A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis
Phase: PHASE3
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences

~ GILEAU 
CLINICAL STUDY PROTOCOL 
Study Title: 
A Phase 3b Open-Label Study to Evaluate the Safety, 
Tolerability, Pharmacokinetics and Efficacy ofE/C/F/TAF 
Fixed Dose Combination (FDC) in HIV -1 Infected Subjects on 
Chronic Hemodialysis 
Sponsor: 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
IND Number: 
111,007 
EudraCT Number: 
2015-002713-30 
Clinical Trials.gov Identifier: Not Available 
Indication: 
HIV -1 Infection 
Protocol ID: 
GS-US-292-1825 
Clinical Program Manager: 
Name: 
Telephone: 
Fax: 
Gilead Medical Monitor: 
Name: 
Telephone: 
Fax: 
Protocol Version/Date: 
Original: 
PPD 
PPD 
PPD 
Devi SenGupta, MD 
PD 
PPD 
08 July2015 
CONFIDENTIALITY STATEMENT 
I 
The infonnation contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Board or Independent Ethics Committee. The infmmation 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 infmmation to others without written authorization 
from Gilead Sciences, Inc., except to the extent necessruy to obtain infmmed consent from those 
persons to whom the dmg may be administered. 

EICIFITAF 
Protocol GS-US-292-1825 
Gilead Sciences, Inc. 
TABLE OF CONTENTS 
Final 
Original 
TABLE OF CONTENTS ........ ................... ............... ............... ............... ............... ............... ............... ................ 2 
LIST OF IN-TEXT TABLES 
...... 4 
LIST OF IN-TEXT FIGURES 
.4 
PROTOCOL SYNOPSIS 
.. .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. .. . 
. 5 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS. 
.9 
1. 
INTRODUCTION .................................................... ............... ............... ............... ............... ................... .. .. 12 
1.1. 
1.2. 
1.3. 
1.4. 
1.5. 
Background ................... ................ ................ .. . 
Tenofovir Alafenamide (TAF, GS-7340) 
1.2.1. 
General Information .. .. .............. .. .............. ... .. 
1.2.2. 
Preclinical Pharmacology and Toxicology 
1.2.3. 
Nonclinical Pharmacokinetics ...................... .. 
1.2.4. 
Nonclinical Toxicology ............. .. .............. .. .............. .. .............. .. .. .. .. 
1. 2. 5. 
Clinical Trials of ElvitegraviriCobicistat/Em tricitabine/T enofovir 
.. .. 12 
.. .. 13 
.. .. 13 
.. .. 13 
.. .. 14 
.. .. 15 
Alafenamide (EIC/F IT AF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 
. ... 16 
Rationale for This Study .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . .. .. . .. . .. .. .. . .. .. . .. . .. .. .. . .. .. . .. . .. 
.. .. 17 
1.3.1. 
Rationale for Dose Selection ...................... ............... ............... ............... ................... .. .. 18 
Risk/Benefit Assessment for the Study ........................ ............... ............... ............... ................... .. .. 20 
Compliance 
.. .. .. .. .. .. .. . .. .. .. .. .. .. .. . 
. .............. ............... ............... ............... ................... .. .. 20 
2. 
OBJECTIVES 
.. .. 21 
.. .. 22 
.. .. 22 
.. .. 22 
.. .. 23 
.. .. 23 
.. .. 23 
.. .. 23 
.. .. 23 
3. 
4. 
5. 
STUDY DESIGN ........... .. 
3. 1. 
Study Design 
3.2. 
Study Treatments ............ .. 
3.3. 
Duration of Treatment 
3.4. 
End of Study ................ ... .. 
3. 5. 
Post Study Care 
3.6. 
Source Data ............ .. 
3.7. 
PPD 
~--------------------------~ 
SUBJECT POPULATION .......................................... .. 
4.1. 
4.2. 
4.3. 
Number of Subjects and Subject Selection 
Inclusion Criteria ......... .. .. ............ .. .. ............ ....... .. 
Exclusion Criteria ................................................ . 
INVESTIGATIONAL MEDICINAL PRODUCTS 
5.1. 
5.2. 
5.3. 
5.4. 
5.5. 
Emollment.. .. .. 
Description and Handling ofEIC/F/TAF FDC Tablets .. 
5. 2. 1. 
Formulation .. 
5.2.2. 
Packaging and Labeling 
5.2.3. 
Storage and Handling ... 
Dosage and Administration of EICIF IT AF 
Prior and Concomitant Medications 
Accountability for EICIF IT AF 
5.5.1. 
Study Drug Return or Disposal 
6. 
STUDY PROCEDURES .... 
6.1. 
6.2. 
Subject Emollment and Treatment Assignment. 
Pretreatment Assessments ............ .. .............. .. ... . 
CONFIDENTIAL 
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.. .. 24 
.... 24 
.. .. 24 
.. .. 26 
.... 28 
.... 28 
.. .. 28 
.. .. 28 
.... 28 
.. .. 29 
.. .. 29 
.. .. 29 
.. .. 35 
.... 35 
.. .. 36 
........ 36 
. ....... 36 
08 July 2015 

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6.2.1.
Screening Visit .....................................................................................................................36
6.2.2.
Day 1 Assessments...............................................................................................................38
6.3.
Treatment Assessments (Weeks 2-48) ...................................................................................................39
6.4.
Post-treatment Assessments ...................................................................................................................41
6.4.1.
30-Day Follow-up Assessments...........................................................................................41
6.4.2.
Early Study Drug Discontinuation Assessments (ESDD)....................................................42
6.4.3.
Criteria for Discontinuation of Study Treatment..................................................................44
6.5.
Other Evaluations...................................................................................................................................44
6.5.1.
Pharmacokinetic (PK) Sub-study .........................................................................................44
6.5.2.
Blood Storage.......................................................................................................................44
6.6.
Virologic Failure....................................................................................................................................45
6.6.1.
Management of Virologic Failure ........................................................................................45
6.6.2.
Subjects with ≥ 400 Copies/mL of HIV-1 in the Absence of VR ........................................45
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................47
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events....................................47
7.1.1.
Adverse Events.....................................................................................................................47
7.1.2.
Serious Adverse Events........................................................................................................47
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................48
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................48
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................48
7.2.2.
Assessment of Severity ........................................................................................................49
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................49
7.3.1.
Adverse Events.....................................................................................................................49
7.3.2.
Serious Adverse Events........................................................................................................49
7.4.
Gilead Reporting Requirements.............................................................................................................51
7.5.
Special Situations Reports......................................................................................................................51
7.5.1.
Definitions of Special Situations..........................................................................................51
7.5.2.
Instructions for Reporting Special Situations.......................................................................52
7.6.
Toxicity Management ............................................................................................................................53
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................53
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................53
7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................54
7.6.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis 
Management in Subjects Co-infected with Hepatitis B........................................................54
8.
STATISTICAL CONSIDERATIONS................................................................................................................56
8.1.
Analysis Objectives and Endpoints........................................................................................................56
8.1.1.
Analysis Objectives..............................................................................................................56
8.1.2.
Primary Endpoint .................................................................................................................56
8.1.3.
Secondary Endpoints............................................................................................................56
8.2.
Analysis Conventions.............................................................................................................................56
8.2.1.
Analysis Sets ........................................................................................................................56
8.3.
Demographic Data and Baseline Characteristics ...................................................................................57
8.4.
Primary and Secondary Analysis ...........................................................................................................57
8.4.1.
Primary Analysis..................................................................................................................57
8.4.2.
Secondary Analyses .............................................................................................................57
8.5.
Safety Analysis.......................................................................................................................................57
8.5.1.
Extent of Exposure...............................................................................................................58
8.5.2.
Adverse Events.....................................................................................................................58
8.5.3.
Laboratory Evaluations ........................................................................................................58
8.5.4.
Other Safety Evaluations......................................................................................................59

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8.6.
Pharmacokinetic Analysis......................................................................................................................59
8.7.
Sample Size............................................................................................................................................59
8.8.
Data Monitoring Committee ..................................................................................................................59
9.
RESPONSIBILITIES..........................................................................................................................................60
9.1.
Investigator Responsibilities ..................................................................................................................60
9.1.1.
Good Clinical Practice..........................................................................................................60
9.1.2.
Institutional Review Board (IRB) / Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................60
9.1.3.
Informed Consent.................................................................................................................61
9.1.4.
Confidentiality......................................................................................................................61
9.1.5.
Study Files and Retention of Records ..................................................................................61
9.1.6.
Case Report Forms...............................................................................................................63
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................63
9.1.8.
Inspections............................................................................................................................63
9.1.9.
Protocol Compliance............................................................................................................64
9.2.
Sponsor Responsibilities ........................................................................................................................64
9.2.1.
Protocol Modifications.........................................................................................................64
9.2.2.
Study Report and Publications .............................................................................................64
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................64
9.3.1.
Payment Reporting...............................................................................................................64
9.3.2.
Access to Information for Monitoring..................................................................................65
9.3.3.
Access to Information for Auditing or Inspections ..............................................................65
9.3.4.
Study Discontinuation..........................................................................................................65
10.
REFERENCES ...................................................................................................................................................66
11.
APPENDICES ....................................................................................................................................................69
Appendix 1.
Investigator Signature Page....................................................................................................70
Appendix 2.
Study Procedures Table..........................................................................................................71
Appendix 3.
Pharmacokinetic Substudy .....................................................................................................74
Appendix 4.
Management of Clinical and Laboratory Adverse Events......................................................75
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............76
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................98
Appendix 7.
Definitions of HIV-1 Related Disease (CDC Guidelines) {35184}.....................................101
LIST OF IN-TEXT TABLES
Table 4-1.
Disallowed Agents .................................................................................................................27
Table 5-1.
Prior and Concomitant Medications.......................................................................................31
LIST OF IN-TEXT FIGURES
Figure 3-1.
Study Schema.........................................................................................................................22
Figure 6-1.
Schema for Management of Virologic Failure .......................................................................46

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3b Open-Label Study to Evaluate the Safety, 
Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF 
Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on 
Chronic Hemodialysis
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
111,007
2015-002713-30
Not available 
Study Centers Planned:
Approximately 50 study sites in North America and Europe
Objectives:
The primary objective of this study is as follows:

To evaluate the safety and tolerability of the
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
(EVG/COBI/FTC/TAF; E/C/F/TAF) fixed dose combination 
(FDC) in HIV-1 infected adults with end stage renal disease 
(ESRD) on chronic hemodialysis (HD) at Week 48
The secondary objectives of this study are as follows: 

To evaluate the proportion of subjects achieving virologic 
response (defined as HIV-1 RNA < 50 copies/mL, 
Snapshot analysis) at Weeks 24 and 48

To evaluate plasma pharmacokinetics (PK) of EVG, COBI, 
FTC, TAF and TFV in HIV-1 infected patients with ESRD on 
HD
Study Design:
Open-label, multicenter, single-arm study to assess the safety, 
tolerability, pharmacokinetics, and efficacy of E/C/F/TAF FDC
dosed once daily in HIV-infected adult subjects with ESRD on 
chronic HD. 
All subjects will switch from their current antiretroviral (ARV) 
regimen to E/C/F/TAF on Day 1. The treatment duration will be 
48 weeks.
Number of Subjects 
Planned:
Approximately 50 subjects with ESRD on chronic HD will be 
enrolled.

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Target Population:
HIV-1 infected adults (≥18 years) with ESRD on chronic HD for 
≥6 months prior to screening, and HIV-1 RNA < 50 copies/mL on 
a stable antiretroviral (ARV) regimen for ≥ 6 consecutive months 
prior to screening.
Duration of Treatment:
Subjects will be treated for 48 weeks.
Diagnosis and Main 
Eligibility Criteria:
HIV-1-infected adults who meet the following criteria:

No documented history of HIV-1 resistance to EVG, FTC,
3TC or TFV

Currently receiving a stable antiretroviral regimen for 
≥6 consecutive months prior to screening

Plasma HIV-1 RNA < 50 copies/mL for at least 6 months 
preceding the screening visit

CD4+ T cell count of ≥ 200 cells/μL

ESRD with eGFR < 15 mL/min by Cockcroft-Gault, 
on chronic HD for ≥ 6 months prior to screening

Chronic Hepatitis B (HBV) infection allowed 

Hepatitis C (HCV) infection allowed 
Study Procedures/
Frequency:
Following Screening, eligible subjects will be required to return 
for study visits at Day 1, Weeks 2, 4, 8, 12, 24, 36 and 48. After 
the Week 48 visit, subjects will stop study drug and complete a 
30-Day Follow-up visit to complete their participation in the study.
For all subjects, HBV and HCV serologies will be analyzed at 
Screening. Adverse events, concomitant medications, complete or 
symptom-directed physical examinations, laboratory analyses 
(hematology and chemistry), fasting lipids and glucose, 
HIV-1 RNA, CD4+ T cell count and estimated GFR will be 
performed at the Screening, Day 1, and all subsequent study visits.
A single pre-dose blood draw for PBMCs will be collected from
all subjects at Week 4 or Week 12, which must be the day of 
hemodialysis. 
All subjects who provide consent will be eligible to participate in 
the pharmacokinetic sub-study (target n = 15).

