Conditions: HIV-1 Infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 578
Healthy volunteers: no

Brief summary:
The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.

Detailed description:

Arms:
arm 1: Randomized Phase: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 48 weeks, without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks or until the product becomes accessible to participants through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first. arm 2: Randomized Phase: Participants remained on current antiretroviral (ARV) regimen consisting of ritonavir (RTV)-boosted or cobicistat (COBI)-boosted atazanavir (ATV) or darunavir (DRV), plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks or until the product becomes accessible to participants through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.

Interventions: intervention 1: RTV intervention 2: ATV intervention 3: DRV intervention 4: COBI intervention 5: ATV/co intervention 6: DRV/co intervention 7: FTC/TDF intervention 8: ABC/3TC intervention 9: B/F/TAF
Intervention descriptions: intervention 1: 100 mg capsule coadministered orally with ATV or DRV once daily with food intervention 2: 300 mg capsule administered orally once daily with food intervention 3: 800 mg tablet administered orally once daily with food intervention 4: 150 mg tablet coadministered orally with ATV or DRV once daily with food intervention 5: 300/150 mg FDC tablet administered orally once daily with food intervention 6: 800/150 mg FDC tablet administered orally once daily with food intervention 7: 200/300 mg FDC tablet administered orally once daily without regard to food intervention 8: 600/300 mg tablet administered orally once daily with or without regard to food intervention 9: 50/200/25 mg FDC tablet administered orally once daily without regard to food

Protocol document:
SAP_008.pdf: 
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Prot_005.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Clinical 
Program Manager: 
Gilead Medical Monitor: 
Gilead Study Director: 
Protocol Version/Date: 
(!') GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and 
Efficacy of Switching from Regimens Consisting ofBoosted Atazanavir or 
Damnavir plus either Emtricitabine/Tenofovir or Abacavir!Lamivudine to 
GS-9883/Emtticitabine/Tenofovi..r Alafenamide in Virologically Suppressed 
HN -1 Infected Adults 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
125589 
2015-004011-20 
NCT02603107 
HN -1 Infection 
GS-US-380-1878 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Mobile: 
Fax: 
Name: 
Telephone: 
Fax: 
Original: 
Amendment 1 
PPD 
PPU 
PPD 
Marshall Fordyce, MD 
PPD 
PPD 
PPU 
PPD 
PPU 
PPD 
21 October 2015 
19 Febmaty 2016 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this document, particularly unpublished data, is the propetiy or 
lmder 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 infotmation is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol. 
You will not disclose any of the infotmation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessaty to obtain infotmed consent from those 
persons to whom the dm g may be administered. 


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 2
19 February 2016
TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................12
1.
INTRODUCTION ..............................................................................................................................................15
1.1.
Background ............................................................................................................................................15
1.2.
GS-9883 .................................................................................................................................................16
1.2.1.
General Information .............................................................................................................16
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................16
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................18
1.3.
Information about Emtricitabine (Emtriva®, FTC).................................................................................27
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)..................................................................27
1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) 
or Fixed Dose Combination emtricitabine/tenofovir alafenamide 
(FTC/TAF)...........................................................................................................................27
1.4.2.
Clinical Trials of FTC/TAF as part of 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) ...........................29
1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) ...........................31
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, 
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................31
1.6.
Rationale for this Study..........................................................................................................................32
1.7.
Rationale for Dose Selection..................................................................................................................33
1.8.
Risk Benefit Assessment for this Study .................................................................................................35
1.9.
Compliance ............................................................................................................................................35
2.
OBJECTIVES.....................................................................................................................................................36
3.
STUDY DESIGN................................................................................................................................................37
3.1.
Endpoints ...............................................................................................................................................37
3.2.
Study Design..........................................................................................................................................37
3.3.
Study Treatments ...................................................................................................................................37
3.4.
Duration of Treatment............................................................................................................................37
3.5.
Biomarker Testing..................................................................................................................................38
3.5.1.
Biomarker Samples for Optional Pharmacogenomic Research............................................38
3.5.2.
Additional Sample Storage...................................................................................................39
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................43
5.1.
Randomization .......................................................................................................................................43
5.2.
Description and Handling.......................................................................................................................43
5.2.1.
Formulation..........................................................................................................................43
5.2.2.
Packaging and Labeling .......................................................................................................44
5.2.3.
Storage and Handling...........................................................................................................44
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide ....................................44
5.4.
Prior and Concomitant Medications.......................................................................................................45


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 3
19 February 2016
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................46
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................47
6.
STUDY PROCEDURES ....................................................................................................................................48
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................48
6.2.
Pretreatment Assessments......................................................................................................................48
6.2.1.
Screening Visit .....................................................................................................................48
6.2.2.
Day 1 Assessments...............................................................................................................50
6.3.
Randomization .......................................................................................................................................52
6.4.
Treatment Assessments (Week 4 -48)....................................................................................................52
6.5.
Treatment Assessments (Post Week 48) ................................................................................................55
6.5.1.
Post Week 48 Assessments ..................................................................................................55
6.6.
Post-treatment Assessments ...................................................................................................................56
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................56
6.6.2.
30-Day Follow-Up ...............................................................................................................57
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................58
6.8.
Other Evaluations...................................................................................................................................59
6.8.1.
Markers of Renal Tubular Function .....................................................................................59
6.9.
Blood and Urine Storage........................................................................................................................59
6.10.
Assessments for Premature Discontinuation from Study.......................................................................59
6.11.
End of Study...........................................................................................................................................60
6.12.
Post Study Care......................................................................................................................................60
6.13.
Virologic Failure....................................................................................................................................60
6.13.1.
Management of Virologic Rebound .....................................................................................60
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Drug 
Discontinuation, or Week 48................................................................................................61
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................62
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................62
7.1.1.
Adverse Events.....................................................................................................................62
7.1.2.
Serious Adverse Events........................................................................................................62
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................63
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................63
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................63
7.2.2.
Assessment of Severity ........................................................................................................64
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................64
7.3.1.
Adverse Events.....................................................................................................................64
7.3.2.
Serious Adverse Events........................................................................................................65
7.4.
Gilead Reporting Requirements.............................................................................................................66
7.5.
Toxicity Management ............................................................................................................................66
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................66
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................67
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................67
7.5.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................67
7.5.5.
Management of Hyperbilirubinemia ....................................................................................69
7.5.6.
Management of Possible Abacavir Hypersensitivity Reaction.............................................69
7.5.7.
Management of Potential Hepatobiliary Toxicity ................................................................70
7.5.8.
On-Treatment Hepatitis C Management...............................................................................71
7.6.
Special Situations Reports......................................................................................................................71
7.6.1.
Definitions of Special Situations..........................................................................................71
7.6.2.
Instructions for Reporting Special Situations.......................................................................71


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8.
STATISTICAL CONSIDERATIONS................................................................................................................74
8.1.
Analysis Objectives and Endpoints........................................................................................................74
8.1.1.
Analysis Objectives..............................................................................................................74
8.1.2.
Primary Endpoint .................................................................................................................74
8.1.3.
Secondary Endpoint .............................................................................................................74
8.2.
Analysis Conventions.............................................................................................................................74
8.2.1.
Analysis Sets ........................................................................................................................74
8.3.
Data Handling Conventions ...................................................................................................................76
8.4.
Demographic Data and Baseline Characteristics ...................................................................................76
8.5.
Efficacy Analysis ...................................................................................................................................76
8.5.1.
Primary Analysis..................................................................................................................76
8.5.2.
Secondary Analyses .............................................................................................................78
8.6.
Safety Analysis.......................................................................................................................................78
8.6.1.
Extent of Exposure...............................................................................................................78
8.6.2.
Adverse Events.....................................................................................................................78
8.6.3.
Laboratory Evaluations ........................................................................................................79
8.6.4.
Other Safety Evaluations......................................................................................................79
8.7.
Pharmacokinetic Analysis......................................................................................................................79
8.8.
Patient Reported Outcomes (PRO).........................................................................................................80
8.9.
Sample Size............................................................................................................................................80
8.10.
Independent Data Monitoring Committee..............................................................................................80
8.11.
Analysis Schedule ..................................................................................................................................80
9.
RESPONSIBILITIES..........................................................................................................................................81
9.1.
Investigator Responsibilities ..................................................................................................................81
9.1.1.
Good Clinical Practice..........................................................................................................81
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................81
9.1.3.
Informed Consent.................................................................................................................81
9.1.4.
Confidentiality......................................................................................................................82
9.1.5.
Study Files and Retention of Records ..................................................................................82
9.1.6.
Case Report Forms...............................................................................................................83
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................84
9.1.8.
Inspections............................................................................................................................84
9.1.9.
Protocol Compliance............................................................................................................84
9.2.
Sponsor Responsibilities ........................................................................................................................85
9.2.1.
Protocol Modifications.........................................................................................................85
9.2.2.
Study Report and Publications .............................................................................................85
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................85
9.3.1.
Payment Reporting...............................................................................................................85
9.3.2.
Access to Information for Monitoring..................................................................................86
9.3.3.
Access to Information for Auditing or Inspections ..............................................................86
9.3.4.
Study Discontinuation..........................................................................................................86
10.
REFERENCES ...................................................................................................................................................87
11.
APPENDICES ....................................................................................................................................................89
Appendix 1.
Investigator Signature Page....................................................................................................90
Appendix 2.
Study Procedures Table..........................................................................................................91
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................94
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............95
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................119


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Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................121
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........20
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................21
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................22
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following GS-9883 
Administration Under Fasting Conditions and Corresponding Protein-Adjusted IQ95 
Values (GS-9883 PK Analysis Set)........................................................................................23
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................34
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)..........................................45
Table 5-2.
Prior and Concomitant Medications (Boosted ATV and DRV regimen) ...............................46
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................23
Figure 3-1.
Study Schema.........................................................................................................................38
Figure 6-1.
Virologic Rebound Schema....................................................................................................61


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety 
and Efficacy of Switching from Regimens Consisting of Boosted
Atazanavir or Darunavir plus either Emtricitabine/Tenofovir or 
Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir 
Alafenamide in Virologically Suppressed HIV-1 Infected Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004011-20
NCT02603107
Study Centers 
Planned:
Approximately 150 centers in North America, Europe, Asia Pacific, 
and Latin America
Objectives:
The primary objective of this study is as follows:

To evaluate the efficacy of switching to a fixed dose combination 
(FDC) of GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus continuing on a regimen consisting of 
boosted atazanavir (ATV) or darunavir (DRV) plus either 
emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or
abacavir/lamivudine (ABC/3TC) in HIV-1 infected adult subjects 
who are virologically suppressed as determined by the proportion 
of subjects with HIV-1 RNA ≥50 copies/mL at Week 48
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of the two treatment groups
through Week 48
Study Design:
Randomized, open-label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to a FDC of 
GS-9883/F/TAF in HIV-1 infected subjects who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of 
ritonavir (RTV) or cobicistat (COBI) boosted ATV or DRV plus 
either FTC/TDF or ABC/3TC for ≥ 6 months prior to screening.


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Subjects who provide written consent and meet all eligibility criteria 
will be randomized in a 1:1 ratio to one of the following 
two treatment groups:
Treatment Group 1: Switch to a FDC of GS-9883/emtricitabine
/tenofovir alafenamide (GS-9883/F/TAF) administered orally,
once daily without regard to food (n=260)
Treatment Group 2: Remain on current antiretroviral regimen 
consisting of ritonavir or cobicistat boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC administered orally, once daily with food 
(n=260)
Investigators must provide a prescription to subjects in Treatment 
Group 2. Subjects in Treatment Group 2 are responsible for obtaining 
their ARV regimen.
Randomization will be stratified by the prior treatment regimen group 
(i.e., TDF containing regimens [ritonavir or cobicistat boosted ATV 
or DRV plus FTC/TDF] and non-TDF containing regimens [ritonavir 
or cobicistat boosted ATV or DRV plus ABC/3TC]) at screening.
Number of Subjects 
Planned:
Approximately 520 subjects in total.
Approximately 260 subjects in each Treatment Group 1 and 
Treatment Group 2
Target Population:
HIV-1 infected subjects ≥18 years old who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a stable regimen 
containing boosted ATV or DRV plus either FTC/TDF or ABC/3TC 
for 6 months prior to screening and who are INSTI naive.
Duration of 
Treatment:
Duration of this study is at least 48 weeks.
At the Week 48 Visit, subjects in a country where GS-9883/F/TAF 
FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for additional 48 weeks, or until the product 
becomes accessible to subjects through an access program, or until 
Gilead Sciences elects to discontinue the study in that country, 
whichever occurs first.
Subjects who complete the study through Week 48 Visit and do not 
further continue participation in the study, will be required to return 
to the clinic 30 days after Week 48 Visit for a 30-Day Follow-Up 
Visit


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Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Currently receiving a once daily antiretroviral regimen consisting 
of ritonavir or cobicistat boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC for 6 months preceding the screening 
visit

Currently on a stable regimen for ≥6 months preceding the 
Screening visit with documented plasma HIV-1 RNA 
< 50 copies/mL for ≥ 6 months preceding the Screening visit (or 
undetectable HIV-1 RNA level according to the local assay being 
used if the limit of detection is ≥50 copies/mL).
Prior changes in antiretroviral regimen are only allowed due 
to tolerability issues or for regimen simplification. 
Unconfirmed virologic elevations of ≥ 50 copies/mL 
(transient detectable viremia, or “blip”) prior to screening are
acceptable. (If the lower limit of detection of the local HIV-1 
RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the 
plasma HIV-1 RNA level cannot exceed 50 copies/mL on 
two consecutive HIV-1 RNA tests)

HIV-1 RNA levels < 50 copies/mL at Screening Visit

No previous use of any approved or experimental integrase strand 
transfer inhibitor (INSTI)

No documented or suspected resistance to FTC, TFV, ABC or 
3TC, including but not limited to the reverse transcriptase 
resistance mutations K65R and M184V/I

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 48 weeks. 
For all eligible subjects, blood will be collected at Day 1,Weeks 4, 8, 
12, and then every 12 weeks through Week 48. Laboratory analyses 
(hematology, chemistry, and urinalysis), HIV-1 RNA, CD4+ cell 
count, and complete or symptom-directed physical examinations will 
be performed at the Screening, Day 1 and all subsequent study visits.
Urine will be collected and stored for possible evaluations of renal 
tubular function including urine albumin, urine creatinine, urine 
protein, retinol binding protein and beta-2 microglobulin.
Adverse events and concomitant medications will be assessed at each 
visit.


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Test Product, Dose, 
and Mode of 
Administration:
FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily without 
regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Current antiretroviral drug regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC 
administered orally, once daily with food.
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests to evaluate the safety and 
tolerability of the treatment regimens.
Efficacy:
The primary efficacy endpoint is the proportion of subjects with HIV-
1 RNA ≥ 50 copies/mLat Week 48 as defined by the United States 
(US) Food and Drug Administration [FDA]-defined snapshot 
algorithm.
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
Pharmacokinetics:
An intensive pharmacokinetic (PK) substudy will be performed at the 
Weeks 4 or 8 visits in a subset of Treatment Group 1 subjects (target 
n=24) at study sites able to conduct this testing.
For all subjects in Treatment Group 1 who are on study drug, a single 
anytime pre or post-dose PK blood sample will be collected at 
Weeks 8, 24 and 36.
For all subjects in Treatment Group 1 who are on study drug, a trough 
PK blood sample will be obtained 20-28 hours following the last dose 
at Weeks 4 and 12.  Following an observed dose, one post-dose PK 
blood sample will be collected between 1 and 4 hours post-dose.
For intensive PK substudy, the following PK parameters for GS-9883 
may be explored as applicable:
Cmax, Tmax, Clast, Tlast, Ctau,T1/2, AUCtau,AUC0-last , Vz/F, CLss/F.
The concentration of GS-9883 may be summarized using descriptive 
statistics. The pharmacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concentrations may be 
analyzed and PK parameters may be summarized as applicable.


GS-9883/F/T AF 
Protocol GS-US-380-1878 
Gilead Sciences, Inc. 
Optional Genomic 
Testing: 
Patient Reported 
Outcomes: 
Statistical Methods: 
CONFIDENTIAL 
PO 
Final 
Amendment 1 
Shoti Fotm 36 Health Smvey (SF-36), HIV Symptoms Distress 
Module fudex, Work Productivity and Activity bnpairment 
Questionnaire (WP AI), and UCLA Sclerodetma Clinical Trial 
Consotiium Gastrointestinal Tract (UCLA SCTC GIT 2.0) will be 
administered at Day 1, Weeks 4, 12 and 48. Visual Analog Scale 
(VAS) Adherence Questionnaire will be administered at Day 1 and all 
visits up to Week 48. 
The primaty analysis will consist of a non-inferiority evaluation of 
switching to GS-9883/F/TAF versus maintaining an antiretroviral 
drug regimen consisting of boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC (i.e., boosted PI plus 2 nucleoside reverse 
transcriptase inhibitors (NRTis) [boosted PI + 2 NRTis]) with respect 
to the propottion of subjects with HIV -1 RNA ~ 50 copies/mL as 
defined by the US FDA-defined snapshot algorithm at Week 48. It 
will be concluded that GS-9883/F/TAF is non-inferior to the boosted 
PI + 2 NRTis if the upper bmmd of the 2-sided 95% confidence 
interval (CI) of the difference between treatment groups 
(GS-9883/F/TAF - boosted PI + 2 NRTis) in the percentage of 
subjects with HIV-1 RNA ~ 50 copies/mL is less than 4% (i.e., a 
margin of 4% is applied to non-inferiority assessment). The 2-sided 
95% Cis will be constmcted based on the exact method. 
The propotiion of subjects with HIV -1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defmed snapshot algorithm will 
also be summati.zed. The 2-sided 95% Cis will be constmcted in the 
same manner as described for the primaty efficacy endpoint. 
Page 10 
19 Februa1y 2016 


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The change from baseline in CD4+ cell count at Week 48 will be 
summarized using descriptive statistics. The differences and the 
associated 95% CIs will be constructed using Analysis of Variance 
(ANOVA) model, including treatment (GS-9883/F/TAF vs. boosted 
PI + 2 NRTIs) as a fixed effect in the model.
Adverse events, clinical laboratory assessments, and pharmacokinetic 
parameters will be summarized using descriptive statistics.
A total of approximately 520 HIV-1 infected subjects, randomized in 
a 1:1 ratio to two treatment groups (260 subjects per treatment group), 
achieves at least 90% power to detect a non-inferiority margin of 4% 
difference in the percentage of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 between the two treatment groups. For 
sample size and power computation, it is assumed that both treatment 
groups have 2% of subjects with HIV-1 RNA ≥50 copies/mL (based 
on historical Gilead E/C/F/TAF and STB studies), that a 
non-inferiority margin is 4%, and that the significance level of the test 
is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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


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


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PSQI
Pittsburgh Sleep Quality Index
PT
preferred term 
PT
prothrombin time 
QD
once daily
RAL
raltegravir
RNA
ribonucleic acid
SA
single agent
SAE
serious adverse event
SF-36
Short Form 36 Health Survey
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide 
TDF
tenofovir disoproxil fumarate, Viread
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UCLA SCTC GIT
UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States
VAS
Visual analog scale
WPAI
Work Productivity and Activity Impairment Questionnaire


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {The Joint United Nations Programme 2014}. The infection, if left untreated or 
suboptimally treated, is characterized by deterioration in immune function, ultimately resulting 
in death. Therapeutic strategies for the treatment of HIV-1 disease have been significantly 
advanced by the availability of highly active antiretroviral therapy (HAART); the introduction of 
HAART was associated with a dramatic decrease in acquired immune deficiency syndrome 
(AIDS)-related morbidity and mortality {Palella et al 1998}, {Mocroft et al 1998}, {Sterne et al 
2005}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {Costagliola 2014}. In addition, there remains a significant 
medical need for new, effective therapies that take into consideration HIV genetic variability, the 
aging HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen 
simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {Department for 
Health and Human Services (DHHS) 2015}. Virologically suppressed, HIV-infected patients 
may switch from their current regimen because of safety or tolerability concerns or for regimen 
simplification. All patient populations may benefit from once-daily fixed-dose combination 
(FDC) regimens as these have been shown to provide increased adherence and improved clinical 
and virologic outcomes {Sterrantino et al 2012}, {Aldir et al 2013}.
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other NRTIs. Tenofovir alafenamide (TAF) is also an 
oral prodrug of TFV. TAF is more stable in plasma than TDF, provides higher intracellular 
levels of the active phosphorylated metabolite tenofovir diphosphate (TFV-DP), and 
approximately 90% lower circulating levels of TFV relative to TDF at the clinical doses. 
The distinct metabolism of TAF offers the potential for an improved clinical profile compared 
with TDF.
GS-9883 is a potent inhibitor of HIV-1 integrase that is being evaluated for the treatment of 
HIV-1 infection.  Antiviral testing has shown that GS-9883 is active against a broad panel of 
HIV-1 viral lab strains and clinical isolates.  GS-9883 is fully active against a panel of mutant 


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


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Additionally, the risk that GS-9883 will affect the OCT2-mediated excretion of co-administered 
drugs is considered to be low.
GS-9883 does not activate AhR and only weakly activates PXR at concentrations up to 50 M 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.
1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL, 
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day.  At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal 
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males.  The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy.
No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL).  The estimated margin of exposure at the 


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NOEL was approximately 5.1-fold based on expected human exposure with the once daily 
dosing of the GS-9883/F/TAF (50/200/25 mg) tablet.
A standard battery of in vitro and in vivo studies was performed to assess the genotoxic potential 
of GS-9883. There was no evidence of mutagenic or clastogenic activity in an in vitro bacterial 
reverse mutation assay (Study TX-141-2026), a chromosomal aberration assay in human 
lymphocytes (Study TX-141-2027), or in a rat micronucleus test (Study TX-141-2029).
1.2.3.
Clinical Trials of GS-9883
Clinical trials entailing the use of GS-9883 include:

GS-US-141-1218, a Phase 1 double blind, randomized, placebo-controlled, first-in-human, 
single- and multiple-ascending dose study evaluating the safety, tolerability, and PK of oral 
GS-9883 in healthy subjects and a randomized, open-label, 2-cohort, 3-period, crossover, PK 
study evaluating the drug interaction potential between F/TAF FDC tablet and GS-9883 in 
healthy subjects (completed)

GS-US-141-1219, a Phase 1b randomized, double-blinded, sequential cohort 
placebo-controlled study of the safety, PK, and antiviral activity of GS-9883 in HIV-1 
infected subjects (5 mg, 25 mg,50 mg, 100 mg) (completed)

GS-US-141-1233, a Phase 1,Open-label, Two-Cohort, Multiple-Period, Fixed-Sequence, 
Crossover Study to Evaluate 1) the Relative Bioavailability of
Two GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg)
Fixed-Dose Combination Tablets Versus a GS-9883 (75 mg) Tablet and a 
Emtricitabine/Tenofovir Alafenamide (200/25 mg) Fixed-Dose Combination Tablet 
Administered Simultaneously and 2) the Effect of Food on the Pharmacokinetics of 
GS-9883, Emtricitabine and Tenofovir Alafenamide When Administered as 
GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg)
Fixed-Dose Combination Tablets (in life portion completed)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)


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
GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled Phase 1 Study 
Evaluating the Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular 
Filtration Rate (in life portion completed)

GS-US-311-1790, a Phase 1Randomized, Open Label, Drug Interaction Study Evaluating the 
Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (completed)

GS-US-380-1761, a Phase 1 Study to Evaluate Pharmacokinetic Drug-Drug Interaction 
Potential between GS-9883/Emtricitabine/Tenofovir Alafenamide Fumarate 
(GS-9883/F/TAF) and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-Dose Combination (FDC) 
Tablets (completed)

GS-US-141-1475, a Phase 2 Randomized, Double-Blinded Study of the Safety and Efficacy 
of GS-9883 + Emtricitabine/Tenofovir Alafenamide Versus 
Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral 
Treatment-Naive Adults (ongoing)
Please refer to the GS-9883/F/TAF Investigators’ Brochure for further information about these 
studies.
1.2.3.1.
Phase 1 Safety and Pharmacokinetics
Study GS-US-141-1218 was a four part, first-in-human study.  Parts A and B were randomized, 
double-blind, placebo-controlled, single and multiple ascending dose studies of GS-9883 in 
healthy male and female subjects.  Part C was an open label, fixed sequence food effect study 
evaluating the effect of food on the PK of GS-9883.  Part D was a randomized, open-label, 
2-cohort, 3-period, crossover PK study evaluating the drug interaction potential between 
FTC/TAF FDC tablet and GS-9883 in healthy subjects.
There was no difference in the overall incidence or type of AEs when GS-9883 was administered 
in the fasted and fed states. There was no difference in the overall incidence of AEs when 
GS-9883 or FTC/TAF was each administered alone or in combination.
No deaths or pregnancies were reported. No Grade 3 or 4 AEs or SAEs, were reported in any 
cohort.
Changes in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2.  In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort. In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF. All 
changes returned to baseline after discontinuation of GS-9883.


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The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood. All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.
Based on results in study GS-US-141-1218, pharmacokinetic profile of GS-9883 was 
characterized by rapid absorption with time to peak plasma concentrations (median Tmax of 
cohorts) ranging between 1 and 4 hours following administration under fasted conditions. 
GS-9883 exposures were appropriately dose proportional following single dose 25-100 mg dose 
administration, with decreasing dose proportional at higher doses.  The half-life of GS-9883 was 
approximately 18 hours, with no changes observed across studied dose range as evidenced by
parallel terminal phase slopes. A high-fat meal increased AUCinf and Cmax (geometric mean, 84% 
and 101%, respectively) following 100 mg single dose administration. Steady state was achieved 
after 4-6 days of once daily dosing of GS-9883 with average accumulation ratios for AUC24hr
of 1.6.
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following 
Single Doses of GS-9883 in Healthy Subjects (GS-9883 PK Analysis 
Set; Part A: Single Dosing)
GS-9883 PK 
Parameter
Mean 
(%CV)
5mg
(N=6)
25 mg
(N=6)
50 mg
(N=6)
100 mg
(N=6)
300 mg
(N=6)
600 mg
(N=6)
Cmax (ng/mL)
691.2
(22.1)
1618.3
(26.7)
3965.0
(40.1)
6998.3
(36.1)
14605.0 
(27.1)
20050.0
(7.5)
Tmax (hr)
1.25 
(1.00-1.50)
2.00
(1.00-3.00)
3.00
(1.50-4.00)
2.25
(1.50-3.00)
3.50
(2.00-6.00)
3.5
(2.00-4.00)
AUCinf 
(ng.hr/mL)
13059.7
(25.1)
35718.2 
(21.3)
78399.5 
(29.7)
163028.2 
(24.3)
355917.3 
(32.9)
454446.8 
(19.9)
T1/2 (hr)
18.51
(16.81-19.99)
18.08
(16.63-19.64)
16.72
(15.77-17.11)
18.90
(17.96-20.05)
18.14
(17.86-20.53)
17.89
(16.38-19.52)
T1/2 and Tmax: Median (Q1, Q3)
Table 1-2 presents GS-9883 plasma PK parameters following administration of GS-9883 
(5, 25, 50, 100, and 300 mg) once daily for 7 days. Following administration of either GS-9883 
(5, 25, 50, 100, or 300 mg) once daily for 7 days, the PK absorption profile observed on Days 1 
and 7 was similar to that observed in Part A (SAD). The median Tmax values ranged from 1.5 to 
2.5 hours on Day 1 and 1.5 to 4.0 hours on Day 7. Linearity was observed comparing GS-9883 
AUC and Cmax on Days 1 and 7 over the dose range of 25 to 50 mg. Steady state levels of 
GS-9883 were achieved between Study Days 4 to 6 of dosing and maintained through Day 14. 
Accumulation is approximately 1.6-fold, which is consistent with the observed half-life of the 
GS-9883 (approximately 18 hours).


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Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by 
GS-9883 Dose Following Multiple-Dose Administration of GS-9883
(Analysis Set: GS-9883 PK Part B: Multiple-Dose)
GS-9883 PK Parameter Mean
(%CV)a
Multiple-Dose GS-9883
5 mg
(N = 6)
25 mg
(N = 6)
50 mg
(N = 6)
100 mg
(N = 6)
300 mg
(N = 6)
Day 1
AUC0-24 (hr*ng/mL)
9033.6
(8.2)
27,775.1
(28.3)
58,371.4
(18.9)
79,773.8
(18.9)
180,714.3
(17.6)
Cmax (ng/mL)
709.7
(9.5)
2220.0
(35.6)
4648.3
(18.7)
6248.3
(26.8)
13,716.7
(19.1)
Tmax (hr)
1.50
(1.50, 1.50)
1.75
(1.00, 3.00)
1.50
(1.00, 2.00)
2.50
(2.00, 3.00)
2.50
(2.00, 4.00)
Day 7
AUCtau (hr*ng/mL)
14,392.0
(16.7)
50,008.2
(26.6)
89,710.1
(22.7)
126,785.8 
(23.7)
277,200.2 
(16.7)
Cmax (ng/mL)
982.5
(7.9)
3455.0
(24.1)
6538.3
(17.6)
9396.7
(20.8)
19,900.0 
(21.2)
Ctau (ng/mL)
400.83
(26.9)
1322.00
(27.8)
2241.67
(28.2)
3145.00 
(26.1)
6758.33 
(21.6)
Tmax (hr)
1.50
(1.00, 2.00)
3.00
(2.00, 3.00)
1.75
(1.50, 2.00)
1.75
(1.50, 3.00)
4.00
(2.00, 4.00)
Accumulation Ratio of AUC (%)
160.5
(19.0)
182.2
(17.1)
154.0
(15.9)
158.5
(12.1)
157.5
(22.6)
a
Data are presented as mean (%CV), except for Tmax, and t½, which are presented as median (Q1, Q3)
Table 1-3 presents the GLSM ratios and associated 90% CIs for the test (fed) versus reference 
(fasted) treatments for the primary plasma PK parameters of GS-9883. Administration of a single 
dose of GS-9883 100 mg with food (high-calorie/high-fat breakfast) increased the GLSM values 
of Cmax and AUCinf 101% (90% CI of GLSM ratio 165.93% to 242.74%) and 84% (90% CI of 
GLSM ratio 152.05% to 222.59%), respectively. There were no apparent changes in clearance 
and T1/2 following administration with food, indicating that food enhanced the bioavailability of 
GS-9883 by improving its solubility and/or absorption.


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Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic 
Parameters Following Single-Dose Administration of GS-9883 in the 
Fasted and Fed States (GS-9883 PK Analysis Set)
GS-9883 PK Parameter 
Mean (%CV)
% GLSM Ratio 
(90% CI)
Test
GS-9883 100 mg Fed
(n=8)
Reference
GS-9883 100 mg Fasted
(n=8)
AUCinf (hr*ng/mL)
214,146.3 (15.9)
117,777.1 (23.3)
183.97 (152.05, 222.59)
AUClast (hr*ng/mL)
209,259.9 (15.1)
115,681.7 (24.0)
183.58 (151.91, 221.86)
Cmax (ng/mL)
11,268.8 (15.1)
5885.0 (34.9)
200.69 (165.93, 242.74)
CI = confidence interval; GLSM = geometric least squares mean
1.2.3.2.
Phase 1b Proof of Concept
The first HIV-1 positive human subjects were dosed in the fasted state with 10 days of GS-9883 
in study (GS-US-141-1219).  Four cohorts of 5 subjects each were randomized 4:1 to receive 
GS-9883 or placebo to match at doses of 5 mg, 25 mg, 50 mg, and 100 mg once daily for 
10 days.
GS-9883 was generally well tolerated at the doses evaluated. A total of 9 of 20 subjects had an 
AE in this study. The most frequently reported AEs across all subjects were diarrhea (2 subjects), 
and headache (3 subjects).  No other AE was reported in more than 1 subject. There was no 
increase in the incidence of AEs with increasing doses of GS-9883.
The majority of AEs were considered by the investigator to be not related to study drug. A total 
of 2 subjects experienced mild diarrhea that was considered related to study drug (1 in the 5 mg 
cohort, 1 in the 100 mg cohort).
No deaths or pregnancies were reported. No Grade 3 or 4 AEs, SAEs, or AEs leading to 
discontinuation of study drug were reported in any cohort.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. No Grade 3 
treatment emergent laboratory abnormalities were observed. Median serum creatinine changes at 
Day 10 were: 0.05 mg/dL (5 mg), 0.04 mg/dL (25 mg), 0.06 mg/dL (50 mg), and 0.15 mg/dL 
(100 mg). These changes in serum creatinine appeared to be transient and returned close to 
baseline values on discontinuation of study drug. One Grade 4 new onset laboratory abnormality 
was seen in 1 subject who received 5 mg GS-9883. This was a Grade 4 CPK seen on Day 17, 
7 days following his last dose of study medication. The subject was asymptomatic. The 
Investigator felt that this was unrelated to study medication and was due to resumption of crystal 
methamphetamine use by the subject. An adverse event of elevated CK was reported unrelated to
study medication.
Based on PK information collected in study GS-US-141-1219, which was in line with PK 
observed in study GS-US-141-1218, the median IQ for each dose were calculated and are 
presented in the Table below.


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Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ95 Values (GS-9883 PK Analysis 
Set)
GS-9883 dose
n
Median (range) Ctau, SS (ng/mL)
Median (range) paIQ95
a
5 mg
4
206.5 (146.0 to 342.0)
1.3 (0.9 to 2.1)
25 mg
4
797.5 (714.0 to 1900.0)
4.9 (4.4 to 11.7)
50 mg
4
2170.0 (852.0 to 3020.0)
13.4 (5.3 to 18.6)
100 mg
4
4190.0 (3730.0 to 5970.0)
25.9 (23.0 to 36.9)
a.
The protein adjusted IQ95 (paIQ95) value is estimated based on steady-state Ctau values and the in vitro paIC95 value for 
wild-type HIV-1 (162 ng/ml).
The mean and 95% CIs of change from baseline in HIV-1 RNA (log10 copies/mL) are presented 
in Figure 1-1.
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set)
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study drug.


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Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group.
1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing 
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, ART-naive adult subjects.
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to 
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 50 mg 
once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 75 mg 
once daily
Week 24 interim data are summarized below. 
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24 
data analysis, 2 subjects (2.0%) had prematurely discontinued from the study, 1 in each treatment 
group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and eGFRCG) were similar 
between the 2 treatment groups.
Median (first quartile [Q1], third quartile [Q3]) baseline HIV-1 RNA was 4.45 (3.96, 4.79) log10
copies/mL, with 82.7% of subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had 
> 400,000 copies/mL at baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 
1 subject was randomized to DTG+F/TAF.
Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 41.8% of subjects 
having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 125.3 (105.7, 
147.0) mL/min.
Efficacy Results
Virologic success at Weeks 12 and 24 was assessed using the US FDA-defined snapshot 
algorithm, defined as plasma HIV-1 RNA < 50 copies/mL. At Weeks 12 and 24, virologic 


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success was high and similar between the 2 treatment groups as follows: Week 12 
GS-9883+F/TAF 93.8%, DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79); Week 24 GS-9883+F/TAF 95.4%, DTG+F/TAF 
93.9% (1.0%; 95% CI: −10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 had 60 copies/mL. 
Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF, +170 (150.0) cells/μL; DTG+F/TAF, +173 (220.5) cells/μL 
(difference in least squares mean [LSM]: 0; 95% CI: −76 to 76; p = 1.00). There were similar 
increases in the mean (SD) CD4 cell count in both treatment groups Week 24: GS-9883+F/TAF, 
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).
Interim Virology Resistance Data
Through Week 24, no emergent drug resistance was detected.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 66.2%, 43 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common treatment-emergent AEs (occurring in > 2 subjects) by treatment group were as 
follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE. One other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator or resulted in 
study drug discontinuation or interruption, and both SAEs resolved.
The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883+F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs reported that were considered related to 
study drug.


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


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
Both GS-9883+F/TAF and DTG+F/TAF were generally well tolerated through 24 weeks of 
treatment. The most commonly reported treatment-emergent AEs were diarrhea and 
headache (7.7% each) in the GS-9883+F/TAF group and nausea (12.1%) and diarrhea (9.1%) 
in the DTG+F/TAF group. There were 2 SAEs, 1 of which was also a Grade 3 AE; neither of 
these events was considered related to study drug by the investigator, or led to study drug 
discontinuation. There were no other Grade 3 or 4 AEs, and no deaths, pregnancies, or AEs 
leading to premature study drug discontinuation reported. The percentage of subjects with at 
least 1 treatment-emergent laboratory abnormality was similar between treatment groups. 
The majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. 
There were similar increases from baseline in serum creatinine in both treatment groups at 
Week 24. 
1.3.
Information about Emtricitabine (Emtriva®, FTC)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US Food and Drug Administration (FDA) for 
marketing on 2 July 2003 and is available under the name Emtriva®. In the European Union 
(EU), marketing authorization was granted for both the 200 mg Emtrivacapsule formulation 
and a 10 mg/mL Emtrivaoral Solution formulation on 24 October 2003, with indications for 
the treatment of HIV infection concurrently with other antiretroviral drugs in both adult and 
pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) or 
Fixed Dose Combination emtricitabine/tenofovir alafenamide (FTC/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected subjects (completed)


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
GS-US-120-0104, a Phase 1b study of the pharmacokinetics and antiviral activity of 
GS-7340 (8 mg, 25 mg, 40 mg) in HIV infected subjects (completed)

GS-US-120-0107, a Phase 1, partially-blinded, randomized, placebo- and positive controlled 
study to evaluate the effect of GS-7340 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-120-0108, a Phase 1, open-label, parallel-design study to evaluate the 
pharmacokinetics of GS-7340 in subjects with severe renal impairment (completed)

GS-US-120-0109, a Phase 1 study to evaluate the pharmacokinetics, metabolism and 
excretion of GS-7340 (completed)

GS-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic 
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug 
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of 
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in 
healthy subjects (completed)

GS-US-311-1386, a Phase 1 study to determine the effect of food on the pharmacokinetics of 
tenofovir alafenamide when administered as F/TAF FDC in healthy volunteers (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential 
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz (EFV) or 
COBI-boosted darunavir (DRV) (completed)

GS-US-311-1088, a Phase 1, Relative Bioavailability Study of Emtricitabine/Tenofovir 
Alafenamide Fixed Dose Combination Tablet to evaluate the formulation performance of 
emtricitabine (FTC) and tenofovir alafenamide (TAF) fixed dose combination tablets relative 
to co-administration of individual agents (completed).

GS-US-311-1089, a Phase 3 study of the safety and efficacy of FTC/TAF in HIV infected, 
virologically suppressed patients (ongoing).
In Study GS-US-311-1386, the effect of food (high-calorie, high-fat meal) on the PK of the TAF 
component of the F/TAF FDC was evaluated. The GLSM ratio of the AUClast of TAF when 
administered with a high-fat meal was 177% (90% CI: 166% to 188%), and the TAF Cmax 
GLSM ratio was 84.5% (90% CI: 74.9% to 95.4%). This ~75% increase in TAF plasma 
exposure and ~15% decrease in TAF plasma Cmax when administered with food was 
accompanied by a delay in Tmax (increase from 1.00 hour under fasted conditions to 2.00 hours 
under fed conditions). The exposures of TAF observed under fed or fasted conditions in this 


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study are within the range of exposures observed in the E/C/F/TAF clinical development 
program and are commensurate with safe and effective plasma levels of TAF (see investigator 
brochure for further details). Therefore, the changes in TAF exposures when F/TAF is 
administered with food should not result in differences in efficacy and thus are not clinically 
relevant. TAF can be administered without regard for food and these findings can be 
extrapolated to F/TAF (as FTC can be taken without regard to food).
1.4.2.
Clinical Trials of FTC/TAF as part of 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)
Clinical trials using tenofovir alafenamide, coformulated into the E/C/F/TAF STR include:

GS-US-292-0101, a Phase 1 healthy volunteer study evaluating the relative bioavailability of 
EVG, FTC, TFV, and COBI administered as E/C/F/TAF STR relative to E/C/F/TDF or TAF 
(completed)

GS-US-292-0103, a Phase 1 healthy volunteer study to evaluate the pharmacokinetics and 
relative bioavailability of the E/C/F/TAF STR relative to the individual components at 
GS-7340 doses of 10 mg (STR) or 25 mg Single Agent (SA) (completed)

GS-US-292-0102, a Phase 2 randomized, double-blinded study of the safety and efficacy of 
E/C/F/TAF STR versus E/C/F/TDF STR in HIV-1 infected, antiretroviral treatment-naive 
adults (ongoing)

GS-US-292-0104 and GS-US-292-0111, Phase 3 randomized, double-blinded study of the 
safety and efficacy of E/C/F/TAF STR versus E/C/F/TDF STR in HIV-1 infected, 
antiretroviral treatment-naive adults (ongoing)

GS-US-292-0109, a Phase 3 open-label study to evaluate switching from a TDF-containing 
combination regimen to a TAF-containing combination single tablet regimen (STR) in 
virologically-suppressed, HIV-1 positive subjects (ongoing)

GS-US-292-0112, a Phase 3 Open-label Safety Study of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide single-tablet Regimen in HIV-1 
positive patients with mild to moderate renal impairment (ongoing)

GS-US-292-0117, a Phase 3, two-part study to evaluate the efficacy of Tenofovir 
Alafenamide versus placebo added to a failing regimen followed by treatment with 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in HIV-1 positive, 
antiretroviral treatment-experienced adults (ongoing)

GS-US-292-0119, a Phase 3 open-label study to evaluate switching from optimized stable 
antiretroviral regimens containing darunavir to 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) single tablet 
regimen (STR) plus darunavir (DRV) in treatment experienced HIV-1 positive adults 
(ongoing)


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
GS-US-292-0106, a Phase 2/3, open-label study of the pharmacokinetics, safety, and 
antiviral activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected antiretroviral treatment-naive 
adolescents (ongoing)
Study GS-US-292-0101 is a Phase 1 study of 40 subjects evaluating the relative bioavailability 
of two different formulations of E/C/F/TAF STR, each with TAF dose of 25 mg or 40 mg, versus 
E/C/F/TDF STR or TAF 25 mg alone. Exposures of EVG, COBI, and FTC were comparable 
between E/C/F/TAF vs E/C/F/TDF regardless of formulation (monolayer or bi-layer). In 
contrast, TAF exposures were ~2.2-fold higher (and corresponding tenofovir exposures ~ 3-fold 
higher) when administered as E/C/F/TAF (25 mg) vs TAF single agent (SA) 25 mg for both 
formulations of the E/C/F/TAF, likely mediated by inhibition of P-gp-mediated intestinal 
secretion of TAF by COBI.
Study GS-US-292-0103 is a completed Phase 1 healthy volunteer study which evaluated the PK 
and relative bioavailability of the E/C/F/TAF STR relative to the individual components at TAF 
doses of 10 (STR) or 25 mg SA. Results indicate that when dosed as the E/C/F/TAF 10 mg STR, 
TAF and TFV exposures were comparable to those observed with TAF 25 mg dosed alone. 
Exposures of EVG, COBI, and FTC were also comparable between the STR and individually 
dosed formulations.
Study GS-US-292-0102 is an ongoing, randomized, active-controlled Phase 2 study, compares 
E/C/F/TAF (10 mg) versus Stribild® (STB, E/C/F/TDF) in treatment-naïve, HIV-1 infected 
subjects. At Week 48, the E/C/F/TAF demonstrated potent antiviral efficacy (HIV-1 RNA 
< 50 copies/mL) similar to STB (88.4% [99/112] vs 87.9% [51/58] using the US FDA-defined 
snapshot algorithm); in the E/C/F/TAF group, no patient had emergent resistance to 1 or more 
components of the E/C/F/TAF. Importantly, E/C/F/TAF demonstrated a potential benefit over 
E/C/F/TDF in terms of renal and bone safety: smaller median decreases in eGFR (mL/min) (at 
Week 48, E/C/F/TAF -5.5 vs E/C/F/TDF -10.0 [P<0.001) and smaller median percentage 
decreases in BMD (at Week 48, spine E/C/F/TAF -1.00 vs E/C/F/TDF -3.37 [p<0.001], hip -0.62 
vs -2.39 [p<0.001]).
Studies GS-US-292-0104 and GS-US-292-0111 are ongoing, Phase 3 randomized, 
double-blinded studies of the safety and efficacy of E/C/F/TAF versus E/C/F/TDF in HIV-1 
infected, antiretroviral treatment-naive adults. The interim Week 48 key conclusions from pooled 
data showed that E/C/F/TAF once daily was noninferior to STB once daily when administered 
for 48 weeks to HIV-infected, ART-naive adults, as assessed using the US FDA-defined 
snapshot algorithm with HIV-1 RNA < 50 copies/mL (E/C/F/TAF 92.4%; STB 90.4%; 
difference in percentages: 2.0%, 95% CI: -0.7% to 4.7%). Administration of E/C/F/TAF resulted 
in > 90% lower plasma TFV and higher intracellular TFV-DP relative to STB.  E/C/F/TAF 
showed an improved renal and bone safety profile with significantly less decline in hip and spine 
BMD, less increase in serum creatinine and reduction in estimated glomerular filtration rate 
(eGFR). 


