Conditions: HIV-1
Keywords: emtricitabine FTC tenofovir TDF antiretroviral adolescents children pediatric TAF
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 41
Healthy volunteers: no

Brief summary:
The primary objective of this study is to confirm the TAF dose and to evaluate the pharmacokinetics (PK) of TAF, safety, and tolerability of F/TAF in children and adolescents with HIV-1 who are virologically suppressed (defined as having \< 50 copies/mL of HIV-1 ribonucleic acid (RNA) for a period of at least 6 months) while on a stable 2 NRTI containing regimen.

Detailed description:
A minimum of 100 participants in total (across all cohorts) aged 1 month to \<18 years of age will be enrolled to receive F/TAF. The study will proceed in sequential cohorts as follows: Cohort 1 will switch their current 2-NRTI-containing regimen to F/TAF while continuing on their 3rd ARV agent through 48 weeks; Cohorts 2, 3, and 4 must be on a boosted protease inhibitor (PI) (Cohort 2 only) or any other 3rd ARV agent and will switch their current 2-NRTI-containing regimen to F/TAF while continuing their boosted PI or 3rd ARV agent through 48 weeks. A minimum of 10 participants each in Groups 1 and 2 of Cohort 2, and Cohorts 3 and 4, who are on boosted-ATV as their 3rd ARV agent will be enrolled. Cohorts 2, 3, and 4 will be enrolled by cohort into a two-part study (Parts A and B).

After completion of 48 weeks, all participants will be given the option to participate in an extension phase of the study. Gilead will provide F/TAF until a) The participant turns 18 years old and F/TAF is commercially available for use in adults in the country in which the participant is enrolled or b), F/TAF becomes commercially available for pediatric use in the country in which the participant is enrolled or c), Gilead Sciences elects to terminate development of F/TAF in the applicable country.

However, Cohort 2 (Part B), Cohorts 3 and 4 were not conducted as planned.

Arms:
arm 1: Participants between 12 to \< 18 years of age and ≥ 35 kg in body weight will switch their current 2-NRTI containing regimen to F/TAF (200/25 mg for unboosted 3rd agent and 200/10 mg for boosted 3rd agent) while continuing on their 3rd ARV agent for 48 weeks. arm 2: Participants between 6 to \< 12 years of age and ≥ 25 kg in body weight must be on a boosted protease inhibitor (PI) as their 3rd ARV agent and will switch their current 2-NRTI regimen to F/TAF 200/25 mg while continuing on their boosted PI for 48 weeks. arm 3: Participants between 2 to \< 12 years of age and between 17 kg to \< 25 kg in body weight must be on a boosted protocol specified 3rd ARV agent and will switch their current 2-NRTI containing regimen to F/TAF 120/15 mg while continuing their 3rd ARV agent for 48 weeks. arm 4: Participants between 2 to \< 6 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks. arm 5: Participants between 1 month to \< 2 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks. arm 6: Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks. arm 7: Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks. arm 8: Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks. arm 9: Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks. arm 10: After completion of 48 weeks, all participants will be given the option to participate in an extension phase of the study. Gilead will provide F/TAF until a) the participant turns 18 and F/TAF is commercially available for use in adults in the country in which the participant is enrolled or, b) F/TAF becomes commercially available for pediatric use in the country in which the participant is enrolled or, c) Gilead Sciences elects to terminate development of F/TAF in the applicable country.

Interventions: intervention 1: F/TAF intervention 2: 3rd ARV agent intervention 3: Boosted PIs
Intervention descriptions: intervention 1: F/TAF tablets administered orally once daily intervention 2: A 3rd antiretroviral (ARV) agent may include one of the following: allowed boosted 3rd ARV agents: lopinavir (LPV), atazanavir (ATV), darunavir (DRV); Allowed unboosted 3rd ARV agents: efavirenz (EFV), raltegravir (RAL), dolutegravir (DTG), or nevirapine (NVP) intervention 3: Allowed boosted PIs: LPV, ATV, DRV.

Protocol document:
Prot_002.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Clinical Program 
Manager: 
Gilead Medical Monitor: 
Clinical Study Director: 
Protocol Version/Date: 
[!'J GI LEAU 
CLINICAL STUDY PROTOCOL 
A Phase 2/3, Open-Label, Multi-Cohort Switch Study to Evaluate 
Emtricitabine/f enofovir Alafenamide (F/f AF) in HIV-1 Infected 
Children and Adolescents Virologically Suppressed on a 
2-NRTI-Containing Regimen 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
111851 
2015-001339-19 
NCT02285114 
HIV-1 
GS-US-311-1269 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Fax: 
Name: 
Telephone: 
Mobile: 
Fax: 
Original: 
Amendment 1: 
Amendment 1.1 (South Africa): 
Amendment 2: 
[PPD 
[PPD 
[PPD 
[PPD 
[PPD 
[PPD 
[PPD 
[PPD 
[PPD 
[PPD 
23 June 2014 
20 November 2014 
04 March 2015 
02 August 2017 
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. 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................15
1.
INTRODUCTION ..............................................................................................................................................19
1.1.
Background ............................................................................................................................................19
1.2.
Tenofovir Alafenamide (TAF, GS-7340)...............................................................................................21
1.2.1.
General Information .............................................................................................................21
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................22
1.2.3.
Nonclinical Pharmacokinetics..............................................................................................22
1.2.4.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed-Dose Combination (FDC) emtricitabine/tenofovir alafenamide 
(F/TAF)................................................................................................................................22
1.3.
Emtricitabine (FTC, Emtriva®) ..............................................................................................................23
1.4.
Rationale for This Study ........................................................................................................................24
1.5.
Rationale for Dose Selection..................................................................................................................24
1.5.1.
F/TAF Dose in Adolescents 12 to < 18 years of Age Weighing ≥ 35 kg.............................24
1.5.2.
F/TAF Dose in Children 6 to < 12 Years of Age Weighing ≥ 25 kg and 
2 to < 12 Years of Age Weighing 17 to < 25 kg ..................................................................25
1.5.3.
Dosing in Cohorts 3 (2 to < 6 Years) and 4 (1 Month to < 2 Years)....................................28
1.6.
Risk/Benefit Assessment for the Study..................................................................................................28
1.7.
Compliance ............................................................................................................................................28
2.
OBJECTIVES.....................................................................................................................................................29
3.
STUDY DESIGN................................................................................................................................................30
3.1.
Primary Endpoints..................................................................................................................................30
3.1.1.
Secondary Endpoints............................................................................................................30
3.2.
Study Design..........................................................................................................................................30
3.2.1.
Cohort 1 (Adolescents 12 to < 18 years, ≥ 35 kg)................................................................31
3.2.2.
Cohorts 2, 3, and 4 ...............................................................................................................31
3.2.3.
Study Procedures and Frequency for All Subjects (All Cohorts and 
Parts A and B)......................................................................................................................32
3.3.
Study Treatments ...................................................................................................................................34
3.4.
Duration of Treatment............................................................................................................................35
3.5.
Criteria for Discontinuation of Study Treatment....................................................................................35
4.
SUBJECT POPULATION..................................................................................................................................37
4.1.
Number of Subjects and Subject Selection ............................................................................................37
4.2.
Inclusion Criteria....................................................................................................................................37
4.3.
Exclusion Criteria...................................................................................................................................39
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................41
5.1.
Enrollment..............................................................................................................................................41
5.2.
Description and Handling.......................................................................................................................41
5.2.1.
Formulations.........................................................................................................................41
5.2.2.
Packaging and Labeling .......................................................................................................42
C