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Test Product, Dose, and 
Mode of Administration:
FDC of elvitegravir 150 mg / cobicistat 150 mg /
emtricitabine 200 mg / tenofovir alafenamide 10 mg 
administered orally once daily with food until the next 
hemodialysis. On the day of hemodialysis, study drug should be 
administered two to four hours following completion of 
hemodialysis. 
Reference Therapy, 
Dose, and Mode of 
Administration:
N/A
Criteria for Evaluation:
Safety:
Safety evaluations will include reporting of adverse events,
clinical laboratory tests, physical examinations, and vital signs. 
An Independent Data Monitoring Committee (IDMC) will be 
convened after the first 25 subjects enrolled in the study complete 
Week 12 of the study. 
Efficacy:
Virologic response will be determined using the percentages of
subjects with HIV-1 RNA < 50 copies/mL at Week 24 and 48
(snapshot analysis).
Pharmacokinetics:
At Week 4 or Week 12, on the day of hemodialysis, observed 
study drug administration will occur 2 to 4 hours after the 
completion of hemodialysis. A pre-dose (within 30 minutes prior 
to study drug administration) PBMC blood sample will be 
collected from all subjects. Plasma concentrations of EVG, COBI, 
FTC, TAF and TFV and intracellular concentrations of TFV-DP 
may be explored.
Pharmacokinetic (PK) Sub-study
All subjects who provide consent will be eligible to participate in 
the PK sub-study (target n = 15). For the PK sub-study, post-dose 
blood samples will be collected at or between Week 4 or Week 8, 
on the day of hemodialysis. The PK of EVG, COBI, FTC, TAF 
and TFV will be evaluated. Study drug administration will be 
observed in-clinic at the sub-study visit. 
Health Related 
Questionnaires:
SF-36, VAS (visual analogues scale), HIV-TSQ 
(HIV Treatment Satisfaction Questionnaire) and 
Health Utilization Questionnaire will be administered per the 
information provided in the study procedures section of this 
protocol.

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Statistical Methods:
The primary endpoint will be the incidence of treatment-emergent 
Grade 3 or higher adverse events at Week 48.
The proportions of subjects with virologic response 
(HIV-1 RNA < 50 copies/mL, snapshot analysis) and the 
associated 95% confidence intervals at Weeks 24 and 48, 
respectively will be constructed.
Concentrations and PK parameters of EVG, COBI, FTC, TAF and 
TFV for the sub-study, and intracellular PBMC concentrations of 
TFV-DP will be summarized using descriptive statistics 
[N, mean, standard deviation, percent coefficient of variation (%CV),
median, minimum, and maximum].
A sample size of approximately 50 subjects is based on practical 
consideration and is considered to be sufficient to evaluate the 
primary objective of this study. The grade 3 or higher AE rate in 
Study GS-US-292-0112 in subjects that had mild to moderate
renal impairment was 8.8% at Week 48 for the E/C/F/TAF arm. 
Therefore, with 50 subjects, and an assumed rate of Grade 3 or 
higher AEs being 10%, this study would provide 95% confidence 
for the primary endpoint to be (1.7%, 18.3%) assuming normal 
approximation to binomial proportions. 
A sample size of at least 15 subjects is considered for estimating 
the PK parameters in the sub-study for practical reasons. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C 
degrees Celsius
F
degrees Fahrenheit
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration versus time curve
bsAP
serum bone specific alkaline phosphatase
BMD
bone mineral density
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
Cmin
minimum plasma concentration
CNS
central nervous system
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
DXA
dual-energy x-ray absorptiometry
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
E/C/F/TAF
elvitegravir (EVG) 150 mg / cobicistat (COBI) 150 mg / emtricitabine (FTC) 200 mg /
tenofovir alafenamide (TAF) 10 mg fixed dose combination
ESRD
End stage renal disease
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination
FS
failure to suppress
FTC
emtricitabine
GCP
Good Clinical Practice (Guidelines)

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
GGT
gamma glutamyl transferase
GSI
Gilead Sciences, Inc.
GS-7340 
tenofovir alafenamide, TAF, L-Alanine, N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-
1-methylethoxy]methyl]/phenoxyphosphinyl]-, 1-methylethyl ester
HAART
highly active antiretroviral therapy
HBsAg
hepatitis B virus surface antigen serology
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb
hepatitis C virus serology
HD
hemodialysis
HDPE
high-density polyethylene
HIV
human immunodeficiency virus
HMG-CoA
5-hydroxy-3-methylglutaryl-coenzyme A
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
DMC
Data Monitoring Committee
IND
Investigational New Drug (Application)
INSTI
integrase strand transfer inhibitor
IRB
institutional review board
IWRS
interactive web response system
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
NNRTI
non-nucleoside reverse transcriptase inhibitor
NOAEL
no observed adverse effect level
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
OC
osteocalcin
P1NP
procollagen Type 1 N-terminal propeptide
PBMCs
peripheral blood mononuclear cells
PI
protease inhibitor
PK
pharmacokinetic
PT
preferred term 
PTH
parathyroid hormone
QD
once daily 

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
RNA
ribonucleic acid
SAE
serious adverse event
SVR
suboptimal virologic response
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide (GS-7340)
TAF fumarate
tenofovir alafenamide fumarate (GS-7340-03)
TDF
tenofovir disoproxil fumarate
TFV-DP
tenofovir diphosphate (TFVpp)
Tmax
the time (observed time point) of Cmax
ULN
upper limit of the normal range
US
United States
VR
virologic rebound

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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 infection is a life-threatening and serious disease of major 
public health significance, with approximately 34 million people infected with HIV worldwide 
{19661}. The goals of highly active antiretroviral therapy (HAART) for HIV-1 infection are to 
delay disease progression and prolong survival by achieving maximal and durable suppression of 
HIV-1 replication. Prompt antiretroviral therapy (ART) initiation after diagnosis is based on 
growing evidence that untreated HIV infection or uncontrolled viremia is associated with 
development of non- acquired immune deficiency syndrome (AIDS)-defining diseases, including 
cardiovascular disease (CVD), kidney disease, liver disease, neurologic complications, and 
malignancies. The success of ART has shifted clinical attention towards regimens that optimize 
long-term adherence, tolerability and safety. Adherence to ART is required to prevent 
development of drug resistance and subsequent loss of virologic suppression, and adherence to 
ART is improved by reducing pill burden and dosing frequency {4266}, {4256}. Once-daily, 
single tablet regimens are associated with high adherence, better clinical outcomes, including 
fewer hospitalizations, improved patient satisfaction, and excellent virologic outcomes {7034}, 
{7035}, {7036}, {16557}, {16560}.
Despite current therapy that effectively suppresses viremia, HIV disease remains a serious 
condition due to non-AIDS associated comorbidities. As treatment guidelines recommend early 
treatment of HIV-1 infection, there is a need for regimens offering enhanced product safety and 
tolerability, effectiveness, and convenience for long-term treatment.
Though antiretroviral drugs have led to dramatic improvements in survival and disease 
progression, complications such as kidney, liver, and cardiac disease have become increasingly 
important causes of morbidity and mortality for HIV patients taking effective therapy {19947}, 
{19948}, {22552}. Recent data has shown that even with treatment, HIV patients experience more 
age-related co-morbidities, such as renal and bone disease, which manifest earlier than their 
age-matched HIV-uninfected peers {19946}. Moreover, the prevalence and incidence of chronic 
kidney disease (CKD) and end stage renal disease (ESRD) in the US are expected to rise as the 
prevalence of HIV infection continues to rise {22553}. Worldwide, prevalence may be even
greater; one cross-sectional study in the East African Republic of Burundi reported 
46% of HIV-positive adults fulfilled criteria for CKD {22551}.
Patients with HIV are at risk for acute and chronic kidney disease from a wide spectrum of 
etiologies, including HIV-associated nephropathy, immune complex kidney disease, thrombotic 
microangiopathy, and kidney disease associated with comorbidities such as diabetes, 
hypertension, hepatitis B and hepatitis C coinfections, as well as medications associated with 
nephrotoxicity. Clearly, new therapies that improve on the current standard of care are needed, 
so that life-long antiviral therapy is more effective, more tolerable, and safer for patients. 
Since the majority of currently available nucleos(t)ide backbones are prescribed as fixed dose 
combinations, HIV-positive patients with chronic kidney disease have particularly limited 
therapeutic options.

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The availability of a single tablet regimen composed of potent agents with improved tolerability 
and long-term safety, that does not require dose adjustment at eGFR < 50 mL/min, would 
represent an important therapeutic innovation in this special patient population, providing more 
convenient dosing and potentially improving patient adherence.
Tenofovir alafenamide (TAF) has a unique metabolism that provides enhanced lymphatic 
delivery of tenofovir, resulting in higher intracellular levels of the active phosphorylated 
metabolite, tenofovir-diphosphate (TFV-DP), and lower circulating levels of TFV {7415}, 
{13119}, {22029}. The distinct metabolism of TAF offers an improved clinical profile compared 
with TDF, which is associated with nephrotoxicity and decreased bone mineral density {21762}, 
{22031}. Compared with TDF, TAF is characterized by lower systemic exposures and higher 
intracellular levels of TFV. Additionally, TFV exposures achieved with TAF in subjects with 
severe renal impairment are comparable to those with normal renal functions receiving 
TDF 300 mg, indicating that TAF can be administered to HIV-1 infected patients with renal 
impairment without dose modification. 
1.2.
Tenofovir Alafenamide (TAF, GS-7340)
1.2.1.
General Information
Tenofovir alafenamide (GS-7340, TAF, or L-Alanine, N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-
1-methylethoxy]methyl]/phenoxyphosphinyl]-, 1-methylethyl ester) is an prodrug of TFV, 
a nucleotide analog that inhibits HIV-1 reverse transcription. TFV is metabolized intracellularly 
to the active metabolite, TFV-DP, a competitive inhibitor of HIV-1 reverse transcriptase (RT) 
that terminates the elongation of the viral deoxyribonucleic acid (DNA) chain. In the 
development of TAF, three forms of the drug substance have been used in various studies: 
GS-7340, synonym for GS-7340 as the free base; GS-7340-02, synonym for TAF monofumarate 
(1:1) molar ratio of TAF to fumaric acid; and GS-7340-03 as the hemifumarate (2:1) molar ratio 
of TAF to fumaric acid. GS-7340-03, also known as TAF fumarate, is considered comparable 
based on physical/chemical properties to GS-7340-02 that has been used in previous studies. 
GS-7340-03 and GS-7340-02 exist as the free base, TAF (GS-7340), in blood and biological 
fluids. 
1.2.2.
Preclinical Pharmacology and Toxicology
1.2.2.1.
Primary Pharmacodynamics
Tenofovir alafenamide is metabolized to TFV, a nucleotide analog (ie, a nucleoside 
monophosphate analog) which is not dependent on an intracellular nucleoside kinase activity 
for the first step in the conversion to the active metabolite, TFV-DP. The cellular enzymes 
responsible for TFV metabolism to the active diphosphorylated form are adenylate kinase (AK) 
{4887} and nucleotide diphosphate kinase, which are highly active and ubiquitous. AK exists as 
multiple isozymes (AK1 to AK4), with the phosphorylation of TFV mediated most efficiently by 
AK2.

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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. Metabolism of TAF was also studied in different 
human blood lymphocyte subpopulations, CD4+ and CD8+ T cells, natural killer (NK) cells,
B-cells and macrophages/monocytes. TAF is metabolized inside host cells to the active 
metabolite TFV-DP. Concentration of the active metabolite TFV-DP was substantial in all 
cell populations.
1.2.2.2.
Safety Pharmacology
Single doses of TAF did not induce pharmacologic effects on the central nervous system of the 
rat (1000 mg/kg), the renal system of the rat (1000 mg/kg), or the cardiovascular system of the 
dog (100 mg/kg).
1.2.3.
Nonclinical Pharmacokinetics
All nonclinical PK experiments were performed using TAF monofumarate (GS-7340-02), and all 
study data described in this section reflect the dosage of the monofumarate. For reference, 
100 mg of TAF monofumarate is equivalent to 80 mg of the GS-7340 free base (TAF).
Key results from nonclinical absorption, distribution, metabolism, and excretion studies of TAF 
are as follows: 

Following oral administration in dogs and monkeys, TAF demonstrated rapid absorption, 
with peak plasma concentrations between 0.25 and 0.5 hours. Thereafter, TAF plasma 
concentrations declined rapidly with a terminal half-life of less than 1 hour. 
Tenofovir alafenamide exposure (Cmax and AUC values) was nonlinear with dose and greater 
than expected with increasing dose. Repeat-dose studies in rats and monkeys showed no 
change in pharmacokinetics over time. 

Peak TFV plasma concentrations occurred following TAF absorption, with TFV Tmax values 
between 0.25 to 1.7 hours in rats, dogs, and monkeys. 

Following oral administration of [14C]-radiolabeled TAF to dogs, a mean total recovery of 
radioactivity at 24 hours of 63% was demonstrated. Radioactivity was detected in all tissues 
except brain with the majority present in the contents of the gastrointestinal tract, liver, 
kidney, and large intestine. Tissue concentrations were the highest in kidney, peripheral 
blood mononuclear cells (PBMCs), liver, large intestine, and bile. Additional studies in dogs, 
TFV concentrations in PBMCs following oral administration of TAF were approximately 
50-fold greater than observed in plasma, with an estimated t½ of greater than 24 hours. 

The major route of elimination of TAF-related radioactivity was via feces, with 
approximately 35% of the dose recovered in feces through 48 hours postdose. The primary 
route of elimination of TFV is renal excretion of unchanged drug based on IV studies of 
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
Tenofovir alafenamide has been found to be a substrate for intestinal efflux transport and in 
nonclinical studies its intestinal absorption was increased by the transport inhibitor 
cyclosporin A. 