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1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF)
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, FTC, and 
TAF between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is an ongoing Phase 1, open-label, 2-cohort, multiple-period,
fixed-sequence, crossover study conducted at a single center in the US to evaluate 1) the relative 
bioavailability (BA) of 2 GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets 
compared with the GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered 
simultaneously and 2) the effect of food on the PK of GS-9883, FTC, and TAF when 
administered as GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets.
Cohort 1 evaluated the relative BA and food effect of GS-9883/F/TAF (75/200/25 mg) FDC 
tablet in a 3-period sequence. Following review of preliminary data from Cohort 1, Cohort 2 was 
added to the study via protocol amendment. Cohort 2 evaluated the relative BA and food effect 
of GS-9883/F/TAF (50/200/25 mg) FDC tablet in a 4-period sequence.
The in-life portion of Cohorts 1 and 2 are complete. Preliminary results are summarized below. 
Cohort 1 Results:
Pharmacokinetic Results
Under fasted conditions, GS-9883 AUCinf and Cmax were 27% and 31% higher, respectively, 
following GS-9883/F/TAF (75/200/25 mg) FDC administration than following administration of 
single-agent GS-9883 (75 mg ) with the F/TAF (200/25 mg) FDC. FTC and TAF exposure was 
similar following administration of GS-9883/F/TAF (75/200/25 mg) or single-agent GS-9883 
(75 mg) with the F/TAF (200/25 mg) FDC. 
Compared with administration under fasted conditions, administration of the GS-9883/F/TAF 
(75/200/25 mg) FDC with a high-fat meal resulted in a 46% higher GS-9883 AUCinf and a 27% 
higher GS-9883 Cmax. The impact of food on TAF and FTC exposure was similar to that 
previously observed for F/TAF (Study GS-US-311-1386). GS-9883/F/TAF may be taken 
without regard to food.  Based on these results, Cohort 2 was added to the study via protocol 
amendment to evaluate the relative BA of the GS-9883/F/TAF (50/200/25 mg) FDC tablet 
compared with the single-agent GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet 
administered simultaneously.
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 1, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 


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severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
Cohort 2 Results:
Pharmacokinetic Results
The PK results from Study GS-US-141-1233 demonstrated that the GS-9883 AUCinf and Cmax
following administration of the 50mg GS-9883 FDC tablets was 79% and 78%, respectively of 
those observed in the same study following co-administration of GS-9883 75 mg single agent 
with F/TAF (200/25 mg) under fasted conditions. The GS-9883 exposures of 50 and 75mg fixed 
dose combination tablets were approximately dose proportional under fasted and fed conditions
and a high fat and moderate fat meal had similar impact on GS-9883 with AUCinf increasing by 
24%. The steady state paIQ95 of GS-9883/F/TAF (50/200/25 mg) was predicted to be 
17 (fasted)-23 (fed). The exposures of TAF and FTC of the 50 mg GS-9883 FDC were similar 
to those of GS-9883 75 mg single agent with F/TAF FDC, and the food effect on TAF and FTC 
was similar to the historical results.  
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 2, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
1.6.
Rationale for this Study
As treatment guidelines recommend early treatment of HIV-1 infection, there is need for 
regimens that maximize long-term efficacy, safety, tolerability, and convenience. These features 
are determined by the specific formulation of the regimen (fixed-dose, or multi-tablet regimens), 
the nucleos(t)ide backbone, and the third agents (PI, NNRTI, or INSTI).
Switching to GS-9883/F/TAF may offer the advantages of a single-tablet FDC containing the 
unboosted, next-generation INSTI, GS-9883, combined with a TAF-containing nucleotide 
backbone. This regimen has the potential to avoid unwanted side effects from PI-based therapy 
(such as hyperbilirubinemia, rash, gastrointestinal upset, and dyslipidemia), decrease the 
potential for drug-drug interactions by removing the need for a boosting agent, avoiding potential 
long term renal and bone side effects from TDF, and avoiding potential long-term cardiovascular 
risk from ABC.
Four FDCs are currently approved in the US and EU for once-daily administration as a complete 
regimen for the treatment of HIV-1 infection, EFV/FTC/TDF, FTC/RPV/TDF, E/C/F/TDF, and 
ABC/DTG/3TC. There is no PI-containing FDC currently available. Studies have shown that a 
once-daily FDC significantly improved adherence, treatment satisfaction, and virologic 
outcomes for patients infected with HIV-1 {Dejesus E 2009}, {Hodder et al 2010}, {Airoldi et al 
2010}, {Bangsberg et al 2010}. Due to longer duration of high adherence, patients taking FDCs 


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also have better clinical outcomes, such as fewer hospitalizations, compared with multiple-tablet 
regimens {Sax et al 2010}.
Boosted protease inhibitors still represent a sizeable portion of the treated HIV-1-infected 
population and are viewed as the class with the greatest barrier to resistance. Boosted DRV is the 
only PI that remains on the DHHS treatment guidelines as a preferred agent, though ATV is still 
widely prescribed. Use of DRV/r and ATV/r in this study will allow comparison of the 
GS-9883/F/TAF FDC with these third agents, regardless of NRTI backbone. The study has the 
potential to demonstrate benefits such as decreased pill burden and adverse events, and improved 
patient reported outcomes.
This study will evaluate the safety, efficacy and tolerability of switching from boosted PI 
regimens to GS-9883/F/TAF, thereby assessing the viability of GS-9883/F/TAF as a FDC option 
for HIV-infected patients.
1.7.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.


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


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1.8.
Risk Benefit Assessment for this Study
All patients with HIV-1 infection should receive effective anti-retroviral therapy. Potential risks 
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and 
lactic acidosis with steatosis.  The risk of class effects is considered to be low.  Important 
identified risks appropriately managed by study inclusion/exclusion criteria as well as through 
close clinical and laboratory monitoring during the study are as follows:  hypersensitivity
reaction to abacavir and allergy to any components of the tablets.  Some observational studies 
have shown increased risk of cardiovascular disease with abacavir.  Protease inhibitors may be 
associated with increased lipid levels and gastrointestinal side effects. If patients are currently 
infected with hepatitis B and discontinue their existing or new therapy, there is a risk of severe 
acute exacerbations of hepatitis B.
In a study of GS-9883 in monkeys, administration of 1000 mg/kg/day (highest dose) for 
39 weeks resulted in histologic findings of bile duct hyperplasia and  hepatocyte hypertrophy.  
No adverse effects were noted at the mid-dose group (200 mg/kg/day), which resulted in 
exposures of GS-9883 5.1 times higher than the expected human exposure with administration of 
GS-9883/F/TAF (50/200/25 mg) tablets. No such findings were seen in rats at any dose.  
However, the risk of liver or biliary abnormalities in humans receiving GS-9883/F/TAF 
(50/200/25 mg) for chronic use is unknown. Potential hepatobiliary toxicity is appropriately 
managed by study inclusion/exclusion criteria, close clinical and laboratory monitoring, as well 
as specific toxicity management guidance to investigators (Refer to Section 7.5.7.).  
Potential benefits of GS-9883 may include provision of a new antiretroviral therapy that is not 
currently available and which may have fewer side effects than alternative therapies.  Other 
potential benefits include provisions of fixed dose combination therapy, and the knowledge that 
patient participation will contribute to the body of knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF is favorable at this time.
1.9.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of switching to a FDC of  GS-9883/F/TAF versus continuing on a 
regimen consisting of boosted atazanavir or darunavir plus either FTC/TDF or ABC/3TC in 
HIV-1 infected adult subjects who are virologically suppressed as determined by the 
proportion of subjects with HIV-1 RNA ≥50 copies/mLat Week 48
The secondary objective of this study is:

To evaluate the safety and tolerability of the two treatment groups through Week 48


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3.
STUDY DESIGN
3.1.
Endpoints
The primary efficacy endpoint is:

The proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 as defined by the 
US FDA-defined snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell counts at Week 48
3.2.
Study Design
This protocol describes a randomized, open-label, multicenter, active-controlled study to
evaluate the safety and efficacy of switching to a FDC of GS-9883/F/TAF in HIV-1 infected 
adult subjects who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen 
consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for 
≥6 months prior to screening.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: Switch to FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily without regard to food
(n=260)
Treatment Group 2: Remain on current antiretroviral regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC administered orally,
once daily with food (n=260)
3.4.
Duration of Treatment
The treatment duration is 48 weeks.
At the Week 48 Visit, treatment group 1 and 2 subjects in a country where GS-9883/F/TAF FDC 
is not available will be given the option to receive GS-9883/F/TAF FDC for additional 48 weeks 
and attend study visits every 12 weeks, or until the product becomes accessible to subjects 
through an access program, or until Gilead Sciences elects to discontinue the study in that 
country, whichever occurs first.


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Figure 3-1. 
Study Schema 
Screening 
S30doys 
prior 
to Day 1 
Day 1• 
Week 4Sb,c 
Treatment Group 2: Remain on current regimen of 
boosted ATV or DRV plus FTCJTDF or ABC/3TC 
QD (n=260) 
30 Day 
FfU< 
a. 
Following the Day 1 visit, subjects will be required to ret1.u11 for st1.1dy visits at Weeks 4, 8, 12, and then every 12 weeks 
through Week 48. 
b. 
After Week 48, subjects in a countty where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F!T AF FDC for additional 48 weeks and attend st1.1dy visits eve1y 12 we.eks, or until the product becomes 
accessible to subjects tiu·ough an access program, or until Gilead Sciences elects to discontinue the study in ti1at c.otmtty, 
whichever occurs fust. 
c. 
Subjects who complete the study tluough ti1e Week 48 Visit and do not wish to receive GS-9883/F !T AF FDC will be 
required to rettun to ti1e clinic 30 days after the completion of study drugs for a 30-Day Follow-Up Visit. 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Pharmacogenomic Research 
PD 
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3.5.2.
Additional Sample Storage
For subjects who provide additional consent, residual blood and urine samples taken throughout 
the study will be stored. Stored samples may be used by the Sponsor or its research partners to 
help answer questions about the study drug, and HIV disease and its associated conditions, or to 
provide additional safety data.  At the conclusion of this study, these samples may be retained in 
storage by Gilead Sciences for a period up to 15 years.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 520 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1. The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2. Age 18 years
3. Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat 
boosted ATV or DRV plus either FTC/TDF or ABC/3TC for 6 months preceding the 
screening visit
4. HIV RNA < 50 copies/mL at the screening visit
5. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6. Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥0.83 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft et al 1976}:
a.
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
         (140 – age in years) (wt in kg)
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
b. Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg)  
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7. Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8. Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin
9. Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥ 50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))


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10. Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11. Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12. Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 6) throughout the study period and for 
90 days following the last dose of study drug.
13. Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14. Life expectancy ≥ 1 year
15. Currently on a stable regimen for ≥ 6 months preceding the Screening visit with documented 
plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months preceding the Screening visit (or 
undetectable HIV-1 RNA level according to the local assay being used if the limit of 
detection is ≥ 50 copies/mL). 
Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for 
regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient 
detectable viremia, or “blip”) prior to screening are acceptable. (If the lower limit of 
detection of the local HIV-1 RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the plasma 
HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
16. Have no documented or suspected resistance to FTC, TFV, ABC or 3TC, including but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I
17. No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1. An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
2. Subjects experiencing decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal 
bleeding)


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3. Have been treated with immunosuppressant therapies or chemotherapeutic agents within 
3 months of study screening, or expected to receive these agents or systemic steroids during 
the study (e.g, corticosteroids, immunoglobulins, and other immune- or cytokine-based 
therapies)
4. Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance
5. A history of or ongoing malignancy (including untreated carcinoma in-situ) other than 
cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous 
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must 
not have received any systemic therapy for KS within 30 days of Day 1 and are not 
anticipated to require systemic therapy during the study
6. Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
7. Participation in any other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9. Any known allergies to the excipients of GS-9883/F/TAF FDC or ATV, RTV, DRV, COBI, 
FTC/TDF or ABC/3TC
10. Females who are pregnant (as confirmed by positive serum pregnancy test)
11. Females who are breastfeeding
12. Subjects receiving ongoing therapy with any of the medications listed in the Table 5-1 and 
Table 5-2. Administration of any Prohibited Medication (Table 5-1 and Table 5-2) must be 
discontinued at least 30 days prior to the Day 1 visit and for the duration of the study.
13. Acute hepatitis in the 30 days prior to study entry
14. Chronic hepatitis B infection in subjects not on a TDF containing regimen, as determined by 
either:

Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit

Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
15. Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day 1 visit the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Treatment Group 1: Switch to a FDC of GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) administered orally once daily without regard to food (n=260)
Treatment Group 2: Remain on current antiretroviral regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC administered orally once 
daily with food (n=260)
Randomization will be stratified by the prior treatment regimen group (ie, TDF containing 
regimens [ritonavir or cobicistat boosted ATV or DRV plus FTC/TDF] and non-TDF containing 
regimens [ritonavir or cobicistat boosted ATV or DRV plus ABC/3TC]) at screening.
Subjects randomized in Treatment Group 1 will be assigned study drug bottle numbers of 
GS-9883/F/TAF FDC at study visits by IWRS.
Investigators must provide a prescription to the subjects in Treatment Group 2. Those subjects 
are responsible for obtaining their ARV treatment prior to or during the study visit.
5.2.
Description and Handling 
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF 
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg Tablets
GS-9883/F/TAF  tablets are packaged in white, high density polyethylene (HDPE) bottles. Each 
bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal 
Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drug GS-9883/F/TAF should be stored at controlled room temperature of 25°C (77°F); 
excursions are permitted between 15°C and 30°C (59°F and 86°F).  Storage conditions are 
specified on the label. Until dispensed to the subjects, all bottles of study drugs should be stored 
in a securely locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide
GS-9883/F/TAF tablets will be provided by Gilead Sciences.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 50 mg/200 mg/25 mg FDC 
will be administered orally, once daily without regard to food at approximately the same time 
each day.
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability.  The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return.


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5.4.
Prior and Concomitant Medications

The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following table and use of herbal/natural supplements are excluded or 
should be used with caution while subjects are participating in the study, depending on subject’s 
treatment regimen. Subjects will refrain from consumption of grapefruit juice and Seville orange 
juice throughout participation in the study.
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With 
Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may 
decrease with antacids. Subjects may not 
take antacids (eg, Tums or Rolaids); the 
ulcer medication sucralfate (Carafate); or 
vitamin or mineral supplements that 
contain calcium, iron or zinc for a 
minimum of 2 hours before and 6 hours 
after any dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of 
the study regimen
GI Motility Agents
Cisapride
Herbal/Natural 
Supplements
St. John’s Wort, Echinacea
Oral Hypoglycemic Agent
Metformin: close monitoring is 
recommended. A dose adjustment of 
Metformin may be necessary. Limit total 
daily doses of Metformin to 1000mg 
either when starting or at study entry.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.


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Table 5-2.
Prior and Concomitant Medications (Boosted ATV and DRV 
regimen)
Drug Class
Agents Disallowed*
Alpha-1 Adrenoreceptor Antagonist
Alfuzosin
Antiarrhythmic Agent
Amiodarone, Dronedarone
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine
Antimycobacterials
Rifampin
Antipsychotics
Lurasidone, Pimozide
Antiretrovirals
Any antiretroviral drug that is not part of the study 
regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort
Anticancer drugs
Irinotecana
Ergot Drivatives
Ergotamine, Ergonovine
Dihydroergotamine
Methylergonovine
Ergometrine
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Phosphodiesterase-5 Inhibitors
Sildenafil ( for PAH)
Sedatives/Hypnotics
Orally administered Midazolam, Triazolam
Calcium Channel Blockers
Bepridil
Chronic angina
Ranolazine
a
Applied to ATV regimen only
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Sciences Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead Sciences as soon as he/she is aware of the use of the excluded 
medication.
Additionally, Investigators should refer to the current product/package inserts of the 
antiretroviral medications for contraindications related to their use.
5.5.
Accountability for Investigational Medicinal Product (IMP)
The investigator is responsible for ensuring adequate accountability of all used and unused IMP.
This includes acknowledgement of receipt of each shipment of IMP (quantity and condition). All 
used and unused IMP dispensed to subjects must be returned to the site.


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Study Drug accountability records will be provided to each study site to:

Record the date received and quantity of IMP kits

Record the date, subject number, subject initials, the IMP kit number dispensed

Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
Return and disposal of study drug GS-9883/F/TAF will be performed as outlined in 
Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that subjects are eligible for study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events, smoking history 
and prior medications within 30 days of the screening visit. 

If available, obtain 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

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled


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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
■
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg) 
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
■
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
       (140 – age in years) (wt in kg) 
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
Plasma HIV-1 RNA
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), 
Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)
The following will be conducted by the central laboratory if the following criteria are 
met:
■
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex 
HBeAb), and quantitative HBsAg
■
If positive HBcAb with negative HBsAg  and negative HBsAb, reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to 
be negative, reflex HBeAb.
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.

Review of adverse events and concomitant medications


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Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for Day 1 Visit. Subjects must continue to take their prior 
treatment regimen up until their scheduled Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. See 
Section 7 Adverse Events and Toxicity Management for additional details.
6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
confirmed subject’s eligibility before proceeding with the Day 1 visit. The subject must 
complete all study procedures before being administered the study drug:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI), UCLA Scleroderma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) and VAS Adherence 
Questionnaire to be completed by the subject. Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate
Urine storage sample for possible additional clinical testing


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Blood sample collection for the following laborat01y analyses: 
-
Chemistly profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassimn, sodium, mic acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 x ULN) and TSH 
-
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 homs prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must retmn within 72 homs in a fasted state to draw blood for the metabolic 
assessments. 
-
Estimated glomerular filtration rate according to the Cockcroft-Gault f01mula 
-
Hematology profile: complete blood count (CBC) with differential and platelet count 
-
Plasma HIV-1 RNA 
-
CD4+ cell count 
-
Plasma storage sample for safety, virology, or PK testing 
-
Whole blood sample for potential HIV DNA genotyping 
-
Subjects who meet the defmition of HBV infection below at Screening Visit (positive 
serum HBsAg or Positive HBcAb with quantifiable HBV DNA), will have plasma HBV 
DNA tested. 
• 
Optional blood sample collection for the following laboratory analyses if 
pharmacogenomic consent is obtained 
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6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 -48)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, and 48 unless 
otherwise specified.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 36, unless otherwise specified.  The visit window at Week 48 will be ± 6 weeks of 
the protocol-specified visit date and this clinical visit window coincides with the Week 48 
statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24 and 48) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Weeks 24 and 48)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and UCLA Scleroderma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) to be completed by the subject  at 
Weeks 4, 12, and 48. Subject is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires.

VAS Adherence Questionnaire. Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin (Weeks 24 and 48)


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Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 12, 24 and 48, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. At Weeks 24 and 48, TSH will also 
be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24 and 48)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
■
At Weeks 12, 24 and 48 (for subjects who meet the definition of HBV infection), the 
following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative 
and quantitative) and HBeAg (if negative, reflex HBeAb)

Pharmacokinetic Blood Collection for subjects who are on study drug in Treatment Group 1 
only. Details of pharmacokinetic blood sampling procedures and sample management will be 
documented in the Pharmacokinetic Sample Collection, Processing, Storage, and Shipment 
Manual.
Single Anytime, Trough and Post Dose PK Samples for all subjects on study drug in 
Treatment Group 1:
■
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 and 
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Observed dosing at the clinic: Subjects will have a trough PK blood sample collected 
between 20-28 hours following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study drugs on the moming of their visit for the trough 
sample collection. Subjects will then take an observed dose of study drug at the clinic. 
A single post dose PK blood sample will be collected between 1 and 4 hours post 
dose. If the subject has taken their dose of study drugs prior to the visit, the visit may 
proceed, but the subject must retum within 72 hours for the trough PK blood sample 
collection. In the event a subject routinely takes their study drug in the evening, a 
single post-dose sample may be drawn at Weeks 4 and 12 as the subject will not be 
instmcted to change their dosing time to accommodate this trough PK draw. 
• 
Dosing diru·ies will be collected from subjects for the single ru1ytime PK and trough 
PK collection. If a dosing diaty is not retumed the site may ask the subject for the 
time of the last dose and if it was taken with or without food. 
-
Optional Pharmacokinetic (PK) Substudy: 
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6.5.
Treatment Assessments (Post Week 48)
6.5.1.
Post Week 48 Assessments
At the Week 48 visit, subjects who completed 48 weeks of study drug treatment and are in a 
country where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for additional 48 weeks and attend study visits every 12 weeks, or until the 
product becomes accessible to subjects through an access program, or until Gilead Sciences 
elects to discontinue the study in that country, whichever occurs first.
Subjects who further continue participation in the study and receive GS-9883/F/TAF FDC will 
return for study visits every 12 weeks. Study visits are to be completed within ±6 days of the 
protocol-specified visit date unless otherwise specified.
Subjects participating in the study post Week 48 will be required to return for study visits 
according to the schedule presented in Appendix 1. Study Procedures Table and described in the 
text below:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination as needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin (Weeks 72 and 96)
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks.


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Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.13.

Document study drug dispensation and accountability for all study drugs dispensed.
6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will 
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drugs Discontinuation Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight 

12-lead ECG performed supine

VAS Adherence Questionnaire. Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.


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
Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30-Day Follow-Up
Subjects who complete the study through Week 48 and who do not further continue participation 
in the study, will be required to return to the clinic 30 days after the completion of study drug for 
the 30-Day Follow-Up visit.
Subjects who permanently discontinue study drug prior to Week 48 and refuse to continue in the 
study will be asked to return to the clinic 30 days after the completion of the Early Study Drugs 
Discontinuation Visit for the 30-Day Follow-Up Visit.
Those subjects who permanently discontinue study drug and continue in the study through 
at least one subsequent visit after the Early Study Drug Discontinuation Visit will not be 
required to complete the 30-Day Follow-Up Visit.


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


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
Pregnancy during the study; refer to Appendix 6

Development of active tuberculosis infection
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator

Lack of efficacy

Subject noncompliance

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)
6.8.
Other Evaluations
6.8.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include but not limited to urine albumin, urine creatinine, urine protein, retinol binding 
protein and beta-2-microglobulin at Day 1 Visit, Weeks 24, 48, and every 24 weeks post 
Week 48.
6.9.
Blood and Urine Storage
A portion of the blood and urine samples drawn at all visits (except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its research partners for HIV-1 genotyping/phenotyping 
assays or their development, for retesting the amount of HIV-1 in the blood, for measurement of 
antiviral drug levels in the blood, or for testing to learn more about how the study drug has 
worked against HIV-1 or clinical laboratory testing to provide additional safety data. No human 
genetic testing will be performed without expressed consent of study subjects. At the conclusion 
of this study, these samples may be retained in storage by Gilead Sciences for a period up to 
15 years.
6.10.
Assessments for Premature Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.7, Criteria for Discontinuation of Study Treatment). If 
this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study.


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6.11.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.12.
Post Study Care
After a subject has completed/terminated their participation in the study, long-term care for the 
subject will remain the responsibility of their primary treating physician.
6.13.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation or Week 48. 
6.13.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any post Day 1 visit, a rebound in HIV-1 RNA ≥ 50 copies/mL, which is subsequently 
confirmed at the following scheduled or unscheduled visit;
OR

Any subject with HIV RNA ≥ 50 copies/mL at study drug discontinuation
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing.  Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-Day 1 resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.
If no resistance is detected from the genotype or phenotype, the subject may remain on study 
drugs and HIV-1 RNA test should be repeated (2 to 3 weeks after date of test with HIV-1 RNA
≥50 copies/mL). Investigators should carefully evaluate the benefits and risks of remaining on 
study drug for each individual subject and document this assessment in the on-site medical 
record.
Subjects who are noncompliant on an ongoing basis will be considered for discontinuation per 
the Investigator’s discretion or local treatment guidelines. Investigators who opt to discontinue 
study drugs for an individual subject must discuss with the Medical Monitor prior to study drug 
discontinuation.
For subjects who are off study drug but remain on study, it will be the Investigator’s discretion to 
manage virologic rebound.


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


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


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


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


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


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
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 4).

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat
testing within 3 calendar days of receipt of results and before investigational medicinal 
product discontinuation, unless such a delay is not consistent with good medical practice

Any questions regarding toxicity management should be directed to the Gilead Medical 
Monitor.
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.


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


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7.5.4.1.
Management of ALT Flare in Subjects Receiving Study Medication
If laboratory results indicate elevation of ALT 2 × Day 1 value and 10 × ULN, the following 
is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally within 3 days after 
initial laboratory results were drawn). During the visit, a clinical assessment of the subject 
will be performed. The assessment should include a physical examination and evaluation of 
the subject’s mental status.

If the ALT elevation is confirmed, request the central clinical laboratory to conduct reflex 
testing for plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM, and 
HCV serology
Check the following laboratory parameters: serum ALT and AST, total bilirubin, INR, and serum 
albumin. Based on the results of the confirmatory tests, the following treatment modifications are 
recommended:
Elevated Liver Enzymes, Normal or Stable relative to Day 1 Liver Function Tests
If ALT levels are elevated (i.e., 2 × Day 1 and 10 × ULN) with normal or stable total 
bilirubin and INR relative to Day 1, the subject may remain on study medication and should be 
monitored weekly as long as ALT levels return to normal or Day 1 level. During monitoring, if 
the ALT values remain persistently elevated, the Investigator should discuss with the Gilead 
Medical Monitor whether the study drug should be discontinued.
Elevated Liver Enzymes, Elevated Liver Function Tests
If ALT values are elevated (i.e., 2 × Day 1 and 10 × ULN), and total bilirubin is confirmed to 
be 2 x Day 1 value, and INR is 0.5 above Day 1, provided both are > ULN,  the investigator 
should consider discontinuing study medication (upon discussion with the Gilead Medical 
Monitor, unless the safety of the patient is of immediate concern).  The subject should be 
monitored weekly as long as ALT, total bilirubin, and INR values remain elevated or above 
Day 1 values.
During monitoring, if the ALT values and the liver function tests remain persistently elevated, 
the Investigator should discuss with the Gilead Medical Monitor whether the study drug should 
be discontinued.
7.5.4.2.
Management of Exacerbation of Hepatitis B in Subjects who have Discontinued 
Study Medication
If laboratory results indicate (1) an ALT elevation 2 × Day 1 and 10 × ULN alone OR 
associated with (2) abnormal laboratory parameters suggestive of worsening hepatic function 
(total bilirubin 2 × Day 1, INR 0.5 above Day 1, provided both are > ULN) and the subject is on 
no post-study therapy for HBV, the following is recommended:


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
Schedule the subject to return to the clinic as soon as possible (ideally no later than 3 days 
after the initial laboratory values were drawn). During the visit, perform a clinical assessment 
of the subject.

Check the following laboratory parameters: serum ALT and AST, bilirubin, INR, and 
albumin.

If the ALT elevation is confirmed, request the clinical laboratory to conduct reflex testing for 
plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM and HCV. If 
serum HBV DNA is increasing, the investigator should consider immediate initiation of 
approved therapy.

The subject should be followed until laboratory parameters (ALT, total bilirubin, INR) return 
to normal or Day 1 up to a maximum of 6 months after the initial occurrence of the event.
7.5.5.
Management of Hyperbilirubinemia
Most patients taking atazanavir sulfate experience asymptomatic elevations in indirect 
(unconjugated) bilirubin related to inhibition of UDP-glucuronyl transferase (UGT). Hepatic 
transaminase elevations that occur with hyperbilirubinemia should be evaluated for alternative 
etiologies. Dose modification of atazanavir sulfate is not permitted. Subjects who experience 
unacceptable jaundice/scleral icterus can be discontinued from study at the discretion of the 
Investigator.

Subjects with bilirubin levels of 5-10 x ULN, if isolated and not accompanied by 
unacceptable clinical jaundice (scleral icterus or cutaneous jaundice) may continue on study,
if agreed upon by the subject and the Investigator. All subjects with serum bilirubin levels
5-10 x ULN must have bilirubin, AST and ALT repeated at least once within 7 days of the
Investigator being notified of the elevated bilirubin level. Thereafter, serum bilirubin
levels 5-10 x ULN without clinically significant elevation in AST or ALT should be
followed according to the clinical judgment of the Investigator.

Subjects whose hyperbilirubinemia (5-10 x ULN) is accompanied by ≥ Grade 2 ALT or AST
elevation or who experience a one Grade worsening in ALT or AST do not qualify as having
isolated hyperbilirubinemia and will be discontinued.

Confirmed hyperbilirubinemia > 10 x ULN will require discontinuation.

Elevation of conjugated (direct) bilirubin > 2 mg/dL in association with Grade 2 ALT or AST
elevation will require discontinuation.
7.5.6.
Management of Possible Abacavir Hypersensitivity Reaction
Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to increased 
risk of hypersensitivity reaction, unless no other therapeutic option is available based on the 
treatment history and resistance testing.


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In a clinical study, 3.4 % of subjects with a negative HLA-B*5701 status receiving abacavir 
developed a hypersensitivity reaction. Therefore, even in the absence of HLA-B*5701 allele, it is 
important to permanently discontinue abacavir and not rechallenge with abacavir if a 
hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe 
or even fatal reaction.
Hypersensitivity reactions are characterized by the appearance of symptoms indicating 
multi-organ system involvement. Almost all hypersensitivity reactions will have fever and/or 
rash as part of the syndrome. Other signs and symptoms may include respiratory signs and 
symptoms such as dyspnoea, sore throat, cough, and abnormal chest x-ray findings 
(predominantly infiltrates, which can be localized), gastrointestinal symptoms, such as nausea, 
vomiting, diarrhea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as 
respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis. Other frequently 
observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and 
musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia). The symptoms related to this 
hypersensitivity reaction worsen with continued therapy and can be life- threatening. 
These symptoms usually resolve upon discontinuation of abacavir.
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. Patients 
should be monitored closely, especially during the first two months of treatment with abacavir.
Regardless of their HLA-B*5701 status, patients who are diagnosed with a hypersensitivity 
reaction whilst on therapy MUST discontinue study drug immediately and MUST NEVER be 
restarted. Restarting study drug following a hypersensitivity reaction results in a prompt return of 
symptoms within hours. This recurrence is usually more severe than on initial presentation, and 
may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimize 
the risk of a life-threatening hypersensitivity reaction, study drug must be permanently 
discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible 
(respiratory diseases, flu-like illness, gastroenteritis or reactions to other medicinal products) 
{Ezzati et al 2003}.
7.5.7.
Management of Potential Hepatobiliary Toxicity
Monkeys given a high dose (1000 mg/kg/day) for 39 weeks had evidence of biliary hyperplasia 
and hepatocyte hypertrophy on histopathologic examination. The risk to humans given the 
clinical dose of GS-9883 (50 mg/day) is unknown. Investigators should be aware of this potential 
toxicity. Any study subject exhibiting signs/symptoms or laboratory abnormalities suggestive of 
possible hepatobiliary toxicity should undergo thorough examination and clinical workup as 
deemed appropriate by the Investigator, and the Investigator must communicate promptly with 
the Gilead Medical Monitor. Consideration should be given to appropriate imaging studies (for 
example, ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. Management of graded 
laboratory and clinical abnormalities will be managed as outlined in section 7.5.


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7.5.8.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus, Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose 
interruption. Should the Investigator feel the need to initiate Hepatitis C treatment the 
Investigator must contact the Gilead Medical Monitor to confirm that no drug-drug interactions 
are expected. Subjects should return to the clinic for scheduled or unscheduled follow up visit(s) 
according to local medical practice for laboratory evaluations. If Hepatitis C treatment is 
initiated, Investigators should use the Gilead provided retest laboratory kits to manage the active 
Hepatitis C.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 


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period, to the Gilead DSPH using the pregnancy report form within 24 hours of becoming aware 
of the pregnancy.
Refer to the below and the eCRF completion guidelines for full instructions on the mechanism of 
pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.3.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post study 
must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows:
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477.
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH, fax number 
+1 650 522-5477 or email Safety_FC@gilead.com.
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications.
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.


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Refer to Section 7.6.2.1 and the eCRF completion guidelines for full instructions on the 
mechanism of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is to evaluate the efficacy of switching to a FDC of 
GS-9883/F/TAF versus continuing on a regimen consisting of boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC (i.e., boosted PI + 2NRTIs) in HIV-1 infected subjects who are 
virologically suppressed as determined by the proportion of subjects withHIV-1 RNA 
≥50 copies/mL at Week 48.
The secondary objective of this study is to evaluate the safety and tolerability of the 
two treatment groups through Week 48.
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 
as defined by the US FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.
8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
randomized.


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8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis 
set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing is due to discontinuation of study drug for lack of efficacy.

Subjects who do not meet the inclusion criterion for no previous use of any approved or 
experimental integrase strand transfer inhibitor (INSTI)

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 4.3 including drugs not to be used with 
FTC, TAF, GS-9883, ATV, RTV, COBI, DRV, FTC/TDF and ABC/3TC
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Substudy Analysis Set
The primary analysis set for intensive PK analyses is defined as the PK substudy analysis set, 
which will include all subjects who (1) are randomized into the study, (2) enrolled into the PK 
Substudy, (3) have received at least 1 dose of study drug, and (4) have at least 1 nonmissing 
intensive PK concentration data for the analyte under evaluation reported by the PK lab.
8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the pharmacokinetic (PK) analysis 
set, which will include all subjects who (1) are randomized into the study, (2) have received at 
least 1 dose of study drug, and (3) have at least 1 nonmissing PK concentration data for the 
analyte under evaluation reported by the PK lab.


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8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (e.g., if the result of a continuous laboratory test is 
< 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (i.e., no toxicity grade) for the laboratory abnormality summary.
All available data for subjects that do not complete the study will be included in data listings.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, body mass index, and eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline 
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm. The primary analysis of the 
efficacy will be based on the FAS.
8.5.1.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, including data collected up to 1 day after the last 
dose date of study drug) will be used in the snapshot algorithm. Virologic outcome will be 
defined as the following categories:


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
HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window

HIV-1 RNA ≥50 copies/mL: this include subjects
Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window , or
Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and
■
Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or
■
Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than lack of efficacy and have the last available on-treatment HIV-1 
RNA ≥50 copies/mL

No Virologic Data in the Week 48 Analysis Window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following:
Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL, or
Missing data during the window but on study drug
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 
48 in the GS-9883/F/TAF group is at least 4% higher than that in the boosted PI + 2NRTIs
group; the alternative hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 
copies/mL in the GS-9883/F/TAF group is less than 4% higher than that in the boosted-PI + 
2NRTIs group.
Non-inferiority will be assessed using the confidence interval (CI) approach. The point estimate 
of treatment difference (GS-9883/F/TAF – boosted PI + 2NRTIs) and the associated 2-sided 
95% CIs will be constructed based on the exact method. It will be concluded that 
GS-9883/F/TAF is non-inferior to boosted PI + 2NRTIs if the upper bound of the 2-sided 95% 
CI of the difference between treatment groups (GS-9883/F/TAF – boosted PI + 2NRTIs) in the 
percentage of subjects with HIV-1 RNA ≥50 copies/mL is less than 4% (ie, a margin of 4% is 
applied to non-inferiority assessment).
If non-inferiority of GS-9883/F/TAF to boosted PI + 2NRTIs 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 
GS-9883/F/TAF over boosted PI + 2NRTIs will be established.


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8.5.2.
Secondary Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the US 
FDA-defined snapshot algorithm will also be evaluated. The 95% CIs will be constructed in the 
same manner as for the primary efficacy endpoint. However, non-inferiority will be assessed 
using a margin of 10%. It will be concluded that GS-9883/F/TAF is noninferior to boosted PI 
+ 2NRTIs if the lower bound of the 2-sided 95% CI of the difference between treatment groups 
(GS-9883/F/TAF – boosted PI + 2NRTIs) in the response rate is greater than -10%.
The change from baseline in CD4+ cell count at Week 48 will be summarized by treatment using 
descriptive statistics. The differences in changes from baseline in CD4+ cell count between
treatment groups and the associated 95% CIs will be constructed using ANOVA models, 
including treatment (GS-9883/F/TAF vs. boosted PI + 2NRTIs) as a fixed effect in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise, will be summarized 
for subjects in the safety analysis set according to the study drug received.
Data for the pretreatment period and the period post the date of last dose of study drug plus 
30 days will be included in data listings for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration page in CRF. Exposure data will be summarized by treatment.
Duration of exposure to study drug will be expressed as the number of weeks between the first 
and last dose of the study drug, inclusive, regardless of temporary interruptions in study drug 
administration and summarized by treatment.
Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study drug start 


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date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum postbaseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the intensive PK substudy, plasma concentrations of GS-9883 may be summarized by 
nominal sampling time using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Ctau, 
AUCtau, and T½, as appropriate) may be listed and summarized using descriptive statistics (eg, 
sample size, arithmetic mean, geometric mean, coefficient of variation %, SD, median, Q1, Q3, 
minimum, and maximum). Plasma concentrations over time will be plotted in semi-logarithmic 
and linear formats as mean ± standard deviation, and median (Q1, Q3).
For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
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TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.
8.8.
Patient Reported Outcomes (PRO)
The PRO measures based on questionnaires (eg, SF-36 and HIV Symptoms Distress Module) 
will be summarized by treatment and visit using descriptive statistics.
8.9.
Sample Size
A total of approximately 520 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (260 subjects per treatment group), achieves at least 90% power to detect a 
non-inferiority margin of 4% difference in percentage of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm between the 
two treatment groups. For sample size and power computation, it is assumed that both treatment 
groups have 2% of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 (based on the 
historical Gilead E/C/F/TAF and STB studies), that a non-inferiority margin is 4%, and that the 
significance level of the test is at a one-sided 0.025 level.
8.10.
Independent Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after all 
subjects enrolled complete Week 24 of the study or prematurely discontinue the study drug. 
However, Gilead will defer to the IDMC for any decision to convene earlier or more frequently. 
The IDMC will examine the safety results of the trial and also focus on logistical issues such as 
accrual, retention, quality of clinical and laboratory data, and implications of results of external 
studies.
No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
An analysis for the Week 24 IDMC meeting will be conducted after the last subjects enrolled 
completes Week 24 of the study.  For each IDMC analysis performed prior to analysis for the 
primary efficacy endpoint, an alpha penalty of 0.00001 will be applied for the primary analysis 
of the primary efficacy endpoint.
8.11.
Analysis Schedule
The Week 48 analysis will be conducted after all subjects either complete their Week 48 visit or 
prematurely discontinue from the study drug, respectively. Final analysis will be performed after 
all subjects complete the study or prematurely discontinue from the study.


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


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


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


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


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


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


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10.
REFERENCES
Airoldi M, Zaccarelli M, Bisi L, Bini T, Antinori A, Mussini C, et al. One-pill once-a-day 
HAART: a simplification strategy that improves adherence and quality of life of 
HIV-infected subjects. Patient preference and adherence 2010;4:115-25.
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? 
Curr Med Res Opin 2013;30 (1):89-97.
Bangsberg DR, Ragland K, Monk A, Deeks SG. A one-pill, once-daily, fixed-dose combination 
(FDC) of efavirenz, emtricitabine, and tenofovir disoproxil fumarate 
(EFV/FTC/TDF) regimen is associated with higher unannounced pill count 
adherence than non-one pill, once-daily [Poster]. 17th Conference on Retroviruses 
and Opportunistic Infections (CROI); 2010 February 16-19; San Francisco, CA. 
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.
Dejesus E YB, Morales-Ramirez JO, Sloan L, Ward DJ, Flaherty JF, et al. . Simplification of 
Antiretroviral Therapy to a Single-Tablet Regimen Consisting of Efavirenz, 
Emtricitabine, and Tenofovir Disoproxil Fumarate Versus Unmodified 
Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients. 
Acquir Immune Defic Syndr 2009;51 (2):163-74.
Department for Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents. Developed by the DHHS 
Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working 
Group of the Office of AIDS Research Advisory Council (OARAC). Downloaded 
from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 08 April, 
2015.
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet 
2003;362 (9387):847-52.
Hodder SL, Mounzer K, Dejesus E, Ebrahimi R, Grimm K, Esker S, et al. Patient-Reported 
Outcomes in Virologically Suppressed, HIV-1-Infected Subjects After Switching 
to a Simplified, Single-Tablet Regimen of Efavirenz, Emtricitabine, and 
Tenofovir DF. AIDS Patient Care STDS 2010;24 (2):87-96.
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of 
mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. 
Lancet 1998;352 (9142):1725-30.


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Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
Sax PE, Meyers J, Mugavero M, Davis KL. Adherence to Antiretroviral Treatment Regimens 
and Correlation with Risk of Hospitalization Among Commercially Insured HIV 
Patients in the United States [Poster O113]. 10th International Congress on Drug 
Therapy in HIV Infection; 2010 November 7-11; Glasgow, UK. 
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.
The Joint United Nations Programme oHAU. Fact Sheet: 2014 Global Statistics. Available at: 
http://www.unaids.org/sites/default/files/media_asset/20150714_FS_MDG6_Rep
ort_en.pdf.  2014.


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


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Amendment 1 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of 
Switching from Regimens Consisting of Boosted Atazanavir or Darunavir plus either 
Emtricitabineffenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabineffenofovir 
Alafenamide in Virologically Suppressed HIV -1 Infected Adults 
GS-US-380-1878 Amendment 1,19 February 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Marshall Fordyce, M 
Pnnted) 
Author 
~PPD 
s 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFfDENTIAL 
Page 90 
19 February 2016 


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 91
19 February 2016
Appendix 2.
Study Procedures Table
Study Procedures
Screeninga
Day 1b
End of Weeke, v
Post-Week 48e, w
30-Day Follow-upu
Early Study 
Drugs DCc
4
8
12
24
36
48
Every 12 Weeksx
Informed Consent
X
Medical History
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed 
Physical Exam 
X
X
Xd
Xd
Xd
X
Xd
X
Xd
Xd,f
Xf
12-Lead ECG (performed 
supine)
X
X
X
X
X
SF-36, HIV Symptoms Distress 
Module, WPAI, and UCLA 
SCTC GIT 2.0 Questionnaires
X
X
X
X
VAS Adherence Questionnaire
X
X
X
X
X
X
X
X
Height
X
Vital signs (blood pressure, 
pulse, respiration rate, and 
temperature), including Weight 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
Xj
Estimated Glomerular Filtration 
Rate (eGFR)
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X


GS-9883/F/T AF 
Protocol GS-US-380-1878 
Gilead Sciences, Inc. 
Study Procedures 
Evaluation of renal tubular 
ftmction1 
Plasma and Urine Storage 
Sample 
Whole Blood sample for 
potential HIV DNA genotyping 
HCV Serology 
HIV -1 Genotype/Phenotype • 
Single PK Samplen 
Trough and post dose PK 
Sample
0 
r
tiorn>ljPPD 
~ 
I 
RandomizationY 
Provide subject dosing diary to 
Treatment Group I subjects 
Optional PK Substudy" 
HBV blood panelq 
Plasma HBV DNA' 
Study Drug Dispensation1 
Study Dmg Accountability 
Screening• 
Day l b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a. 
Evaluations to be completed within 30 days prior to Day I. 
End ofWeek•,v 
Post-Week 48•· w 
4 
8 
12 
24 
36 
48 
Every 12 Weeks" 
X 
X 
:xm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
xs xs 
X 
x• 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b. 
Initiation of the first dose of study dmg is to take place in-clinic following completion of study procedures on the Day I visit.. 
30-Day Follow-up
0 
Final 
Amendment 1 
Early Study 
Drugs DC< 
X 
X" 
X 
X 
c. 
Early Study Drugs Discontinuation visit to occm· within 72 hours of last dose of study dmg. Subjects will be asked to c.ontinue attending the scheduled study visits through the 
Week 48 Visit even if the subject discontinues study dmg. 
d. 
Symptom-du·ected physical examination as needed. 
e. 
HIV -1 genotype and phenotype testing for subjects with vu·ologic failure. Follo\¥ing vu·ologic rebound, subjects will be asked to return to the cluuc (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV -1 RNA and HIV -1 genotype and phenotype (reverse transcriptase, protease and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed acc.ording to the Virologic Rebotmd Schema (Sections 6.13) 
CONFIDENTIAL 
Page 92 
19 Febmaty 2016 


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 93
19 February 2016
f.
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained.
g.
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN) At Day 1, Weeks 12, 24, 48 and every 24 weeks post Week 48, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of 
the chemistry profile. Additionally, TSH will be analyzed at Screening, Day 1, Weeks 24, 48, followed by every 24 weeks post Week 48, and Early Study Drugs 
Discontinuation visit.
i.
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides).  If the subject 
has not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
j.
Every 24 weeks post Week 48 Visit
k.
CBC with differential and platelet count.
l.
Evaluation of renal biomarker includes analyses of urine albumin, urine creatinine, urine protein, retinol binding protein and beta-2-microglobulin 
m.
To be performed at Weeks 72 and 96
n.
A single PK blood sample will be collected at any time pre or post dose from subjects in Treatment Group 1.
o.
A trough PK blood sample will be collected between 20-28 hours following the last dose from subjects in Treatment Group 1. Following an observed dose, a single post dose
blood sample will be collected between 1 and 4 hours post dose.
p.
A PK substudy will be performed in a subset of Treatment Group 1subjects (n=24) at selected study sites.  The pharmacokinetic substudy visit must occur at the Week 4 or
Week 8 visits. The substudy will include intensive PK profiling in plasma.
q.
HBV blood panel will be performed at Screening (Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody 
(HBcAb)). 
r.
To be performed for subjects who meet the definition of HBV infection
s.
At Weeks 12, 24 and 48 the following will be performed by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) and HBeAg (if negative reflex, HBeAb)
t.
Study drug GS-9883/F/TAF to be dispensed to Treatment Group 1 subjects.
u.
Only required for those subjects who permanently discontinue study drugs prior to Week 48 visit and do not continue in the study through at least one subsequent visit after 
the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used.
v.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to
Week 36, unless otherwise specified. The visit window at Weeks 48 will be ± 6 weeks of the protocol-specified visit date. 
w.
Visit window of 6 days for study visits post Week 48.
x.
GS-9883/F/TAF FDC will be dispensed to subjects participating in the study post Week 48 visit.
y.
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit provided that all screening procedures have been completed and subject eligibility has been 
confirmed.


