A Phase 3, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection
Phase: PHASE3
Conditions: Pre-Exposure Prophylaxis of HIV-1 Infection
Sponsor: Gilead Sciences

Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Indication: 
Protocol ID: 
(_r) GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 3, Randomized, Double-blind Study to Evaluate the Safety 
and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/T AF) 
Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in 
Men and Transgender Women Who Have Sex with Men and Are At 
Risk of HIV -1 Infection 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
127728 
2016-001399-31 
Pre-Exposure Prophylaxis of HIV -1 Infection 
GS-US-412-2055 
Oinical Program Manager: 
Name: 
[PPD 
[PPD 
[PPD 
Telephone: 
Fax: 
Gilead Medical Monitor: 
Name: 
Telephone: 
Fax: 
Protocol Version/Date: 
Original: 
Amendment 1: 
Amendment 2: 
Amendment 3: 
Amendment 4: 
Amendment 5: 
Amendment 6: 
Amendment 7: 
[PPD 
[PPD 
[PPD 
07 April 2016 
06 June 2016 
15 July 2016 
16 November 2016 
06 April 2018 
05 September 2018 
10 November 2020 
19 October 2021 
This study will be conducted in compliance with this protocol and in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, and that are consistent with International 
Council for Harmonisation (ICH) Good Clinical Practice (GCP) and applicable regulatory 
requirements. 

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
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19 October 2021
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or under 
control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, potential 
investigator, or consultant, for review by you, your staff, and an applicable Institutional Review Board 
or Independent Ethics Committee. The information is only to be used by you in connection with 
authorized clinical studies of the investigational drug described in the protocol. You will not disclose 
any of the information to others without written authorization from Gilead Sciences, Inc., except to the 
extent necessary to obtain informed consent from those persons to whom the drug may be 
administered.

Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Final 
Amendment 7 
Gilead Sciences, Inc. 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................................................ 3 
LIST OF IN TEXT-APPENDICES ................................................................................................................................ 5 
LIST OF IN-TEXT TABLES ......................................................................................................................................... 6 
LIST OF IN-TEXT FIGURES ........................................................................................................................................ 6 
PROTOCOL SYNOPSIS ................................................................................................................................................ 7 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 15 
1. 
INTRODUCTION ................................................................................................................................................ 19 
1.1. 
Background .............................................................................................................................................. 19 
1.2. 
Tenofovir Alafenamide (TAF, GS-7340) ................................................................................................ 20 
1.2.1. 
General Infonnation .............................................................................................................. 20 
1.2.2. 
Nonclinical Studies ofF/TAF for PrEP ................................................................................. 21 
1.2.3. 
Preclinical Phannacology and Toxicology ............................................................................ 23 
1.2.4. 
Nonclinical Pha1macokinetics ............................................................................................... 23 
1.2.5. 
Nonclinical Toxicology ......................................................................................................... 24 
1.2.6. 
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed-Dose Combination Emtricitabine/Tenofovir Alafenamide 
(F/TAF) ................................................................................................................................. 25 
1.3. 
E1nt1·icitabine (FTC, E1ntriva®) ............................................................................................................... 27 
1.3.1. 
General Infonnation .............................................................................................................. 28 
1.4. 
Fixed-Dose Combination ofEmtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) ............................ 28 
1.5. 
Rationale for This Study .......................................................................................................................... 28 
1.6. 
Rationale for Dose ................................................................................................................................... 29 
1.7. 
Risk/Benefit Assessment for the Study ................................................................................................... 29 
1.8. 
Coinpliance .............................................................................................................................................. 30 
2. 
OBJECTIVES ....................................................................................................................................................... 31 
3. 
STUDY DESIGN ................................................................................................................................................. 32 
3.1. 
3.2. 
3.3. 
Endpoints ................................................................................................................................................. 32 
3.1.1. 
Pri1nruy Endpoint. .................................................................................................................. 32 
3.1.2. 
Secondru End oints ............................................................................................................. 32 
.
Design ........................................................................................................................................... 33 
Stud Treatments ..................................................................................................................................... 35 
4. 
PARTICIPANTPOPULATION .......................................................................................................................... 37 
4.1. 
Number of Participants and Prut icipant Selection ................................................................................... 37 
4.2. 
Inclusion Criteria ..................................................................................................................................... 37 
4.3. 
Exclusion Criteria .................................................................................................................................... 38 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS ............................................................................................. 39 
5.1. 
Enrollment ............................................................................................................................................... 39 
5.2. 
Description and Handling ....................................................................................................................... .40 
5.2.1. 
Fo1mulation .......................................................................................................................... .40 
5.2.2. 
Packaging and Labeling ....................................................................................................... .40 
5.2.3. 
Storage and Handling ........................................................................................................... .41 
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5.3. 
Dosage and Ad1ninist1·ation .................................................................................................................... .41 
5.4. 
Prior and Concolllitant Medications ....................................................................................................... .41 
5.5. 
Dispensing and Accountability oflnvestigational Medicinal Product.. .................................................. 43 
6. 
STUDY PROCEDURES ...................................................................................................................................... 44 
6.1. 
6.2. 
6.3. 
6.4. 
6.5. 
6.6. 
6.7. 
6.8. 
6.9. 
6.10. 
6.11. 
Participant Enrollment and Treatment Assignment ................................................................................ 44 
Preti·eatinent Assessments ....................................................................................................................... 44 
6.2.1. 
Screening Visit ...................................................................................................................... 44 
6.2.2. 
Day 1 Visit (Baseline) .......................................................................................................... .46 
Treatment Assessments Blinded Phase (Weeks 4, 12, and Eve1y 12 Weeks Until the end of 
blinded ti·eatment phase visit) ................................................................................................................. .47 
End of Blinded Treatinent Phase Visit .................................................................................................... 51 
Treatment Assessments Open-Label Phase and Open-Label Extension Phase ....................................... 54 
6.5.1. 
Open-Label Phase (Prior to OL Week 96) ............................................................................ 54 
6.5.2. 
Open-Label Extension Phase (From OL Week 96) ............................................................... 57 
Unscheduled Visits .................................................................................................................................. 60 
Posttreatment Assess1nents ...................................................................................................................... 60 
6.7.1. 
Early Study Drng Discontinuation Assessments (Prior to OL Week 96) ............................. 60 
6.7.2. 
Early Study Drng Discontinuation Assessments (From OL Week 96) ................................. 62 
6.7.3. 
30-Day Follow-Up Assessinent ............................................................................................. 63 
Criteria for Resta1ting Study Drng After an Intenuption ........................................................................ 66 
Criteria for Discontinuation of Study Treatment. .................................................................................... 67 
Bone Evaluations ..................................................................................................................................... 68 
HIV Infection ........................................................................................................................................... 68 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ................................................................................ 70 
7 .1. 
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events ................................. 70 
7 .1.1. 
Adverse Events ...................................................................................................................... 70 
7.1.2. 
Serious Adverse Events ......................................................................................................... 70 
7 .1.3. 
Clinical Laborat01y Abnonnalities and Other Abno1mal Assessments as 
Adverse Events or Serious Adverse Events .......................................................................... 71 
7.2. 
Assessment of Adverse Events and Serious Adverse Events .................................................................. 71 
7.2.1. 
Assessment of Causality for Study Thugs and Procedw-es ................................................... 71 
7.2.2. 
Assess1nent of Severity .......................................................................................................... 72 
7.3. 
Investigator Requirements and Instiuctions for Repo1ting Adverse Events and Serious 
Adverse Events to Gilead ........................................................................................................................ 72 
7 .3 .1. 
Requirements for Collection Prior to Study Drng Initiation: ................................................ 72 
7.3.2. 
Adverse Events ...................................................................................................................... 72 
7.3.3. 
Serious Adverse Events ......................................................................................................... 73 
7.4. 
Gilead Repo1ting Requirements .............................................................................................................. 74 
7.5. 
Special Situations .................................................................................................................................... 74 
7 .5 .1. 
Repo1ting Special Situations ................................................................................................. 7 5 
7.6. 
Toxicity Manageinent .............................................................................................................................. 76 
7.6.1. 
Grades 1 and 2 Laborat01y Abnonnality or Clinical Event .................................................. 76 
7.6.2. 
Grades 3 Laborato1y Abno1mality or Clinical Event ............................................................ 76 
7.6.3. 
Grade 4 Laborato1y Abno1mality or Clinical Event.. ............................................................ 77 
7.6.4. 
Manage1nent of Bone Evaluation .......................................................................................... 77 
7 .6.5. 
Management of Changes in Estimated Glomernlar Filti·ation Rate ...................................... 77 
7.6.6. 
Potential High-Risk Exposure ............................................................................................... 77 
8. 
STATISTICAL CONSIDERATIONS ................................................................................................................. 78 
8.1. 
Analysis Objectives and Endpoints ......................................................................................................... 78 
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Emtricitabine and Tenofovir Alafenamide (F/TAF) 
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Gilead Sciences, Inc. 
8.2. 
8.3. 
8.4. 
8.5. 
8.6. 
8.8. 
8.9. 
8.1.1. 
8.1.2. 
8.1.3. -
Analysis Objectives ............................................................................................................... 78 
Pri1nruy Endpoints ................................................................................................................. 79 
Secondru End oints ............................................................................................................. 79 
Analysis Conventions .............................................................................................................................. 80 
8.2.1. 
Analysis Sets ......................................................................................................................... 80 
Demographic Data and Baseline Characteristics .................................................................................... 82 
Efficacy Analysis ..................................................................................................................................... 82 
8.4.1. 
Pri1nruy Analysis ................................................................................................................... 82 
8.4.2. 
Secondruy Efficacy Analysis ................................................................................................. 82 
Safety Analysis ........................................................................................................................................ 82 
8.5.1. 
Extent ofExposw·e ................................................................................................................ 83 
8.5.2. 
Adverse Events ...................................................................................................................... 83 
8.5.3. 
Laborato1 Evaluations ......................................................................................................... 83 
8.5.6. 
Other Safety Evaluations ....................................................................................................... 84 
Statistical Testino Procedure ................................................................................................................... 84 
Sample Size ............................................................................................................................................. 85 
Data Monitoring Co1nmittee .................................................................................................................... 87 
9. 
RESPONSIBILITIES ........................................................................................................................................... 88 
9 .1. 
Investigator Responsibilities ................................................................................................................... 88 
9.1.1. 
Good Clinical Practice ........................................................................................................... 88 
9.1.2. 
Institutional Review Board (IRB)/Independent Ethics Collllllittee (IEC) 
Review and Approval ............................................................................................................ 88 
9.1.3. 
Info1med Consent .................................................................................................................. 89 
9.1.4. 
Confidentiality ....................................................................................................................... 89 
9.1.5. 
Study Files and Retention of Records ................................................................................... 89 
9.1.6. 
CaseReportFoims ................................................................................................................ 91 
9 .1. 7. 
Investigational Medicinal Product Accountability and Retwn ............................................. 91 
9 .1. 8. 
Inspections ............................................................................................................................. 92 
9.1.9. 
Protocol Compliance ............................................................................................................. 92 
9.2. 
Sponsor Responsibilities ......................................................................................................................... 92 
9.2.1. 
Protocol Modifications .......................................................................................................... 92 
9.2.2. 
Study Report and Publications .............................................................................................. 92 
9.3. 
Joint Investigator/Sponsor Responsibilities ............................................................................................ 93 
9.3.1. 
Payment Reporting ................................................................................................................ 93 
9.3.2. 
Access to Infonnation for Monitoring ................................................................................... 93 
9.3.3. 
Access to Infonnation for Auditing or Inspections ............................................................... 93 
9.3.4. 
Study Discontinuation ........................................................................................................... 93 
10. REFERENCES ..................................................................................................................................................... 94 
11. APPENDICES ...................................................................................................................................................... 97 
Appendix 1. 
Appendix 2. 
Appendix 3. 
Appendix 4. 
Appendix 5. 
CONFIDENTIAL 
LIST OF IN TEXT-APPENDICES 
Investigator Signature Page ..................................................................................................... 98 
Study Procedures Table ........................................................................................................... 99 
Study Procedures Table (OL Week 96 and beyond) ............................................................. 103 
Management of Clinical and Laborat01y Adverse Events ..................................................... 105 
Gilead Grading Scale for Severity of Adverse Events and Laborato1y Abno1malities ......... 106 
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Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
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Appendix 6.
HIV Testing Algorithm .........................................................................................................128
Appendix 7.
HIV Infection Endpoint Definition........................................................................................129
Appendix 8.
Pandemic Risk Assessment and Mitigation Plan ..................................................................130
LIST OF IN-TEXT TABLES
Table 5-1.
Prior and Concomitant Medications........................................................................................42
Table 8-1.
Efficacy Information from Truvada as PrEP in MSMs...........................................................86
LIST OF IN-TEXT FIGURES
Figure 1-1.
Design of Study PC-412-2001 of F/TAF for PrEP in Rhesus Macaques................................21
Figure 1-2.
Plasma RNA and Serology Results from Study PC-412-2001 of F/TAF for PrEP in 
Rhesus Macaques ....................................................................................................................22
Figure 3-1.
Study Schema ..........................................................................................................................35

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 7
19 October 2021
PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title:
A Phase 3, Randomized, Double-blind Study to Evaluate the Safety 
and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis 
in Men and Transgender Women Who Have Sex with Men and Are 
At Risk of HIV-1 Infection
IND Number:
EudraCT Number:
127728
2016-001399-31
Study Centers Planned:
Approximately 100 centers in North America and Europe
Objectives:
The primary objective of this study is:

To assess the rates of HIV-1 infection in men who have sex with 
men (MSM) and transgender women (TGW) who have sex with 
men who are administered daily emtricitabine/tenofovir 
alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil 
fumarate (F/TDF) with a minimum follow up of 48 weeks and at 
least 50% of the participants have 96 weeks of follow up after 
randomization
The secondary objectives of this study are:

To compare bone safety between the treatments as determined by 
dual-energy X-ray absorptiometry (DXA) tests of hip and spine 
bone mineral density (BMD) in a subset of participants at 
Week 48 and Week 96 in the blinded phase

To compare renal safety between the treatments as determined 
by urine retinol-binding protein (RBP) to creatinine ratio, 
urine beta-2-microglobulin to creatinine ratio, urine protein to 
creatinine ratio (UPCR), and serum creatinine at Week 48 and 
Week 96 in the blinded phase

To assess the rates of HIV-1 infection in MSM and TGW who 
have sex with men who are administered daily F/TAF or F/TDF 
when all participants have 96 weeks of follow up after 
randomization

To compare the general safety between the treatments

Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Final 
Amendment 7 
Gilead Sciences, Inc. 
Study Design: 
CONFIDENTIAL 
Randomized, double-blind comparison of the safety and efficacy of 
F!IAF versus F/TDF administered orally once daily. 
All pa1ticipants must meet eligibility criteria in order to receive 
treatment in the stt1dy. Once randomized to receive treatment in the 
stt1dy, all pa1ticipants must rettnn to the study center for required 
visits at Weeks 4, 12, and eve1y 12 weeks thereafter. 
All pa1ticipants will remain blinded to study drng for at least 
96 weeks. The prima1y endpoint data will be collected and analyzed 
after all paiticipants have a minimum follow up of 48 weeks and at 
least 50% of paiticipants have 96 weeks of follow up after 
randomization. 
Once all pa1ticipants have at least 96 weeks of follow up after 
randomization and upon notification by Gilead, all paiticipants will 
re nun to the study center for an end of blinded treatment phase visit 
(may coincide with their next scheduled visit). 
Paiticipants who are still on blinded study drng at the end of blinded 
treatment phase visit will be offered entiy into the OL phase of the 
stt1dy. Paiticipants who continue pa1ticipation in the OL phase will 
be administered F!IAF once daily and will return to the stt1dy center 
for visits eve1y 12 weeks. 
Paiticipants who have 
discontinued study drng prior to the end of blinded ti·eatinent phase 
visit due to HIV infection will be eligible to continue paiticipation in 
the OL hase, but will not be adininistered F/TAF once dail . From 
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Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Final 
Amendment 7 
Gilead Sciences, Inc. 
OL Week 48, paiticipants who acquire HIV must complete the early 
stt1dy diug discontinuation (ESDD) visit and discontinue the study at 
the 30-Day Follow-up visit, 30 days after the last dose of study drng. 
Paiticipants who have discontinued study diug for any other reason 
plior to the end of blinded treatment phase visit will not be eligible 
to paiticipate in the OL Phase. 
Number of Pa1ticipants 
5000 
Planned: 
Target Population: 
MSM and TGW (male at bilth) who ai·e at risk of HIV-1 infection 
through sexual exposure with other men 
Duration of Treatment: 
Blinded Phase: 
CONFIDENTIAL 
Paiticipants will receive stt1dy diug for at least 96 weeks. After 
completing the Week 96 visit, all pa1ticipants will continue to take 
thefr blinded study di11g and attend visits eve1y 12 weeks until the 
last paiticipant reaches Week 96. All paiticipants will renun to the 
stt1dy center for an end of blinded treatment phase visit (may 
coincide with thefr next scheduled visit) upon notification by Gilead. 
Open-Label Phase: 
Paiticipants will receive OL F/TAF for up to 96 weeks and will 
continue OL study visits eve1y 12 weeks. From OL Week 48, 
pa1ticipants who acqufre HIV must complete the ESDD visit and 
discontinue the study at the 30-Day Follow-up visit 30 days after the 
last dose of study di11g. 
Open-Label Extension Phase: 
Pa1ticipants who have been diagnosed and 
confumed as HIV positive during this phase must complete the 
ESDD visit and discontinue the study at the 30-Day Follow-up visit, 
30 days after the last dose of stt1dy diug. 
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Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
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Diagnosis and Main 
Eligibility Criteria:

HIV-1negative status

MSM or TGW (male at birth) who have at least one of the 
following:
a) condomless anal intercourse with at least 2 unique male 
partners in the past 12 weeks (partners must be either 
HIV-infected or of unknown HIV status)
b) documented history of syphilis in the past 24 weeks
c) documented history of rectal gonorrhea or chlamydia in the 
past 24 weeks

Age ≥ 18 years

No suspected or known active, serious infection(s)

Estimated glomerular filtration rate > 60 mL/min according to 
the Cockcroft-Gault formula

Adequate liver and hematologic function:

Aspartate aminotransferase (AST) and alanine aminotransferase 
(ALT) ≤ 2.5 × upper limit of normal (ULN) and total bilirubin 
≤ 1.5 mg/dL, or normal direct bilirubin

Absolute neutrophil count ≥ 1000/mm3, platelets ≥ 75,000/mm3, 
and hemoglobin ≥ 10 g/dL

Have not received investigational agents for the treatment or 
prevention of HIV-1 infection in the 30 days prior to screening

No evidence of acute viral hepatitis A, B or C, and no evidence 
of chronic hepatitis B virus infection. Participants found to be 
susceptible to hepatitis B virus (HBV) infection should be 
referred for HBV vaccination. Participants found to be positive 
for hepatitis C virus (HCV) must not have active infection or 
must have completed treatment and achieved a sustained 
virologic response

No history of osteoporosis or bone fragility fractures
Study Procedures/
Frequency:
Screening Visit
Upon providing written informed consent, participants will be 
evaluated for eligibility at the screening visit, including medical 
history review, concomitant medication review, complete physical 
examination including height, weight, and vital signs, sexually 
transmitted infection (STI) testing for gonorrhea, chlamydia, and 
syphilis, fourth generation rapid HIV-1 antibody (Ab)/antigen (Ag) 
or third generation rapid HIV-1 Ab test, HIV Ab/Ag testing, HIV-1 
RNA testing if applicable, Hepatitis B testing, Hepatitis C testing, 
clinical laboratory assessments for blood and urine samples, 

Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Final 
Amendment 7 
Gilead Sciences, Inc. 
CONFIDENTIAL 
computer-assisted self-interview (CASI) for: recent sexual risk 
events; interest in using PrEP; self-identification of transgender 
status; education and employment histo1y; and use of tobacco and 
recreational diugs, and risk reduction counseling including provision 
of condoms. 
Prior to the Day 1 visit and randomization, the investigator will 
review the screening assessments to confilm eligibility. The Day 1 
visit must occur within 30 days after the screening visit. 
Blinded Treatment Phase 
Dming the blinded treatment phase, pa1ticipants will be seen at the 
stt1dy center for visits at Day 1, Weeks 4, 12, 24, and eve1y 12 weeks 
thereafter until the end of blinded treatment phase visit. 
At the Day 1 visit, pa1ticipants will be assessed with fomth 
generation rapid HIV-1 Ab/ Ag or third generation rapid HIV-1 Ab 
test, HIV-1 RNA if applicable, adverse event (AE) and concomitant 
medication review, targeted physical examination and vital signs if 
applicable, CASI, and adherence and 1isk reduction counseling 
including provision of condoms. 
At all other study visits during the blinded treatment phase, 
pa1ticipants will be assessed with targeted physical examination 
(complete physical examination at Week 48 and 96), AE and 
concomitant medication review, vital signs if clinically indicated, 
weight, STI testing for gono1Thea, chlamydia, and syphilis, fomth 
generation rapid HIV-1 Ab/ Ag or third generation rapid HIV-1 Ab 
test, HIV Ag/Ab testing, HIV-1 RNA testing if applicable, Hepatitis 
B testing (eve1y 24 weeks), Hepatitis C testing (eve1y 48 weeks), 
clinical laborato1y assessments for blood and urine samples, plasma 
storage sample collection, 
If the paiticipant discontinues study diug prior to the end of blinded 
treatment phase visit, the paiticipant will be asked to rettnn to the 
stt1dy center within 72 hours of stopping study di11g for the ESDD 
visit. The paiticipant will be asked to continue attending the 
scheduled study visits through the end of blinded treatment phase 
visit of the study. 
Paiticipants who are still on study di11g at the end of blinded 
treatment hase visit will be offered entl into the OL hase and OL 
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Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Final 
Amendment 7 
Gilead Sciences, Inc. 
Test Product, Dose, and 
Mode of Administration: 
CONFIDENTIAL 
extension phase of the study. Paiticipants who have discontinued 
stt1dy diug prior to the end of blinded treatment phase visit due to 
HIV infection will be eligible to continue paiticipation in the OL 
phase up to OL Week 48, but will not be administered F/TAF once 
daily. 
Open-Label Phase 
Dming the OL phase, pa1ticipants will be seen at the stt1dy center for 
visits eve1y 12 weeks up to OL Week 96. 
At all study visits dming the OL phase, paiticipants will be assessed 
with tai·geted physical examination ( complete physical exainination 
at OL Week 48), AE and concomitant medication review, vital signs 
if clinically indicated, weight, STI testing for gonoIThea, chlamydia, 
and syphilis, fomth generation rapid HIV-1 Ab/ Ag or 
third generation rapid HIV-1 Ab test, HIV Ab/ Ag testing, HIV-1 
RNA testing if applicable, Hepatitis B testing (eve1y 24 weeks), 
Hepatitis C testing (eve1y 48 weeks), clinical laborato1y assessments 
for blood and mine samples, plasma storage sample collection, 
Throughout the stt1dy, paiticipants may be asked to provide daily 
info1mation on adherence and sexual lisk events through the use of a 
dia1y. Paiticipants may also receive peliodic contacts to relnind them 
to take their study diug and to provide any additional suppo1t needed. 
Open-Label Extension Phase 
Dming the OL extension phase, paiticipants will be seen at the study 
center for visits eve1y 12 weeks from OL Week 96 up to OL 
Week 408. 
At all study visits dming the OL extension phase, pa1ticipants will be 
assessed with targeted physical examination (eve1y 24 weeks), AE 
and concolnitant medication review, vital signs (eve1y 24 weeks), 
weight (eve1y 24 weeks), STI testing for gonoIThea, chlamydia, and 
syphilis, at a 1ninimum fomth generation rapid HIV-1 Ab/ Ag or 
third generation rapid HIV-1 Ab test, HIV Ab/ Ag testing, HIV-1 
RNA testing if applicable, Hepatitis B testing (eve1y 48 weeks), 
Hepatitis C testing (eve1y 48 weeks), clinical laborato1y assessments 
for blood samples, DBS collection and risk reduction counseling 
including provision of condoms. 
Blinded Phase: 
F/TAF fixed-dose combination (FDC) (200 mg emtricitabine/25 mg 
tenofovir alafenalnide), adininistered orally once daily. 
Open-Label and Open-Label Extension Phase: 
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Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Final 
Amendment 7 
Gilead Sciences, Inc. 
Reference Product, Dose, 
and Mode of 
Administration: 
Criteria for Evaluation: 
Safety: 
Efficacy: 
Risk Behavior 
Assessment: 
Statistical Methods: 
CONFIDENTIAL 
F!TAF FDC (200 mg emtricitabine/25 mg tenofovir alafenamide), 
administered orally once daily. 
Blinded Phase: 
F!TDF FDC (200 mg emtricitabine/300 mg tenofovir disoproxil 
fumarate), administered orally once daily. 
• 
Adverse events 
• 
Physical examinations, vital signs 
• 
Clinical laborato1y tests of blood and urine 
• 
• 
STI testing 
• 
Adherence measures including tablet collection, responses to 
adherence questions as paii of the CASI, and FTC and/or TFV 
levels in the plasma or DBS 
Incidence ofHIV-1 infection defined by one or more of the following 
criteria of contributing HIV tests perfonned via central lab or local 
lab: 
1) Serologic evidence of seroconversion (reactive screening HIV 
Ag/Ab or Ab test, confumed by the reactive HIV-1/HIV-2 
differentiation assay), excluding HIV vaccinated paiticipants, or 
2) Virologic evidence of HIV-1 infection (positive qualitative 
HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), 
or 
3) Evidence of acute HIV-1 infection (reactive p24 Ag or positive 
qualitative or quantitative RNA, in the absence of reactive HIV-1 
Ab results) 
Please refer to Appendix 7 for more details. 
Computer-Assisted Self-Interview (CASI) sexual risk event 
evaluation 
The primaiy endpoint will be the incidence ofHIV-1 infection 
(as defined above) per 100 person years (PY). 
The primaiy analysis will occur when all paiticipants have a 
minimum of 48 weeks of follow up and at least 50% of the 
a1tici ants have at least 96 weeks of follow u after randomization. 
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The primary analysis will consist of a non-inferiority evaluation of 
F/TAF versus F/TDF, with respect to the HIV-1 infection rate in PY 
as determined by rate ratios. It will be concluded that F/TAF is 
non-inferior to F/TDF if the upper bound of the 95% CI of the ratio 
between the two arms (F/TAF over F/TDF) is less than 1.62. The 
95% CI will be constructed using a generalized model associated 
with a Poisson distribution and logarithmic link with the treatment 
group being the covariate. A sample size of 2500 in each arm 
provides at least 82% power to show F/TAF is non-inferior to F/TDF 
with respect to the HIV-1 infection rate, and assumes an HIV-1 
infection rate of 1.44 per 100 PY in the F/TAF and F/TDF treatment 
arms, a 2-sided Type 1 error rate of 5%, and an average follow up of 
2 years (ie, last participant has a minimum of 48 weeks of follow up 
and at least 50% of the participants have at least 96 weeks of follow 
up after randomization).
An independent data monitoring committee (IDMC) will be 
convened to primarily evaluate the safety of the treatments in this 
population. There are no prior plans to stop for efficacy or futility 
with formal boundaries. At a minimum, the IDMC will include 
2 clinicians (including a chairperson), a biostatistician, a prevention 
expert, and a community member. The initial evaluation by the 
IDMC will occur either (1) after 50% of participants have completed 
Week 24 (or prematurely discontinued from the study drug) or 
(2) after 50 HIV-1 infections have been reported, whichever occurs 
earlier. The second evaluation by the IDMC will occur either 
(1) after 50% of participants have completed Week 48 
(or prematurely discontinued from the study drug) or (2) after 
100 HIV-1 infections have been reported, whichever occurs earlier. 
The third evaluation by the IDMC will occur either (1) after 50% of 
participants have completed Week 72 (or prematurely discontinued 
from the study drug) or (2) after 150 HIV-1 infections have been 
reported, whichever occurs earlier.
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
Ab
antibody
AE
adverse event
Ag
antigen
AK
adenylate kinase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANOVA
analysis of variance
ART
antiretroviral therapy
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
BMD
bone mineral density
BUN
blood urea nitrogen
CASI
computer-assisted self-interview
CBC
complete blood count
CD4
cluster determinant 4
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
CLcr
creatinine clearance
Cmax
maximum observed concentration of drug
CNS
central nervous system
COVID-19
coronavirus disease 2019
CRF
case report form
CSR
clinical study report
Ctrough
concentration at the end of the dosing interval
CYP
cytochrome P450
DBS
dried blood spot
DNA
deoxyribonucleic acid
DXA
dual-energy X-ray absorptiometry
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (coformulated; Genvoya®)
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
eGFR
estimated glomerular filtration rate
ESDD
early study drug discontinuation

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EU
European Union
F
emtricitabine (Emtriva®)
F/TAF
emtricitabine/tenofovir alafenamide (coformulated; Descovy®)
F/TDF
emtricitabine/tenofovir disoproxil fumarate
FAS
Full Analysis Set
FDA
Food and Drug Administration
FDC
fixed-dose combination
FTC
emtricitabine
FTC-TP
emtricitabine 5′-triphosphate
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GGT
gamma glutamyltransferase
GI
gastrointestinal
Gilead
Gilead Sciences
GLPS
Global Patient Safety
HBcAb
hepatitis B virus core antibody
HBsAb
hepatitis B virus surface antibody
HBsAg
hepatitis B virus surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HDL
high-density lipoprotein
HDPE
high-density polyethylene
HIV
human immunodeficiency virus
HIV-1
human immunodeficiency virus type 1
HIV-2
human immunodeficiency virus type 2
IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
IDMC
independent data monitoring committee
IEC
independent ethics committee
IMP
Investigational Medicinal Product
IRB
institutional review board
IV
intravenous
IXRS
interactive voice/web response system
LDH
lactate dehydrogenase
LDL
low-density lipoprotein
LOCF
last observation carried forward
MSM
men who have sex with men
NA
not applicable

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NOAEL
no observed adverse effect level
NRTIs
nucleotide reverse transcriptase inhibitors
OL
open label
PBMC
peripheral blood mononuclear cell
PBO
placebo
PCR
polymerase chain reaction
PD
pharmacodynamics
PEP
postexposure prophylaxis
PI
principal investigator
PK
pharmacokinetics
PP
Per Protocol
PrEP
pre-exposure prophylaxis
PRT
proximal renal tubulopathy
PT
Preferred Term
PY
person years
QT
electrocardiographic interval between the beginning of the Q wave and termination of 
the T wave, representing the time for both ventricular depolarization and 
repolarization to occur
QTc
QT interval corrected for heart rate
RBC/HPF
red blood cells per high power field
RBP
retinol-binding protein
RNA
ribonucleic acid
SAE
serious adverse event
SD
standard deviation
SDV
source data verification
SHIV
simian/human immunodeficiency virus
SOC
System Organ Class
SOP
standard operating procedure
STB
Stribild®
STI
sexually transmitted infection
SUSAR
suspected unexpected serious adverse reaction
TAF
tenofovir alafenamide
TDF
tenofovir disoproxil fumarate
TFV
tenofovir
TFV-DP
tenofovir diphosphate
TGW
transgender women
ULN
upper limit of normal
UNAIDS
United Nations Programme on HIV/AIDS
UP
urine protein
UPCR
urine protein to creatinine ratio

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URAI
unprotected receptive anal intercourse
US
United States

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1.
INTRODUCTION
1.1.
Background
The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that there were 
1.5 million new HIV-1 infections in 2020 despite widespread knowledge of the protective effects 
of abstinence, monogamy, and condoms in preventing new HIV-1 infections {UNAIDS, 2020}. 
The principal interventions used to prevent HIV transmission have been voluntary testing and 
counseling and the promotion of condoms. The effectiveness of these interventions has been 
variable {Coates 2000, Higgins 1991, Wolitski 1997} and the prevalence of HIV-1 infection 
remains high even in settings with 100% condom promotion policies {Lertpiriyasuwat 2003}. 
Additionally, new HIV-1 infections in the United States (US) have been consistently stable at 
about 50,000 per year, and 70% of these are in men who have sex with men (MSM), with or 
without concurrent injection drug use {Centers for Disease Control (CDC) 2015}; in fact, the 
proportion of new infections due to male-to-male transmission increased from 2010-2014. 
Although intense research has been conducted to develop a conventional vaccine against HIV-1 
infection, these efforts have failed to produce a viable option. Thus, an important medical need 
exists for a novel approach to augment HIV-1 prevention services and reduce the spread of 
HIV-1 infection.
Pre-exposure prophylaxis strategies have been used to prevent transmission of infectious 
diseases such as malaria and HIV-1. Evidence supporting the efficacy of prophylaxis with 
antiretroviral (ARV) therapy (ART) in decreasing HIV-1 seroconversion can be found in 
experience with postexposure prophylaxis (PEP) in animal models {Tsai 1995, Van Rompay 
2000, Van Rompay 2001} and in other clinical settings such as with occupational exposure with 
healthcare workers or with maternal-to-child transmission {Gerberding 1993}.
Truvada®, a fixed-dose combination (FDC) of emtricitabine (F, FTC) and tenofovir disoproxil 
fumarate (TDF), was first granted marketing approval by the US Food and Drug Administration 
(FDA) for use in combination with other agents for the treatment of HIV-1 infection in adults on 
02 August 2004. On 16 July 2012, a supplemental New Drug Application (sNDA) 021752/S-030 
was approved to expand the use of Truvada in combination with safer sex practices for 
pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high 
risk. While TDF is an effective drug used broadly (as part of multiple combination regimens) in 
both the treatment and prevention of HIV-1 infection, nephrotoxicity has been reported with the 
use of TDF and manifests as increased creatinine, increased protein loss (particularly tubular), 
and occasional cases of proximal renal tubulopathy (PRT) (including Fanconi Syndrome). These 
TDF-associated renal risks necessitate increased renal monitoring, placing burden on the patient 
and healthcare provider. In addition, early onset bone demineralization in adults has also been 
reported with use of TDF, specifically reductions in bone mineral density (BMD); the decreases 
in BMD with TDF are larger than those seen with other nucleoside/nucleotide reverse 
transcriptase inhibitors (NRTIs) {Gilead Sciences International Limited 2016, VIREAD® 2016}.

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Gilead has coformulated FTC with tenofovir alafenamide (TAF) into a FDC for use once daily in 
combination with other ARV agents for the treatment of HIV-1 in adults and pediatric patients 
12 years of age and older. Tenofovir alafenamide is a new prodrug of the N(t)RTI tenofovir 
(TFV) that is more stable in plasma than TDF. TAF has pharmacokinetic (PK) properties that 
distinguish it from TDF, with clinically important consequences. TAF 25 mg achieves > 4-fold 
higher intracellular levels of the pharmacologically active phosphorylated metabolite tenofovir 
diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) and ~90% lower 
circulating levels of TFV relative to TDF (300 mg). This marked reduction in circulating TFV is 
associated with smaller changes in clinical markers of renal function (eg, proteinuria) and in 
BMD that are consistent with those seen in participants receiving non-TDF containing regimens.
Key Phase 3 clinical data from the Genvoya® clinical program demonstrates that 
F/TAF-containing regimens significantly improve bone safety profile as compared with 
TDF-based regimens, specifically, significantly less reduction in BMD at both the hip and spine 
for ART-naive participants compared to Stribild® (STB), and significant improvements in BMD 
for participants who switched from a TDF-based regimen to Genvoya. Additionally the data 
demonstrates that F/TAF-containing regimens significantly improve renal safety profile as 
compared with TDF-based regimens, specifically, significantly less change in serum creatinine, 
proteinuria, and specific renal tubular proteinuria for ART-naive participants compared with 
STB; and a significant reduction in serum creatinine levels and significant improvements in renal 
tubular protein parameters for participants who switched from a TDF-based regimen to Genvoya.
F/TAF has favorable characteristics that make it suitable for evaluation as chemoprophylaxis, 
including higher PBMC intracellular concentrations of the pharmacologically active metabolite 
TFV-DP than TDF-based regimens with potent antiviral effects, a long intracellular half-life of 
more than 24 hours for TFV-DP, convenient once-daily oral dosing, a favorable tolerability 
profile, and infrequent selection of drug resistance mutations. Efficacy of F/TAF for 
chemoprophylaxis has been demonstrated by preventing simian/human immunodeficiency virus 
(SHIV) infection in a rhesus monkey model (see Section 1.2.2).
Use of F/TAF is less likely to impact bone mineralization in younger adults 18-25 and less likely 
to impact kidney function in older adults who are at increased risk of chronic kidney disease. 
Once commercially available, the use of F/TAF for PrEP in uninfected individuals at high risk of 
acquiring HIV infection may provide an effective prevention regimen with a significantly 
improved renal and bone safety profile relative to Truvada.
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 oral prodrug of 
TFV, a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, TFV-DP, a competitive inhibitor of HIV-1 reverse 
transcriptase that terminates the elongation of the viral DNA chain. In the development of TAF, 
3 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); and GS-7340-03 

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as the hemifumarate (2:1). 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 and 
a number of ongoing studies. GS-7340-03 was also used in the Phase 2 Study GS-US-292-0102 
and is being used in several ongoing Phase 3 studies (for example: GS-US-292-0104 and 
GS-US-292-0111). GS-7340-03 and GS-7340-02 exist as the free base, TAF (GS-7340), in blood 
and biological fluids.
For further information on F/TAF, refer to the current investigator’s brochure (IB) for F/TAF.
1.2.2.
Nonclinical Studies of F/TAF for PrEP
Nonclinical pharmacology studies in rhesus macaques show that orally administered F/TAF, at 
doses resulting in PBMC exposures that are consistent with those achieved in humans 
administered a dose of F/TAF 200/25 mg, effectively prevents SHIV infection.
Using a design similar to a previous Centers for Disease Control and Prevention (CDC) study of 
F/TDF in rhesus macaques {Garcia-Lerma 2010}, researchers at the CDC demonstrated that oral 
administration of F/TAF in rhesus macaques prevents infection with a chimeric SHIV 
(PC-412-2001). The dose of TAF selected for administration in the SHIV viral challenge study 
was based on an initial PK study in macaques wherein a TAF dose of 1.5 mg/kg was shown to 
result in intracellular concentrations of the active moiety TFV-DP in PBMCs consistent with 
those seen with use of a TAF 25 mg dose in humans (see PK section below). FTC was dosed at 
20 mg/kg based on a similar rationale, and consistent with the previous study with F/TAF in 
macaques. In the SHIV viral challenge study, 12 healthy rhesus macaques were administered 
weekly inoculations of intrarectal SHIV. Twenty-four hours before each rectal inoculation and 
2 hours after each rectal inoculation, one group of 6 animals was administered 20 mg/kg FTC 
and 1.5 mg/kg TAF by oral gavage and one group of 6 animals was administered placebo 
(saline control) by oral gavage. SHIV challenges and paired gavages were administered once a 
week for up to 19 weeks (schematic of the study design is provided in Figure 1-1). All 
6/6 macaques given placebo (saline control) became infected with SHIV, while 0/6 macaques 
given F/TAF became infected with SHIV (results shown in Figure 1-2).
Figure 1-1.
Design of Study PC-412-2001 of F/TAF for PrEP in Rhesus Macaques
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
 
 
  
 

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Figure 1-2.
Plasma RNA and Serology Results from Study PC-412-2001 of F/TAF 
for PrEP in Rhesus Macaques
Note: Each colored line represents an individual rhesus monkey. The Weeks 1-5 represent viral challenges with the initial viral 
stock. Weeks 1’-19’ represent viral challenges with a second viral stock with higher infectivity.
The dose of TAF used in Study PC-412-2001 was chosen to target the PBMC exposure range 
observed in humans following administration of TAF 25 mg. While the definitive correlate of 
protection against mucosal viral exposure is not established, intracellular levels of TFV-DP have 
been consistently associated with both virologic suppression and with prophylaxis across a 
variety of human and animal studies {Abdool Karim 2010, Anderson 2012, Baeten 2012, 
Castillo-Mancilla 2013, Garcia-Lerma 2008, Grant 2010, Van Rompay 2012, 
Van Rompay 2001}.
The results of Study PC-412-2001 in rhesus macaques are consistent with the previously 
published CDC study of FTC and TDF conducted in the same nonhuman primate model 
{Garcia-Lerma 2010}. In the prior SHIV viral challenge study, rhesus macaques were inoculated 
with SHIV once a week for 14 weeks via intrarectal administration. Various dosing regimens 
using orally administered 20 mg/kg FTC and 22 mg/kg TDF (given 1, 3, or 7 days before 
exposure followed by a second dose 2 hours after exposure) were evaluated. In that study, 
5 of 6 animals given oral F/TDF at 24 hours prior to SHIV inoculation and 2 hours after 
SHIV inoculation at doses equivalent to those administered to humans for treatment remained 
seronegative through 14 inoculation challenges of rectally administered SHIV. Protection against 
SHIV in rhesus macaques subject to rectal challenge has also been observed following daily 
subcutaneous administration of 20 mg/kg FTC and 22 mg/kg TFV, suggesting that local 
concentrations possible in the gastrointestinal tract following oral administration are not required 
for protection and that systemic loading of HIV-target cells (ie PBMCs) drives efficacy 
{Garcia-Lerma 2008}.
 
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
   
 
 
 
 

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1.2.3.
Preclinical Pharmacology and Toxicology
1.2.3.1.
Primary Pharmacodynamics
TAF 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) {Tsai 1995} 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.
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, cluster of determinant 4+ (CD4+) and cluster 
determinant 8+ (CD8+) T-cells, 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.
1.2.3.2.
Safety Pharmacology
TAF monofumarate (GS-7430-02) has been evaluated to determine potential effects on the 
central nervous system (R990188), renal system (R990186), cardiovascular (D2000006) and 
gastrointestinal systems (R990187). Single doses 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). TAF monofumarate (at 1000 mg/kg reduced 
distal transit and increased stomach weights starting 2 hours postdosing with reversibility 
beginning by 6 hours after dosing. The no observed effect level (NOEL) for gastrointestinal 
motility was 100 mg/kg. The half-maximal inhibitory concentration (IC50) for the inhibitory 
effect of TAF fumarate (GS-7340-03) on human ether-a-go-go-related gene (hERG) potassium 
current was estimated to be greater than 10 μM.
1.2.4.
Nonclinical Pharmacokinetics
All nonclinical PK experiments in this section 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).
Plasma PK of the intact prodrug, TAF, following oral administration of GS-7340-02 in dogs and 
monkeys demonstrated rapid absorption with peak plasma concentrations between 0.25 and 
0.5 hours.
Peak TFV plasma concentrations occurred following TAF absorption, with TFV Tmax values 
between 0.25 to 1.7 hours in rats, dogs, and monkeys. TFV plasma concentrations declined with 
a terminal half-life of 11.2 to 16.4 hours in rats (fasted), > 24 hours in dogs (fasted) and 
8.1 to 12.5 hours in rhesus monkeys.

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The tissue distribution and recovery of [14C] radiolabeled GS-7340-02 was examined in beagle 
dogs. 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, PBMCs, liver, large intestine, and bile. Significant concentrations of 
TFV-related radioactive material were observed in lymph nodes suggesting that TAF may be 
selectively cleaved to tenofovir in the cells of the lymphoreticular system.
The primary route of elimination of tenofovir is renal excretion of unchanged drug based on 
IV studies of tenofovir. Following oral administration of GS-7340-02, approximately 15% of a 
radiolabeled dose is recovered in dog urine in 24 hours. Tenofovir was the major species present 
in the urine (90%), with about 3.4% of TAF also present. Biliary excretion of tenofovir in dogs 
and fecal elimination of tenofovir in rats and dogs are negligible.
Tenofovir was the only species found in the intestinal contents and feces. In human systems, 
TAF is metabolized by hydrolytic cleavage and, to a lesser extent, by cytochrome P450 
(CYP)3A4 catalyzed oxidation (AD-120-2004). As a result of the limited metabolism of TAF by 
CYP3A4 inhibition or induction of this enzyme should have little consequence on TAF exposure 
in vivo. TAF has limited potential to alter CYP enzyme activity through inhibition and does not 
inhibit uridine glucuronosyltransferase (UGT)1A1 function. In addition, TAF is not an activator 
of either the aryl hydrocarbon receptor (AhR) or human pregnane-X-receptor (PXR). These 
features combined with the relatively low plasma exposures of TAF in humans suggest that the 
potential of TAF to cause or be affected by clinically relevant drug-drug interactions is very low.
1.2.5.
Nonclinical Toxicology
TAF monofumarate (GS-7340-02) was evaluated in mice, rats, dogs, and monkeys for treatment 
periods up to 9-months and was negative in genetic toxicology studies.
In chronic studies in rats, bone (atrophy of metaphyseal cancellous bone) and kidneys 
(karyomegaly) were the primary target organs after 26 weeks of treatment. GS-7340-02 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 with GS-7340-02, the primary target organs were 
kidney and bone. This chronic toxicity study of TAF in beagle dogs given 2 mg/kg/day, 
6 mg/kg/day or 12-18 mg/kg/day for 9 months found non-specific mononuclear cell infiltrates 
seen on histopathology in the lungs, spleen and posterior uvea (eye) of animals in the 
12-18 mg/kg group. This group of animals experienced generalized debility at the 18 mg/kg/day 
dose, so the dose was decreased after Week 6. The histopathologic changes were felt to be due to 
the overall condition of the animals and not specific TAF-related toxicity. There were no 
findings in the eyes of dogs treated with lower doses (2 mg/kg and 6 mg/kg), and it was 
concluded that the no observed adverse effect level (NOAEL) in beagle dogs was 2 mg/kg/day.

