onset) 
NA
1 seizure 
2–4 seizures 
Seizures of any kind that are 
prolonged, repetitive (eg, 
status epilepticus), or difficult 
to control (eg, refractory 
epilepsy)

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 97
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 98
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 99
27 June 2018
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]

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 100
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 101
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 102
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 103
27 June 2018
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

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 104
27 June 2018
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}

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 105
27 June 2018
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.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 106
27 June 2018
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:

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 107
27 June 2018
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 
drug immediately.

B/F/TAF
Protocol GS-US-380-4580
Final
Gilead Sciences, Inc. 
Original
CONFIDENTIAL
Page 108
27 June 2018
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