No significant inhibition of human drug metabolizing cytochrome P450 (CYP) enzymes, 
uridine diphosphate glucuronyltransferase (UGT) 1A1 or transporters including 
P-glycoprotein, breast cancer resistance protein, organic anion-transporting polypeptide 
(OATP)1B1 and OATP1B3 was observed with TAF in vitro.

Tenofovir alafenamide did not activate human pregnane X receptor (hPXR) or 
aryl hydrocarbon receptor (AhR).

Tenofovir alafenamide was not a substrate for drug-metabolizing CYP enzymes except for 
CYP3A4, which metabolized the compound slowly. 
1.2.4.
Nonclinical Toxicology
Key results from nonclinical toxicology studies of TAF are as follows:

Based on TFV exposure, the no observed adverse effect levels (NOAELs) in the 6-month rat, 
9-month dog, and 1-month monkey studies provide 14-, 4-, and 22-fold safety margins, 
respectively, for a human dose of 25 mg/day.

In chronic studies in rats, bone (atrophy of metaphyseal cancellous bone) and kidneys 
(karyomegaly) were the primary target organs after 26 weeks of treatment with TAF 
100 mg/kg/day; however, effects were not seen at lower doses. Tenofovir alafenamide also 
appeared to increase biochemical markers of bone turnover and decrease serum 
1,25-dihydroxy- and 25-hydroxyvitamin D3 at doses of 25 mg/kg/day and above.

In chronic studies in dogs after 9 months of treatment at doses up to TAF 18/12 mg/kg/day 
(the high dose was reduced from 18 to 12 mg/kg/day due to the occurrence of death, severe 
clinical signs and reduced body weight), the primary target organs were kidney 
(slight to moderate renal tubular degeneration and karyomegaly) and bone 
(decreased bone mineral density [BMD] in metaphyseal cancellous bone). 

Tenofovir alafenamide had no discernable electrocardiograph effect at the low dose of 
2 mg/kg/day. There was some evidence at 6 and 18/12 mg/kg/day for an effect to slightly 
prolong PR intervals. 

After 9 months of treatment, some dogs administered the highest dose of TAF 
(18/12 mg/kg/day) had minimal mononuclear cell infiltration in the posterior uvea, 
considered secondary to general debilitation; this finding did not occur in animals given 
lower doses and it has not occurred in other animal studies. 

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
There were no clear treatment-related effects observed in monkeys following 28 days of 
TAF treatment at 3 and 30 mg/kg/day, including no changes in mitochondrial function and 
mitochondrial DNA (mtDNA) content in the liver, kidney, and skeletal muscle, and 
characterization of lymphocyte populations.

Tenofovir alafenamide was not genotoxic in either in vitro or in vivo assays. 
Tenofovir alafenamide had no adverse effects on male or female fertility parameters in rats. 
There was no effect on fetal viability or fetal development in pregnant rats administered 
doses of TAF up to 250 mg/kg/day or in pregnant rabbits administered TAF up to 
100 mg/kg/day; the highest doses were maternally toxic.
1.2.5.
Clinical Trials of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide
(E/C/F/TAF)
Emtricitabine and TAF have been combined with the integrase inhibitor EVG and its 
pharmacoenhancer COBI in the E/C/F/TAF FDC, which has been designed to be a complete 
treatment regimen for HIV-1 infection and is being evaluated in a broad clinical development 
program. The details of the key clinical studies are provided below:

GS-US-292-0102, a randomized, double-blinded controlled Phase 2 study in which 
E/C/F/TAF is compared to Stribild® (STB), as initial treatment of HIV-infection in 
ART-naive patients. This is a single-variable clinical comparison of the 2 tenofovir prodrugs, 
TAF and TDF 

GS-US-292-0104 and GS-US-292-0111, 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 are as 
follows: 1) 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%), 
2) administration of E/C/F/TAF resulted in > 90% lower plasma TFV and higher intracellular 
TFV-DP relative to STB, 3) 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), 4) Increases from baseline in fasting 
total cholesterol fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides 
were noted in the E/C/F/TAF group;

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
GS-US-292-0112, a Phase 3 open-label safety study of E/C/F/TAF in HIV-1 positive patients 
with mild to moderate renal impairment; Week 48 results demonstrated that patients who 
switched to E/C/F/TAF had no change in eGFR, and had significant improvements in 
measures of renal function including proteinuria, albuminuria, retinol binding protein and 
beta-2-microglobulin. These subjects also had improvements in measures of bone mineral 
density. Importantly, because FTC was given without dose adjustment to patients with 
eGFR 30-50 mL/min, these patients had comparable safety profile to patients with 
eGFR 50-69 mL/min, with no increased rate of potential FTC related drug reactions, 
supporting the safety of FTC at higher exposures. In addition, 92% of study participants 
maintained virologic suppression (HIV-1 RNA < 50 copies/ml) at Week 48 after switching to 
E/C/F/TAF.

GS-US-292-0109, a Phase 3 study designed to evaluate the safety, efficacy, and tolerability 
of switching to E/C/F/TAF in individuals who are virologically suppressed on regimens 
containing TDF. The interim Week 48 key conclusions from this study are as follows: 
1) switching to E/C/F/TAF was noninferior to maintaining FTC/TDF + 3rd Agent 
(STB, efavirenz/emtricitabine/tenofovir DF (ATR), atazanavir (ATV)/boosted + Truvada®) 
as assessed using the FDA snapshot algorithm (Week 48 FAS) with HIV-1 RNA cutoff at 
50 copies/mL (E/C/F/TAF 95.6%; FTC/TDF + 3rd Agent 92.9%; difference in percentages: 
2.7%, 95.01% CI: -0.3% to 5.6%), 2) An improved renal and bone safety profile was 
observed in subjects who switched to E/C/F/TAF, 3) there were no differences in ocular 
findings between treatment groups and no reported cases of uveitis.
1.3.
Rationale for This Study
Because of the increasing average age of HIV-infected patients, the high prevalence of chronic 
kidney disease, and the increasing prevalence of co-morbid conditions that require medical 
management, medical regimens in ESRD patients are complex and can impact a patient’s overall 
risk of morbidity and mortality. The availability of a single-tablet regimen composed of potent 
agents with improved tolerability and long-term safety that does not require dose adjustment at 
eGFR < 15 mL/min, would represent an important therapeutic innovation for HIV infected
patients with ESRD. EVG, COBI, and TAF are not renally eliminated, while the metabolite of 
TAF (TFV) and FTC, are renally eliminated. 
The E/C/F/TAF FDC was recently shown to be safe and efficacious in HIV-infected patients 
with mild to moderate chronic kidney disease (CKD; eGFR 30-69 mL/min) in study 
GS-US-292-0112 through 48 weeks. The long-term safety of E/C/F/TAF remains to be 
established in subjects at more advanced stages of renal impairment, including those with ESRD 
on hemodialysis. The present study will provide the pharmacokinetic data describing TFV and 
FTC exposures in these patients when administered as the E/C/F/TAF FDC, dosed once daily, as 
well as safety and efficacy data in this special population through 48 weeks. 

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1.3.1.
Rationale for Dose Selection
The E/C/F/TDF FDC containing EVG (150 mg), COBI (150 mg), FTC (200 mg), and TAF (10 mg),
is currently under review for use once daily for the treatment of human immunodeficiency virus 
type 1 (HIV-1) infection in adults and pediatric patients 12 years of age and older without any 
known resistance to the individual components. This FDC contains the equivalent doses of 
EVG and COBI in the marketed product, Stribild®. The FTC (200 mg) in the E/C/F/TAF FDC 
represents the marketed dose in several approved FDC products: emtricitabine/tenofovir DF, 
efavirenz/emtricitabine/tenofovir DF, and emtricitabine/rilpivirine/tenofovir DF for the treatment 
of HIV-1 infection.
EVG, COBI, and TAF are not renally eliminated, while the metabolite of TAF (TFV) and FTC, 
are renally eliminated. 
TAF
The Phase 3 study GS-US-292-0112 demonstrated that patients with moderate renal impairment 
(baseline eGFR 30-50 mL/min) who switched to E/C/F/TAF had no change in eGFR, and had 
significant improvements in measures of renal function including proteinuria, albuminuria, 
retinol binding protein and beta-2-microglobulin. These subjects also had improvements in 
measures of bone mineral density. TAF PK in subjects with screening eGFR 30-69 mL/min was 
consistent with data following administration of E/C/F/TAF in nonrenally-impaired 
HIV-infected subjects in Phase 2 and Phase 3 studies. 
Data from GS-US-120-0108 demonstrated that in HIV uninfected subjects with an eGFR of 
15-29 mL/min, plasma TAF exposures increased < 2-fold. Study GS-US-292-1825 will evaluate 
TAF (as well as TFV and FTC) PK in the setting of daily administration of E/C/F/TAF STR in 
treatment-experienced subjects with eGFR < 15 mL/min on chronic hemodialysis.
TFV
In subjects with ESRD, systemic TFV exposures are expected to be higher, but not as high as 
TDF 300 mg. Data from several studies have demonstrated ~90% lower AUC and ~95% lower Cmax
of TFV following administration of TAF vs. TDF (GS-US-120-1101, GS-US-120-0104), 
and the renal impairment study (GS-US-120-0108) showed a mean (% CV) TFV AUCinf of
2074.4 (47.1) ng•h/mL in severe renal impairment, which is within or lower than the range of 
TFV exposures observed in subjects with normal renal function receiving TDF 300 mg once 
daily (2020-2480 ng•h/mL). Given the extensive safety data available for TDF at these 
therapeutic exposures, TFV exposures in renally impaired subjects in the range of those from 
TDF in patients with normal renal function would not require TAF dose modification. PK 
modeling of TAF in ESRD in hemodialysis also indicates that the mean TFV AUC for a daily 
TAF dose of 25 mg is equivalent to a TDF dose of 300 mg plus atazanavir boosted with ritonavir 
in a subject with CrCl > 50 mL/min.

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FTC
The FTC dose (200 mg) in the E/C/F/TAF FDC represents the marketed dose as part of the 
approved products FTC (Emtriva®), FTC/TDF (Truvada®), efavirenz/FTC/TDF (Atripla®), 
FTC/rilpivirine/TDF (Complera® or Eviplera®), and E/C/F/TDF (Stribild®) for the treatment of 
HIV-1 infection. Emtricitabine is principally eliminated by the kidney and higher exposures are 
observed in patients with moderate to severe renal impairment. For eGFR of 30-49 mL/min, 
Emtriva prescribing information recommends dose interval adjustment of the 200 mg oral 
capsule to q48h. However, available clinical experience suggests the plasma FTC may not 
require dose adjustment in the setting of renal impairment. In study GS-US-292-0112, FTC was 
given without dose adjustment to patients with eGFR 30-50 mL/min, and these patients had 
comparable safety profile to patients with eGFR 50-69 mL/min, with no increased rate of 
potential FTC related drug reactions, supporting the safety of FTC at higher exposures. 
In Study FTC-107, an open-label, parallel-group study of single-dose emtricitabine 200 mg in 
HIV uninfected subjects with varying degrees of renal impairment, 6 subjects with moderate 
renal impairment (30-49 mL/min), 5 subjects with severe renal impairment (< 30 mL/min) and 
6 subjects on dialysis were treated. Of note, subjects with baseline eGFR of 30-49 mL/min had 
only twice the mean FTC systemic exposure (mean (%CV) AUCinf: 25.08 hr•μg/mL (23)) 
compared to subjects with eGFR > 80 mL/min (mean (%CV) AUCinf: 11.78 (25) hr•μg/mL. 
Subjects on dialysis had an AUCinf of 53.22 hr•μg/mL (19). In all cohorts, the overall incidence 
of adverse events was low and there was no apparent relationship between the incidence of AEs 
and the degree of renal impairment. 
In study GS-US-104-0235, the safety and tolerability of FTC+TDF (200/300 mg) in 
treatment-naïve and treatment-experienced HIV infected subjects with various degrees of renal 
impairment were assessed. One subject in this study assigned to the mild impairment group was 
later found to have moderate impairment (eGFR ≥30 and < 50 mL/min) and one subject 
assigned to moderate impairment was found to have severe impairment (eGFR < 30 mL/min) 
after 40 days of treatment. Based on PK analyses of these subjects, the subject with moderate 
renal impairment was continued on FTC 200 mg daily because FTC exposures remained within 
the predicted range for subjects without renal impairment and the subject with severe renal 
impairment continued to receive FTC 200 mg every 48 hours based upon appropriate FTC 
systemic exposures. 
Consistent with the renal impairment Study FTC-107 described above, results from the PK sub-
study of GS-US-292-0112 (n = 30) showed that FTC exposure was slightly higher in subjects 
with mild to moderate renal impairment as compared with historical data on FTC in subjects 
with normal renal function (mean [%CV] FTC AUCtau 20968.6 [25.5] ng•h/mL versus 
11,714.1 [16.6] ng•h/mL in Phase 2 Study GS-US-292-0102 of non-renally-impaired 
HIV-infected subjects), as expected due to the renal elimination of FTC. Further population PK 
analysis on all subjects treated in Study GS-US-292-0112 with available FTC data (n = 241), 
confirmed the findings from the PK sub-study, showing slightly higher FTC exposures in 
subjects with baseline eGFRCG < 50 mL/min, as compared with subjects with baseline 
eGFRCG ≥50 mL/min. Importantly, these observed differences in FTC exposure by 