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TAF monofumarate had no discernible electrocardiograph effect at the low dose of 2 mg/kg/day 
and slightly prolong PR intervals at 6 and 12-18 mg/kg/day. Additionally, at Week 39, 
TAF monofumarate appeared to reversibly reduce heart rate with an associated mild QT 
prolongation. At Week 39, decreases in serum triiodothyronine (T3) were noted for animals 
receiving 18/12 mg/kg/day but was reversible at the 3-month recovery period. Minor 
hematological and biochemistry parameters changes were observed but remained within normal 
historical ranges with the following exceptions: aspartate aminotransferase (AST) 
(~100% increase) and total bilirubin (~40% increase). There were no clear treatment-related 
effects observed in monkeys following 28 days of treatment including no changes in 
mitochondrial function.
The data from the 6-month rat study determined a NOAEL of 25 mg/kg/day 
(tenofovir AUC = 3758 ng•h/mL); the 9-month dog study defined a NOAEL of 2 mg/kg/day 
(tenofovir AUC = 1180 ng•h/mL), and the 28-day nonhuman primate study defined a NOAEL of 
30 mg/kg/day (tenofovir AUC = 5870 ng•h/mL). In conjunction with the nonclinical data with 
TDF and the clinical experience with TDF and TAF, these toxicology studies support studies in 
humans of doses up to 150 mg/day (120 mg free base, the highest anticipated human dose) for 
chronic treatment.
At the time of the rodent toxicity studies, the bioassay could not detect plasma TAF, possibly due 
to instability in the matrix.
Because of the lack of exposure to the prodrug in mice and rats and achievable tenofovir 
exposures less than previously tested in chronic and carcinogenicity studies with TDF, 
carcinogenicity studies in mice and rats with TAF are not required per agreement with the FDA.
Also, TAF does not need to be evaluated in perinatal-postnatal reproductive toxicology studies 
per agreement with the FDA. Reproductive tissues were examined in repeat-dose toxicology 
studies in the rat, dog, and monkey. There were no clearly treatment-related histologic alterations 
or changes in organ weights in the rat and the dog following chronic daily dosing, or in the 
monkey.
The TAF fumarate (GS-7340-03) oral rat fertility study is ongoing (Report No. TX-120-2012, 
report in progress).
1.2.6.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) or 
Fixed-Dose Combination Emtricitabine/Tenofovir Alafenamide (F/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected participants (completed)

GS-US-120-0104, a Phase 1b study of the pharmacokinetics and antiviral activity of 
GS-7340 (8 mg, 25 mg, 40 mg) in HIV-infected participants (completed)

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
GS-US-120-0107, a Phase 1, partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-7340 on the QT/QTc interval in healthy participants 
(completed)

GS-US-120-0108, a Phase 1, open-label, parallel-design study to evaluate the 
pharmacokinetics of GS-7340 in participants with severe renal impairment (completed)

GS-US-120-0109, a Phase 1 study to evaluate the pharmacokinetics, metabolism and 
excretion of GS-7340 (completed)

GS-US-120-0114, a Phase 1, open-label, parallel-group, single-dose study to evaluate the 
pharmacokinetics of tenofovir alafenamide in participants with normal and impaired hepatic 
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug 
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a pharmacokinetic study evaluating the drug interaction potential of 
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in 
healthy participants (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential 
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz or 
cobicistat-boosted darunavir (completed)

GS-US-311-1088, a Phase 1, Relative Bioavailability Study of Emtricitabine/Tenofovir 
Alafenamide Fixed Dose Combination Tablet to evaluate the formulation performance of 
FTC and TAF fixed dose combination tablets relative to co-administration of individual 
agents (completed).
The first proof-of-concept study, GS-US-120-1101, as well as GS-US-120-0104 and 
GS-US-292-0101 were performed using TAF monofumarate (GS-7340-02). All subsequent 
studies were performed using TAF fumarate (GS-7340-03), with the exception of 
GS-US-311-0101 Cohort 4, which used the monofumarate (GS-7340-02) for the GS-7340 single 
agent 8-mg tablet.
GS-US-120-1101 was a Phase 1/2 randomized, double-blind, active-controlled, dose escalation 
study of the safety, tolerance, PK, and antiviral activity of TAF in ARV-naive patients who were 
chronically infected with HIV-1. The participants were randomized to receive 14 days of 
monotherapy, fasting, with TAF monofumarate 50 mg once daily, 150 mg once daily, or TDF 
300 mg once daily (n = 10 per group). TAF was rapidly absorbed into the systemic circulation, 
and following attainment of Cmax, was eliminated rapidly with a short plasma half-life 
(20-40 minutes). Compared with TDF, TAF monofumarate 50 mg provided a ~16-fold lower 
tenofovir Cmax (207 ng/mL vs 13 ng/mL), about two-fold longer elimination half-life (26 hours 
vs 48 hours) and lower overall systemic tenofovir exposure (AUCinf: 1814 ng•h/mL vs 
383 ng•h/mL). TAF monofumarate 150 mg provided lower Cmax (42 ng/mL), but comparable 

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AUCinf: (1740 ng•h/mL) as TDF. In PBMCs, tenofovir was detectable earlier, more frequently, 
and in higher concentrations following dosing of TAF monofumarate. The intracellular delivery 
of tenofovir is approximately 30-fold greater for TAF monofumarate versus TDF. The decrease 
from baseline to Day 14 in plasma HIV-RNA levels was greater for groups treated with TAF 
monofumarate 50 mg (p = 0.0257) or 150 mg (p = 0.0010) than the group that received TDF 
300 mg. The median changes from baseline in plasma HIV-1 RNA after 14 days of monotherapy 
were −0.96 log10 copies/mL for TDF 300 mg, −1.65 log10 copies/mL for TAF monofumarate 
50 mg, and −1.68 for TAF monofumarate 150 mg.
A second proof-of-concept study, GS-US-120-0104, evaluated monotherapy, with 3 lower doses 
of TAF or TDF 300 mg, or placebo, administered in a fasted state for 10 days. Potent antiviral 
activity was achieved in treatment-naive HIV-1 infected patients, with mean (± SD) change from 
baseline in HIV-1 RNA of −0.98 ± 0.46, −1.50 ± 0.41, −1.74 ± 0.19, and 
−0.81 ± 0.58 log10 copies/mL at 8 mg, 25 mg, 40 mg dose of TAF, and TDF 300 mg, 
respectively. Mean viral load declines for both the 25 mg and 40 mg doses were statistically 
greater than the 8-mg dose. TAF exposure (AUC) was best associated with antiviral activity 
despite its short plasma half-life (~30 min). TFV AUC were 97%, 87%, and 80% lower at 8 mg, 
25 mg, and 40 mg TAF compared to TDF administration. When compared with 40 mg and 
historical 120 mg data, 25 mg TAF provides near maximal activity (predicted to 
be ~ −1.7 to1.8 log10 c/mL). From this PK-pharmacodynamic (PD) analysis, a target dose of 
20-25 mg TAF monotherapy is expected to provide near maximal activity and ~90% reduction in 
circulating TFV.
Study GS-US-120-0107 is a Phase 1, partially-blinded, randomized, placebo- and 
positive-controlled study to evaluate the effect of TAF on the QT/QTc interval in healthy 
participants. This was a negative thorough QTc study. No effect of TAF was observed on the 
QTcF interval (ie, no QTc interval prolongation > 10 msec at any time point postdose and assay 
sensitivity was confirmed via the positive control [moxifloxacin]). As such, these findings satisfy 
the guidelines set forth in the International Council for Harmonisation (ICH) E14 guidance and 
support the conclusion that there is no significant effect of TAF on the QT/QTc interval.
Study GS-US-120-0108 was a Phase 1, open-label (OL), parallel-design study to evaluate the PK 
of TAF in participants with severe renal impairment. TAF was well tolerated in the study. 
Patients with severe renal impairment had < 2-fold higher TAF and 5-6 fold higher TFV 
systemic exposures as assessed by AUC relative to participants with normal renal function. TFV 
exposures in participants with severe renal impairment are comparable to those with normal 
renal function receiving 300 mg TDF. Given the extensive safety data available for TDF at a 
dose of 300 mg, TFV exposures in severely renally impaired participants similar to those 
associated with TDF 300 mg are deemed appropriate for further study of TAF in HIV-infected 
patients without TAF dose modification.
1.3.
Emtricitabine (FTC, Emtriva®)
Further information regarding Emtriva is available in the prescribing information, an overview is 
provided below.

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1.3.1.
General Information
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg once daily dose concurrently with other ARV drugs. The 
200 mg FTC capsule formulation was approved by the US FDA for marketing on 2 July 2003 
and is available under the name Emtriva. In the European Union (EU), marketing authorization 
was granted for both the 200 mg Emtriva capsule formulation and a 10 mg/mL Emtriva oral 
solution formulation on 24 October 2003, with indications for the treatment of HIV infection 
concurrently with other ARV drugs in both adult and pediatric patients. In pediatric patients, the 
recommended dose of Emtriva is 6 mg/kg once daily, up to a maximum of 200 mg once daily 
when administered using the capsule formulation (for children weighing > 33 kg) or up to a 
maximum of 240 mg when administered using the oral solution formulation.
1.4.
Fixed-Dose Combination of Emtricitabine/Tenofovir Disoproxil Fumarate 
(F/TDF)
Further information is available in the Prescribing Information for Truvada 
(emtricitabine/tenofovir disoproxil fumarate).
1.5.
Rationale for This Study
Based on available data, the use of F/TAF for PrEP would provide a new option for persons with 
high sexual risk of HIV-1 acquisition. Based on data with F/TAF-based regimens used for 
treatment of chronic HIV-1 infection, the improved safety profile of F/TAF (relative to F/TDF) 
reduces the risk of a negative impact on bone mineralization in younger adults (18-25 years 
of age) who are still in a bone growth phase, and also reduces the risk of a negative impact on 
renal function in older adults with risk factors for chronic kidney disease. Use of F/TAF once 
daily for PrEP is expected to be similarly efficacious to Truvada but also have an improved 
safety profile.
Nonclinical pharmacology studies in rhesus macaques show that orally administered F/TAF, at 
doses resulting in PBMC exposures that are consistent with those achieved in humans 
administered a dose of F/TAF 200/25 mg, effectively prevents SHIV infection.
Oral administration of TAF results in rapid accumulation of TFV-DP in the intracellular PBMC 
compartment with levels that are at least 4-fold higher than with use of TDF. When used as 
monotherapy for 10 days (Study GS-US-120-0104), TAF 25 mg has increased antiviral potency 
relative to TDF 300 mg. Treatment of chronic HIV-1 infection with TAF-based regimens have 
similar or higher rates of undetectable viral load at 48 and 96 weeks when administered as 
Genvoya compared to STB in treatment-naive patients, and when administered as 
F/TAF + a third agent in virologically suppressed patients who switch from a Truvadabased 
regimen to F/TAF (Study GS-US-311-1089). Refer to the Genvoya Prescribing Information for 
more details.

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There is considerable data demonstrating that F/TAF (administered as either Genvoya or as 
F/TAF + a third agent) has statistically significant improvement in both renal and bone safety 
profiles in both treatment-naive patients and in virologically suppressed patients who switch 
from a TDF based regimen (Refer to the Genvoya Prescribing Information for more details). 
These improvements in measures of renal and bone safety, most notably no reported cases of 
PRT (including Fanconi Syndrome), are most likely due to the 90% reduction in plasma TFV 
levels observed in participants receiving TAF-based regimens. The use of F/TAF for PrEP to 
reduce the risk of sexually acquired HIV-1 in uninfected individuals at high risk may provide an 
effective prevention regimen with a significantly improved renal and bone safety profile relative 
to Truvada. This is of particular importance for HIV-1–negative persons who are otherwise 
likely to be healthy, in whom the acceptability of medication related risks relative to benefit must 
be weighed carefully.
The present study will be conducted in MSM and transgender women (TGW) who are at least 
18 years of age, a population consistently at highest risk of HIV-1 acquisition through sexual 
behavior.
1.6.
Rationale for Dose
The 200 mg dose represents the dose of FTC in the FDC, Truvada, which is approved for a PrEP 
indication in the US.
Based upon results of the Phase 1 Study GS-US-120-0104, in which increasing doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-1–infected participants in 10 days of 
monotherapy, the range of plasma and PBMC exposure achieved with TAF 25 mg was chosen as 
the reference exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity with 
significantly increased TFV-DP levels in PBMCs and significantly decreased plasma TFV 
exposure relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered as Genvoya, for which an extensive efficacy and safety database exists. The 
recommended TAF dose (10 or 25 mg) is based on whether or not the co-administered 
third agent requires a PK enhancer. As F/TAF for PrEP will be administered in the absence of a 
third ARV agent, the 25 mg dose of TAF (with FTC 200 mg) has been selected for evaluation in 
the proposed Phase 3 study.
1.7.
Risk/Benefit Assessment for the Study
During a pandemic, additional potential risks to participants may include adequate study drug 
availability, interruptions to the study visit schedule, and adherence to protocol-specified safety 
monitoring or laboratory assessments. Refer to Appendix 8 for further details on the risks and 
risk mitigation strategy.

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1.8.
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 prima1y objective of this study is: 
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• 
To assess the rates of HIV-I infection in MSM and TGW who have sex with men who are 
administered daily F/TAF or F/TDF with a minimum follow up of 48 weeks and at least 50% 
of paiiicipants have 96 weeks of follow up after randomization 
The secondaiy objectives of this study are: 
• 
To compai·e bone safety between the treatments as detennined by dual-energy X-ray 
absorptiometiy (DXA) tests of hip and spine BMD in a subset of paiiicipants at Week 48 and 
Week 96 in the blinded phase 
• 
To compare renal safety between the treatments as determined by urine retinol-binding 
protein (RBP) to creatinine ratio, urine beta-2-microglobulin to creatinine ratio, urine protein 
to creatinine ratio (UPCR), and sernm creatinine at Week 48 and Week 96 in the blinded 
phase 
• 
To assess the rates of HIV-I infection in MSM and TGW who have sex with men who ai·e 
administered daily F/TAF or F/TDF, when all paiticipants have 96 weeks of follow up after 
randomization 
• 
To compare the general safety between the treatments 
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3.
STUDY DESIGN
3.1.
Endpoints
3.1.1.
Primary Endpoint
The primary endpoint will be the incidence of HIV-1 infection per 100 person years (PY) when 
all participants have a minimum follow up of 48 weeks and at least 50% of the participants have 
96 weeks of follow up after randomization. HIV-1 infection is defined by one or more of the 
following criteria of contributing HIV tests performed via central lab or local lab:
Serologic evidence of seroconversion (reactive screening HIV Antigen [Ag]/Antibody [Ab] or 
Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV 
vaccinated participants, or
Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable 
quantitative HIV-1 RNA test), or
Evidence of acute HIV-1 infection (reactive p24 Ag or positive qualitative or quantitative RNA, 
in the absence of reactive HIV-1 Ab results).
Please refer to Appendix 7 for more details.
3.1.2.
Secondary Endpoints
The key (α-controlled) secondary endpoints in the blinded phase are (in the following order):

The percent change from baseline in hip BMD at Week 48 in a subset of participants

The percent change from baseline in spine BMD at Week 48 in a subset of participants

Assessment of renal biomarkers at Week 48
percent change from baseline in urine beta-2-microglobulin to creatinine ratio
percent change from baseline in urine RBP to creatinine ratio
distribution of urine protein (UP) and UPCR categories

The change from baseline in serum creatinine at Week 48
Other secondary endpoints include:
The incidence of HIV-1 infection (as per Appendix 7) per 100 PY when all participants have 
96 weeks of follow up after randomization

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• 
The percent change from baseline in hip and spine BMD at Week 96 in the blinded phase in a 
subset of paiiicipants 
• 
Assessment of renal biomarkers at Week 96 in the blinded phase 
-
percent change from baseline in mine beta-2-microglobulin to creatinine ratio 
-
percent change from baseline in mine RBP to creatinine ratio 
-
distribution of UP and UPCR categories 
• 
The change from baseline in sennn creatinine at Week 96 in the blinded phase 
• 
The incidence of ti·eatment-emergent adverse events (AEs) and laborato1y toxicities 
-
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3.2. 
Study Design 
This protocol describes a randomized, double-blind comparison of the safety and efficacy of 
F/TAF versus F/TDF administered once daily for at least 96 weeks in HIV-I-negative adult 
MSM or TGW (male at birth) who have sex with men and ai·e at risk of HIV-1 infection. 
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All participants must meet all eligibility criteria in order to receive ti·eatment in the study. Once 
randomized to receive ti·eatment in the study, all participants must return to the study center for 
required visits at Weeks 4, 12, and eve1y 12 weeks thereafter. 
All pa1t icipants will remain blinded to study drng for at least 96 weeks. The primaiy endpoint 
data will be collected and analyzed when all paiticipants have a minimum follow up of 48 weeks 
and 50% of the paiticipants have 96 weeks of follow up after randomization. 
Once all paiticipants have at least 96 weeks of follow up after randomization and upon 
notification by Gilead, all paiticipants will return to the study center for an end of blinded 
ti·eatment phase visit (may coincide with their next scheduled visit). 
Paiticipants who are still on blinded study drn 
offered enti into the OL hase of the stud . 
Paiticipants who have discontinued study drng prior to the end of blinded ti·eatinent phase visit 
due to HIV infection will be eligible to continue pa1t icipation in the OL phase up to OL Week 
48, but will not be administered F/TAF once daily. From OL Week 48 paiticipants who acquire 
HIV must complete the eai·ly study drng discontinuation (ESDD) visit and discontinue the study 
at the 30-Day Follow-up visit, 30 days after the last dose of study diug. Paiticipants who have 
discontinued study diug for any other reason prior to the end of blinded treatment phase visit will 
not be eligible to paiticipate in the OL phase. 
During the blinded ti·eatment phase, paiticipants may choose to continue to paiticipate in the 
study without taking study di11g ("on-study, off-study diug"). Paiticipants who pe1manently 
discontinue study diug and continue to attend nonnal study visits ( at minimum one visit at least 
30 days after last dose) ai·e not required to complete the follow-up visit. Any paiticipant who has 
an ESDD visit and who will not continue paiticipating in the study, or any paiticipant who will 
not continue paiticipation in the OL phase of the study, must complete the 30-Day Follow-Up 
visit 30 days after the last dose of study diug. 
DXA scans will be perfo1med during regular intervals throughout the study (blinded and 
OL phase) in a subset of approximately 400 pa1t icipants at a subset of sites (excluding 
Ge1many). 
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Figure 3-1. 
Screening 
s30days 
Study Schema 
Double-Blind Treatment Period 
at least 96 weeks 
Treatment Arm 1: 
F/TAF + placebo; n=2500 
Treatment Arm 2: 
F/TDF + placebo; n=2500 
Open-Label b 
Open-Label 
F/TAF 
Screening 
Day 1 
Wk 96 Every 
End of Blinded 
OLWk96 
12 wks • 
Treatment 
OL = open label; Wk = week 
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Follow-
up 
30days 
30-Day 
Follow-Up 
a 
Pa1ticipants will continue blinded treatment until the last pa1ticipant has reached Week 96, and upon notification by Gilead, 
all participants will return to the study center for the end of blinded treatment phase visits. 
b 
Pa1tici ants will continue in the OL hase eve 
12 weeks u to OL Wk 96. 
r 
Study Treatments 
Blinded Phase: 
Paiiicipants who provide written consent and meet all eligibility criteria will be randomized in a 
1: 1 ratio to one of the following 2 treatment aims: 
• 
Treatment Arm 1: F/TAF (200 mg/25 mg)+ placebo-to-match F/TDF (n = 2500) 
• 
Treatment Arm 2: F/TDF (200 mg/300 mg)+ placebo-to-match F/TAF (n = 2500) 
Open Label Phase and Open Label Extension Phase: 
During the OL phase and OL extension phase, all paiiicipants will be administered OL F/TAF 
(200 mg/25 mg). 
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4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection
Five thousand participants who meet all of the Inclusion and none of the Exclusion criteria will 
be enrolled.
4.2.
Inclusion Criteria
Participants must be at high risk of sexual acquisition of HIV and meet all of the following 
inclusion criteria to be eligible for participation in this study.
1) HIV-1–negative status
2) MSM or TGW (male at birth) who have at least one of the following:
a) condomless anal intercourse with at least 2 unique male partners in the past 12 weeks 
(partners must be either HIV-infected or of unknown HIV status)
b) documented history of syphilis in the past 24 weeks
c) documented history of rectal gonorrhea or chlamydia in the past 24 weeks
3) Age ≥ 18 years
4) Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance {Cockcroft 1976}:
(140 ― age in years) × (wt in kg)
72 × (serum creatinine in mg/dL) = CLcr(mL/min)
5) Adequate liver and hematologic function:

AST and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); and total 
bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

Absolute neutrophil count ≥ 1000/mm3, platelets ≥ 75,000/mm3, and hemoglobin ≥ 10 g/dL
6) Willing and able to comply with study procedures

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4.3.
Exclusion Criteria
Participants who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Known hypersensitivity to the study drug, the metabolites, or formulation excipient.
2) Have a suspected or known active, serious infection(s)
3) Acute viral hepatitis A, B or C or evidence of chronic hepatitis B infection. Participants 
found to be susceptible to hepatitis B virus (HBV) infection should be referred for HBV 
vaccination. Participants found to be positive for hepatitis C virus (HCV) at screening must 
not have active infection or must have completed treatment and achieved a sustained 
virologic response.
4) Need for continued use of any contraindicated concomitant medications
5) Have an implanted defibrillator or pacemaker
6) Have a history of osteoporosis or bone fragility fractures
7) Current alcohol or substance abuse judged by the investigator to be problematic such that it 
potentially interferes with participant study compliance
8) Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or not clinically 
manageable.
9) Any other clinical condition or prior therapy that, in the opinion of the investigator, would 
make the participant unsuitable for the study or unable to comply with dosing requirements
10) Have received investigational agents for the treatment or prevention of HIV-1 infection in the 
30 days prior to screening
11) Participation in any other clinical trial (including observational trials) without prior approval 
from the sponsor is prohibited while participating in this trial

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Enrollment
This is a randomized, double-blind study.
It is the responsibility of the investigator to ensure that the participant is eligible for the study 
prior to randomization.
Randomization cannot occur until participant eligibility has been confirmed. Once 
eligibility has been confirmed, each participant will be assigned a unique participant number 
using interactive voice/web response system (IXRS): either Interactive Web Response System 
(IWRS) or Interactive Mobile Response System (IMRS). Once a participant number has been 
assigned to a participant, it will not be reassigned to any other participant.
Participants will be randomized in a 1:1 ratio to Treatment Arm 1 or Treatment Arm 2.
IXRS will assign study drug bottle numbers at each study visit until the participant’s last study 
visit. Study drug will be dispensed to the participant in a blinded fashion from Day 1 through the 
end of blinded treatment phase visit. All Day 1 visit tests and procedures must be completed 
prior to the administration of the first dose of the study drug. Initiation of treatment with the 
study drug must take place within 24 hours after the Day 1 visit. Study drug will be dispensed to 
the participant in an OL fashion from the end of blinded treatment phase visit through the final 
study visit.
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the participant, the investigator may obtain treatment assignment directly from the IXRS 
system for that participant. Gilead strongly recommends but does not require that the investigator 
contact the Gilead medical monitor before breaking the blind. Treatment assignment should 
remain blinded unless that knowledge is necessary to determine participant emergency medical 
care. The rationale for unblinding must be clearly explained in source documentation, along with 
the date on which the treatment assignment was obtained. The investigator is requested to 
contact the Gilead medical monitor promptly in case of any treatment unblinding.
Blinding of study drug is critical for the integrity of this clinical study and therefore, if a 
participant’s treatment assignment is disclosed to the investigator, the participant will have study 
drug discontinued. All participants will be followed until study completion unless consent to do 
so is specifically withdrawn by the participant.
Gilead Global Patient Safety (GLPS) (formerly Pharmacovigilance and Epidemiology) may 
independently unblind cases for expedited reporting of Suspected Unexpected Serious Adverse 
Reactions (SUSARs).