GS-9883/F/TAF 
Protocol GS-US-380-1878 
Final 
Gilead Sciences, Inc. 
Amendment 1 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
Grade I 
~-----G-ra_d_e_2----~ 
~~ ______ 
G_rn_d_e_3----~~ 
~~ ---------G-rn--de-4--------~ 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
If conftrmed and possibly and/or probably related to investigational 
medicinal products: 
L 
Withhold investigational medicinal products until !> Grade 2 
2. 
Restart all investigational medicinal products at full dose 
1 
If Grade 3 or 4 recurrence that is con finned and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
1 
Repeat lab to 
confirm toxicity 
grade 
1 
lfc 
inve 
dosi 
oft 
onfirmed and unrelated to 
stigational medicinal products, 
ng may continue at the discretion 
he investigator 
ff confirmed and 
possibly or probably 
_. related to 
investigational 
medicinal, products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
Page 94 
19 Febnwy 2016 


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 95
19 February 2016
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count  
(ANC)
Adult and Pediatric, 
≥ 7 Months# 
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 96
19 February 2016
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 97
19 February 2016
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects.  Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 98
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant  <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L                
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L                 
2.0 t o <2.5 mmolL
2.0 mEq/L                         
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant  <1 Year
>ULN to 6.0 mEq/L           
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L             
6.5 to 7.0 mmol/L
7.0 mEq/L                  
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 99
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL                          
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL              
1.74 to <1.94 mmolL
6.1 to  <7.0 mg/dL                      
1.51 to < 1.74 mmolL
< 6.1 mg/dL                           
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia (corrected 
for albumin if appropriate*)
Adult and Pediatric 
7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
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


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 1 
CONFIDENTIAL
Page 100
19 February 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


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


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Amendment 1 
CONFIDENTIAL
Page 102
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects >70 yrs.  Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.


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Amendment 1 
CONFIDENTIAL
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ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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

Prot_004.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Clinical 
Program Manager: 
Gilead Medical 
Monitor: 
Gilead Study Director: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety 
and Efficacy of Switching from Regimens Consisting of Boosted 
Atazanavir or Damnavir plus either Emtricitabine/Tenofovir or 
Abacavir/Lamivudine to GS-9883/Emtricitabine/T enofovir 
Alafenamide in Virologically Suppressed HN -1 Infected Adults 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
125589 
2015-004011-20 
Not Available 
HN -1 Infection 
GS-US-380-1878 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Mobile: 
Fax: 
Name: 
Telephone: 
Fax: 
Original: 
PPD 
PPD 
PPD 
Marshall Fordyce, MD 
PPD 
PPD 
PPD 
PPD 
PPD 
PPD 
21 October 2015 
CONFIDENTIALITY STATEMENT 
The inf01mation contained in this document, pmi icularly unpublished data, is the propetiy 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 infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessaty to obtain infonned consent from those 
persons to whom the dmg may be administered. 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................12
1.
INTRODUCTION ..............................................................................................................................................15
1.1.
Background ............................................................................................................................................15
1.2.
GS-9883 .................................................................................................................................................16
1.2.1.
General Information .............................................................................................................16
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................16
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................18
1.3.
Information about Emtricitabine (Emtriva®, FTC).................................................................................26
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)..................................................................26
1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) 
or Fixed Dose Combination emtricitabine/tenofovir alafenamide 
(FTC/TAF)...........................................................................................................................27
1.4.2.
Clinical Trials of FTC/TAF as part of 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) ...........................28
1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) ...........................30
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, 
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................30
1.6.
Rationale for this Study..........................................................................................................................31
1.7.
Rationale for Dose Selection..................................................................................................................32
1.8.
Risk Benefit Assessment for this Study .................................................................................................33
1.9.
Compliance ............................................................................................................................................34
2.
OBJECTIVES.....................................................................................................................................................35
3.
STUDY DESIGN................................................................................................................................................36
3.1.
Endpoints ...............................................................................................................................................36
3.2.
Study Design..........................................................................................................................................36
3.3.
Study Treatments ...................................................................................................................................36
3.4.
Duration of Treatment............................................................................................................................36
3.5.
Biomarker Testing..................................................................................................................................37
3.5.1.
Biomarker Samples for Optional Pharmacogenomic Research............................................37
3.5.2.
Additional Sample Storage...................................................................................................38
4.
SUBJECT POPULATION..................................................................................................................................39
4.1.
Number of Subjects and Subject Selection ............................................................................................39
4.2.
Inclusion Criteria....................................................................................................................................39
4.3.
Exclusion Criteria...................................................................................................................................40
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................42
5.1.
Randomization .......................................................................................................................................42
5.2.
Description and Handling.......................................................................................................................42
5.2.1.
Formulation..........................................................................................................................42
5.2.2.
Packaging and Labeling .......................................................................................................43
5.2.3.
Storage and Handling...........................................................................................................43
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide ....................................43


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5.4.
Prior and Concomitant Medications.......................................................................................................44
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................45
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................46
6.
STUDY PROCEDURES ....................................................................................................................................47
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................47
6.2.
Pretreatment Assessments......................................................................................................................47
6.2.1.
Screening Visit .....................................................................................................................47
6.2.2.
Day 1 Assessments...............................................................................................................49
6.3.
Randomization .......................................................................................................................................51
6.4.
Treatment Assessments (Week 4 -48)....................................................................................................51
6.5.
Treatment Assessments (Post Week 48) ................................................................................................54
6.5.1.
Post Week 48 Assessments ..................................................................................................54
6.6.
Post-treatment Assessments ...................................................................................................................55
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................55
6.6.2.
30-Day Follow-Up ...............................................................................................................56
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................58
6.8.
Other Evaluations...................................................................................................................................58
6.8.1.
Markers of Renal Tubular Function .....................................................................................58
6.9.
Blood and Urine Storage........................................................................................................................58
6.10.
Assessments for Premature Discontinuation from Study.......................................................................59
6.11.
End of Study...........................................................................................................................................59
6.12.
Post Study Care......................................................................................................................................59
6.13.
Virologic Failure....................................................................................................................................59
6.13.1.
Management of Virologic Rebound .....................................................................................59
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Drug 
Discontinuation, or Week 48................................................................................................61
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................62
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................62
7.1.1.
Adverse Events.....................................................................................................................62
7.1.2.
Serious Adverse Events........................................................................................................62
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................63
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................63
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................63
7.2.2.
Assessment of Severity ........................................................................................................64
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................64
7.3.1.
Adverse Events.....................................................................................................................64
7.3.2.
Serious Adverse Events........................................................................................................65
7.4.
Gilead Reporting Requirements.............................................................................................................66
7.5.
Toxicity Management ............................................................................................................................66
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................66
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................67
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................67
7.5.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................67
7.5.5.
Management of Hyperbilirubinemia ....................................................................................69
7.5.6.
Management of Possible Abacavir Hypersensitivity Reaction.............................................70
7.5.7.
On-Treatment Hepatitis C Management...............................................................................70
7.6.
Special Situations Reports......................................................................................................................71
7.6.1.
Definitions of Special Situations..........................................................................................71
7.6.2.
Instructions for Reporting Special Situations.......................................................................71


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8.
STATISTICAL CONSIDERATIONS................................................................................................................73
8.1.
Analysis Objectives and Endpoints........................................................................................................73
8.1.1.
Analysis Objectives..............................................................................................................73
8.1.2.
Primary Endpoint .................................................................................................................73
8.1.3.
Secondary Endpoint .............................................................................................................73
8.2.
Analysis Conventions.............................................................................................................................73
8.2.1.
Analysis Sets ........................................................................................................................73
8.3.
Data Handling Conventions ...................................................................................................................75
8.4.
Demographic Data and Baseline Characteristics ...................................................................................75
8.5.
Efficacy Analysis ...................................................................................................................................75
8.5.1.
Primary Analysis..................................................................................................................75
8.5.2.
Secondary Analyses .............................................................................................................77
8.6.
Safety Analysis.......................................................................................................................................77
8.6.1.
Extent of Exposure...............................................................................................................77
8.6.2.
Adverse Events.....................................................................................................................77
8.6.3.
Laboratory Evaluations ........................................................................................................78
8.6.4.
Other Safety Evaluations......................................................................................................78
8.7.
Pharmacokinetic Analysis......................................................................................................................78
8.8.
Patient Reported Outcomes (PRO).........................................................................................................79
8.9.
Sample Size............................................................................................................................................79
8.10.
Independent Data Monitoring Committee..............................................................................................79
9.
RESPONSIBILITIES..........................................................................................................................................80
9.1.
Investigator Responsibilities ..................................................................................................................80
9.1.1.
Good Clinical Practice..........................................................................................................80
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................80
9.1.3.
Informed Consent.................................................................................................................80
9.1.4.
Confidentiality......................................................................................................................81
9.1.5.
Study Files and Retention of Records ..................................................................................81
9.1.6.
Case Report Forms...............................................................................................................82
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................83
9.1.8.
Inspections............................................................................................................................83
9.1.9.
Protocol Compliance............................................................................................................83
9.2.
Sponsor Responsibilities ........................................................................................................................84
9.2.1.
Protocol Modifications.........................................................................................................84
9.2.2.
Study Report and Publications .............................................................................................84
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................84
9.3.1.
Payment Reporting...............................................................................................................84
9.3.2.
Access to Information for Monitoring..................................................................................85
9.3.3.
Access to Information for Auditing or Inspections ..............................................................85
9.3.4.
Study Discontinuation..........................................................................................................85
10.
REFERENCES ...................................................................................................................................................86
11.
APPENDICES ....................................................................................................................................................88
Appendix 1.
Investigator Signature Page....................................................................................................89
Appendix 2.
Study Procedures Table..........................................................................................................90
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................94
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............95
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................119
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................121


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LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........20
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................21
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................22
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following GS-9883 
Administration Under Fasting Conditions and Corresponding Protein-Adjusted 
IQ95 Values (GS-9883 PK Analysis Set)...............................................................................23
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................32
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)..........................................44
Table 5-2.
Prior and Concomitant Medications (Boosted ATV and DRV regimen) ...............................45
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................23
Figure 3-1.
Study Schema.........................................................................................................................37
Figure 6-1.
Virologic Rebound Schema....................................................................................................60


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety 
and Efficacy of Switching from Regimens Consisting of Boosted
Atazanavir or Darunavir plus either Emtricitabine/Tenofovir or 
Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir 
Alafenamide in Virologically Suppressed HIV-1 Infected Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004011-20
Not Available
Study Centers 
Planned:
Approximately 60 centers in North America
Approximately 31 centers in Europe
Approximately 4 centers in Asia Pacific
Objectives:
The primary objective of this study is as follows:

To evaluate the efficacy of switching to a fixed dose combination 
(FDC) of GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus continuing on a regimen consisting of 
boosted atazanavir (ATV) or darunavir (DRV) plus either 
emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or
abacavir/lamivudine (ABC/3TC) in HIV-1 infected adult subjects 
who are virologically suppressed as determined by the proportion 
of subjects with virologic failure (HIV-1 RNA ≥50 copies/mL) at 
Week 48
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of the two treatment groups
through Week 48
Study Design:
Randomized, open-label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to a FDC of 
GS-9883/F/TAF in HIV-1 infected subjects who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of 
ritonavir (RTV) or cobicistat (COBI) boosted ATV or DRV plus 
either FTC/TDF or ABC/3TC for ≥ 6 months prior to screening.


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Subjects who provide written consent and meet all eligibility criteria 
will be randomized in a 1:1 ratio to one of the following 
two treatment groups:
Treatment Group 1: Switch to a FDC of GS-9883/emtricitabine
/tenofovir alafenamide (GS-9883/F/TAF) administered orally,
once daily without regard to food (n=260)
Treatment Group 2: Remain on current antiretroviral regimen 
consisting of ritonavir or cobicistat boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC administered orally, once daily with food 
(n=260)
Investigators must provide a prescription to subjects in Treatment 
Group 2. Subjects in Treatment Group 2 are responsible for obtaining 
their ARV regimen.
Randomization will be stratified by the prior treatment regimen group 
(i.e., TDF containing regimens [ATV+RTV or ATV+COBI or 
DRV+RTV or DRV+COBI or COBI boosted DRV as fixed dose 
combination plus FTC/TDF] and non-TDF containing regimens 
[ATV+RTV or ATV+COBI or DRV+RTV or DRV+COBI or COBI 
boosted DRV as fixed dose combination plus ABC/3TC]) at 
screening.
Number of Subjects 
Planned:
Approximately 520 subjects in total.
Approximately 260 subjects in each Treatment Group 1 and 
Treatment Group 2
Target Population:
HIV-1 infected subjects ≥18 years old who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a stable regimen 
containing boosted ATV or DRV plus either FTC/TDF or ABC/3TC 
for 6 months prior to screening and who are INSTI naive.
Duration of 
Treatment:
Duration of this study is at least 48 weeks.
At the Week 48 Visit, subjects in a country where GS-9883/F/TAF 
FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for additional 48 weeks, or until the product 
becomes accessible to subjects through an access program, or until 
Gilead Sciences elects to discontinue the study in that country, 
whichever occurs first.
Subjects who complete the study through Week 48 Visit and do not 
further continue participation in the study, will be required to return 
to the clinic 30 days after Week 48 Visit for a 30-Day Follow-Up 
Visit


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After Week 48 Visit, subjects in the United Kingdom (UK) will stop 
taking study drug and complete a 30-Day Follow-Up Visit and return 
to the standard of care.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Currently receiving  antiretroviral regimen consisting of ritonavir 
or cobicistat boosted ATV or DRV plus either FTC/TDF or 
ABC/3TC for 6 months preceding the screening visit

Currently on the first or second antiretroviral regimen with 
documented plasma HIV 1 RNA < 50 copies/mL on a stable 
regimen (or undetectable HIV-1 RNA level according to the local 
assay being used if the limit of detection is ≥50 copies/mL) for 
≥6 months preceding the Screening visit.

Prior changes in antiretroviral regimen are only allowed due to 
tolerability issues or for regimen simplification. Unconfirmed 
virologic elevations of ≥ 50 copies/mL (transient detectable 
viremia, or “blip”) prior to screening are acceptable. (If the lower 
limit of detection of the local HIV-1 RNA assay is 
< 50 copies/mL [e.g., < 20 copies/mL], the plasma HIV-1 RNA 
level cannot exceed 50 copies/mL on two consecutive HIV-1 
RNA tests)

HIV-1 RNA levels < 50 copies/mL at Screening Visit

No previous use of any approved or experimental integrase strand 
transfer inhibitor (INSTI)

No documented or suspected resistance to FTC, TFV, ABC or 
3TC, including but not limited to the reverse transcriptase 
resistance mutations K65R and M184V/I

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 48 weeks. 
For all eligible subjects, blood will be collected at Day 1,Weeks 4, 8, 
12, and then every 12 weeks through Week 48. Laboratory analyses 
(hematology, chemistry, and urinalysis), HIV-1 RNA, CD4+ cell 
count, and complete or symptom-directed physical examinations will 
be performed at the Screening, Day 1 and all subsequent study visits.
Urine will be collected and stored for possible evaluations of renal 
tubular function including urine albumin, urine creatinine, urine 
protein, retinol binding protein and beta-2 microglobulin.


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Adverse events and concomitant medications will be assessed at each 
visit.
Test Product, Dose, 
and Mode of 
Administration:
FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily without 
regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Current antiretroviral drug regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC 
administered orally, once daily with food.
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests to evaluate the safety and 
tolerability of the treatment regimens.
Efficacy:
The primary efficacy endpoint is the proportion of subjects with 
virologic failure (HIV-1 RNA ≥ 50 copies/mL) at Week 48 as defined 
by the modified United States (US) Food and Drug Administration
[FDA] snapshot algorithm.
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
Pharmacokinetics:
An intensive pharmacokinetic (PK) substudy will be performed at the 
Weeks 4 or 8 visits in a subset of Treatment Group 1 subjects (target 
n=24) at study sites able to conduct this testing.
For all subjects in Treatment Group 1 who are on study drug, a single 
anytime pre or post-dose PK blood sample will be collected at 
Weeks 8, 24 and 36.
For all subjects in Treatment Group 1 who are on study drug, a trough 
PK blood sample will be obtained 20-28 hours following the last dose 
at Weeks 4 and 12.  Following an observed dose, one post-dose PK 
blood sample will be collected between 1 and 4 hours post-dose.
For intensive PK substudy, the following PK parameters for GS-9883 
may be explored as applicable:
Cmax, Tmax, Clast, Tlast, Ctau,T1/2, AUCtau,AUC0-last , Vz/F, CLss/F.
The concentration of GS-9883 may be summarized using descriptive 
statistics. The pharmacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concentrations may be 
analyzed and PK parameters may be summarized as applicable.


GS-9883/F/T AF 
Protocol GS-US-380-1878 
Gilead Sciences, Inc. 
Optional Genomic 
Testing: 
Patient Reported 
Outcomes: 
Statistical Methods: 
CONFIDENTIAL 
PD 
Final 
Original 
Shmi Fmm 36 Health Smvey (SF-36), HIV Symptoms Distress 
Module Index, Work Productivity and Activity Impailment 
Questionnaii·e (WP AI), and UCLA Sclerode1ma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) will be 
administered at Day 1, Weeks 4, 12 and 48. Visual Analog Scale 
(VAS) Adherence Questionnaii·e will be administered at Day 1 and all 
visits up to Week 48. 
The primruy analysis will consist of a non-inferiority evaluation of 
switching to GS-9883/F/TAF versus maintaining an antii·etrovii·al 
dmg regimen consisting of boosted ATV or DRV plus either 
FTCITDF or ABC/3TC (i.e., boosted PI plus 2 nucleoside reverse 
transcriptase inhibitors (NRTis) [boosted PI + 2 NRTis], with respect 
to the propmiion of subjects with vii·ologic failme (HIV-1 RNA 
:::: 50 copies/mL as defmed by the modified US FDA snapshot 
algorithm) at Week 48. It will be concluded that GS-9883/F/TAF is 
non-inferior to the boosted PI+ 2 NRTis if the upper bmmd of the 
2-sided 95% confidence interval (CI) of the difference between 
treatment groups (GS-9883/F/TAF- boosted PI+ 2 NRTis) in the 
virologic failme rate is less than 4% (i.e., a mru·gin of 4% is applied to 
non-inferiority assessment). The 2-sided 95% Cis will be constructed 
based on the exact method. 
The propmiion of subjects with HIV -1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA snapshot algorithm will also be 
summarized. The 95% Cis will be constructed in the same manner as 
described for the primruy efficacy endpoint. 
Page 10 
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The change from baseline in CD4+ cell count at Week 48 will be 
summarized using descriptive statistics. The differences and the 
associated 95% CIs will be constructed using Analysis of Variance 
(ANOVA) model, including treatment (GS-9883/F/TAF vs. boosted 
PI + 2 NRTIs) as a fixed effect in the model.
Adverse events, clinical laboratory assessments, and pharmacokinetic 
parameters will be summarized using descriptive statistics.
A total of approximately 520 HIV-1 infected subjects, randomized in 
a 1:1 ratio to two treatment groups (260 subjects per treatment group), 
achieves at least 90% power to detect a non-inferiority margin of 4% 
in Week 48 virologic failure rate (HIV-1 RNA ≥50 copies/mL) 
difference between the two treatment groups. For sample size and 
power computation, it is assumed that both treatment groups have a 
virologic failure rate of 2% (based on historical Gilead E/C/F/TAF 
and STB studies), that a non-inferiority margin is 4%, and that the 
significance level of the test is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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


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


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PSQI
Pittsburgh Sleep Quality Index
PT
preferred term 
PT
prothrombin time 
QD
once daily
RAL
raltegravir
RNA
ribonucleic acid
SA
single agent
SAE
serious adverse event
SF-36
Short Form 36 Health Survey
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide 
TDF
tenofovir disoproxil fumarate, Viread
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UCLA SCTC GIT
UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States
VAS
Visual analog scale
WPAI
Work Productivity and Activity Impairment Questionnaire


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {36201}. The infection, if left untreated or suboptimally treated, is characterized by 
deterioration in immune function, ultimately resulting in death. Therapeutic strategies for the 
treatment of HIV-1 disease have been significantly advanced by the availability of highly active 
antiretroviral therapy (HAART); the introduction of HAART was associated with a dramatic 
decrease in acquired immune deficiency syndrome (AIDS)-related morbidity and mortality 
{27881}, {5125}, {8284}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {29705}. In addition, there remains a significant medical need 
for new, effective therapies that take into consideration HIV genetic variability, the aging 
HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {34898}. 
Virologically suppressed, HIV-infected patients may switch from their current regimen because 
of safety or tolerability concerns or for regimen simplification. All patient populations may 
benefit from once-daily fixed-dose combination (FDC) regimens as these have been shown to 
provide increased adherence and improved clinical and virologic outcomes {21053}, {29702}.
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other NRTIs. Tenofovir alafenamide (TAF) is also an 
oral prodrug of TFV. TAF is more stable in plasma than TDF, provides higher intracellular 
levels of the active phosphorylated metabolite tenofovir diphosphate (TFV-DP), and 
approximately 90% lower circulating levels of TFV relative to TDF at the clinical doses. 
The distinct metabolism of TAF offers the potential for an improved clinical profile compared 
with TDF.
GS-9883 is a potent inhibitor of HIV-1 integrase that is being evaluated for the treatment of 
HIV-1 infection.  Antiviral testing has shown that GS-9883 is active against a broad panel of 
HIV-1 viral lab strains and clinical isolates.  GS-9883 is fully active against a panel of mutant 
viruses with resistance to 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 GS-9883.


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


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


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A standard battery of in vitro and in vivo studies was performed to assess the genotoxic potential 
of GS-9883. There was no evidence of mutagenic or clastogenic activity in an in vitro bacterial 
reverse mutation assay (Study TX-141-2026), a chromosomal aberration assay in human 
lymphocytes (Study TX-141-2027), or in a rat micronucleus test (Study TX-141-2029).
1.2.3.
Clinical Trials of GS-9883
Clinical trials entailing the use of GS-9883 include:

GS-US-141-1218, a Phase 1 double blind, randomized, placebo-controlled, first-in-human, 
single- and multiple-ascending dose study evaluating the safety, tolerability, and PK of oral 
GS-9883 in healthy subjects and a randomized, open-label, 2-cohort, 3-period, crossover, PK 
study evaluating the drug interaction potential between F/TAF FDC tablet and GS-9883 in 
healthy subjects (completed)

GS-US-141-1219, a Phase 1b randomized, double-blinded, sequential cohort 
placebo-controlled study of the safety, PK, and antiviral activity of GS-9883 in HIV-1 
infected subjects study of the pharmacokinetics and antiviral activity of GS-7340 (8 mg, 
25 mg, 40 mg) in HIV infected subjects (completed)

GS-US-141-1233, a Phase 1,Open-label, Two-Cohort, Multiple-Period, Fixed-Sequence, 
Crossover Study to Evaluate 1) the Relative Bioavailability of
Two GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg)
Fixed-Dose Combination Tablets Versus a GS-9883 (75 mg) Tablet and a 
Emtricitabine/Tenofovir Alafenamide (200/25 mg) Fixed-Dose Combination Tablet 
Administered Simultaneously and 2) the Effect of Food on the Pharmacokinetics of 
GS-9883, Emtricitabine and Tenofovir Alafenamide When Administered as 
GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg)
Fixed-Dose Combination Tablets (ongoing)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (ongoing)

GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled Phase 1 Study 
Evaluating the Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular 
Filtration Rate (ongoing)


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


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Based on results in study GS-US-141-1218, pharmacokinetic profile of GS-9883 was 
characterized by rapid absorption with time to peak plasma concentrations (median tmax of 
cohorts) ranging between 1 and 4 hours following administration under fasted conditions. 
GS-9883 exposures were appropriately dose proportional following single dose 25-100 mg dose 
administration, with decreasing dose proportional at higher doses.  The half-life of GS-9883 was 
approximately 18 hours, with no changes observed across studied dose range as evidenced by 
parallel terminal phase slopes. A high-fat meal increased AUCinf and Cmax (geometric mean, 84% 
and 101%, respectively) following 100 mg single dose administration. Steady state was achieved 
after 4-6 days of once daily dosing of GS-9883 with average accumulation ratios for AUC24hr
of 1.6.
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following 
Single Doses of GS-9883 in Healthy Subjects (GS-9883 PK Analysis 
Set; Part A: Single Dosing)
GS-9883 PK 
Parameter
Mean 
(%CV)
5mg
(N=6)
25 mg
(N=6)
50 mg
(N=6)
100 mg
(N=6)
300 mg
(N=6)
600 mg
(N=6)
Cmax (ng/mL)
691.2
(22.1)
1618.3
(26.7)
3965.0
(40.1)
6998.3
(36.1)
14605.0 
(27.1)
20050.0
(7.5)
Tmax (hr)
1.25 
(1.00-1.50)
2.00
(1.00-3.00)
3.00
(1.50-4.00)
2.25
(1.50-3.00)
3.50
(2.00-6.00)
3.5
(2.00-4.00)
AUCinf 
(ng.hr/mL)
13059.7
(25.1)
35718.2 
(21.3)
78399.5 
(29.7)
163028.2 
(24.3)
355917.3 
(32.9)
454446.8 
(19.9)
T1/2 (hr)
18.51
(16.81-19.99)
18.08
(16.63-19.64)
16.72
(15.77-17.11)
18.90
(17.96-20.05)
18.14
(17.86-20.53)
17.89
(16.38-19.52)
T1/2 and Tmax: Median (Q1, Q3)
Table 1-2 presents GS-9883 plasma PK parameters following administration of GS-9883 
(5, 25, 50, 100, and 300 mg) once daily for 7 days. Following administration of either GS-9883 
(5, 25, 50, 100, or 300 mg) once daily for 7 days, the PK absorption profile observed on Days 1 
and 7 was similar to that observed in Part A (SAD). The median Tmax values ranged from 1.5 to 
2.5 hours on Day 1 and 1.5 to 4.0 hours on Day 7. Linearity was observed comparing GS-9883 
AUC and Cmax on Days 1 and 7 over the dose range of 25 to 50 mg. Steady state levels of 
GS-9883 were achieved between Study Days 4 to 6 of dosing and maintained through Day 14. 
Accumulation is approximately 1.6-fold, which is consistent with the observed half-life of the 
GS-9883 (approximately 18 hours).


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


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Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic 
Parameters Following Single-Dose Administration of GS-9883 in the 
Fasted and Fed States (GS-9883 PK Analysis Set)
GS-9883 PK Parameter 
Mean (%CV)
% GLSM Ratio 
(90% CI)
Test
GS-9883 100 mg Fed
(n=8)
Reference
GS-9883 100 mg Fasted
(n=8)
AUCinf (hr*ng/mL)
214,146.3 (15.9)
117,777.1 (23.3)
183.97 (152.05, 222.59)
AUClast (hr*ng/mL)
209,259.9 (15.1)
115,681.7 (24.0)
183.58 (151.91, 221.86)
Cmax (ng/mL)
11,268.8 (15.1)
5885.0 (34.9)
200.69 (165.93, 242.74)
CI = confidence interval; GLSM = geometric least squares mean
1.2.3.2.
Phase 1b Proof of Concept
The first HIV-1 positive human subjects were dosed in the fasted state with 10 days of GS-9883 
in study (GS-US-141-1219).  Four cohorts of 5 subjects each were randomized 4:1 to receive 
GS-9883 or placebo to match at doses of 5 mg, 25 mg, 50 mg, and 100 mg once daily for 
10 days.
GS-9883 was generally well tolerated at the doses evaluated. A total of 9 of 20 subjects had an 
AE in this study. The most frequently reported AEs across all subjects were diarrhea (2 subjects), 
and headache (3 subjects).  No other AE was reported in more than 1 subject. There was no 
increase in the incidence of AEs with increasing doses of GS-9883.
The majority of AEs were considered by the investigator to be not related to study drug. A total 
of 2 subjects experienced mild diarrhea that was considered related to study drug (1 in the 5 mg 
cohort, 1 in the 100 mg cohort).
No deaths or pregnancies were reported. No Grade 3 or 4 AEs, SAEs, or AEs leading to 
discontinuation of study drug were reported in any cohort.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. No Grade 3 
treatment emergent laboratory abnormalities were observed. Median serum creatinine changes at 
Day 10 were: 0.05 mg/dL (5 mg), 0.04 mg/dL (25 mg), 0.06 mg/dL (50 mg), and 0.15 mg/dL 
(100 mg). These changes in serum creatinine appeared to be transient and returned close to 
baseline values on discontinuation of study drug. One Grade 4 new onset laboratory abnormality 
was seen in 1 subject who received 5 mg GS-9883. This was a Grade 4 CPK seen on Day 17, 
7 days following his last dose of study medication. The subject was asymptomatic. The 
Investigator felt that this was unrelated to study medication and was due to resumption of crystal 
methamphetamine use by the subject. An adverse event of elevated CK was reported unrelated to
study medication.
Based on PK information collected in study GS-US-141-1219, which was in line with PK 
observed in study GS-US-141-1218, the median IQ for each dose were calculated and are 
presented in the Table below.


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Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ95 Values (GS-9883 PK Analysis 
Set)
GS-9883 dose
n
Median (range) Ctau, SS (ng/mL)
Median (range) paIQ95
a
5 mg
4
206.5 (146.0 to 342.0)
1.3 (0.9 to 2.1)
25 mg
4
797.5 (714.0 to 1900.0)
4.9 (4.4 to 11.7)
50 mg
4
2170.0 (852.0 to 3020.0)
13.4 (5.3 to 18.6)
100 mg
4
4190.0 (3730.0 to 5970.0)
25.9 (23.0 to 36.9)
a.
The protein adjusted IQ95 (paIQ95) value is estimated based on steady-state Ctau values and the in vitro paIC95 value for 
wild-type HIV-1 (162 ng/ml).
The mean and 95% CIs of change from baseline in HIV-1 RNA (log10 copies/mL) are presented 
in Figure 1-1.
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set)
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study drug.


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Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group.
1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing 
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, antiretroviral therapy 
(ART)-naive adult subjects. 
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 50 mg 
once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 75 mg 
once daily
Interim data at Week 12 are summarized below.  Data from the Week 24 primary endpoint are 
included in the GS-9883/F/TAF Investigator’s Brochure.
1.2.3.4.
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 12 
data analysis, 2 subjects (2.0%) had prematurely discontinued study treatment, one in each 
treatment group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and estimated glomerular 
filtration rate [eGFR] using the Cockcroft-Gault method [eGFRCG]) were similar between the 
2 treatment groups. 
Median (Q1, Q3) baseline HIV-1 RNA was 4.45 (3.96, 4.79) log10 copies/mL, with 82.7% of 
subjects having ≤ 100,000 copies/mL at baseline; 5 subjects had > 400,000 copies/mL at 
baseline; 4 of these subjects were randomized to GS-9883+F/TAF and 1 subject was randomized 
to DTG+F/TAF.

Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 41.8% of 
subjects having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 125.3 
(105.7, 147.0) mL/min.


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1.2.3.5.
Efficacy Results
Virologic success at Week 12 when assessed using the US FDA snapshot algorithm, defined as 
plasma HIV-1 RNA < 50 copies/mL, was similar between the 2 treatment groups as follows: 
GS-9883+F/TAF 93.8%; DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79).
Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF +170 (150.0) cells/μL; DTG+F/TAF +173 (220.5) cells/μL 
(difference in LSM: 0; 95% CI: −76 to 76; p = 1.00).
Interim Virology Resistance Data
Through Week 12, no emergent drug resistance was detected.
1.2.3.6.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 58.5%, 38 subjects; DTG+F/TAF 57.6%, 19 subjects). The most 
common TEAEs (occurring in > 1 subject) by treatment group were as follows:
GS-9883+F/TAF: diarrhea and headache (6.2%, 4 subjects each); and fatigue and nausea (3.1%, 
2 subjects each)
DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects); and fatigue, flatulence, 
and furuncle (6.1%, 2 subjects each)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (diabetic ketoacidosis); this event was also reported as an SAE, and 1 other SAE 
(appendicitis) was reported. Neither SAE was considered related to study drug by the 
investigator, resulted in study drug discontinuation, or required interruption of study drug, and 
both SAEs resolved. 
The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 12.3%, 8 subjects; DTG+F/TAF 15.2%, 
5 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs (somnolence and headache) were reported in 
1 subject. No Grade 3 or 4 treatment-emergent AEs or treatment-emergent SAEs were 
considered related to study drug.
No deaths, pregnancies, or AEs leading to premature study drug discontinuation were reported.


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Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality (ie, at least 
1 grade level increase from baseline in graded abnormality) was similar between treatment 
groups as follows: GS-9883+F/TAF 70.3%, 45 subjects; DTG+F/TAF 75.0%, 24 subjects. The 
majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. The 
percentage of subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory abnormality 
was similar between treatment groups as follows: GS-9883+F/TAF 10.9%, 7 subjects; 
DTG+F/TAF 12.5%, 4 subjects. Grade 4 treatment-emergent laboratory abnormalities (creatine 
kinase) were reported in only 2 subjects.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. Changes from 
baseline in serum creatinine were similar between treatment groups. Median (Q1, Q3) changes in 
serum creatinine at Week 12 were as follows: GS-9883+F/TAF 0.11 (0.06, 0.16) mg/dL; 
DTG+F/TAF 0.14 (0.06, 0.24) mg/dL. Changes from baseline in eGFR were similar between 
treatment groups. Median (Q1, Q3) changes in eGFR at Week 12 were as follows: 
GS-9883+F/TAF −12.2 (−18.0, −6.4) mL/min; DTG+F/TAF −15.8 (−30.1, −9.5) mL/min.
1.3.
Information about Emtricitabine (Emtriva®, FTC)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US Food and Drug Administration (FDA) for 
marketing on 2 July 2003 and is available under the name Emtriva®. In the European Union 
(EU), marketing authorization was granted for both the 200 mg Emtrivacapsule formulation 
and a 10 mg/mL Emtrivaoral Solution formulation on 24 October 2003, with indications for 
the treatment of HIV infection concurrently with other antiretroviral drugs in both adult and 
pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in anti-
HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.


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1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) or 
Fixed Dose Combination emtricitabine/tenofovir alafenamide (FTC/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected subjects (completed)

GS-US-120-0104, a Phase 1b study of the pharmacokinetics and antiviral activity of 
GS-7340 (8 mg, 25 mg, 40 mg) in HIV infected subjects (completed)

GS-US-120-0107, a Phase 1, partially-blinded, randomized, placebo- and positive controlled 
study to evaluate the effect of GS-7340 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-120-0108, a Phase 1, open-label, parallel-design study to evaluate the 
pharmacokinetics of GS-7340 in subjects with severe renal impairment (completed)

GS-US-120-0109, a Phase 1 study to evaluate the pharmacokinetics, metabolism and 
excretion of GS-7340 (completed)

GS-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the 
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic 
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug 
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of 
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in 
healthy subjects (completed)

GS-US-311-1386, a Phase 1 study to determine the effect of food on the pharmacokinetics of 
tenofovir alafenamide when administered as F/TAF FDC in healthy volunteers (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential 
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz (EFV) or 
COBI-boosted darunavir (DRV) (completed)

GS-US-311-1088, a Phase 1, Relative Bioavailability Study of Emtricitabine/Tenofovir 
Alafenamide Fixed Dose Combination Tablet to evaluate the formulation performance of 
emtricitabine (FTC) and tenofovir alafenamide (TAF) fixed dose combination tablets relative 
to co-administration of individual agents (completed).

GS-US-311-1089, a Phase 3 study of the safety and efficacy of FTC/TAF in HIV infected, 
virologically suppressed patients (ongoing).


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


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


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


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Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 1, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
1.6.
Rationale for this Study
As treatment guidelines recommend early treatment of HIV-1 infection, there is need for 
regimens that maximize long-term efficacy, safety, tolerability, and convenience. These features 
are determined by the specific formulation of the regimen (fixed-dose, or multi-tablet regimens), 
the nucleos(t)ide backbone, and the third agents (PI, NNRTI, or INSTI).
Switching to GS-9883/F/TAF may offer the advantages of a single-tablet FDC containing the 
unboosted, next-generation INSTI, GS-9883, combined with a TAF-containing nucleotide 
backbone. This regimen has the potential to avoid unwanted side effects from PI-based therapy 
(such as hyperbilirubinemia, rash, gastrointestinal upset, and dyslipidemia), decrease the 
potential for drug-drug interactions by removing the need for a boosting agent, avoiding potential 
long term renal and bone side effects from TDF, and avoiding potential long-term cardiovascular 
risk from ABC.
Four FDCs are currently approved in the US and EU for once-daily administration as a complete 
regimen for the treatment of HIV-1 infection, EFV/FTC/TDF, FTC/RPV/TDF, E/C/F/TDF, and 
ABC/DTG/3TC. There is no PI-containing FDC currently available. Studies have shown that a 
once-daily FDC significantly improved adherence, treatment satisfaction, and virologic 
outcomes for patients infected with HIV-1 {13840}, {15302}, {15951}, {15415}. Due to longer 
duration of high adherence, patients taking FDCs also have better clinical outcomes, such as 
fewer hospitalizations, compared with multiple-tablet regimens {16560}.
Boosted protease inhibitors still represent a sizeable portion of the treated HIV-1-infected 
population and are viewed as the class with the greatest barrier to resistance. Boosted DRV is the 
only PI that remains on the DHHS treatment guidelines as a preferred agent, though ATV is still 
widely prescribed. Use of DRV/r and ATV/r in this study will allow comparison of the 
GS-9883/F/TAF FDC with these third agents, regardless of NRTI backbone. The study has the 
potential to demonstrate benefits such as decreased pill burden and adverse events, and improved 
patient reported outcomes.
This study will evaluate the safety, efficacy and tolerability of switching from boosted PI 
regimens to GS-9883/F/TAF, thereby assessing the viability of GS-9883/F/TAF as a FDC option 
for HIV-infected patients.


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1.7.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days.
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady 
State Following GS-9883 Administration Under Fasting Conditions 
and Corresponding Protein-Adjusted IQ95 Values
GS-9883 dose
n
Median (range) Ctau,SS (ng/mL)
Median (range) paIQ95
a
5 mg
4
206.5 (146.0 – 342.0)
1.3 (0.9 – 2.1)
25 mg
4
797.5 (714.0 – 1900.0)
4.9 (4.4 – 11.7)
50 mg
4
2170.0 (852.0 – 3020.0)
13.4 (5.3 – 18.6)
100 mg
4
4190.0 (3730.0 – 5970.0)
25.9 (23 – 36.9)
a
The paIQ95 value is estimated based on steady-state Ctau values and the in vitro paIC95 value for wild-type HIV-1 
(162 ng/mL).
Source: Data on File


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Single-agent GS-9883 was well tolerated at all doses administered. The range of GS-9883 
plasma exposure at steady state (Ctau,SS) observed in the 50-mg cohort correlated with protein 
adjusted 95% inhibitory quotient (paIQ95) values ranging from 5.3 to 19, while the range of 
GS-9883 plasma exposure at steady state (Ctau,SS) observed in the 100-mg cohort correlated with 
paIQ95 values ranging from 23 to 37 (Table 1-5).
Based on PK/PD analyses, exposure following a 75-mg dose of single-agent GS-9883 is 
expected to provide near-maximal virologic response, with a predicted paIQ95 of approximately 
20, providing considerable coverage above the target concentration of 162 ng/mL (paIC95).
GS-9883 (75 mg) single agent coadministered with F/TAF (200/25 mg) is currently being 
evaluated in a Phase 2 study, GS-US-141-1475 (GS-9883+F/TAF vs DTG+F/TAF). The 
Week 12 interim data from this study, support the safety and efficacy of GS-9883 exposures 
obtained with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF is being developed for use in Phase 3 studies. 
Preliminary results from the relative bioavailability (rBA) study (GS-US-141-1233) of 
GS-9883/F/TAF (75/200/25 mg) showed that GS-9883 plasma exposure was higher (with Cmax
and AUCinf increase of 31% and 27%, respectively) following administration of the FDC as 
compared with exposure following administration of GS-9883 (75 mg) + F/TAF (200/25 mg) 
under fasted conditions. The increase in GS-9883 exposures associated with the FDC 
formulation results in an estimated mean paIQ95 of 24.3, compared to an estimated mean paIQ95
of 19.2 for the GS-9883 (75 mg) single agent coadministered with F/TAF, in the fasted state.
In order to bridge exposures of GS-9883 in the FDC to the exposure observed with GS-9883 
75 mg administered as a single agent, and to bridge to the safe and effective exposures observed 
in the Phase 2 study GS-US-141-1475, a lower strength GS-9883/F/TAF FDC is being 
developed for use in the Phase 3 studies. Comparability of GS-9883 exposures will be confirmed 
in an rBA study of GS-9883/F/TAF (50/200/25 mg) and GS-9883 (75 mg) + F/TAF prior to 
initiation of dosing in the Phase 3 studies.
1.8.
Risk Benefit Assessment for this Study
All patients with HIV-1 infection should receive effective anti-retroviral therapy. Potential risks 
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and 
lactic acidosis with steatosis.  The risk of class effects is considered to be low.  Important 
identified risks appropriately managed by study inclusion/exclusion criteria as well as through 
close clinical and laboratory monitoring during the study are as follows:  hypersensitivity 
reaction to abacavir and allergy to any components of the tablets.  Some observational studies 
have shown increased risk of cardiovascular disease with abacavir.  Protease inhibitors may be 
associated with increased lipid levels and gastrointestinal side effects. If patients are currently 
infected with hepatitis B and discontinue their existing or new therapy, there is a risk of severe 
acute exacerbations of hepatitis B.


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Potential benefits may include provision of a new antiretroviral therapy that is not currently 
available and which may have fewer side effects than alternative therapies.  Other potential 
benefits include provisions of fixed dose combination therapy, and the knowledge that patient 
participation will contribute to the body of knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF is favorable at this time.
1.9.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of switching to a FDC of  GS-9883/F/TAF versus continuing on a 
regimen consisting of boosted atazanavir or darunavir plus either FTC/TDF or ABC/3TC in 
HIV-1 infected adult subjects who are virologically suppressed as determined by the 
proportion of subjects with virologic failure (HIV-1 RNA ≥50 copies/mL) at Week 48
The secondary objective of this study is:

To evaluate the safety and tolerability of the two treatment groups through Week 48


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3.
STUDY DESIGN
3.1.
Endpoints
The primary efficacy endpoint is:

The proportion of subjects with virologic failure (HIV-1 RNA ≥ 50 copies/mL) at Week 48 
as defined by the modified US FDA snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA snapshot algorithm

The change from baseline in CD4+ cell counts at Week 48
3.2.
Study Design
This protocol describes a randomized, open-label, multicenter, active-controlled study to
evaluate the safety and efficacy of switching to a FDC of GS-9883/F/TAF in HIV-1 infected 
adult subjects who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen 
consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for 
≥6 months prior to screening.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: Switch to FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily without regard to food
(n=260)
Treatment Group 2: Remain on current antiretroviral regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC administered orally,
once daily with food (n=260)
3.4.
Duration of Treatment
The treatment duration is 48 weeks.
At the Week 48 Visit, treatment group 1 and 2 subjects in a country where GS-9883/F/TAF FDC 
is not available will be given the option to receive GS-9883/F/TAF FDC for additional 48 weeks 
and attend study visits every 12 weeks, or until the product becomes accessible to subjects 
through an access program, or until Gilead Sciences elects to discontinue the study in that 
country, whichever occurs first.