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renal impairment subgroup did not result in a different safety profile. The incidence of adverse 
events that occurred in ≥ 5% of subjects and of treatment-related adverse events that occurred in 
≥1% of subjects was similar between groups after 48 weeks of treatment. Adverse reactions 
from the Emtriva SmPC were also specifically evaluated. Despite higher FTC exposure in this 
study, incidence of these events was similar in subjects with eGFRCG < 50 mL/min and in 
subjects with eGFRCG ≥50 mL/min. The current study will evaluate FTC exposures and safety, 
and an IDMC will be convened to monitor safety data.
1.4.
Risk/Benefit Assessment for the Study
Potential risks of a patient’s study involvement include switching to an unfamiliar regimen with 
potential loss of virologic control and/or new adverse events, the inconvenience of more frequent 
clinic visits and laboratory blood draws and the associated pain and discomfort of phlebotomy. 
Strategies to mitigate these risks include close monitoring of viral load, CD4+ T cell count and 
other lab values as well as monitoring of adverse events. Parameters for discontinuation of the 
study drug due to adverse events or lack of efficacy will be well-defined and closely followed. 
In addition, an independent data monitoring committee will be convened at Week 12 to evaluate 
safety data and determine whether the risks/benefits warrant continuation of the study. 
Potential benefits may include the patient receiving a FDC antiretroviral regimen that is more 
convenient leading to improved adherence, with potentially fewer adverse events than the current 
regimen, E/C/F/TAF may provide an alternative treatment for a patient population with fewer 
therapeutic options than the general HIV-1-infected population. 
Considering the above, the benefit-risk balance for this study is considered positive.
1.5.
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 safety and tolerability of E/C/F/TAF FDC in HIV-1 infected adults with
ESRD on chronic HD at Week 48
The secondary objectives of this study are:

To evaluate the proportion of subjects achieving virologic response (defined as 
HIV-1 RNA < 50 copies/mL, Snapshot analysis) at Weeks 24 and 48

To evaluate plasma pharmacokinetics (PK) of EVG, COBI, FTC, TAF and TFV in 
HIV-1 infected patients with ESRD on HD

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3. 
STUDY DESIGN 
3.1. 
Study Design 
This is an open-label, multicenter, single-rum study to assess the safety, tolerability, 
phrumacokinetics, and efficacy ofEICIFITAF FDC in HIV-1 infected adult subjects with 
ESRD on chronic HD. 
Final 
Original 
Approximately 50 subjects with ESRD on chronic HD will be enrolled. All subjects will switch 
from their cunent antiretroviral regimen to EICIFITAF on Day 1. The total treatment dmation 
will be 48 weeks. After Week 48 visit, all subjects will stop study dmg and complete a 30-Day 
Follow-up visit. 
Figure 3-1. 
Screening 
:::; 30 days 
prior to 
Baseline 
Study Schema 
Day 1 
Week48 
(Primmy Endpoint) 
48 Weeks of Treatment on EICIFITAF 
(n = approximately sot 
30-Day 
Follow-upb.c 
a 
Following the Day 1 visit, subjects will retmn for study visits at Weeks 2, 4, 8, 12, 24, 36 and 48. 
b 
After 48 weeks, subjects will stop study dmg and c.omplete a 30-Day Follow-up visit to end their patticipation in the study. 
c 
Subjects who discontinue study dmg administration before their Week 48 visit, will complete and ESDD visit. 
These subjects may remain on the study off study dtug up to the Week 48 visit. Upon completion of Week 48 visit, subjects 
may be required to rehun to d1e clinic for a 30-Day Follow-up visit to complete their patticipation in d1e study. 
3.2. 
Study Treatments 
Subjects who provide written consent and meet all eligibility criteria will receive 
elvitegravir 150 mg I cobicistat 150 mg I emtricitabine 200 mg I tenofovir alafenamide 10 mg 
(EICIFITAF), on Day 1. 
Study dmg will be administered orally once daily with food at approximately the same time 
every day. On the day of hemodialysis, study chug administration should occm 2 hours following 
the completion ofhemodialysis. 
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3.3. 
Duration of Treatment 
Final 
Original 
The study will consist of a 30-day screening period (within 30 days before Day 1 visit), followed 
by a 48 weeks treatment period. After Day 1, subjects will retum for study visits at 
Weeks 2, 4, 8, 12, 24, 36 and 48. 
After Week 48, subjects will stop study dmg and complete a 30-Day Follow-up visit. 
3.4. 
End of Study 
End of the study will occur when the last subject emolled in the study has completed Week 48 
visit followed by a 30-Day Follow-up visit. 
3.5. 
Post Study Care 
After a subject has completed/te1minated their participation in the study, long-tenn care for the 
subject will remain the responsibility of their primmy treating physician. 
3.6. 
Source Data 
Sponsor will provide somce document worksheets for all study visits. 
3.7. 
~PD 
PD 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 50 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 screening procedures
2) Age ≥ 18 years
3) Currently receiving a stable antiretroviral regimen for ≥ 6 consecutive months prior to 
screening
4) Documented plasma HIV-1 RNA concentrations < 50 copies/mL for at least 6 months 
preceding the screening visit (measured at least twice using the same assay) and have 
HIV-1 RNA < 50 copies/mL at screening
a) In the preceding 6 months prior to screening, one episode of “blip” (HIV-1 RNA 
≥50 copies/mL and < 400 copies/mL) is acceptable, only if HIV-1 RNA is 
< 50 copies/mL immediately before and after the blip. 
b) To determine virologic suppression in the preceding 6 months prior to screening, the 
lower limit of quantification (LLOQ) by the local HIV-1 RNA assay may be used, only if 
its LLOQ is greater than 50 copies/mL (e.g. LLOQ of 75 copies/mL)
5) No documented history of HIV-1 resistance to EVG, FTC, 3TC or TFV and no history of 
switching off EVG, FTC, 3TC or TFV due to concern for resistance
6) CD4+ T cell count of ≥200 cells/μL
7) ESRD with eGFR < 15 mL/min by Cockcroft-Gault formula for creatinine clearance {2202}
Male:
(140 – age in years) (wt in kg) Clcr (mL/min)
72 (serum creatinine in mg/dL)
Female:
(140 – age in years) (wt in kg) 0.85 Clcr (mL/min)
72 (serum creatinine in mg/dL)
8) On chronic HD for ≥ 6 months prior to screening

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9) Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
10) Hepatitis B (HBV) infection allowed if liver function is stable for ≥ 6 months prior to 
screening: ALT ≤ 10 × ULN, AST ≤ 10 × ULN, total bilirubin ≤ 2.5, or normal direct 
bilirubin (subjects with documented Gilbert’s Syndrome or hyperbilirubinemia due to 
atazanavir therapy may have total bilirubin up to 5 × ULN), INR ≤ 1.5 and albumin ≥3 g/dL; 
no evidence of cirrhosis or hepatocellular carcinoma by imaging in the last 12 months
11) Chronic Hepatitis C (HCV) infection allowed if liver function is stable (see above for criteria)
12) Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm3; 
platelets ≥50,000/mm3; hemoglobin ≥ 8.5 g/dL)
13) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤ 5 × ULN)
14) A female subject is eligible to enter the study if it is confirmed that she is:
a) Not pregnant confirmed by a negative serum pregnancy test (unless permanently sterile 
or greater than two years post-menopausal)
b) Of non-child bearing potential (i.e. women who have had a hysterectomy, have had both 
ovaries removed or medically documented ovarian failure, or are postmenopausal women 
> 54 years of age with cessation (for ≥ 12 months) of previously occurring menses
Female subjects who have stopped menstruating for ≥ 12 months but do not have 
documentation of ovarian hormonal failure must have a serum follicle stimulating 
hormone (FSH) level at screening within the post-menopausal range based on the 
Central Laboratory Reference range. 
c) Of childbearing potential and agrees to utilize the protocol specified method of 
contraception or be non-heterosexually active or practice abstinence from screening 
throughout the duration of the study treatment and for 30 days following study drug 
discontinuation (as defined in Appendix 6)
d) Female subjects who utilize hormonal contraception as one of the birth control methods 
must have used the same method for at least three months prior to the study dosing. 
15) Male subjects must agree to use protocol specified method(s) of contraception from 
screening throughout the duration of study treatment and for 30 days following 
discontinuation of study drugs (Appendix 6).
16) Male subjects must agree to refrain from sperm donation from first dose until at least 30 days 
after the last study drug dose.
17) Lactating females must agree to discontinue nursing before the study drug is administered.

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4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
2) Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening
3) Treatment with radiation, cytotoxic chemotherapeutic agents, or any immunomodulator 
within 30 days of screening
4) Any other clinical history, condition, or test result that, in the opinion of the Investigator, 
would make the subject unsuitable for the study or unable to comply with dosing 
requirements
5) Administration of other investigational agents (unless approved by Gilead Sciences). 
Participation in any other clinical trial, including observational trials, without prior approval 
from the sponsor is prohibited while participating in this trial.
6) History or presence of allergy or intolerance to the study drugs or their components
7) A new AIDS-defining condition (excluding CD4+ T cell count and percentage criteria) 
diagnosed within the 30 days prior to screening, with the exception of 
oropharyngeal candidiasis (see Appendix 7)
8) Have an implanted defibrillator or pacemaker
9) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance
10) A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy 
other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive 
carcinoma
11) Received solid organ or bone marrow transplant
12) Significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, 
osteochrondroses), or multiple bone fractures
13) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
14) Systemic chemotherapeutic agents, systemic corticosteroids (except short-term use of 
prednisone as a steroid burst [ ≤ 1 week of use]), immunosuppressant, or 
immunomodulating agents
15) Subjects receiving ongoing therapy with any of the following medications in the Table 4-1
below, including drugs not to be used with EVG, COBI, FTC, TAF

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Table 4-1.
Disallowed Agents
Drug Class
Agents Disallowed*
Alpha Adrenergic Receptor Antagonists
Alfuzosin
Calcium Channel Blockers
Bepridil
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine, 
Oxcarbazepine
Antihistamines
Astemizole, Terfenadine
Antimycobacterials
Rifampin, Rifapentine, Rifabutin
Ergot Derivatives
Ergotamine, Ergonovine
Dihydroergotamine
Methylergonovine
Ergometrine
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Neuroleptics
Pimozide
Phosphodiesterase-5 Inhibitors
Sildenafil (for PAH)
Sedatives/Hypnotics
Orally administered Midazolam, Triazolam
*
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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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Enrollment
This is an open-label, single arm study. All eligible subjects will receive open-label E/C/F/TAF.
Enrollment and Day 1 visit cannot occur until subject eligibility has been confirmed.
It is the responsibility of the Investigator to ensure that the subject is eligible for the study prior 
to enrollment. Once eligibility is confirmed, each subject will be assigned a unique subject 
number using 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 may be performed up to 3 days prior to the in-clinic Day 1 visit, provided that all 
other screening procedures have been completed and subject eligibility has been confirmed. 
Eligibility must be confirmed and all Day 1 tests and procedures must be completed prior 
to the administration of the first dose of study drug.
IWRS will assign study drug bottle numbers at each study visit. Initiation of study drug must 
take place within 24 hours after Day 1 visit.
5.2.
Description and Handling of E/C/F/TAF FDC Tablets
5.2.1.
Formulation
E/C/F/TAF tablets are capsule-shaped, film-coated green tablets and are debossed with “GSI” on
one side of the tablet and “510” on the other side of the tablet. E/C/F/TAF tablets contain 150 mg
of EVG, 150 mg of COBI, 200 mg of FTC, and 10 mg of TAF (as 11.2 mg of TAF fumarate).
The E/C/F/TAF tablet core contains silicon dioxide, croscarmellose sodium, hydroxypropyl
cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and 
sodium lauryl sulfate as inactive ingredients and are film-coated with indigo carmine aluminum 
lake, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and yellow iron oxide.
5.2.2.
Packaging and Labeling
E/C/F/TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle
contains 30 tablets, silica gel desiccant and polyester packaging material. Each bottle is enclosed
with a white, continuous thread, child-resistant polypropylene screw cap with an 
induction-sealed, aluminum-faced liner.
Study drug to be distributed to centers in the US and other participating countries shall be labeled 
to meet applicable requirements of the United States Food and Drug Administration (FDA), 
EU Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal Products), 
and/or other local regulations.

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5.2.3.
Storage and Handling
E/C/F/TAF tablets 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 drug should be stored in a securely
locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug 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 E/C/F/TAF
E/C/F/TAF FDC tablets will be provided by Gilead Sciences.
E/C/F/TAF FDC tablets containing 150 mg of EVG, 150 mg of COBI, 200 mg of FTC, and 
10 mg of TAF will be provided to all eligible subjects at Day 1. Study drug will be administered
orally at approximately the same time each day with food. 
On the day of hemodialysis study drug administration should occur two to four hours 
following the completion of hemodialysis. 
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability (unless otherwise specified in the study procedures sections of this 
protocol). The Investigator will be responsible for maintaining accurate records for all study drug 
bottles dispensed and tablets returned. The inventory and dispensing logs must be available for 
inspection by the study monitor. Study medication supplies, including partially used or empty 
bottles, must be accounted for by the study monitor prior to destruction or return.
5.4.
Prior and Concomitant Medications

Subjects receiving hormonal contraceptives should consider additional methods of 
contraception as concentrations of ethinyl estradiol may decrease and progestin level may 
increase on co-administration with study drug. 

The use of medications for the treatment of HIV, other than study drug, is prohibited.

Subjects receiving concomitant medications that are highly dependent on CYP3A for 
clearance and for which elevated plasma concentrations are associated with serious adverse 
events should consider alternative concomitant medications.