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5.2.
Description and Handling
5.2.1.
Formulation
5.2.1.1.
Emtricitabine/Tenofovir Alafenamide (F/TAF) 200 mg/25 mg and Matching 
Placebo
Emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets are blue, rectangular-shaped, 
filmcoated tablets, debossed with "GSI" on one side of the tablet and with "225" on the other 
side of the tablet. Each tablet core contains 200 mg of emtricitabine and 25 mg of tenofovir 
alafenamide. In addition to the active ingredients, the F/TAF tablets contain croscarmellose 
sodium, magnesium stearate, and microcrystalline cellulose. The tablet cores are film-coated 
with FD&C blue #2/indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, 
and titanium dioxide.
Placebo-to-match F/TAF tablets are identical in appearance to the active tablets and are blue, 
rectangular-shaped, film-coated tablets. Placebo tablets contain croscarmellose sodium, 
magnesium stearate, lactose and microcrystalline cellulose. The tablet cores are film-coated with 
Blue #2/indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, and 
titanium dioxide.
5.2.1.2.
Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) Tablets and Matching 
Placebo
Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg tablets are blue, capsule-shaped, 
film-coated tablets debossed with "GILEAD" on one side and are plain-faced on the other side of 
the tablet. Each tablet core contains 200 mg of emtricitabine and 300 mg of tenofovir disoproxil 
fumarate. In addition to active ingredients, the F/TDF tablets contain microcrystalline cellulose, 
croscarmellose sodium, pregelatinized starch, lactose monohydrate and magnesium stearate. The 
tablet cores are film coated with FD&C blue #2/indigo carmine aluminum lake, lactose 
monohydrate, hypromellose, titanium dioxide and triacetin.
Placebo-to-match F/TDF tablets are identical in appearance to the active tablets and are blue, 
capsule-shaped, film-coated tablets. Placebo tablets contain denatonium benzoate, lactose 
monohydrate, pregelatinized starch, croscarmellose sodium and magnesium stearate. The tablet 
cores are film-coated to mask taste. The film coating consists of FD&C blue #2/indigo carmine 
aluminum lake, lactose monohydrate, hypromellose, titanium dioxide, and triacetin.
5.2.2.
Packaging and Labeling
Emtricitabine/Tenofovir Alafenamide (F/TAF) tablets and placebo-to-match F/TAF tablets are 
packaged in a white high-density polyethylene (HDPE) bottle. Each bottle contains 30 tablets, 
silica gel desiccant, and polyester packing material. Each bottle is enclosed with a white, 
continuous thread, child-resistant polypropylene screw cap fitted with an induction-sealed and 
aluminum-faced liner.

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Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) tablets and placebo-to-match F/TDF 
tablets are packaged in a white HDPE bottle. Each bottle contains 30 tablets and silica gel 
desiccant. Each bottle is enclosed with a white, continuous thread, child-resistant polypropylene 
screw cap fitted with an induction-sealed and aluminum-faced liner.
Study drug(s) bottles to be distributed to centers in the US and EU shall be labeled to meet all 
applicable requirements of the US FDA, EU Guideline to Good Manufacturing Practice –
 Annex 13 (Investigational Medicinal Products), and/or other local regulations as applicable.
5.2.3.
Storage and Handling
Emtricitabine/Tenofovir Alafenamide (F/TAF) and the placebo-to-match F/TAF tablets should 
be stored at a 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.
Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) and the placebo-to-match F/TDF tablets 
should be stored at a controlled room temperature of 25°C (77°F); excursions are permitted 
between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label.
Until dispensed to the participants, all bottles of study drugs should be stored in a securely 
locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure when handling.
5.3.
Dosage and Administration
Emtricitabine/Tenofovir Alafenamide (F/TAF), placebo-to-match F/TAF, F/TDF, and 
placebo-to-match F/TDF tablets will be provided by Gilead. Study drug will be dispensed to 
participants at the Day 1 visit. Participants will be instructed to take their first dose of study 
medication following completion of the study procedures at the Day 1 visit. Initiation of 
treatment with the study drug must take place within 24 hours after the Day 1 visit and after the 
investigator has confirmed eligibility with the participant.
Participants will be instructed to bring all study medication in the original container at each 
clinic visit for drug accountability.
5.4.
Prior and Concomitant Medications
Medications and use of herbal/natural supplements listed in the following table are excluded or 
should be used with caution while participants are taking study drug on the study due to potential 
drug-drug interactions with F/TAF.

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Table 5-1.
Prior and Concomitant Medications
Medication Class
Medications to be Used with Caution
Prohibited Medications
Antiarrhythmics
amiodarone, quinidine: May increase 
concentration of TAF and/or TFV
Anticonvulsants
carbamazepine, oxcarbazepine, 
phenobarbital, phenytoin
Antimycobacterials
clarithromycin: may increase 
concentration of TAF and/or TFV
rifapentine, rifabutin, rifampin
Antifungals
itraconazole, ketoconazole, 
voriconazole: may increase 
concentration of TAF and/or TFV
Calcium channel blockers
diltiazem, felodipine, verapamil: 
may increase concentration of 
TAF and/or TFV
Digoxin
Concomitant use may result in an 
increased or decreased digoxin 
concentration; use with caution and 
with appropriate monitoring of serum 
digoxin concentrations.
Herbal/Natural 
Supplements
St. John’s Wort, echinacea, milk thistle 
(eg, silymarin), Chinese herb 
sho-saiko-to (or Xiao-Shai-Hu-Tang)
Hepatitis C therapies
Ledipasvir/sofosbuvir: has been shown 
to increase tenofovir exposure
boceprevir, telaprevir
Nephrotoxic medications
high dose or multiple NSAIDS
systemic chemotherapeutic agents, 
aminoglycoside antibiotics, 
amphotericin B, cidofovir, cisplatin, 
foscarnet, IV pentamidine, or, other 
agents with significant nephrotoxic 
potential
Systemic glucocorticoids
dexamethasone (more than 1 dose), or 
chronic use of other systemic 
glucocorticoids
Other
Probenecid
NSAIDS = nonsteroidal anti-inflammatory drugs
Should participants have a need to initiate treatment with any prohibited concomitant 
medication, the Gilead medical monitor must be consulted and approval granted prior to 
initiation of the new medication. In instances where a prohibited medication is initiated prior to 
discussion with the sponsor, the investigator must notify Gilead as soon as he/she is aware of the 
use of the prohibited medication.

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There are no substantial safety data regarding the concomitant administration of the coronavirus 
disease 2019 (COVID-19) vaccines and F/TAF. Participants are allowed to receive the 
COVID‑19 vaccine, and study visits should continue as planned if vaccination occurs while the 
participant is on the study. Investigators should follow local guidelines for concomitant 
administration of the COVID-19 vaccines with the study drugs.
5.5.
Dispensing and Accountability of Investigational Medicinal Product
The investigator is responsible for ensuring adequate accountability of all used and unused 
Investigational Medicinal Product (IMP) or study drug. The investigator [or designee 
(eg, study center pharmacist)] will acknowledge receipt of the study drugs from Gilead (or 
designee) after reviewing the shipment’s content and condition. The investigator (or designee) 
will be responsible for maintaining an accurate inventory (on study drug accountability records) 
of the dates and quantities of all study drugs received, dispensed, and returned. The requirements 
of all applicable Federal and State drug dispensing laws will apply to all doses of study drugs 
dispensed by the investigator (or designee).
The study drug inventory and dispensing logs must be available for inspection by the study 
monitor. Study drug supplies, including partially used or empty bottles, must be accounted for by 
the study monitor prior to destruction or return.

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6.
STUDY PROCEDURES
The study procedures to be conducted for each participant enrolled in the study are presented in 
tabular form in Appendix 2 and Appendix 3 and described in the text that follows. The 
investigator must document any deviation from protocol procedures and notify the sponsor or 
contract research organization (CRO).
6.1.
Participant Enrollment and Treatment Assignment
It is the responsibility of the investigator to ensure that participants are eligible for study prior to 
enrollment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
The following assessments will be performed at the screening visit:

Written informed consent completed prior to any other assessments

Medical history including information about alcohol use in the past year and self-reported 
sexual risk events and medications used by the participant in the 30 days prior to the 
screening visit

Complete physical examination, vital signs measurements (blood pressure, pulse, respiration 
rate, and temperature), height, and weight

Sexually transmitted infection (STI) testing. Participants who test positive for any STI will be 
treated in accordance with local STI guidelines.
Genital, rectal, and pharyngeal examination
Pharyngeal and rectal swabs for gonorrhea and chlamydia (per local lab). Swabs may be 
self-administered by the participant at the discretion of the investigator.
Urine sample for gonorrhea and chlamydia (per central lab)
Blood sample for syphilis testing (per local lab)

Fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test. If test is 
positive, a retest will be completed. If the retest is positive, the participant is a screen failure.
Any participant with a positive repeat HIV-1 rapid test will receive counseling and be 
referred for appropriate care

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
Urine sample for dipstick urinalysis (per local lab)

Urine sample for urinalysis, urine proteins, urine chemistry (uric acid, phosphate, and 
creatinine)
Participants who test positive for Grade 3 or Grade 4 proteinuria or glycosuria that is 
unexplained or not clinically manageable will be excluded from the study

Blood sample collection for the following central laboratory analyses:
Hematology profile: complete blood count (CBC) with differential and platelet count
Chemistry profile: alkaline phosphatase, AST, ALT, gamma glutamyltransferase (GGT), 
total bilirubin, direct and indirect bilirubin, total protein, albumin, lactate dehydrogenase 
(LDH), bicarbonate, blood urea nitrogen (BUN), calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing 
is performed in participants with total amylase > 1.5 × ULN)
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
Lipid panels (total cholesterol, high-density lipoprotein [HDL], direct low-density 
lipoprotein [LDL], and triglycerides). It is recommended that participants fast for 8 hours 
prior to the blood draw.
HIV testing
■
HIV-1 Ab/Ag
■
HIV-1 RNA by polymerase chain reaction (PCR) for those participants who show 
symptoms consistent with acute infection and who have a negative fourth generation 
rapid HIV-1 Ab/Ag test or third generation rapid HIV-1 Ab test
■
Any participant with HIV-1 Ab/Ag or an HIV-1 infection (per Appendix 7) is a 
screen failure and will receive counseling and be referred for appropriate care
Hepatitis B testing (hepatitis B virus surface antigen [HBsAg], hepatitis B virus surface 
antibody [HBsAb], hepatitis B virus core antibody [HBcAb])
■
If a participant has a negative HBsAg, negative HBsAb, and positive HBcAb, HBV 
DNA testing will be completed. If the HBV DNA result is positive, the participant is 
a screen failure.
■
Participants found to be susceptible to HBV infection should be referred for HBV 
vaccination

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Hepatitis C testing
■
If the HCV Ab result is positive, then HCV RNA will be completed unless there is 
documented evidence that sustained virologic response has been achieved. If the 
HCV RNA result is positive, the participant is a screen failure

Computer-assisted self-interview (CASI) for: recent sexual risk events; interest in using 
PrEP; self-identification of transgender status; education and employment history; and use of 
tobacco and recreational drugs

Risk reduction counseling including provision of condoms
6.2.2.
Day 1 Visit (Baseline)
Day 1 procedures and randomization may occur as soon as all eligibility criteria are confirmed. 
The Day 1 visit must occur within 30 days after the screening visit. The participant must 
complete all Day 1 procedures before being dispensed study drug. Initiation of treatment with 
study drug must take place within 24 hours after the Day 1 visit.

Fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test. If test is 
positive, a retest will be completed. If the retest is positive, the participant will no longer be 
permitted to participate in the study.
A negative HIV-1 RNA by PCR result is required prior to receiving study drug for those 
participants who show symptoms consistent with acute infection and who have a negative 
HIV-1 rapid test
Any participant with a positive repeat HIV-1 rapid test or HIV-1 infection (per 
Appendix 7) will receive counseling and be referred for appropriate care

Review of AEs and changes in concomitant medications, including assessment of whether 
STIs were diagnosed and any treatments were received since the screening visit

Targeted (symptom directed) physical examination and vital signs (blood pressure, pulse, 
respiration rate, and temperature) if the Day 1 visit is > 7 days after the screening visit

Weight

CASI for sexual risk events since the last visit

Randomization in IXRS if all screening assessments meet eligibility criteria

Drug dispensation

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• 
Adherence and risk reduction counseling including provision of condoms. Paiticipants will 
be educated on the signs and symptoms of acute HIV-1 infection and will be instructed to 
call and/or present to the site immediately for evaluation and HIV-1 testing if they develop 
such symptoms. Investigator or site suppo1t staff must emphasize the impo1tance of the use 
of baITier protection during the first 2 weeks from baseline . 
• 
• 
Record any serious adverse events (SAEs) and all AEs related to protocol-mandated 
procedures occmTing after signing of the info1med consent fonn (ICF). 
Throughout the study, paiticipants may be asked to provide daily info1mation on adherence and 
sexual risk events through the use of a diaiy. Pait icipants may also receive periodic contacts to 
remind them to take their study drng and to provide any additional suppo1t needed. 
From the time of obtaining infonned consent through the first administI'ation of study drng, 
record all SAEs, as well as any AEs related to protocol-mandated procedures on the adverse 
events electi·onic case repo1t f01m (eCRF). All other untowai·d medical occmTences observed 
during the screening period, including exacerbation or changes in medical histo1y ai·e to be 
captured on the medical histo1y eCRF. See Section 7 Adverse Events and Toxicity Management 
for additional details. 
6.3. 
Treatment Assessments Blinded Phase (\Veeks 4, 12, and Every 12 Weeks 
Until the end of blinded treatment phase visit) 
The following evaluations ai·e to be completed at the Weeks 4, 12, and eve1y 12 weeks visits 
until the end of blinded ti·eatinent phase visit unless othe1wise specified. 
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-specified visit date based on the Day 1 visit through 
Week 12 and study visits thereafter completed within ± 14days of the protocol-specified visit 
date through the end of blinded tI'eatment phase visit, unless othe1w ise specified. 
Regularly scheduled evaluations will be perfo1med for all pa1ticipants whether or not they 
continue to receive study diug, unless othe1wise specified. 
• 
T ai·geted ( symptom directed) physical examination ( complete physical examination at 
Weeks 48 and 96 only) 
• 
Review of AEs and changes in conc01nitant medications, including assessment of whether 
any STis were diagnosed and any ti·eatinents were received since last visit 
• 
When clinically indicated, vital signs measurement (blood pressure, pulse, respiration rate, 
and temperature) 
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
Weight

STI testing. Participants who test positive for any STI will be treated in accordance with local 
STI guidelines.
Genital, rectal, and pharyngeal examination as appropriate
Pharyngeal and rectal swabs for gonorrhea and chlamydia (per local lab). Swabs may be 
self-administered by the participant at the discretion of the investigator (rectal swab not 
required at Week 4).
Urine sample for gonorrhea and chlamydia (per central lab)
Blood sample for syphilis testing (per local lab)

Fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test (not done for 
HIV-infected participants)
If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed.

Urine collection for urinalysis, urine proteins, urine chemistry (uric acid, phosphate, and 
creatinine), and sample storage

Blood sample collection for the following central laboratory analyses:
Hematology profile: CBC with differential and platelet count
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in participants with total amylase > 1.5 × ULN)
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
Lipid panel (total cholesterol, HDL, direct LDL, and triglycerides). Participants should be 
instructed to fast (no food or drinks, except water, at least 8 hours prior to blood 
collection) (every 24 weeks)
HIV-1 Ab/Ag (not done for participants who acquire HIV)
■
If the HIV-1 Ab/Ag test is positive, an HIV-1 RNA by PCR test and sample 
collection for possible genotypic resistance testing will be completed as soon as 
possible.

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HIV-I RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any paiiicipants who: 
I) have a positive retest rapid HIV-I Ab/ Ag test ( either fourth generation rapid 
HIV-I Ab/ Ag or third generation rapid HIV-I Ab test) 
2) have a positive HIV-I Ab/ Ag test 
3) show symptoms consistent with acute infection regai·dless of the results of the rapid 
tests 
4) have a recent exposure that is considered high risk for HIV infection 
5) have been confnmed HIV-infected 
For details regarding confmnation of HIV infection, please refer to Section 6. I I. 
-
Hepatitis B testing (HBsAg, HBsAb, HBcAb) (every 24 weeks) 
If a pa1iicipant has a negative HBsAg, negative HBsAb, and positive HBcAb, HBV 
DNA testing will be completed. 
o Paiiicipants who have tested positive for HBcAb on the study during a prior visit 
do not need to repeat the Hepatitis B testing panel during subsequent visits and 
instead will have HBV DNA testing perfo1med at visits eve1y 24 weeks 
If the HBsAg or HBV DNA result is positive, the pa1iicipant will be discontinued and 
refened to appropriate HBV treatment. If the paiiicipant has acquired HIV, they may 
continue pa1iicipation in the study at the discretion of the investigator. 
-
Hepatitis C testing ( every 48 weeks) 
If the HCV Ab result is positive, then HCV RNA will be completed unless there is 
documented evidence that sustained virologic response has been achieved. If the 
HCV RNA result is positive, the paiiicipant may continue in the study at the 
discretion of the investigator. 
Paiiicipants who have tested positive for HCV Ab on the study during a prior visit do 
not need to repeat the HCV Ab test during subsequent visits and instead will have 
HCV RNA testing perfo1med at visits eve1y 48 weeks 
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Plasma sample storage for virology, safety, and/or PK testing 
-
CD4, CD8, and CD4/CD8 ratio (only for participants who acquire HIV) 
-
Large volume blood draw for the following ( only for paiiicipants who acquire HIV. All 
blood draws will be done at the first study visit upon confnmation of HIV infection, and 
at the additional timepoints as indicated below. Subsequent draws will be perfo1med at 
the paiiicipants' regulai·ly scheduled study visit): 
Latent and Active Reservoir assessment (24 weeks and 48 weeks after HIV infection, 
and eve1y 48 weeks thereafter) 
T cell response and phenotype (24 weeks and 48 weeks after HIV infection, and 
eve1y 48 weeks thereafter) 
Viral Sequence Diversity assessment (24 weeks after HIV infection only) 
-
Inflammato1y/immune activation biomai·kers (only for pa1iicipants who acquire HIV. 
Done at the first study visit upon confnmation of HIV infection, at 24 weeks and 
48 weeks after HIV infection, and eve1y 48 weeks thereafter) 
• 
CASI for sexual risk events and adherence since the last visit 
• 
Collect and review used and unused blinded study diug for accountability and calculate 
compliance (not done for participants who have permanently discontinued study drug) 
• 
Dmg dispensation (not done for paiticipants who have been or will be pe1manently 
discontinued from study di11g) 
• 
Adherence and risk reduction counseling including provision of condoms. Pa1iicipants will 
be educated on the signs and symptoms of acute HIV-1 infection and will be instructed to 
call and/or present to the site for evaluation and HIV-1 testing if they develop such 
symptoms. (Adherence and risk reduction counseling not done for participants who 
acquire HIV.) 
• 
Paiiicipants may be asked to provide daily info1mation on adherence and sexual risk events 
through the use of a diaiy 
I 
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6.4. 
End of Blinded Treatment Phase Visit 
Final 
Amendment 7 
Once all participants have had at least 96 weeks of follow up after randomization and upon 
notification by Gilead, all participants will return to the study center for an end of blinded 
treatment phase visit (may coincide with their next scheduled study visit). 
Paiiicipants who do not paiiicipate in the OL phase will discontinue their blinded study diug and 
will return for a 30-Day Follow-Up visit following the end of blinded ti·eatment phase visit. 
The following will be perfonned at the end of blinded ti·eatment phase visit: 
• 
Targeted (symptom directed) physical examination 
• 
Review of AEs and changes in concomitant medications, including assessment of whether 
any STis were diagnosed and any ti·eatments were received since the last visit 
• 
When clinically indicated, vital signs measurement (blood pressure, pulse, respiration rate, 
and temperature) 
• 
Weight 
• 
STI testing. Paiiicipants who test positive for any STI will be u-eated in accordance with local 
STI guidelines. 
-
Genital, rectal, and phaiyngeal exainination as appropriate 
-
Phaiyngeal and rectal swabs for gononhea and chlamydia (per local lab). Swabs may be 
self-adininistered by the paiiicipant at the discretion of the investigator. 
-
Urine sample for gononhea and chlamydia (per centi·al lab) 
-
Blood sample for syphilis testing (per local lab) 
• 
Fomih generation rapid HIV-1 Ag/Ab or third generation rapid HIV-1 Ab test (not done for 
participants who acquire HIV) 
-
If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed. 
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
Urine collection for urinalysis, urine proteins, urine chemistry (uric acid, phosphate, and 
creatinine), and sample storage