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After Week 48 Visit, subjects in the United Kingdom (UK) will stop taking study dmg and 
complete a 30 day follow up visit and retum to the standard of care. 
Figure 3-1. 
Screening 
S30 da,·s 
prior 
to Day l 
Study Schema 
Day 1* 
T1·E!atment Group 1: GS-9883/F/TAF FDC 
QD (n- 260) 
Week 4Sb,c 
Treatment Grouo 2: Remain on current regimen of 
boosted ATV or DRV plus FTC/TDF or ABC/3TC 
QD (n=260) 
30Day 
FlU" 
a. 
Following the Day 1 visit, subjects will be required to retum for study visits at Weeks 4, 8, 12, and then every 12 weeks 
through Week 48. 
b. 
After Week 48, subjects in a cmmtry where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F!T AF FDC for additional 48 weeks and attend study visits eve1y 12 weeks, or until the product becomes 
accessible to subjects through an access program, or 1mtil Gilead Sciences elects to discontinue the study in that cotmtly, 
whichever occurs first. 
c. 
Subjects who complete the study through the Week 48 Visit and do not wish to receive GS-9883/F!TAF FDC and subjects 
in the United Kingdom (UK) who complete the study through the Week 48 Visit w'ill be required to retwn to the clinic 
30 days after the completion of study dmgs for a 30-Day Follow-Up Visit. 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Pharmacogenomic Research 
PPD 
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3.5.2.
Additional Sample Storage
For subjects who provide additional consent, residual blood and urine samples taken throughout 
the study will be stored. Stored samples may be used by the Sponsor or its research partners to 
help answer questions about the study drug, and HIV disease and its associated conditions, or to 
provide additional safety data.  At the conclusion of this study, these samples may be retained in 
storage by Gilead Sciences for a period up to 15 years.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 520 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1. The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2. Age 18 years
3. Currently receiving antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV
or DRV plus either FTC/TDF or ABC/3TC for 6 months preceding the screening visit
4. HIV RNA < 50 copies/mL at the screening visit
5. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6. Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥0.83 mL/sec) according to the 
Cockcroft-Gault formula {2202}:
a.
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
         (140 – age in years) (wt in kg)
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
b. Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg)  
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7. Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8. Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin
9. Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥ 50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))


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10. Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11. Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12. Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 6) throughout the study period and for 
90 days following the last dose of study drug.
13. Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14. Life expectancy ≥ 1 year
15. Currently on the first or second antiretroviral regimen with documented plasma HIV-1 RNA 
< 50 copies/mL on a stable regimen (or undetectable HIV-1 RNA level according to the local 
assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 6 months preceding the 
Screening visit. 
Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for 
regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient 
detectable viremia, or “blip”) prior to screening are acceptable. (If the lower limit of 
detection of the local HIV-1 RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the plasma 
HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
16. Have no documented or suspected resistance to FTC, TFV, ABC or 3TC, including but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I
17. No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1. An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
2. Subjects experiencing decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal 
bleeding)


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3. Have been treated with immunosuppressant therapies or chemotherapeutic agents within 
3 months of study screening, or expected to receive these agents or systemic steroids during 
the study (e.g, corticosteroids, immunoglobulins, and other immune- or cytokine-based 
therapies)
4. Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance
5. A history of or ongoing malignancy (including untreated carcinoma in-situ) other than 
cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous 
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must 
not have received any systemic therapy for KS within 30 days of Day 1 and are not 
anticipated to require systemic therapy during the study
6. Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
7. Participation in any other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9. Any known allergies to the excipients of GS-9883/F/TAF FDC or ATV, RTV, DRV, COBI, 
FTC/TDF or ABC/3TC
10. Females who are pregnant (as confirmed by positive serum pregnancy test)
11. Females who are breastfeeding
12. Subjects receiving ongoing therapy with any of the medications listed in the Table 5-1 and 
Table 5-2. Administration of any Prohibited Medication (Table 5-1 and Table 5-2) must be 
discontinued at least 30 days prior to the Day 1 visit and for the duration of the study.
13. Acute hepatitis in the 30 days prior to study entry
14. Chronic hepatitis B infection in subjects not on a TDF containing regimen, as determined by 
either:

Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit

Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
15. Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day 1 visit the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Treatment Group 1: Switch to a FDC of GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) administered orally once daily without regard to food (n=260)
Treatment Group 2: Remain on current antiretroviral regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC administered orally once 
daily with food (n=260)
Randomization will be stratified by the prior treatment regimen group (ie, TDF containing 
regimens [ritonavir or cobicistat boosted ATV or DRV plus FTC/TDF] and non-TDF containing 
regimens [ritonavir or cobicistat boosted ATV or DRV plus ABC/3TC]) at screening.
Subjects randomized in Treatment Group 1 will be assigned study drug bottle numbers of 
GS-9883/F/TAF FDC at study visits by IWRS.
Investigators must provide a prescription to the subjects in Treatment Group 2. Those subjects 
are responsible for obtaining their ARV treatment prior to or during the study visit.
5.2.
Description and Handling 
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF 
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg Tablets
GS-9883/F/TAF  tablets are packaged in white, high density polyethylene (HDPE) bottles. Each 
bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal 
Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drug GS-9883/F/TAF should be stored at controlled room temperature of 25°C (77°F); 
excursions are permitted between 15°C and 30°C (59°F and 86°F).  Storage conditions are 
specified on the label. Until dispensed to the subjects, all bottles of study drugs should be stored 
in a securely locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide
GS-9883/F/TAF tablets will be provided by Gilead Sciences.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 50 mg/200 mg/25 mg FDC 
will be administered orally, once daily without regard to food at approximately the same time 
each day.
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability.  The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return.


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5.4.
Prior and Concomitant Medications

The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following table and use of herbal/natural supplements are excluded or 
should be used with caution while subjects are participating in the study, depending on subject’s 
treatment regimen. Subjects will refrain from consumption of grapefruit juice and Seville orange 
juice throughout participation in the study.
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With 
Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may 
decrease with antacids. Subjects may not 
take antacids (eg, Tums or Rolaids); the 
ulcer medication sucralfate (Carafate); or 
vitamin or mineral supplements that 
contain calcium, iron or zinc for a 
minimum of 2 hours before and 6 hours 
after any dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of 
the study regimen
GI Motility Agents
Cisapride
Herbal/Natural 
Supplements
St. John’s Wort, Echinaccea
Oral Hypoglycemic Agent
Metformin: close monitoring is 
recommended. A dose adjustment of 
Metformin may be necessary. Limit total 
daily doses of Metformin to 1000mg 
either when starting or at study entry.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.


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Table 5-2.
Prior and Concomitant Medications (Boosted ATV and DRV 
regimen)
Drug Class
Agents Disallowed*
Alpha-1 Adrenoreceptor Antagonist
Alfuzosin
Antiarrhythmic Agent
Amiodarone, Dronedarone
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine
Antimycobacterials
Rifampin
Antipsychotics
Lurasidone, Pimozide
Antiretrovirals
Any antiretroviral drug that is not part of the study 
regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort
Anticancer drugs
Irinotecana
Ergot Drivatives
Ergotamine, Ergonovine
Dihydroergotamine
Methylergonovine
Ergometrine
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Phosphodiesterase-5 Inhibitors
Sildenafil ( for PAH)
Sedatives/Hypnotics
Orally administered Midazolam, Triazolam
Calcium Channel Blockers
Bepridil
Chronic angina
Ranolazine
a
Applied to ATV regimen only
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Sciences Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead Sciences as soon as he/she is aware of the use of the excluded 
medication.
Additionally, Investigators should refer to the current product/package inserts of the 
antiretroviral medications for contraindications related to their use.
5.5.
Accountability for Investigational Medicinal Product (IMP)
The investigator is responsible for ensuring adequate accountability of all used and unused IMP.
This includes acknowledgement of receipt of each shipment of IMP (quantity and condition). All 
used and unused IMP dispensed to subjects must be returned to the site.


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Study Drug accountability records will be provided to each study site to:

Record the date received and quantity of IMP kits

Record the date, subject number, subject initials, the IMP kit number dispensed

Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
Return and disposal of study drug GS-9883/F/TAF will be performed as outlined in 
Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that subjects are eligible for study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events, smoking history 
and prior medications within 30 days of the screening visit. 

If available, obtain 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

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled


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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
■
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg) 
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
■
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
       (140 – age in years) (wt in kg) 
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
Plasma HIV-1 RNA
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), 
Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)
The following will be conducted by the central laboratory if the following criteria are 
met:
■
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex 
HBeAb), and quantitative HBsAg
■
If positive HBcAb with negative HBsAg  and negative HBsAb, reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to 
be negative, reflex HBeAb.
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.

Review of adverse events and concomitant medications


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Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for Day 1 Visit. Subjects must continue to take their prior 
treatment regimen up until their scheduled Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. See 
Section 7 Adverse Events and Toxicity Management for additional details.
6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
confirmed subject’s eligibility before proceeding with the Day 1 visit. The subject must 
complete all study procedures before being administered the study drug:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI), UCLA Scleroderma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) and VAS Adherence 
Questionnaire to be completed by the subject. Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate
Urine storage sample for possible additional clinical testing


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Blood sample collection for the following laborat01y analyses: 
-
Chemis1:Iy profile: alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and 
indirect bilimbin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphoms, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is perf01med in subjects with total amylase > 1.5 x ULN) and TSH 
-
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
u·iglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must retu.m within 72 hours in a fasted state to draw blood for the metabolic 
assessments. 
-
Estimated glomemlar filu·ation rate according to the Cockcroft-Gault f01mula 
-
Hematology profile: complete blood cmmt (CBC) with differential and platelet cmmt 
-
Plasma HIV-1 RNA 
-
CD4+ cell count 
-
Plasma storage sample for safety, virology, or PK testing 
-
Whole blood sample for potential HIV DNA genotyping 
-
Subjects who meet the defmition of HBV infection below at Screening Visit (positive 
sennn HBsAg or Positive HBcAb with quantifiable HBV DNA), will have plasma HBV 
DNA tested. 
• 
Optional blood sample collection for the following laboratory analyses if 
pharmacogenomic consent is obtained 
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6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 -48)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, and 48 unless 
otherwise specified.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 36, unless otherwise specified.  The visit window at Week 48 will be ± 6 weeks of 
the protocol-specified visit date and this clinical visit window coincides with the Week 48 
statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24 and 48) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Weeks 24 and 48)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and UCLA Scleroderma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) to be completed by the subject  at 
Weeks 4, 12, and 48. Subject is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires.

VAS Adherence Questionnaire. Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin (Weeks 24 and 48)


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Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 12, 24 and 48, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. At Weeks 24 and 48, TSH will also 
be analyzed.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Weeks 12, 24 and 48)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
■
At Weeks 12, 24 and 48 (for subjects who meet the definition of HBV infection), the 
following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative 
and quantitative) and HBeAg (if negative, reflex HBeAb)

Pharmacokinetic Blood Collection for subjects who are on study drug in Treatment Group 1 
only. Details of pharmacokinetic blood sampling procedures and sample management will be 
documented in the Pharmacokinetic Sample Collection, Processing, Storage, and Shipment 
Manual.
Single Anytime, Trough and Post Dose PK Samples for all subjects on study drug in 
Treatment Group 1:
■
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 and 
36.


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• 
Observed dosing at the clinic: Subjects will have a trough PK blood sample collected 
between 20-28 hours following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study <hu gs on the moming of their visit for the tr·ough 
sample collection. Subjects will then take an observed dose of study <hug at the clinic. 
A single post dose PK blood sample will be collected between 1 and 4 hours post 
dose. If the subject has taken their dose of study <hu gs prior to the visit, the visit may 
proceed, but the subject must retum within 72 hours for the tr·ough PK blood sample 
collection. In the event a subject routinely takes their study dm g in the evening, a 
single post-dose sample may be <h·awn at Weeks 4 and 12 as the subject will not be 
instructed to change their dosing time to accommodate this tr·ough PK <h·aw. 
• 
Dosing diaries will be collected from subjects for the single anytime PK and tr·ough 
PK collection. If a dosing diaty is not retumed the site may ask the subject for the 
time of the last dose and if it was taken with or without food. 
-
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6.5.
Treatment Assessments (Post Week 48)
6.5.1.
Post Week 48 Assessments
At the Week 48 visit, subjects who completed 48 weeks of study drug treatment and are in a 
country where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for additional 48 weeks and attend study visits every 12 weeks, or until the 
product becomes accessible to subjects through an access program, or until Gilead Sciences 
elects to discontinue the study in that country, whichever occurs first.
Subjects who further continue participation in the study and receives GS-9883/F/TAF FDC will 
return for study visits every 12 weeks. Study visits are to be completed within ±6 days of the 
protocol-specified visit date unless otherwise specified.
At the Week 48 Visit, subjects in the United Kingdom will stop taking study drug and complete a 
30 day follow up visit and return to the standard of care.
Subjects participating in the study post Week 48 will be required to return for study visits 
according to the schedule presented in Appendix 1. Study Procedures Table and described in the 
text below:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination as needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin (Weeks 72 and 96)
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued.
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 


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assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.13.

Document study drug dispensation and accountability for all study drugs dispensed.
6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will 
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drugs Discontinuation Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight 

12-lead ECG performed supine

VAS Adherence Questionnaire. Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.


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
Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30-Day Follow-Up
Subjects who complete the study through Week 48 and who do not further continue participation 
in the study, will be required to return to the clinic 30 days after the completion of study drug for 
the 30-Day Follow-Up visit.
Subjects in the United Kingdom will complete a 30-Day Follow-Up visit after the completion of 
the Week 48 visit and return to the standard of care.
Subjects who permanently discontinue study drug prior to Week 48 and refuse to continue in the 
study will be asked to return to the clinic 30 days after the completion of the Early Study Drugs 
Discontinuation Visit for the 30-Day Follow-Up Visit.


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Those subjects who permanently discontinue study drug and continue in the study through 
at least one subsequent visit after the Early Study Drug Discontinuation Visit will not be 
required to complete the 30-Day Follow-Up Visit.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly (or as 
often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained.


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6.7.
Criteria for Discontinuation of Study Treatment
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Lack of efficacy

Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study; refer to Appendix 6

Development of active tuberculosis infection

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)
6.8.
Other Evaluations
6.8.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include but not limited to urine albumin, urine creatinine, urine protein, retinol binding 
protein and beta-2-microglobulin at Day 1 Visit, Weeks 24, 48, and every 24 weeks post 
Week 48.
6.9.
Blood and Urine Storage
A portion of the blood and urine samples drawn at all visits (except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its research partners for HIV-1 genotyping/phenotyping 
assays or their development, for retesting the amount of HIV-1 in the blood, for measurement of 
antiviral drug levels in the blood, or for testing to learn more about how the study drug has 
worked against HIV-1 or clinical laboratory testing to provide additional safety data. No human 
genetic testing will be performed without expressed consent of study subjects. At the conclusion 
of this study, these samples may be retained in storage by Gilead Sciences for a period up to 
15 years.


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6.10.
Assessments for Premature Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.7, Criteria for Discontinuation of Study Treatment). If 
this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study.
6.11.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.12.
Post Study Care
After a subject has completed/terminated their participation in the study, long-term care for the 
subject will remain the responsibility of their primary treating physician.
6.13.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation or Week 48. 
6.13.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any post Day 1 visit, a rebound in HIV-1 RNA ≥ 50 copies/mL, which is subsequently 
confirmed at the following scheduled or unscheduled visit;
OR

Any subject with HIV RNA ≥ 50 copies/mL at study drug discontinuation
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing.  Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-Day 1 resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.
If no resistance is detected from the genotype or phenotype, the subject may remain on study 
drugs and HIV-1 RNA test should be repeated (2 to 3 weeks after date of test with HIV-1 RNA
≥50 copies/mL). Investigators should carefully evaluate the benefits and risks of remaining on 
study drug for each individual subject and document this assessment in the on-site medical 
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Subjects who are noncompliant on an ongoing basis will be considered for discontinuation per 
the Investigator’s discretion or local treatment guidelines. Investigators who opt to discontinue 
study drugs for an individual subject must discuss with the Medical Monitor prior to study drug 
discontinuation.
For subjects who are off study drug but remain on study, it will be the Investigator’s discretion to 
manage virologic rebound.
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
rebound.
Figure 6-1.
Virologic Rebound Schema
a.
If virologic rebound is not confirmed, the subject will remain on their current regimen.
b.
If virologic rebound is confirmed and the HIV-1 RNA is ≥ 200 copies/mL, the HIV-1 genotype and phenotype (reverse 
transcriptase, protease and integrase) will be analyzed.
c.
Based on the results of the genotypic and phenotypic assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping assay fails, a new ARV regimen may be configured at the discretion of the 
Investigator.
d.
If no resistance is detected, HIV-1 RNA will be repeated (2-3 weeks later).  Investigator reviews study drug 
continuation/discontinuation options and discuss with the Medical Monitor prior to study drug discontinuation
e.
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study.


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6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Drug Discontinuation, or 
Week 48
Subjects with HIV-1 RNA ≥ 50 copies/mL at study drug discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 will be 
asked to return for an unscheduled visit within the visit window for a retest.
Subjects with HIV-1 RNA ≥ 200 copies/mL at study drug discontinuation, last visit or Week 48, 
will also have resistance testing conducted.


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


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


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


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


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
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 4).

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat
testing within 3 calendar days of receipt of results and before investigational medicinal 
product discontinuation, unless such a delay is not consistent with good medical practice

Any questions regarding toxicity management should be directed to the Gilead Medical 
Monitor.
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.


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


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


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


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7.5.6.
Management of Possible Abacavir Hypersensitivity Reaction
Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to increased 
risk of hypersensitivity reaction, unless no other therapeutic option is available based on the 
treatment history and resistance testing.
In a clinical study, 3.4 % of subjects with a negative HLA-B*5701 status receiving abacavir 
developed a hypersensitivity reaction. Therefore, even in the absence of HLA-B*5701 allele, it is 
important to permanently discontinue abacavir and not rechallenge with abacavir if a 
hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe 
or even fatal reaction.
Hypersensitivity reactions are characterized by the appearance of symptoms indicating 
multi-organ system involvement. Almost all hypersensitivity reactions will have fever and/or 
rash as part of the syndrome. Other signs and symptoms may include respiratory signs and 
symptoms such as dyspnoea, sore throat, cough, and abnormal chest x-ray findings 
(predominantly infiltrates, which can be localized), gastrointestinal symptoms, such as nausea, 
vomiting, diarrhea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as 
respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis. Other frequently 
observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and 
musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia). The symptoms related to this 
hypersensitivity reaction worsen with continued therapy and can be life- threatening. 
These symptoms usually resolve upon discontinuation of abacavir.
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. Patients 
should be monitored closely, especially during the first two months of treatment with abacavir.
Regardless of their HLA-B*5701 status, patients who are diagnosed with a hypersensitivity 
reaction whilst on therapy MUST discontinue study drug immediately and MUST NEVER be 
restarted. Restarting study drug following a hypersensitivity reaction results in a prompt return of 
symptoms within hours. This recurrence is usually more severe than on initial presentation, and 
may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimize 
the risk of a life-threatening hypersensitivity reaction, study drug must be permanently 
discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible 
(respiratory diseases, flu-like illness, gastroenteritis or reactions to other medicinal products) 
{25149}.
7.5.7.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus, Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose 
interruption. Should the Investigator feel the need to initiate Hepatitis C treatment the 
Investigator must contact the Gilead Medical Monitor to confirm that no drug-drug interactions 
are expected. Subjects should return to the clinic for scheduled or unscheduled follow up visit(s) 


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according to local medical practice for laboratory evaluations. If Hepatitis C treatment is 
initiated, Investigators should use the Gilead provided retest laboratory kits to manage the active 
Hepatitis C.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to the Gilead DSPH using the pregnancy report form within 24 hours of becoming aware 
of the pregnancy.
Refer to the below and the eCRF completion guidelines for full instructions on the mechanism of 
pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
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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 
Sections 7.3.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post study 
must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows:
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477.
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH, fax number 
+1 650 522-5477 or email Safety_FC@gilead.com.
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications.
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.6.2.1 and the eCRF completion guidelines for full instructions on the 
mechanism of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is to evaluate the efficacy of switching to a FDC of 
GS-9883/F/TAF versus continuing on a regimen consisting of boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC (i.e., boosted PI + 2NRTIs) in HIV-1 infected subjects who are 
virologically suppressed as determined by the proportion of subjects with virologic failure 
(HIV-1 RNA ≥ 50 copies/mL) at Week 48.
The secondary objective of this study is to evaluate the safety and tolerability of the 
two treatment groups through Week 48.
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects with virologic failure (HIV-1 RNA 
≥50 copies/mL) at Week 48 as defined by the modified US FDA snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.
8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
randomized.


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8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis 
set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing is due to discontinuation of study drug for lack of efficacy.

Subjects who do not meet the inclusion criterion for no previous use of any approved or 
experimental integrase strand transfer inhibitor (INSTI)

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 4.3 including drugs not to be used with 
FTC, TAF, GS-9883, ATV, RTV, COBI, DRV, FTC/TDF and ABC/3TC
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Substudy Analysis Set
The primary analysis set for intensive PK analyses is defined as the PK substudy analysis set, 
which will include all subjects who (1) are randomized into the study, (2) enrolled into the PK 
Substudy, (3) have received at least 1 dose of study drug, and (4) have at least 1 nonmissing 
intensive PK concentration data for the analyte under evaluation reported by the PK lab.
8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the pharmacokinetic (PK) analysis 
set, which will include all subjects who (1) are randomized into the study, (2) have received at 
least 1 dose of study drug, and (3) have at least 1 nonmissing PK concentration data for the 
analyte under evaluation reported by the PK lab.


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8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (e.g., if the result of a continuous laboratory test is 
< 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (i.e., no toxicity grade) for the laboratory abnormality summary.
All available data for subjects that do not complete the study will be included in data listings.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, body mass index, and eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline 
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects with virologic failure (HIV-1 RNA 
≥50 copies/mL) at Week 48 as defined by the modified US FDA snapshot algorithm. The 
primary analysis of the efficacy will be based on the FAS.
8.5.1.1.
Modified FDA Snapshot Algorithm
The US FDA snapshot algorithm has been modified to classify subjects who discontinue study 
drug due to adverse event or death and have the last available on-treatment HIV-1 RNA value 
≥50 copies/mL as a Virologic Failure. , In the original US FDA snapshot algorithm, these 
subjects would be classified as having No Virologic Data in the Week 48 Analysis Window.


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The modified US FDA snapshot algorithm appears below.
The analysis window at Week 48 is defined as from Study Day 294 to Study Day 377, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, including data collected up to 1 day after the last 
dose date of study drug) will be used in the snapshot algorithm. Virologic outcome will be 
defined as the following categories:

Virologic Success: this includes subjects who have the last available on-treatment HIV-1 
RNA < 50 copies/mL in the Week 48 analysis window

Virologic Failure: this include subjects
Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window , or
Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and
■
Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or
■
Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than lack of efficacy and have the last available on-treatment HIV-1 
RNA ≥50 copies/mL

No Virologic Data in the Week 48 Analysis Window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following:
Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL, or
Missing data during the window but on study drug
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects with virologic failure (HIV-1 RNA 
≥50 copies/mL) at Week 48 in the GS-9883/F/TAF group is at least 4% higher than the 
virologic failure rate in the boosted PI + 2NRTIs group; the alternative hypothesis is that the 
virologic failure rate in the GS-9883/F/TAF group is less than 4% higher than that in the 
boosted-PI + 2NRTIs group.
Non-inferiority will be assessed using the confidence interval (CI) approach. The point estimate 
of treatment difference (GS-9883/F/TAF – boosted PI + 2NRTIs) and the associated 2-sided 
95% CIs will be constructed based on the exact method. It will be concluded that 
GS-9883/F/TAF is non-inferior to boosted PI + 2NRTIs if the upper bound of the 2-sided 95% 
CI of the difference between treatment groups (GS-9883/F/TAF – boosted PI + 2NRTIs) in the 
virologic failure rate is less than 4% (ie, a margin of 4% is applied to non-inferiority assessment).


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If non-inferiority of GS-9883/F/TAF to boosted PI + 2NRTIs 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 
GS-9883/F/TAF over boosted PI + 2NRTIs will be established.
8.5.2.
Secondary Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the US 
FDA snapshot algorithm will also be evaluated. The 95% CIs will be constructed in the same 
manner as for the primary efficacy endpoint. However, non-inferiority will be assessed using a 
margin of 10%. It will be concluded that GS-9883/F/TAF is noninferior to boosted PI + 2NRTIs
if the lower bound of the 2-sided 95% CI of the difference between treatment groups 
(GS-9883/F/TAF – boosted PI + 2NRTIs) in the response rate is greater than -10%.
The change from baseline in CD4+ cell count at Week 48 will be summarized by treatment using 
descriptive statistics. The differences in changes from baseline in CD4+ cell count between
treatment groups and the associated 95% CIs will be constructed using ANOVA models, 
including treatment (GS-9883/F/TAF vs. boosted PI + 2NRTIs) as a fixed effect in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise, will be summarized 
for subjects in the safety analysis set according to the study drug received.
Data for the pretreatment period and the period post the date of last dose of study drug plus 
30 days will be included in data listings for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration page in CRF. Exposure data will be summarized by treatment.
Duration of exposure to study drug will be expressed as the number of weeks between the first 
and last dose of the study drug, inclusive, regardless of temporary interruptions in study drug 
administration and summarized by treatment.
Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.


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Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study drug start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum postbaseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.
8.7.
Pharmacokinetic Analysis
For the intensive PK substudy, plasma concentrations of GS-9883 may be summarized by 
nominal sampling time using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Ctau, 
AUCtau, and T½, as appropriate) may be listed and summarized using descriptive statistics (eg, 
sample size, arithmetic mean, geometric mean, coefficient of variation %, SD, median, Q1, Q3, 
minimum, and maximum). Plasma concentrations over time will be plotted in semi-logarithmic 
and linear formats as mean ± standard deviation, and median (Q1, Q3).


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For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
descriptive statistics or population approaches.
TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.
8.8.
Patient Reported Outcomes (PRO)
The PRO measures based on questionnaires (eg, SF-36 and HIV Symptoms Distress Module) 
will be summarized by treatment and visit using descriptive statistics.
8.9.
Sample Size
A total of approximately 520 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (260 subjects per treatment group), achieves at least 90% power to detect a 
non-inferiority margin of 4% in Week 48 virologic failure rate (HIV-1 RNA ≥50 copies/mL as 
defined by the modified US FDA snapshot algorithm) difference between the two treatment 
groups. For sample size and power computation, it is assumed that both treatment groups have a 
virologic failure rate of 2% (based on the historical Gilead E/C/F/TAF and STB studies), that a 
non-inferiority margin is 4%, and that the significance level of the test is at a one-sided 
0.025 level.
8.10.
Independent Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after all 
subjects enrolled complete Week 24 of the study or prematurely discontinue the study drug. 
However, Gilead will defer to the IDMC for any decision to convene earlier or more frequently. 
The IDMC will examine the safety results of the trial and also focus on logistical issues such as 
accrual, retention, quality of clinical and laboratory data, and implications of results of external 
studies.
No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
An analysis for the Week 24 IDMC meeting will be conducted after the last subjects enrolled 
completes Week 24 of the study.  For each IDMC analysis performed prior to analysis for the 
primary efficacy endpoint, an alpha penalty of 0.00001 will be applied for the primary analysis 
of the primary efficacy endpoint.


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


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


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


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


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


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


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10.
REFERENCES
2202
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum 
creatinine. Nephron 1976;16:31-41.
5125
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. 
Changing patterns of mortality across Europe in patients infected with HIV-1. 
Lancet 1998;352 (9142):1725-30.
8284
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term 
effectiveness of potent antiretroviral therapy in preventing AIDS and death: a 
prospective cohort study. Lancet 2005;366 (9483):378-84.
13840
Dejesus E YB, Morales-Ramirez JO, Sloan L, Ward DJ, Flaherty JF, et al. . 
Simplification of Antiretroviral Therapy to a Single-Tablet Regimen Consisting 
of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate Versus 
Unmodified Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected 
Patients. Acquir Immune Defic Syndr 2009;51 (2):163-74.
15302
Hodder SL, Mounzer K, Dejesus E, Ebrahimi R, Grimm K, Esker S, et al. Patient-
Reported Outcomes in Virologically Suppressed, HIV-1-Infected Subjects After 
Switching to a Simplified, Single-Tablet Regimen of Efavirenz, Emtricitabine, 
and Tenofovir DF. AIDS Patient Care STDS 2010;24 (2):87-96.
15415
Bangsberg DR, Ragland K, Monk A, Deeks SG. A one-pill, once-daily, fixed-
dose combination (FDC) of efavirenz, emtricitabine, and tenofovir disoproxil 
fumarate (EFV/FTC/TDF) regimen is associated with higher unannounced pill 
count adherence than non-one pill, once-daily [Poster]. 17th Conference on 
Retroviruses and Opportunistic Infections (CROI); 2010 February 16-19; San 
Francisco, CA. 
15951
Airoldi M, Zaccarelli M, Bisi L, Bini T, Antinori A, Mussini C, et al. One-pill 
once-a-day HAART: a simplification strategy that improves adherence and 
quality of life of HIV-infected subjects. Patient preference and adherence 
2010;4:115-25.
16560
Sax PE, Meyers J, Mugavero M, Davis KL. Adherence to Antiretroviral 
Treatment Regimens and Correlation with Risk of Hospitalization Among 
Commercially Insured HIV Patients in the United States [Poster O113]. 10th 
International Congress on Drug Therapy in HIV Infection; 2010 November 7-11; 
Glasgow, UK. 
21053
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported 
adherence supports patient preference for the single tablet regimen (STR) in the 
current cART era. Patient preference and adherence 2012;6:427-33.


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25149
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 
2000. Lancet 2003;362 (9387):847-52.
27881
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. 
Declining Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
29702
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a 
difference? Curr Med Res Opin 2013;30 (1):89-97.
29705
Costagliola D. Demographics of HIV and aging. Curr Opin HIV AIDS 2014;9 
(4):294-301.
34898
Department for Health and Human Services (DHHS). Guidelines for the Use of 
Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Developed by 
the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A 
Working Group of the Office of AIDS Research Advisory Council (OARAC). 
Downloaded from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 
08 April, 2015.
35184
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.
36201
The Joint United Nations Programme oHAU. Fact Sheet: 2014 Global Statistics. 
Available at: 
http://www.unaids.org/sites/default/files/media_asset/20150714_FS_MDG6_Rep
ort_en.pdf. 2014.


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


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Original 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of 
Switching from Regimens Consisting of Boosted Atazanavir or Darunavir plus either 
Emtricitabineffenofovir or Abacavir!Lamivudine to GS-9883/Emtricitabineffeoofovir 
Alafenamide in Virologically Suppressed HIV-1 Infected Adults 
GS-US-380-1878 Original, 21 October 2015 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
1:1_ o L h orL~ £;., b. ors~ .I( Fbal7 tc_ P P D 
Marshall Fordyce, MD (Printed) 
........,,..--------------' 
Author 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. 1 will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies ofthe protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principallnvestigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 89 
21 October 2015 


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Appendix 2.
Study Procedures Table
Study Procedures
Screeninga
Day 1b
End of Weeke, v
Post-Week 48e, w
30-Day Follow-upu
Early Study 
Drugs DCc
4
8
12
24
36
48
Every 12 Weeksx
Informed Consent
X
Medical History
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed 
Physical Exam 
X
X
Xd
Xd
Xd
X
Xd
X
Xd
Xd,f
Xf
12-Lead ECG (performed 
supine)
X
X
X
X
X
SF-36, HIV Symptoms Distress 
Module, WPAI, and UCLA 
SCTC GIT 2.0 Questionnaires
X
X
X
X
VAS Adherence Questionnaire
X
X
X
X
X
X
X
X
Height
X
Vital signs (blood pressure, 
pulse, respiration rate, and 
temperature), including Weight 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
Xj


GS-9883/F/T AF 
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Gilead Sciences, Inc. 
Study Procedures 
Estimated Glomemlar Filtration 
Rate (eGFR) 
Hematology Profilek 
Plasma HIV -1 RNA 
CD4+ Cell Connt 
Evaluation of renal tubular 
fimction
1 
Plasma and Urine Storage 
Sample 
Whole Blood sample for 
potential HIV DNA genotyping 
HCV Serology 
HIV -1 Genotype/Phenotype e 
Single PK Samplen 
Trough and post dose PK 
Sample
0 
OptionaliPPD 
I 
r 
RandomizationY 
Provide subject dosing diary to 
Treatment Group I subjects 
Optional PK Substudy" 
CONFIDENTIAL 
Screening• 
Day 1b 
4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
End ofWeek•,v 
8 
12 
24 
36 
48 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 91 
Post-Week 48e,w 
Every 12 Weeks" 
30-Day Follow-up
0 
X 
X 
X 
xr 
X 
X 
X 
X 
xm 
X 
Final 
Original 
Early Study 
Drugs DC< 
X 
xr 
X 
X 
X 
x< 
21 October 2015 


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Study Procedures
Screeninga
Day 1b
End of Weeke, v
Post-Week 48e, w
30-Day Follow-upu
Early Study 
Drugs DCc
4
8
12
24
36
48
Every 12 Weeksx
HBV blood panelq
X
Plasma HBV DNAr
X
X
X
Xs
Xs
X
Xs
X
X
Study Drug Dispensationt
X
X
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
a.
Evaluations to be completed within 30 days prior to Day 1.
b.
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures on the Day 1 visit.
c.
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Week 48 Visit even if the subject discontinues study drug.
d.
Symptom-directed physical examination as needed.
e.
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Sections 6.13)
f.
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained.
g.
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN) At Day 1, Weeks 12, 24, 48 and every 24 weeks post Week 48, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of 
the chemistry profile. Additionally, TSH will be analyzed at Screening, Day 1, Weeks 24, 48, followed by every 24 weeks post Week 48, and Early Study Drugs 
Discontinuation visit.
i.
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides).  If the subject 
has not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
j.
Every 24 weeks post Week 48 Visit
k.
CBC with differential and platelet count.
l.
Evaluation of renal biomarker includes analyses of urine albumin, urine creatinine, urine protein, retinol binding protein and beta-2-microglobulin 
m.
To be performed at Weeks 72 and 96
n.
A single PK blood sample will be collected at any time pre or post dose from subjects in Treatment Group 1.
o.
A trough PK blood sample will be collected between 20-28 hours following the last dose from subjects in Treatment Group 1. Following an observed dose, a single post dose
blood sample will be collected between 1 and 4 hours post dose.
p.
A PK substudy will be performed in a subset of Treatment Group 1subjects (n=24) at selected study sites.  The pharmacokinetic substudy visit must occur at the Week 4 or
Week 8 visits. The substudy will include intensive PK profiling in plasma.


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q.
HBV blood panel will be performed at Screening (Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody 
(HBcAb)). 
r.
To be performed for subjects who meet the definition of HBV infection
s.
At Weeks 12, 24 and 48 the following will be performed by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) and HBeAg (if negative reflex, HBeAb)
t.
Study drug GS-9883/F/TAF to be dispensed to Treatment Group 1 subjects.
u.
Only required for those subjects who permanently discontinue study drugs prior to Week 48 visit and do not continue in the study through at least one subsequent visit after 
the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used.
v.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to
Week 36, unless otherwise specified. The visit window at Weeks 48 will be ± 6 weeks of the protocol-specified visit date. After Week 48 Visit, subjects in the United 
Kingdom (UK) will stop taking study drug and complete a 30 day follow up visit
w.
Visit window of 6 days for study visits post Week 48.
x.
GS-9883/F/TAF FDC will be dispensed to subjects participating in the study post Week 48 visit.
y.
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit provided that all screening procedures have been completed and subject eligibility has been 
confirmed.


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Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grade 1 
~------G-r-ad-e-2------~~ 
~~------G-r-ad-e-3------~~~ ~ ___________ G_r_a_d_e-4----------~ 
~ 
~ 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
If confirmed and possibly and/or probably related to investigational 
medicinal products: 
1. 
Withhold investigational medicinal products until :s; Grade 2 
2. 
Restart all investigational medicinal products at full dose 
l 
If Grade 3 or 4 recurrence that is confirmed and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
l 
Ifc 
Repeat lab to 
confirm toxicity 
grade 
l 
mve 
onfirmed and unrelated to 
stigational medicinal products, 
mg may continue at the discretion 
he investigator 
dos 
oft 
If confirmed and 
possibly or probably 
----+ related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 


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


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects.  Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.


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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant  <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L                
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L                 
2.0 t o <2.5 mmolL
2.0 mEq/L                         
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant  <1 Year
>ULN to 6.0 mEq/L           
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L             
6.5 to 7.0 mmol/L
7.0 mEq/L                  
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L


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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


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Original
CONFIDENTIAL
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to  <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63  to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to <LLN mg/dL
1.12 to <LLN mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia 
Adult and Pediatric 
> 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L


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


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


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ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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23. Salmonella septicemia, recurrent
24. Toxoplasmosis of brain
25. Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {35184}


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


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


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

SAP_009.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3, Randomized, Open-Label Study to Evaluate the 
Safety and Efficacy of Switching from Regimens Consisting of 
Boosted Atazanavir or Darunavir plus either 
Emtricitabine/Tenofovir or Abacavir/Lamivudine to 
GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically 
Suppressed HIV-1 Infected Adults
Name of Test Drug:
Bictegravir/Emtricitabine/Tenofovir Alafenamide 
(B/F/TAF; GS-9883/F/TAF)
Study Number:
GS-US-380-1878
Protocol Version (Date):
Amendment 2 (19 October 2016)
Analysis Type:
Final Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
24 April 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(rJ GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF ABBREVIATIONS........................................................................................................................................5
1.
INTRODUCTION ................................................................................................................................................8
1.1.
Study Objectives ......................................................................................................................................8
1.2.
Study Design............................................................................................................................................8
1.3.
Sample Size and Power..........................................................................................................................11
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................12
2.1.
Data Monitoring Committee Analyses...................................................................................................12
2.2.
Interim Analyses ....................................................................................................................................12
2.2.1.
Week 48 Analysis.................................................................................................................12
2.3.
Final Analysis ........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................13
3.1.
Analysis Sets..........................................................................................................................................14
3.1.1.
Analysis Sets Used for the Randomized Phase Analysis .....................................................14
3.1.2.
Analysis Set Used for the All B/F/TAF Analysis.................................................................15
3.2.
Subject Grouping ...................................................................................................................................15
3.3.
Strata and Covariates..............................................................................................................................16
3.4.
Examination of Subject Subgroups........................................................................................................16
3.4.1.
Subject Subgroups for Safety Analyses ...............................................................................16
3.5.
Multiple Comparisons............................................................................................................................16
3.6.
Missing Data and Outliers......................................................................................................................16
3.6.1.
Missing Data ........................................................................................................................16
3.6.2.
Outliers.................................................................................................................................17
3.7.
Data Handling Conventions and Transformations .................................................................................17
3.8.
Analysis Windows .................................................................................................................................18
3.8.1.
Definition of Study Day .......................................................................................................18
3.8.2.
Analysis Windows................................................................................................................19
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window................................................................................................................................23
4.
SUBJECT DISPOSITION ..................................................................................................................................25
4.1.
Subject Enrollment and Disposition.......................................................................................................25
4.1.1.
Subject Enrollment...............................................................................................................25
4.1.2.
Subject Disposition ..............................................................................................................25
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................26
4.2.1.
Duration of Exposure to Study Drug....................................................................................26
4.2.2.
Adherence to Study Drug Regimen......................................................................................26
4.3.
Protocol Deviations................................................................................................................................28
5.
BASELINE CHARACTERISTICS....................................................................................................................29
5.1.
Demographics and Baseline Characteristics ..........................................................................................29
5.2.
Baseline Disease Characteristics............................................................................................................29
5.3.
Medical History......................................................................................................................................30
6.
EFFICACY ANALYSES ...................................................................................................................................31
6.1.
Primary Efficacy Endpoint.....................................................................................................................31


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6.2. 
Secondary Efficacy Endpoints ............................................................................................................... 31 
6.2.1. 
Definition of the Secondary Efficacy Endpoints .................................................................. 31 
6.2.2. 
Anal sis ofCD4+ Cell Count .............................................................................................. 31 
6.4. 
7. 
SAFETY ANALYSES ........................................................................................................................................ 34 
7.1. 
Adverse Events and Deaths .................................................................................................................... 34 
7.1.1. 
Adverse Event Dictionary .................................................................................................... 34 
7.1.2. 
Adverse Event Severity ........................................................................................................ 34 
7.1.3. 
Relationship of Adverse Events to Study Drug .................................................................... 34 
7.1.4. 
Serious Adverse Events ........................................................................................................ 35 
7.1.5. 
Treatment-Emergent Adverse Events ................................................................................... 35 
7 .1.6. 
Summaries of Adverse Events and Death ............................................................................ 36 
7.1.7. 
Additional Analysis of Adverse Events ............................................................................... 37 
7.2. 
Laboratory Evaluations .......................................................................................................................... 38 
7.2.1. 
Summaries ofNumeric Laboratory Results ......................................................................... 38 
7.2.2. 
Graded Laboratory Values ................................................................................................... 39 
7.2.3. 
Metabolic Laboratory Evaluations ....................................................................................... 40 
7.2.4. 
Liver-Related Laboratory Evaluations ................................................................................. 41 
7.2.5. 
Renal-Related Laboratory Evaluations ................................................................................. 41 
7.3. 
Body Weight, Height, and Yitai Signs ................................................................................................... 42 
7.4. 
Prior and Concomitant Medications ....................................................................................................... 43 
7.4.1. 
Antiretroviral Medications ................................................................................................... 43 
7.4.2. 
Prior Antiretroviral Medications .......................................................................................... 43 
7.4.3. 
Concomitant Non-Antiretroviral Medications ...................................................................... 43 
7.5. 
Electrocardiogram Results ..................................................................................................................... 44 
7.6. 
Other Safety Measures ........................................................................................................................... 44 
7.7. 
Subject Subgroup for Safety Endpoints ................................................................................................. 44 
7.8. 
Changes from Protocol-Specified Safety Analyses ................................................................................ 44 
8. 
PHARMACOKINETIC ANALYSES ................................................................................................................ 45 
9. 
SPECIAL POPULATION ANALYSES ............................................................................................................. 46 
9.1. 
Analyses for HIV/HBV Coinfected Subjects ......................................................................................... 46 
9.2. 
Analyses for HIV/HCV Coinfected Subjects ......................................................................................... 47 
10. REFERENCES ................................................................................................................................................... 49 
11 . SOFTWARE ....................................................................................................................................................... 50 
12. SAP REYISION .................................................................................................................................................. 51 
13. APPENDICES .................................................................................................................................................... 52 
Appendix I. 
Appendix 2. 
Appendix 3. 
Appendix 4. 
Appendix 5. 
CONFIDENTIAL 
Study Procedures Table .......................................................................................................... 53 
Region Definition ................................................................................................................... 56 
Cardiovascular or Cerebrovascular Events ............................................................................. 57 
Hepatic Events ........................................................................................................................ 58 
Programming Specification .................................................................................................... 59 
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LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Windows for HIV-1 RNA, CD4+ cell count, 
 HBV DNA, 
Hematology, Chemistry, Urinalysis, and Urine Pregnancy Laboratory Tests, 
eGFRCG, Vital Signs, and Weight for Randomized Phase Analysis.......................................19
Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, 
 HBV DNA, 
Hematology, Chemistry, Urinalysis, and Urine Pregnancy Laboratory Tests, 
eGFRCG, Vital Signs, and Weight for All B/F/TAF Analysis.................................................20
Table 3-3.
Analysis Windows for Metabolic Assessments and HBV Serology for Randomized 
Phase Analysis........................................................................................................................21
Table 3-4.
Analysis Windows for Metabolic Assessments and HBV Serology for all B/F/TAF 
Analysis..................................................................................................................................21
Table 3-5.
Analysis Windows for TSH, Renal Function, and Safety ECG for Randomized 
Phase Analysis........................................................................................................................22
Table 3-6.
Analysis Windows for TSH, Renal Function, and Safety ECG for all B/F/TAF 
Analysis..................................................................................................................................22
Table 3-7.
Analysis Windows for HCV Serology and HCV RNA Assessments for Randomized 
Phase Analysis........................................................................................................................23
Table 3-8.
Analysis Windows for HCV Serology and HCV RNA Assessments for all B/F/TAF 
Analysis..................................................................................................................................23
CCI
CCI--


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LIST OF ABBREVIATIONS
3TC
lamivudine
ABC
abacavir
ABC/3TC
fixed dose combination of abacavir (ABC) 600 mg / lamivudine (3TC) 300 mg
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir
AUC
area under curve
BIC
bictegravir
B/F/TAF
fixed dose combination of bictegravir (BIC; B) 50 mg / emtricitabine (FTC) 200 mg /
tenofovir alafenamide (TAF) 25 mg
BMI
body mass index
CDER
Center for Drug Evaluation and Research
CI
confidence interval
CMH
Cochran-Mantel-Haenszel 
COBI
cobicistat
CSR
clinical study report 
DC
premature study drug discontinuation
DNA
deoxyribonucleic acid
DRV
darunavir
E/C/F/TAF
fixed dose combination of elvitegravir (EVG) 150 mg / cobicistat (COBI) 150 mg /
emtricitabine (FTC) 200 mg / tenofovir alafenamide (TAF) 10 mg 
E/C/F/TDF
fixed dose combination of elvitegravir (EVG) 150 mg / cobicistat (COBI) 150 mg / 
emtricitabine (FTC) 200 mg / tenofovir disoproxil fumarate (TDF) 300 mg
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
full analysis set
FDA
Food and Drug Administration
FDC
fixed dose combination
FTC
emtricitabine
FTC/TDF
fixed dose combination of emtricitabine (FTC) 200 mg / tenofovir disoproxil fumarate 
(TDF) 300 mg
GEN
Genvoya, E/C/F/TAF
GFR
glomerular filtration rate