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
During the study, subjects may not receive any of the following concomitant medications:
Competitors of renal excretion (e.g., probenecid; high-dose non-steroidal 
anti-inflammatory drugs)
Known nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, 
cidofovir, foscarnet, cisplatin and pentamidine)

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. Any concomitant 
medication requiring adjustment or discontinuation due to renal impairment or a change in 
renal function on study should be managed per that drug’s prescribing information.

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Table 5-1.
Prior and Concomitant Medications
Drug Class
Agents Disallowed
Use Discouraged and To Be Used With Caution
Acid Reducing Agents
Antacids
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids 
(eg, Tums, Mylanta); the ulcer medication sucralfate
(Carafate); or vitamin or mineral supplements that 
contain calcium, iron or zinc for a minimum of 2 hours 
before and 2 hours after any dose of study drug.
Alpha Adrenergic Receptor 
Antagonists
Alfuzosin
Analgesics
Tramadol, Propoxyphene: 
Concentrations may increase with study drug(s); 
clinical monitoring is recommended.
Antiarrhythmics
Amiodarone, Flecainide Quinidine, Propafenone, 
Systemic Lidocaine, Mexiletine, Disopyramide: 
Concentrations may increase with study drug(s) 
resulting in a potential for cardiac arrhythmias; 
clinical and ECG monitoring is recommended.
Calcium Channel Blockers
Bepridil
Felodipine, Nifedipine, Nicardipine, Verapamil, 
Diltiazem, Amlodipine:
Concentrations may increase with study drug(s). 
Clinical and ECG monitoring of subjects is 
recommended
Digoxin
Digoxin:
Concomitant use may result in increased levels; use 
with caution and with appropriate monitoring of 
serum digoxin levels. Digoxin therapy should be 
initiated at the lower dose, and the dose should be 
titrated to clinical response.
Antibacterials
Clarithromycin and Telithromycin: 
Concentrations may be altered with study drug(s); 
consider an alternative.
Anticoagulants
Warfarin: Concentrations may increase or decrease 
with study drug(s); appropriate INR 
(International Normalized Ratio) monitoring 
is recommended.
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, 
Oxcarbazepine
Ethosuximide, Divalproex, Lamotrigine:
Concentrations may increase with study drug(s); 
clinical monitoring is recommended.

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Drug Class
Agents Disallowed
Use Discouraged and To Be Used With Caution
Antidepressants
Selective serotonin reuptake inhibitors (SSRIs): 
A dose reduction may be required for most drugs of 
this class with the exception of sertraline.
Tricyclics:
Concentrations may increase or decrease with study 
drug(s). Concentration monitoring is recommended 
to ensure adequate clinical response.
Trazodone:
Concomitant use with CYP3A inhibitors results in 
increased concentrations and adverse events; dose 
reduction should be considered.
Antifungals
Ketoconazole and Itraconazole:
Concomitant use with study drug may result in an 
increase in concentrations. Daily dose of 
ketoconazole and itraconazole should be restricted 
to 200 mg. Subjects receiving ketoconazole or 
itraconazole should be monitored for adequate 
clinical response.
Voriconazole:
Concomitant use with study drug may result in an 
increase in concentrations. Clinical monitoring may 
be needed.
Antigout
Colchicine:
Concentrations may increase with study drug(s). 
Dose reductions of colchicine may be required. 
Should not be coadministered in patients with 
renal or hepatic impairment.
Treatment of Gout Flare:
0.6 mg (1 tablet) × 1 dose, followed by 0.3 mg 
(half tablet) 1 hour later. Treatment course may be 
repeated no earlier than 3 days.
Prophylaxis of Gout Flares:
If the original regimen was 0.6 mg twice a day, 
the regimen should be adjusted to 0.3 mg once a 
day. If the original regimen was 0.6 mg once a day, 
the regimen should be adjusted to 0.3 mg 
once every other day.
Treatment of Familial Mediterranean Fever:
Maximum daily dose of 0.6 mg 
(may be given as 0.3 mg twice a day).
Antihistamines
Astemizole, Terfenadine
Antimycobacterials
Rifampin, Rifapentine, 
Rifabutin

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Drug Class
Agents Disallowed
Use Discouraged and To Be Used With Caution
β-Blockers
Metoprolol, Timolol:
Clinical and ECG monitoring of subjects is 
recommended. A dose decrease may be needed.
Corticosteroids: Inhaled/Nasal
Concomitant use of inhaled fluticasone and study 
drug(s) may increase plasma concentrations of 
fluticasone. Use is not recommended unless the 
potential benefit to the subject outweighs the risks 
of corticosteroid side effects. Alternatives should be 
considered, particularly for long-term use.
Corticosteroids: Systemic
Systemic dexamethasone, a CYP3A inducer, may 
significantly decrease elvitegravir and cobicistat 
plasma concentrations, which may result in loss of 
therapeutic effect and development of resistance. 
Alternative corticosteroids should be considered.
Use of Prednisone as a steroid burst (≤1 week of use)
should be monitored appropriately.
Endothelin receptor antagonists
Bosentan:
coadministration may lead to decreased elvitegravir 
exposures and loss of therapeutic effect and 
development of resistance. Alternative endothelin 
receptor antagonists may be considered.
Ergot Derivatives
Ergotamine, Ergonovine
Dihydroergotamine
Methylergonovine
Ergometrine
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
HMG-CoA Reductase Inhibitors
Simvastatin, Lovastatin
Atorvastatin:
Concentrations may increase with study drug(s). 
Start with the lowest dose; gradual increase in dose 
may be tailored to clinical response. Careful 
monitoring for signs and symptoms of muscle 
weakness or myopathy, including rhabdomyolysis.
Immunosuppressants
Cyclosporine, Rapamycin, Sirolimus, Tacrolimus: 
Concentrations may increase with study drug(s).
Therapeutic monitoring should be considered.
Inhaled Beta Agonist
Salmeterol:
Concentrations may increase with study drug. 
Coadministration of salmeterol with study drug may 
result in increased risk of cardiovascular adverse 
events associated with salmeterol, including QT 
prolongation, palpitations, and sinus tachycardia.
Neuroleptics
Pimozide
Perphenazine, Risperidone, Thioridazine: 
A dose decrease may be needed.

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Drug Class
Agents Disallowed
Use Discouraged and To Be Used With Caution
Opiates
Methadone:
Methadone exposures are unaffected upon 
coadministration with elvitegravir and cobicistat. 
No dose adjustment of methadone is required upon 
coadministration with study drug(s).
Meperidine (Pethidine):
Dosage increase and long-term use are not 
recommended due to increased levels of metabolite 
normeperidine, which has analgesic and 
CNS stimulant (eg, seizures) activities.
Buprenorphine:
Concentrations of buprenorphine and 
norbuprenorphine are modestly increased and 
concentrations of naloxone are modestly decreased 
when coadministered with elvitegravir and cobicistat, 
with no effect on opioid pharmacodynimcs.
The concentration changes are not considered 
clinically relevant and no dose adjustment of 
buprenorphine/naloxone is required upon
coadministration with study drug(s).
Phosphodiesterase-5 Inhibitors
Sildenafil (for PAH)
Pulmonary Arterial Hypertension:
Tadalafil:
Caution should be exercised, including consideration 
of dose reduction, when coadministered for treatment 
of pulmonary arterial hypertension.
Erectile Dysfunction:
Sildenafil, Vardenafil, Tadalafil:
It is recommended that a single dose of Sildenafil 
no more than 25 mg in 48 hours, Vardenafil no 
more than 2.5 mg in 72 hours, or Tadalafil no more 
than 10 mg in 72 hours be coadministered.
Sedatives/Hypnotics
Orally administered 
Midazolam, Triazolam
Buspirone, Clorazepate, Diazepam, Estazolam, 
Flurazepam, Zolpidem:
A dose decrease may be needed for these drugs. 
Clinical monitoring is recommended.

Should subjects have a need to initiate treatment with any disallowed 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 disallowed medication.

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5.5.
Accountability for E/C/F/TAF
The Investigator is responsible for ensuring adequate accountability of all used and unused study 
drug. Accountability records (Study Drug Inventory Log) will be provided to each study site in 
order to:

Record the date received and the quantity of study drug bottles.

Record the date, subject number, subject initials, the study drug bottle number dispensed.

Record the date, quantity of used and unused study drug returned by the subject, along with 
the initials of the person recording the information.
The Investigator [or designee (e.g., study center pharmacist)] will acknowledge receipt of the 
study drugs from Gilead Sciences (or designee) after reviewing the shipment’s content and 
condition. The Investigator (or designee) will be responsible for maintaining an accurate 
inventory of the dates and quantities of all study drugs received, dispensed, and returned. 
Subjects should be instructed to return all unused study drug to the site at their study visits.  
Each dose of the study drug administered at the study center will be administered by qualified 
study center personnel. All doses of study drug administered to subjects in the clinic under the 
supervision of staff will be accurately recorded on the Study Drug Inventory Logs provided by 
Gilead Sciences (or on equivalent documentation maintained by the study center), which 
indicates the date and quantity of all doses of study drug dispensed to individual subjects. 
The requirements of all applicable drug dispensing laws will apply to all doses of study drugs 
dispensed by the Investigator (or designee). 
The study drug inventory log must be available for inspection by the study monitor. 
Study medication supplies, including partially used or empty bottles, must be accounted for by 
the study monitor prior to destruction or return.
5.5.1.
Study Drug Return or Disposal
The study monitor will provide instructions to the sites regarding the return of used and unused 
study drug. If return is not possible, the study monitor will evaluate each study center’s study 
drug disposal procedures and provide appropriate instruction for destruction of unused study 
drug. 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 study 
drug bottles in accordance with that site’s approved SOP. A copy of the site’s approved SOP will 
be obtained for central files.
If the study drug is destroyed on site, the investigator must maintain accurate records for all 
study drug destroyed. Records must show the identification and quantity of each unit destroyed, 
the method of destruction, and the person who disposed of the IMP. Upon study completion, 
copies of the study drug accountability records must be filed at the site. Another copy will be 
returned to Gilead. The study monitor will review study drug inventory and associated records at 
periodic intervals.

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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 in the subject’s source 
documents and electronic Case Report Forms (eCRFs). In addition, the Sponsor and the Contract 
Research Organization (CRO) should be promptly notified of any protocol deviations. 
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the investigator to ensure that each subject is eligible for the study 
before enrollment. 
Subjects who provide written consent and meet all eligibility criteria will receive 
elvitegravir 150 mg / cobicistat 150 mg / emtricitabine 200 mg / tenofovir alafenamide 10 mg 
(E/C/F/TAF), on Day 1. Please refer to Section 5.1 for details about enrollment and 
treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30 days before Day 1 visit 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, substance use and 
prior medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate and temperature) and weight

12-lead ECG performed supine

Height

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.
FSH test is required for female subjects (age > 54 years) who have stopped menstruating 
for > 12 months but do not have documentation of ovarian hormonal failure.

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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium,
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
PT/INR, amylase (reflex lipase testing is performed in subjects with 
total amylase > 1.5 × ULN) and parathyroid hormone (PTH)
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ T cell count
Plasma HIV-1 RNA (Taqman v2.0)
Hepatitis B virus surface antigen serology (HBsAg)
Hepatitis C virus (HCVAb) serology. If the antibody test result is positive, 
HCV RNA test will be performed to confirm HCV viremia.

Review of AEs and concomitant medications (adverse events related to protocol mandated 
procedures occurring after signing of the consent form)
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 assessments. 
From the time of obtaining informed consent through the first administration of study drug, 
record all serious adverse events (SAEs), as well as any adverse events related to 
protocol-mandated procedures on the adverse events case report form (eCRF). All other 
untoward medical occurrences observed during the screening period, including exacerbation or 
changes in medical history are to be captured on the medical history eCRF. See Section 7
Adverse Events and Toxicity Management for additional details.

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6.2.2.
Day 1 Assessments
The following evaluations are to be completed after confirmation of eligibility and before the 
study drug is dispensed to the subject. Initiation of treatment with the study drug must take place 
within 24 hours after the Day 1 visit.

Obtain subject number and study drug bottle assignment from IWRS. The subject number 
assignment and enrollment 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.

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 (blood pressure, pulse, respiration rate, and temperature) and weight

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, phosphorus, magnesium, potassium, sodium, uric acid, amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN) and PTH
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the 
subject must return within 72 hours in a fasted state to draw blood for the metabolic 
assessments
Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA (Taqman v2.0)
Plasma HBV DNA (only required if HBV DNA positive at screening visit)
CD4+ T cell count
Whole blood storage sample collection for virology analyses
Plasma storage sample for virology, safety and/or PK testing

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Serum storage sample for possible additional clinical testing (for subjects who 
provide consent)
Serum pregnancy test (females of childbearing potential only)

SF-36, VAS and HIV-TSQs should be completed by the subject. Subject is to read the 
questionnaire by him/herself and write/mark answers directly onto the questionnaire.

Site-administered questions for Health Utilization Assessment to be completed

Study drug dispensation. Study drug will be dispensed in an open-label fashion. Subjects 
must initiate dosing of study drug within 24 hours after the Day 1 visit.