Blood sample collection for the following central laboratory analyses:
Hematology profile: CBC with differential and platelet count
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in participants with total amylase > 1.5 × ULN)
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
HIV-1 Ab/Ag (not done for participants who acquire HIV)
■
If the HIV-1 Ab/Ag test is positive, an HIV-1 RNA by PCR test and sample 
collection for possible genotypic resistance testing will be completed as soon as 
possible.
HIV-1 RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any participants who:
1) have a positive retest rapid HIV-1 Ab/Ag test (either fourth generation rapid 
HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test) 
2) have a positive HIV-1 Ab/Ag test 
3) show symptoms consistent with acute infection regardless of the results of the rapid 
tests
4) have a recent exposure that is considered high risk for HIV infection
5) have been confirmed HIV-infected
For details regarding confirmation of HIV infection, please refer to Section 6.11.
Hepatitis B testing (HBsAg, HBsAb, HBcAb) (if > 24 weeks from prior testing)
■
If a participant has a negative HBsAg, negative HBsAb, and positive HBcAb, HBV 
DNA testing will be completed.
○
Participants who have tested positive for HBcAb on the study during a prior visit 
do not need to repeat the Hepatitis B testing panel during subsequent visits and 
instead will have HBV DNA testing performed at visits every 24 weeks

Emtricitabine and Tenofovir Alafenamide (F/TAF) 
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If the HBsAg or HBV DNA result is positive, the participant will be discontinued and 
refen ed to appropriate HBV treatment. If the paiiicipant has acquired HIV, they may 
continue in the study at the discretion of the investigator. 
-
Hepatitis C testing (if> 48 weeks from prior testing) 
I 
I 
If the HCV Ab result is positive, then HCV RNA will be completed. If the HCV RNA 
result is positive, the participant may continue in the study at the discretion of the 
investigator. 
Paiiicipants who have tested positive for HCV Ab on the study during a prior visit do 
not need to repeat the HCV Ab test during subsequent visits and instead will have 
HCV RNA testing perfo1med at visits eve1y 48 weeks 
-
Plasma sample storage for virology, safety, and/or PK testing 
-
CD4, CD8, and CD4/CD8 ratio (only for participants who acquire HIV) 
-
Large volume blood draw for the following ( only for paii icipants who acquire HIV. All 
blood draws will be done at the first study visit upon confnmation of HIV infection and 
at the additional time points as indicated below. Subsequent draws will be perfo1med at 
the paiiicipants' regularly scheduled study visit): 
Latent and Active Reservoir assessment (24 weeks and 48 weeks after HIV infection, 
and eve1y 48 weeks thereafter) 
T cell response and phenotype (24 weeks and 48 weeks after HIV infection, and 
eve1y 48 weeks thereafter) 
Viral Sequence Diversity assessment (24 weeks after HIV infection only) 
-
Inflammato1y/immune activation biomai·kers (only for pa1iicipants who acquire HIV. 
Done at the first study visit upon confnmation of HIV infection, at 24 weeks and 
48 weeks after HIV infection, and eve1y 48 weeks thereafter) 
• 
CASI for sexual risk events and adherence since the last visit 
• 
Collect and review used and unused blinded study dmg for accountability and calculate 
compliance (not done for participants who have permanently discontinued study drug) 
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• 
OL drng dispensation (not done for participants who acquire HIV). If the paiticipant has 
aheady taken a dose of blinded study drng on the day of the end of blinded treatment phase 
visit, they should not begin dosing with OL F/TAF until the next day. If the paiticipant has 
not taken a dose of blinded study drng on the day of the visit, they should take their first dose 
of OL F/TAF on the same day of the end of blinded treatment phase visit. 
• 
Adherence and risk reduction counseling including provision of condoms. Paiticipants will 
be educated on the signs and symptoms of acute HIV-1 infection and will be instructed to 
call and/or present to the site for evaluation and HIV-1 testing if they develop such 
symptoms. (Adherence and risk reduction counseling not done for participants who 
acquire HIV.) 
I 
6.5. 
Treatment Assessments Open-Label Phase and Open-Label Extension Phase 
All study visits in the OL phase and OL extension phase ai·e to be scheduled relative to the end 
of blinded ti·eatment phase visit date. Study visits ai·e to be completed within ± 14 days of the 
protocol-specified visit date based on the end of blinded treatment phase visit. Paiticipants 
paiticipating in the OL phase and OL extension phase will return for study visits eve1y 12 weeks. 
From OL Week 48, paiticipants who acquire HIV must complete the ESDD visit and discontinue 
the study at the 30-Day Follow-up visit, 30 days after the last dose of study diug. 
6.5.1. 
Open-Label Phase (Prior to OL Week 96) 
Regulai·ly scheduled evaluations will be made on all paiticipants, unless othe1wise specified. 
• 
Tai·geted (symptom directed) physical examination (complete physical examination at 
OL Week 48 only) 
• 
Review of AEs and changes in concomitant medications, including assessment of whether 
any STis were diagnosed and any ti·eatments were received since last visit 
• 
When clinically indicated, vital signs measurement (blood pressure, pulse, respiration rate, 
and temperature) 
• 
Weight 
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
STI testing. Participants who test positive for any STI will be treated in accordance with local 
STI guidelines.
Genital, rectal, and pharyngeal examination as appropriate
Pharyngeal and rectal swabs for gonorrhea and chlamydia (per local lab). Swabs may be 
self-administered by the participant at the discretion of the investigator.
Urine sample for gonorrhea and chlamydia (per central lab)
Blood sample for syphilis testing (per local lab)

Fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test (not done for 
participants who acquire HIV)
If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed.

Urine collection for urinalysis, urine proteins, urine chemistry (uric acid, phosphate, and 
creatinine), and sample storage

Blood sample collection for the following central laboratory analyses:
Hematology profile: CBC with differential and platelet count
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in participants with total amylase > 1.5 × ULN)
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
Lipid panel (total cholesterol, HDL, direct LDL, and triglycerides) Participants should be 
instructed to fast (no food or drinks, except water, at least 8 hours prior to blood 
collection) (every 24 weeks)

HIV-1 Ab/Ag (not done for participants who acquire HIV)
■
If the HIV-1 Ab/Ag test is positive, an HIV-1 RNA by PCR test and sample 
collection for possible genotypic resistance testing will be completed as soon as 
possible.
HIV-1 RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any participants who:

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1) have a positive retest rapid HIV-1 Ab/Ag test (either fourth generation rapid 
HIV1 Ab/Ag or third generation rapid HIV-1 Ab test) 
2) have a positive HIV-1 Ab/Ag test 
3) show symptoms consistent with acute infection regardless of the results of the rapid 
tests
4) have a recent exposure that is considered high risk for HIV infection
5) have been confirmed HIV-infected
For details regarding confirmation of HIV infection, please refer to Section 6.11.
Hepatitis B testing (HBsAg, HBsAb, HBcAb) (every 24 weeks)
■
If a participant has a negative HBsAg, negative HBsAb, and positive HBcAb, HBV 
DNA testing will be completed.
○
Participants who have tested positive for HBcAb on the study during a prior visit 
do not need to repeat the Hepatitis B testing panel during subsequent visits and 
instead will have HBV DNA testing performed at visits every 24 weeks
■
If the HBsAg or HBV DNA result is positive, the participant will be discontinued and 
referred to appropriate HBV treatment. If the participant has acquired HIV, they must 
complete the ESDD visit and discontinue the study at the 30-Day Follow-up visit, 
30 days after the last dose of study drug.
Hepatitis C testing (every 48 weeks)
■
If the HCV Ab result is positive, then HCV RNA will be completed. If the HCV RNA 
result is positive, the participant may continue in the study at the discretion of the 
investigator.
■
Participants who have tested positive for HCV Ab on the study during a prior visit do 
not need to repeat the HCV Ab test during subsequent visits and instead will have 
HCV RNA testing performed at visits every 48 weeks
Plasma sample storage for virology, safety, and/or PK testing
CD4, CD8, and CD4/CD8 ratio (only for participants who acquire HIV)
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Large volume blood draw for the following (only for paiticipants who acquire HIV [up to 
OL Week 48]. All blood draws will be done at the first study visit upon confinnation of 
HIV infection, and at the additional time points as indicated below. Subsequent draws 
will be perfo1med at the pa1ticipants' regularly scheduled study visit): 
Latent and Active Reservoir assessment (24 weeks and 48 weeks after HIV infection, 
and eve1y 48 weeks thereafter up to OL Week 48) 
T cell response and phenotype (24 weeks and 48 weeks after HIV infection, and 
eve1y 48 weeks thereafter up to OL Week 48) 
Viral Sequence Diversity assessment (24 weeks after HIV infection only, up to OL 
Week48) 
-
Inflammato1y/immune activation biomai·kers (only for pa1ticipants who acquire HIV. 
Done at the first study visit upon confnmation of HIV infection, at 24 weeks and 
48 weeks after HIV infection, and eve1y 48 weeks thereafter up to OL Week 48) 
• 
CASI for sexual risk events and adherence since the last visit 
• 
Collect and review used and unused study drng for accountability and calculate compliance 
(not done for participants who acquire HIV) 
• 
Drng dispensation (not done for pa1ticipants who acquire HIV) 
• 
Adherence and risk reduction counseling including provision of condoms. Paiticipants will 
be educated on the signs and symptoms of acute HIV-1 infection and will be instructed to 
call and/or present to the site for evaluation and HIV-1 testing if they develop such 
symptoms. (Adherence and risk reduction counseling not done for participants who 
acquire HIV.) 
• 
Paiticipants may be asked to provide daily info1mation on adherence and sexual risk events 
through the use of a diaiy 
I 
6.5.2. 
Open-Label Extension Phase (From OL Week 96) 
The following assessments are to be completed at eve1y visit for paiticipants continuing in the 
OL extension phase, unless othe1wise specified. For paiticipants who choose not to continue in 
the OL extension phase, the ESDD assessments (prior to OL Week 96) should be completed. 
• 
Tai·geted (symptom directed) physical examination (every 24 weeks) 
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• 
Review of AEs and changes in concomitant medications, including assessment of whether 
any STis were diagnosed and any ti·eatments were received since last visit 
• 
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature) ( eve1y 
24 weeks) 
• 
Weight ( eve1y 24 weeks) 
• 
STI testing. Paiiicipants who test positive for any STI will be u-eated in accordance with local 
STI guidelines. 
-
Genital, rectal, and phaiyngeal exainination as appropriate 
-
Phaiyngeal and rectal swabs for gononhea and chlamydia (per local lab). Swabs may be 
self-administered by the paiiicipant at the discretion of the investigator. 
-
Urine sample for gononhea and chlamydia (per centi·al lab) 
-
Blood sample for syphilis testing (per local lab) 
• 
At a minimum, fomih generation rapid HIV-1 Ab/ Ag or third generation rapid HIV-1 Ab test 
-
If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed. 
• 
Blood sample collection for the following centi·al laborato1y analyses: 
-
Chemistry profile: bicai·bonate, BUN, calcium, chloride, creatinine, glucose, phosphoms, 
potassium, sodium ( every 24 weeks) 
-
Estimated GFR according to the Cockcroft-Gault fo1mula for creatinine clearance (every 
24 weeks) 
I 
-
HIV-1 Ab/Ag 
If the HIV-1 Ab/ Ag test is positive, an HIV-1 RNA by PCR test and sainple 
collection for possible genotypic resistance testing will be completed as soon as 
possible. 
-
HIV-1 RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any paiiicipants who: 
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1) have a positive retest rapid HIV-1 Ab/Ag test (either fourth generation rapid 
HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test) 
2) have a positive HIV-1 Ab/Ag test 
3) show symptoms consistent with acute infection regardless of the results of the rapid 
tests
4) have a recent exposure that is considered high risk for HIV infection
5) have been confirmed HIV-infected
For details regarding confirmation of HIV infection, please refer to Section 6.11.
Hepatitis B testing (HBsAg, HBsAb, HBcAb) (every 48 weeks)
■
If a participant has a negative HBsAg, negative HBsAb, and positive HBcAb, HBV 
DNA testing will be completed.
○
Participants who have tested positive for HBcAb on the study during a prior visit 
do not need to repeat the Hepatitis B testing panel during subsequent visits and 
instead will have HBV DNA testing performed at visits every 48 weeks.
■
If the HBsAg or HBV DNA result is positive, the participant will be discontinued and 
referred to appropriate HBV treatment. If the participant has acquired HIV, they will 
discontinue the study, receive counseling, and be referred for appropriate care.
Hepatitis C testing (every 48 weeks)
■
If the HCV Ab result is positive, then HCV RNA will be completed. If the HCV RNA 
result is positive, the participant may continue in the study at the discretion of the 
investigator.
■
Participants who have tested positive for HCV Ab on the study during a prior visit do 
not need to repeat the HCV Ab test during subsequent visits and instead will have 
HCV RNA testing performed at visits every 48 weeks.

Collect and review used and unused study drug for accountability and calculate compliance 

Drug dispensation 

Adherence and risk reduction counseling including provision of condoms. Participants will 
be educated on the signs and symptoms of acute HIV-1 infection and will be instructed to 
call and/or present to the site for evaluation and HIV-1 testing if they develop such 
symptoms.
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6.6.
Unscheduled Visits
Additional unscheduled assessments may be performed at the discretion of the investigator 
(eg, for evaluation of AEs and/or laboratory abnormalities, including assessment of whether any 
STIs were diagnosed and any treatments were received since last visit). Participants who test 
HIV positive during an unscheduled visit will have a DBS sample collected.
6.7.
Posttreatment Assessments
6.7.1.
Early Study Drug Discontinuation Assessments (Prior to OL Week 96)
If the participant discontinues study drug prior to the OL Week 96 visit, the participant will be 
asked to return to the clinic within 72 hours of stopping study drug for the ESDD visit.

Targeted (symptom directed) physical examination

Review of AEs and changes in concomitant medications, including assessment of whether 
any STIs were diagnosed and any treatments were received since last visit

When clinically indicated, vital signs measurements (blood pressure, pulse, respiration rate, 
and temperature)

Weight

STI testing. Participants who test positive for any STI will be treated in accordance with local 
STI guidelines.
Genital, rectal, and pharyngeal examination as appropriate
Pharyngeal and rectal swabs for gonorrhea and chlamydia (per local lab). Swabs may be 
self-administered by the participant at the discretion of the investigator.
Urine sample for gonorrhea and chlamydia (per central lab)
Blood sample for syphilis testing (per local lab)

Fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test (not done for 
participants who acquire HIV)
If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed.

Urine collection for urinalysis, urine proteins, urine chemistry (uric acid, phosphate, and 
creatinine), and sample storage

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• 
Blood sample collection for the following centrnl laborato1y analyses: 
-
Hematology profile: CBC with differential and platelet count 
-
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and 
indirect bilimbin, total protein, albumin, LDH, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, phosphoms, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is perfo1med in participants with total amylase > 1.5 x ULN) 
-
Estimated GFR according to the Cockcroft-Gault fo1m ula for creatinine clearance 
-
HIV-1 Ab/ Ag (not done for paiiicipants who acquire HIV) 
If the HIV-1 Ab/ Ag test is positive, an HIV-1 RNA by PCR test and sample 
collection for possible genotypic resistance testing will be completed as soon as 
possible. 
-
HIV-1 RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any paiiicipants who: 
1) have a positive retest rapid HIV-1 Ab/ Ag test ( either fomih generation rapid 
HIV-1 Ab/ Ag or third-generation rapid HIV-1 Ab test) 
2) have a positive HIV-1 Ab/ Ag test 
3) show symptoms consistent with acute infection regardless of the results of the rapid 
tests 
4) have a recent exposure that is considered high risk for HIV infection 
5) have been confnmed HIV-infected 
For details regarding confmnation of HIV infection, please refer to Section 6.11. 
I 
-
Plasma sample storage for virology, safety, and/or PK testing 
-
CD4, CD8, and CD4/CD8 ratio (only for participants who acquire HIV) 
• 
CASI for sexual risk events and adherence since the last visit 
• 
Collect and review used and unused study diug for accountability and calculate compliance 
I 
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6.7.2.
Early Study Drug Discontinuation Assessments (From OL Week 96)
If the participant discontinues study drug from OL Week 96 visit, the participant will be asked to 
return to the clinic within 72 hours of stopping study drug for the ESDD visit.

Targeted (symptom directed) physical examination

Review of AEs and changes in concomitant medications, including assessment of whether 
any STIs were diagnosed and any treatments were received since last visit

When clinically indicated, vital signs measurement (blood pressure, pulse, respiration rate, 
and temperature)

Weight

STI testing. Participants who test positive for any STI will be treated in accordance with local 
STI guidelines.
Genital, rectal, and pharyngeal examination as appropriate
Pharyngeal and rectal swabs for gonorrhea and chlamydia (per local lab). Swabs may be 
self-administered by the participant at the discretion of the investigator.
Urine sample for gonorrhea and chlamydia (per central lab)
Blood sample for syphilis testing (per local lab)

At a minimum fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test 
(not done for participants who acquire HIV)
If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed.

Blood sample collection for the following central laboratory analyses:
Chemistry profile: bicarbonate, BUN, calcium, chloride, creatinine, glucose, phosphorus, 
potassium, sodium
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
HIV-1 Ab/Ag (not done for participants who acquire HIV)
■
If the HIV-1 Ab/Ag test is positive, an HIV-1 RNA by PCR test and sample 
collection for possible genotypic resistance testing will be completed as soon as 
possible.

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HIV-1 RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any participants who:
1) have a positive retest rapid HIV-1 Ab/Ag test (either fourth generation rapid 
HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test) or
2) have a positive HIV-1 Ab/Ag test or
3) show symptoms consistent with acute infection regardless of the results of the rapid 
tests
4) have a recent exposure that is considered high risk for HIV infection
5) have been confirmed HIV-infected
For details regarding confirmation of HIV infection, please refer to Section 6.11.
CD4, CD8, and CD4/CD8 ratio (for participants that acquire HIV)

Collect and review used and unused study drug for accountability and calculate compliance
At the ESDD visit, any evaluations showing abnormal results that the investigator determines 
to have a possible or probable causal relationship with the study drug, will be repeated 
weekly (or as often as deemed prudent by the investigator) until the abnormality is resolved, 
returns to baseline, or is otherwise explained.
6.7.3.
30-Day Follow-Up Assessment
All participants who have received at least one dose of study drug will be required to complete a 
follow-up visit 30 days (+ 14 days) after discontinuation of the study drug. Participants who 
permanently discontinue study drug and continue to attend normal study visits (at minimum 
one visit at least 30 days after last dose) are not required to complete the follow-up visit.
At the 30-Day Follow-Up visit, any evaluations showing abnormal results that the 
investigator determines to have a possible or probable causal relationship with the study 
drug will be repeated weekly (or as often as deemed prudent by the investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained.
The following evaluations are to be completed at the 30-Day Follow-Up visit (Prior to OL 
Week 96):

Targeted (symptom directed) physical examination

Review of AEs and changes in concomitant medications, including assessment of whether 
any STIs were diagnosed and any treatments were received since last visit

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
When clinically indicated, vital signs measurement (blood pressure, pulse, respiration rate, 
and temperature)

Weight

STI testing. Participants who test positive for any STI will be treated in accordance with local 
STI guidelines.
Genital, rectal, and pharyngeal examination as appropriate
Pharyngeal and rectal swabs for gonorrhea and chlamydia (per local lab). Swabs may be 
self-administered by the participant at the discretion of the investigator.
Urine sample for gonorrhea and chlamydia (per central lab)
Blood sample for syphilis testing (per local lab)

Fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test (not done for 
participants who acquire HIV)
If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed.

Urine collection for urinalysis, urine proteins, urine chemistry (uric acid, phosphate, and 
creatinine), and sample storage

Blood sample collection for the following central laboratory analyses:
Hematology profile: CBC with differential and platelet count
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in participants with total amylase > 1.5 × ULN)
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
HIV-1 Ab/Ag (not done for participants who acquire HIV)
■
If the HIV-1 Ab/Ag test is positive, an HIV-1 RNA by PCR test and sample 
collection for possible genotypic resistance testing will be completed as soon as 
possible.
HIV-1 RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any participants who:

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1) have a positive retest rapid HIV-1 Ab/Ag test (either fourth generation rapid 
HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test) 
2) have a positive HIV-1 Ab/Ag test 
3) show symptoms consistent with acute infection regardless of the results of the rapid 
tests
4) have a recent exposure that is considered high risk for HIV infection
5) have been confirmed HIV-infected
For details regarding confirmation of HIV infection, please refer to Section 6.11.
Plasma sample storage for virology, safety, and/or PK testing
CD4, CD8, and CD4/CD8 ratio (only for participants who acquire HIV)
The following evaluations are to be completed at the 30-Day Follow-Up visit (From OL 
Week 96):

Targeted (symptom directed) physical examination

Review of AEs and changes in concomitant medications, including assessment of whether 
any STIs were diagnosed and any treatments were received since last visit

When clinically indicated, vital signs measurement (blood pressure, pulse, respiration rate, 
and temperature)

Weight

STI testing. Participants who test positive for any STI will be treated in accordance with local 
STI guidelines.
Genital, rectal, and pharyngeal examination as appropriate
Pharyngeal and rectal swabs for gonorrhea and chlamydia (per local lab). Swabs may be 
self-administered by the participant at the discretion of the investigator.
Urine sample for gonorrhea and chlamydia (per central lab)
Blood sample for syphilis testing (per local lab)

At a minimum, fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test 
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If the result for rapid testing is positive, a retest will be completed. If the retest is positive, 
an HIV-1 RNA by PCR test and sample collection for possible genotypic resistance 
testing will be completed.

Blood sample collection for the following central laboratory analyses:
Chemistry profile: bicarbonate, BUN, calcium, chloride, creatinine, glucose, phosphorus, 
potassium, sodium
Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance
HIV-1 Ab/Ag (not done for participants who acquire HIV)
■
If the HIV-1 Ab/Ag test is positive, an HIV-1 RNA by PCR test and sample 
collection for possible genotypic resistance testing will be completed as soon as 
possible.
HIV-1 RNA by PCR test (see HIV Testing Algorithm, Appendix 6) and sample 
collection for possible genotypic resistance testing for any participants who:
1) have a positive retest rapid HIV-1 Ab/Ag test (either fourth generation rapid 
HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test) or
2) have a positive HIV-1 Ab/Ag test or
3) show symptoms consistent with acute infection regardless of the results of the rapid 
tests
4) have a recent exposure that is considered high risk for HIV infection
5) have been confirmed HIV-infected
For details regarding confirmation of HIV infection, please refer to Section 6.11.
CD4, CD8, and CD4/CD8 ratio (only for participants who acquire HIV)
6.8.
Criteria for Restarting Study Drug After an Interruption
If a participant interrupts study dosing temporarily for more than 14 consecutive days, the 
participant should have samples collected for the following HIV tests prior to restarting study 
dosing:

At a minimum, fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test

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If the result for rapid HIV testing is positive, a retest will be completed. If the retest is 
positive, the participant must not restart study drug, and may opt to begin a full HIV 
treatment regimen until the HIV-1 diagnosis is confirmed, at investigator discretion 
{Center for Disease Control and Prevention (CDC) 2018}.
Upon testing negative for the rapid HIV-1 test, the participant may restart study dosing 
while pending the central lab HIV tests, at the investigator’s discretion.