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GGT
gamma-glutamyl transferase
Gilead 
Gilead Sciences, Inc.
GS-9883
bictegravir
HBcAb
hepatitis B core antibody 
HBeAb
hepatitis B e-antibody
HBeAg
hepatitis B e-antigen
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus 
HCVAb
hepatitis C antibody
HDL
high density lipoprotein
HIV
human immunodeficiency virus
HIV-1
human immunodeficiency virus (Type 1) 
HLGT
high level group term
HLT
high level term
ID
Identification
IDMC
independent data monitoring committee
INSTI
integrase strand transfer inhibitor
KM
Kaplan-Meier
LDL
low density lipoprotein
LLOQ
lower limit of quantitation
LLT
lowest level term
INR
International normalized ratio
LOCF
last observation carried forward
M = E
missing = excluded 
MedDRA
Medical Dictionary for Regulatory Activities
NRTI
nucleoside reverse transcriptase inhibitor
PI
protease inhibitor
PK
pharmacokinetic
PT
preferred term
PT
prothrombin time
PVE
Pharmacovigilance and Epidemiology
Q1
first quartile
Q3
third quartile
RBP
retinol binding protein
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SBR
stay on baseline regimen 


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SD
standard deviation
SE
standard error 
SMQ
Standardised MedDRA Query
SOC
system organ class
STB
Stribild, E/C/F/TDF 
TAF
tenofovir alafenamide 
TDF
tenofovir disoproxil fumarate
TEAE
treatment-emergent adverse event 
TFLs
tables, figures, and listings
TFV
tenofovir
TSH
thyroid stimulating hormone; thyrotropin
UACR
urine albumin to creatinine ratio
UK
United Kingdom
ULN
upper limit of normal
US
United States 
WHO
World Health Organization


B/FffAF 
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Statistical Analysis Plan - Final Analysis 
1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) of the final analysis for 
Version 1.0 
Study GS-US-380-1878, which will be perfonned when all subjects have completed the study or 
prematurely discontinued from the study drug. This SAP is based on the study protocol 
amendment 2 dated 19 October 2016 and the electronic case report fonn ( eCRF). The SAP will 
be finalized before data finalization for the final analysis. Any changes made after the 
finalization of the SAP will be documented in the clinical study report (CSR). 
1.1. 
Study Objectives 
The primary objective of this study is: 
• 
To evaluate the efficacy of switching to a fixed dose combination (FDC) of bictegravir 
(GS-9883; BIC; B)/emtricitabine (FTC; F)/tenofovir alafenamide (TAF) versus continuing 
on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRY) plus either 
emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) 
in HIV-infected adult subjects who are virologically suppressed as detenn ined by the 
proportion of subjects with HIV-1 ribonucleic acid (RNA) 
50 copies/mL at Week 48. 
The secondary objective of this study is: 
• 
To evaluate the safety and tolerability of the 2 treatment groups through Week 48. 
I 
I 
1.2. 
Study Design 
Design Configuration and Subject Population 
GS-US-380-1878 is a randomized, open-label, multicenter, active-controlled study to evaluate 
the safety and efficacy of switching to a FDC of B/F IT AF in HIV-infected subjects who are 
virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of boosted ATV 
or DRY plus either FTC/TDF or ABC/3TC for~ 6 months prior to screening and who are 
integrase strand transfer inhibitor (INSTI) naive. 
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Treatment Groups
Subjects who provide written consent and meet all eligibility criteria will be randomized in a 
1:1 ratio to one of the following 2 treatment groups:

Treatment Group 1: Switch to a FDC of bictegravir 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (B/F/TAF) administered orally, once daily without regard to food (n 260)

Treatment Group 2: Remain on current antiretroviral regimen consisting of ritonavir (RTV) 
or cobicistat (COBI) boosted ATV or DRV plus either FTC/TDF or ABC/3TC administered 
orally, once daily with food (n 260)
From this point on, this document will refer Treatment Group 2 as SBR (ie, Stay on baseline 
regimen) for simplicity.
Key Eligibility Criteria
Medically stable HIV-infected subjects who meet the following criteria:

Currently receiving a once daily antiretroviral regimen consisting of RTV or COBI boosted 
ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the Screening 
visit

Currently on a stable regimen for ≥6 months preceding the Screening visit with documented 
plasma HIV-1 RNA < 50 copies/mL for ≥6 months preceding the Screening visit 
(note: prior changes in antiretroviral regimen are only allowed due to tolerability issues or for 
regimen simplification; unconfirmed virologic elevation of ≥ 50 copies/mL 
[transient detectable viremia, or “blip”] prior to screening is acceptable)

HIV-1 RNA levels < 50 copies/mL at Screening visit 

No previous use of any approved or experimental INSTI

No documented or suspected resistance to FTC, TFV, ABC, or 3TC, including but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I

Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance

No chronic Hepatitis B Virus (HBV) infection in subjects not on a TDF containing regimen


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Statistical Analysis Plan - Final Analysis 
Studv Periods / Phases 
Sub· ects will be treated for at least 48 weeks. 
Version 1.0 
Subjects who complete the study through Week 48 visit and who do not continue participation in 
the study will be required to return to the clinic 30 days after the completion of study drug for the 
30-Day Follow-Up visit. 
Note: After the Week 48 visit, subjects in the UK will continue to take their assigned regimen 
and attend visits every 12 weeks. 
Schedule of Assessments 
After screening procedures, eligible subjects will be randomized 1: 1 to Treatment Group 1 or 
Treatment Group 2 and treated for 48 weeks. Following the Day 1 visit, subjects will be required 
to return for study visits at Weeks 4, 8, and 12, and then every 12 weeks through Week 48. After 
48 weeks, subjects who continue participation in the study will receive B/F IT AF for additional 
96 weeks and attend study visits every 12 weeks. 
For all eligible subjects, blood will be collected at Day 1, Weeks 4, 8, 12, and then every 
12 weeks through Week 48. Laboratory analyses (hematology, chemistry, and urinalysis), HIV-1 
RNA, CD4+ cell count, and complete or symptom directed physical examinations will be 
perfonned at Screening, Day 1 and all subsequent visits. Urine will be collected for evaluations 
of renal function including urine albmnin, urine creatinine, urine protein, retinol binding protein 
(RBP), and beta-2 microglobulin. 
Adverse events and concomitant medications will be assessed at each visit. 
More details for study procedures could be found in Appendix 1. 
Pharmacokinetics 
For all subjects who are randomized in to the B/F/TAF group and who are on study drug, a 
single anytime pre- or post-dose PK blood sample will be collected at Weeks 8, 24, and 36. 
For all subjects who are randomized into the B/F/TAF group and who are on study drug, a trough 
PK blood sample will be obtained 20-28 hours following the last dose at Weeks 4 and 12. 
Following an observed dose, one post-dose PK blood sample will be collected between 
1 and 4 hours post-dose. 
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Statistical Analysis Plan - Final Analysis 
Randomization 
Version 1.0 
Subjects will be randomized in a 1: 1 ratio to 1 of 2 Treatment Groups (Treatment Group 1: 
Treatment Group 2). Randomization will be stratified by the prior treatment regimen group 
(ie, TDF containing regimens [RTV or COBI boosted ATV or DRY plus FTC!TDF] and non-TDF 
containing regimens [RTV or COBI boosted ATV or DRY plus AB03TC]) at screening. 
Site and/or Stratum Enrollment Limits 
Approximately 150 study sites in North America, Europe, Asia Pacific, and Latin America 
participated. There was no enrollment limit for individual sites. 
Studv Duration 
The randomization phase of this study is at least 48 weeks in duration. 
1.3. 
Sample Size and Power 
A total of approximately 520 HIV-infected subjects, randomized in a 1: 1 ratio to 2 treatment 
groups (260 subjects per treatment group), achieves at least 90% power to detect a noninferiority 
margin of 4% in Week 48 response rate (HIV-1 RNA 
50 copies/mL as detennined by the 
United States [US] Food and Drug Administration [FDA]-defined snapshot algorithm) difference 
between the 2 treatment groups. For sample size and power computation, it is assumed that both 
treatment groups have 2% of subjects with HIV-1 RNA ~ 50 copies/mL (based on Gilead 
Genvoya [GEN; E/C/F/f AF] and Stribild [STB; E/C/F/TDF] studies) and that the significance 
level of the test is at a 1-sided 0.025 level. Sample size and power calculations were made using 
the statistical software package nQuery Advisor (Version 6.0). 
The actual number ofrandomized and treated subjects is 577. A total of 577 subjects increased 
the statistical power from 90% to 93% for evaluation of noninferiority of the primary efficacy 
endpoint. 
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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee Analyses
The Week 12 Independent Data Monitoring Committee (IDMC) analysis was conducted after 
approximately the first 30% subjects enrolled completed their Week 12 visit or prematurely 
discontinued the study drug. The Week 24 IDMC analysis was conducted after all subjects 
enrolled completed their Week 24 visit or prematurely discontinued the study drug. The purpose 
of these interim analyses was to provide the IDMC with a statistical report for review. More 
details are documented in the IDMC charter.
Gilead does not have a prior intent to ask the IDMC to review Week 48 results or to consider
early termination of the study even if there is early evidence of favorable efficacy for B/F/TAF. 
2.2.
Interim Analyses
2.2.1.
Week 48 Analysis
The Week 48 analysis was conducted after all subjects had completed the Week 48 visit or 
prematurely discontinued study drug. This is the primary analysis of this study.
2.3.
Final Analysis
The final statistical analysis for the study will be conducted after all subjects either complete the 
study or prematurely discontinue from the study. This analysis will include all data collected from 
the randomized and the extension phases of the study.
This SAP describes the analysis plan for the final analysis.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
The final analysis will include two sets of analysis: the randomized phase analysis and the all
B/F/TAF analysis.
Randomized Phase Analysis:

The randomized phase analysis will include all available data for subjects who are never 
treated in the extension phase of the study including those who prematurely discontinue the 
randomized study drug or who complete the randomized study drug and do not receive any 
dose of B/F/TAF in the extension phase.

The randomized phase analysis will include (1) all available adverse event (AE), concomitant 
medication, pregnancy, and death data collected prior to the extension phase first dose date;
(2) all available other data, such as laboratory, vital sign, ECG, and PK data, collected on or 
prior to the extension phase first dose date for subjects who receive at least 1 dose of 
B/F/TAF in the extension phase.
All B/F/TAF Analysis:

For the all B/F/TAF analysis, all available data for subjects who actually receive B/F/TAF in 
the randomized phase will be included.

The all B/F/TAF analysis will include (1) all available AE, concomitant medication, 
pregnancy, and death data with start date on or after the extension phase first dose date and
(2) all available other data, such as laboratory, vital sign, and ECG data, collected after the 
extension phase first dose date for subjects who actually receive SBR in the randomized 
phase and receive at least 1 dose of B/F/TAF in the extension phase. Except that the data
collected on or prior to the first dose date of B/F/TAF will be used to derive the baseline
value for the all B/F/TAF analysis.
Note: All data for subjects who actually receive SBR in the randomized phase and do not receive 
any dose of B/F/TAF in the extension phase will be excluded. In addition, the actual treatment 
received will differ from the randomized treatment only when the actual treatment received 
differs from randomized treatment for the entire treatment duration. 
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
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By-subject listings will be presented for all subjects in the all randomized analysis set unless 
otherwise specified, and sorted by subject identification (ID) number, visit date, and time 
(if applicable). Data collected on log forms, such as AEs, will be presented in chronological 
order within a subject. The treatment group to which subjects were randomized in the 
randomized phase will be used in the listings.
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. For randomized but never dosed subjects, age on the date of randomization 
will be used. For screen failures, age on the date of the informed consent was signed will be used.
If only birth year is collected on the eCRF, “01 January” will be used for the unknown birth day 
and month for the purpose of age calculation, similarly, if only birth year and month are collected 
on the eCRF, “01” will be used for the unknown birth day for the purpose of age calculation.
In general, permanent discontinuation of the randomized study drug refers to premature 
discontinuation of the randomized study drug or completion of the randomized study drug. 
Similarly, permanent discontinuation of the extension phase study drug refers to premature 
discontinuation of the extension phase study drug or completion of the extension phase study 
drug. More specifically, for randomized phase analysis, study drug refers to the randomized
study drugs (B/F/TAF or SBR); for all B/F/TAF analysis, study drug refers to B/F/TAF.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. Subjects included in each analysis set will be determined before data 
finalization. The analysis set will be included as a subtitle of each table, figure, and listing. A 
summary of the number and percentage of subjects in each analysis set will be provided by 
treatment group and in total.
3.1.1.
Analysis Sets Used for the Randomized Phase Analysis
3.1.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set will include all subjects who are randomized into the 
randomized phase of the study. This is the primary analysis set for by-subject listings.
3.1.1.2.
Full Analysis Set
The Full Analysis Set (FAS) will include all subjects who (1) are randomized into the 
randomized phase of the study and (2) have received at least 1 dose of randomized study drug. 
Subjects will be grouped according to the treatment to which they were randomized. For the 
FAS, all efficacy data collected in the randomized phase, including data collected after the last 
dose date of the randomized study drug and on or prior to the first dose date of the extension 
study drug (if applicable), will be included, unless specified otherwise. This is the primary 
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3.1.1.3.
Safety Analysis Set 
The Safety Analysis Set will include all subjects who (1) are randomized into the study and 
(2) have received at least 1 dose of randomized study drug. Subjects will be grouped according 
to the treatment they actually received. This is the primary analysis set for safety analyses.
Adverse event (AE), concomitant medication, pregnancy, and death data collected up to 30 days 
after permanent discontinuation of the randomized phase study drug and prior to the first dose 
date of extension phase study drug (if applicable) will be included in the safety summaries, 
unless specified otherwise.
Laboratory data (eg, hematology, chemistry, and urine analysis), vital sign, ECG data collected 
up to 30 days after permanent discontinuation of the randomized phase study drug and on or 
prior to the first dose date of extension phase study drug (if applicable) will be included in the 
safety summaries, unless specified otherwise.
3.1.2.
Analysis Set Used for the All B/F/TAF Analysis
3.1.2.1.
All B/F/TAF Analysis Set
The All B/F/TAF Analysis Set will include all subjects who (1) are randomized into the 
randomized phase of the study and (2) have received at least 1 dose of the B/F/TAF in the 
randomized phase or in the extension phase. This is the primary analysis set for the all B/F/TAF 
efficacy and safety analyses.
For efficacy analyses, all efficacy data collected for the all B/F/TAF analysis will be included.
For safety analyses, all safety data collected up to 30 days after permanent discontinuation of the 
B/F/TAF will be included in the safety summaries, unless specified otherwise.
3.2.
Subject Grouping
For analyses based on the All Randomized Analysis Set or the FAS in the randomized phase 
analysis, subjects will be grouped by the randomized treatment (labeled as B/F/TAF vs. SBR). 
For all other analyses in the randomized phase analysis, subjects will be grouped by the actual 
treatment received. The actual treatment received will differ from the randomized treatment only 
when the actual treatment received differs from randomized treatment for the entire treatment 
duration.
For all analyses included in the all B/F/TAF analysis, subjects will be grouped into the following
3 groups:

B/F/TAF group: This group includes all subjects who actually received B/F/TAF in the 
randomized phase of this study, regardless whether subjects receive any B/F/TAF in the 
extension phase or not.


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
SBR to B/F/TAF group: This group includes all subjects who actually received the SBR 
regimen in the randomized phase of this study and then receive at least 1 dose of B/F/TAF in 
the extension phase.

All B/F/TAF group: This group includes all subjects who actually received at least 1 dose of 
B/F/TAF in either phase. This group includes the B/F/TAF group and the SBR to B/F/TAF 
group. Only data collected on and after the first dose date of B/F/TAF may be included.
Treatment comparisons will only be made between B/F/TAF and SBR for the randomized phase 
analysis.
3.3.
Strata and Covariates
Randomization was stratified by the prior treatment regimen group (ie, TDF containing regimens 
[RTV or COBI boosted ATV or DRV plus FTC/TDF] and non-TDF containing regimens [RTV or 
COBI boosted ATV or DRV plus ABC/3TC]) at screening. However, no stratified analysis is 
planned for the final analysis.
3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Safety Analyses
Selected safety endpoints may be analyzed for the following subject subgroups (see Section 9.1
and Section 9.2 for details):

Subjects with HIV/ hepatitis C virus (HCV) coinfection at baseline (if any)

Subjects with HIV/ hepatitis B virus (HBV) coinfection at baseline (if any)

Subjects with incident HIV/HBV coinfection while on study drug (if any)

Subjects with incident HIV/HCV coinfection while on study drug (if any)
3.5.
Multiple Comparisons
Not applicable for this analysis, as no treatment comparison is planned for the final analysis. All 
analyses are exploratory in nature.
3.6.
Missing Data and Outliers 
3.6.1.
Missing Data
A missing datum for a given study analysis window may be due to any of the following reasons:

A visit occurring in the window but data were not collected or were unusable 

A visit not occurring in the window

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In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.
For missing last dosing date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for 
concomitant non-antiretroviral (ARV) medications in Section 7.4.3.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety
outcomes, unless specified otherwise. All data will be included in the analyses.
3.7.
Data Handling Conventions and Transformations
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed as follows except for urine creatinine:

A value that is 1 unit less than the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “x” (where x is considered the 
limit of quantitation). For example, if the values are reported as < 50 and < 5.0, values of 
49 and 4.9, respectively, will be used for calculation of summary statistics. An exception to 
this rule is any value reported as < 1 or < 0.1, etc. For values reported as < 1 or < 0.1, a value 
of 0.9 or 0.09, respectively, will be used for calculation of summary statistics.

A value that is 1 unit above the limit of quantitation will be used for calculation of 
descriptive statistics if the datum is reported in the form of “> x” (where x is considered the 
limit of quantitation). Values with decimal points will follow the same logic as above.

The limit of quantitation will be used for calculation of descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the limit of quantitation).
For urine creatinine, a value of “< 1” is handled as a missing value in its summary and the 
calculation of related ratios.
Logarithmic (base 10) transformations will be applied to HBV deoxyribonucleic acid (DNA)
data for efficacy analysis. HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “<20 cp/mL 
HIV-1 RNA Detected” will be imputed as 19 copies/mL for analysis purposes. HBV DNA 
results of “<20 IU/mL HBV DNA detected” or “No HBV DNA detected” will be imputed as 
19 IU/mL for analysis purposes. HCV RNA results of “<15 IU/mL HCV RNA detected” or 
“No HCV RNA detected” will be imputed as 14 IU/mL for analysis purposes. 


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3.8.
Analysis Windows
3.8.1.
Definition of Study Day
Study Day 1 for the Randomized Phase Analysis is defined as the day when the first dose of 
randomized study drug (ie, B/F/TAF or SBR) was taken. For subjects randomized to the 
B/F/TAF group, the first dose date is recorded on the “Randomized Phase” Study Drug 
Administration eCRF. For subjects randomized to the SBR group, the first dose date is defined 
as Day 1 visit date on the Visit Date eCRF. 
Last Dose Date for the Randomized Phase Analysis is defined as follows: 

For subjects randomized to the B/F/TAF group, the last dose date is defined as the latest of 
the randomized study drug end dates recorded on the “Randomized Phase” Study Drug 
Administration eCRF.

For subjects randomized to the SBR group, the last dose date is the earliest of the latest end 
dates from each baseline regimen component (ie, protease inhibitor [PI] and nucleoside 
reverse transcriptase inhibitors [NRTIs] as defined in Section 7.4.2) recorded on the 
“Current” ARV eCRF for the randomized phase of the study. 
If the last dose date for randomized phase is missing (eg, only year of last dose date is known or 
completely missing due to lost to follow-up), the latest of nonmissing randomized study drug 
start dates and end dates, the clinical visit dates, and the laboratory visit dates, excluding the date 
of 30-day follow-up visit, from the randomized phase data, will be used to impute the 
randomized phase last dose date. For other partial missing last dose date, please see 
programming specification for imputation rule details.
Study Day 1 for the all B/F/TAF analysis is defined as the day when the first dose of B/F/TAF 
(in the randomized phase for B/F/TAF group, and in the extension phase for SBR to B/F/TAF 
treatment group) was taken, as recorded on the Study Drug Administration eCRF form.
Last Dose Date for the All B/F/TAF Analysis is defined as the latest of B/F/TAF 
(including both phases) recorded on the Study Drug Administration eCRF form with 
“Permanently Withdrawn” box checked.
If the last dose date for the all B/F/TAF analysis is missing (eg, only year of last dose date is 
known or completely missing due to lost to follow-up), the latest B/F/TAF start dates and end 
dates, the latest clinical and laboratory visit dates, excluding the 30-day follow-up visit date, will 
be used to impute the last dose date.
Study Days are calculated relative to Study Day 1 for either the randomized phase or all 
B/F/TAF analysis, as appropriate. For events that occurred on or after the Study Day 1 date, 
study days are calculated as (visit date minus date of Study Day 1 plus 1). For events that 
occurred prior to the randomized phase Study Day 1, study days are calculated as (visit date 
minus date of Study Day 1).


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Last Study Date is the latest of the randomized or extension phase (if available) study drug start
dates and end dates, the clinic visit dates, and the laboratory visit dates, including the 30-day 
follow-up visit date.
Baseline Value is defined as the last nonmissing value obtained on or prior to Study Day 1 for 
either the randomized phase analysis or the all B/F/TAF analysis, as appropriate. Subjects who 
actually received SBR in the randomized phase and received at least 1 dose of extension 
B/F/TAF will have a new baseline value for the all B/F/TAF analysis.
3.8.2.
Analysis Windows
Subject visits might not occur on protocol specified days. Therefore, for the purpose of analysis, 
observations will be assigned to two different analysis windows based on the following tables: 
the analysis windows for the randomized phase analysis are derived relative to the Study Day 1 
for the randomized phase analysis, while the analysis windows for the all B/F/TAF analysis are 
derived relative to the study day 1 for the all B/F/TAF analysis. 
The analysis windows for HIV-1 RNA, CD4+ cell count, 
 HBV DNA, hematology, 
chemistry, urinalysis, urine pregnancy laboratory tests, eGFRCG, vital signs, and weight are 
presented in Table 3-1 and Table 3-2 for randomized phase analysis and all B/F/TAF analysis,
respectively. 
Table 3-1.
Analysis Windows for HIV-1 RNA, CD4+ cell count, 
 
HBV DNA, Hematology, Chemistry, Urinalysis, and Urine Pregnancy
Laboratory Tests, eGFRCG, Vital Signs, and Weight for Randomized 
Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 4
28
2
42
Week 8
56
43
70
Week 12
84
71
126
Week 24
168
127
210
Week 36
252
211
294
Week 48
336
295
378
Week 60 
420
379
462
Week 72
504
463
546
Week 84
588
547
630
Week 96
672
631
714
Week k
(k is every 12 weeks after 
previous visit)
k*7
(k 6)*7+1
(k+6)*7
Note: HBV DNA collection schedules are as follows: (1) For subjects who meet the definition of HBV infection at screening, 
HBV DNA will be collected at baseline, Weeks 4, 8, 12, 24, 36, and 48. (2) For subjects who meet the definition of HBV 
infection at any postbaseline visit, HBV DNA test will be performed at all subsequent visits. (3) For subjects who do not meet the 
definition of HBV infection at any visit, HBV DNA will be collected at baseline and Week 48.
CCI
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Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, 
 
HBV DNA, Hematology, Chemistry, Urinalysis, and Urine Pregnancy
Laboratory Tests, eGFRCG, Vital Signs, and Weight for All B/F/TAF 
Analysis
Visit ID
B/F/TAF Group
SBR to B/F/TAF
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 4
28
2
42
NA
NA
NA
Week 8
56
43
70
NA
NA
NA
Week 12
84
71
126
84
2
126
Week 24
168
127
210
168
127
210
Week 36
252
211
294
252
211
294
Week 48
336
295
378
336
295
378
Week 60
420
379
462
420
379
462
Week 72
504
463
546
504
463
546
Week 84
588
547
630
588
547
630
Week 96
672
631
714
672
631
714
Week k
(k is every 
12 weeks 
after 
previous 
visit)
k*7
(k-6)*7+1
(k+6)*7
k*7
(k-6)*7+1
(k+6)*7
NA  Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the SBR to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension phase. 
The analysis windows for metabolic assessments (including fasting glucose and lipid panel: total 
cholesterol, high density lipoprotein [HDL], direct low density lipoprotein [LDL], triglycerides, 
and total cholesterol to HDL ratio) and HBV serology (including hepatitis B surface antibody 
[HBsAb], hepatitis B surface antigen [HBsAg], hepatitis B e-antigen [HBeAg], hepatitis B 
e-antibody [HBeAb], and hepatitis B core antibody [HBcAb]) are presented in Table 3-3 and
Table 3-4 for randomized phase analysis and all B/F/TAF analysis, respectively.
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Table 3-3.
Analysis Windows for Metabolic Assessments and HBV Serology for 
Randomized Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 12
84
2
126
Week 24
168
127
252
Week 48
336
253
420
Week 72
504
421
588
Week 96
672
589
756
Week k (k is every 24 
weeks after previous 
visit)
k*7
(k-12)*7+1
(k+12)*7
Note: HBV serology collection schedules are as follows: (1) For subjects who meet the definition of HBV infection at screening, 
HBV serology will be collected at Weeks 12, 24, and Week 48. (2) For subjects who meet the definition of HBV infection at any 
postbaseline visit, HBV serology will be performed at all subsequent visits. (3) For subjects who do not meet the definition of 
HBV infection at any visit, HBV serology will be collected at baseline and Week 48.
Table 3-4.
Analysis Windows for Metabolic Assessments and HBV Serology for 
all B/F/TAF Analysis
Visit ID
B/F/TAF Group
SBR to B/F/TAF
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 12
84
2
126
NA
NA
NA
Week 24
168
127
252
168
2
252
Week 48
336
253
420
336
253
420
Week 72
504
421
588
504
421
588
Week 96
672
589
756
672
589
756
Week k (k 
is every 24 
weeks after 
previous 
visit)
k*7
(k-12)*7+1
(k+12)*7
k*7
(k-12)*7+1
(k+12)*7
NA  Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the SBR to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension phase. 
The analysis windows for thyroid stimulating hormone (TSH; thyrotropin), renal function 
(including: urine albumin, urine creatinine, urine RBP, and urine beta-2 microglobulin, and 
derived ratios), and safety electrocardiogram (ECG) are presented in Table 3-5 and Table 3-6.


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Table 3-5.
Analysis Windows for TSH, Renal Function, and Safety ECG for 
Randomized Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 24
168
2
252
Week 48
336
253
420
Week 72
504
421
588
Week 96
672
589
756
Week k (k is every 24 
weeks after previous 
visit)
k*7
(k-12)*7+1
(k+12)*7
Table 3-6.
Analysis Windows for TSH, Renal Function, and Safety ECG for all 
B/F/TAF Analysis
Visit ID
B/F/TAF Group
SBR to B/F/TAF
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 24
168
2
252
168
2
252
Week 48
336
253
420
336
253
420
Week 72
504
421
588
504
421
588
Week 96
672
589
756
672
589
756
Week k (k 
is every 24 
weeks after 
previous 
visit)
k*7
(k-12)*7+1
(k+12)*7
k*7
(k-12)*7+1
(k+12)*7
NA  Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the SBR to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension phase. 
The analysis windows for HCV serology (including HBsAb, HBsAg, hepatitis B e-antigen 
[HBeAg], hepatitis B e-antibody [HBeAb], HBcAb, HCV antibody [HCVAb]), and HCV RNA 
assessments are presented in Table 3-7 and Table 3-8.


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Table 3-7.
Analysis Windows for HCV Serology and HCV RNA Assessments for 
Randomized Phase Analysis
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 48
336
2
504
Week 96
672
505
840
Week k (k is every 48
weeks after previous 
visit)
k*7
(k-24)*7+1
(k+24)*7
Table 3-8.
Analysis Windows for HCV Serology and HCV RNA Assessments for 
all B/F/TAF Analysis
Visit ID
B/F/TAF Group
SBR to B/F/TAF
Nominal Day
Lower Limit
Upper Limit
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1
Week 48
336
2
504
336
2
504
Week 96
672
505
840
672
505
840
Week k (k 
is every 48 
weeks after 
previous 
visit)
k*7
(k-24)*7+1
(k+24)*7
k*7
(k-24)*7+1
(k+24)*7
NA  Not applicable 
Note: For the B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the randomized phase; 
Note: For the SBR to B/F/TAF group, Study Day 1 is the first dose date of the B/F/TAF received in the extension phase. 
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Window
Depending on the statistical analysis method, single values are required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time to event analysis would not require one value per analysis window. When a single value is 
needed, the following rule(s) will be used. 
If multiple nonmissing numeric observations exist in a window, records will be chosen as 
follows:

For baseline, the latest available record on or prior to the first dose date of randomized study 
drug will be selected. If there are multiple records with the same collection time or no 
collection time recorded on the same day, average will be used for the baseline value, except 
for HIV-1 RNA (see below).


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
For postbaseline visits:
For CD4+ cell count, CD4%, and HBV DNA, the record(s) collected on the latest day in 
the window will be selected for analysis.
For other numeric observations (ie, except HIV-1 RNA, CD4+ cell count, CD4%, and 
HBV DNA), the record(s) collected on the day closest to the nominal day for that visit 
will be selected. If there are 2 days equidistant from the nominal day, the later day will be 
selected.
For any numeric observations except HIV-1 RNA, if there are multiple records on the
selected day, the arithmetic mean will be used. 

For baseline and postbaseline HIV-1 RNA, the latest (considering both collection date and 
time) record(s) in the window will be selected. If both “HIV RNA Taqman 2.0” and “HIV 
RNA Repeat” (ie, the HIV-1 RNA result obtained from an additional aliquot of the original 
sample) are available with the same collection time, the results from the “HIV RNA Repeat” 
will be selected for analysis purposes; otherwise, if there are multiple “HIV RNA 
Taqman 2.0” records with the same collection time, the geometric mean will be taken for 
analysis purposes.
If multiple valid nonmissing categorical observations exist in a window, records will be chosen 
as follows:

For baseline, the last available record on or prior to the first dose date of randomized study 
drug will be selected. If there are multiple records with the same collection time or no 
collection time recorded on the same day, the value with the lowest severity will be selected 
(eg, normal will be selected over abnormal for safety ECG findings).

For postbaseline visits, the most conservative value within the window will be selected 
(eg, abnormal will be selected over normal for safety ECG findings).


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
4.1.1.
Subject Enrollment
All summaries on subject enrollment have been performed as part of the Week 48 analysis, and
will not be repeated in the final analysis.
4.1.2.
Subject Disposition
The summary of subject disposition will be provided by treatment group and overall for all 
Randomized subjects. This summary will include the number of subjects randomized, subjects 
randomized but never treated, subjects in the Safety Analysis Set, and subjects in the FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:

Subjects completing study drug in the randomized phase

Prematurely discontinuing study drug in the randomized phase (with summary of reasons for 
discontinuing study drug)

Subjects completing study in the randomized phase

Prematurely discontinuing from study in the randomized phase (with summary of reasons for 
discontinuing study).

Subjects completing study drug in the randomized phase and not entering the extension phase

Subjects completing study drug in the randomized phase and entering the extension phase

Subjects discontinuing study drug in the randomized phase but entering the extension phase

Subjects entering in the extension phase 

Subjects treated in the extension phase

Subjects completing study drug in the extension phase

Prematurely discontinuing study drug in the extension phase (with summary of reasons for 
discontinuing study drug in the extension phase)

Subjects completing the study in the extension phase

Prematurely discontinuing from study in the extension phase (with summary of reasons for 
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The denominator for the percentages of subjects in each category in the randomized phase, 
including “Subjects entering in the extension phase”, will be the number of subjects in the safety 
analysis set. The denominator for the percentages of subjects in each category in the extension 
phase will be the number of subjects who were treated in extension phase.
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
4.2.
Extent of Study Drug Exposure and Adherence
4.2.1.
Duration of Exposure to Study Drug
Duration of exposure to study drug will be defined for both the randomized phase analysis and 
the all B/F/TAF analysis. For the randomized phase analysis, the terms “first dose date” and 
“last dose date” in the text below refer to the first dose date and last dose date defined for the 
randomized phase analysis. For the all B/F/TAF analysis, the terms “first dose date” and 
“last dose date” in the text below refer to the first dose date and last dose date defined for the all
B/F/TAF phase analysis. Duration of exposure is defined as (last dose date first dose date + 1), 
regardless of temporary interruptions in study drug administration, and will be expressed in 
weeks using up to 1 decimal place (eg, 4.5 weeks).
Duration of exposure to study drug will be summarized using descriptive statistics (sample size, 
mean, SD, median, Q1, Q3, minimum, and maximum) and as the number and percentage of 
subjects exposed for specified periods, eg, ≥4 weeks (28 days), ≥8 weeks (56 days), ≥12 weeks 
(84 days), ≥ 24 weeks (168 days), ≥ 36 weeks (252 days), ≥48 weeks (336 days), ≥60 weeks 
(420 days), ≥72 weeks (504 days), ≥84 weeks (588 days), ≥96 weeks (672 days), ≥108 weeks 
(756days), ≥120 weeks (840 days), ≥ 132 weeks (924 days), ≥144 weeks (1008 days), etc. 
Summaries will be provided by treatment group for subjects in the Safety Analysis Set and All 
B/F/TAF Analysis Set for the randomized phase analysis and all B/F/TAF analysis, respectively. 
No inferential statistics will be provided. 
Time to premature discontinuation of randomized study drug will be analyzed using the 
Kaplan-Meier (KM) method by treatment group based on the safety analysis set and the all 
B/F/TAF analysis set, respectively. The log rank test will be used to compare the difference in 
study drug exposure between the 2 randomized treatment groups for the safety analysis set only. 
A plot of KM estimates for the time to permanent discontinuation of study drug by treatment 
group will be generated for the safety analysis set only. Subjects who completed study drug will 
be censored at the last dose date. 
4.2.2.
Adherence to Study Drug Regimen
Adherence to study drug regimen will be defined for both the randomized phase analysis and the 
all B/F/TAF analysis. For randomized phase analysis, study drug accountability (ie, numbers of 
pills of B/F/TAF dispensed and returned) is only captured for subjects randomized into the B/F/TAF 
group. Therefore, adherence will only be computed for Treatment Group 1 in the randomized phase 
of the study. For all B/F/TAF analysis, adherence will be computed for both treatment groups as 
defined in Section 3.1.2.


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Study drug regimen adherence will be computed based on pill counts for B/F/TAF only. The 
numbers of pills of each study drug dispensed and returned are captured on study drug 
accountability forms.
Adherence (%) of B/F/TAF will be calculated as follows:
Adherence (%) = 100 ×
 No. of pills taken
Total No. of pills prescribed
= 100 ×
∑No. of pills taken at each dispensing period[']
∑No. of pills prescribed at each dispensing period[)]
[1]
Number of pills taken at a distinct dispensing period for B/F/TAF is calculated as the minimum of (a) the daily number of 
pills prescribed multiplied by the duration of treatment at the dispensing period, and (b) the number of pills taken (number 
of pills dispensed minus the number of pills returned). Total number of pills taken is determined by summing the number of 
pills taken from all evaluable dispensing periods.
[2]
Number of pills prescribed at a distinct dispensing period for B/F/TAF is calculated as the daily number of pills prescribed 
multiplied by the duration of treatment at the dispensing period. Total number of pills prescribed is determined by summing 
the number of pills prescribed from all evaluable dispensing periods.
The duration of treatment at a dispensing period for B/F/TAF is calculated as the minimum of 
(a) the last returned date of B/F/TAF at a dispensing period, (b) date of premature 
discontinuation of B/F/TAF, and (c) next pill dispensing date of B/F/TAF, minus dispensing date 
of B/F/TAF.
The next pill dispensing date is the following dispensing date of the study drug regardless of the 
bottle return date. 
For a record where the number of pills returned was missing (with “Yes” answered for “Was 
Bottle returned?” question), it is assumed the number of pills returned was zero. If the number of 
pills dispensed was missing or any study drug bottle was not returned or the bottle return status 
was unknown, all records in that dispensing period for that study drug will be excluded from 
both denominator and numerator calculation.
Overall adherence will be calculated for both the randomized phase analysis and the all B/F/TAF 
analysis. Overall adherence for the randomized analysis will use all data from the entire dosing 
period up to the date of permanent discontinuation of the randomized study drug. Overall 
adherence for the all B/F/TAF analysis will use all available data for subjects who actually 
received B/F/TAF in the randomized phase, and data on or after the first dose date of extension 
B/F/TAF for subjects who actually received SBR in the randomized phase and received at least 
1 dose of B/F/TAF in the extension phase.
Descriptive statistics for B/F/TAF adherence (sample size, mean, SD, median, Q1, Q3, 
minimum, and maximum) along with the number and percentage of subjects belonging to 
adherence categories (eg, < 80%, ≥ 80% to < 90%, ≥ 90% to < 95%, ≥ 95%) will be provided for 
subjects who return at least 1 bottle of randomized study drug, and who have calculable 
adherence for the randomized phase analysis and the all B/F/TAF analysis, respectively. No
inferential statistics will be provided.


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4.3.
Protocol Deviations
A listing will be provided for all randomized subjects who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met. A listing of subjects who 
received the wrong study drug will also be provided.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, race, and ethnicity) and baseline characteristics 
(eg, body weight, height, and body mass index [BMI]) will be summarized by treatment group 
and overall using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
for continuous data and by the number and percentage of subjects for categorical data. The 
summaries of demographic data and baseline characteristics will be provided by treatment for 
subjects in the Safety Analysis Set and All B/F/TAF Analysis Set, respectively. 
For the randomized phase analysis using safety analysis set, the Cochran-Mantel-Haenszel 
(CMH) test (ie, general association statistic for nominal data) will be used to compare the 2 
treatment groups for categorical data, and the 2-sided Wilcoxon rank sum test will be used to 
compare the 2 treatment groups for continuous data. No statistical comparisons will be made for 
the all B/F/TAF analysis.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics for subjects in the safety analysis set and all B/F/TAF analysis 
set, respectively:

HIV-1 RNA categories (copies/mL): (a) < 50, (b) ≥ 50

CD4+ cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, 
(d) ≥350 to < 500, and (e) ≥500

Mode of infection (HIV risk factors)

HIV disease status

eGFRCG (mL/min)

HIV/HBV co-infection status (Yes/No/Missing, only for all B/F/TAF analysis, 
see Section 9.1 for definition) 

HIV/HCV co-infection status (Yes/No/Missing, only for all B/F/TAF analysis, 
see Section 9.2 for definition)
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For the randomized phase analysis using Safety Analysis Set, the Cochran-Mantel-Haenszel 
(CMH) test (ie, general association statistic for nominal data) will be used to compare the 2 
treatment groups for categorical data, and the 2-sided Wilcoxon rank sum test will be used to 
compare the 2 treatment groups for continuous data. No statistical comparisons will be made for 
the all B/F/TAF analysis.
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will be coded using the current version of Medical Dictionary for Regulatory 
Activities (MedDRA).


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6. 
EFFICACY ANALYSES 
Analyses for all the primary and secondary efficacy endpoints have been 
Week 48 anal sis and will not be re eated in the final anal sis. 
6.1. 
Primary Efficacy Endpoint 
Version 1.0 
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA ~ 50 copies/mL at 
Week 48 as detennined by the US Food and Drug Administration (FDA)-defined snapshot 
algorithm {U. S. Department of Health and Human Services 2015}. 
The statistical analysis methods for the primary efficacy endpoint were described in the Week 48 
SAP and the analysis was perfonned in the Week 48 analyses. 
6.2. 
Secondary Efficacy Endpoints 
6.2.1. 
Definition of the Secondary Efficacy Endpoints 
The secondary efficacy endpoints include: 
• 
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as detennined by 
the US FDA-defined snapshot algorithm 
• 
The change from baseline in CD4+ cell com1t at Week 48 
All the secondary efficacy endpoints indicated above have been perfonned in the Week 48 
analyses. Endpoints based on the snapshot algorithm will not be repeated in the final analysis. 
However, change from baseline in CD4 cell counts at each visit will be perfonned for both 
randomized phase analysis and all B/F/T AF analysis in this final analysis. 
6.2.2. 
Analysis of CD4+ Cell Count 
The analysis of CD4 cell com1t will be based on on-treatment data (ie, up to 1 day after the last 
dose date of study drug) using the FAS for the randomized phase analysis and the All B/F/TAF 
Analysis Set for the all B/F/T AF analysis. 
The changes from baseline in CD4+ cell count at each visit including visit past Week 48 will be 
smmnarized by treatment group using descriptive statistics. For the randomized phase analysis, the 
differences in changes from baseline in CD4+ cell count between the 2 treatment groups and the 
associated 95% CI will be constructed using analysis of variance (ANOVA) models, including 
treatment group as a fixed effect. No statistical comparisons will be made for the all B/F/TAF 
analysis. 
The mean and 95% CI of change from baseline in CD4+ cell count over time will be plotted for 
the FAS in the randomized phase analysis. 
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Changes From Protocol-Specified Efficacy Analyses 
No change from protocol-specified efficacy analysis is planned. 
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7.
SAFETY ANALYSES
Safety data will be summarized for the subjects in the Safety Analysis Set for the randomized 
phase analysis and the All B/F/TAF Analysis Set for the all B/F/TAF analysis, unless specified
otherwise. For randomized phase, only the following analysis will be done: 
(1) Treatment-Emergent Adverse Events: Overall Summary; (2) Treatment-Emergent Adverse 
Events by Preferred Term;(3) Treatment-Emergent Laboratory Abnormalities. No treatment 
comparison will be performed for all B/F/TAF analysis. All safety data from both phases of the 
study will be included in data listings.
For the randomized phase analysis, the terms “study drug start date (ie, the first dose date)”, 
“study drug stop date (ie, the last dose date)”, and “baseline” in the text below refer to the 
first dose date, the last dose date, and baseline defined for the randomized phase analysis; the 
term “study drug” in the text below refer to the randomized study drugs.
For the all B/F/TAF analysis, the terms “study drug start date (ie, the first dose date)”, 
“study drug stop date (ie, the last dose date)”, and “baseline” in the text below refer to the 
first dose date, the last dose date, and baseline defined for the all B/F/TAF phase analysis; the 
term “study drug” in the text below refer to B/F/TAF.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of Medical Dictionary for
Regulatory Activities (MedDRA). System organ class (SOC), high-level group term (HLGT), 
high-level term (HLT), preferred term (PT), and lowest-level term (LLT) will be provided in the 
AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe) or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will be left as 
“missing” in the data listings. The missing category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.


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7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Drug Pharmacovigilance and 
Epidemiology (PVE) database before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of the study drug, or 

Any AEs leading to premature discontinuation of study drug
For the randomized phase analysis, the AE onset date will be compared with the first and 
last dose dates for the randomized phase analysis. For the all B/F/TAF analysis, the AE onset 
date will be compared with the first and last dose dates for the All B/F/TAF phase analysis.
7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, the month and year (or year alone if month is not recorded) of onset determine 
whether an AE is treatment emergent. 
The event is considered treatment emergent if both of the following 2 criteria are met:

The month and year (or year) of the AE onset is the same as or after the month and year 
(or year) of the first dosing date of study drug, and

The month and year (or year) of the AE onset is the same as or before the month and year 
(or year) of the date corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date on or after the first dosing date of study drug, will be considered to be treatment emergent. 
In addition, an AE with the onset date missing and incomplete stop date with the same or later
month and year (or year alone if month is not recorded) as the first dosing date of study drug will
be considered treatment emergent.


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7.1.6.
Summaries of Adverse Events and Death
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group using both Safety Analysis Set and All 
B/F/TAF Analysis Set, respectively. For other AEs described below, summaries will be provided 
by SOC, PT, and treatment group using the All B/F/TAF Analysis Set only:

Any Grade 2, 3, or 4 treatment-emergent AEs

Any Grade 3 or 4 treatment-emergent AEs

All treatment-emergent study drug-related AEs

Any Grade 2, 3, or 4 treatment-emergent study drug-related AEs

Any Grade 3 or 4 treatment-emergent study drug-related AEs

All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs

All treatment-emergent AEs that caused premature discontinuation from study drug
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs using both the Safety 
Analysis Set and All B/F/TAF Analysis Set, respectively. Treatment-emergent deaths observed 
in the study will be also included in this summary.
Treatment-emergent death refers to deaths that occurred between the first dose date and the last 
dose date plus 30 days (inclusive).
Multiple events will be counted only once per subject in each summary. Treatment-emergent 
AEs will be summarized and listed first in alphabetic order of SOC and HLT within each SOC 
(if applicable), and then by PT in descending order of total frequency within each SOC. For 
summaries by severity grade, the most severe grade will be used for those Treatment-emergent 
AEs that occurred more than once in an individual subject during the study.
In addition to the above summary tables, all TEAEs, Grade 3 or 4 TEAEs, treatment-emergent 
study drug-related AEs, Grade 2, 3, or 4 treatment-emergent study drug-related AEs, and 
treatment-emergent SAEs will be summarized by PT only, in descending order of total
frequency.