Subjects should be instructed to take E/C/F/TAF FDC tablets once daily with food at the 
same time each day. On the days of hemodialysis, subjects should be instructed to take study 
drug 2 to 4 hours following hemodialysis. Subjects should also be counseled regarding the 
importance of adherence and taking their study drugs at approximately the same time each 
day.
6.3.
Treatment Assessments (Weeks 2-48)
All study visits are to be scheduled relative to the Day 1 visit date. Study visits are to be 
completed within ± 2 days of the protocol-specific visit date through Week 12 and completed 
within ± 6 days of the protocol-specific visit date through Week 36. The visit window at 
Week 48 will be ± 6 weeks of the protocol-specific visit date, and this clinical visit window 
coincides with the Week 48 statistical analysis window for HIV RNA. Unless notified by the 
Sponsor, Week 48 visit should be completed within ± 6 days of the protocol-specific visit date. 
The following evaluations are to be completed at the end of Weeks 2, 4, 8, 12, 24, 36 and 48 
unless otherwise specified. 
Note: Regularly scheduled evaluations will be made on all subjects whether or not they continue 
to receive study drug. 

Single, pre-dose (within 30 minutes prior to study drug administration) whole blood sample 
collection (Week 4 or Week 12 only). PBMC sample processing will be performed by the 
central laboratory. 
Note: Week 4 or Week 12 visit should occur on the day of hemodialysis for this sample 
collection. Study drug administration should occur 2 to 4 hours following the completion 
of hemodialysis and should be observed on-site. 

All subjects who are willing to consent will be eligible to participate in the pharmacokinetic 
sub-study (target n = 15) at or between Week 4 or Week 8. Please see Section 6.5.1 and 
Appendix 3, Pharmacokinetic (PK) Sub-study for additional details. 

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
Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24 and 48 only) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator)

Symptom-directed physical examination as needed (Weeks 2, 4, 8, 12 and 36)

12-lead ECG performed supine

Vital signs (blood pressure, pulse, respiration rate, and temperature) and weight

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, PT/INR, amylase (reflex lipase testing is performed in subjects with 
total amylase > 1.5 × ULN) and PTH
o
Note: At Weeks 24 and 48, analyses of glucose will be done as part of the fasting 
metabolic assessments and not as part of the chemistry profile.
o
Chemistry profile will include PT/INR only at Week 24 and Week 48.
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 24 and 48 only)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA (Taqman v2.0)
o
Subjects who meet the criteria for virologic rebound should be managed according to 
Management of Suspected Virologic Failure (Section 6.6.1).
Plasma HBV DNA (only required if HBV DNA positive at screening visit)
CD4+ T cell count
Plasma storage sample for virology, safety and/or PK testing

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Serum storage sample for possible additional clinical testing (for subjects who 
provide consent)
Serum pregnancy test (females of childbearing potential only)

Subject completed questionnaires:
SF-36 and HIV-TSQc completed at Weeks 24 and 48 only
VAS completed at all visits
The questionnaires should be completed by the subject. Subject is to read the questionnaire 
by him/herself and write/mark answers directly onto the questionnaire.

Site-administered questions for Health Utilization Assessment to be completed

Study drug dispensation (except at Week 2 and Week 48). Document study drug dispensation 
and accountability. 
At Day 1, study drug will be dispensed for 30 days. At the Week 2 visit, study drug will 
not be dispensed. 
At Week 48, study drug dispensation will not occur. Schedule the subject for a 30-Day 
Follow-Up visit. 

Note: At the Week 2 visit, provide the scheduled Week 4 visit date to the subject. Week 4 
visit should occur on day of hemodialysis. Instruct the subject to take study drug at Week 4 
on-site, 2 to 4 hours following hemodialysis.

Subjects should be instructed to take E/C/F/TAF FDC tablets once daily with food at the 
same time each day.

Subjects should also be counseled regarding the importance of adherence and taking their 
study drugs at approximately the same time each day.
6.4.
Post-treatment Assessments
6.4.1.
30-Day Follow-up Assessments
Subjects who complete the study through the Week 48 visit will be required to return to the 
clinic for a 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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Subjects who permanently discontinue study drug prior to the Week 48 visit and refuse to 
continue in the study through the Week 48 visit will be asked to return to the clinic 30 days after 
the completion of the ESDD Visit for the 30-Day Follow-Up Visit. For the purpose of scheduling 
a 30-Day Follow-Up Visit, a ± 6 days window may be used. The following evaluations are to be 
completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination as needed 

Weight

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT,  total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, amylase (reflex lipase 
testing is performed in subjects with total amylase > 1.5 × ULN) and PTH.
Hematology profile: CBC with differential and platelet count
Plasma HIV-1 RNA (Taqman v2.0)
CD4+ T cell count
Serum pregnancy test (females of childbearing potential only)
Serum storage sample for possible additional clinical testing (for subjects who 
provide consent)
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 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.
6.4.2.
Early Study Drug Discontinuation Assessments (ESDD)
If the subject discontinues study drug prior to the Week 48 visit, the subject will be asked to 
return to the clinic within 72 hours of stopping study drug for the ESDD visit. 
Every attempt should be made to keep the subject in the study through Week 48 visit and 
continue to perform the required study-related follow-up and procedures (see Section 6.4.3, 
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.
Subjects who permanently discontinue study drug prior to the Week 48 visit and refuse to 
continue in the study through Week 48 visit will be asked to return to the clinic 30 days after the 
completion of ESDD visit for the 30-Day Follow-up visit.

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At the Early Study Drug Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, 
should 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 Drug Discontinuation Visit

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Vital signs (blood pressure, pulse, respiration rate, and temperature) and weight

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, amylase (reflex lipase testing is performed in subjects with 
total amylase > 1.5 × ULN) and PTH
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA (Taqman v2.0)
o
Subjects who meet the criteria for virologic rebound should be managed according to 
Management of Suspected Virologic Failure (Section 6.6.1).
Plasma HBV DNA (only required if HBV DNA positive at screening visit)
CD4+ T cell count
Plasma sample for virology testing or pharmacokinetic testing
Serum storage sample for possible additional clinical testing (for subjects who 
provide consent)
Serum pregnancy test (females of childbearing potential only)

SF-36, HIV-TSQc and VAS questionnaires should be completed by the subject. Subject is to 
read the questionnaire by him/herself and write/mark answers directly onto the questionnaire.

Site-administered questions for Health Utilization Assessment to be completed

Drug accountability

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6.4.3.
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

Therapeutic failure 

Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study; refer to Appendix 6

Discontinuation of the study at the request of Gilead, a regulatory agency or an 
institutional review board or independent ethics committee (IRB/IEC)
6.5.
Other Evaluations
6.5.1.
Pharmacokinetic (PK) Sub-study
All subjects who are willing to consent will be eligible to participate in the pharmacokinetic sub-
study (target n = 15). 
Post-dose blood sample collection will be performed at hours 0.5, 1, 2, 3, 4, 6, 8, and 24.
PK sub-study visit must occur at or between Week 4 or Week 8, on the day of hemodialysis. 
Study drug administration will be observed in-clinic at the sub-study visit. The sub-study will 
include intensive PK profiling in plasma. Details of the blood sampling procedures and sample 
management will be documented in the Pharmacokinetic Sample Collection, Processing, 
Storage, and Shipment Manual. 
6.5.2.
Blood Storage
From subjects who provide additional consent, a portion of the blood drawn at all visits 
(except the Screening Visit and Unscheduled Visits) will be frozen and stored. These stored 
blood samples may be used by the Sponsor or its research partners for future 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, Inc. for a period up to 15 years.

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6.6.
Virologic Failure
Subjects who experience virologic rebound (VR), as defined below, will be considered to have 
virologic failure.
Subjects will be considered to have virologic rebound if they have confirmed HIV-1 RNA 
≥50 copies/mL (two consecutive tests) at a scheduled or unscheduled visit.
6.6.1.
Management of Virologic Failure

If the viral load is ≥ 50 copies/mL, HIV-1 RNA should be repeated at a scheduled or 
unscheduled visit (2-4 weeks after the date of the original test with HIV-1 RNA ≥50 copies/mL).

Upon confirmation of HIV-1 RNA ≥ 50 copies/mL, potential causes of virologic failure 
should be documented. Assessments should include:
Adherence
Concomitant medication
Comorbidities (for example: active substance abuse, depression, other intercurrent illnesses)

If virologic rebound is confirmed, and the HIV-1 RNA is < 400 copies/mL, subjects may 
remain on their current regimen at the discretion of the Investigator. Subject will return for a 
repeat within 2-4 weeks. 

If virologic failure is confirmed at the scheduled or unscheduled visit and HIV-1 RNA value 
is ≥ 400 copies/mL, the blood samples from the confirmation visit will be used for 
HIV-1 genotype/phenotype testing.

If genotype/phenotype resistance to study drug is documented, study drugs should be 
discontinued. 

If no resistance is detected from genotype/phenotype testing, subject may remain on study 
drug and HIV-1 RNA should be repeated (2-4 weeks from the date of confirmed 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 
subjects source documents. Investigators who opt to discontinue study drugs for an 
individual subject must discuss with the Medical Monitor prior to study drug discontinuation.
6.6.2.
Subjects with ≥ 400 Copies/mL of HIV-1 in the Absence of VR
Subjects with HIV-1 RNA < 50 copies/mL could subsequently experience unconfirmed blips of 
HIV-1 RNA ≥ 400 copies/mL. Such subjects will be analyzed for resistance if the unconfirmed 
rebound happens at Week 24 or Week 48, or at the last visit while receiving study drugs 
(or within 72 hours of discontinuation of study treatment).
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
failure.

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Figure 6-1. 
Schema for Management of Virologic Failure 
Screening 
Treatment Period 
30-Day Follow-up 
D ayl 
~ 
I 
At any visit, a rebound in HIV-1 RNA to ~ 50 copies/mL 
I 
Unconfu·med 
Return for scheduled/unscheduled HIV-1 
vii·ologic rebound: 
.... 
RNA and potential genotype/phenotype 
remain on cmTent 
(2-4 weeks later) 
regimen• 
' 
Confit•med virologic rebound and 
HIV-1 RNA to <!: 400 copies/mLb 
,, 
Remain on study 
I 
HIV-1 genotype/phenotype' I 
' 
' 
If no revet·se transcriptase t•esistance 
If reverse transc.riptase, protease, 
detected, continue on study drugs. 
or integrase resistance detected, 
Repeat HIV-1 RNAb,d 
discontinue study drugs and 
constt·uct a new ARV regimen• 
a 
If virologic rebOlmd is not confmned, the subje.ct will remain on their cmrent regin1en. 
b 
If virologic rebotmd is confmned, and the HIV-1 RNA is< 400 copies/mL, subjects may remain on their cun·ent regimen at 
the discretion of the Investigator. Subject will rettun for a repeat within 2-4 weeks. If virologic rebom1d is confinned, and 
HIV -1 RNA is :::: 400 copies/mL, the HIV -1 genotype and phenotype (reverse transcriptase, protease, and, if applicable, 
integrase resistance) will be analyzed. 
c 
Base·d on the results of the genotype/phenotype assays, the subject will remain on study chugs or study drugs will be 
discontinued. If genotyping/phenotyping assay fails, a new ARV regin1en may be configm·ed at the discretion of the 
Investi2ator. 
d 
If no r.;istance detected, HIV-1 RNA will be repeated (2-4 weeks later). Investigator reviews study dt·ug 
continuation/discontinuation options and discuss with Medical Monitor prior to study dt·ug discontinuation. 
e 
A new ARV regimen will be configtu·ed, at the Investigator's discretion, and the subject will remain in the study. 
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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 7.5)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history CRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (e.g., 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 (e.g., 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 (e.g., anemia), not the 
laboratory result (i.e., decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 7.6.
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 
study drug 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 (e.g., pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 

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The relationship to study procedures (e.g., 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, (e.g., venipuncture)
7.2.2.
Assessment of Severity
Severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 5) 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.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): all SAEs and adverse events related to 
protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 4 weeks after last administration of study drug 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.
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. 

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All SAEs should be followed up until resolution if possible. If by the last day on study 
(including the off-study medication follow-up period) the SAE has not resolved, then the SAE 
will be followed up until the investigator and/or Gilead Sciences determine that the subject's 
condition is stable. However, Gilead Sciences may request that certain SAEs be followed until 
resolution.
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period, 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of study drug, he/she should promptly document and 
report the event to Gilead DSPH. 

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.
Serious Adverse Event Paper Reporting Process

Serious Adverse Event Paper Reporting Process (only to be used if EDC System is not available)
All SAEs will be recorded on the serious adverse event report form and submitted by 
faxing the report form within 24 hours of the investigator’s knowledge of the event to the 
attention of:
Gilead Sciences DSPH:
Fax:
E-mail:
+1 (650) 522 5477
safety_fc@gilead.com
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 the SAE was reported via paper, it 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.

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.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form.

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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.
Special Situations Reports
7.5.1.
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.  

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7.5.2.
Instructions for Reporting Special Situations
7.5.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to Gilead DSPH using the pregnancy report form within 24 hours of becoming aware of 
the pregnancy.
Refer to 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 (e.g., a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3.2. 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: 
Gilead Sciences DSPH:
Fax:
E-mail:
+1 (650) 522 5477
safety_fc@gilead.com
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.5.2.2.
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. 

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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 the CRF/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.
7.6.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 4 as outlined below.

All clinically significant Grades 3 and 4 laboratory abnormalities should be repeated within 
3 calendar days to confirm toxicity grade. Confirmation of toxicity grade is required prior to 
the next dose of investigational medicinal product for any Grade 3 and 4 laboratory 
abnormality that in the opinion of the Investigator is clinically significant and may pose a 
risk to the subject’s safety.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(refer to Appendix 5).

Any questions regarding toxicity management should be directed to the Medical Monitor.
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue investigational medicinal product at the discretion of the Investigator.
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, 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.