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5.2.3.
Storage and Handling...........................................................................................................42
5.3.
Dosage and Administration....................................................................................................................43
5.3.1.
Cohort 1 (12 years to < 18 years, ≥ 35 kg)...........................................................................43
5.3.2.
Cohorts 2, 3, and 4 ...............................................................................................................43
5.4.
Prior and Concomitant Medications.......................................................................................................44
5.5.
Accountability........................................................................................................................................45
5.6.
Investigational Medicinal Product Return or Disposal...........................................................................45
6.
STUDY PROCEDURES ....................................................................................................................................46
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................46
6.2.
Pretreatment Assessments......................................................................................................................46
6.2.1.
Screening Visit .....................................................................................................................46
6.2.2.
Baseline/Day 1 Assessments................................................................................................48
6.3.
Treatment Assessments through 48 Weeks (Weeks 1 (Day 7) − 48).....................................................50
6.4.
Early Study Drug Discontinuation (ESDD) ...........................................................................................55
6.5.
30-Day Follow-Up Visit.........................................................................................................................56
6.6.
Post Week 48 Assessments (every 12 weeks)........................................................................................58
6.7.
Bone Evaluations ...................................................................................................................................60
6.8.
Bone and Renal Safety Evaluations .......................................................................................................60
6.10.
Virologic Failure and Management of Virologic Rebound....................................................................61
6.10.1.
Subjects with ≥ 400 copies/mL of HIV-1 in Absence of Confirmed 
Virologic Failure..................................................................................................................62
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................63
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................63
7.1.1.
Adverse Events.....................................................................................................................63
7.1.2.
Serious Adverse Events........................................................................................................63
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................64
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................64
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................64
7.2.2.
Assessment of Severity ........................................................................................................65
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................65
7.4.
Gilead Reporting Requirements.............................................................................................................67
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events..........................................................................................................................68
7.5.1.
Toxicity Management...........................................................................................................68
7.5.2.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................68
7.5.3.
Grades 3 Laboratory Abnormality or Clinical Event ...........................................................68
7.5.4.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................69
7.5.5.
Management of Hyperbilirubinemia in Patients Receiving Ritonavir 
Boosted Atazanavir ..............................................................................................................69
7.6.
Special Situations Reports......................................................................................................................70
7.6.1.
Definitions of Special Situations..........................................................................................70
7.6.2.
Instructions for Reporting Special Situations.......................................................................70
8.
STATISTICAL CONSIDERATIONS................................................................................................................72
8.1.
Analysis Objectives and Endpoints........................................................................................................72
8.1.1.
Analysis Objectives..............................................................................................................72
8.1.2.
Primary Endpoints................................................................................................................72
8.1.3.
Secondary Endpoints............................................................................................................72
CCI
CCI


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8.2.
Analysis Conventions.............................................................................................................................73
8.2.1.
Analysis Sets ........................................................................................................................73
8.3.
Data Handling Conventions ...................................................................................................................74
8.4.
Demographic Data and Baseline Characteristics ...................................................................................74
8.5.
Efficacy Analysis ...................................................................................................................................74
8.5.1.
Primary Analysis..................................................................................................................74
8.5.2.
Secondary Analyses .............................................................................................................75
8.6.
Safety Analysis.......................................................................................................................................75
8.6.1.
Extent of Exposure...............................................................................................................75
8.6.2.
Adverse Events.....................................................................................................................75
8.6.3.
Laboratory Evaluations ........................................................................................................76
8.6.4.
Bone Mineral Density ..........................................................................................................76
8.6.5.
Bone and Renal Safety Evaluations .....................................................................................76
8.6.6.
Tanner Stage Assessment.....................................................................................................76
8.6.7.
Acceptability and Palatability ..............................................................................................76
8.6.8.
Other Safety Evaluations......................................................................................................77
8.7.
Pharmacokinetic Analysis......................................................................................................................77
8.8.
Acceptability and Palatability ................................................................................................................77
8.9.
Sample Size............................................................................................................................................77
8.10.
Data Monitoring Committee ..................................................................................................................78
8.11.
Analysis Schedule ..................................................................................................................................79
8.12.
Endpoint Adjudication Committee.........................................................................................................79
9.
RESPONSIBILITIES..........................................................................................................................................80
9.1.
Investigator Responsibilities ..................................................................................................................80
9.1.1.
Good Clinical Practice..........................................................................................................80
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................80
9.1.3.
Informed Consent.................................................................................................................80
9.1.4.
Confidentiality......................................................................................................................81
9.1.5.
Study Files and Retention of Records ..................................................................................81
9.1.6.
Case Report Forms...............................................................................................................82
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................83
9.1.8.
Inspections............................................................................................................................83
9.1.9.
Protocol Compliance............................................................................................................83
9.2.
Sponsor Responsibilities ........................................................................................................................84
9.2.1.
Protocol Modifications.........................................................................................................84
9.2.2.
Study Report and Publications .............................................................................................84
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................84
9.3.1.
Payment Reporting...............................................................................................................84
9.3.2.
Access to Information for Monitoring..................................................................................85
9.3.3.
Access to Information for Auditing or Inspections ..............................................................85
9.3.4.
Study Discontinuation..........................................................................................................85
10.
REFERENCES ...................................................................................................................................................86
11.
APPENDICES ....................................................................................................................................................88
Appendix 1.
Investigator Signature Page....................................................................................................89
Appendix 2.
Study Procedures Table..........................................................................................................90
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................94
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............95
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................115


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Appendix 6.
Definitions of HIV-1 Related Disease..................................................................................118
Appendix 7.
Tanner Stages .......................................................................................................................120
LIST OF IN-TEXT TABLES
Table 1-1.
TAF AUC upon Co-administration of TAF (10 or 25 mg) with 3rd Agent in Adults.............23
Table 1-2.
Pediatric F/TAF Dosing and Tablet Strength by Body Weight..............................................25
Table 4-1.
Prohibited Medication while on Study ...................................................................................40
Table 5-1.
Cohort 1 Dosing Recommendation for F/TAF in combination with 3rd ARV Agents ...........43
Table 5-2.
Cohorts 2, 3, and 4 Dosing Recommendations for F/TAF .....................................................44
Table 5-3.
List of Prohibited Medications and Medications That Are To Be Used With Caution ..........44
Table 5-4.
List of Prohibited Medications with Adverse Skeletal Effects...............................................45
LIST OF IN-TEXT FIGURES
Figure 1-1.
Predicted TAF AUC in Children Following Administration of F/TAF 200/25 mg or 
120/15 mga,b,c..........................................................................................................................26
Figure 1-2.
Predicted TFV AUC in Children Following Administration of F/TAF 200/25 mg or 
120/15 mga,b,c..........................................................................................................................27
Figure 3-1.
Study Schema.........................................................................................................................34
Figure 6-1.
Virologic Rebound Schema....................................................................................................62


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc. 
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 2/3, Open-Label, Multi-Cohort Switch Study to Evaluate 
Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected 
Children and Adolescents Virologically Suppressed on a 
2-NRTI-Containing Regimen
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
111851
2015-001339-19
NCT02285114
Study Centers Planned:
Approximately 25 centers globally.
Objectives:
The primary objectives of this study are:

To evaluate the pharmacokinetics (PK) of tenofovir alafenamide 
(TAF) and confirm the TAF dose in HIV-1 infected children and 
adolescents virologically suppressed on a 2-NRTI-containing 
regimen

To evaluate the safety and tolerability of emtricitabine/tenofovir 
alafenamide (F/TAF) through Week 24
The secondary objectives of this study are: 

To evaluate the PK of tenofovir (TFV) and emtricitabine (FTC)

To evaluate the safety, tolerability, and efficacy of F/TAF 
through Week 48
Study Design:
Open-label, multi-cohort switch study to evaluate the PK, safety, and 
efficacy of F/TAF in HIV-1 infected children (1 month to < 12 years) 
and adolescents (12 to <18 years) who are virologically suppressed 
(HIV-1 RNA < 50 copies/mL for at least 6 consecutive months) on a
stable 2-NRTI-containing regimen.
A minimum of 100 subjects aged 1 month to < 18 years of either sex 
will be enrolled as follows:
Cohort 1 (adolescents 12 to < 18 years, ≥ 35 kg):
All subjects in Cohort 1 (n = 25) will switch their current 
2-NRTI-containing regimen to F/TAF while continuing their
3rd antiretroviral (ARV) agent through 48 weeks. 