HIV-1 Ab/Ag (per central lab)

HIV-1 RNA by PCR test and sample collection for possible genotypic resistance testing 
(per central lab)
For details regarding confirmation of HIV infection, please refer to Section 6.11.
6.9.
Criteria for Discontinuation of Study Treatment
If a participant discontinues study dosing (for example, as a result of an AE), every attempt 
should be made to keep the participant in the study and continue to perform the required study-
related follow up and procedures until the end of blinded treatment phase visit. If this is not 
possible or acceptable to the participant or investigator, the participant may be withdrawn from 
the study.
Study medication will be discontinued as applicable in the following instances:

HIV-1 infection is confirmed

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the participant’s 
best interest

Participant request to discontinue for any reason
Study medication may be discontinued as applicable in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the 
participant may resume study dosing at the discretion of the investigator (see Section 6.8 for 
criteria for restarting study drug after an interruption).

Participant noncompliance

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board (IRB) or independent ethics committee (IEC)

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Bone Evaluations 
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In a subset of participants (except in Ge1many), DXA scans of the hip and spine will be 
perfo1med throughout the study. 
During the blinded phase of the study, all DXA substud 
a · · 
The Day 1 scan must be completed± 14 days from staii of treatment. All other scans should be 
completed± 6 weeks of the protocol-specified visit date. 
DXA substudy paiiicipants who plan to temporarily intenupt study dmg for more than 14 days 
should have the DXA scans perfonned within 14 days of the last dose of study diug, unless the 
aii ici ant has had scans erfo1med for a Week 48, Week 96, end of blinded treatment 
DXA scans will be completed at the ESDD visit if the ESDD visit is > 12 weeks after the 
previous DXA scan. Pa1i icipants who have pe1manently discontinued study diug will not have 
DXA scans perfo1med during subsequent study visits. 
DXA scans will cover the spine and hip to measure changes in BMD. DXA scan results will be 
provided to study sites as they become available. 
A complete description of the procedures perfo1med for the DXA scans will be provided in a 
DXAmanual. 
6.11. 
HIV Infection 
Paiiicipants will be assessed for any recent exposures that the investigator considers high risk for 
HIV infection at each study visit (including phone contacts and any unscheduled visits) from 
randomization through the end of study, with HIV testing done as clinically appropriate. 
Paiiicipants with results confnming HIV infection (per Appendix 7) will immediately 
discontinue study diug, receive counseling, and be refen ed for appropriate care. If the 
paii icipant's HIV-1 RNA is > 400 copies/mL, the stored sample for possible genotypic resistance 
will be sent for testing. An ESDD visit should also be completed within 72 hours of the 
paii icipant's last dose of study di11g. 
Once HIV infection is confnmed (per Appendix 7), all records pe1iaining to the event including 
laborato1y results, clinic notes, prescribed medications, and other relevant info1mation (including 
local records and records from other clinics) should be collected and submitted together with the 
HIV-1 infection questionnaire. 
After OL Week 48, paiticipants who acquire HIV must complete ESDD visit and discontinue the 
study at the 30-Day Follow up visit, 30 days after the last dose of study diug. 
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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 AE is any untoward medical occurrence in a clinical study participant administered a study 
drug, 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 study drug, whether or not considered related to the study drug. AEs may also 
include pre-treatment or posttreatment 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 performed (eg, elective procedures, surgery, endoscopy, tooth 
extraction, transfusion). The condition that led to the procedure may be an adverse event and 
must be reported.

Preexisting diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.5.)
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the ICF is signed and not related to a protocol-associated procedure is not an AE. It is considered 
to be preexisting and should be documented on the medical history eCRF.
7.1.2.
Serious Adverse Events
An SAE is defined as an event that, at any dose, results in the following:

Death

A life-threatening situation (Note: The term “life-threatening” in the definition of “serious” 
refers to an event in which the participant was at risk of death at the time of the event; it does 
not refer to an event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to study drug interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram [ECG], X-rays, vital signs) that 
are associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin). For specific information on handling of clinical 
laboratory abnormalities in this study, please refer to Appendix 4.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to study 
drug using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study drug. For 
SAEs, an alternative causality must be provided (eg, preexisting condition, underlying 
disease, intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study drug.

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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures (eg, venipuncture).
7.2.2.
Assessment of Severity
Severity should be recorded and graded according to the Gilead Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 5). For AEs associated with laboratory 
abnormalities, the event should be graded on the basis of the clinical severity in the context of 
the underlying conditions; this may or may not be in agreement with the grading of the 
laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
7.3.1.
Requirements for Collection Prior to Study Drug Initiation:
Prior treatment history is collected as part of the study entry criteria and evaluation of individual 
patient characteristics and will not be generating lack of effect reports as this is outside the scope 
of the present clinical study. However, investigators should report any cases of lack of effect that 
they feel appropriate regarding the previous treatment regimen as spontaneous reports to the 
relevant authorities or marketing authorization holders.
After informed consent, but prior to initiation of study drug, the following types of events must 
be reported on the applicable eCRFs: all SAEs and AEs related to protocol-mandated procedures.
7.3.2.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30 days after last administration of study drug must be reported to the eCRF database as 
instructed.
All AEs should be followed until resolution or until the adverse event is stable. Gilead may 
request that certain AEs be followed beyond the protocol-defined follow-up period.

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Serious Adverse Events 
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All SAEs, regardless of cause or relationship, that occur after the participant first consents to 
paiiicipate in the study (ie, signing the ICF) and throughout the duration of the study, including 
the protocol-required posttr·eatment follow-up period, must be repo1ied on the applicable eCRFs 
and Gilead GLPS as instructed below. This also includes any SAEs resulting from 
protocol-associated procedures perfonned after ICF is signed. 
Any SAEs and deaths that occur after the posth'eatment follow-up visit but within 30 days of the 
last dose of study dmg, regai·dless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period; 
however, if the investigator leains of any SAEs that occur after study pa1iicipation has concluded 
and the event is deemed relevant to the use of study diug, he/she should promptly document and 
repo1i the event to Gilead GLPS. 
Instructions for repo1iing SAEs ai·e described in Section 7. 3. 3 .1. 
• 
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
The investigator must take all therapeutic measures necessa1y for resolution of the SAE. Any 
medications necessaiy for tr·eatment of the SAE must be recorded onto the concomitant 
medication section of the paiiicipant's eCRF and the event description section of the SAE eCRF. 
Follow up of AEs will continue through the last day on study (including the follow-up off-study 
diug period of the study) and/or until the investigator and/or Gilead detennine that the 
paiiicipant's condition is stable. Gilead may request that certain AEs be followed until 
resolution. 
7.3.3.1. 
Elech'onic Serious Adverse Event ( eSAE) Repo1iing Process 
• 
Site personnel will record all SAE data in the eCRF database and from there tr·ansmit the 
SAE info1mation to Gilead GLPS within 24 hours of the investigator's knowledge of the 
event from ICF signature throughout the duration of the study, including the 
protocol-required postti·eatment follow-up period. 
• 
If it is not possible to record and tr·ansmit the SAE infonnation elech'onically, record the SAE 
on the paper serious adverse event repo1i f01m and submit by e-mail or fax within 24 hours 
of the investigator's knowledge of the event to: 
Gilead GLPS contact info1mation: 
Email: 
Fax: 
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
As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the participant’s eCRF and the event description section of the 
Safety Report eCRF.

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 participant identification, 
maintaining the traceability of a document to the participant identifiers.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA 
Code of Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant 
updates, and other country-specific legislation or regulations, Gilead may be required to expedite 
to worldwide regulatory agencies reports of SAEs which may be in the form of line-listings, 
serious adverse drug reactions (SADRs), or SUSARs. In accordance with the EU Clinical Trials 
Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB/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
Special situation reports include reports of medication error, abuse, misuse, or overdose, 
occupational exposure with an AE, and reports of adverse reactions associated with product 
complaints. Medication error is any preventable event that can cause or lead to inappropriate 
medication use or patient harm while the medication is in the control of a healthcare 
professional, patient or consumer. Abuse is defined as persistent, sporadic or intentional 
excessive use of a medicinal product by a patient accompanied by harmful, physical, and/or 
psychological effects. Misuse is defined as any use of a medicinal product in a way that is not in 

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accordance with the protocol instructions or the local prescribing infonnation and may be 
accompanied by han nful physical and/or psychological effects. An overdose is defined as a dose 
taken (accidentally or intentionally) exceeding the dose as prescribed by the protocol or the 
maximal recommended daily dose as stated in the Product Labeling, specifically notated in the 
IB, (as it applies to the daily dose for the pa1t icipant/patient in question). Occupational exposure 
is defined as exposure to a medicinal product as a result of one's professional or nonprofessional 
occupation. 
In cases of a discrepancy in diu g accountability, overdose will be established only when it is 
clear that the paiticipant has taken the excess dose(s) or the investigator has reason to suspect 
that the paiticipant has taken the additional dose(s). 
Product complaint is defined as any written or verbal repo1t ai·ising from potential deviations in 
the manufacture, packaging or distr·ibution of the product. 
7.5.1. 
Reporting Special Situations 
Elect:I-onic Special Situations Rep01ting 
• 
Site personnel record all special situations data in the eCRF database and from there tr·ansmit 
the special situations infonnation to Gilead GLPS within 24 hours of the investigator's 
knowledge of the event. Detailed instructions can be found in the eCRF completion 
guidelines. 
• If it is not possible to record and submit the special situations infonnation electronically, 
because the eCRF database cannot be accessed or is not available (including at study start), 
record the infonnation on the paper special situations repo1t fonn and submit by e-mail or fax 
within 24 hours of the investigator's knowledge of the event to: 
Gilead GLPS conta.ct infonnation: 
Email: 
Fax: 
PPD 
PD 
• 
As soon as it is possible to do so, any special situations repo1ted via paper must be 
tr·anscribed into the eCRF database according to instructions in the eCRF completion 
guidelines. 
• If any special situations have been repo1ted via a paper f01m because the eCRF database has 
been locked, no further action is necessaiy. 
• 
All special situations data. will be recorded in the eCRF database within the timelines 
outlined in the eCRF completion guideline. 
Additional infonnation may be requested to ensure the timely completion of accurate special 
situations repo1ts. Special situations involving non-Gilead concomitant medications does not 
need to be repo1ted on the special situations repo1t eCRF; however, for special situations that 
result in AEs due to a non-Gilead concomitant medication, the AE should be recorded on the AE 
eCRF. 
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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 Section 7.5 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
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 Grade 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 study drug 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 participant’s safety.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the Gilead 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 study drug at the discretion of the investigator.
7.6.2.
Grades 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, study drug may be 
continued if the event is considered to be unrelated to study drug.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to study drug, study drug should be withheld 
until the toxicity returns to ≤ Grade 2.

If a laboratory abnormality recurs to ≥ Grade 3 following rechallenge with study drug and is 
considered related to study drug, then study drug should be permanently discontinued and the 
participant managed according to local practice. Recurrence of laboratory abnormalities 
considered unrelated to study drug may not require permanent discontinuation.

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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 study drug, study drug should be permanently 
discontinued and the participant managed according to local practice. The participant should be 
followed as clinically indicated until the laboratory abnormality returns to baseline or is 
otherwise explained, whichever occurs first. A clinically significant Grade 4 laboratory 
abnormality that is not confirmed by repeat testing should be managed according to the 
algorithm for the new toxicity grade.
Study drug may be continued without dose interruption for a clinically nonsignificant Grade 3-4 
laboratory abnormality (eg, CK elevation after strenuous exercise, or triglyceride elevation that is 
nonfasting or that can be medically managed) or a Grade 3-4 clinical event considered unrelated 
to study drug.
7.6.4.
Management of Bone Evaluation
As there may be uncertainty surrounding the clinical significance and management of decreases 
in BMD, Gilead recommends that any participant who has a DXA scan that demonstrates a 
decrease from baseline of > 5% in the spine region or > 7% in the hip region be followed per 
local medical standards and as per the discretion of the investigator.
7.6.5.
Management of Changes in Estimated Glomerular Filtration Rate
Estimated GFR, according to the Cockcroft-Gault formula, will be followed postbaseline during 
the study. All participants with eGFR < 60 mL/min must have serum creatinine and participant’s 
weight measured again within 3 calendar days of receipt of results. If a participant has confirmed 
eGFR < 60 mL/min, the investigator should notify the medical monitor, evaluate potential 
causes, re-assess the potential risks and benefits of continued treatment in the study, and consider 
consultation with a qualified nephrologist.
7.6.6.
Potential High-Risk Exposure
For participants who present after a high-risk sexual exposure, were non-adherent to study drug, 
and request PEP, investigators may discontinue the participant’s study medication and provide 
PEP in accordance with local medical practice and/or guidelines. Participants who complete their 
PEP regimen and wish to continue on study may resume with study medication following the 
criteria as detailed in Section 6.8. Participants who present after a high-risk sexual exposure with 
reported good adherence to study drug do not require PEP.

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8.1. 
8.1.1. 
STATISTICAL CONSIDERATIONS 
Analysis Objectives and Endpoints 
Analysis Objectives 
The prirmuy objective of this study is: 
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• 
To assess the rates of HIV-I infection in MSM and TGW who have sex with men who are 
administered daily F/TAF or F/TDF with a minimum follow up of 48 weeks and at least 50% 
of paiiicipants have 96 weeks of follow up after randomization 
The secondaiy objectives of this study ai·e: 
• 
To compare bone safety between the treatments as detennined by DXA tests of hip and spine 
BMD in a subset of paiiicipants at Week 48 and Week 96 in the blinded phase 
• 
To compai·e renal safety between the treatments as detennined by urine RBP to creatinine 
ratio, urine beta-2-microglobulin to creatinine ratio, UPCR, and sernm creatinine at Week 48 
and Week 96 in the blinded phase 
• 
To assess the rates of HIV-I infection in MSM and TGW who have sex with men who ai·e 
administered daily F/TAF or F/TDF when all paiticipants have 96 weeks of follow up after 
randomization 
• 
To compare the general safety between the treatments 
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8.1.2.
Primary Endpoints
The primary endpoint will be the incidence of HIV-1 infection per 100 PY when all participants 
have a minimum follow up of 48 weeks and at least 50% of the participants have 96 weeks of 
follow up after randomization. HIV-1 infection is defined by one or more of the following 
criteria of contributing HIV tests performed via central lab or local lab:
1) Serologic evidence of seroconversion (reactive screening HIV Ag/Ab or Ab test, confirmed 
by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or
2) Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any 
detectable quantitative HIV-1 RNA test), or
3) Evidence of acute HIV-1 infection (reactive p24 Ag or positive qualitative or quantitative 
RNA, in the absence of reactive HIV-1 Ab results).
Please refer to Appendix 7 for more details.
8.1.3.
Secondary Endpoints
The key (α-controlled) secondary endpoints in the blinded phase are (in the following order):

The percent change from baseline in hip BMD at Week 48 in a subset of participants

The percent change from baseline in spine BMD at Week 48 in a subset of participants

Assessment of renal biomarkers at Week 48
percent change from baseline in urine beta-2-microglobulin to creatinine ratio
percent change from baseline in urine RBP to creatinine ratio
distribution of UP and UPCR categories

The change from baseline in serum creatinine at Week 48
Other secondary endpoints include:

The incidence of HIV-1 infection (as defined in Appendix 7) per 100 PY when all 
participants have 96 weeks of follow up after randomization

The percent change from baseline in hip and spine BMD at Week 96 in the blinded phase in a 
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Assessment of renal biomarkers at Week 96 in the blinded phase 
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percent change from baseline in mine beta-2-microglobulin to creatinine ratio 
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percent change from baseline in mine RBP to creatinine ratio 
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distribution of UP and UPCR categories 
• 
The change from baseline in sennn creatinine at Week 96 in the blinded phase 
• 
The incidence of ti·eatment-emergent AEs and laborato1y toxicities 
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8.2. 
8.2.1. 
8.2.1.1. 
Analysis Conventions 
Analysis Sets 
Randomized Analysis Set 
Paiiicipants that ai·e randomized into the study will be included in this analysis set. This is the 
primaiy analysis set for by-paiiicipant listings. 
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Full Analysis Set (FAS) 
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The FAS will include all the participants who randomize and receive at least one dose of study 
diug. The FAS will exclude paiiicipants with major protocol violations ( eg, HIV-1 positive at 
baseline). The FAS analysis set is the prima1y analysis set for the efficacy endpoints. 
8.2.1.3. 
Per Protocol (PP) Analysis Set 
The PP analysis set will include all paiiicipants who (1) randomize into the study, (2) receive at 
least one dose of study diug, and (3) have not committed any major protocol violation, including 
the violation of key entiy criteria. 
Paiiicipants meeting any of the following criteria will be excluded from the PP analysis set: 
• 
HIV-I-positive at baseline 
• 
Paiiicipants who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 5.4 including diugs not to be used with 
FTC and TAF 
• 
Nonadherence to study dmg: paiiicipants with poor adherence rate for active study diug 
8.2.1.4. 
Safety Analysis Set 
The prima1y analysis set for safety analyses is defined as all pa1iicipants who randomize in to the 
study and received at least one dose of study diug. 
8.2.1.5. 
Hip DXA Analysis Set 
The Hip DXA analysis set will include all paiiicipants who randomize and receive at least 
one dose of study diug, had nonmissing hip BMD value for the baseline visit and at least 
one postbaseline visit. Paiiicipants will be grouped according to the ti·eatment they actually 
received. 
8.2.1.6. 
Spine DXA Analysis Set 
The Spine DXA analysis set will include all paiiicipants who randomize and receive at least 
one dose of study diug, and had nonmissing spine BMD value for the baseline visit and at least 
one postbaseline visit. Paiiicipants will be grouped according to the ti·eatment they actually 
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Demographic Data and Baseline Characteristics 
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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 summaiy of body weight, height and body mass index, number of 
sexual paitners in the last 3 months prior to screening, and number of acts of condomless anal 
intercourse. 
8.4. 
8.4.1. 
Efficacy Analysis 
Primary Analysis 
The primaiy endpoint will be the incidence of HIV-1 infection per 100 PY (HIV-1 infection 
defined by the HIV Infection Endpoint Definition in Appendix 7). The timing of the primaiy 
analysis will occur when the last pa1ticipant has a minimum of 48 weeks of follow up and at least 
50% of the paiticipants have 96 weeks of follow up after randomization. The primaiy analysis 
will consist of a noninferiority evaluation of F /T AF versus F ffDF, with respect to the HIV-1 
infection rate in PY as detennined by rate ratios. It will be concluded that F/TAF is non-inferior 
to FffDF if the upper bound of the 95% CI of the rate ratio (F/TAF divided by FffDF) is less 
than 1.62 using a generalized model associated with a Poisson distribution and logai·ithmic link 
with the treatment group being the covariate. 
If non-inferiority of F/TAF is established to F/TDF, and the upper bound of the 95% CI is less 
than 1, then superiority ofFffAF over FffDF will be established. 
8.4.2. 
Secondary Efficacy Analysis 
A similai· analysis to the prima1y analysis, when all pa1ticipants have 96 weeks of follow up after 
randomization will be conducted. Similai· incidence rates and Cis will be repo1ted for the 
extended follow up time. 
8.5. 
Safety Analysis 
All safety analyses will be perfo1m ed 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 by treatment group. Data 
for the pretreatment and treatment-free follow-up period will be included in data listings. 
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8.5.1.
Extent of Exposure
A participant’s extent of exposure to study medication will be generated from the study 
medication administration data. Exposure data will be summarized by treatment group.
Duration of exposure to study drug will be expressed as the number of weeks between the first 
and last dose of the study drug, inclusive, regardless of temporary interruptions in study drug 
administration. Dosing information for individual participants will be listed.
8.5.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), 
High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to 
the clinical database.
Events will be summarized on the basis of the date of onset for the event. Adverse events 
meeting the following criteria are defined as treatment-emergent AEs:

Events with onset dates on or after the first dose date of study drug, and no later than 30 days 
after the study drug stop date, and/or

Events that result in premature permanent study medication discontinuation
Summaries (number and percentage of participants) of treatment-emergent AEs (by SOC and 
PT) will be provided. Additional summaries will include summaries for AEs by grade, 
investigator’s assessment of relationship to study medication, 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 Gilead 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 postbaseline up to the date of last dose of study 
medication plus 30 days, will be summarized. If baseline data are missing, then any graded 
abnormality (ie, 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 medication or after the 
participant has been discontinued from treatment plus 30 days will be included in a data listing.