If a laboratory abnormality recurs to Grade 3 following re-challenge 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.

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7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event

For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to 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 3-4 laboratory abnormality (e.g., CK elevation after strenuous exercise, or 
triglyceride elevation that is non-fasting or that can be medically managed) or a Grade 3-4 
clinical event considered unrelated to investigational medicinal product.
7.6.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis 
Management in Subjects Co-infected with Hepatitis B
On-Treatment ALT Flare is defined as:

Confirmed (within 3 days of receipt of initial laboratory results) serum ALT > 2 × Day 1 value
and >10 × ULN, with or without associated symptoms
7.6.4.1.
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.  

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For subjects with bridging fibrosis or cirrhosis, study drug discontinuation with treatment-free 
follow-up is to be avoided due to the potential risk of exacerbation of hepatitis in the setting of 
low hepatic reserve which could lead to decompensation. Subjects with bridging fibrosis or 
cirrhosis should be placed on an HIV regimen containing commercially available HBV therapy if 
study drug is 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 × 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.
For subjects with bridging fibrosis or cirrhosis, study drug discontinuation with treatment-free 
follow-up is to be avoided due to the potential risk of exacerbation of hepatitis in the setting of 
low hepatic reserve which could lead to decompensation. Subjects with bridging fibrosis or 
cirrhosis should be placed on an HIV regimen containing commercially available HBV therapy if 
study drug is discontinued.
7.6.4.2.
Management of Exacerbation of Hepatitis 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.

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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 safety and tolerability of the elvitegravir/cobicistat/emtricitabine/
tenofovir alafenamide (EVG/COBI/FTC/TAF; E/C/F/TAF) fixed dose combination (FDC) in 
HIV-1 infected adults with end stage renal disease (ESRD) on chronic hemodialysis (HD) at 
Week 48
The secondary objectives of this study are:

To evaluate the proportion of subjects with virologic response (HIV-1 RNA < 50 copies/mL, 
Snapshot analysis) at Weeks 24 and 48

To evaluate plasma pharmacokinetics (PK) of EVG, COBI, FTC, TAF and TFV in HIV-1 
infected patients with ESRD on HD
8.1.2.
Primary Endpoint
The primary endpoint is the incidence of treatment-emergent grade 3 or higher adverse events at
Week 48.
8.1.3.
Secondary Endpoints

Proportion of subjects with HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as defined by 
the FDA snapshot algorithm

The pharmacokinetics parameters of EVG, COBI, FTC, TAF and TFV, including 
AUCtau/AUClast, Cmax, and Cmin for the sub-study.
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
Full Analysis Set
Full Analysis Set (FAS): The Full Analysis Set will include all the subjects who were enrolled
and received at least one dose of study drug. The FAS will exclude subjects with major protocol 
violations. The FAS analysis set is the primary analysis set for the efficacy analyses.

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8.2.1.2.
Safety Analysis Set
The primary analysis set for safety analyses is defined as all subjects that received at least 
one dose of study medication.
All data collected during treatment will be included in the safety summaries.
8.2.1.3.
Pharmacokinetics
The Pharmacokinetic (PK) analysis set will include all subjects in the safety analysis set who 
participated in the sub-study and for whom concentration data of any one analyte (e.g., TAF, EVG,
COBI, TFV and FTC) of interest are available.
8.3.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized using standard descriptive 
methods.
Demographic summaries will include sex, race/ethnicity and age.
Baseline data will include a summary of body weight, height, body mass index and HIV-1 infection.
8.4.
Primary and Secondary Analysis
8.4.1.
Primary Analysis
The primary endpoint is the incidence of treatment-emergent grade 3 or higher adverse events at 
Week 48. Treatment-emergent adverse events are defined in Section 8.5.2.
8.4.2.
Secondary Analyses
The proportion of subjects achieving HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 will be 
computed using the FDA snapshot algorithm. The measures of pharmacokinetics of EVG, COBI, 
FTC, TAF and TFV, AUC, Cmax, and Cmin, will be summarized using descriptive statistics 
[N, mean, standard deviation, percent coefficient of variation (%CV), median, minimum, 
and maximum] for the sub-study.
8.5.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that study medication was first dispensed up to the 
date of last dose of study medication plus 30 days will be summarized. Data for pre-treatment 
period and the period post the date of last dose plus 30 days will be included in data listings.

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8.5.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug
administration data. Exposure data will be summarized.
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. Dosing information for individual subjects will be listed.
8.5.2.
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.
Treatment-emergent adverse events are adverse events that meet one of the following criteria:

Adverse events with onset dates on or after the first dose date of study drug, and no later than 
30 days after permanent discontinuation of study drug, or

Adverse events that result in permanent study drug discontinuation
Summaries (number and percentage of subjects) of treatment-emergent adverse events 
(by SOC and PT) will be provided. Additional summaries will include summaries for adverse 
events by grade, Investigator’s assessment of relationship to study drug, and effect on study drug 
dosing.
8.5.3.
Laboratory Evaluations
Selected laboratory data will be summarized using only observed data. Absolute values and 
changes from baseline at all scheduled time points will be summarized.
Graded laboratory abnormalities will be defined using the GSI Grading Scale for severity of 
Adverse Events and Laboratory Abnormalities (Appendix 5).
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
one toxicity grade from baseline at any time post baseline up to the date of last dose of study 
drug plus 30 days, will be summarized. If baseline data are missing, then any graded abnormality 
(i.e., at least a Grade 1) will be considered treatment-emergent. The maximum toxicity grade will 
be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the subject has
been discontinued from treatment plus 30 days will be included in a data listing.

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8.5.4.
Other Safety Evaluations
Weight will be summarized by visit. 
Safety ECGs will be listed and summarized for subjects in the Safety Analysis Set. The number 
and percent of subjects with abnormal safety ECG will be summarized by visit.
8.6.
Pharmacokinetic Analysis
Pharmacokinetic parameters will be listed and summarized for using descriptive statistics 
(eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard 
deviation, median, minimum, and maximum). Plasma concentrations of the study drug over time 
will be plotted in semi logarithmic and linear formats as mean ± standard deviation.
8.7.
Sample Size
A sample size of approximately 50 subjects is based on practical considerations and is 
considered to be sufficient to evaluate the primary objective of this study. The Grade 3 or higher 
AE rate in Study GS-US-292-0112 in subjects that had mild to moderate renal impairment was 
8.8% at Week 48 for the E/C/F/TAF arm. Therefore, with 50 subjects, and an assumed rate of 
Grade 3 or higher AEs being 10%, this study would provide 95% confidence for the primary 
endpoint to be (1.7%, 18.3%) assuming normal approximation to binomial proportions. 
A sample size of at least 15 subjects is considered for estimating the PK parameters in the sub-
study for practical reasons. 
8.8.
Data Monitoring Committee
An external multidisciplinary independent data monitoring committee (IDMC) will review the 
progress of the study and perform interim reviews of safety, efficacy data and provide 
recommendation to Gilead whether the nature, frequency, and severity of adverse effects 
associated with study drug warrant the early termination of the study in the best interests of the 
participants, whether the study should continue as planned, or the study should continue with 
modifications. The committee will convene after the first 25 subjects enrolled complete Week 12
of the study. The IDMC’s specific activities will be defined by a mutually agreed charter, which 
will define the IDMC’s membership, conduct and meeting schedule.

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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 sub-investigators 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 sub-investigator’s) participation in the study. The investigator and 
sub-investigator 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.

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9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IRB/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, IRB or IEC, or laboratory. Laboratory specimens 
must be labeled in such a way as to protect subject identity while allowing the results to be 
recorded to the proper subject. Refer to specific laboratory instructions. NOTE: The investigator
must keep a screening log showing codes, names, and addresses for all subjects screened and for 
all subjects enrolled in the trial. Subject data will be processed in accordance with all applicable 
regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, and any other study information, remain the 
sole and exclusive property of Gilead during the conduct of the study and thereafter. This 
information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms,
IRB or IEC and governmental approval with correspondence, informed consent, drug records, 
staff curriculum vitae and authorization forms, and other appropriate documents and 
correspondence.

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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, i.e., history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

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 (i.e. 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.

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9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data. The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received. Subsequent to data entry, a study monitor will perform source data 
verification within the EDC system. Original entries as well as any changes to data fields will be 
stored in the audit trail of the system. Prior to database lock (or any interim time points as 
described in the clinical data management plan), 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. The eCRF capture the data required per the protocol 
schedule of events and procedures. 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). 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, IRBs or IECs, or regulatory authority or health authority 
inspectors.

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9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB 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
1238
Centers for Disease Control and Prevention. 1993 revised classification system 
for HIV infection and expanded surveillance case definition for AIDS among 
adolescents and adults. MMWR 1992;41 (RR-17):1-19.
2202
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum 
creatinine. Nephron 1976;16:31-41.
4256
Chesney M. Factors affecting adherence to antiretroviral therapy. Clin Infect Dis. 
2000;30 (Suppl 2):S-171-S6.
4266
Stone VE JJ, Tolson J, Pilon T. Potential impact of once daily regimens on 
adherence to HAART [abstract]. . 40th Annual Meeting of the Infectious Disease 
Society of America; 2002 Oct 24-27; Chicago. pp. p.129, Abstract 486.
4887
Kalayjian RC, Landay A, Pollard RB, Taub DD, Gross BH, Francis IR, et al. 
Age-related immune dysfunction in health and in human immunodeficiency virus 
(HIV) disease: association of age and HIV infection with naive CD8+ cell 
depletion, reduced expression of CD28 on CD8+ cells, and reduced thymic 
volumes. J Infect Dis 2003;187 (12):1924-33.
7034
Maggiolo F MM, Maserati R, Rizzi L, Pan A, Rizzi A, et al. . Once-a-day 
treatment for HIV infection: Final 48-week results. [Abstract 320]. 8th 
Conference on Retroviruses and Opportunistic Infections; 2001 February 4-8; 
Chicago, IL. 
7035
Felizarta F BS, Bellos N, Jayaweera D, Sands M, Slater L, et al. Adherence and 
efficacy with a once-daily efavirenz-based regimen: 48-week results from the 
Daily Antiretroviral Therapy II (DART II) Study [Poster 5842]. . XV 
International AIDS Conference; 2004 July 11-16; Bangkok, Thailand. 
7036
Arribas JR IJ, Knobel H, Ribera E, Rubio R, Viciana P, et al. . Adherence, 
treatment satisfaction and effectiveness of once-daily (QD) vs twice-daily (BID) 
antiretroviral therapy (AT), in a large prospective observational cohort (CUVA 
Study).  [Poster WePeB5780]. . XV International AIDS Conference; 2004 July 
11-16; Bangkok, Thailand. 
7415
Lee WA, He G-X, Eisenberg E, Cihlar T, Swaminathan S, Mulato A, et al. 
Selective intracellular activation of a novel prodrug of the human 
immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to 
preferential distribution and accumulation in lymphatic tissue. Antimicrob Agents 
Chemother 2005;49 (5):1898-906.

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7896
Centers for Disease Control and Prevention. 1994 Revised Classification System 
for Human Immunodeficiency Virus Infection in Children Less Than 13 Years of 
Age. MMWR 1994;43 (RR-12):1-28.
13119
Birkus G, Kutty N, He GX, Mulato A, Lee W, McDermott M, et al. Activation of 
9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino] phenoxyphosphinyl]-
methoxy]propyl]adenine (GS-7340) and other tenofovir phosphonoamidate 
prodrugs by human proteases. Mol Pharmacol 2008;74 (1):92-100.
16557
Parienti JJ, Bangsberg DR, Verdon R, Gardner EM. Better adherence with once-
daily antiretroviral regimens: a meta-analysis. Clin Infect Dis 2009;48 (4):484-8.
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. 
19661
World Health Organization, UNAIDS, UNICEF. Global HIV/AIDS Response: 
Epidemic update and health sector progress towards universal access. Progress 
Report 2011.  
19946
Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, et al. Premature 
age-related comorbidities among HIV-infected persons compared with the general 
population. Clin Infect Dis 2011;53 (11):1120-6.
19947
Center for Disease Control and Prevention. HIV/AIDS Surveillance Report, 2005. 
Vol. 17. Rev ed. Atlanta: U.S. Department of Health and Human Services, 
Centers for Disease Control and Prevention; 2007: 1-54. Also available at: 
http://www.cdc.gov/hiv/topics/surveillance/resources/reports/.  
19948
Linley L, Hall H, An Q, Wheeler W. HIV/AIDS diagnoses among persons fifty 
years and older in 33 states, 2001-2005 [Abstract B08-1]. Presented at: 2007 
National HIV Prevention Conference; 2007 December 2-5; Atlanta, GA. 
21762
VIREAD® (tenofovir disoproxil fumarate) Tablets and Powder for oral use. US 
Prescribing Information. Gilead Sciences, Inc. Foster City, CA. Revised August 
2012.  
22029
Birkus G, Kutty N, He G-X, Mulato A, Lee W, McDermott M, et al. Activation of 
GS-7340 and Other Tenofovir Phosphonoamidate Prodrugs by Human Proteases. 
Antiviral Res 2007;74:A57.