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An intensive PK (IPK) evaluation will be conducted at the Week 2
visit. TAF dose confirmation will be established if the exposure is 
comparable to that associated with efficacy in adults.
All subjects in Cohort 1 will continue to receive F/TAF plus their 
3rd ARV agent and return for study visits through Week 48.
Cohorts 2, 3, and 4
Cohorts 2, 3, and 4 will be enrolled by cohort into two parts 
(Parts A and B). Cohort 2 consists of 2 groups: Group 1 weighing 
≥25 kg and Group 2 weighing 17 kg to < 25 kg.
All subjects in Cohort 2 Group 1 must be on a boosted protease 
inhibitor (PI) as their 3rd ARV agent and will switch their current 
2-NRTI-containing regimen to open-label F/TAF while continuing 
their boosted PI through 48 weeks. 
All subjects in Cohort 2, Group 2 and Cohorts 3 and 4 will be on a 
boosted PI or other protocol-specified 3rd agents and will switch their 
current 2-NRTI-containing regimen to open-label F/TAF while 
continuing their 3rd agents through 48 weeks. 
A minimum of 10 subjects who are on boosted-ATV as their 
3rd ARV agent will be enrolled into Part A of each group of Cohort 2, 
as well as Cohorts 3 and 4. 
Cohorts 2, 3, and 4 will be enrolled as follows: 
Part A
Cohort
Age Range
Weight 
Range
Number of Subjects
ATV + 
F/TAF
LPV or 
DRV 
+ F/TAF
Other 3rd
ARV Agents 
+ F/TAF
2, Group 1
6 to < 12 years
≥ 25 kg
n ≥ 10
n ≥6
n/a
2, Group 2 
(subjects able
to swallow a 
tablet)
2 to < 12 years
17 kg to 
< 25 kg 
n ≥ 10
n ≥7
3b (subjects 
unable to 
swallow a
tablet)
2 to < 6 years
TBD
n ≥ 10
n ≥7
4a,b
1 month to 
< 2 years
TBD
n ≥ 10
n ≥7
a
DRV is not approved for Cohort 4
b
Formulation, dosing, and population specific details for Cohorts 3 and 4 will be added 
via a protocol amendment after data is obtained from Cohort 2.
All subjects in Part A will undergo an IPK evaluation at either the 
Week 2 or Week 4 visit (+7 days) to confirm the dose of TAF.


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Part B
Screening will be initiated for Part B following confirmation of TAF 
dose in Part A for each group of Cohort 2 and Cohorts 3 and 4. 
Approximately 10 additional total subjects will be enrolled in Part B 
and will receive F/TAF while continuing their 3rd ARV agent
through 48 weeks.
Number of Subjects 
Planned:
A minimum of 100 subjects will be enrolled. 
Target Population:
HIV-1 infected adolescents and children who have been virologically 
suppressed for ≥6 consecutive months prior to screening on a stable 
2-NRTI-containing regimen.
Duration of 
Treatment:
Subjects will receive study treatment for at least 48 weeks. 
After completion of 48 weeks of treatment in the study, all eligible
subjects will be given the option to participate in an extension phase 
of the study in which visits will occur every 12 weeks. Gilead will 
provide F/TAF until: 
a) the subject turns 18 years old and F/TAF is commercially available 
for use in adults in the country in which the subject is enrolled, or
b) F/TAF becomes commercially available for pediatric use in the 
country in which the subject is enrolled, or 
c) Gilead Sciences elects to terminate development of F/TAF in the 
applicable country.
Diagnosis and Main 
Eligibility Criteria:
HIV-1 infected pediatric patients at Baseline/Day 1. 
Currently on a stable 2-NRTI-containing regimen that includes a 
3rd ARV agent for ≥6 consecutive months prior to screening.
Body weight and age at screening for all cohorts is as follows:
Cohort
Age Range
Weight
1
12 years to < 18 years
≥ 35 kg
2 (Group 1)
6 years to < 12 years
≥ 25 kg
2 (Group 2) (subjects able to 
swallow a tablet)
2 years to < 12 years
17 kg to < 25 kg
3 (subjects unable to swallow a tablet)
2 years to < 6 years
TBDa
4
1 month to < 2 years
TBDb
a
Body weight cutoff at screening to be determined based upon analysis of short-term
safety and PK data from Cohort 2 Part A before initiating Cohort 3 Part A
b
Body weight cutoff at screening to be determined based upon analysis of short-term
safety and PK data from Cohort 2 Part A & Cohort 3 Part A


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No documented or suspected resistance to TFV or FTC, including, 
but not limited to, the presence of reverse transcriptase mutations 
K65R, K70E, M184V/I, or 3 or more thymidine analog-associated 
mutations (TAMs) that include M41L or L210W (TAMs are M41L, 
D67N, K70R, L210W, T215Y/F, K219Q/E/N/R).
No laboratory evidence of current active HBV or HCV infection.
Plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 consecutive 
months.
Estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 by 
(Schwartz) formula.
Study Procedures/
Frequency:
At the Screening, Baseline/Day 1, and all subsequent study visits,
laboratory analyses (hematology, chemistry, and urinalysis), 
HIV-1 RNA, CD4+ cell count, complete or symptom directed 
physical examinations, and eGFR using the Schwartz formula will be 
performed. Serum (screening) or urine (all other visits) pregnancy 
tests will be performed on female subjects of childbearing potential.
At screening, HBV and HCV serology will be analyzed.
Subjects will return for study visits at Weeks 1, 2, 4, 8, 12, 24, 36,
and 48. After completion of 48 weeks of treatment in the study, all 
eligible subjects will be given the option to participate in an 
extension phase of the study in which visits will occur every 
12 weeks.
Adverse events and concomitant medications will be assessed at each 
visit.
Serum will be collected for bone safety tests (collected fasted):

Cohort 1 only: Baseline/Day 1, Weeks 4, 12, 24, and 48 and 
every 24 weeks thereafter.

Cohorts 2, 3, and 4: Baseline/Day 1, Weeks 8, 12, 24, 48, and 
every 24 weeks thereafter
For all Cohorts, urine will be collected for urine chemistry and 
selected renal safety tests, including retinol binding protein and 
beta-2-microglobulin, at Baseline/Day 1, Weeks 2, 4, 8, 12, 24, 48,
and every 12 weeks thereafter.
For Cohorts 1 and 2 (all groups), metabolic assessments will be 
collected for fasting glucose and lipid panel (total cholesterol, HDL, 
direct LDL, and triglycerides) at Baseline/Day 1, Weeks 24, 48, and 
every 24 weeks (±10 days) thereafter. The fasting requirement for 
Cohorts 3 and 4 will be specified in a future protocol amendment.


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Tanner stage assessment (Appendix 7) will be performed for subjects 
≥6 years of age at the time of the visit at Baseline/Day 1, 
Weeks 24, 48, and every 12 weeks thereafter, or until subjects reach 
Tanner Stage 5, after which point Tanner assessments will no longer 
be performed.
For all Cohorts, dual energy x-ray absorptiometry (DXA) scans of 
the lumbar spine and total body will be performed at Baseline/Day 1, 
Weeks 24, 48, and every 24 weeks thereafter to measure spine bone 
mineral density (BMD) and total body BMD.
PK sampling:
Single PK samples will be collected at the following visits for all 
cohorts:

Weeks 1 and 24: a single random PK sample.

Weeks 4 and 12: a single observed dosing PK sample at any time 
between 15 min to 4 hours post dose. (Note: Single observed 
dosing PK sample does not need to be collected at Week 4 if 
Intensive PK is also collected at the Week 4 visit)

Week 8: a trough sample at 0 hours (pre-dose, ≤ 30 minutes prior 
to dosing) at Week 8.
Intensive PK sampling:

Cohort 1 will participate in an Intensive PK (IPK) evaluation at 
the Week 2 visit as detailed in the PK manual.

Cohort 2 Part A will participate in an IPK evaluation during
either the Week 2 or Week 4 visit or within 7 days after the 
completion of Week 2 or Week 4 visit as detailed in the PK 
manual. The IPK collection schedule and fasting requirement for 
Cohorts 3 and 4 will be specified in a future protocol amendment.
PBMC collection:

PBMC collection will be performed at study sites that can 
perform PBMC processing. 

Cohorts 1 and 2: PBMC collection will be performed at the 
Week 8 visit. 

Cohort 3, and 4: PBMC collection schedule will be specified in a
future protocol amendment.


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Palatability and Acceptability Assessment:

Cohort 1: At the Week 2 visit, palatability and acceptability will 
be assessed 30 - 60 minutes after study drug dosing for all 
subjects undergoing IPK sampling. Acceptability will also be 
assessed 30 - 60 minutes after study drug dosing for active 
subjects at the next study visit immediately following approval of 
this protocol at the site.

Cohort 2 Part A: Palatability and acceptability will be assessed at 
the Week 2 or Week 4 visit, or within 7 days after the completion 
of the Week 2 or Week 4 visit, 30 - 60 minutes after study drug 
dosing for all subjects undergoing IPK sampling.