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8.5.6. 
Other Safety Evaluations 
Weight will be summarized by visit. 
8.6. 
Statistical Testing Procedure 
Final 
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The prima1y hypothesis of non-inferiority ofF/TAF relative to F/TDF, with respect to the 
incidence of HIV-1 infection rate per 100 PY will be tested first. Non-inferiority test will be 
perfo1med at one-sided, 0.025 alpha level. Multiplicity adjustments for safety endpoints will be 
perfo1med at Week 48 of the blinded phase with a fallback procedure {Wiens 2005} in the 
sequential order given below with pre-specified two-sided alpha levels: 
a) Hip BMD (alpha = 0.02) 
b) Spine BMD (alpha = 0.01) 
c) Renal biomarkers (alpha = 0.02) 
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8.8. 
Sample Size 
Final 
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A sample size of 2500 in each aim (1: 1 randomization) provides at least 82% power to show 
F/TAF is non-inferior to F/TDF with respect to the HIV-I infection rate. In this power analysis, a 
HIV-I infection rate of 1.44 per 100 PY in the FIT AF and F /TDF treatment aims, a 2-sided 
Type 1 enor rate of 5%, a non-inferiority margin of 1.62, and an average follow up of 2 years are 
assumed. 
The non-inferiority mai·gin of 1.62 and HIV-I infection rate of 1.44 per 100 PY ai·e based on an 
equal weighting approach using 3 historical studies of F/TDF versus placebo/untreated aims in 
MSM populations that are ve1y similar to the population intended for this study (see Table 8-1 
below; the NI margin of 1.62 per 100 PY is the square-root of the lower bound of the 95% CI 
(2.64) ofrate ratio to preserve 50% of treatment effect). The largest of the 3 studies is the IPREX 
study and the unprotected receptive anal intercomse (URAi) subgroup of the IPREX study is a 
high-risk population similai· to the intended population of this study. Equal weighting for the 
3 studies gives relatively more weight to the 2 smaller contemporaiy studies (PROUD and 
IPERGA Y) than the alternative method of inverse vai·iance weighting, thus providing an 
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estimate that is likely to be closer to the hue estimate ofFffDF efficacy for PrEP. PROUD and 
IPERGAY were conducted when F/TDF was aheady established as an effective PrEP medication 
and represent the status for participants in the proposed study. IPREX, the largest and earliest of 
these 3 studies, was conducted when the effectiveness of F/TDF for PrEP was not established; 
thus, patients were info1med of the unproven efficacy of F/TDF, which likely conh'ibuted to the 
much lower adherence rate in the IPREX h'ial. In conh'ast, PROUD and IPERGA Y are more 
recent studies and were conducted after F/TDF was approved for prevention of HIV in a similar 
risk population, and likely conh'ibuted to the much higher adherence rate repo1i ed. 
Table 8-1. 
Efficacy Information from Truvada as PrEP in MSMs 
HIV Infections 
Rate 
(Incidence pe1· 100 PY 
Ratios in 
(95% CI)) 
mv 
Infection 
Sample Size 
Sample Size 
Rates, 
Placebo 
F/IDF 
per 
(PY 
(PY 
lO0 PY 
Clinical Trial 
Follow-Up) 
Follow-Up) 
PBO 
F/TDF 
(95% CI] 
Enrollment 
IPREX 
56 (5.3) 
23 (2.2) 
2.4 
July I 0, 2007 -
(URAI subgroup) 
753 (1054) 
732 (1055) 
at screening 
[4.0, 6.8] 
[1.4, 3.2] 
[1.5, 3.9] 
Dec 17, 2009 
20 (9.0) 
3 (1.2) 
7.3 
Nov 29, 2012 -
PROUD 
255 (222) 
268 (243) 
[2.2, 
[5.6, 13.4] 
[0.3, 3.5] 
24.2] 
Apr 30, 2014 
14 (6.6) 
2 (0.9) 
7.3 
Feb 22, 2012 -
IPERGAY 
201 (212) 
199 (220) 
[1.7, 
[3.9, 10.6] 
[0.2, 3.2] 
31.6] 
Oct 23, 2014 
90 (6.0) 
28 (1.9) 
5.1 
Pool 
1209 (1488) 
1199 (1518) 
[4.9, 7.5] 
[1.3, 2.6] 
[2.64, 
{6.96}* 
{1.44}* 
9.70] 
Sotu·ce: iPrEX from { Grant 2010}; Ipergay from {Molina 2015}; Pre-expostu·e prophylaxis to prevent the acquisition of HIV-1 
infection (PROUD) from {McConnack 2015} 
* 
The pooled incidence rate for placebo and F/TDF, based on equal weighting of 3 studies are within {} which are used for 
estimating the rate ratio and its 95% CI. 
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For the percent change in renal biomarkers of urine beta 2-microglobulin to creatinine ratio and 
urine RBP to creatinine ratio from baseline to Week 48, the sample size of 2500 in each arm will 
have at least 95% power, given the probability of a participant from F/TAF is less than that from 
F/TDF, P(F/TAF < F/TDF), is at least 55% using a 2 sided Wilcoxon rank sum test at 0.02 level.
The sample size of 2500 in each arm will also provide at least 95% power to demonstrate that 
F/TAF has 0.014 mg/dL less increase at Week 48 in serum creatinine than F/TDF, assuming the 
standard deviation is 0.114 and 0.097 in F/TAF and F/TDF, respectively, and 2 sided t-test will 
be conducted at 0.02 level. The mean differences and standard deviations are based on 
Gilead HIV Studies GS-US-292-0104/GS-US-292-0111 (E/C/F/TAF vs E/C/F/TDF) and HBV 
Studies GS-US-320-0108/GS-US-320-0110 (TAF vs TDF). To be conservative, the smaller 
effect size from HBV Studies GS-US-320-0108/GS-US-320-0110 was used for the estimation of 
mean difference and standard deviation between the 2 treatments in the sample size calculation.
The above power calculations for BMD and renal biomarkers are based on historical data from 
studies where patients take study drug daily, if patients are less than fully adherent, the observed 
benefit of F/TAF compared to F/TDF will be less than these historical estimates, and thus the 
above power calculation may be overly optimistic.
8.9.
Data Monitoring Committee
An independent data monitoring committee (IDMC) will be convened to primarily evaluate the 
safety of the treatments in this population. There are no a priori plans to stop for efficacy or 
futility with formal boundaries. At a minimum, the IDMC will include 2 clinicians (including a 
chairperson), a biostatistician, a prevention expert, and a community member. The initial 
evaluation by the IDMC will occur either (1) after 50% of participants have completed Week 24 
(or prematurely discontinued from the study drug) or (2) after 50 HIV-1 infection events have 
been reported, whichever occurs earlier. The second evaluation by the IDMC will occur either 
(1) after 50% of participants have completed Week 48 (or prematurely discontinued from the 
study drug) or (2) after 100 HIV-1 infection events have been reported, whichever occurs earlier. 
The third evaluation by the IDMC will occur either (1) after 50% of participants have completed 
Week 72 (or prematurely discontinued from the study drug) or (2) after 150 HIV-1 infection 
events have been reported, whichever occurs earlier. Other specifics regarding roles and 
responsibilities will be described in the IDMC charter.

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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), ICH guidelines, or with the laws and regulations of the country in which the 
research is conducted, whichever affords the greater protection to the study participant. These 
standards are consistent with the EU Clinical Trials Directive 2001/20/EC and GCP Directive 
2005/28/EC.
The investigator will ensure adherence to the basic principles of GCP, as outlined in 21 Code of 
Federal Regulations (CFR) 312, subpart D, “Responsibilities of Sponsors and Investigators,” 
21 CFR, part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last participant completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, ICF, and any accompanying material to be provided to the participant (such as 
advertisements, participant information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study participant 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 participant after initial IRB/IEC approval, with the exception of those necessary 
to reduce immediate risk to study participants.

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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 ICF for documenting written informed 
consent. Each ICF (or assent as applicable) will be appropriately signed and dated by the 
participant or the participant’s legally authorized representative and the person conducting the 
consent discussion, and also by an impartial witness if required by IRB/IEC or local 
requirements.
9.1.4.
Confidentiality
The investigator must assure that participants’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties. Only participant initials, date of birth, 
another unique identifier (as allowed by local law) and an identification code will be recorded on 
any form or biological sample submitted to the sponsor, IRB/IEC, or laboratory. Laboratory 
specimens must be labeled in such a way as to protect participant identity while allowing the 
results to be recorded to the proper participant. Refer to specific laboratory instructions 
NOTE: The investigator must keep a screening log showing codes, names, and addresses for all 
participants screened and for all participants enrolled in the study. Participant data will be 
processed in accordance with all applicable regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
IB, this protocol, eCRF, the study drug, 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 2 categories: (1) investigator’s study file, and 
(2) participant clinical source documents.
The investigator’s study file will contain the protocol/amendments, case report form (CRF) and 
query forms, IRB/IEC and governmental approval with correspondence, ICFs, 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 participant:

Participant identification (name, date of birth, gender)

Documentation that participant meets eligibility criteria, ie history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria)

Documentation of the reason(s) a consented participant is not enrolled

Participation in study (including study number)

Study discussed and date of informed consent

Dates of all visits

Documentation that protocol specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of study drug, including dates of dispensing and 
return

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity)

Concomitant medication (including start and end date, dose if relevant; dose changes)

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie US, Europe, or Japan) and until there are no pending or planned marketing 
applications in an ICH region; or, if no application is filed or if the application is not approved 
for such indication, until 2 years after the investigation is discontinued and regulatory authorities 
have been notified. Investigators may be required to retain documents longer if specified by 
regulatory requirements, by local regulations, or by an agreement with Gilead. The investigator 
must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
participant, appropriate copies should be made for storage away from the site.

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9.1.6.
Case Report Forms
An eCRF casebook will be completed by an authorized study personnel member whose training 
for this function is completed in the electronic data capture (EDC) system unless otherwise 
directed. The eCRF casebook will only capture the data required per the protocol schedule of 
events and procedures, unless collected by a nonelectronic data capture vendor system (eg, 
central laboratory). The Inclusion/Exclusion Criteria and Enrollment eCRFs should be completed 
only after all data related to eligibility are available. Data entry should be performed in 
accordance with the case report form Completion Guidelines provided by the sponsor. 
Subsequent to data entry, a study monitor may perform source data verification. 
System-generated or manual queries will be issued in the EDC system as data discrepancies are 
identified by the study monitor or Gilead personnel who routinely review the data for 
completeness, correctness, and consistency. The site investigator, site coordinator, or other 
designee is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (eg, data entry error). Original entries as well as any changes to data fields will be 
stored in the audit trail of the system. Regular oversight by the principal investigator of the data 
entered into the EDC system is expected to occur on an ongoing basis throughout the study to 
ensure quality and completeness. At a minimum, before any interim, final, or other time points 
(as instructed by Gilead), the investigator will apply his/her electronic signature to confirm that 
the forms have been reviewed and that the entries accurately reflect the information in the source 
documents. At the conclusion of the study, Gilead will provide the site investigator with a read 
only archive copy of the data entered. 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
The study monitor will provide instructions for return to the designated disposal site. If return is 
not possible, the study monitor will evaluate each study center’s study drug disposal procedures 
and provide appropriate instruction for destruction of unused study drug supplies. If the site has 
an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused study drug supplies 
in accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files.
If study drug is destroyed on site, the investigator must maintain accurate records for all study 
drug destroyed. Records must show the identification and quantity of each unit destroyed, the 
method of destruction, and the person who disposed of the study drug. Upon study completion, 
copies of the study drug accountability records must be filed at the site. Another copy will be 
returned to Gilead.
The study monitor will review study drug supplies and associated records at periodic intervals.

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9.1.8.
Inspections
The investigator will make available all source documents and other records for this study to 
Gilead’s appointed study monitors, to IRBs/IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study participants, 
may be made only by Gilead. The investigator must submit all protocol modifications to the 
IRB/IEC in accordance with local requirements and receive documented IRB/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.

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9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg, attendance at Investigator's Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any participant records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the participants’ interests.

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10.
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VIREAD®, Gilead Sciences Inc. VIREAD® (tenofovir disoproxil fumarate) tablets, for oral use/ 
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Information. Revised February.  2016:
Wiens BL, Dmitrienko A. The fallback procedure for evaluating a single family of hypotheses. J 
Biopharm Stat 2005;15 (6):929-42.
Wolitski RJ, MacGowan RJ, Higgins DL, Jorgensen CM. The effects of HIV counseling and 
testing on risk-related practices and help-seeking behavior. AIDS Educ Prev 
1997;9 (3 Suppl):52-67.

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 97
19 October 2021
11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Study Procedures Table (OL Week 96 and beyond)
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Appendix 5.
Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 6.
HIV Testing Algorithm
Appendix 7.
HIV Infection Endpoint Definition
Appendix 8.
Pandemic Risk Assessment and Mitigation Plan

Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Gilead Sciences, Inc. 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
Final 
Amendment 7 
A Phase 3, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of 
Emti·icitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for 
Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex with Men and Are 
At Risk of HIV-1 Infection 
GS-US-412-2055, Amendment 7, 19 October 2021 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
[See appended electronic signature} 
[See appended electronic signature} 
(Printed) 
Signature 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessa1y 
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 effo1t to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
infonnation provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully info1med about the diugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 98 
19 October 2021 

Prot-GS-US-412-2055_amd-7
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Research eSigned
20-Oct-2021
16:10:40
PPD

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 99
19 October 2021
Appendix 2.
Study Procedures Table
Double-Blind Treatment
End of Weeka
Post 
Week 96
Open-Label Treatment
End of Weekc
Study Procedure
Screening
Day
1
4
12
24
36
48
60
72
84
96
Every 
12 Weeks
end of 
blinded 
treatment 
phase 
visitb
12
24
36
48
Every 
12 Weeks Up 
to OL Week 
96d
30-Day 
Follow-upe
ESDDf
Informed Consent
X
Medical History 
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam
X
X
X
X
Targeted Physical Exam 
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signsg
X
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Genital, Rectal, and 
Pharyngeal Examination 
for STIs as appropriate 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharyngeal Swab for 
Gonorrhea and 
Chlamydiaab 
(Local Laboratory)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Rectal Swab for 
Gonorrhea and 
Chlamydia 
(Local Laboratory)ab
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Sample for 
Gonorrhea and 
Chlamydia
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Rapid HIV-1 Ag/Ab Test 
(In-Clinic)p
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV-1 Ab/Agq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV-1 RNA by PCRr
X
Xs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 100
19 October 2021
Double-Blind Treatment
End of Weeka
Post 
Week 96
Open-Label Treatment
End of Weekc
Study Procedure
Screening
Day
1
4
12
24
36
48
60
72
84
96
Every 
12 Weeks
end of 
blinded 
treatment 
phase 
visitb
12
24
36
48
Every 
12 Weeks Up 
to OL Week 
96d
30-Day 
Follow-upe
ESDDf
Dipstick Urinalysis 
(In-Clinic)
X
Urinalysis, Urine Protein, 
Urine Chemistry 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sample for 
Chemistry Profileh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sample for 
Hematology Profilei
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sample for 
Syphilis testingk 
(Local Laboratory)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hepatitis B Testing 
(HBsAg/HBsAb/HBcAb)
X
X
X
X
X
Xac
Xac
X
X
Xac
Hepatitis C Testing 
(HCV Ab)
X
X
X
Xad
Xad
X
Xad
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Plasma Storage Samplem
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CASI Questionnairen
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization in IXRS
X
Risk Reduction/ 
Adherence Counseling
Xu
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CCI
CCI
CCI
CCI
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Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 101
19 October 2021
Double-Blind Treatment
End of Weeka
Post 
Week 96
Open-Label Treatment
End of Weekc
Study Procedure
Screening
Day
1
4
12
24
36
48
60
72
84
96
Every 
12 Weeks
end of 
blinded 
treatment 
phase 
visitb
12
24
36
48
Every 
12 Weeks Up 
to OL Week 
96d
30-Day 
Follow-upe
ESDDf
Study Drug Dispensation 
and Accountability
Xy
X
X
X
X
X
X
X
X
X
X
Xz
X
X
X
X
X
Xaa
CD4, CD8, and 
CD4/CD8 (for 
participants who acquire 
HIV)
Performed at all visits after HIV infection.
X
X
Latent and Active 
Reservoir assessment (for 
participants who acquire 
HIV)
Performed for participants who acquire HIV only. Performed at first study visit after HIV infection and 
at regularly scheduled study visits 24 weeks and 48 weeks after HIV infection, and every 48 weeks 
thereafter.
T cell response and 
phenotype (for 
participants who acquire 
HIV)
Performed for participants who acquire HIV only. Performed at first study visit after HIV infection and 
at regularly scheduled study visits 24 weeks and 48 weeks after HIV infection, and every 48 weeks 
thereafter.
Viral Sequence Diversity 
assessment (for 
participants who acquire 
HIV)
Performed for participants who acquire HIV only. Performed at first study visit after HIV infection and 
at regularly scheduled study visit 24 weeks after HIV infection only.
Inflammatory/Immune 
Activation Biomarkers 
(for participants who 
acquire HIV)
Performed for participants who acquire HIV only. Performed at first study visit after HIV infection and 
at regularly scheduled study visits 24 weeks and 48 weeks after HIV infection, and every 48 weeks 
thereafter.
Ab = antibody; Ag = antigen; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CASI = Computer-Assisted Self-Interview; CD = cluster 
determinant; 
 
; ESDD = early study drug discontinuation; GFR = glomerular filtration rate; GGT = gamma glutamyl 
transferase; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; IXRS = interactive voice/web 
response system; LDH = lactate dehydrogenase; OL = open-label; 
 PCR = polymerase chain reaction; PK = pharmacokinetic; STI = sexually 
transmitted infection; ULN = upper limit of normal
a
All study visits in the double-blind phase are to be scheduled relative to the Day 1 visit date. Visit windows are ± 2 days of the protocol-specified date through Week 12, 
± 14 days of the protocol-specified date through the end of blinded treatment phase visit, unless otherwise specified.
b
end of blinded treatment phase visit to occur after all participants reach Week 96.
c
Study visits are to be completed within ± 14 days of the protocol-specified visit date based on the end of blinded treatment phase visit.
d
Participants will continue study visits every 12 weeks in the OL phase up to OL Week 96 (not including OL Week 96). From OL Week 96, refer to Appendix 3.
CCI
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Emtricitabine and Tenofovir Alafenamide (F/TAF) 
Protocol GS-US-412-2055 
Gilead Sciences, Inc. 
Final 
Amendment 7 
e 
For 30-Day Follow-up visits conducted prior to OL Week 96, must be completed 30 days after discontinuing study dmg. All pa1ticipants who have received at least one dose 
of study dmg will be required to complete a follow-up visit. For the ptupose of scheduling a 30-Day Follow-Up visit, a± 14 days window may be used. 
f 
For Early Study Dmg Discontinuation Visits conducted prior to OL Week 96, visit to occur within 72 hotu·s of last dose of study dmg. Pa1ticipants will be asked to continue 
attending the scheduled study visits through the end of blinded treatment phase visit. 
g 
Vital signs measurement including blood pressure, pulse, respiration rate, and temperature. After the Day 1 visit, vital signs completed when clinically indicated. 
h 
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and indirect bilimbin, total protein, albmuin, LDH, bicarbonate, BUN, calcimu, chloride, 
creatinine, glucose, phosphoms, magnesium, potassium, sodium, tu-ic acid, and amylase (reflex lipase testing is performed in participants with total amylase> 1.5 x ULN). 
1 
Com lete blood count CBC with differential and latelet count 
r 
r 
m 
or poss1 e 
, v11·0 ogy, an or sa ety testmg 
n 
Computer-assisted self-interview (CASI) 
o 
If Day 1 is completed > 7 days after the screening visit 
p 
F otuth generation rapid HIV-1 Ab/ Ag or third generation rapid HIV-1 Ab test may be used. If fomth generation rapid HIV-1 Ag/ Ab or third generation rapid HIV-1 Ab test is 
positive, a retest will be completed. At screening or Day 1, if rapid retest is positive the participant is a screen failm·e. At all other visits if rapid retest is positive, then HIV-1 
RNA by PCR test and sample collection for possible genotypic testing will be completed. 
q 
At screening, ifHIV-1 Ab/Ag is positive the participant is a screen failure. At all other visits ifHIV-1 Ab/Ag is positive, then HIV-1 RNA by PCR test and sample collection 
for possible genotypic testing will be completed. 
r 
At screening or Day 1, if the pa1ticipant has a negative rapid test, but has signs or symptoms of acute HIV-1 infection, an HIV-1 RNA by PCR test will be completed and if 
HIV-1 RNA by PCR is positive, pa1ticipant cannot participate in the study. At all other visits, HIV-1 RNA by PCR and sample collection for possible genotypic resistance 
testing will be completed for any pa1t icipants who (1) have a positive retest rapid HIV-1 Ab/Ag test or (2) have a positive HIV-1 Ab/Ag test or (3) show symptoms consistent 
with acute infection regardless of the results of the rapid tests, ( 4) have a recent expostu·e that is considered high risk for HIV infection, or (5) have been confinued 
HIV-infected. IfHIV infection is confomed, pa1t icipant will discontinue study dmg inuuediately and should rettun for an ESDD visit within 72 hours. The participant will 
receive counseling and be refeffed for appropriate care. If viral load > 400 copies/mL the collected sample will be sent for genotypic resistance testing. 
s 
At Day 1, HIV-1 RNA by PCR and sample collection for possible genotypic testing will be completed for any pa1t icipants who show symptoms consistent with acute HIV-1 
f 
~
f the results of the rapid tests. 
u 
~
ounselino at screenino 
I 
y 
On y stu y 
"t1g 1spensation at Day 1 
z 
OL dmg dispensation (all eligible participants will receive F/TAF) 
aa 
No study dmg dispensed. 
ab Swabs may be self-administered by the pa1t icipant at the discretion of the investigator. 
ac 
Hepatitis B testing (HBsAg, HBsAb, HBcAb) to be completed every 24 weeks. Hepatitis B testing to be completed at the end of blinded freatiuent phase visit if> 24 weeks 
from prior testing. 
ad Hepatitis C testing (HCV Ab) to be completed every 48 weeks. Hepatitis C testing to be completed at the end of blinded treatment phase visit if > 48 weeks from prior testing. 
CONFIDENTIAL 
Page 102 
19 October 2021 

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 103
19 October 2021
Appendix 3.
Study Procedures Table (OL Week 96 and beyond)
Open-Label Extension Treatment
End of Weeka
Study Procedure
OL Week 96 and Every 12 Weeks until OL Week 408b
30-Day Follow-upc
ESDDd
Concomitant Medications
X
X
X
Adverse Events 
X
X
X
Targeted Physical Examf
Xf
X
X
Vital Signse
Xe
X
X
Weightf
Xf
X
X
Genital, Rectal, and 
Pharyngeal Examination 
for STIs as appropriate 
X
X
X
Pharyngeal Swab for 
Gonorrhea and Chlamydia
(Local Laboratory) g
X
X
X
Rectal Swab for Gonorrhea 
and Chlamydia 
(Local Laboratory) g
X
X
X
Urine Sample for 
Gonorrhea and Chlamydia
X
X
X
Rapid HIV-1 Ag/Ab Test 
(In-Clinic)h
X
X
X
HIV-1 Ab/Agi
X
X
X
HIV-1 RNA by PCRj
X
X
X
Blood Sample for 
Chemistry Profilek
Xk
X
X
Blood Sample for Syphilis 
Testing (Local Laboratory)
X
X
X
Hepatitis B Testing 
(HBsAg/HBsAb/HBcAb)
Xm
Hepatitis C Testing 
(HCV Ab)
Xn
Estimated GFR
Xo
X
X
CCI