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22031
Department of Health and Human Services (DHHS). HHS Panel on Antiretroviral 
Guidelines for Adults and Adolescents Recommends a Fixed-Dose Combination 
Product of Elvitegravir/Cobicistat/Tenofovir/Emtricitabine as an Alternative 
Regimen in Antiretroviral Treatment-Naive Individuals with HIV-1 Infection.  
2012:1-2. 
22551
Cailhol J, Nkurunziza B, Izzedine H, Nindagiye E, Munyana L, Baramperanye E, 
et al. Prevalence of chronic kidney disease among people living with HIV/AIDS 
in Burundi: a cross-sectional study. BMC nephrology 2011;12:40.
22552
Selik RM, Byers RH, Jr., Dworkin MS. Trends in diseases reported on U.S. death 
certificates that mentioned HIV infection, 1987-1999. J Acquir Immune Defic 
Syndr 2002;29 (4):378-87.
22553
Schwartz EJ, Szczech LA, Ross MJ, Klotman ME, Winston JA, Klotman PE. 
Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal 
disease. J Am Soc Nephrol 2005;16 (8):2412-20.
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.

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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Pharmacokinetic Substudy
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 6.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 7.
Definitions of HIV-1 Related Disease (CDC Guidelines) {35184}

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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Phrumacokinetics and 
Efficacy of E/C/F/T AF Fixed Dose Combination (FDC) in HlV -1 Infected Subjects on 
Chronic Hemodialysis 
GS-US-292-1825, Original, 08 July 2015 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Devi SenGupta, MD (Printed) 
Medical Monitor 
Date 
PPD 
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 aJI 
information provided by Gilead Sciences, Inc. I will discuss this material with them to enswe 
that they are fuJiy informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 70 
08 July 2015 

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Appendix 2.
Study Procedures Table
Study Procedure
Screena
Day 1b
Week 2 to Week 48c
30-Day 
Follow-upd
ESDDe
2
4
8
12
24
36
48
Written Informed Consent
X
Medical History 
X
Complete Physical Examinationf
X
X
X
X
X
Symptom-directed Physical Examinationg
X
X
X
X
X
X
Vital Signs and Weight
X
X
X
X
X
X
X
X
X
Xh
X
Height
X
12-Lead ECG
X
X
X
Chemistry Profilei
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessmentsj
X
Xj
Xj
Serum Pregnancy Testk
X
X
X
X
X
X
X
X
X
X
X
CD4+ T Cell Count
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNAl
X
X
X
X
X
X
X
X
X
X
X
HIV-1 Genotype/Phenotypem
X
X
X
X
X
X
X
X
X
X
X
Estimated eGFR
X
X
X
X
X
X
X
X
X
X
Hematology profilen
X
X
X
X
X
X
X
X
X
X
X
Plasma Storage Samples
X
X
X
X
X
X
X
X
X
Serum Storage Sampleso
X
X
X
X
X
X
X
X
X
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
HBV and HCV Serologyp
X

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Study Procedure
Screena
Day 1b
Week 2 to Week 48c
30-Day 
Follow-upd
ESDDe
2
4
8
12
24
36
48
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
SF-36 and HIV-TSQq
X
X
X
X
VAS
X
X
X
X
X
X
X
X
Health Utilization Assessmentr
X
X
X
X
X
X
X
X
X
Drug Dispensation and Accountability
X
Xs
X
X
X
X
X
Xs
Xs
Single Pre-dose Whole Blood Sample Collectiont
X
X
Post-dose PK Sub-studyu
X
X
Whole Blood Storage Samplev
X
Plasma HBV DNAw
X
X
X
X
X
X
X
X
X
a
Evaluations to be completed within 30 days prior to Day 1.
b
Subjects will be dispensed study drug on the Day 1 visit; initiation of treatment with the study drug must take place within 24 hours after the Day 1 visit.
c
All study visits are to be scheduled relative to the Day 1 visit date. Visit windows are ± 2 days of the protocol specified date through Week 12, ± 6 days of the protocol 
specified date through Week 48, except Week 48. Weeks 48 visit window is ± 6 weeks of the protocol specified date. Week 48 visit should be completed within ± 6 day 
window, unless otherwise specified by the Sponsor.
d
Required for those subjects who complete Week 48 visit or those subjects who permanently discontinue study drug and do not continue in the study through at least 
one subsequent visit after the Early Study Drug Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used.
e
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through 
Week 48, if the subject discontinues study drug prior to completion of Week 48 visit.
f
Complete physical examination (urogenital/anorectal exams will be performed at the discretion of the Investigator).
g
Symptom-directed physical examination as needed
h
Weight only
i
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, PT/INR and amylase (reflex lipase testing is performed in subjects with total amylase 
> 1.5 × ULN). At Day 1, Weeks 24 and 48 analyses of glucose will be done as part of the fasting metabolic assessments and not as part of the chemistry profile. PT/INR will 
be included in the chemistry profile at Screening, Weeks 24 and 48 only.
j
Fasting glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, but the subject must 
return within 72 hours in a fasted state to draw blood for the metabolic assessments. At Weeks 24 and 48 analyses of glucose will be done as part of the chemistry profile. 

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k
Females of childbearing potential only. FSH test is required for female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian 
hormonal failure.
l
If the HIV-1 RNA value is ≥50 copies/mL a retest should be collected at a scheduled or unscheduled visit, 2-4 weeks after the date of the original test (except for screening 
and baseline results). See Section 6.6.1.
m
HIV-1 genotype/phenotype resistance testing only conducted for subjects with confirmed virologic rebound with HIV-1 RNA value ≥ 400 copies/mL. Subjects should be 
managed according to the Virologic Rebound Schema (Section 6.6.1). HIV-1 genotype/phenotype sample collection to occur if subjects HIV-1 RNA lab values meet the 
criteria described in this section.
n
CBC with differential and platelet count
o
For subjects who provide consent −serum storage samples for possible future testing will be collected.
p
See Section 4.2 to confirm subject eligibility prior to enrollment.
q
SF-36 and HIV-TSQ are to be completed by subjects at Day 1, Week 24 and Week 48 visits. HIV-TSQs to be completed by the subjects at Day 1 visit, HIV-TSQc to be 
completed by the subjects at Week 24 and Week 48 visits. 
r
Subjects will be asked about their health utilization at Day 1 visit and every visit thereafter, including the ESDD and Unscheduled Visits.
s
Drug accountability only; study drug will not be dispensed at these visit.
t
At Week 4 or Week 12, a single pre-dose whole blood sample will be collected for subjects enrolled in the study. Sample collection should occur within 30 minutes prior to 
the study drug administration which should be observed on-site. PBMC processing will be completed by the central laboratory. 
u
At or between Week 4 or Week 8, subjects who are willing to consent will be eligible to participate in the pharmacokinetic sub-study (target n = 15). Please see Section 6.5.1
and Appendix 3 Pharmacokinetic (PK) Sub-study for additional details.
v
Whole blood storage sample collected at baseline visit for virology assessments.
w
Plasma HBV DNA testing required only subject tests HBV positive at screening visit. 

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Appendix 3.
Pharmacokinetic Sub-study
Blood Sampling Time Points for Intensive PK:
Study Day
Time Point (hrs) Post-dose
0.5
1
2
3
4
6
8
24
At or between 
Week 4 or 
Week 8
X
X
X
X
X
X
X
X
1) All subjects who are willing to consent will be eligible to participate in the pharmacokinetic 
sub-study (target n = 15). 
2) PK sub-study visit must occur at or between Week 4 or Week 8 on the day of hemodialysis. 
3) Subject should be instructed to dose 2 to 4 hours after the completion hemodialysis. 
Study drug administration should be observed in-clinic. 
4) The sub-study will include intensive PK profiling in plasma. Details of the blood sampling 
procedures and sample management will be documented in the Pharmacokinetic Sample 
Collection, Processing, Storage, and Shipment Manual. 

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Appendix 4.
Management of Clinical and Laboratory Adverse Events
Gradf 1 
L------G-'r-ad_f_2----~~ 
~~------G-·r-ad_f_3----~~ ~~---------G-r-·a_d_e_~---------" 
! 
! 
l\Iay coutinuf 
Rfpfat lab to 
dosing at rhf 
confirm toiicity 
discrfrion ofthf 
gradf' 
in\·~stigator 
1 
If confinnl'<l and possibly and/or probably rflatfd to 
inwsrigarionru mroicinal products: 
1. Withhold inwsrigational ml'<licinal products until~ Gradf 2 
2. 
Rfsrart. all inwstigational mfdicinal produc.rs at full dosf 
1 
lf Grade 3 or ~ rfcwTence that is confit1ned and possibly or 
probably relatfd to inwstigational mfclicinal pt·oducrs, 
discontinuf all inwstigatioual medicinal products dosing 
pHmaufntly 
1 
r---------, 
Rfpfat Jab to 
confirm to:ticity 
gradf 
· 
1 
lf co 
inw 
dos 
nfirmro and uw'flatfd to 
stigarionru mfdicinal products, 
mg may continue at the 
disc rfrion of thf in,·estigator 
If confit·ml'<l and 
possibly or probably 
-. rflatedto 
inYestigarionaJ 
medicinal products, 
cliscoutinue 
iuYestigarionaJ 
medicinal products 
dosing pmnanfntly 
and follow at periodic 
intervals at !fast 
wHklY until a retw·u 
to ba;eline or is 
otltftmsf explainfd 
If GraM 3 or 4 recwnncf that is considHro uw·flarfd to 
inYesrigational medidnaJ proclucr.s, continue all investigational 
medicinal products at tbf same dose at the discrftion of tbf 
in,·esrigatoJ· 

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Appendix 5.
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
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

E/C/F/TAF
Protocol GS-US-292-1825
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 79
08 July 2015
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

E/C/F/TAF
Protocol GS-US-292-1825
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 80
08 July 2015
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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Protocol GS-US-292-1825
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 81
08 July 2015
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
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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Protocol GS-US-292-1825
Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
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08 July 2015
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

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Final
Gilead Sciences, Inc.
Original
CONFIDENTIAL
Page 83
08 July 2015
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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Gilead Sciences, Inc.
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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

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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
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
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

E/C/F/TAF
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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

E/C/F/TAF
Protocol GS-US-292-1825
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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Dysphagia-Odynophagia 
Symptomatic but able to eat 
usual diet
Symptoms causing altered 
dietary intake without 
medical intervention 
indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention 
indicated
Life-threatening reduction in 
oral intake
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, Dysphagia-
Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal 
bleeding OR Life-threatening 
consequences 
(eg, aspiration, choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference with 
oral intake
Persistent nausea resulting in 
decreased oral intake for 
24-48 hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (eg, 
IV fluids)
Life-threatening 
consequences 
(eg, hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening 
consequences 
(eg, sepsis, circulatory 
failure, hemorrhage)
Proctitis 
(functional- symptomatic)
Also see Mucositis/ Stomatitis 
for Clinical Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities OR 
Medical intervention 
indicated 
Symptoms causing inability 
to perform usual social/
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences 
(eg, perforation)
Vomiting
Transient or intermittent 
vomiting with no or minimal 
interference with oral intake
Frequent episodes of 
vomiting with no or mild 
dehydration
Persistent vomiting resulting 
in orthostatic hypotension 
OR Aggressive rehydration 
indicated
Life-threatening 
consequences 
(eg, hypotensive shock)

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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 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 of 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 of study drugs on 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 toxicity studies for human pregnancy do not indicate a strong suspicion of human 
teratogenicity/fetotoxicity. Data from clinical pharmacokinetic interaction studies of study drug 
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 
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 also not rely on hormone-containing contraceptives as a form 
of birth control during the study. They must have a negative serum pregnancy test at Screening 
prior to study enrollment. A serum pregnancy test will be performed at all study visits and the 
end of relevant system exposure. In the event of a delayed menstrual period (over one month 
between menstruations), a serum 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
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
o
Diaphragm with spermicide
o
Cervical cap with spermicide
o
Male condom (with or without spermicide)
Hormonal methods (the hormonal contraceptive should contain at least 30 mcg of 
ethinyl estradiol)
o
Intrauterine hormone-releasing system (IUS) with a failure rate of < 1% per year
o
Oral contraceptives (either combined or progesterone only)
o
Injectable progesterone
o
Implants of levonorgestrel
o
Transdermal contraceptive patch
o
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
During the study, male subjects with female partners of childbearing potential should use 
condoms when engaging in intercourse of reproductive potential. 
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (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 30days 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 7.5.2.1.

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Appendix 7.
Definitions of HIV-1 Related Disease (CDC Guidelines) {35184}

Bacterial infections, multiple or recurrent*

Candidiasis of bronchi, trachea, or lungs

Candidiasis of esophagus

Cervical cancer, invasive†

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (> 1 month's duration)

Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age > 1 month

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy attributed to HIV§

Herpes simplex: chronic ulcers (> 1 month's duration) or bronchitis, pneumonitis, or 
esophagitis (onset at age > 1 month)

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (> 1 month's duration)

Kaposi sarcoma

Lymphoma, Burkitt (or equivalent term)

Lymphoma, immunoblastic (or equivalent term)

Lymphoma, primary, of brain

Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary

Mycobacterium tuberculosis of any site, pulmonary†, disseminated, or extrapulmonary

Mycobacterium, other species or unidentified species, disseminated or extrapulmonary

Pneumocystis jirovecii (previously known as "Pneumocystis carinii") pneumonia

Pneumonia, recurrent†

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
Progressive multifocal leukoencephalopathy

Salmonella septicemia, recurrent

Toxoplasmosis of brain, onset at age > 1 month

Wasting syndrome attributed to HIV§
*
Only among children aged < 6 years
†
Only among adults, adolescents, and children aged ≥ 6 years
§
Suggested diagnostic criteria for these illnesses, which might be particularly important for HIV encephalopathy 
and HIV wasting syndrome, are described in the following references {7896}, {1238}.