Cohorts 3 and 4 Part A: Palatability and acceptability will be 
assessed for subjects undergoing IPK sampling. Assessment 
schedule will be specified in a future protocol amendment.
Subjects who prematurely discontinue from the study or do not 
participate in the extension phase will be required to return to the 
clinic for a 30-Day Follow-up Visit.
Test Product, Dose, and 
Mode of 
Administration:
F/TAF tablets administered orally QD in combination with a 
3rd ARV agent, with or without food (as determined by the 3rd ARV 
agent), dosed as follows:
Cohort
Age and body weight
F/TAF dose (mg) with 3rd agent
1
12 to <18 years, ≥35 kg
200/25 for unboosted 3rd agent
200/10 for boosted 3rd agent
2, Group 1
6 to < 12 years, ≥25 kg
200/25
2, Group 2
(subjects able to 
swallow a tablet)
2 to < 12 years,
≥17 to < 25 kg
120/15 
3 (subjects unable 
to swallow a 
tablet)
2 to < 6 years, TBD
TBDa
4
1 month to < 2 years, TBD
TBDa
a
Dose, formulation, and population specific details will be specified by protocol 
amendment after clinical safety, efficacy, and PK data from Cohorts 1 and 2 are 
available to guide dose and formulation selection of F/TAF to be administered in 
Cohorts 3 and 4.


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Criteria for Evaluation:
Safety:
Adverse events and clinical laboratory tests, including selected renal
and bone safety tests and BMD (assessed by DXA)
Efficacy:
The efficacy endpoints are:

The percentage of subjects with HIV-1 RNA < 50 copies/mL at 
Weeks 24 and 48 as defined by the US FDA-defined snapshot 
algorithm 

The change from baseline in CD4+ cell count (cells/μL) and 
CD4+ percentage at Weeks 24 and 48
Pharmacokinetics:
The following plasma PK parameters will be calculated for TAF, 
TFV and FTC (as applicable): AUCtau, AUClast, Ctau, Cmax, Clast, Tmax, 
Tlast, λz, apparent CL, apparent Vz, and T½.
 
Statistical Methods:
Plasma concentration and parameters of TAF, TFV, and FTC will be 
summarized using descriptive statistics by cohort, dose level and 
type of boosted PI (eg, ATV/r or other PIs/r) if applicable. The 
AUCtau of TAF obtained in subjects from Cohort 1 or Part A of 
Cohort 2 Groups 1 and 2, Cohort 3, and Cohort 4, respectively, will 
be compared to historical adult data (ie, Study GS-US-311-1089). 
The comparisons will be conducted within each cohort and by dose 
level (ie. 200/25 mg vs 200/10 mg), when applicable. TAF dose 
confirmation will be established if the lower bound of the 
90% confidence interval (CI) of the geometric mean ratio (pediatric 
subjects vs adult subjects) is above 70% for TAF AUCtau. The 
95% CI of the geometric mean estimates of Cl/F and Vz /F will also 
be constructed for TAF. 
For efficacy and safety endpoints, results from each group or cohort
will be descriptive in nature. F/TAF results from each cohort will 
also be combined to describe the overall efficacy and safety profile 
of F/TAF in pediatric subjects. 
The percentage of subjects with HIV-1 RNA < 50 copies/mL at 
Weeks 24 and 48 as defined by the US FDA-defined snapshot 
algorithm will be summarized by group or cohort. The 95% CI for 
the point estimate for F/TAF will be constructed. 
CCI


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The change from baseline in CD4+ cell count and CD4+ percentage 
will be summarized by visit, group, and coho1i using descriptive 
statistics. 
Bone and renal safety test data will be summarized by visit, group, 
and coho1i. The incidences of treatment-emergent adverse events and 
treatment-emergent laborato1y abno1malities will be summarized by 
group, coho1i, and overall. 
Cohort 1: Twenty-five subjects in Coho1i 1 will provide at least 
90% power to target a 95% confidence interval within 60% and 
140% of the geometric mean estimate of apparent CL and apparent 
V2 of TAF, respectively, assuming a standard deviation of 0.60 for 
CL and 0.58 for V2 (natural log scale) estimated from 
Study GS-US-292-0106 Cohort 1 Pait A. 
Cohort 2 (Group 1) Part A: At least 10 subjects on boosted 
ATV+ F/TAF and 6 subjects on boosted LPV or DRV + F/TAF, 
compared with the population PK data from 44 adult subjects on 
boosted ATV+ F/TAF and 87 adult subjects on boosted LPV or 
DRV + F/TAF in Study GS-US-311-1089, respectively, will each 
provide at least 80% power to show the lower bound of a 90% CI of 
geometric mean ratio (pediatric subjects vs. adult subjects) greater 
than 70% for AUC1au of TAF, assuming that the expected geometric 
mean ratios of TAF AUC1au between pediatric subjects and adult 
subjects are equal to 1 and the standai·d deviations are 0.40 
(with boosted ATV + F/TAF) and 0.33 (with boosted LPV or 
DRV + F/TAF) ng*hr/mL for TAF AUCiau (natural log scale) 
estimated from the population PK data in Study GS-US-311-1089. 
Cohorts 2 (Group 2), 3, and 4, Part A: At least 10 subjects on 
boosted ATV+F/TAF and at least 7 subjects on any other 
3rd agent + F/TAF in each group or cohort, compai·ed with the 
population PK data from 292 adult subjects on any 3rd agent + F/TAF 
in Study GS-US-311-1089, will provide 90% power to show the 
lower bound of a 90% CI of geometric mean ratio (pediatric subjects 
vs. adult subjects) greater than 70% for AUCiau ofTAF, assuming 
that the expected geometric mean ratio ofTAF AUCtau between 
pediatric subjects and adult subjects is equal to 1 and the standard 
deviation is 0.48 ng*hr/mL for TAF AUCiau (natural log scale) 
estimated from the population PK data in Study GS-US-311-1089. 
Page 13 
02 August 2017 


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A total of at least 100 subjects receiving F/TAF from Cohort 1, 
Parts A and B of Cohort 2 (Groups 1 and 2), Cohort 3, and Cohort 4 
combined will provide reasonable assessment of safety through 
Week 48 in pediatric subjects.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents. 


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
° C 
degrees Celsius
° F
degrees Fahrenheit
AE
adverse event
AIDS
Acquired Immune Deficiency Syndrome
AK
adenylate kinase
ALT
alanine aminotransferase
ARV
Antiretroviral
AST
aspartate aminotransferase
ATV/r
ritonavir boosted atazanavir 
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration versus time 
curve
AUCtau
area under the concentration verses time curve over the dosing interval
BsAP
Bone specific alkaline phosphatase
BMD
bone mineral density
BUN
blood urea nitrogen
CBC
complete blood count
Clast
the last observed quantifiable plasma concentration of drug
CL/F
the apparent oral clearance after administration of the drug: 
CL/F Dose/AUCinf
where “Dose” is the dose of the drug
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CNS
central nervous system
COBI, /co
cobicistat 
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CSR
Clinical Study Report
CTX
type 1 collagen crosslinked C-telopeptide
DXA
Dual-energy X-ray absorptiometry
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DRV/r
ritonavir boosted darunavir
DSPH
Drug Safety and Public Health
DTG
Dolutegravir
D2000006
Gilead pre-clinical study: “A cardiovascular profile study following a single oral 
administration of GS-7340 in the unrestrained conscious beagle dog”
ECG
Electrocardiogram
EDC
electronic data capture


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eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
EFV
Efavirenz
EVG
elvitegravir 
E/C/F/TAF
elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 
200 mg/tenofovir alafenamide (TAF) 10 mg single tablet regimen
ESDD
Early Study Drug Discontinuation
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
Fixed-Dose Combination
FTC
Emtricitabine
F/TAF
emtricitabine/tenofovir alafenamide
GCP
Good Clinical Practice (Guidelines)
GSI
Gilead Sciences, Inc.
GS-7340
tenofovir alafenamide, TAF, L-Alanine, N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-
methylethoxy]methyl]/ phenoxyphosphinyl]-, 1-methylethyl ester
HAART
highly active antiretroviral therapy
HBsAg
hepatitis B virus surface antigen serology
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb
hepatitis C virus serology
HDPE
high-density polyethylene
HIV
human immunodeficiency virus
HLGT
high-level group term
HLT
high-level term
HSP
Hysterosalpingogram
IB
investigator’s brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
Indpendent Ethics Committee
IND
Investigational New Drug (Application)
INSTI
integrase strand transfer inhibitor
IMP
Investigational Medicinal Product
IRB
institutional review board
IUD
intrauterine device
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LLN
lower limit of the normal range
LLOQ
lower limit of quantification