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In addition, data listings for all AEs regardless of the study phases will be provided for the
following:

All AEs

Grade 3 and 4 AEs

SAEs

Study Drug-Related SAEs

Deaths report

AEs leading to premature discontinuation of study drug
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Stage 3 Opportunistic Illnesses in HIV
On an ongoing basis, AEs will be reviewed for events that might meet the definition of stage 3 
opportunistic illnesses in HIV that are indicative of an AIDS-defining diagnoses (see Protocol 
Appendix 5). The Gilead medical monitor will review the possible stage 3 opportunistic illnesses
and approve the events that meet the definition. Events that meet the stage 3 opportunistic illness
definition of an AIDS-Defining Diagnosis will be listed.
7.1.7.2.
Cardiovascular or Cerebrovascular Events
Preferred terms for defining cardiovascular or cerebrovascular events are selected based on 
relevant Standardised MedDRA Query (SMQ). The selected PT listing was provided by 
Gilead PVE and reviewed by Gilead medical monitors (see details in Appendix 3).
The number and percentage of subjects with treatment-emergent cardiovascular or 
cerebrovascular events and serious cardiovascular or cerebrovascular events by PT will be 
provided by treatment group based on the All B/F/TAF Analysis Set. Statistical comparisons of 
the subject incidence rates between the 2 treatment groups will not be performed. A data listing 
of cardiovascular or cerebrovascular events will be provided.
7.1.7.3.
Hepatic Events
Preferred terms for defining hepatic events are from 15 relevant SMQs, which are identified as 
non-infectious and non-congenital hepatobiliary disorders. The selected PT listing was provided 
by Gilead PVE and reviewed by Gilead medical monitors (see details in Appendix 4).
The number and percentage of subjects with treatment-emergent hepatic events and serious 
hepatic events by PT will be summarized by treatment group based on the All B/F/TAF Analysis 
Set. Statistical comparisons of the subject incidence rates between the 2 treatment groups will 
not be performed. A data listing of hepatic events will be provided.


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7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the All 
B/F/TAF Analysis Set, except that the summaries (number and percentage of subjects) for 
treatment-emergent laboratory abnormalities will be provided for subjects in the Safety Analysis 
Set and All B/F/TAF Analysis Set, respectively. The analysis will be based on values reported in 
conventional units. When values are below the LOQ, they will be listed as such, and the imputed 
value will be used for the purpose of calculating summary statistics as specified in Section 3.7.
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately for all data 
collected from both phases of the study. Values falling outside of the reference range and/or 
having a severity grade of 1 or higher on the Gilead Grading Scale for Severity of Adverse 
Events and Laboratory Abnormalities will be flagged in the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values 

Values at each postbaseline analysis window

Change from baseline at each postbaseline analysis window

Percentage change from baseline to each postbaseline analysis window (if specified)
A baseline laboratory value will be defined as the last nonmissing value obtained on or prior to 
the date of first dose of study drug. Change from baseline to a postbaseline visit will be defined 
as the postbaseline value minus the baseline value. The mean, median, Q1, Q3, minimum, and 
maximum values will be displayed to the reported number of digits; SD values will be displayed 
to the reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 0.
Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 

Calcium corrected for albumin (mg/dL)
serum calcium (mg/dL) + 0.8 × (4.0
albumin (g/dL))
Toxicity grading for calcium will be applied based on the corrected values.


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Estimate GFR
The following formulae will be used to calculate eGFRCG: 

eGFRCG (mL/min)  [(140 age (yrs)) × weight (kg) × (0.85 if female)] / (SCr (mg/dL) × 72), 
where weight is total body mass in kilograms and SCr is serum creatinine.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used for assigning toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction (ie, increased, 
decreased) will be presented separately.
If there is any laboratory toxicity grading scale overlapping with the normal reference ranges 
(eg, grade 1 scale overlaps with normal reference ranges), laboratory values that are within the 
normal range will be grade 0, except for lipid tests.
For triglycerides, LDL, and cholesterol, protocol-specified toxicity grading scale is for fasting 
test values, so nonfasting lipid results (or lipid results without a known fasting status) will not be 
graded or summarized by toxicity grades. 
For the international normalized ratio (INR) of prothrombin time (PT), protocol-specified toxicity 
grading scale depends on the upper limit of normal range (ULN). While the ULN of INR depends 
on whether the subject is taking anticoagulant medication or not (ie, Not taking oral anticoagulant: 
0.8 1.2; Taking oral anticoagulant: 2.0 3.0), this information is not collected by the reference 
laboratory. As a result, INR will be graded by assuming subject is not taking an oral anticoagulant, 
which is a conservative approach that may lead to over-reporting of abnormalities for INR. 
Consequently, INR and PT will not be included in summaries of laboratory abnormalities, but will 
be included in listings for the following reasons: 1) INR and PT are reflexive tests; 2) only the 
absolute values, not the toxicity grade, are needed for subject management purposes; and 
3) more importantly, the toxicity grades for INR may be over-reported.
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to 30 days after permanent 
discontinuation of the study drug. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
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Fasting glucose and nonfasting glucose (including glucose results without a known fasting 
status) are graded based on different grading scales as specified in the protocol.
Treatment-emergent laboratory abnormalities will be summarized for fasting glucose. Maximum 
postbaseline grade, instead of treatment-emergent grade, for nonfasting glucose 
(including glucose results without a known fasting status) will be summarized, as nonfasting 
glucose was not assessed at baseline visit for most of the subjects; therefore, an abnormality is 
treatment-emergent or not cannot be determined for these subjects.
Both urine RBC based on microscopic examination, labeled as Hematuria (Quantitative), and 
urine blood based on dipstick, labeled as Hematuria (Dipstick), are assessed routinely and 
assigned a toxicity grade in this study. Urine RBC based on microscopic examination will be 
presented in laboratory toxicity summary tables and listings while urine blood based on dipstick 
will be presented in the listings only.
7.2.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities

Treatment-emergent Grade 2, 3, and 4 laboratory abnormalities 
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
any nonmissing postbaseline values up to 30 days after the last dose date.
A by-subject listing of all treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities will be provided by subject ID number and visit in 
chronological order. This listing will include all test results that were collected throughout the 
study for the lab test of interest, with all applicable severity grades displayed.
7.2.3.
Metabolic Laboratory Evaluations 
For metabolite assessments, including fasting glucose and the lipid panel (ie, total cholesterol, 
triglycerides, LDL, HDL, total cholesterol to HDL ratio), only those measurements under fasting 
status will be summarized. 
In addition, the number and percentage of subjects who took lipid-modifying medication at the 
first dose of B/F/TAF and subjects who initiated the lipid modifying medication while receiving 
B/F/TAF will be provided. 
A lipid modifying medication is defined as a medication with ATC2 term  “LIPID 
MODIFYING AGENTS” and CMDECOD containing the wording of “STATIN”.


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


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7.2.5.2.
Urine Retinol Binding Protein to Creatinine Ratio, Beta-2-Microglobulin to 
Creatinine Ratio, and Urine Creatinine
Baseline, postbaseline, change from baseline, and percentage change from baseline in urine RBP 
to creatinine ratio and beta-2 microglobulin to creatinine ratio will be summarized by treatment 
group and visit using descriptive statistics. 
Median (Q1, Q3) percentage change from baseline in urine RBP to creatinine ratio and 
beta-2 microglobulin to creatinine ratio over time will be plotted by treatment group. 
Baseline, postbaseline, and change from baseline in urine creatinine will be summarized by 
treatment group and visit using descriptive statistics. 
7.2.5.3.
Albuminuria by Quantitative Assessment
The baseline, postbaseline, changes from baseline, and percentage change from baseline in urine 
albumin to creatinine ratio (UACR) will be summarized by treatment group and visit using 
descriptive statistics. 
The number and percentage of subjects with UACR < 30 mg/g versus ≥30 mg/g will be 
summarized by baseline category at Weeks 24, 48, 72, 96 and based on the last on-treatment 
value (ie, data collected after the first dose date up to 1 day after the last dose date of B/F/TAF) 
{KDIGO Guideline Development Staff 2013}.
Median (Q1, Q3) percentage change from baseline in UACR over time will be plotted by 
treatment group.
7.3.
Body Weight, Height, and Vital Signs
Descriptive statistics will be provided by treatment group for vital signs and body weight as 
follows:

Baseline values

Values at each postbaseline analysis window

Change from baseline to each postbaseline analysis window 
A baseline value will be defined as the last nonmissing value obtained on or prior to the date of 
first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 0. No formal statistical testing is planned.


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A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. In the same listing, a by-subject listing of body weight, height, and BMI 
will be provided.
7.4.
Prior and Concomitant Medications
7.4.1.
Antiretroviral Medications
Any nonstudy ARV medications used prior to, during, or after the study (if collected) and study 
ARV medications used during study for subjects randomized to the SBR group are all recorded 
on the ARV eCRF. All ARV medications recorded on the ARV eCRF will be coded using the 
Gilead-modified World Health Organization (WHO) Drug Dictionary for ARV medications. The 
WHO preferred name and drug code will be attached to the clinical database. All ARV 
medications recorded on the ARV eCRF will be listed. No inferential statistics will be provided.
7.4.2.
Prior Antiretroviral Medications
Prior ARV medications are defined as ARV medications taken on or up to 2 days prior to the 
first dose date of randomized study drug based on ARVs reported on ARV eCRF
(see Appendix 5 for details). For summary purposes, prior ARV medications will be classified 
into one of the following regimens. The number and percentage of subjects in each prior ARV 
regimen will be summarized as part of baseline disease characteristics table.

Boosted ATV + ABC/3TC

Boosted DRV + ABC/3TC

Boosted ATV + FTC/TDF

Boosted DRV + FTC/TDF 
7.4.3.
Concomitant Non-Antiretroviral Medications
Concomitant non-ARV medications (ie, medications other than study drug that are taken while 
receiving study drug) will be coded using the WHO Drug Dictionary. The WHO preferred name 
and drug code will be attached to the clinical database. Use of concomitant medications from the 
Study Day 1 up to the last dose date of the study drug will be summarized (number and 
percentage of subjects) by treatment group, WHO drug class and preferred name for the All 
B/F/TAF Analysis Set. Multiple drug use (by preferred drug name) will be counted only once per 
subject. The summary will be sorted alphabetically by decreasing total frequency of preferred 
drug name. For drug with the same frequency, sorting will be done alphabetically.


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If the start or stop date of non-ARV medications is incomplete, the month and year (or year 
alone, if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARVs are concomitant or not. The medication is concomitant if the month and year of the 
start or stop (or year of the start or stop, if month is not recorded) of the medication does not 
meet either of the following criteria:

The month and year (or year alone) of start of the medication is after the last dose date of the 
study drug

The month and year (or year alone) of stop of the medication is before the first dose date of 
the study drug
If the start and stop date of non-ARV medications are complete, the start date is not after the last 
dose date of the study drug and the stop date is not before the first dose date of the study drug, or 
the non-ARV medications are marked as ongoing and start date is on or before the last dose date
of the study drug, the non-ARV medications are concomitant of the study.
Subjects with any non-ARV concomitant medications will be listed. No inferential statistics will 
be provided.
7.5.
Electrocardiogram Results
A shift table of the investigators’ assessment of ECG results at each scheduled postbaseline visit 
compared with baseline values will be presented by treatment group using the following 
categories: normal; abnormal, not clinically significant; abnormal, clinically significant; or 
missing. The number and percentage of subjects in each cross-classification group of the shift 
table will be presented. Subjects with a missing value at baseline or postbaseline will not be 
included in the denominator for percentage calculation. Summary of ECG results will be 
presented by treatment group for the All B/F/TAF Analysis Set. No inferential statistics will be 
provided.
A by-subject listing for ECG assessment results will be provided by subject ID number and visits 
in chronological order.
7.6.
Other Safety Measures
A data listing will be provided for subjects experiencing pregnancy during the study. Physical 
examination was not collected in the eCRF. Therefore, it will not be included in the analysis. 
7.7.
Subject Subgroup for Safety Endpoints
Incidence of all treatment-emergent AEs will be repeated within each subgroup defined in 
Section 3.4.1 using the All B/F/TAF Analysis Set.
7.8.
Changes from Protocol-Specified Safety Analyses
No change from protocol-specified safety analysis is planned.


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


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9.
SPECIAL POPULATION ANALYSES
Special population analyses will be performed using all B/F/TAF analyses set only.
9.1.
Analyses for HIV/HBV Coinfected Subjects
Subjects with HIV/HBV coinfection at baseline are defined as subjects meet any of the following 
two criteria on or prior to the first dose date of B/F/TAF: 

Positive HBsAg on or prior to the first dose date of B/F/TAF, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 29 IU/mL) on or prior to the first dose date of B/F/TAF
The following analyses will be provided by treatment and overall for subjects with HIV/HBV 
coinfection at baseline: 

The proportion of subjects with HBV DNA < 29 IU/mL at baseline and Week 48 by M
E 
approach 

The change from baseline in log10 HBV DNA (log10 IU/mL)

Treatment-emergent adverse events overall summary

Treatment-emergent adverse events by SOC, HLT, and PT

Treatment-emergent laboratory abnormalities

The change from baseline for liver-related laboratory tests, including ALT, AST, ALP, 
gamma-glutamyl transferase (GGT), total bilirubin, direct and indirect bilirubin 

Listing of AEs

Listing of liver-related laboratory tests and HBV DNA results 
HBV DNA will be analyzed using observed, on-treatment data (ie, data collected up to the 1 day 
after the last dose date of B/F/TAF) for subject in the all B/F/TAF analysis set with HIV/HBV 
coinfection at baseline. 
Subjects with incident HIV/HBV coinfection while on study drug (if any) are defined as subjects 
who are not HIV/HBV coinfected at baseline and meet any of the following criteria:

Positive HBsAg after the first dose date of B/F/TAF and on or prior to the last dose date of 
B/F/TAF plus 1 day, or

Negative HBsAg, negative HBsAb, positive HBcAb, and quantifiable HBV DNA 
(ie, HBV DNA ≥ 29 IU/mL) after the first dose date of B/F/TAF and on or prior to the 
last dose date of B/F/TAF plus 1 day, or


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
Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the first dose date of B/F/TAF and on or prior to the last dose date of 
B/F/TAF: Acute hepatitis B, Chronic hepatitis B, Congenital hepatitis B infection, Hepatitis 
B, Hepatitis B core antibody positive, Hepatitis B DNA assay positive, Hepatitis B surface 
antigen positive, Hepatitis B virus test positive.
The following listings will be provided for subjects with incident HIV/HBV coinfection while on 
study drug (if any): 

Listing of AEs

Listing of liver-related laboratory tests and HBV DNA results
9.2.
Analyses for HIV/HCV Coinfected Subjects
Subjects with HIV/HCV coinfection at baseline are defined as subjects with positive HCV 
antibody (HCVAb) and quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) on or prior to the 
first dose date of B/F/TAF. The following analyses will be conducted for subjects with 
HIV/HCV coinfection at baseline: 

Treatment-emergent AEs overall summary

Treatment-emergent AEs by SOC, HLT, and PT

Treatment-emergent laboratory abnormalities

Listing of AEs

Listing of liver-related laboratory tests and HCV RNA results
Subjects with incident HIV/HCV coinfection while on study drug are defined as subjects who are 
not HIV/HCV coinfected at baseline and meet any of the following criteria:

Positive HCVAb after the first dose date of B/F/TAF and on or prior to the last dose date of 
B/F/TAF plus 1 day with baseline HCVAb Negative or missing, or

Quantifiable HCV RNA (ie, HCV RNA ≥ 15 IU/mL) after the first dose date of B/F/TAF and 
on or prior to the last dose date of B/F/TAF plus 1 day, or

Experience any of the following adverse events (ie, selected MedDRA PTs from the SMQ of 
“Liver Infections”) after the first dose date of B/F/TAF and on or prior to the last dose date of 
B/F/TAF plus 1 day: Acute hepatitis C, Chronic hepatitis C, Hepatitis C, Hepatitis C 
antibody positive, Hepatitis C RNA positive, Hepatitis C virus test positive.


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The following listings will be provided for subjects with incident HIV/HCV coinfection while on
study drug:

Listing of AEs

Listing of liver-related laboratory tests and HCV RNA results


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


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11.
SOFTWARE
SASVersion 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
nQuery Advisor® Version 6.0 (Statistical Solutions, Cork, Ireland) is to be used for sample size 
and power calculation. 
Phoenix WinNonlin® Version 6.4 (Certara USA, Inc., Princeton, NJ, USA.) is to be used for all 
PK analyses.


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


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13.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Region Definition
Appendix 3.
Cardiovascular or Cerebrovascular Events
Appendix 4.
Hepatic Events
Appendix 5.
Programming Specification


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Appendix 1.
Study Procedures Table
Study Procedures
Screeninga
Day 1b
End of Weeke,v
Post-Week 48e,w
30-Day 
Follow-
upu
Early Study 
Drugs DCc
4
8
12
24
36
48
Every 12 Weeksx
Informed Consent
X
Medical History
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed 
Physical Exam 
X
X
Xd
Xd
Xd
X
Xd
X
Xd,aa
Xd,f
Xf
12-Lead ECG (performed supine)
X
X
X
X
Xm
Xbb
SF-36, HIV Symptoms Distress 
Module, WPAI, and UCLA SCTC 
GIT 2.0 Questionnaires
X
X
X
X
VAS Adherence Questionnaire
X
X
X
X
X
X
X
X
Height
X
Vital signs (blood pressure, pulse, 
respiration rate, and temperature), 
including Weight 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
Xj
Estimated Glomerular Filtration Rate 
(eGFR)
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
Evaluation of renal tubular functionl
X
X
X
Xj


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Study Procedures
Screeninga
Day 1b
End of Weeke,v
Post-Week 48e,w
30-Day 
Follow-
upu
Early Study 
Drugs DCc
4
8
12
24
36
48
Every 12 Weeksx
Plasma and Urine Storage Sample 
X
X
X
X
X
X
X
X
X
Whole Blood sample for potential 
HIV DNA genotyping
X
HCV Serology
X
X
Xm
HIV-1 Genotype/Phenotype e
Xe
Single PK Samplen
X
X
X
Trough and post dose PK Sampleo
X
X
Randomizationy
X
Provide subject dosing diary to 
Treatment Group 1 subjects
X
X
X
X
X
HBV blood panel
Xq
Xs
Xs
Xs,z
Xs,z
Plasma HBV DNAr
X
X
X
X
X
X
X
X
X
Study Drug Dispensationt
X
X
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Initiation of the first dose of study drug is to take place in clinic following completion of study procedures on the Day 1 visit.
c
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
Week 48 Visit even if the subject discontinues study drug.
d
Symptom directed physical examination as needed. 
e
HIV 1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2 3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV 1 RNA and HIV 1 genotype and phenotype (reverse transcriptase, protease and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema.
f
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained.
g
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN) At Day 1, Weeks 12, 24, 48 and every 24 weeks post Week 48, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of 
CCI
CCI


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the chemistry profile. Additionally, TSI-I will be analyzed at Screening, Day I, Weeks 24, 48, followed by every 24 weeks post Week 48, and Early Study Dmgs 
Discontinuation visit. PT/INR will be perfom1ed at Day I. 
Version 0.1 
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments. 
j 
Every 24 weeks post Week 48 Visit 
k 
CBC with differential and platelet count. 
I 
Evaluation of renal tubular function includes analyses of urine albumin, urine creatinine, urine protein, retinal binding protein and beta 2 microglobulin 
m 
To be perfom1ed every 48 weeks post Week 48 Visit 
n 
A single PK blood sample will be collected at any time pre or post dose from subjects in Treatment Group I. 
o 
A trough PK blood sample will be collected between 20 28 hours following the last dose from subjects in Treatment Group I. Following an observed dose, a single post dose 
blood sam le will be collected between I and 4 hours ost dose. 
I' 
q 
oo pane w1 
vims sur ace antigen (HBsAg), Hepatitis B vims surface antibody (1-IBsAb) and Hepatitis B vims core antibody 
(1-IBcAb)). 
r 
To be perfom1ed for subjects who meet the definition of HBV infection 
s 
At Weeks 12, 24, 48, 72, 96, and 120, for subjects who meet the definition of HBV infection at any visit, the following will be perfom1ed by the central laboratory: 
1-IBsAb, HBsAg (qualitative and quantitative) and 1-IBeAg (if negative reflex, 1-IBeAb). 
Study dmg GS 9883/F/T AF to be dispensed to Treatment Group I subjects. 
u 
For the purpose of scheduling a 30 Day Follow Up Visit, a ± 6 days window may be used. Those subjects who prematurely discontinue study dmg and continue in the study 
through at least one subsequent visit after the Early Study Dmg Discontinuation Visit will not be required to complete the 30 Day Follow Up Visit. 
v 
Study visits are to be completed within ± 2 days of the protocol specified visit date based on the Day I visit through Week 12 and completed within ± 6 days through to 
Week 36, unless otherwise specified. The visit window at Weeks 48 will be ± 6 weeks of the protocol specified visit date. 
w 
Visit window of± 6 days for study visits post Week 48. 
x 
GS 9883/F/TAF FDC will be dispensed to subjects participating in the study post Week 48 visit. 
y 
Randomization may be perfomied up to 3 days prior to the in clinic Day I visit provided that all screening procedures have been completed and subject eligibility has been 
confimied. 
z 
At Weeks 48, 96 and 144, for subjects who do NOT meet the definition ofHBV infection at any visit, the following will be perfomied by the central laboratory: 
1-IBsAg, HBsAb, and 1-IBcAb. Subjects who are 1-IBsAg and/or HBcAb positive will have a reflex test for HBV DNA (viral load). 
aa 
A complete physical exam should be done every 48 weeks post Week 48 Visit. 
bb 
Only to be completed for Early Study Dmgs Discontinuation Visits up to Week 48. 
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Appendix 2.
Region Definition
Region
Country Name
State
No. of Subjects in 
Safety Analysis Set or 
FAS (N=577)
Total No. of Subjects by 
Region in Safety Analysis 
Set or FAS (N=577)
Region 1
AUSTRALIA (AUS)
31
64
CANADA (CAN)
33
Region 2
BELGIUM (BEL)
5
172
FRANCE (FRA)
34
GERMANY (DEU)
61
ITALY (ITA)
8
SPAIN (ESP)
10
UNITED KINGDOM (GBR)
54
Region 3
UNITED STATES (USA)
CA
53
68
UNITED STATES
WA
9
UNITED STATES
HI
6
Region 4
UNITED STATES
TX
39
53
UNITED STATES
CO
4
UNITED STATES
AZ
5
UNITED STATES
KS
5
Region 5
UNITED STATES
MO
14
48
UNITED STATES
MI
7
UNITED STATES
MN
5
UNITED STATES
IL
18
UNITED STATES
KY
4
Region 6
UNITED STATES
NY
5
31
UNITED STATES
MA
9
UNITED STATES
DC
14
UNITED STATES
VA
3
Region 7
UNITED STATES
GA
21
52
UNITED STATES
SC
7
UNITED STATES
NC
16
UNITED STATES
LA
1
UNITED STATES
TN
7
Region 8
UNITED STATES
FL
60
89
UNITED STATES
PR*
18
DOMINICAN REPUBLIC (DOM)
11
*
PR  Puerto Rico.
Note: In general, a region is defined as multiple sites combined based on geographical locations. For example, for international 
studies, sites from each country or multiple neighboring counties were combined; and for US studies, sites from each state or 
multiple neighboring states were combined.


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Appendix 3.
Cardiovascular or Cerebrovascular Events
An adverse event record will be flagged as a cardiovascular or cerebrovascular event if its 
MedDRA PT is included in the pre-specified PT list, which includes all PTs from the narrow 
search of the following 3 SMQs under MedDRA 22.1 provided by Gilead PVE and reviewed by 
Gilead medical monitors.
SMQ Source
Cardiovascular or Cerebrovascular 
Events
Ischaemic central nervous system vascular conditions (SMQ) 
Narrow Scope Term
Myocardial infarction (SMQ) Narrow Scope Term
Other ischaemic heart disease (SMQ) Narrow Scope Term


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Appendix 4.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT included in the 
prespecified PT list, which includes all PTs from the broad search of the following 15 SMQs 
under MedDRA 22.1 provided by Gilead PVE and reviewed by Gilead medical monitors. 
SMQ Source
Hepatic Events (HEP)
Biliary neoplasms benign (incl cysts and polyps) (SMQ)
Biliary malignant tumours (SMQ)
Biliary tumours of unspecified malignancy (SMQ)
Biliary system related investigations, signs and symptoms (SMQ)
Biliary tract disorders (SMQ)
Gallbladder related disorders (SMQ)
Gallstone related disorders (SMQ)
Cholestasis and jaundice of hepatic origin (SMQ)
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ)
Hepatitis, non-infectious (SMQ)
Liver neoplasms, benign (incl cysts and polyps) (SMQ)
Liver malignant tumours (SMQ)
Liver tumours of unspecified malignancy (SMQ)
Liver related investigations, signs and symptoms (SMQ)
Liver-related coagulation and bleeding disturbances (SMQ)


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Appendix 5.
Programming Specification
1) AGE calculated as follows: two AGE variables will be derived, one is for randomized phase 
analysis, and one is for all B/F/TAF analysis.
I.
AGE (years) for randomized phase analysis is calculated from the number of days 
between the date of birth (DOB) and Day 1 (randomized phase first dose date);
II.
AGE (years) for all B/F/TAF phase analysis is calculated from the number of days 
between the date of birth (DOB) and Day 1 (first dose date of B/F/TAF);
a) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
b) Divide the result in (b) by 12,
c) AGE  the integer of the result in (c),
d) If the DOB and randomized phase Day 1 have the month in common and the 
birthday is later in the month than the date of Study Day 1, then subtract one from 
the AGE result above.
For subjects randomized and never dosed with study drug, age will be calculated from the 
date of randomization.
2) Subjects in the all randomized analysis set are defined as subjects randomized into the study. 
IXRSRAND is the source to determine whether the subject is randomized (ie, subject with 
nonmissing RGMNDTN in the IXRSRAND dataset) and confirmed by the eCRF ENROLL 
dataset (ie, ENROLLYN  “Yes” in ENROLL dataset).
3) Randomized treatment (ie, TRT01P in ADSL) are derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if subject 
took at least 1 dose of randomized study drug and assigned as blank if subject never dosed.
4) In disposition table, the reasons for premature discontinuation are displayed in the order as 
they appear on the eCRF.


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5) For disposition table, please follow the following specification to classify subjects into 
different categories:
Q2: "Did subject 
complete study drug 
dosing as specified per 
protocol?” during 
Randomized phase in 
“Study Drug 
Completion" eCRF form
Q3: "Did subject 
complete study drug 
dosing as specified per 
protocol?” during 
Extension study phase in 
"Study Drug 
Completion" eCRF form
Q4: “Did the subject 
complete the protocol
planned duration of 
the study?” in 
“Study Completion” 
eCRF form
Case 
ID
Q1: “Do subject 
participate in 
the extension 
phase of the 
study?” in 
“Extension 
Entry” eCRF
Blank or no 
Record / No
No
Blank or no Record
No
1
No
No
Blank or no Record
Yes
2
Yes
Blank or no Record
Yes
3
Yes
Yes
No
No
4
Yes
Yes
Yes
5
No
No
No
6
No
Yes
Yes
7

Subjects completing study drug in the randomized phase are subjects with Case ID  3, 4, and 5.

Subjects prematurely discontinuing study drug in the randomized phase are subjects with Case ID  1, 2, 6, and 7. 

Subjects completing study in the randomized phase are subjects with Case ID  2, 3, 4, and 5.

Subjects prematurely discontinuing from study in the randomized phase are subjects with Case ID  1.

Subjects completing study in the randomized phase and not entering the extension phase are subjects with Case ID  2 and 3

Subjects who entered extension phase of the study are subjects with Case ID  4, 5, 6, and 7.

Subjects who entered extension phase of the study and prematurely discontinuing study drug in the extension phase are 
subjects with Case ID  4 and 6.

Subjects who entered extension phase of the study and completing study in the extension phase are subjects with 
Case ID
5 and 7.

Subjects who prematurely discontinuing study drug in the randomized phase and entered the extension phase are subjects 
with CaseID
6 and 7. 

Subjects who prematurely discontinuing study drug in the randomized phase and entered and completed in the extension 
phase are subjects with CaseID  7. 

Data query will be issued for other cases not listed in above table.
6) Body mass index (BMI)
BMI and BSA will be calculated only at randomized phase baseline as follows:

BMI
 (weight [kg]) / (height [meters]2)
Baseline height and weight in the randomized phase of the study will be used for this 
calculation. 
7) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
a) CMH test for nominal variable (Y), the p-value from general association test should be 
used for nominal variable:
proc freq order=adsl;
tables trtgrp * Y /cmh /*general association test*/
run;


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b) CMH test for ordinal variable (Y), the p-value from row mean score test should be used 
for ordinal variable:
proc freq order=adsl;
tables trtgrp * Y / cmh2 ; /*row mean score test*/
run;
c) Wilcoxon rank sum test for continuous variable (Y), the p-value from the normal 
approximation two-sided test should be used for continuous variable:
proc npar1way wilcoxon data=adsl;
class trtgrp; 
var Y;  
run;
Note: “Not Permitted”, “Unknown”, or missing categories will be excluded for percentage 
calculation and also be excluded for p-value generation for categorical data analysis 
(eg, CMH test or Fisher exact test), except for Mode of Infection (HIV Risk Factors), where 
“Unknown” will be included for percentage calculation since a subject may fit more than 
1 HIV risk factors. For this variable, percentage may add up to be more than 100% and no 
p-value will be generated.
Subjects with Race  “Not Permitted” will also be excluded to define Race subgroup 
(ie, back vs. nonblack) for efficacy subgroup analysis.
8) SAS code for the treatment comparison for duration of exposure. The p-value from log rank 
test should be used. 
proc lifetest data=adsl method=km; 
time TRTDURD*ESDD (0); /*Derived ESDD from COMT01FL, where ESDD
= 0 indicates censored observation (ie, subject is still on
study drug)*/
strata TRT01AN;
label TRTDURD = "Duration of Exposure (Days)";
run;
9) Last Dose Date and Last Study Date
Last Dose Date (ie, TR01EDTC and TR01EDT for randomized phase last dose date, and 
TR02EDTC and TR02EDT for extension phase last dose date) in ADSL.
Randomized Phase Last Dose Date:
For B/F/TAF subjects with a partial last dosing date (ie, month and year of last dose are 
known), the minimum of {(extension phase first dose date 1 day, if available), (the latest of 
the dispensing dates of study drug bottles, study drug start dates and end dates (based on EX 
dataset with Study Phase  “Randomized Treatment”), and the imputed last dose date 
[day imputed as 15])} will be used as the final imputed last dose date. However, if dispensing 
date’s month is after last dose date’s month, data query is needed. If subject died and the 
death date is complete (ie, not partial date) and before the imputed last dose date, the 
complete death date should be used as the imputed last dose date.


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For SBR subject with a partial last dosing date (ie, month and year of last dose are known), 
the minimum of {(extension phase first dose date 1 day, if available), (the latest of the 
study drug start dates and end dates (based on ARV dataset) and the imputed last dose date 
[day imputed as 15])} will be used as the final imputed last dose date. However, if dispensing 
date’s month is after last dose date’s month, data query is needed. If subject died and the 
death date is complete (ie, not partial date) and before the imputed last dose date, the 
complete death date should be used as the imputed last dose date.
Please note the follows: 

When defining randomized phase last dose date for SBR subjects, please only include 
records on “Current” ARV eCRF for the randomized phase of the study, defined as 
“Current” ARV records with start date prior to the extension phase 1st dose date for 
subjects entering the extension phase of the study or all “Current” ARV records for 
subjects not entering the extension phase of the study.

When defining randomized phase last dose date for SBR subjects, subjects might have 
baseline regimen switched from 1 pill of ATV or DRV to 1 pill of ATV/COBI or 
DRV/COBI. Such change is not considered as an ARV switch. The randomized phase 
last dose date will be defined based on the end date of ATV/COBI or DRV/COBI. 
Extension Phase Last Dose Date:
For subjects with a partial last dosing date (ie, month and year of last dose are known), the 
minimum of { (the latest of the dispensing dates of study drug bottles, study drug start dates 
and end dates (based on EX dataset with Study Phase  “Extension Treatment”), and the 
imputed last dose date [day imputed as 15])} will be used as the final imputed last dose date.
However, if dispensing date’s month is after last dose date’s month, data query is needed. If 
subject died and the death date is complete (ie, not partial date) and before the imputed last 
study date, the complete death date should be used as the imputed last study date.
Last Study Date is the latest of the randomized or extension phase (if available) study drug 
start dates and end dates, the clinic visit dates, and the laboratory visit dates, including the 
30-day follow-up visit date. If study drug start dates or end dates is partially missing (ie, only 
year and month are known), the day will be imputed as 15 for the purpose of this analysis.
10) Toxicity Grades:
Two toxicity grades variables will be derived, one is for randomized phase analysis, and one 
is for all B/F/TAF analysis. For toxicity grade variable for all B/F/TAF analysis, the baseline 
will be adjusted based on the first dose of B/F/TAF, as specified in SAP Section 7.2.2.1. As a 
result, treatment-emergent laboratory abnormalities will be summarized for both randomized 
phase analysis and all B/F/TAF analysis, respectively, following the same rule bellows.
a) For toxicity grade summaries, include all postbaseline graded results up to 30 days after 
the last dose of study drug, not just those used in by-visit summaries.


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b) For glucose grading, as specified in SAP Section 7.2.2.1, the treatment-emergent flag 
cannot be determined for nonfasting glucose (including glucose results without a known 
fasting status). As a result, these records will be excluded from the “Maximum 
Treatment-emergent Toxicity Grade” summary in the “Treatment-emergent Laboratory 
Abnormalities” or “Treatment-emergent Grade 3 or 4 Laboratory Abnormalities” 
summary tables. In addition, fasting glucose and non-fasting glucose will be listed as two 
separate laboratory tests in the “Laboratory Abnormalities” and “Grade 3 or 4 Laboratory 
Abnormalities” listings. Only a maximum postbaseline toxicity flag will be displayed and 
the treatment-emergent flag will not be displayed for nonfasting glucose as the 
treatment-emergent flag cannot be determined for nonfasting glucose. 
CCI


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


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Battery
Lab Test Label Used in 
l-labtox Listing
Toxicity 
Direction
Lab Test Label Used in 
t-labtox Table
Triglycerides (Fasting)
Increase
Triglycerides (Fasting, Increased)
LDL (Fasting)
Increase
LDL (Fasting, Increased)
Urea Nitrogen (BUN)
Increase
Urea Nitrogen (Increased)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Uric Acid
Decrease
Uric Acid (Hypouricemia)
Prothrombin Intl. Normalized 
Ratio (INR)
Increase
N/A
Prothrombin Time (PT)
Increase
N/A
Urinalysis
Urine Blood
Increase
N/A
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine Protein
Increase
Urine Protein (Proteinuria)
Urine RBC
Increase
Urine RBC (Hematuria, Quantitative)
Note: Prothrombin Intl. Normalized Ratio (INR) and Prothrombin Time (PT) were graded based on the protocol defined toxicity 
grade scale. The results and toxicity grade will be listed in listing, but not be summarized in lab toxicity summary table. 
13) Renal related laboratory evaluation
a) Unit conversion for renal safety tests derived from related tests with conventional units

Urine RBP (ug/L) to creatinine (mg/dL) ratio: 1 (ug/L) / (mg/dL)  100 × ug/g

Urine Beta-2-microglobulin (mg/L) to creatinine (mg/dL) ratio: 1 (mg/L) / (mg/dL)  
105 ug/g 

Urine Albumin (mg/dL) to creatinine (mg/dL) ratio: 1 (mg/dL) / (mg/dL)  
1000 × mg/g
b) Calculation of ratios: 
To calculate laboratory ratios (eg, urine RBP to creatinine ratio), the lab value of each 
test in the ratio needs to be from the same accession number; if any test value used for the 
ratio calculation from the same accession number is missing, then the ratio is not 
calculable (ie, missing). 
14) Non-study drug ARV medications (ie, ARV medications other than study drug that are taken 
while receiving study drug) will be flagged in “Antiviral Medication” listing. Please note that 
for ARVs recorded on the “Prior ARV” eCRF will NOT be considered as ARVs taken during 
study. All Prior ARVs with missing end date will be queried to confirm the ARVs were 
stopped before the randomized phase 1st dose date. 
15) Lipid modifying medication analyses:

Lipid modifying medication is defined to be the concomitant medication with ATC2 
term
 “LIPID MODIFYING AGENTS” and CMDECOD contains wording of 
“STATIN” in the ADCM dataset.


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
Subjects who took lipid modifying medications at first dose of B/F/TAF refer to the 
subjects who use of the lipid modifying agents at study day 1 of all B/F/TAF analysis. 
More specifically, subjects with “Lipid Modifying Agent Use at First Dose of B/F/TAF” 
include those subjects in all B/F/TAF analysis set with: 1) any selected CM record with 
the start date ≤the first dose date of B/F/TAF, and 2) the end date of the selected CM 
record is ongoing or the end date of the selected CM record ≥the first dose date of 
B/F/TAF.

Subjects who initiated lipid modifying medications while subject receiving B/F/TAF 
includes the following subjects in the all B/F/TAF analysis set: (1) for subjects who 
permanently discontinued study drug with any selected CM record started after the 
first dose date of B/F/TAF and on or prior to last dose of B/F/TAF. (2)for subjects who 
meet criteria (1) above, if they took lipid modification medications before first dose of 
B/F/TAF, they will NOT be considered initiated lipid modifications while receiving 
B/F/TAF for the all B/F/TAF analysis.

For lipid modifying medications with start date completely unknown, we assume the start 
date is on or before the first dose date of B/F/TAF, lipid modifying medication was 
considered as being taken at first dose of B/F/TAF if the end date is not prior to the 
first dose date of B/F/TAF (ie, the end date is on or after the first dose date of B/F/TAF, 
completely unknown, or ongoing).

Lipid modifying medications with the start date on or prior to the first dose date of 
B/F/TAF and the end date completely unknown were considered as being taken at 
first dose of B/F/TAF.
16) For figures, if at a visit where n (sample size) for any treatment group ≤ 5, data for that 
treatment group will not be displayed at the visit in figure (except the KM figure), but all data 
will be included in the corresponding table summary.
17) Prior ARV regimen 
All subjects will have one of the following prior ARV regimen identified based on ARVs 
entered in the ARV eCRF.

Boosted ATV + ABC/3TC

Boosted DRV + ABC/3TC

Boosted ATV + FTC/TDF

Boosted DRV + FTC/TDF
Boosted agent is RTV or COBI taken as a separate pill or as a single tablet with protease 
inhibitor (DRV or ATV). For analysis purpose, we are not interested in type of boosting 
agent. We would only like to identify PI (ATV or DRV) and NRTI (ABC/3TC or FTC/TDF) 
used at baseline.


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Definition of Prior (Baseline) Regimen: please use ARV dataset and include all prior and/or 
current ARVs (ARV.INGRED where ARV.CMSCAT ’Prior ARV” or “Current ARV”) with 
taken on or up to 2 days prior to the randomized phase first dose date excluding 
ARV.INGRED  ‘COBI’ or “RTV”. For subjects with missing prior ARV regimen based on 
above logics, please apply the ARV start date window up to 14 days prior to the randomized 
phase first dose date to account for subjects with potential ARV interruption around Study 
Day 1. Please use the following table to define baseline regimen: 
If INGRED contains ONLY the specified ARVs: 
Re-code as follows for baseline regimen 
ABC 3TC ATV
Boosted ATV + ABC/3TC
ABC 3TC ATV COBI
Boosted ATV + ABC/3TC
ABC 3TC ATV
Boosted ATV + ABC/3TC
ABC 3TC ATV COBI
Boosted ATV + ABC/3TC
3TC ABC DRV
Boosted DRV + ABC/3TC
3TC ABC DRV COBI
Boosted DRV + ABC/3TC
ABC 3TC DRV
Boosted DRV + ABC/3TC
ABC 3TC DRV COBI
Boosted DRV + ABC/3TC
FTC TDF ATV
Boosted ATV + FTC/TDF
FTC TDF ATV COBI
Boosted ATV + FTC/TDF
FTC TDF ATV
Boosted ATV + FTC/TDF
FTC TDF ATV COBI
Boosted ATV + FTC/TDF
FTC TDF DRV
Boosted DRV + FTC/TDF
FTC TDF DRV COBI
Boosted DRV + FTC/TDF
FTC TDF DRV
Boosted DRV + FTC/TDF
FTC TDF DRV COBI
Boosted DRV + FTC/TDF
Note: if subject has ARVs other than specified in the first column above, please leave baseline regimen blank and query for data 
issues. 
18) HIV/HBV and HIV/HCV Coinfection:

The following table presents the HBV and HCV tests with all possible values. Values that 
have an asterisk after them denote a “positive” (or “quantifiable” for HBV DNA and 
HCV RNA) result while all others denote a “negative” result.
Label
LBTESTCD
LBTEST
Possible Values
HBsAg
CNT63
Hep B Surface Ag
“Positive”*, “Positive, Confirmed”*,“Negative”
HBsAg
ATT2
Hep. B Surf. Ag Qual( 70) PS
“Repeat reactive, confirmed”*, “Repeat Reactive 
Unconfirmed”, “Non Reactive”
HBsAb
CNT353
anti Hep B Surface Ag2 Qual
“Positive”*, “Negative”
HBcAb
CNT68
Hepatitis B Core Total
“Positive”*, “Negative”
HBV DNA
GET1883
HBV DNA CAP/CTM 
2.0 EDTA CL
“No HBV DNA detected”, “<20 IU/mL HBV DNA 
detected”, “>170000000”*, NUMERICAL VALUE when 
< 29 IU/mL, NUMERICAL VALUE when ≥29 IU/nL*
HCVAb
CNT350
Hepatitis C Virus Antibody
“Positive”*, “Indeterminate”, “Negative”
HCV RNA
GET1881
HCV RNA CAP/CTM 
2.0EDTA CL
“No HCV RNA detected”, “<15 IU/mL HCV RNA 
detected”, NUMERICAL VALUE*


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


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


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Version 1.0
CONFIDENTIAL
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One AE will be included either in the randomized phase or extension phase, but not both, 
except that an AE is treatment-emergent in the randomized phase, but continuing into 
extension phase which will be counted as treatment-emergent for both phases.
When an AE with missing onset date and according to the following rules for incomplete 
dates, an AE is treatment emergent in the extension phase, then the AE will be included in 
extension phase and considered treatment emergent in extension phase only.
Events with Missing Onset Day and/or Month
An AE is treatment emergent if the following 3 criteria are met:
1) The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
2) The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
3) End date is as follows: 
a.
The (complete) end date is on or after the first dose date, or
b. The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
c.
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
criteria specified in 3) above.
21) The number of decimal places in reporting p-values should be as follows:
a) values less than 0.001 < 0.001
b) values 0.001 to less than 0.10 round to 3 decimal places
c) values 0.10 and greater round to 2 decimal places
22) TSH: Conversions between 2nd and 3rd generations
TSH was analyzed by 2 different assays in the study: 2nd generation (Beckman Coulter, 
Reference # 33820) and 3rd generation (Beckman Coulter, Reference # B63284). Samples 
collected before October 14th, 2019 were using TSH 2nd generation assay. Samples collected 
on or after October 14th, 2019 were using 3rd generation assay. Comparative studies 
demonstrated that the 2nd and 3rd generations are comparable and the results are showed in 
the following table. For this analysis, we do not request any conversion and display collected 
results. 


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TSH 
2nd generation (μIU/mL) 
(HYPERSensitive TSH)
Beckman Material Number 33820
3rd generation(μIU/mL)
(TSH 3rd IS)
Beckman Material Number 100T; B63284
LLOQ 
0.02
0.01
AMR 
0.02- 100.0
0.01 – 46.0
ULOQ 
3200
3220
RR 
Male and Female: 0.34- 5.60
Male and Female* (non-pregnant): 0.45-
5.33
Serum
Correlation
Deming Regression
Y= 0.942X +0.1515
Correlation Coefficient
0.9951
Bias (% Bias)
-0.327 (-4.059%)
23) LDL: Conversions between 2nd and 3rd generations
LDL was analyzed by 2 different assays in the study: 2nd generation (including RCT2394, 
RCT2312, and RCT2811) and 3rd generation (RCT3870). Samples collected at earlier visits 
were analyzed using LDL 2nd generation assay. Samples collected at later visits were 
analyzed using LDL 3rd generation assay. The conversion formulas are as follow:

2nd Gen (mmol/L)  (3rd Gen - 0.0626)/0.882

3rd Gen (mmol/L)  (0.882 x 2nd Gen) + 0.0626
For this analysis, since LDL samples were analyzed by 2nd generation assay at Baseline, we 
only requested conversion from 3rd generation to 2nd generation.
For the analysis of change from baseline in fasting direct LDL: the sample analyzed by LDL 
3rd generation assay will be converted to 2nd generation as a new record with test codes of 
LIP.LDL.00.02 in raw data. During ADaM stage, a derived parameter code (FLDL2) for 
“Fasting LDL Cholesterol 2ND GEN Combined” will be generated to pool the records from 
both original (including test codes RCT2394, RCT2312, and RCT2811) and converted 
(LIP.LDL.00.02) 2nd generation results to calculate the change from baseline in fasting 
direct LDL.
For the analysis of toxicity grade for fasting direct LDL: toxicity grade will be based on the 
Gilead grading results (ie, toxgrg) from original values before conversion. In another words, 
during ADaM stage, a derived parameter code (FLDLTOX) for “Fasting LDL Cholesterol 
for Toxicity” will be generated to pool the records from 2nd generation (including RCT2394, 
RCT2312, and RCT2811) and 3rd generation (ie, RCT3870) to derive treatment-emergent 
toxicity grades, maximum postbaseline toxicity grades, etc.