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 104
19 October 2021
Open-Label Extension Treatment
End of Weeka
Study Procedure
OL Week 96 and Every 12 Weeks until OL Week 408b
30-Day Follow-upc
ESDDd
Risk Reduction/Adherence 
Counseling
X
Study Drug Dispensation 
and Accountability
X
Xq
CD4, CD8, and CD4/CD8 
cell count (for participants 
who acquire HIV)
X
X
Ab = antibody; Ag = antigen; BUN = blood urea nitrogen; CD4 = cluster determinant 4; CD8 = cluster determinant 8; DBS = dried blood spot; ESDD = early study drug 
discontinuation; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; OL = open label; 
PCR = polymerase chain reaction; STI = sexually transmitted infection
a
Visit windows are ± 14 days of the protocol-specified date, based on the end of blinded treatment phase visit, through the Open Label Extension phase visit, unless otherwise 
specified.
b
Participants will continue study visits in the OL extension phase every 12 weeks until OL Week 408.
c
Must be completed 30 days after discontinuing study drug. All participants who have received at least one dose of study drug will be required to complete a follow-up visit. 
For the purpose of scheduling a 30-Day Follow-Up visit, a ± 14 days window may be used.
d
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug.
e
Vital signs measurement including blood pressure, pulse, respiration rate, and temperature, every 24 weeks
f
Every 24 weeks
g
Swabs may be self-administered by the participant at the discretion of the investigator.
h
At a minimum, fourth generation rapid HIV-1 Ab/Ag or third generation rapid HIV-1 Ab test may be used. If fourth generation rapid HIV-1 Ag/Ab or third generation rapid 
HIV-1 Ab test is positive, retest will be completed. If rapid retest is positive, then HIV-1 RNA by PCR test and sample collection for possible genotypic testing will be 
completed.
i
If HIV-1 Ab/Ag is positive, then HIV-1 RNA by PCR test and sample collection for possible genotypic testing will be completed.
j
HIV-1 RNA by PCR and sample collection for possible genotypic resistance testing will be completed for any participants who (1) have a positive retest rapid HIV-1 Ab/Ag 
test or (2) have a positive HIV-1 Ab/Ag test or (3) show symptoms consistent with acute infection regardless of the results of the rapid tests, (4) have a recent exposure that is 
considered high risk for HIV infection, or (5) have been confirmed HIV-infected. If HIV infection is confirmed, participant will discontinue study drug immediately and 
should return for an ESDD visit within 72 hours. The participant will receive counseling and be referred for appropriate care. If viral load > 400 copies/mL the collected 
sample will be sent for genotypic resistance testing.
k
Chemistry profile: bicarbonate, BUN, calcium, chloride, creatinine, glucose, phosphorus, potassium, sodium every 24 weeks.
m
Hepatitis B testing (HBsAg, HBsAb, HBcAb) to be completed every 48 weeks.
n
Hepatitis C testing to be completed every 48 weeks.
o
Estimated GFR every 24 weeks
q
No study drug dispensed.
CCI
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Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 105
19 October 2021
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Grade 1
Grade 4
Grade 3
Grade 2
May continue 
dosing at the 
discretion of the 
investigator
Repeat lab to 
confirm toxicity 
grade
Repeat lab to 
confirm toxicity 
grade
If confirmed and possibly and/or probably related to 
investigational medicinal products:
1.
Withhold investigational medicinal products until Grade 2
2.
Restart all investigational medicinal products at full dose
If confirmed and unrelated to 
investigational medicinal products, 
dosing may continue at the 
discretion of the investigator
If confirmed and 
possibly or probably 
related to 
investigational 
medicinal products,
discontinue 
investigational 
medicinal products
dosing permanently 
and follow at periodic 
intervals at least 
weekly until a return 
to baseline or is 
otherwise explained
If Grade 3 or 4 recurrence that is confirmed and possibly or 
probably related to investigational medicinal products, 
discontinue all investigational medicinal products dosing 
permanently
f Grade 3 or 4 recurrence that is considered unrelated to 
inve tigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator
 
 
  
 
 
 
 
 
 
 
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Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 106
19 October 2021
Appendix 5.
Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric  57 
Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to  8.5 g/dL 
75 to  85 g/L
6.5 to  7.5 g/dL 
65 to  75 g/L
 6.5 g/dL
 65 g/L
HIV NEGATIVE
Adult and Pediatric  57 
Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to  3.5 g/dL
25 to  35 g/L
9.0 to  10.0 g/dL
90 to  100 g/L
OR
Any decrease from Baseline
3.5 to  4.5 g/dL
35 to  45 g/L
7.0 to  9.0 g/dL
70 to  90 g/L
OR
Any decrease from Baseline
 4.5 g/dL
 45 g/L
 7.0 g/dL
 70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR 
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to  8.5 g/dL
70 to  85 g/L
6.0 to  7.0 g/dL
60 to < 70 g/L
 6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR 
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to  9.5 g/dL
80 to  95 g/L
7.0 to  8.0 g/dL
70 to  80 g/L
 7.0 g/dL
 70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR 
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to  12.0 g/dL
100 to  120 g/L
9.0 to  10.0 g/dL
90 to  100 g/L
 9.0 g/dL
 90 g/L
1000 to 1300/mm3
750 to  1000/mm3
500 to  750/mm3
 500/mm3
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 
≥ 7 Months# 
1.00 to 1.30 GI/L
0.75 to  1.00 GI/L
0.50 to  0.75 GI/L
 0.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to  300/mm3
200 to  300/μL
100 to  200/mm3
100 to  200/μL
 100/mm3
 100/μL

Emtricitabine and Tenofovir Alafenamide (F/TAF)
Protocol GS-US-412-2055
Final
Gilead Sciences, Inc.
Amendment 7
CONFIDENTIAL
Page 107
19 October 2021
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
 13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to  600/mm3
0.50 to  0.60 GI/L
350 to  500/mm3
0.35 to  0.50 GI/L
 350/mm3
 0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to  125 GI/L
50,000 to  100,000/mm3
50 to  100 GI/L
25,000 to  50,000/mm3
25 to  50 GI/L
 25,000/mm3
 25 GI/L
2000/mm3 to 2500/mm3
1,500 to  2,000/mm3
1000 to  1,500/mm3
 1000/mm3
WBCs 
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
100 to 200 mg/dL
75 to  100 mg/dL
50 to  75 mg/dL
 50 mg/dL
Hypofibrinogenemia
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
 ULN to 600 mg/dL
 600 mg/dL
—
—
Hyperfibrinogenemia
 ULN to 6.0 g/L
 6.0 g/L
—
—
20 to 40 μg/mL
 40 to 50 μg/mL
 50 to 60 μg/mL
 60 μg/mL
Fibrin Split Product 
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  ULN
> 1.5 to 2.0  ULN
> 2.0 to 3.0  ULN
> 3.0  ULN
Activated Partial
Thromboplastin Time 
(APTT)
 1.00 to 1.66  ULN
 1.66 to 2.33  ULN
 2.33 to 3.00  ULN
 3.00  ULN
Methemoglobin 
5.0 to 10.0%
 10.0 to 15.0%
 15.0 to 20.0%
 20.0%
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric participants. Please follow the Gilead convention of 
grading any result within the LLN and ULN a 0.

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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
130 to < LLN mEq/L
125 to  130 mEq/L
121 to  125 mEq/L
 121 mEq/L
Hyponatremia 
130 to < LLN mmol/L
125 to  130 mmol/L
121 to  125 mmol/L
 121 mmol/L
> ULN to 150 mEq/L
 150 to 154 mEq/L
 154 to 159 mEq/L
 159 mEq/L
Hypernatremia 
> ULN to 150 mmol/L
 150 to 154 mmol/L
 154 to 159 mmol/L
 159 mmol/L
3.0 to < LLN mEq/L
2.5 to  3.0 mEq/L
2.0 to  2.5 mEq/L
 2.0 mEq/L
Hypokalemia 
Adult and Pediatric
 1 Year
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 mmol/L
2.0 to  2.5 mEq/L
2.0 to < 2.5 mmol/L
 2.0 mEq/L 
< 2.0 mmol/L
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
116 to 160 mg/dL
 160 to 250 mg/dL
 250 to 500 mg/dL
 500 mg/dL
Hyperglycemia, Nonfasting 
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

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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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 mmol/L
6.1 to < 7.0 mg/dL
1.51 to < 1.74 mmol/L
< 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
> ULN to 11.5 mg/dL
 11.5 to 12.5 mg/dL
 12.5 to 13.5 mg/dL
 13.5 mg/dL
Hypercalcemia (corrected for 
albumin if appropriate*) 
Adult and Pediatric 
 7 Days
> 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
3.0 mg/dL to  LLN
2.5 to < 3.0 mg/dL
2.0 to  2.5 mg/dL
 2.0 mg/dL
Hypocalcemia (ionized)
0.74 mmol/L to  LLN
0.62 to  0.74 mmol/L
0.49 to  0.62 mmol/L
 0.49 mmol/L
 ULN to 6.0 mg/dL
 6.0 to 6.5 mg/dL
 6.5 to 7.0 mg/dL
 7.0 mg/dL
Hypercalcemia (ionized)
 ULN to 1.50 mmol/L
 1.50 to 1.63 mmol/L
 1.63 to 1.75 mmol/L
 1.75 mmol/L
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
Hypomagnesemia
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

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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Pediatric 1 Year–14 Years 
3.0 to < LLN mg/dL
0.96 to < LLN mmol/L
2.5 to  3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to  2.5 mg/dL
0.47 to < 0.80 mmol/L
 1.5 mg/dL
< 0.47 mmol/L
Pediatric  1 Year
3.5 to < LLN mg/dL
1.12 to < LLN mmol/L
2.5 to  3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to  2.5 mg/dL
0.47 to < 0.80 mmol/L
 1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia 
Adult and Pediatric 
> 14 Days
 1.0 to 1.5  ULN
 1.5 to 2.5  ULN
 2.5 to 5.0  ULN
 5.0  ULN
Infant,  14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
 25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
 30.0 mg/dL
> 513 μmol/L
Infant,  14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
 25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50  ULN
 2.50 to 5.00  ULN
 5.00 to 10.00  ULN
 10.00  ULN
> ULN to 10.0 mg/dL
 10.0 to 12.0 mg/dL
 12.0 to 15.0 mg/dL
 15.0 mg/dL
Hyperuricemia
> ULN to 597 μmol/L
 597 to 716 μmol/L
 716 to 895 μmol/L
 895 μmol/L
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
Hypouricemia
Adult and Pediatric
≥ 1 year
Infant < 1 Year
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
16.0 mEq/L to  LLN
11.0 to  16.0 mEq/L
8.0 to  11.0 mEq/L
 8.0 mEq/L
Bicarbonate
Adult and Pediatric
≥ 4 Years
16.0 mmol/L to  LLN
11.0 to  16.0 mmol/L
8.0 to  11.0 mmol/L
 8.0 mmol/L
11.0 mEq/L to < LLN
8.0 to  11.0 mEq/L
 8.0 mEq/L
Pediatric < 4 Years
NA
11.0 mmol/L to < LLN
8.0 to  11.0 mmol/L
 8.0 mmol/L

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19 October 2021
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
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
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
LDL (Fasting)
Adult
3.35 to 4.15 mmol/L
> 4.15 to 4.92 mmol/L
> 4.92 mmol/L
110 to 130 mg/dL
> 130 to 190 mg/dL
> 190 mg/dL
NA
LDL (Fasting)
Pediatric >2 to <18 years
2.84 to 3.37 mmol/L
> 3.37 to 4.92 mmol/L
> 4.92 mmol/L
200 to 239 mg/dL
 239 to 300 mg/dL
 300 mg/dL
NA
Hypercholesterolemia
(Fasting)
5.16 to 6.19 mmol/L
 6.19 to 7.77 mmol/L
 7.77 mmol/L
Pediatric  18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
 199 to 300 mg/dL
 5.15 to 7.77 mmol/L
 300 mg/dL
 7.77 mmol/L
NA
Creatine Kinase
3.0 to  6.0  ULN
6.0 to  10.0  ULN
10.0 to  20.0  ULN
 20.0  ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male participants > 70 yrs. Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.

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

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URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
Females
> ULN - 10 RBC/HPF
 10-75 RBC/HPF
> 75 RBC/HPF
NA
Males
6-10 RBC/HPF
 10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour 
Collection
Adult and Pediatric 
 10 Years
200 to 999 mg/24 h
> 999 to 1999 mg/24 h
> 1999 to 3500 mg/24 h
 3500 mg/24 h
Pediatric  3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
> 499 to 799 mg/m2/24 h
> 799 to 1000 mg/m2/24 h
 1000 mg/m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes:

Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by the central laboratory (Prior to OL Week 96); however, for other laboratories, toxicity grades will 
only be assigned to Dipstick Hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.

If the severity of a clinical AE could fall under either one of two grades (eg, the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.

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

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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
with nonurgent 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 2 or 
more distinct mucosal sites 
OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized
Marked or generalized
NA
NA
Pruritis 
(itching – no skin lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities
NA

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

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

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

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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
screening tool appropriate 
for the setting
developmental screening tool 
appropriate for the setting
screening tool appropriate 
for the setting
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
Seizure: (new onset) 
NA
1 seizure
2–4 seizures
Seizures of any kind that are 
prolonged, repetitive 
(eg, status epilepticus), or 
difficult to control 
(eg, refractory epilepsy)

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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Seizure: (preexisting) 
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 
preexisting 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
ADD = attention deficit disorder.

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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 
antimicrobial treatment 
indicated AND Symptoms 
causing no or minimal 
interference with usual social 
& functional activities
Systemic antimicrobial 
treatment indicated OR 
Symptoms causing greater 
than minimal interference 
with usual social & 
functional activities
Systemic antimicrobial 
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. 
HIV Testing Algorithm 
At all study visits (except screening and Day I), the following algorithm* applies to the 
below evaluations: 
I) Retest Rapid HN-1 Ab/Ag test (at site)** 
2) HIV-I Ab/Ag test (at Central Lab, except at Day I) 
3) Signs and symptoms consistent with acute infection 
4) Pruticipant had a recent exposure that the investigator considers high 1isk for HIV 
infection 
~' 
-
Any Evaluation Positive 
All Evaluations Negative 
-.it 
1 
HIV-I RNA tests***, including 
Continue 
qualitative and quantitative tests 
Treatment in Study 
( at Central Lab) 
J; 
HIV-I Infection 
Confmned * * * * 
t 
Stop Treatment 
* 
The HIV testing algorithm does not apply to pa1ticipants who acquire HIV. 
Final 
Amendment 7 
** 
If the result for rapid testing is positive, a retest will be completed. If the retest rapid is positive, an HIV-I RNA by PCR 
test and sample collection for possible genotypic resistance testing will be completed. 
*** May continue study dmg, or may begin a full HIV treatment regimen until HIV-I diagnosis is confirmed, at investigator 
discretion { Center for Disease Contrnl and Prevention ( CDC) 2018}. 
**** HIV infection as defined per Appendix 7 
CONFIDENTIAL 
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Appendix 7.
HIV Infection Endpoint Definition
HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests 
performed via central lab or local lab:
1) Serologic evidence of seroconversion (reactive screening HIV Ag/Ab or Antibody test, 
confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated 
participants, or
2) Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any 
detectable quantitative HIV-1 RNA test), or
3) Evidence of acute HIV-1 infection (reactive p24 Antigen and positive qualitative or 
quantitative RNA, in the absence of reactive HIV-1 Antibody results)
Please refer to the flowchart below which focuses on contributions from the central laboratory 
and provides a general assessment of contributing HIV tests performed by the central laboratory. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 8.
Pandemic Risk Assessment and Mitigation Plan
During an ongoing pandemic, potential risks associated with participants being unable to attend 
study visits have been identified for this study.
These risks can be summarized as follows:
1) Study drug supplies to participants and sites:
a) Participants may be unable to return to the site for a number of visits to get the study drug, 
or the site may be unable to accept any participant visits.
Mitigation plan: Study drug supplies may be provided to the participant from the site without 
a clinic visit, once it is confirmed that the HIV test result is negative and the participant may 
safely continue on study drug as determined by the principal investigator (PI). A virtual study 
visit, via phone or video conferencing, must be performed prior to remote study drug 
resupply. Prior to the virtual visit, the PI or qualified designee should contact the participant 
to obtain verbal consent from the participant to ship and perform the home rapid HIV test or 
arrange for the participant to attend a local lab/facility for HIV testing. Participant should be 
given clear instructions on how to perform the HIV test. The date and time that consent was 
obtained must be documented in the participant’s medical records. The PI or qualified 
designee will then perform the virtual visit, including review of the HIV test result, within 
the protocol target visit window dates whenever possible. The calls should be documented in 
the source documents at the site and relevant information entered in EDC. At the earliest 
opportunity, the site will schedule in-person participant visits and return to the protocol’s 
regular schedule of assessments. The HIV test result must be obtained prior to dispensing 
and/or shipping of the study drug to the participant. A qualified courier may be utilized to 
ship the study drug from sites to study participants if permitted by local ethics committee 
(EC)/institutional review boards (IRB)/Regulatory Authority as applicable and with sponsor's 
approval.
b) Shipments of study drug could be delayed because of transportation issues. Without study 
drug participant would not be able to stay on the study drug as planned per protocol.
Mitigation plan: The sites' study drug inventory should be closely monitored. Site staff 
should notify the sponsor or delegate if they foresee shortage in study drug inventory or if 
there is any interruption in local shipping service. The sponsor will continue to monitor 
inventory at the study drug depot and study sites. Manual shipments will be triggered as 
necessary.
c) Stopping or interrupting study drug may lead to resistance to study drug components.
Mitigation plan: Participant may stop study drug per protocol and go on a preapproved 
drug-holiday. Drug holidays are approved by the Gilead medical monitor. Following a drug 
holiday or drug interruption for more than 14 days, protocol Section 6.8 must be followed 
when study drug is re-started. Drug holidays will not be approved after OL Week 96.

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2) Participant safety monitoring and follow-up:
a) Participants may be unable or unwilling to come to the study site for their scheduled 
study visits as required per protocol.
Mitigation plan: For participants who may be unable or unwilling to visit the study site for 
their scheduled study visits as required per protocol, the PI or qualified delegate will conduct 
a virtual study visit, via phone or video conferencing, to assess the participant within target 
visit window date whenever possible. During the virtual study visit, the following 
information at minimum will be reviewed:
i)
Confirm if participant has experienced any adverse events (AEs/serious adverse 
events [SAEs]/special situations) and follow up on any unresolved AE/SAEs.
ii)
Review current list of concomitant medications and document any new 
concomitant medications.
iii)
Confirm participants study drug supply is sufficient to last until the next planned 
visit date. If study drug resupply is needed it will be provided as described above 
in (1).
iv)
Remind participant to maintain current dosing and to keep all dispensed study 
drug kits for return at the next on-site visit.
b) Participants may be unable or unwilling to travel to the site for planned assessments (eg, 
safety blood draws); hence samples may not be sent for central lab analyses.
Mitigation plan: A local lab may be utilized per PI discretion to monitor the participant safety 
until the participant can return for their regular follow up per protocol. Any laboratory 
assessments conducted at a local lab due to the pandemic will be documented accordingly.
A)
HIV testing must occur every 3 months per PrEP standard of care. Per protocol, 
HIV testing is performed locally by site. If a participant is unable to attend a study 
visit, participant may either utilize a local laboratory/facility/resource to perform 
the HIV test or may perform home HIV testing prior to receiving study drug in 
agreement with CDC guidance.
B)
If study drug was shipped without HIV testing and no subsequent rapid HIV test 
result is available, site should arrange for HIV testing to be performed 
immediately either via an onsite visit or via remote testing (home or local lab) and 
the result should be provided to the site. If it has been more than 6 months since 
the last rapid HIV test, participant should attend site for an on-site fourth or fifth 
generation Ab/Ag test or should have this test performed at a local lab and if this 
is not possible discuss with the medical monitor regarding study continuation. 
Information on study-drug adherence and site’s risk / benefit assessment must be 
documented in the source notes and in EDC (and the IPD if applicable). Where 

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HIV testing was not completed, the medical monitor should be provided the 
participant risk-benefit assessment for review.
C)
If participants are unable to go to site for more than 6 months, safety labs should 
be sent to the central lab where possible. If labs cannot be sent to the central lab, 
the participant may have safety labs performed locally, which should include at 
minimum a serum creatinine level to assess renal function and STI testing, in 
accordance with PrEP standard of care.
c) Participants may be unable or unwilling to attend the study visit to sign an updated 
informed consent form (ICF) version.
Mitigation plan: The site staff will follow their approved consent process and remain in 
compliance with local EC/IRB and national laws and regulations. Remote consent will be 
allowed if has been approved by the local EC/IRB. The consent process will be documented 
in the source and confirmed by normal consent procedure at the earliest opportunity.
3) Protocol and monitoring compliance:
a) Protocol deviations may occur, in case scheduled visits cannot occur as planned per 
protocol.
Mitigation plan: If it is not possible to complete a required procedure, an unscheduled visit 
should be conducted as soon as possible when conditions allow. The situation should be 
recorded and explained as a protocol deviation. Any missed participant visits or deviation to 
the protocol due to the pandemic must be reported in the eCRF and described in the clinical 
study report. Any virtual study visits that are conducted in lieu of clinic visits due to the 
pandemic will be documented as a protocol deviation related to the pandemic. Home HIV 
testing or HIV testing at a local lab will be recorded as a protocol deviation.
i)
If ESDD is performed remotely, where possible, the safety follow-up visit should 
be completed on-site including all required assessments to ensure that we are not 
transferring participants to off-study PrEP services who have HIV or should not 
be on PrEP for safety reasons. If the CASI questionnaire (prior to OL Week 96) 
and DXA scan was not completed, where possible site should schedule both at the 
safety-follow-up visit (DXA only for applicable sites).
b) Monitors may be unable to carry out source data review (SDR) or source data verification 
(SDV), or study drug accountability or assess protocol and GCP compliance. This may 
lead to delays in SDV, an increase in protocol deviations, or under reporting of AEs.
Mitigation plan: The study monitor is to remain in close communication with the site to 
ensure data entry and query resolution. The study monitor is to reference the Study 
Monitoring Plan for guidance on how to conduct a remote monitoring visit. The study staff is 
to save and document all relevant communication in the study files. The status of sites that 
cannot accept monitoring visits and/or participants on site, must be tracked centrally and 
updated on a regular basis.

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4) Missing data and data integrity:
a) There may be an increased amount of missing data due to participants missing 
visits/assessments. This could have an impact on the analysis and the interpretation of 
clinical trial data.
Mitigation plan: Implications of a pandemic on methodological aspects for the study will 
be thoroughly assessed and documented, and relevant actions will be taken as appropriate 
(ie, modification of the statistical analysis plan) and in compliance with Regulatory 
Authorities’ guidance. Overall, the clinical study report will describe the impact of the 
pandemic on the interpretability of study data.
Risks will be assessed continuously, and temporary measures will be implemented to mitigate 
these risks as part of a mitigation plan, as described above. These measures will be 
communicated to the relevant stakeholders as appropriate and are intended to provide alternate 
methods that will ensure the evaluation and assessment of the safety of participants who are 
enrolled in this study.
Since these potential risks are considered mitigated with the implementation of these measures, 
the expected benefit-risk assessment of study drug in study participants remains unchanged.