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LLT
low-level term
LPV/r
ritonavir boosted lopinavir
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram
min
Minute
mmHg
millimeters mercury
NNRTI
non-nucleoside reverse transcriptase inhibitor
NtRTI
nucleotide reverse transcriptase inhibitor
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
NVP
Nevirapine
P1NP
procollagen Type 1 N-terminal propeptide
PBMC
peripheral blood mononuclear cell
PC-120-2005
Gilead pre-clinical study: “Effect of GS-7340-03 on Cloned hERG Potassium Channels 
Expressed in Human Embryonic Kidney Cells”
PI
protease inhibitor
PK
Pharmacokinetic
PTH
parathyroid hormone
QD
once daily 
R990186
Gilead pre-clinical study: “A pharmacologic assessment of the effect of GS-7340-02 on 
the renal system of the rat”
R990187
Gilead pre-clinical study: “A pharmacologic assessment of the effect of GS-7340-02 on 
the gastrointestinal motility in the rat”
R990188
Gilead pre-clinical study: “A pharmacologic assessment of the effect of GS-7340-02 on 
the central nervous system of the rat”
RAL
Raltegravir
RBC
Red blood cells
RNA
ribonucleic acid
RPV
Rilpivirine
SAE
serious adverse event
SOC
system organ class
SOP
Standard Operating Procedure
STB
Stribild®, EVG/COBI/FTC/TDF (E/C/F/TDF) STR
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide (GS-7340)
TAF fumarate
tenofovir alafenamide fumarate (GS-7340-03)
TAM
thymidine analog-associated mutations
TBD
to be determined
TDF
tenofovir disoproxil fumarate
TFV
Tenofovir
TFV-DP
tenofovir diphosphate (TFVpp)
Tmax
the time (observed time point) of Cmax


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UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States
Vz /F
apparent volume of distribution during the terminal phase
z
terminal elimination rate constant, estimated by linear regression of the terminal 
elimination phase of the serum, plasma concentration of drug versus time curve


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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-1 (HIV-1) infection is a life-threatening and serious disease that 
is of major public health interest around the world. There are approximately 2.1 million people in 
North America and Western and Central Europe living with HIV-1 and 36.7 million people 
worldwide {Joint United Nations Programme on HIV/AIDS (UNAIDS) 2016}, including 
2.1 million children under 15 years of age {Joint United Nations Programme on HIV/AIDS 
(UNAIDS) 2016}. This figure is likely to underestimate the HIV disease burden in the pediatric 
population using the European Medicines Agency (EMA) categorization of adolescence as from 
12 to 16 or 18 years, depending on the region (EMA, Note for Guidance CPMP/ICH/2711/99).
The infection, if left untreated or suboptimally treated, is characterized by deterioration in 
immune function, ultimately resulting in death. Therapeutic strategies for the treatment of HIV-1 
disease have been significantly advanced by the availability of highly active antiretroviral 
therapy (HAART); the introduction of HAART was associated with a dramatic decrease in 
acquired immune deficiency syndrome (AIDS)-related morbidity and mortality {Mocroft 1998, 
Palella 1998, Sterne 2005}.
Disease Pathophysiology
The pathogenesis of HIV-1 infection and the general virologic and immunologic principles 
underlying the use of ARV therapy are similar between HIV-1 infected adult and pediatric 
patients. However, there are some important and unique issues for HIV-1 infected infants, 
children, and adolescents, including the following {Panel on Antiretroviral Therapy and Medical 
Management of HIV-infected Children 2011}:

Acquisition of infection through perinatal exposure for many infected children

In utero, intrapartum, and/or postpartum neonatal exposure to zidovudine and other ARV
medications in most perinatally infected children

Age-specific differences in CD4+ cell counts and percentages

Changes in pharmacokinetic parameters with age caused by the continuing development and 
maturation of organ systems involved in drug metabolism and clearance

Differences in the clinical and virologic manifestations of perinatal HIV-1 infection secondary 
to the occurrence of primary infection in growing, immunologically immature persons

Special considerations associated with adherence to ARV treatment for infants, children, and 
adolescents

Need for longer duration of therapy, with potentially greater implications than in adults for 
long-term toxicity and development of resistance

Differences in physiological development of certain body systems, including the skeletal 
system, where peak bone mass is not achieved until early adulthood


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Additional issues that may need to be considered include the fact that the processes involved in 
growth and development during childhood and adolescence can affect the adverse event profile 
of drugs, and that developmental changes associated with aging and growth are often not linear 
{Ginsberg 2004, McCarver 2004}.
Treatment
The goal of ARV therapy for HIV-1 infection is to delay disease progression, improve immune 
function, and increase the duration of survival by achieving maximal and prolonged suppression 
of HIV-1 replication. The availability of highly active antiretroviral therapy (HAART) 
combinations for the treatment of HIV-1 infection has resulted in a dramatic reduction in 
Acquired Immunodeficiency Syndrome (AIDS) related morbidity and mortality in the US and 
Europe {Mocroft 1998, Palella 1998, Sterne 2005}. However, eradication of the virus is not 
possible with therapies that are currently available. These therapies have several distinct adverse 
events such as mitochondrial dysfunction, metabolic abnormalities, hematologic toxicities, and 
allergic reactions.
The 2017 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection generally 
recommend the use of 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in 
combination with a 3rd agent (a non-nucleoside reverse transcriptase inhibitor [NNRTI], a 
boosted protease inhibitor [PI] or an integrase strand transfer inhibitor [INSTI]) for treatment of 
children and adolescents with HIV infection. The choice of a regimen, including the 3rd agent, is 
individualized based on a number of factors including characteristics of the proposed regimen, 
patient characteristics and results of resistance testing {HHS Panel on Antiretroviral Therapy and 
Medical Management of HIV-Infected Children with HIV 2017, Welch 2009}.
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other NRTIs. Tenofovir alafenamide (TAF) is also an 
oral prodrug of TFV. TAF is more stable in plasma than TDF, provides higher intracellular levels 
of the active phosphorylated metabolite tenofovir diphosphate (TFV-DP), and approximately 90% 
lower circulating levels of TFV relative to TDF at the clinical doses. The distinct metabolism of 
TAF offers the potential for an improved clinical profile compared with TDF. TAF is 
coformulated with the integrase strand transfer inhibitor elvitegravir (EVG), cobicistat (COBI), 
and emtricitabine (FTC) as Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
[E/C/F/TAF]) and with FTC as Descovy® (emtricitabine/tenofovir alafenamide [F/TAF]). The
fixed-dose combination (FDC) Genvoya® has been approved by the FDA and EMA for the 
treatment of HIV infection in ARV-naive individuals aged ≥12 years with estimated creatinine 
clearance ≥30 mL/min. The FDC Descovy® has also been approved in combination with other 
antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 12 years 
of age and older weighing at least 35 kg.
Development of F/TAF increases the options available for the construction of ARV regimens for 
HIV-1 infected pediatric patients, and simplifies dosing of the NRTI/NtRTI backbone. The small 
F/TAF tablet size due to the low predicted mg dose of TAF in combination with FTC should 
improve acceptability for children who can swallow tablets.


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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 a second generation 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 (RT) that terminates the elongation of the viral DNA chain. 
The intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
TAF has been evaluated in a broad range of patients (e.g. treatment-naïve, virologically 
suppressed, etc) as part of Genvoya® (E/C/F/TAF), Descovy® (F/TAF), or Odefsey®
(rilpivirine/emtricitabine/tenofovir alafenamide [F/R/TAF]). Specifically, Study GS-US-292-0106 
evaluated E/C/F/TAF (adult dose) in treatment-naïve adolescents. The conclusions for Cohort 1 
(ART-naive adolescents treated with E/C/F/TAF) in this study are as follows:

High virologic success was achieved (as assessed using the FDA-defined snapshot algorithm 
with HIV-1 RNA < 50 copies/mL) in ART-naive adolescents (90.0% and 92.0% virologic 
success at Weeks 24 and 48, respectively), demonstrating efficacy of the E/C/F/TAF FDC in 
this age group. These results are in accordance with pharmacokinetic (PK) data (presented in 
an earlier CSR) that confirmed the E/C/F/TAF 150/150/200/10 mg doses for each component.

There was evidence of a robust immunological response to E/C/F/TAF in ART-naive 
adolescents. The mean (SD) increase from baseline in CD4 cell count was 
191 (175.2) cells/μL at Week 24 and 224 (170.3) cells/μL at Week 48. The mean (SD) 
increase from baseline in CD4% was 7.7% (4.77%) at Week 24 and 9.3% (5.19%) at 
Week 48.

E/C/F/TAF was well tolerated, as evidenced by the low incidence of study-drug-related 
SAEs and the absence of AEs leading to discontinuation of study drug.