GS-US-380-1878-Final-SAP-v1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Project Team
Leader eSigned
22-Apr-2020
23:33:13
Biostatistics eSigned
23-Apr-2020
00:30:39
PPD
PPD--

Prot_006.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Study Clinical 
Program Manager: 
Gilead Medical Monitor: 
Gilead Study Director: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and 
Efficacy of Switching from Regimens Consisting of Boosted Atazanavir or 
Danmavir plus either Emt:ricitabine/Tenofovir or Abacavir/Lamivudine to 
GS-9883/Emtiicitabine/Tenofovir Alafenamide in Virologically Suppressed 
HIV -1 Infected Adults 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
125589 
2015-004011-20 
NCT02603107 
HIV -1 Infection 
GS-US-380-1878 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Original: 
Amendment 1 
Amendment2 
PPD 
PPU 
PPD 
E1in Quirk, MD 
PPD 
PPD 
PPD 
PPU 
PPD 
21 October 2015 
19 Febmruy 2016 
19 October 2016 
CONFIDENTIALITY STATEMENT 
The inf01m ation contained in this document, pmiicularly 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 Boru·d or Independent Ethics Committee. The infonnation is only to be used by you in 
connection with authorized clinical studies of the investigational dmg described in the protocol. 
You will not disclose any of the infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessmy to obtain infonned consent from those 
persons to whom the dmg may be administered. 


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Amendment 2 
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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................12
1.
INTRODUCTION ..............................................................................................................................................15
1.1.
Background ............................................................................................................................................15
1.2.
GS-9883 .................................................................................................................................................16
1.2.1.
General Information .............................................................................................................16
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................16
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................18
1.3.
Information about Emtricitabine (Emtriva®, FTC).................................................................................27
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)..................................................................27
1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) 
or Fixed Dose Combination emtricitabine/tenofovir alafenamide 
(FTC/TAF)...........................................................................................................................27
1.4.2.
Clinical Trials of FTC/TAF as part of 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) ...........................29
1.5.
Information about GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) ...........................31
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, 
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................31
1.6.
Rationale for this Study..........................................................................................................................32
1.7.
Rationale for Dose Selection..................................................................................................................33
1.8.
Risk Benefit Assessment for this Study .................................................................................................35
1.9.
Compliance ............................................................................................................................................35
2.
OBJECTIVES.....................................................................................................................................................36
3.
STUDY DESIGN................................................................................................................................................37
3.1.
Endpoints ...............................................................................................................................................37
3.2.
Study Design..........................................................................................................................................37
3.3.
Study Treatments ...................................................................................................................................37
3.4.
Duration of Treatment............................................................................................................................37
3.5.
Biomarker Testing..................................................................................................................................38
3.5.1.
Biomarker Samples for Optional Pharmacogenomic Research............................................38
3.5.2.
Additional Sample Storage...................................................................................................39
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................43
5.1.
Randomization .......................................................................................................................................43
5.2.
Description and Handling.......................................................................................................................43
5.2.1.
Formulation..........................................................................................................................43
5.2.2.
Packaging and Labeling .......................................................................................................44
5.2.3.
Storage and Handling...........................................................................................................44
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide ....................................44
5.4.
Prior and Concomitant Medications.......................................................................................................45


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5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................46
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................47
6.
STUDY PROCEDURES ....................................................................................................................................48
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................48
6.2.
Pretreatment Assessments......................................................................................................................48
6.2.1.
Screening Visit .....................................................................................................................48
6.2.2.
Day 1 Assessments...............................................................................................................50
6.3.
Randomization .......................................................................................................................................52
6.4.
Treatment Assessments (Week 4 -48)....................................................................................................52
6.5.
Treatment Assessments (Post Week 48) ................................................................................................55
6.5.1.
Post Week 48 Assessments ..................................................................................................55
6.6.
Post-treatment Assessments ...................................................................................................................57
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................57
6.6.2.
30-Day Follow-Up ...............................................................................................................58
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................59
6.8.
Other Evaluations...................................................................................................................................60
6.8.1.
Markers of Renal Tubular Function .....................................................................................60
6.9.
Blood and Urine Storage........................................................................................................................60
6.10.
Assessments for Premature Discontinuation from Study.......................................................................60
6.11.
End of Study...........................................................................................................................................60
6.12.
Post Study Care......................................................................................................................................60
6.13.
Virologic Failure....................................................................................................................................60
6.13.1.
Management of Virologic Rebound .....................................................................................60
6.13.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Drug 
Discontinuation, or Week 48................................................................................................62
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................63
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................63
7.1.1.
Adverse Events.....................................................................................................................63
7.1.2.
Serious Adverse Events........................................................................................................63
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................64
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................64
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................64
7.2.2.
Assessment of Severity ........................................................................................................65
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................65
7.3.1.
Adverse Events.....................................................................................................................65
7.3.2.
Serious Adverse Events........................................................................................................66
7.4.
Gilead Reporting Requirements.............................................................................................................67
7.5.
Toxicity Management ............................................................................................................................67
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................67
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................68
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................68
7.5.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................68
7.5.5.
Management of Hyperbilirubinemia ....................................................................................70
7.5.6.
Management of Possible Abacavir Hypersensitivity Reaction.............................................71
7.5.7.
Management of Potential Hepatobiliary Toxicity ................................................................71
7.5.8.
On-Treatment Hepatitis C Management...............................................................................72
7.6.
Special Situations Reports......................................................................................................................72
7.6.1.
Definitions of Special Situations..........................................................................................72
7.6.2.
Instructions for Reporting Special Situations.......................................................................73


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8.
STATISTICAL CONSIDERATIONS................................................................................................................75
8.1.
Analysis Objectives and Endpoints........................................................................................................75
8.1.1.
Analysis Objectives..............................................................................................................75
8.1.2.
Primary Endpoint .................................................................................................................75
8.1.3.
Secondary Endpoint .............................................................................................................75
8.2.
Analysis Conventions.............................................................................................................................75
8.2.1.
Analysis Sets ........................................................................................................................75
8.3.
Data Handling Conventions ...................................................................................................................77
8.4.
Demographic Data and Baseline Characteristics ...................................................................................77
8.5.
Efficacy Analysis ...................................................................................................................................77
8.5.1.
Primary Analysis..................................................................................................................77
8.5.2.
Secondary Analyses .............................................................................................................79
8.6.
Safety Analysis.......................................................................................................................................79
8.6.1.
Extent of Exposure...............................................................................................................79
8.6.2.
Adverse Events.....................................................................................................................80
8.6.3.
Laboratory Evaluations ........................................................................................................80
8.6.4.
Other Safety Evaluations......................................................................................................80
8.7.
Pharmacokinetic Analysis......................................................................................................................81
8.8.
Patient Reported Outcomes (PRO).........................................................................................................81
8.9.
Sample Size............................................................................................................................................81
8.10.
Independent Data Monitoring Committee..............................................................................................81
8.11.
Analysis Schedule ..................................................................................................................................82
9.
RESPONSIBILITIES..........................................................................................................................................83
9.1.
Investigator Responsibilities ..................................................................................................................83
9.1.1.
Good Clinical Practice..........................................................................................................83
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................83
9.1.3.
Informed Consent.................................................................................................................83
9.1.4.
Confidentiality......................................................................................................................84
9.1.5.
Study Files and Retention of Records ..................................................................................84
9.1.6.
Case Report Forms...............................................................................................................85
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................86
9.1.8.
Inspections............................................................................................................................86
9.1.9.
Protocol Compliance............................................................................................................86
9.2.
Sponsor Responsibilities ........................................................................................................................87
9.2.1.
Protocol Modifications.........................................................................................................87
9.2.2.
Study Report and Publications .............................................................................................87
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................87
9.3.1.
Payment Reporting...............................................................................................................87
9.3.2.
Access to Information for Monitoring..................................................................................88
9.3.3.
Access to Information for Auditing or Inspections ..............................................................88
9.3.4.
Study Discontinuation..........................................................................................................88
10.
REFERENCES ...................................................................................................................................................89
11.
APPENDICES ....................................................................................................................................................91
Appendix 1.
Investigator Signature Page....................................................................................................92
Appendix 2.
Study Procedures Table..........................................................................................................93
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................96
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............97
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................120


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Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................122
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........20
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................21
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................22
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following GS-9883 
Administration Under Fasting Conditions and Corresponding Protein-Adjusted IQ95 
Values (GS-9883 PK Analysis Set)........................................................................................23
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................34
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)..........................................45
Table 5-2.
Prior and Concomitant Medications (Boosted ATV and DRV regimen) ...............................46
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................23
Figure 3-1.
Study Schema.........................................................................................................................38
Figure 6-1.
Virologic Rebound Schema....................................................................................................62


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Amendment 2 
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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety 
and Efficacy of Switching from Regimens Consisting of Boosted
Atazanavir or Darunavir plus either Emtricitabine/Tenofovir or 
Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir 
Alafenamide in Virologically Suppressed HIV-1 Infected Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125589
2015-004011-20
NCT02603107
Study Centers 
Planned:
Approximately 150 centers in North America, Europe, Asia Pacific, 
and Latin America
Objectives:
The primary objective of this study is as follows:

To evaluate the efficacy of switching to a fixed dose combination 
(FDC) of GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus continuing on a regimen consisting of 
boosted atazanavir (ATV) or darunavir (DRV) plus either 
emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or
abacavir/lamivudine (ABC/3TC) in HIV-1 infected adult subjects 
who are virologically suppressed as determined by the proportion 
of subjects with HIV-1 RNA ≥50 copies/mL at Week 48
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of the two treatment groups
through Week 48
Study Design:
Randomized, open-label, multicenter, active-controlled study to 
evaluate the safety and efficacy of switching to a FDC of 
GS-9883/F/TAF in HIV-1 infected subjects who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a regimen consisting of 
ritonavir (RTV) or cobicistat (COBI) boosted ATV or DRV plus 
either FTC/TDF or ABC/3TC for ≥ 6 months prior to screening.


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Amendment 2 
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Subjects who provide written consent and meet all eligibility criteria 
will be randomized in a 1:1 ratio to one of the following 
two treatment groups:
Treatment Group 1: Switch to a FDC of GS-9883/emtricitabine/
tenofovir alafenamide (GS-9883/F/TAF) administered orally,
once daily without regard to food (n=260)
Treatment Group 2: Remain on current antiretroviral regimen 
consisting of ritonavir or cobicistat boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC administered orally, once daily with food 
(n=260)
Investigators must provide a prescription to subjects in Treatment 
Group 2. Subjects in Treatment Group 2 are responsible for obtaining 
their ARV regimen.
Randomization will be stratified by the prior treatment regimen group 
(i.e., TDF containing regimens [ritonavir or cobicistat boosted ATV 
or DRV plus FTC/TDF] and non-TDF containing regimens [ritonavir 
or cobicistat boosted ATV or DRV plus ABC/3TC]) at screening.
Number of Subjects 
Planned:
Approximately 520 subjects in total.
Approximately 260 subjects in each Treatment Group 1 and 
Treatment Group 2
Target Population:
HIV-1 infected subjects ≥18 years old who are virologically 
suppressed (HIV-1 RNA < 50 copies/mL) on a stable regimen 
containing boosted ATV or DRV plus either FTC/TDF or ABC/3TC 
for 6 months prior to screening and who are INSTI naive.
Duration of 
Treatment:
Duration of this study is at least 48 weeks.
At the Week 48 Visit, subjects in a country where GS-9883/F/TAF 
FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for an additional 96 weeks, or until the product 
becomes accessible to subjects through an access program, or until 
Gilead Sciences elects to discontinue the study in that country, 
whichever occurs first.
Subjects who complete the study through Week 48 Visit and do not 
further continue participation in the study, will be required to return 
to the clinic 30 days after the completion of the study drugs for a 30-
Day Follow-Up Visit


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Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Currently receiving a once daily antiretroviral regimen consisting 
of ritonavir or cobicistat boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC for 6 months preceding the screening 
visit

Currently on a stable regimen for ≥6 months preceding the 
Screening visit with documented plasma HIV-1 RNA 
< 50 copies/mL for ≥ 6 months preceding the Screening visit (or 
undetectable HIV-1 RNA level according to the local assay being 
used if the limit of detection is ≥50 copies/mL).
Prior changes in antiretroviral regimen are only allowed due 
to tolerability issues or for regimen simplification. 
Unconfirmed virologic elevations of ≥ 50 copies/mL 
(transient detectable viremia, or “blip”) prior to screening are
acceptable. (If the lower limit of detection of the local HIV-1 
RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the 
plasma HIV-1 RNA level cannot exceed 50 copies/mL on 
two consecutive HIV-1 RNA tests)

HIV-1 RNA levels < 50 copies/mL at Screening Visit

No previous use of any approved or experimental integrase strand 
transfer inhibitor (INSTI)

No documented or suspected resistance to FTC, TFV, ABC or 
3TC, including but not limited to the reverse transcriptase 
resistance mutations K65R and M184V/I

Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 48 weeks. 
For all eligible subjects, blood will be collected at Day 1,Weeks 4, 8, 
12, and then every 12 weeks through Week 48. Laboratory analyses 
(hematology, chemistry, and urinalysis), HIV-1 RNA, CD4+ cell 
count, and complete or symptom-directed physical examinations will 
be performed at the Screening, Day 1 and all subsequent study visits.
Urine will be collected and stored for possible evaluations of renal 
tubular function including urine albumin, urine creatinine, urine 
protein, retinol binding protein and beta-2 microglobulin.
Adverse events and concomitant medications will be assessed at each 
visit.


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Test Product, Dose, 
and Mode of 
Administration:
FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily without 
regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Current antiretroviral drug regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC 
administered orally, once daily with food.
Criteria for 
Evaluation:
Safety:
Adverse events, clinical laboratory tests to evaluate the safety and 
tolerability of the treatment regimens.
Efficacy:
The primary efficacy endpoint is the proportion of subjects with HIV-
1 RNA ≥ 50 copies/mLat Week 48 as defined by the United States 
(US) Food and Drug Administration [FDA]-defined snapshot 
algorithm.
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
Pharmacokinetics:
An intensive pharmacokinetic (PK) substudy will be performed at the 
Weeks 4 or 8 visits in a subset of Treatment Group 1 subjects (target 
n=24) at study sites able to conduct this testing.
For all subjects in Treatment Group 1 who are on study drug, a single 
anytime pre or post-dose PK blood sample will be collected at 
Weeks 8, 24 and 36.
For all subjects in Treatment Group 1 who are on study drug, a trough 
PK blood sample will be obtained 20-28 hours following the last dose 
at Weeks 4 and 12.  Following an observed dose, one post-dose PK 
blood sample will be collected between 1 and 4 hours post-dose.
For intensive PK substudy, the following PK parameters for GS-9883 
may be explored as applicable:
Cmax, Tmax, Clast, Tlast, Ctau,T1/2, AUCtau,AUC0-last , Vz/F, CLss/F.
The concentration of GS-9883 may be summarized using descriptive 
statistics. The pharmacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concentrations may be 
analyzed and PK parameters may be summarized as applicable.


GS-9883/F/T AF 
Protocol GS-US-380-1878 
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Optional Genomic 
Testing: 
Patient Reported 
Outcomes: 
Statistical Methods: 
CONFIDENTIAL 
PD 
Final 
Amendment2 
Shmi Fmm 36 Health Smvey (SF-36), HIV Symptoms Distress 
Module Index, Work Productivity and Activity Impailment 
Questionnaii·e (WP AI), and UCLA Sclerode1ma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) will be 
administered at Day 1, Weeks 4, 12 and 48. Visual Analog Scale 
(VAS) Adherence Questionnaii·e will be administered at Day 1 and all 
visits up to Week 48. 
The primruy analysis will consist of a non-inferiority evaluation of 
switching to GS-9883/F/TAF versus maintaining an antii·etrovii·al 
dmg regimen consisting of boosted ATV or DRV plus either 
FTCITDF or ABC/3TC (i.e., boosted PI plus 2 nucleoside reverse 
transcriptase inhibitors (NRTis) [boosted PI + 2 NRTis]) with respect 
to the propmiion of subjects with HIV -1 RNA~ 50 copies/mL as 
defined by the US FDA-defined snapshot algorithm at Week 48. It 
will be concluded that GS-9883/F/TAF is non-inferior to the boosted 
PI + 2 NRTis if the upper bound of the 2-sided 95% confidence 
interval (CI) of the difference between treatment groups 
(GS-9883/F/TAF - boosted PI + 2 NRTis) in the percentage of 
subjects with HIV-1 RNA ~ 50 copies/mL is less than 4% (i.e., a 
margin of 4% is applied to non-inferiority assessment). The 2-sided 
95% Cis will be constmcted based on the exact method. 
The propmiion of subjects with HIV -1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defmed snapshot algorithm will 
also be surmnru·ized. The 2-sided 95% Cis will be constmcted in the 
srune manner as described for the primruy efficacy endpoint. 
Page 10 
19 October 2016 


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The change from baseline in CD4+ cell count at Week 48 will be 
summarized using descriptive statistics. The differences and the 
associated 95% CIs will be constructed using Analysis of Variance 
(ANOVA) model, including treatment (GS-9883/F/TAF vs. boosted 
PI + 2 NRTIs) as a fixed effect in the model.
Adverse events, clinical laboratory assessments, and pharmacokinetic 
parameters will be summarized using descriptive statistics.
A total of approximately 520 HIV-1 infected subjects, randomized in 
a 1:1 ratio to two treatment groups (260 subjects per treatment group), 
achieves at least 90% power to detect a non-inferiority margin of 4% 
difference in the percentage of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 between the two treatment groups. For 
sample size and power computation, it is assumed that both treatment 
groups have 2% of subjects with HIV-1 RNA ≥50 copies/mL (based 
on historical Gilead E/C/F/TAF and STB studies), that a 
non-inferiority margin is 4%, and that the significance level of the test 
is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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


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


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PSQI
Pittsburgh Sleep Quality Index
PT
preferred term 
PT
prothrombin time 
QD
once daily
RAL
raltegravir
RNA
ribonucleic acid
SA
single agent
SAE
serious adverse event
SF-36
Short Form 36 Health Survey
SmPC
Summary of Product Characteristics
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide 
TDF
tenofovir disoproxil fumarate, Viread
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UCLA SCTC GIT
UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States
VAS
Visual analog scale
WPAI
Work Productivity and Activity Impairment Questionnaire


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.4 million people in 
North America and Western and Central Europe living with HIV-1 and 36 million people 
worldwide {The Joint United Nations Programme on HIV/AIDS (UNAIDS) 2014}. The infection, if 
left untreated or suboptimally treated, is characterized by deterioration in immune function, 
ultimately resulting in death. Therapeutic strategies for the treatment of HIV-1 disease have been 
significantly advanced by the availability of highly active antiretroviral therapy (HAART); the 
introduction of HAART was associated with a dramatic decrease in acquired immune deficiency 
syndrome (AIDS)-related morbidity and mortality {Palella et al 1998}, {Mocroft et al 1998}, 
{Sterne et al 2005}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {Costagliola 2014}. In addition, there remains a significant 
medical need for new, effective therapies that take into consideration HIV genetic variability, the 
aging HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen 
simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {Department for 
Health and Human Services (DHHS) 2015}. Virologically suppressed, HIV-infected patients 
may switch from their current regimen because of safety or tolerability concerns or for regimen 
simplification. All patient populations may benefit from once-daily fixed-dose combination 
(FDC) regimens as these have been shown to provide increased adherence and improved clinical 
and virologic outcomes {Sterrantino et al 2012}, {Aldir et al 2014}.
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other NRTIs. Tenofovir alafenamide (TAF) is also an 
oral prodrug of TFV. TAF is more stable in plasma than TDF, provides higher intracellular 
levels of the active phosphorylated metabolite tenofovir diphosphate (TFV-DP), and 
approximately 90% lower circulating levels of TFV relative to TDF at the clinical doses. 
The distinct metabolism of TAF offers the potential for an improved clinical profile compared 
with TDF.
GS-9883 is a potent inhibitor of HIV-1 integrase that is being evaluated for the treatment of 
HIV-1 infection.  Antiviral testing has shown that GS-9883 is active against a broad panel of 
HIV-1 viral lab strains and clinical isolates.  GS-9883 is fully active against a panel of mutant 


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


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GS-9883 does not activate AhR and only weakly activates PXR at concentrations up to 50 M 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.
1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL, 
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day.  At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal 
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males.  The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy.
No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL).  The estimated margin of exposure at the 
NOEL was approximately 5.1-fold based on expected human exposure with the once daily 
dosing of the GS-9883/F/TAF (50/200/25 mg) tablet.


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A standard battery of in vitro and in vivo studies was performed to assess the genotoxic potential 
of GS-9883. There was no evidence of mutagenic or clastogenic activity in an in vitro bacterial 
reverse mutation assay (Study TX-141-2026), a chromosomal aberration assay in human 
lymphocytes (Study TX-141-2027), or in a rat micronucleus test (Study TX-141-2029).
1.2.3.
Clinical Trials of GS-9883
Clinical trials entailing the use of GS-9883 include:

GS-US-141-1218, a Phase 1 double blind, randomized, placebo-controlled, first-in-human, 
single- and multiple-ascending dose study evaluating the safety, tolerability, and PK of oral 
GS-9883 in healthy subjects and a randomized, open-label, 2-cohort, 3-period, crossover, PK 
study evaluating the drug interaction potential between F/TAF FDC tablet and GS-9883 in 
healthy subjects (completed)

GS-US-141-1219, a Phase 1b randomized, double-blinded, sequential cohort 
placebo-controlled study of the safety, PK, and antiviral activity of GS-9883 in HIV-1 
infected subjects (5 mg, 25 mg,50 mg, 100 mg) (completed)

GS-US-141-1233, a Phase 1,Open-label, Two-Cohort, Multiple-Period, Fixed-Sequence, 
Crossover Study to Evaluate 1) the Relative Bioavailability of
Two GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg)
Fixed-Dose Combination Tablets Versus a GS-9883 (75 mg) Tablet and a 
Emtricitabine/Tenofovir Alafenamide (200/25 mg) Fixed-Dose Combination Tablet 
Administered Simultaneously and 2) the Effect of Food on the Pharmacokinetics of 
GS-9883, Emtricitabine and Tenofovir Alafenamide When Administered as 
GS-9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg)
Fixed-Dose Combination Tablets (completed)

GS-US-141-1478, a Phase 1, Open Label, Parallel Group, Adaptive, Single-Dose Study to 
Evaluate the Pharmacokinetics of GS-9883 in Subjects with Normal and Impaired Hepatic 
Function (in life portion completed)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)


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
GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled Phase 1 Study 
Evaluating the Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular 
Filtration Rate (completed)

GS-US-311-1790, a Phase 1Randomized, Open Label, Drug Interaction Study Evaluating the 
Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (completed)

GS-US-380-1761, a Phase 1 Study to Evaluate Pharmacokinetic Drug-Drug Interaction 
Potential between GS-9883/Emtricitabine/Tenofovir Alafenamide Fumarate 
(GS-9883/F/TAF) and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-Dose Combination (FDC) 
Tablets (completed)

GS-US-380-1991, a Phase I Single and Multiple Dose Study Evaluating the 
Pharmacokinetics, Safety, and Tolerability of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Fumarate (GS-9883/FTC/TAF) in Healthy Japanese and Caucasian Subjects (ongoing)

GS-US-380-1999, a Phase 1 Multiple Dose Study to Evaluate the Pharmacokinetic Drug-
Drug Interaction Potential between GS-9883/Emtricitabine/Tenofovir Alafenamide Fumarate 
and Sofosbuvir/Velpatasvir/GS-9857 in Healthy Subjects (completed)

GS-US-380-3908, a Phase 1, Blinded, Placebo-controlled, Two-period Crossover Drug 
Interaction Study to Assess the Effect of GS-9883/F/TAF on Metformin Pharmacokinetics in 
Healthy Subjects (completed)

GS-US-380-3909, a Phase 1, Open Label, Multiple-Cohort, Multiple-Period, 
Fixed-Sequence, Drug Interaction Study to Evaluate the Effect of Antacid and Mineral 
Supplements on GS-9883 Pharmacokinetics (completed)

GS-US-141-1475, a Phase 2 Randomized, Double-Blinded Study of the Safety and Efficacy 
of GS-9883 + Emtricitabine/Tenofovir Alafenamide Versus 
Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral 
Treatment-Naive Adults (ongoing)
Please refer to the GS-9883/F/TAF Investigators’ Brochure for further information about these 
studies.
1.2.3.1.
Phase 1 Safety and Pharmacokinetics
Study GS-US-141-1218 was a four part, first-in-human study.  Parts A and B were randomized, 
double-blind, placebo-controlled, single and multiple ascending dose studies of GS-9883 in 
healthy male and female subjects.  Part C was an open label, fixed sequence food effect study 
evaluating the effect of food on the PK of GS-9883.  Part D was a randomized, open-label, 
2-cohort, 3-period, crossover PK study evaluating the drug interaction potential between 
FTC/TAF FDC tablet and GS-9883 in healthy subjects.


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There was no difference in the overall incidence or type of AEs when GS-9883 was administered 
in the fasted and fed states. There was no difference in the overall incidence of AEs when 
GS-9883 or FTC/TAF was each administered alone or in combination.
No deaths or pregnancies were reported. No Grade 3 or 4 AEs or SAEs, were reported in any 
cohort.
Changes in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2.  In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort. In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF. All 
changes returned to baseline after discontinuation of GS-9883.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood. All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.
Based on results in study GS-US-141-1218, pharmacokinetic profile of GS-9883 was 
characterized by rapid absorption with time to peak plasma concentrations (median Tmax of 
cohorts) ranging between 1 and 4 hours following administration under fasted conditions. 
GS-9883 exposures were appropriately dose proportional following single dose 25-100 mg dose 
administration, with decreasing dose proportional at higher doses.  The half-life of GS-9883 was 
approximately 18 hours, with no changes observed across studied dose range as evidenced by 
parallel terminal phase slopes. A high-fat meal increased AUCinf and Cmax (geometric mean, 84% 
and 101%, respectively) following 100 mg single dose administration. Steady state was achieved 
after 4-6 days of once daily dosing of GS-9883 with average accumulation ratios for AUC24hr
of 1.6.
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following 
Single Doses of GS-9883 in Healthy Subjects (GS-9883 PK Analysis 
Set; Part A: Single Dosing)
GS-9883 PK 
Parameter
Mean 
(%CV)
5mg
(N=6)
25 mg
(N=6)
50 mg
(N=6)
100 mg
(N=6)
300 mg
(N=6)
600 mg
(N=6)
Cmax (ng/mL)
691.2
(22.1)
1618.3
(26.7)
3965.0
(40.1)
6998.3
(36.1)
14605.0 
(27.1)
20050.0
(7.5)
Tmax (hr)
1.25 
(1.00-1.50)
2.00
(1.00-3.00)
3.00
(1.50-4.00)
2.25
(1.50-3.00)
3.50
(2.00-6.00)
3.5
(2.00-4.00)
AUCinf 
(ng.hr/mL)
13059.7
(25.1)
35718.2 
(21.3)
78399.5 
(29.7)
163028.2 
(24.3)
355917.3 
(32.9)
454446.8 
(19.9)
T1/2 (hr)
18.51
(16.81-19.99)
18.08
(16.63-19.64)
16.72
(15.77-17.11)
18.90
(17.96-20.05)
18.14
(17.86-20.53)
17.89
(16.38-19.52)
T1/2 and Tmax: Median (Q1, Q3)


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Table 1-2 presents GS-9883 plasma PK parameters following administration of GS-9883 
(5, 25, 50, 100, and 300 mg) once daily for 7 days. Following administration of either GS-9883 
(5, 25, 50, 100, or 300 mg) once daily for 7 days, the PK absorption profile observed on Days 1 
and 7 was similar to that observed in Part A (SAD). The median Tmax values ranged from 1.5 to 
2.5 hours on Day 1 and 1.5 to 4.0 hours on Day 7. Linearity was observed comparing GS-9883 
AUC and Cmax on Days 1 and 7 over the dose range of 25 to 50 mg. Steady state levels of 
GS-9883 were achieved between Study Days 4 to 6 of dosing and maintained through Day 14. 
Accumulation is approximately 1.6-fold, which is consistent with the observed half-life of the 
GS-9883 (approximately 18 hours).
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by 
GS-9883 Dose Following Multiple-Dose Administration of GS-9883 
(Analysis Set: GS-9883 PK Part B: Multiple-Dose)
GS-9883 PK Parameter Mean
(%CV)a
Multiple-Dose GS-9883
5 mg
(N = 6)
25 mg
(N = 6)
50 mg
(N = 6)
100 mg
(N = 6)
300 mg
(N = 6)
Day 1
AUC0-24 (hr*ng/mL)
9033.6
(8.2)
27,775.1
(28.3)
58,371.4
(18.9)
79,773.8
(18.9)
180,714.3
(17.6)
Cmax (ng/mL)
709.7
(9.5)
2220.0
(35.6)
4648.3
(18.7)
6248.3
(26.8)
13,716.7
(19.1)
Tmax (hr)
1.50
(1.50, 1.50)
1.75
(1.00, 3.00)
1.50
(1.00, 2.00)
2.50
(2.00, 3.00)
2.50
(2.00, 4.00)
Day 7
AUCtau (hr*ng/mL)
14,392.0
(16.7)
50,008.2
(26.6)
89,710.1
(22.7)
126,785.8 
(23.7)
277,200.2 
(16.7)
Cmax (ng/mL)
982.5
(7.9)
3455.0
(24.1)
6538.3
(17.6)
9396.7
(20.8)
19,900.0 
(21.2)
Ctau (ng/mL)
400.83
(26.9)
1322.00
(27.8)
2241.67
(28.2)
3145.00 
(26.1)
6758.33 
(21.6)
Tmax (hr)
1.50
(1.00, 2.00)
3.00
(2.00, 3.00)
1.75
(1.50, 2.00)
1.75
(1.50, 3.00)
4.00
(2.00, 4.00)
Accumulation Ratio of AUC (%)
160.5
(19.0)
182.2
(17.1)
154.0
(15.9)
158.5
(12.1)
157.5
(22.6)
a
Data are presented as mean (%CV), except for Tmax, and t½, which are presented as median (Q1, Q3)
Table 1-3 presents the GLSM ratios and associated 90% CIs for the test (fed) versus reference 
(fasted) treatments for the primary plasma PK parameters of GS-9883. Administration of a single 
dose of GS-9883 100 mg with food (high-calorie/high-fat breakfast) increased the GLSM values 
of Cmax and AUCinf 101% (90% CI of GLSM ratio 165.93% to 242.74%) and 84% (90% CI of 
GLSM ratio 152.05% to 222.59%), respectively. There were no apparent changes in clearance 
and T1/2 following administration with food, indicating that food enhanced the bioavailability of 
GS-9883 by improving its solubility and/or absorption.


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Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic 
Parameters Following Single-Dose Administration of GS-9883 in the 
Fasted and Fed States (GS-9883 PK Analysis Set)
GS-9883 PK Parameter 
Mean (%CV)
% GLSM Ratio 
(90% CI)
Test
GS-9883 100 mg Fed
(n=8)
Reference
GS-9883 100 mg Fasted
(n=8)
AUCinf (hr*ng/mL)
214,146.3 (15.9)
117,777.1 (23.3)
183.97 (152.05, 222.59)
AUClast (hr*ng/mL)
209,259.9 (15.1)
115,681.7 (24.0)
183.58 (151.91, 221.86)
Cmax (ng/mL)
11,268.8 (15.1)
5885.0 (34.9)
200.69 (165.93, 242.74)
CI = confidence interval; GLSM = geometric least squares mean
1.2.3.2.
Phase 1b Proof of Concept
The first HIV-1 positive human subjects were dosed in the fasted state with 10 days of GS-9883 
in study (GS-US-141-1219).  Four cohorts of 5 subjects each were randomized 4:1 to receive 
GS-9883 or placebo to match at doses of 5 mg, 25 mg, 50 mg, and 100 mg once daily for 
10 days.
GS-9883 was generally well tolerated at the doses evaluated. A total of 9 of 20 subjects had an 
AE in this study. The most frequently reported AEs across all subjects were diarrhea (2 subjects), 
and headache (3 subjects).  No other AE was reported in more than 1 subject. There was no 
increase in the incidence of AEs with increasing doses of GS-9883.
The majority of AEs were considered by the investigator to be not related to study drug. A total 
of 2 subjects experienced mild diarrhea that was considered related to study drug (1 in the 5 mg 
cohort, 1 in the 100 mg cohort).
No deaths or pregnancies were reported. No Grade 3 or 4 AEs, SAEs, or AEs leading to 
discontinuation of study drug were reported in any cohort.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. No Grade 3 
treatment emergent laboratory abnormalities were observed. Median serum creatinine changes at 
Day 10 were: 0.05 mg/dL (5 mg), 0.04 mg/dL (25 mg), 0.06 mg/dL (50 mg), and 0.15 mg/dL 
(100 mg). These changes in serum creatinine appeared to be transient and returned close to 
baseline values on discontinuation of study drug. One Grade 4 new onset laboratory abnormality 
was seen in 1 subject who received 5 mg GS-9883. This was a Grade 4 CPK seen on Day 17, 
7 days following his last dose of study medication. The subject was asymptomatic. The 
Investigator felt that this was unrelated to study medication and was due to resumption of crystal 
methamphetamine use by the subject. An adverse event of elevated CK was reported unrelated to
study medication.
Based on PK information collected in study GS-US-141-1219, which was in line with PK 
observed in study GS-US-141-1218, the median IQ for each dose were calculated and are 
presented in Table 1-4 below.


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Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ95 Values (GS-9883 PK Analysis 
Set)
GS-9883 dose
n
Median (range) Ctau, SS (ng/mL)
Median (range) paIQ95
a
5 mg
4
206.5 (146.0 to 342.0)
1.3 (0.9 to 2.1)
25 mg
4
797.5 (714.0 to 1900.0)
4.9 (4.4 to 11.7)
50 mg
4
2170.0 (852.0 to 3020.0)
13.4 (5.3 to 18.6)
100 mg
4
4190.0 (3730.0 to 5970.0)
25.9 (23.0 to 36.9)
a.
The protein adjusted IQ95 (paIQ95) value is estimated based on steady-state Ctau values and the in vitro paIC95 value for 
wild-type HIV-1 (162 ng/ml).
The mean and 95% CIs of change from baseline in HIV-1 RNA (log10 copies/mL) are presented 
in Figure 1-1.
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (PP Analysis Set)
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study drug.
Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 log10 in the 50 mg 
cohort, and -2.43 log10 in the 100 mg cohort. Time weighted average change from baseline at 
Day 11 (DAVG11) was -0.92 log10 in the 5 mg cohort, -1.33 log10 in the 25 mg 
cohort, -1.37 log10 in the 50 mg cohort and -1.61 log10 in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group.


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1.2.3.3.
Summary of Phase 2 Study (GS-US-141-1475)
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing 
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, ART-naive adult subjects.
Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to 
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 50 mg 
once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 75 mg 
once daily
Week 24 interim data are summarized below. 
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24 
data analysis, 2 subjects (2.0%) had prematurely discontinued from the study, 1 in each treatment 
group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and eGFRCG) were similar 
between the 2 treatment groups.
Median (first quartile [Q1], third quartile [Q3]) baseline HIV-1 RNA was 4.45 (3.96, 
4.79) log10 copies/mL, with 82.7% of subjects having ≤ 100,000 copies/mL at baseline; 
5 subjects had > 400,000 copies/mL at baseline; 4 of these subjects were randomized to 
GS-9883+F/TAF and 1 subject was randomized to DTG+F/TAF.
Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 41.8% of subjects 
having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 125.3 (105.7, 
147.0) mL/min.
Efficacy Results
Virologic success at Weeks 12 and 24 was assessed using the US FDA-defined snapshot 
algorithm, defined as plasma HIV-1 RNA < 50 copies/mL. At Weeks 12 and 24, virologic 
success was high and similar between the 2 treatment groups as follows: Week 12 
GS-9883+F/TAF 93.8%, DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79); Week 24 GS-9883+F/TAF 95.4%, DTG+F/TAF 
93.9% (1.0%; 95% CI: −10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 had 60 copies/mL. 


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Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF, +170 (150.0) cells/μL; DTG+F/TAF, +173 (220.5) cells/μL 
(difference in least squares mean [LSM]: 0; 95% CI: −76 to 76; p = 1.00). There were similar 
increases in the mean (SD) CD4 cell count in both treatment groups Week 24: GS-9883+F/TAF, 
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).
Interim Virology Resistance Data
Through Week 24, no emergent drug resistance was detected.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 66.2%, 43 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common treatment-emergent AEs (occurring in > 2 subjects) by treatment group were as 
follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE. One other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator or resulted in 
study drug discontinuation or interruption, and both SAEs resolved.
The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883+F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs reported that were considered related to 
study drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation 
were reported in either treatment group.


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


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
Both GS-9883+F/TAF and DTG+F/TAF were generally well tolerated through 24 weeks of 
treatment. The most commonly reported treatment-emergent AEs were diarrhea and 
headache (7.7% each) in the GS-9883+F/TAF group and nausea (12.1%) and diarrhea (9.1%) 
in the DTG+F/TAF group. There were 2 SAEs, 1 of which was also a Grade 3 AE; neither of 
these events was considered related to study drug by the investigator, or led to study drug 
discontinuation. There were no other Grade 3 or 4 AEs, and no deaths, pregnancies, or AEs 
leading to premature study drug discontinuation reported. The percentage of subjects with at 
least 1 treatment-emergent laboratory abnormality was similar between treatment groups. 
The majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. 
There were similar increases from baseline in serum creatinine in both treatment groups at 
Week 24. 
1.3.
Information about Emtricitabine (Emtriva®, FTC)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US Food and Drug Administration (FDA) for 
marketing on 2 July 2003 and is available under the name Emtriva®. In the European Union 
(EU), marketing authorization was granted for both the 200 mg Emtrivacapsule formulation 
and a 10 mg/mL Emtrivaoral Solution formulation on 24 October 2003, with indications for 
the treatment of HIV infection concurrently with other antiretroviral drugs in both adult and 
pediatric patients.
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information about Tenofovir alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain. The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.4.1.
Clinical Trials of Single Agent Tenofovir alafenamide (TAF, GS-7340) or 
Fixed Dose Combination emtricitabine/tenofovir alafenamide (FTC/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected subjects (completed)

GS-US-120-0104, a Phase 1b study of the pharmacokinetics and antiviral activity of 
GS-7340 (8 mg, 25 mg, 40 mg) in HIV infected subjects (completed)


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
GS-US-120-0107, a Phase 1, partially-blinded, randomized, placebo- and positive controlled 
study to evaluate the effect of GS-7340 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-120-0108, a Phase 1, open-label, parallel-design study to evaluate the
pharmacokinetics of GS-7340 in subjects with severe renal impairment (completed)

GS-US-120-0109, a Phase 1 study to evaluate the pharmacokinetics, metabolism and 
excretion of GS-7340 (completed)

GS-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the 
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic 
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug 
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of 
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in 
healthy subjects (completed)

GS-US-120-1538, a Fixed-Sequence, Open-Label, Study Evaluating the Pharmacokinetics 
and Drug Interaction Potential between Tenofovir Alafenamide and Midazolam (Oral and 
Intravenous) in Healthy Volunteers (completed) 

GS-US-120-1554, a Fixed-Sequence, Randomized, Open-Label, 2-Cohort, 2-Period, 
Multiple-Dose Study Evaluating the Pharmacokinetics and Drug Interaction Potential 
between Tenofovir Alafenamide and Rilpivirine in Healthy Subjects (completed)

GS-US-311-1386, a Phase 1 study to determine the effect of food on the pharmacokinetics of 
tenofovir alafenamide when administered as F/TAF FDC in healthy volunteers (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential 
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz (EFV) or 
COBI-boosted darunavir (DRV) (completed)

GS-US-311-1088, a Phase 1, Relative Bioavailability Study of Emtricitabine/Tenofovir 
Alafenamide Fixed Dose Combination Tablet to evaluate the formulation performance of 
emtricitabine (FTC) and tenofovir alafenamide (TAF) fixed dose combination tablets relative 
to co-administration of individual agents (completed).

GS-US-311-1089, a Phase 3 study of the safety and efficacy of FTC/TAF in HIV infected, 
virologically suppressed patients (ongoing).


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


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


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


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Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 1, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
Cohort 2 Results:
Pharmacokinetic Results
The PK results from Study GS-US-141-1233 demonstrated that the GS-9883 AUCinf and Cmax
following administration of the 50mg GS-9883 FDC tablets was 79% and 78%, respectively of 
those observed in the same study following co-administration of GS-9883 75 mg single agent 
with F/TAF (200/25 mg) under fasted conditions. The GS-9883 exposures of 50 and 75 mg fixed 
dose combination tablets were approximately dose proportional under fasted and fed conditions
and a high fat and moderate fat meal had similar impact on GS-9883 with AUCinf increasing by 
24%. The steady state paIQ95 of GS-9883/F/TAF (50/200/25 mg) was predicted to be 
17 (fasted)-23 (fed). The exposures of TAF and FTC of the 50 mg GS-9883 FDC were similar 
to those of GS-9883 75 mg single agent with F/TAF FDC, and the food effect on TAF and FTC 
was similar to the historical results.  
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 2, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
1.6.
Rationale for this Study
As treatment guidelines recommend early treatment of HIV-1 infection, there is need for 
regimens that maximize long-term efficacy, safety, tolerability, and convenience. These features 
are determined by the specific formulation of the regimen (fixed-dose, or multi-tablet regimens), 
the nucleos(t)ide backbone, and the third agents (PI, NNRTI, or INSTI).
Switching to GS-9883/F/TAF may offer the advantages of a single-tablet FDC containing the 
unboosted, next-generation INSTI, GS-9883, combined with a TAF-containing nucleotide 
backbone. This regimen has the potential to avoid unwanted side effects from PI-based therapy 
(such as hyperbilirubinemia, rash, gastrointestinal upset, and dyslipidemia), decrease the 
potential for drug-drug interactions by removing the need for a boosting agent, avoiding potential 
long term renal and bone side effects from TDF, and avoiding potential long-term cardiovascular 
risk from ABC.


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Four FDCs are currently approved in the US and EU for once-daily administration as a complete 
regimen for the treatment of HIV-1 infection, EFV/FTC/TDF, FTC/RPV/TDF, E/C/F/TDF, and 
ABC/DTG/3TC. There is no PI-containing FDC currently available. Studies have shown that a 
once-daily FDC significantly improved adherence, treatment satisfaction, and virologic 
outcomes for patients infected with HIV-1 {Dejesus E 2009}, {Hodder et al 2010}, {Airoldi et al 
2010}, {Bangsberg et al 2010}. Due to longer duration of high adherence, patients taking FDCs 
also have better clinical outcomes, such as fewer hospitalizations, compared with multiple-tablet 
regimens {Sax et al 2010}.
Boosted protease inhibitors still represent a sizeable portion of the treated HIV-1-infected 
population and are viewed as the class with the greatest barrier to resistance. Boosted DRV is the 
only PI that remains on the DHHS treatment guidelines as a preferred agent, though ATV is still 
widely prescribed. Use of DRV/r and ATV/r in this study will allow comparison of the 
GS-9883/F/TAF FDC with these third agents, regardless of NRTI backbone. The study has the 
potential to demonstrate benefits such as decreased pill burden and adverse events, and improved 
patient reported outcomes.
This study will evaluate the safety, efficacy and tolerability of switching from boosted PI 
regimens to GS-9883/F/TAF, thereby assessing the viability of GS-9883/F/TAF as a FDC option 
for HIV-infected patients.
1.7.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.