The lack of notable changes from baseline in height-age spine and TBLH BMD Z-scores at 
Weeks 24 and 48 indicates that subjects mineralized bone at rates consistent with those of the 
reference population. Few subjects experienced a clinically relevant decrease from baseline 
in BMD.

Changes from baseline in serum creatinine and eGFR were consistent with the inhibitory 
effect of COBI on renal tubular secretion of creatinine, and are not considered reflective of 
changes in actual glomerular filtration. There were decreases from baseline in proteinuria, as 
assessed by UPCR (urine protein to creatinine ratio).

E/C/F/TAF has been approved in adults and pediatric patients 12 years of age and older in 
the US and EU {Gilead Sciences Inc 2016, Gilead Sciences International Limited 2016}.
Please refer to the respective Investigator’s Brochure for further information, including data from 
adult studies.


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1.2.2.
Preclinical Pharmacology and Toxicology
1.2.2.1.
Primary Pharmacodynamics
TAF, like TDF, is an orally bioavailable prodrug of TFV. Following oral administration, TAF is 
metabolized to TFV, a nucleotide analog (i.e., 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) {Robbins 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, CD4+ and 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.
1.2.2.2.
Safety Pharmacology
TAF monofumarate (GS-7430-02) has been evaluated to determine potential effects on the 
central nervous system (Study R990188), renal system (Study R990186), cardiovascular system 
(Study D2000006) and gastrointestinal systems (Study 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 NOEL for gastrointestinal motility was 
100 mg/kg. The IC50 for the inhibitory effect of TAF fumarate (GS-7340-03) on hERG 
potassium current was estimated to be greater than 10 μM (Study PC-120-2005).
1.2.3.
Nonclinical Pharmacokinetics
Information regarding the TAF nonclinical PK is available in the current F/TAF IB.
1.2.4.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) or 
Fixed-Dose Combination (FDC) emtricitabine/tenofovir alafenamide 
(F/TAF)
Clinical trials entailing the use of TAF or F/TAF FDC are included in the F/TAF IB.
Drug Interaction Studies with TAF and 3rd ARV Agents
TAF systemic exposure was found to be increased by COBI via P-glycoprotein inhibition. This 
led to the selection of TAF 10 mg in the E/C/F/TAF FDC tablet, which achieved TAF exposure 
bioequivalent to that achieved with TAF 25 mg (Study GS-US-292-0103), which is considered 
the reference exposure.


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Three drug-drug interaction studies (GS-US-311-0101, GS-US-120-0117, and GS-US-120-0118) 
have been conducted to determine the drug interaction potential of commonly used 3rd agents 
with TAF. In combination, Studies GS-US-311-0101, GS-US-120-0117, and GS-US-120-0118 
provide drug interaction data between TAF and boosted protease inhibitors (DRV/r, ATV/r, 
LPV/r), non-nucleoside reverse transcriptase inhibitors (EFV and RPV), and the integrase strand 
transfer (INSTI) inhibitor dolutegravir (DTG), and the effect of these 3rd agents on TAF 
exposure is shown in Table 1-1. 
While no clinical drug-drug interaction studies of TAF were conducted with RAL, MVC and 
NVP, no clinically relevant drug-drug interaction is expected based upon preclinical and clinical 
information.
Table 1-1.
TAF AUC upon Co-administration of TAF (10 or 25 mg) with 
3rd Agent in Adults
Study 
Co-administered 
3rd agent
TAF dose evaluated in the 
DDI study (mg)
Effect of 3rd agent on 
TAF AUClast
GS-US-120-0118
ATV/r
10
↑ 91%
LPV/r
10
↑47%
DRV/r
10
↑ 6%
DTG
10
↑19%
GS-US-120-0117
RPV
25
↓ 4%
GS-US-311-0101
EFV
40
↓ 14%
Study GS-US-311-1089 is an ongoing 48-week, randomized, double-blinded, switch study to 
evaluate F/TAF in HIV-1 infected, virologically suppressed adults on regimens containing 
FTC/TDF. Safety and efficacy of F/TAF 200/10 or 200/25 mg in combination with the 
appropriate 3rd agent is being evaluated in addition to TAF and TFV PK.
1.3.
Emtricitabine (FTC, Emtriva®)
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
an NRTI that has demonstrated potent and selective inhibition of HIV. In HIV-infected adults,
FTC is administered as a 200 mg QD dose concurrently with other ARV drugs. The 200 mg FTC
capsule formulation was approved by the US Food and Drug Administration (FDA) for
marketing on 02 July 2003 and is available under the name Emtriva®. In the European Union
(EU), marketing authorization was granted for both the 200 mg Emtriva® capsule formulation
and a 10 mg/mL Emtriva® oral solution formulation on 24 October 2003, with indications for the
treatment of HIV infection concurrently with other antiretroviral drugs in both adult and
pediatric patients. Further information is available in the current Prescribing Information for 
Emtriva®.


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Amendment 2
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1.4.
Rationale for This Study
The success of HAART and the apparent benefits of maximally suppressed viremia have shifted
clinical attention towards ARV agents that optimize long-term safety and tolerability. Young, 
newly infected patients are diagnosed earlier, initiate therapy earlier and look ahead towards 
lifelong therapy {Prejean 2011}. Renal and bone health, in both of these contexts are 
increasingly important {Capeau 2011}
Although more than 20 different ARV agents in five classes are available for the treatment of 
HIV infection in adults, adolescents have limited treatment options for effective, safe and well 
tolerated once daily therapy. Adolescents with HIV infection are in need of ARV regimens for 
which therapeutic dosing has been validated by pharmacokinetic data. Many adolescents with 
HIV infection would benefit from the availability of a simplified, fixed dose combination of 
F/TAF that combines potent efficacy, tolerability, a favorable toxicity profile, and practical, 
convenient dosing.
Gilead has developed the FDC product F/TAF. Children ages 2 to < 12 years old will benefit 
from the availability of an NRTI/NtRTI backbone in a single formulation to be administered with 
other ARV agents. 
Switching from a 2-NRTI-containing ARV regimen to a TAF-containing ARV regimen may lead 
to improvement in renal and bone safety parameters due to lower plasma TFV exposure. 
HIV-infected pediatric subjects may benefit from a fixed dose tablet or age appropriate 
formulation of F/TAF, which has the potential for an improved renal and bone safety profile 
relative to TDF, an important consideration for a population in which peak bone mass has not yet 
been achieved and for whom HIV treatment is anticipated to be life-long. 
1.5.
Rationale for Dose Selection
The proposed F/TAF doses for this study are expected to provide plasma exposures in the 
pediatric population that are comparable to those associated with safety and efficacy in adults. 
1.5.1.
F/TAF Dose in Adolescents 12 to < 18 years of Age Weighing ≥35 kg
The recommended F/TAF dose in adolescents 12 to < 18 years is 200/10 mg or 200/25 mg based 
on the coadministered 3rd agent. Exposures of TAF, TAF-metabolite TFV, and FTC observed 
following administration of F/TAF 200/10 mg or 200/25 mg in adolescents are consistent with 
exposures observed in adults.
For boosted regimens, such as LPV/r, DRV/r and ATV/r, the recommended F/TAF dose is the 
adult strength tablet, 200/10 mg. For unboosted regimens, such as EFV, NVP, RAL and DTG, 
the recommended F/TAF dose is the adult strength tablet, 200/25 mg. 


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Amendment 2
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1.5.2.
F/TAF Dose in Children 6 to < 12 Years of Age Weighing ≥25 kg and 
2 to < 12 Years of Age Weighing 17 to < 25 kg
In the US, F/TAF 200/25 mg is approved for use in adults and adolescents (greater than 12 years 
of age and weighing ≥ 35 kg) when used with unboosted or boosted 3rd agents.
For children 6 to < 12 years old weighing ≥25 kg, the proposed F/TAF dose for evaluation is
200/25 mg (Table 1-2).
For children 2 to < 12 years old weighing 17 to ˂ 25 kg, a reduced F/TAF dose of 120/15 mg is 
proposed for evaluation (Table 1-2).
Table 1-2.
Pediatric F/TAF Dosing and Tablet Strength by Body Weight
Weight Band in (kg)
Strength F/TAFa (mg)
≥25 to < 35
200/25b
≥17 to < 25
120/15
a
These doses are regardless of 3rd agent.
b
This group will enroll only boosted PIs and this is the dose that will be used.
The dosing nomogram is structured to simplify dosing and formulations and to avoid 
subtherapeutic dosing in a population requiring lifelong therapy from a young age, in which the 
implications of virologic failure may be greater than in adults. The predicted exposures following 
administration of F/TAF 200/25 mg in children weighing ≥25 kg or F/TAF 120/15 mg in 
children weighing 17 to ˂ 25 kg are generally within the range of those observed in adults and 
simulations of TAF and TFV (TAF-metabolite) exposures for these doses are shown in 
Figure 1-1 and Figure 1-2 below.
Rationale for TAF Doses in Children 6 to < 12 Years of Age Weighing ≥25 kg and 
Children 2 to 12 Years of Age Weighing 17 to < 25 kg
TAF and TFV exposures were predicted by allometric scaling of adult exposures considering 
correlations between body weight and clearance (CL) capacity. Model-predicted systemic 
exposures of TAF and TFV in children 6 to < 12 years old and weighing ≥ 25 kg administered 
F/TAF 200/25 mg or children 2 to < 12 years weighing 17 to < 25 kg with unboosted or boosted 
3rd agents are presented in Figure 1-1 and Figure 1-2 respectively. These simulations indicate 
similar predicted ranges of TAF and TFV exposure in children 6 to < 12 years weighing ≥25 kg 
and children 2 to < 12 years weighing 17 to < 25 kg following administration of F/TAF 
200/25 mg or 120/15 mg respectively with unboosted or boosted 3rd agents. Additionally, the 
range of expected TAF and TFV exposures are generally within the range of those observed in 
the adult Phase 2/3 population, with TFV exposures that are generally less than median TFV 
exposures (median AUC: 2360 h*ng/mL) observed in children 6 to < 12 years old with TDF 
(Study GS-US-104-0352).


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Amendment 2
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Figure 1-1.
Predicted TAF AUC in Children Following Administration of 
F/TAF 200/25 mg or 120/15 mga,b,c
a
The adult exposures for TAF were the population PK predicted exposures from GEN Phase 3 studies
(Genvoya NDA 207561, m5.3.3.5, Population PK Analysis of TAF and TFV following Administration of E/C/F/TAF STR)
b
The observed AUC values for TAF in children ≥ 25 kg are from Study GS-US-292-0106.
c
For boosted agents, predicted exposures of TAF upon administration of TAF 25 mg with ATV/r are shown and are expected 
to encompass exposures of TAF upon coadministration with other boosted 3rd agents (LPV/r or DRV/r) (Table 1-1).
 
 
 
 
 
 
                                                                                         
 
 
 
 
 
 
 
 
  
  
 
  
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                         
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 


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Amendment 2
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Figure 1-2.
Predicted TFV AUC in Children Following Administration of 
F/TAF 200/25 mg or 120/15 mga,b,c
a
The adult exposures for TFV were the population PK predicted exposures from GEN Phase 3 studies
(Genvoya NDA 207561, m5.3.3.5, Population PK Analysis of TAF and TFV following Administration of E/C/F/TAF STR)
b
The observed AUC values for TFV in children ≥ 25 kg are from Study GS-US-292-0106.
c
For boosted agents, predicted exposures of TFV upon administration of TAF 25 mg with ATV/r are shown and are expected 
to encompass exposures of TFV upon coadministration with other boosted 3rd agents (LPV/r or DRV/r) (Table 1-1).
Rationale for FTC Doses in Children 6 to < 12 Years of Age Weighing ≥25 kg and 
Children 2 to < 12 Years of Age Weighing 17 to < 25 kg
Emtricitabine is approved to be dosed at ≤6.1 mg/kg in children as either a capsule or oral 
solution formulation {EMTRIVA® 2012}. Per the current Emtriva label, the approved dose of 
200 mg FTC can be administered in adults with normal renal function and those with mild renal 
impairment (50-80 mL/min), in whom FTC exposures were shown to be approximately 70% 
higher than adults with normal renal function {EMTRIVA® 2012}. In addition, a proposal for 
FTC/TDF low-dose tablets from the WHO Paediatric Antiretroviral Working Group 
{World Health Organization (WHO) 2011} allows FTC doses up to 8.57 mg/kg (corresponding 
to a 40% increase over 6.1 mg/kg) for use in children. Given the approved doses for FTC and its 
dose-proportional pharmacokinetics, the proposed FTC doses for evaluation in children 
6 to < 12 years weighing ≥25 kg or 2 to < 6 years weighing 17 to < 25 kg are expected to result 
in exposures in the range of those providing a favorable risk:benefit profile.
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
                                              
 
 
 
 
 
 
 
   
 
 
 
 
 
                                                                                         
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Amendment 2
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The F/TAF FDC tablets for use in patients 6 to < 12 years weighing ≥25 kg or 2 to < 6 years 
weighing 17 to < 25 kg provide a range of FTC doses comparable to the approved doses which 
do not exceed 8.57 mg/kg.
1.5.3.
Dosing in Cohorts 3 (2 to < 6 Years) and 4 (1 Month to < 2 Years)
The protocol will be amended to add dosing and formulation and specific inclusion/exclusion for 
Cohorts 3 and 4 once dose confirmation is established in Cohort 2.
1.6.
Risk/Benefit Assessment for the Study
All patients with HIV-1 infection should receive effective antiretroviral therapy. Potential risks 
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and 
lactic acidosis with steatosis. The risk of class effects is considered to be low. Important 
identified risks will be appropriately managed by study inclusion/exclusion criteria as well as 
through close clinical and laboratory monitoring during the study. Interim data will also be 
reviewed by an independent data monitoring committee. Potential benefits may include provision 
of a new antiretroviral therapy that is not currently available and which may have fewer side
effects than alternative therapies. Other potential benefits include the knowledge that patient 
participation will contribute to the body of knowledge of HIV therapies. 
Potential toxicity is appropriately managed by study inclusion/exclusion criteria, close clinical 
and laboratory monitoring, as well as specific toxicity management guidance to investigators 
(refer to Section 7.5.1). 
The overall benefit-risk assessment for F/TAF administered orally once-daily with food, in 
combination with boosted-PI or any other 3rd ARV agent, is favorable at this time.
1.7.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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Amendment 2
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2.
OBJECTIVES
The primary objectives of this study are:

To evaluate the PK of TAF and confirm the TAF dose in HIV-1 infected children and 
adolescents virologically suppressed on a 2 NRTI-containing regimen.

To evaluate the safety and tolerability of F/TAF through Week 24.
The secondary objectives of this study are: 

To evaluate the PK of TFV and FTC.

To evaluate the safety, tolerability, and efficacy of F/TAF through Week 48.