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


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In order to bridge exposures of GS-9883 in the FDC to the exposure observed with GS-9883 
75 mg administered as a single agent, and to bridge to the safe and effective exposures observed 
in the Phase 2 study GS-US-141-1475, a lower strength GS-9883/F/TAF FDC was developed for 
use in the Phase 3 studies. Comparability of GS-9883 exposures was confirmed in an rBA study 
of GS-9883/F/TAF (50/200/25 mg) and GS-9883 (75 mg) + F/TAF prior to initiation of dosing 
in the Phase 3 studies.
1.8.
Risk Benefit Assessment for this Study
All patients with HIV-1 infection should receive effective anti-retroviral therapy. Potential risks 
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and 
lactic acidosis with steatosis.  The risk of class effects is considered to be low.  Important 
identified risks appropriately managed by study inclusion/exclusion criteria as well as through 
close clinical and laboratory monitoring during the study are as follows:  hypersensitivity
reaction to abacavir and allergy to any components of the tablets.  Some observational studies 
have shown increased risk of cardiovascular disease with abacavir.  Protease inhibitors may be 
associated with increased lipid levels and gastrointestinal side effects. If patients are currently 
infected with hepatitis B and discontinue their existing or new therapy, there is a risk of severe 
acute exacerbations of hepatitis B.  Interim data will also be reviewed by an independent data 
monitoring committee.  Potential benefits of GS-9883 may include provision of a new 
antiretroviral therapy that is not currently available and which may have fewer side effects than 
alternative therapies.  Other potential benefits include provisions of fixed dose combination 
therapy, and the knowledge that patient participation will contribute to the body of knowledge of 
HIV therapies.
Following a chronic 39 week study in monkeys, animals administered the highest dose of  
GS-9883 (1000 mg/kg/day) had bile duct hyperplasia (increased cell growth) and hypertrophy 
(increased cell size), and some increased cell growth and inflammation in nearby liver cells. 
These effects were not seen in monkeys administered the mid-level dose (200 mg/kg/day), and 
these animals had plasma GS-9883 exposures that were approximately 5-fold above human 
exposures when given the  GS-9883/F/TAF FDC.   No adverse drug reactions associated with 
liver or bile duct problems have been identified in humans treated with GS-9883.
Potential hepatobiliary toxicity is appropriately managed by study inclusion/exclusion criteria, 
close clinical and laboratory monitoring, as well as specific toxicity management guidance to 
investigators (Refer to Section 7.5.7).  
The overall benefit-risk assessment for GS-9883/F/TAF is favorable at this time.
1.9.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of switching to a FDC of  GS-9883/F/TAF versus continuing on a 
regimen consisting of boosted atazanavir or darunavir plus either FTC/TDF or ABC/3TC in 
HIV-1 infected adult subjects who are virologically suppressed as determined by the 
proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48
The secondary objective of this study is:

To evaluate the safety and tolerability of the two treatment groups through Week 48


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3.
STUDY DESIGN
3.1.
Endpoints
The primary efficacy endpoint is:

The proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 as defined by the 
US FDA-defined snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell counts at Week 48
3.2.
Study Design
This protocol describes a randomized, open-label, multicenter, active-controlled study to
evaluate the safety and efficacy of switching to a FDC of GS-9883/F/TAF in HIV-1 infected 
adult subjects who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a regimen 
consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for 
≥6 months prior to screening.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: Switch to FDC of GS-9883 50 mg/ emtricitabine 200 mg/ tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily without regard to food
(n=260)
Treatment Group 2: Remain on current antiretroviral regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC administered orally,
once daily with food (n=260)
3.4.
Duration of Treatment
The treatment duration is 48 weeks.
At the Week 48 Visit, treatment group 1 and 2 subjects in a country where GS-9883/F/TAF FDC 
is not available will be given the option to receive GS-9883/F/TAF FDC for an additional
96 weeks and attend study visits every 12 weeks, or until the product becomes accessible to 
subjects through an access program, or until Gilead Sciences elects to discontinue the study in 
that country, whichever occurs first.


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Figure 3-1. 
Study Schema 
Screening 
S 30 days 
prior 
tooap 
Day 1' 
T1·eatment G1·oup L GS-9883/FffAF FDC 
QD (n=260) 
Week48"·c 
Treatment Group 2: Remain on current regimen of 
boosted ATV or DRV plus FTCrfDF or ABC/3TC 
QD (n=260) 
30 Day 
FJUC 
a. 
Following the Day 1 visit, subjects will be required to retum for study visits at Weeks 4, 8, 12, and then every 12 weeks 
through Week 48. 
b. 
After Week 48, subjects in a countly where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/FfTAF FDC for an additional96 weeks and attend study visits every 12 weeks, or until the product becomes 
accessible to subjects through an access program, or until Gilead Sciences elects to discontinue the study in that cotmhy, 
whichever occm'S first. 
c. 
Subjects who complete the studydmg through the Week 48 Visit and do not wish to receive GS-9883/FfTAF FDC w'ill be 
required to retum to the clinic 30 days after the completion of study drugs for a 30-Day Follow-Up Visit. 
3.5. 
Biomarker Testing 
3.5.1. 
Biomarker Samples for Optional Pharmacogenomic Research 
PPD 
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3.5.2.
Additional Sample Storage
For subjects who provide additional consent, residual blood and urine samples taken throughout 
the study will be stored. Stored samples may be used by the Sponsor or its research partners to 
help answer questions about the study drug, and HIV disease and its associated conditions, or to 
provide additional safety data.  At the conclusion of this study, these samples may be retained in 
storage by Gilead Sciences for a period up to 15 years.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 520 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1. The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2. Age 18 years
3. Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat 
boosted ATV or DRV plus either FTC/TDF or ABC/3TC for 6 months preceding the 
screening visit
4. HIV RNA < 50 copies/mL at the screening visit
5. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6. Adequate renal function:
Estimated glomerular filtration rate ≥50 mL/min (≥0.83 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft et al 1976}:
a.
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
         (140 – age in years) (wt in kg)
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
b. Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg)  
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7. Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8. Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin
9. Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥ 50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))


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10. Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11. Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 6) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12. Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 6) throughout the study period and for 
90 days following the last dose of study drug.
13. Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14. Life expectancy ≥ 1 year
15. Currently on a stable regimen for ≥ 6 months preceding the Screening visit with documented 
plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months preceding the Screening visit (or 
undetectable HIV-1 RNA level according to the local assay being used if the limit of 
detection is ≥ 50 copies/mL). 
Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for 
regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient 
detectable viremia, or “blip”) prior to screening are acceptable. (If the lower limit of 
detection of the local HIV-1 RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the plasma 
HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests)
16. Have no documented or suspected resistance to FTC, TFV, ABC or 3TC, including but not 
limited to the reverse transcriptase resistance mutations K65R and M184V/I
17. No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1. An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to 
screening (refer to Appendix 5)
2. Subjects experiencing decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal 
bleeding)


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3. Have been treated with immunosuppressant therapies or chemotherapeutic agents within 
3 months of study screening, or expected to receive these agents or systemic steroids during 
the study (e.g, corticosteroids, immunoglobulins, and other immune- or cytokine-based 
therapies)
4. Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance
5. A history of or ongoing malignancy (including untreated carcinoma in-situ) other than 
cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous 
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must 
not have received any systemic therapy for KS within 30 days of Day 1 and are not 
anticipated to require systemic therapy during the study
6. Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
7. Participation in any other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with the dosing requirements
9. Any known allergies to the excipients of GS-9883/F/TAF FDC or ATV, RTV, DRV, COBI, 
FTC/TDF or ABC/3TC
10. Females who are pregnant (as confirmed by positive serum pregnancy test)
11. Females who are breastfeeding
12. Subjects receiving ongoing therapy with any of the medications listed in the Table 5-1 and 
Table 5-2. Administration of any Prohibited Medication (Table 5-1 and Table 5-2) must be 
discontinued at least 30 days prior to the Day 1 visit and for the duration of the study.
13. Acute hepatitis in the 30 days prior to study entry
14. Chronic hepatitis B infection in subjects not on a TDF containing regimen, as determined by 
either:

Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit

Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit
15. Active tuberculosis infection


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day 1 visit the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2.
Treatment Group 1: Switch to a FDC of GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) administered orally once daily without regard to food (n=260)
Treatment Group 2: Remain on current antiretroviral regimen consisting of ritonavir or 
cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC administered orally once 
daily with food (n=260)
Randomization will be stratified by the prior treatment regimen group (ie, TDF containing 
regimens [ritonavir or cobicistat boosted ATV or DRV plus FTC/TDF] and non-TDF containing 
regimens [ritonavir or cobicistat boosted ATV or DRV plus ABC/3TC]) at screening.
Subjects randomized in Treatment Group 1 will be assigned study drug bottle numbers of 
GS-9883/F/TAF FDC at study visits by IWRS.
Investigators must provide a prescription to the subjects in Treatment Group 2. Those subjects 
are responsible for obtaining their ARV treatment prior to or during the study visit.
5.2.
Description and Handling 
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF 
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg Tablets
GS-9883/F/TAF  tablets are packaged in white, high density polyethylene (HDPE) bottles. Each 
bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal 
Products), and/or other local regulations.
5.2.3.
Storage and Handling
Study drug GS-9883/F/TAF should be stored at controlled room temperature of 25°C (77°F); 
excursions are permitted between 15°C and 30°C (59°F and 86°F).  Storage conditions are 
specified on the label. Until dispensed to the subjects, all bottles of study drugs should be stored 
in a securely locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide
GS-9883/F/TAF tablets will be provided by Gilead Sciences.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 50 mg/200 mg/25 mg FDC 
will be administered orally, once daily without regard to food at approximately the same time 
each day.
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability.  The Investigator will be responsible for maintaining accurate
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return.


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5.4.
Prior and Concomitant Medications

The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following table and use of herbal/natural supplements are excluded or 
should be used with caution while subjects are participating in the study, depending on subject’s 
treatment regimen. Subjects will refrain from consumption of grapefruit juice and Seville orange 
juice throughout participation in the study.
Table 5-1.
Prior and Concomitant Medications (GS-9883/F/TAF Regimen)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With 
Caution
Acid Reducing Agents
Antacids
Buffered medications 
Concentration of study drug may decrease 
with antacids. Subjects may not take antacids 
(eg, Tums or Rolaids); the ulcer medication 
sucralfate (Carafate); or vitamin or mineral 
supplements that contain calcium, iron or 
zinc for a minimum of 6 hours before and 
2 hours after any dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not 
part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural 
Supplements
St. John’s Wort, Echinacea
Oral Hypoglycemic Agent
Metformin: close monitoring is 
recommended. A dose adjustment of 
Metformin may be necessary. Limit total 
daily doses of Metformin to 1000mg either 
when starting or at study entry.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.


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Table 5-2.
Prior and Concomitant Medications (Boosted ATV and DRV 
regimen)
Drug Class
Agents Disallowed*
Alpha-1 Adrenoreceptor Antagonist
Alfuzosin
Antiarrhythmic Agent
Amiodarone, Dronedarone
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine
Antimycobacterials
Rifampin
Antipsychotics
Lurasidone, Pimozide
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort
Anticancer drugs
Irinotecana
Ergot Drivatives
Ergotamine, Ergonovine
Dihydroergotamine
Methylergonovine
Ergometrine
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Phosphodiesterase-5 Inhibitors
Sildenafil ( for PAH)
Sedatives/Hypnotics
Orally administered Midazolam, Triazolam
Calcium Channel Blockers
Bepridil
Chronic angina
Ranolazine
a
Applied to ATV regimen only
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study.
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Sciences Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead Sciences as soon as he/she is aware of the use of the excluded 
medication.
Additionally, Investigators should refer to the current product/package inserts of the 
antiretroviral medications for contraindications related to their use.
5.5.
Accountability for Investigational Medicinal Product (IMP)
The investigator is responsible for ensuring adequate accountability of all used and unused IMP.
This includes acknowledgement of receipt of each shipment of IMP (quantity and condition). All 
used and unused IMP dispensed to subjects must be returned to the site.


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Study Drug accountability records will be provided to each study site to:

Record the date received and quantity of IMP kits

Record the date, subject number, subject initials, the IMP kit number dispensed

Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
Return and disposal of study drug GS-9883/F/TAF will be performed as outlined in 
Section 9.1.7.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that subjects are eligible for study prior to 
enrollment. Please refer to Section 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events, smoking history 
and prior medications within 30 days of the screening visit. 

If available, obtain 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

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled


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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
■
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
        (140 – age in years) (wt in kg) 
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786
■
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
       (140 – age in years) (wt in kg) 
0.85 CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
Plasma HIV-1 RNA
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen (HBsAg), 
Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)
The following will be conducted by the central laboratory if the following criteria are 
met:
■
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, reflex 
HBeAb), and quantitative HBsAg
■
If positive HBcAb with negative HBsAg  and negative HBsAb, reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found to 
be negative, reflex HBeAb.
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.

Review of adverse events and concomitant medications


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Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for Day 1 Visit. Subjects must continue to take their prior 
treatment regimen up until their scheduled Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF). All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. See 
Section 7 Adverse Events and Toxicity Management for additional details.
6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
confirmed subject’s eligibility before proceeding with the Day 1 visit. The subject must 
complete all study procedures before being administered the study drug:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI), UCLA Scleroderma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) and VAS Adherence 
Questionnaire to be completed by the subject. Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate
Urine storage sample for possible additional clinical testing


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• 
Blood sample collection for the following laborat01y analyses: 
-
Chemis1:Iy profile: alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and 
indirect bilimbin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphoms, magnesium, potassium, sodium, mic acid, and amylase 
(reflex lipase testing is perf01med in subjects with total amylase > 1.5 x ULN) and TSH. 
PT IINR (prothrombin time/intemational n01malized ratio) 
-
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 homs prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
u·iglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must retu.m within 72 homs in a fasted state to draw blood for the metabolic 
assessments. 
-
Estimated glomemlar filu·ation rate according to the Cockcroft-Gault f01mula 
-
Hematology profile: complete blood cmmt (CBC) with differential and platelet cmmt 
-
Plasma HIV-1 RNA 
-
CD4+ cell count 
-
Plasma storage sample for safety, virology, or PK testing 
-
Whole blood sample for potential HIV DNA genotyping 
-
Subjects who meet the defmition of HBV infection below at Screening Visit (positive 
sennn HBsAg or Positive HBcAb with quantifiable HBV DNA), will have plasma HBV 
DNA tested. 
• 
Optional blood sample collection for the following laboratory analyses if 
pharmacogenomic consent is obtained 
I 
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6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 -48)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, and 48 unless 
otherwise specified.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 36, unless otherwise specified.  The visit window at Week 48 will be ± 6 weeks of 
the protocol-specified visit date and this clinical visit window coincides with the Week 48 
statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24 and 48) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Weeks 24 and 48)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and UCLA Scleroderma Clinical Trial 
Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) to be completed by the subject at 
Weeks 4, 12, and 48. Subject is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires.

VAS Adherence Questionnaire. Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin (Weeks 24 and 48)


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


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Phrumacokinetic Blood Collection for subjects who ru·e on study dmg in Treatment Group 1 
only. Details of phrumacokinetic blood sainpling procedures and sainple management will be 
documented in the Phrumacokinetic Sample Collection, Processing, Storage, and Shipment 
Manual. 
I 
-
Single Anytime, Trough and Post Dose PK Samples for all subjects on study drug in 
Treatment Group 1: 
• 
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 
and 36. 
• 
Observed dosing at the clinic: Subjects will have a trough PK blood sainple collected 
between 20-28 hours following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study <hugs on the moming of their visit for the tr·ough 
sainple collection. Subjects will then take an observed dose of study <hug at the clinic. 
A single post dose PK blood sample will be collected between 1 and 4 hours post 
dose. If the subject has taken their dose of study <hugs prior to the visit, the visit may 
proceed, but the subject must retum within 72 hours for the tr·ough PK blood sainple 
collection. In the event a subject routinely takes their study <h11g in the evening, a 
single post-dose sainple may be <h·awn at Weeks 4 and 12 as the subject will not be 
instructed to change their dosing time to accommodate this tr·ough PK <h·aw. 
• 
Dosing diru·ies will be collected from subjects for the single anytime PK and tr·ough 
PK collection. If a dosing diaty is not retumed the site may ask the subject for the 
time of the last dose and if it was taken with or without food. 
-
Optional Pharmacokinetic (PK) Substudy: 
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6.5. 
6.5.1. 
Treatment Assessments (Post Week 48) 
Post Week 48 Assessments 
Final 
Amendment2 
At the Week 48 visit, subjects who completed 48 weeks of study dmg tr·eatment and are in a 
country where GS-9883/F/TAF FDC is not available will be given the option to receive 
GS-9883/F/TAF FDC for an additional 96 weeks and attend study visits eve1y 12 weeks, or until 
the product becomes accessible to subjects through an access program, or until Gilead Sciences 
elects to discontinue the study in that country, whichever occurs first. 
Subjects who fmi her continue pa1iicipation in the study and receive GS-9883/F/TAF FDC will 
retum for study visits eve1y 12 weeks. Study visits are to be completed within ±6 days of the 
protocol-specified visit date unless othe1wise specified. 
Subjects pruiicipating in the study post Week 48 will be required to retum for study visits 
according to the schedule presented in Appendix 1. Study Procedures Table and described in the 
text below: 
• 
Review of AEs and changes in concomitant medications 
• 
Complete physical examination (Every 48 weeks) (urogenital/anorectal exams will be 
perf01med at the discretion of the Investigator) or symptom-directed physical examination as 
needed 
• 
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight 
• 
12-lead ECG perfonned supine (Every 48 weeks) 
• 
Urine collection for the following laborat01y procedures: 
-
Urinalysis 
-
Urine albumin, urine creatinine, urine protein, retinol binding protein and 
beta-2-microglobulin (Every 24 weeks) 
-
Urine pregnancy test (females of childberu·ing potential only); positive urine pregnancy 
tests will be confnmed with a sennn test. If the test is positive, the subject will be 
discontinued. 
-
Urine storage sample for possible additional clinical testing 
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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks.
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments. (Every 24 weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology or PK testing
For subjects that meet the definition of HBV Infection at any visit:
■
The following will be conducted by the central laboratory: HBsAb, HBsAg 
(qualitative and quantitative) and HBeAg (if negative, reflex HBeAb) (Every 
24 weeks)
■
Plasma HBV DNA 
For subjects who do NOT meet the definition of HBV infection at any visit:
■
The following will be conducted by the central laboratory: HBsAb, HBcAb, and 
HBsAg. Subjects who are HBsAg and/or HBcAb positive will have a reflex test for 
HBV DNA (viral load) (Every 48 weeks)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed. (Every 48 weeks)

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.13.

Document study drug dispensation and accountability for all study drugs dispensed.


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6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
If the subject discontinues study drug, the subject will be asked to return to the clinic within 72 
hours of stopping the study drug for the Early Study Drugs Discontinuation Visit.  
Subjects who complete the study drug through Week 48 and who do not continue participation in 
the study, will not be required to complete the Early Study Drugs Discontinuation Visit.
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will 
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drugs Discontinuation Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight 

12-lead ECG performed supine (for discontinuation visits up to Week 48 only)

VAS Adherence Questionnaire. Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test
Urine storage sample for possible additional clinical testing

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH


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Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30-Day Follow-Up
If the subject discontinues study drug, the subject will be required to return to the clinic 30 days 
after the completion of the Early Study Drugs Discontinuation Visit for the 30-Day Follow-Up 
visit.
Subjects who complete the study drug through Week 48 and who do not further continue 
participation in the study, will be required to return to the clinic 30 days after the completion of 
study drug for the 30-Day Follow-Up visit.
Those subjects who prematurely discontinue study drug and continue in the study through 
at least one subsequent visit after the Early Study Drug Discontinuation Visit will not be 
required to complete the 30-Day Follow-Up Visit.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.


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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly (or as 
often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained.
6.7.
Criteria for Discontinuation of Study Treatment
Study medication will be discontinued in the following instances:

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Subject request to discontinue for any reason

Pregnancy during the study; refer to Appendix 6

Development of active tuberculosis infection
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator

Lack of efficacy

Subject noncompliance

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)


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6.8.
Other Evaluations
6.8.1.
Markers of Renal Tubular Function
For all subjects, urine will be collected for selected evaluations of renal tubular function, which 
will include but not be limited to urine albumin, urine creatinine, urine protein, retinol binding 
protein and beta-2-microglobulin at Day 1 Visit, Weeks 24, 48, and every 24 weeks post 
Week 48. Samples may be stored for a period of 15 years at the end of the study.
6.9.
Blood and Urine Storage
A portion of the blood and urine samples drawn at all visits (except the Screening Visit, 30-day 
follow-up Visit and Unscheduled Visits) will be frozen and stored. These stored blood and urine 
samples may be used by the Sponsor or its research partners for HIV-1 genotyping/phenotyping 
assays or their development, for retesting the amount of HIV-1 in the blood, for measurement of 
antiviral drug levels in the blood, or for testing to learn more about how the study drug has 
worked against HIV-1 or clinical laboratory testing to provide additional safety data. No human 
genetic testing will be performed without expressed consent of study subjects. At the conclusion 
of this study, these samples may be retained in storage by Gilead Sciences for a period up to 
15 years.
6.10.
Assessments for Premature Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.7, Criteria for Discontinuation of Study Treatment). If 
this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study.
6.11.
End of Study
The end of study will be the last patient’s last observation (or visit).
6.12.
Post Study Care
After a subject has completed/terminated their participation in the study, long-term care for the 
subject will remain the responsibility of their primary treating physician.
6.13.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study 
drug discontinuation or Week 48. 
6.13.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:


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


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


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


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


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


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


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
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure, EU Summary of Product Characteristics 
(SmPC), or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 4).

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat
testing within 3 calendar days of receipt of results and before investigational medicinal 
product discontinuation, unless such a delay is not consistent with good medical practice

Any questions regarding toxicity management should be directed to the Gilead Medical 
Monitor.
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.


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


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


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


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7.5.6.
Management of Possible Abacavir Hypersensitivity Reaction
Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to increased 
risk of hypersensitivity reaction, unless no other therapeutic option is available based on the 
treatment history and resistance testing.
In a clinical study, 3.4 % of subjects with a negative HLA-B*5701 status receiving abacavir 
developed a hypersensitivity reaction. Therefore, even in the absence of HLA-B*5701 allele, it is 
important to permanently discontinue abacavir and not rechallenge with abacavir if a 
hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe 
or even fatal reaction.
Hypersensitivity reactions are characterized by the appearance of symptoms indicating 
multi-organ system involvement. Almost all hypersensitivity reactions will have fever and/or 
rash as part of the syndrome. Other signs and symptoms may include respiratory signs and 
symptoms such as dyspnoea, sore throat, cough, and abnormal chest x-ray findings 
(predominantly infiltrates, which can be localized), gastrointestinal symptoms, such as nausea, 
vomiting, diarrhea, or abdominal pain, and may lead to misdiagnosis of hypersensitivity as 
respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis. Other frequently 
observed signs or symptoms of the hypersensitivity reaction may include lethargy or malaise and 
musculoskeletal symptoms (myalgia, rarely myolysis, arthralgia). The symptoms related to this 
hypersensitivity reaction worsen with continued therapy and can be life- threatening. 
These symptoms usually resolve upon discontinuation of abacavir.
Hypersensitivity reaction symptoms usually appear within the first six weeks of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. Patients 
should be monitored closely, especially during the first two months of treatment with abacavir.
Regardless of their HLA-B*5701 status, patients who are diagnosed with a hypersensitivity 
reaction whilst on therapy MUST discontinue study drug immediately and MUST NEVER be 
restarted. Restarting study drug following a hypersensitivity reaction results in a prompt return of 
symptoms within hours. This recurrence is usually more severe than on initial presentation, and 
may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimize 
the risk of a life-threatening hypersensitivity reaction, study drug must be permanently 
discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible 
(respiratory diseases, flu-like illness, gastroenteritis or reactions to other medicinal products) 
{Ezzati et al 2003}.
7.5.7.
Management of Potential Hepatobiliary Toxicity
Monkeys given a high dose (1000 mg/kg/day) for 39 weeks had evidence of biliary hyperplasia 
and hepatocyte hypertrophy on histopathologic examination. The risk to humans given the 
clinical dose of GS-9883 (50 mg/day) is unknown. Investigators should be aware of this potential 
toxicity. Any study subject exhibiting signs/symptoms or laboratory abnormalities suggestive of 
possible hepatobiliary toxicity should undergo thorough examination and clinical workup as 
deemed appropriate by the Investigator, and the Investigator must communicate promptly with 


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the Gilead Medical Monitor. Consideration should be given to appropriate imaging studies (for 
example, ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. Management of graded 
laboratory and clinical abnormalities will be managed as outlined in Section 7.5.
7.5.8.
On-Treatment Hepatitis C Management
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus, Gilead recommends that local medical practice is followed at the discretion of 
the Investigator. Investigational medicinal product may be continued without dose 
interruption. Should the Investigator feel the need to initiate Hepatitis C treatment the 
Investigator must contact the Gilead Medical Monitor to confirm that no drug-drug interactions 
are expected. Subjects should return to the clinic for scheduled or unscheduled follow up visit(s) 
according to local medical practice for laboratory evaluations. If Hepatitis C treatment is 
initiated, Investigators should use the Gilead provided retest laboratory kits to manage the active 
Hepatitis C.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, reports of adverse reactions in infants 
following exposure from breastfeeding, occupational exposure with an adverse event, and 
pregnancy reports regardless of an associated AE.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.


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7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to the Gilead DSPH using the pregnancy report form within 24 hours of becoming aware 
of the pregnancy.
Refer to the below and the eCRF completion guidelines for full instructions on the mechanism of 
pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.3.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post study 
must be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows:
Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477.
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH, fax number 
+1 650 522-5477 or email Safety_FC@gilead.com.
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications.


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Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.6.2.1 and the eCRF completion guidelines for full instructions on the 
mechanism of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective of this study is to evaluate the efficacy of switching to a FDC of 
GS-9883/F/TAF versus continuing on a regimen consisting of boosted ATV or DRV plus either 
FTC/TDF or ABC/3TC (i.e., boosted PI + 2NRTIs) in HIV-1 infected subjects who are 
virologically suppressed as determined by the proportion of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48.
The secondary objective of this study is to evaluate the safety and tolerability of the 
two treatment groups through Week 48.
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 
as defined by the US FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the 
US FDA-defined snapshot algorithm

The change from baseline in CD4+ cell count at Week 48
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.
8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
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8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis 
set:

Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing is due to discontinuation of study drug for lack of efficacy.

Subjects who do not meet the inclusion criterion for no previous use of any approved or 
experimental integrase strand transfer inhibitor (INSTI)

Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the Table 5-1 and Table 5-2. 
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 dose of study 
drug. All the data collected up to 30 days after subjects permanently discontinue their study drug 
will be included in the safety summaries, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.
8.2.1.4.
Pharmacokinetics
8.2.1.4.1.
Pharmacokinetic (PK) Substudy Analysis Set
The primary analysis set for intensive PK analyses is defined as the PK substudy analysis set, 
which will include all subjects who (1) are randomized into the study, (2) enrolled into the PK 
Substudy, (3) have received at least 1 dose of GS-9883/F/TAF, and (4) have at least 
1 nonmissing intensive PK concentration data for any analyte of interest reported by the PK lab.
8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the pharmacokinetic (PK) analysis 
set, which will include all subjects who (1) are randomized into the study, (2) have received at 
least 1 dose of GS-9883/F/TAF, and (3) have at least 1 nonmissing PK concentration data for 
any analyte of interest reported by the PK lab.


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8.3.
Data Handling Conventions
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (e.g., if the result of a continuous laboratory test is 
< 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (i.e., no toxicity grade) for the laboratory abnormality summary.
All available data for subjects that do not complete the study will be included in data listings.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include sex, race, ethnicity, and age.
Baseline characteristics will include body weight, height, body mass index, and eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline 
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA ≥50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm. The primary analysis of the 
efficacy endpoint will be based on the FAS.


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8.5.1.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, including data collected up to 1 day after the last 
dose date of study drug) will be used in the snapshot algorithm. Virologic outcome will be 
defined as the following categories:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 48 analysis window

HIV-1 RNA ≥50 copies/mL: this include subjects
Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 
analysis window , or
Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and
■
Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or
■
Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than lack of efficacy and have the last available on-treatment HIV-1 
RNA ≥50 copies/mL

No Virologic Data in the Week 48 Analysis Window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following:
Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL, or
Missing data during the window but on study drug
8.5.1.2.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects with HIV-1 RNA ≥50 copies/mL at
Week 48 in the GS-9883/F/TAF group is at least 4% higher than that in the boosted PI + 2NRTIs
group; the alternative hypothesis is that the proportion of subjects with HIV-1 RNA 
≥50 copies/mL in the GS-9883/F/TAF group is less than 4% higher than that in the boosted-PI + 
2NRTIs group.
Non-inferiority will be assessed using the confidence interval (CI) approach. The point estimate 
of treatment difference (GS-9883/F/TAF – boosted PI + 2NRTIs) and the associated 2-sided 
95% CIs will be constructed based on the exact method. It will be concluded that 
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CI of the difference between treatment groups (GS-9883/F/TAF – boosted PI + 2NRTIs) in the 
percentage of subjects with HIV-1 RNA ≥50 copies/mL is less than 4% (ie, a margin of 4% is 
applied to non-inferiority assessment).
If non-inferiority of GS-9883/F/TAF to boosted PI + 2NRTIs 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 
GS-9883/F/TAF over boosted PI + 2NRTIs will be established.
8.5.2.
Secondary Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the US 
FDA-defined snapshot algorithm will also be evaluated. The 95% CIs will be constructed in the 
same manner as for the primary efficacy endpoint. However, non-inferiority will be assessed 
using a margin of 10%. It will be concluded that GS-9883/F/TAF is noninferior to boosted PI 
+ 2NRTIs if the lower bound of the 2-sided 95% CI of the difference between treatment groups 
(GS-9883/F/TAF – boosted PI + 2NRTIs) in the response rate is greater than -10%.
The change from baseline in CD4+ cell count at Week 48 will be summarized by treatment using 
descriptive statistics. The differences in changes from baseline in CD4+ cell count between
treatment groups and the associated 95% CIs will be constructed using ANOVA models, 
including treatment (GS-9883/F/TAF vs. boosted PI + 2NRTIs) as a fixed effect in the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise, will be summarized 
for subjects in the safety analysis set according to the study drug received.
Data for the pretreatment period and the period post the date of last dose of study drug plus 
30 days will be included in data listings for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration page in CRF. Exposure data will be summarized by treatment.
Duration of exposure to study drug will be expressed as the number of weeks between the first 
and last dose of the study drug, inclusive, regardless of temporary interruptions in study drug 
administration and summarized by treatment.
Dosing information for individual subjects will be listed.


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8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study drug start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.
On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. The 
Gilead medical personnel will review the possible Stage 3 events and approve the events that 
meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of an 
AIDS-Defining Diagnosis will be listed.
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 5.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to and including the date of last dose 
of study drug plus 30 days, will be summarized by treatment. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum postbaseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.


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8.7.
Pharmacokinetic Analysis
For the intensive PK substudy, plasma concentrations of GS-9883 may be summarized by 
nominal sampling time using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Ctau, 
AUCtau, and T½, as appropriate) may be listed and summarized using descriptive statistics (eg, 
sample size, arithmetic mean, geometric mean, coefficient of variation %, SD, median, Q1, Q3, 
minimum, and maximum). Plasma concentrations over time will be plotted in semi-logarithmic 
and linear formats as mean ± standard deviation, and median (Q1, Q3).
For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
descriptive statistics or population approaches.
TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.
8.8.
Patient Reported Outcomes (PRO)
The PRO measures based on questionnaires (eg, SF-36 and HIV Symptoms Distress Module) 
may be summarized by treatment and visit using descriptive statistics.
8.9.
Sample Size
A total of approximately 520 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (260 subjects per treatment group), achieves at least 90% power to detect a 
non-inferiority margin of 4% difference in percentage of subjects with HIV-1 RNA 
≥50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm between the 
two treatment groups. For sample size and power computation, it is assumed that both treatment 
groups have 2% of subjects with HIV-1 RNA ≥50 copies/mL at Week 48 (based on the 
historical Gilead E/C/F/TAF and STB studies), that a non-inferiority margin is 4%, and that the 
significance level of the test is at a one-sided 0.025 level. Sample size and power calculations 
were made using the statistical software package nQuery Advisor (Version 6.0).
8.10.
Independent Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after 
approximately the first 30% subjects enrolled have completed Week 12 of the study or 
prematurely discontinued from the study drug, and will also convene after all subjects have 
completed Week 24 of the study or prematurely discontinued from study drug. However, Gilead 
will defer to the IDMC for any decision to convene earlier or more frequently. The IDMC will 
examine the safety results of the trial and also focus on logistical issues such as accrual, 
retention, quality of clinical and laboratory data, and implications of results of external studies.
No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.


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For each IDMC analysis performed prior to analysis for the primary efficacy endpoint, an alpha 
penalty of 0.00001 will be applied for the primary analysis of the primary efficacy endpoint.
8.11.
Analysis Schedule
The Week 48 analysis will be conducted after all subjects either complete their Week 48 visit or 
prematurely discontinue from the study drug, respectively. Final analysis will be performed after 
all subjects complete the study or prematurely discontinue from the study.


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


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


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


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


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


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


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10.
REFERENCES
Airoldi M, Zaccarelli M, Bisi L, Bini T, Antinori A, Mussini C, et al. One-pill once-a-day 
HAART: a simplification strategy that improves adherence and quality of life of 
HIV-infected subjects. Patient preference and adherence 2010;4:115-25.
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.
Bangsberg DR, Ragland K, Monk A, Deeks SG. A one-pill, once-daily, fixed-dose combination 
(FDC) of efavirenz, emtricitabine, and tenofovir disoproxil fumarate 
(EFV/FTC/TDF) regimen is associated with higher unannounced pill count 
adherence than non-one pill, once-daily [Poster]. 17th Conference on Retroviruses 
and Opportunistic Infections (CROI); 2010 February 16-19; San Francisco, CA. 
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.
Dejesus E YB, Morales-Ramirez JO, Sloan L, Ward DJ, Flaherty JF, et al. . Simplification of 
Antiretroviral Therapy to a Single-Tablet Regimen Consisting of Efavirenz, 
Emtricitabine, and Tenofovir Disoproxil Fumarate Versus Unmodified 
Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients. 
Acquir Immune Defic Syndr 2009;51 (2):163-74.
Department for Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents. Developed by the DHHS 
Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working 
Group of the Office of AIDS Research Advisory Council (OARAC). Downloaded 
from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 08 April, 
2015.
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet 
2003;362 (9387):847-52.
Hodder SL, Mounzer K, Dejesus E, Ebrahimi R, Grimm K, Esker S, et al. Patient-Reported 
Outcomes in Virologically Suppressed, HIV-1-Infected Subjects After Switching 
to a Simplified, Single-Tablet Regimen of Efavirenz, Emtricitabine, and 
Tenofovir DF. AIDS Patient Care STDS 2010;24 (2):87-96.
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of 
mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. 
Lancet 1998;352 (9142):1725-30.


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Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.
Sax PE, Meyers J, Mugavero M, Davis KL. Adherence to Antiretroviral Treatment Regimens 
and Correlation with Risk of Hospitalization Among Commercially Insured HIV 
Patients in the United States [Poster O113]. 10th International Congress on Drug 
Therapy in HIV Infection; 2010 November 7-11; Glasgow, UK. 
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.
The Joint United Nations Programme on HIV/AIDS (UNAIDS). Fact Sheet: 2014 Global 
Statistics. Available at: 
http://www.unaids.org/sites/default/files/media_asset/20150714_FS_MDG6_Rep
ort_en.pdf.  2014.


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


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of 
Switching from Regimens Consisting of Boosted Atazanavir or Darunavir plus either 
Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir 
Alafenamide in Virologically Suppressed HIV-1 Infected Adults 
GS-US-380-1878 Amendment 2, 19 October 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
~1 
N (JJ;u m__ !\it 0 
Erin Quirk, MD (Printed) 7 
PPD 
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 ail study personnel under my supervision copies of the protocol and access to all 
infonnation provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
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Appendix 2.
Study Procedures Table
Study Procedures
Screeninga
Day 1b
End of Weeke, v
Post-Week 48e, w
30-Day 
Follow-upu
Early Study 
Drugs DCc
4
8
12
24
36
48
Every 12 Weeksx
Informed Consent
X
Medical History
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed 
Physical Exam 
X
X
Xd
Xd
Xd
X
Xd
X
Xd, aa
Xd,f
Xf
12-Lead ECG (performed supine)
X
X
X
X
Xm
Xbb
SF-36, HIV Symptoms Distress 
Module, WPAI, and UCLA SCTC 
GIT 2.0 Questionnaires
X
X
X
X
VAS Adherence Questionnaire
X
X
X
X
X
X
X
X
Height
X
Vital signs (blood pressure, pulse, 
respiration rate, and temperature), 
including Weight 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
Xj
Estimated Glomerular Filtration Rate
(eGFR)
X
X
X
X
X
X
X
X
X
X
X
Hematology Profilek
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X


GS-9883/F/T AF 
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Study Procedures 
Evaluation of renal tubular fimction1 
Plasma and Urine Storage Sample 
Whole Blood sample for potential 
HIV DNA genotyping 
HCV Serology 
HIV -1 Genotype/Phenotype e 
Single PK Samplen 
Trough and post dose PK Sample
0 
OptionaliPPD 
1 
r 
RandomizationY 
Provide subject dosing diary to 
Treatment Group !subjects 
Optional PK Substudy" 
HBV blood panel 
Plasma HBV DNAr 
Study Drug Dispensation
1 
Study Drug Accountability 
Screening• 
Day l b 
X 
X 
X 
X 
X 
X 
X 
X'l 
X 
X 
a. 
Evaluations to be completed within 30 days prior to Day 1. 
4 
X 
X 
X 
X 
X 
X 
X 
End of Week•,v 
Post-Week 48e,w 
8 
12 
24 
36 
48 
Every 12 Weeksx 
X 
X 
xi 
X 
X 
X 
X 
X 
X 
X 
xm 
X 
X 
X 
X 
X 
X 
X 
X 
X' 
X' 
X',z 
xs,z 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
b. 
Initiation of the ftrst dose of study dmg is to take place in-clinic following completion of study procedures on the Day 1 visit. 
30-Day 
Follow-upu 
Final 
Amendment2 
Early Study 
Drugs De< 
X 
x< 
X 
X 
c. 
Early Study Drugs Discontinuation visit to occtu· within 72 hom-s of last dose of study dmg. Subjects will be asked to continue attending the scheduled study visits tlu·ough the 
Week 48 Visit even if the subject discontinues study dmg. 
d. 
Symptom-directed physical examination as needed. 
e. 
HIV-1 genotype and phenotype testing for subjects with vit·ologic failm·e. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV -1 RNA and HIV -1 genotype and phenotype (reverse transcriptase, protease and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebotmd Schema (Sections 6.13) 
f. 
Any adve1-se event or test showing abn01malresults that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) tmtil the abn01mality is resolved, rettuns to baseline, or is otherwise explained. 
g. 
Females of childbearing potential only. Positive m-ine pregnancy tests will be confumed with a senun test. 
CONFIDENTIAL 
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h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN) At Day 1, Weeks 12, 24, 48 and every 24 weeks post Week 48, analyses of glucose will be done as part of the fasting metabolic assessments and not as part of 
the chemistry profile. Additionally, TSH will be analyzed at Screening, Day 1, Weeks 24, 48, followed by every 24 weeks post Week 48, and Early Study Drugs 
Discontinuation visit. PT/INR will be performed at Day 1.
i.
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides).  If the subject 
has not fasted prior to the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments.
j.
Every 24 weeks post Week 48 Visit
k.
CBC with differential and platelet count.
l.
Evaluation of renal tubular function includes analyses of urine albumin, urine creatinine, urine protein, retinol binding protein and beta-2-microglobulin 
m.
To be performed every 48 weeks post Week 48 Visit
n.
A single PK blood sample will be collected at any time pre or post dose from subjects in Treatment Group 1.
o.
A trough PK blood sample will be collected between 20-28 hours following the last dose from subjects in Treatment Group 1. Following an observed dose, a single post dose
blood sample will be collected between 1 and 4 hours post dose.
p.
A PK substudy will be performed in a subset of Treatment Group 1subjects (n=24) at selected study sites.  The pharmacokinetic substudy visit must occur at the Week 4 or
Week 8 visits. The substudy will include intensive PK profiling in plasma.
q.
HBV blood panel will be performed at Screening (Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody 
(HBcAb)). 
r.
To be performed for subjects who meet the definition of HBV infection
s.
At Weeks 12, 24, 48, 72, 96, and 120, for subjects who meet the definition of HBV infection at any visit, the following will be performed by the central laboratory: HBsAb, 
HBsAg (qualitative and quantitative) and HBeAg (if negative reflex, HBeAb).  
t.
Study drug GS-9883/F/TAF to be dispensed to Treatment Group 1 subjects.
u.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. Those subjects who prematurely discontinue study drug and continue in the study 
through at least one subsequent visit after the Early Study Drug Discontinuation Visit will not be required to complete the 30 Day Follow Up Visit.
v.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to
Week 36, unless otherwise specified. The visit window at Weeks 48 will be ± 6 weeks of the protocol-specified visit date. 
w.
Visit window of 6 days for study visits post Week 48.
x.
GS-9883/F/TAF FDC will be dispensed to subjects participating in the study post Week 48 visit.
y.
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit provided that all screening procedures have been completed and subject eligibility has been 
confirmed.
z.
At Weeks 48, 96 and 144, for subjects who do NOT meet the definition of HBV infection at any visit, the following will be performed by the central laboratory: HBsAg, 
HBsAb, and HBcAb. Subjects who are HBsAg and/or HBcAb positive will have a reflex test for HBV DNA (viral load).
aa.
A complete physical exam should be done every 48 weeks post Week 48 Visit.
bb. Only to be completed for Early Study Drugs Discontinuation Visits up to Week 48.


GS-9883/Fff AF 
Protocol GS-US-380-1878 
Final 
Gilead Sciences, Inc. 
Amendment 2 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
Grade I 
~-----G-r_a_d_e-2----~~ 
~~ ______ G_r_a_de-3------~~ 
~~ __________ G_m_d_e_4--------~ 
! 
May continue dosing 
Repeat lab to 
at the discretion of 
confrrm toxicity 
the investigator 
grade 
If confrrmed and possibly and/or probably related to investigational 
medicinal products: 
I. Withhold investigational medicinal products until :5 Grade 2 
2. 
Restart all investigational medicinal products at Full dose 
l 
If Grade 3 or 4 recurrence that is confirmed and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
Repeat lab to 
confirm toxicity 
grade 
1 
1 
lfc 
nrelated to 
onfirmed and u 
stigational me 
ng may contin 
he investigator 
inve 
dicinal products, 
dosi 
ue at the discretion 
oft 
If confirmed and 
possibly or probably 
1_. related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently and 
follow at periodic 
intervals at least weekly 
until a return to 
baseline or is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 
CONFIDENTIAL 
Page 96 
19 October 2016 


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 97
19 October 2016
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count  
(ANC)
Adult and Pediatric, 
≥ 7 Months# 
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 98
19 October 2016
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 99
19 October 2016
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects.  Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 100
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to  <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant  <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L                
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L                 
2.0 t o <2.5 mmolL
2.0 mEq/L                         
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant  <1 Year
>ULN to 6.0 mEq/L           
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L             
6.5 to 7.0 mmol/L
7.0 mEq/L                  
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 101
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL                          
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL              
1.74 to <1.94 mmolL
6.1 to  <7.0 mg/dL                     
1.51 to < 1.74 mmolL
< 6.1 mg/dL                           
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia (corrected 
for albumin if appropriate*)
Adult and Pediatric 
7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
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


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 102
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
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


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 103
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypouricemia               
Adult and Pediatric           
≥ 1 year   
Infant  < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L
LDL (Fasting)
Adult
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
LDL (Fasting)
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to  4.92 mmol/L
>4.92 mmol/L


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 104
19 October 2016
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects >70 yrs.  Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 105
19 October 2016
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
                              Females
>ULN - 10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
                              Males
6-10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 h
>1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
>499 to 799 mg/m2/24 h
>799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes:

Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by Covance Laboratory, however for other laboratories, toxicity grades will only be assigned to 
Dipstick Hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.

If the severity of a clinical AE could fall under either one of two grades (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.


GS-9883/F/TAF
Protocol GS-US-380-1878
Final
Gilead Sciences, Inc.
Amendment 2 
CONFIDENTIAL
Page 106
19 October 2016
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Arrhythmia (general)
(By ECG or physical exam)
Asymptomatic AND No 
intervention indicated
Asymptomatic AND Non-
urgent medical intervention 
indicated
Symptomatic, non-life-
threatening AND Non-
urgent medical intervention 
indicated 
Life-threatening arrhythmia 
OR Urgent intervention 
indicated
Cardiac-ischemia/Infarction
NA
NA
Symptomatic ischemia 
(stable angina) OR Testing 
consistent with ischemia 
Unstable angina OR Acute 
myocardial infarction
Hemorrhage (significant acute 
blood loss)
NA
Symptomatic AND No 
transfusion indicated
Symptomatic AND 
Transfusion of 2 units 
packed RBCs (for children 
10 cc/kg) indicated 
Life-threatening hypotension 
OR Transfusion of 2 units 
packed RBCs indicated (for 
children 10 cc/kg) indicated
Hypertension (with repeat 
testing at same visit)
140–159 mmHg systolic 
OR 
90–99 mmHg diastolic
159–179 mmHg systolic 
OR 
99–109 mmHg diastolic
179 mmHg systolic 
OR 
109 mmHg diastolic
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization (other than 
ER visit) indicated
Pediatric 17 Years (with 
repeat testing at same visit)
NA
91st–94th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
≥95th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization indicated 
(other than emergency room 
visit)
Hypotension
NA
Symptomatic, corrected with 
oral fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure
Pericardial Effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, moderate or 
larger effusion requiring no 
intervention
Effusion with non-life-
threatening physiologic 
consequences OR Effusion 
with nonurgent intervention 
indicated
Life-threatening consequences 
(eg, tamponade) OR Urgent 
intervention indicated


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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