F!TAF 
Protocol GS-US-311-1269 
Gilead Sciences, Inc. 
3_ 
STUDY DESIGN 
3.1. 
Primary Endpoints 
The prima1y endpoints are: 
• 
The PK parameter AUCtau for TAF 
Final 
Amendment2 
• 
fucidence of treatment-emergent SAEs and all treatment-emergent adverse events through 
Week24 
3.1.1. 
Secondary Endpoints 
The secondaiy endpoints are: 
• 
PK parameters of Cmax, C1ast, Cl/F, and V2 IF for TAF, AUCtau, Cma.x, and Ctau for FTC and 
TFV 
• 
fucidence of treatment-emergent SAEs and all treatment-emergent adverse events through 
Week48 
• 
The percentage of subjects with HIV-I RNA < 50 copies/mL at Weeks 24 and 48 as defined 
by the US FDA-defined snapshot algorithm 
• 
The change from baseline in CD4+ cell count (cells/µL) and CD4+ percentage at 
Weeks 24 and 48 
• 
The palatability and acceptability of the age-appropriate F/TAF fo1mulation 
I 
I 
I 
3.2. 
Study Design 
This protocol describes an open-label, multi-coho1t switch study to evaluate the PK, safety, and 
efficacy of FIT AF in HIV-I infected children (1 month to < 12 yeai·s) and adolescents 
(12 to <18 yeai·s) who are virologically suppressed while on a stable 2-NRTI-containing regimen. 
A minimum of 100 children and adolescent subjects, 1 month to < 18 years of age of either sex, 
will be emolled to receive F/TAF. The study will proceed in sequential cohorts as follows: 
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3.2.1.
Cohort 1 (Adolescents 12 to < 18 years, ≥ 35 kg)
All subjects in Cohort 1 (n = 25) will switch their current 2-NRTI-containing regimen to 
open-label F/TAF while continuing on their 3rd ARV agent through 48 weeks.
Subjects will be enrolled to evaluate the steady state PK and confirm the dose of TAF. 
An intensive PK (IPK) evaluation will be conducted at the Week 2 visit to confirm the dose of 
TAF and to characterize TFV and FTC exposures as appropriate. Samples will be collected over 
24 hours (pre and post dose) and will be analyzed once they are available from all subjects.
Replacement subjects may be enrolled if subjects do not complete all IPK procedures or if IPK 
data is incomplete. Replacement subjects will not be enrolled in Cohort 1 for subjects who 
discontinue the study due to treatment-related toxicity.
Following completion of the Week 2 IPK visit, all subjects will continue to receive F/TAF plus 
their 3rd ARV agent and return for study visits through Week 48. 
3.2.2.
Cohorts 2, 3, and 4
Subjects in Cohorts 2, 3, and 4 must be on a boosted protease inhibitor (PI) (Cohort 2 only) or 
any other 3rd ARV agent and will switch their current 2-NRTI-containing regimen to open-label 
F/TAF while continuing their boosted PI or 3rd agent through 48 weeks. A minimum of 
10 subjects each in Groups 1 and 2 of Cohort 2, and Cohorts 3 and 4, who are on boosted-ATV
as their 3rd ARV agent will be enrolled. Cohorts 2, 3, and 4 will be enrolled by cohort into a 
two-part study (Parts A and B) as follows: 
Part A
A minimum of 67 subjects will be enrolled to evaluate the steady state PK and confirm the dose 
of TAF with boosted ATV, LPV, DRV or other agents. 
Cohort #
Age Range
ATV + F/TAF
LPV or DRV 
+ F/TAF
Other 3rd ARV Agents
+ F/TAF
2, Group 1a
6 to < 12 years
n ≥ 10
n ≥6
n/a
2, Group 2b
2 to < 12 years
n ≥ 10
n ≥7
3
2 to < 6 years
n ≥ 10
n ≥7
4
1 month to < 2 years
n ≥ 10
n ≥7c
a
Cohort 2, Group 1 subjects must weigh ≥ 25 kg at screening
b
Cohort 2, Group 2 subjects must weigh 17 to < 25 kg at screening
c
DRV is not approved for Cohort 4
All subjects in Cohort 2 Part A will undergo an IPK evaluation at either the Week 2 or Week 4 
visit or within 7 days after the completion of the Week 2 or Week 4 visit to confirm the dose of 
TAF and to characterize the exposure of TFV. TAF dose confirmation will be established if the 
exposure is comparable to that associated with efficacy in adults. Samples will be collected over 
8 hours (pre and post dose) and will be analyzed once they are available from all subjects. 


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Amendment 2
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Replacement subjects may be enrolled if subjects do not complete all IPK procedures or if the 
IPK data is incomplete but will not be enrolled for subjects who discontinue the study due to 
treatment-related toxicity.
Following completion of the IPK, all subjects will continue to receive F/TAF plus their 
3rd ARV agent and return for study visits through Week 48.
The IPK collection schedule and fasting requirement for Cohorts 3 and 4 will be specified in a 
future protocol amendment.
Part B
After confirmation of TAF dose in Part A (IDMC review required) for each cohort (and group
for Cohort 2), approximately 10 additional total subjects will receive F/TAF while continuing
their 3rd ARV agent through 48 weeks in Part B to evaluate the safety, tolerability and efficacy of 
the treatment regimen.
3.2.3.
Study Procedures and Frequency for All Subjects (All Cohorts and 
Parts A and B)
At the Screening, Baseline/Day 1, and all subsequent study visits laboratory analyses 
(hematology, chemistry, and urinalysis), HIV-1 RNA, CD4+ cell count, eGFR using the 
Schwartz formula, and a complete or symptom directed physical examinations will be 
performed. Serum (screening) or urine (all other visits) pregnancy tests will be performed on 
female subjects of childbearing potential.
At screening HBV and HCV serology will be analyzed.
Subjects will return for study visits at Weeks 1, 2, 4, 8, 12, 24, 36, and 48. After completion of 
48 weeks of treatment in the study, all eligible subjects will be given the option to participate in 
an extension phase of the study in which visits will occur every 12 weeks. Adverse events and 
concomitant medications will be assessed at each visit.
Tanner stage assessment will be performed at Baseline/Day 1, Weeks 24 and 48, and every 
12 weeks thereafter or until subjects reach Tanner Stage 5, after which point Tanner assessments 
will no longer be performed.
Dual energy x-ray absorptiometry (DXA) scans of the lumbar spine and total body will be 
performed at Baseline/Day 1, Weeks 24 and 48, and every 24 weeks thereafter to measure spine 
bone mineral density (BMD) and total body BMD.
For all subjects, single PK samples will be collected: A single random PK sample will be 
collected at Weeks 1 and 24, and a single observed dosing PK sample will be collected at any 
time between 15 min to 4 hours post dose during Weeks 4 and 12 (Note: For subjects in Cohort 2
Part A, a single observed dosing PK sample does not need to be collected at Week 4 if Intensive 
PK is also collected at the Week 4 visit). A trough sample will be collected at 0 hours (pre-dose, 
≤ 30 minutes prior to dosing) during Week 8.


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PBMC collection will be performed at sites that have PBMC processing capability. For subjects 
in Cohorts 1 and 2, PBMC collection will be performed at the Week 8 visit. PBMC collection 
schedule for Cohorts 3 and 4 will be addressed in a future protocol amendment. For PK profiling 
in PBMCs, blood samples will be collected at 0 hours (≤ 30 minutes pre-dose). Details of PBMC 
collection and processing will be documented in the Pharmacokinetic Sample Collection, 
Processing, Storage, and Shipment Manual (PK manual).
Palatability and acceptability will be assessed in Cohort 1 subjects 30 - 60 minutes after study 
drug dosing for all subjects undergoing IPK sampling. For Cohort 1 subjects that are currently on 
study and are beyond the Week 2 visit, an acceptability assessment is required once, preferably 
at the next clinic visit following the approval of this protocol amendment at the site. Palatability
and acceptability will be assessed 30 - 60 minutes after study drug dosing for all subjects 
undergoing IPK sampling in Part A of Cohorts 2, 3, and 4. 
Serum will be collected for bone safety tests (collected fasted), including bone specific alkaline 
phosphatase (BsAP), serum phosphorous, procollagen type 1-N-terminal propeptide (P1NP), 
C-type collagen sequence (CTX), parathyroid hormone (PTH), 1,25-OH vitamin D, and 25-OH 
vitamin D (for Cohort 1: Baseline and Weeks 4, 12, 24, and 48 (±6 days) and every 24 weeks 
thereafter; for Cohorts 2,3, and 4: Baseline and Weeks 8, 12, 24, and 48 (±6 days) and every 24 
weeks thereafter).
For all cohorts and groups, urine will be collected for urine chemistry, and selected renal safety 
tests, including retinol binding protein, and beta-2-microglobulin at Baseline/Day 1, 
Weeks 2, 4, 8, 12, 24, 48, and every 12 weeks thereafter. 
For Cohorts 1 and 2 (all groups), metabolic assessments will be collected for fasting glucose and 
lipid panel (total cholesterol, HDL, direct LDL, and triglycerides) at Baseline/Day 1, 
Weeks 24, 48, and every 24 weeks (±10 days) thereafter.
Tanner stage assessment will be performed at Baseline/Day 1, Weeks 24 and 48, and every 
12 weeks thereafter, or until subjects reach Tanner Stage 5, after which point Tanner assessments 
will no longer be performed.
Dual energy x-ray absorptiometry (DXA) scans of the lumbar spine and total body will be 
performed at Baseline/Day 1, Weeks 24 and 48, and every 24 weeks thereafter to measure spine 
bone mineral density (BMD) and total body BMD.
Subjects who prematurely discontinue the study or do not participate in the extension phase, as 
well as subjects who prematurely discontinue prior to Week 48, will be required to return to the 
clinic 30 days after the completion of the study drug for a 30 Day Follow up visit. 


F!TAF 
Protocol GS-US-31 1-1269 
Gilead Sciences, Inc. 
Final 
Amendment2 
Subjects will receive their assigned tr·eatment for 48 weeks. After completion of 48 weeks, all 
subjects will be given the option to paiiicipate in an extension phase of the study. Gilead will 
provide F/TAF until a) the subject turns 18 and F/TAF is commercially available for use in 
adults in the country in which the subject is emolled or, b) F/TAF becomes commercially 
available for pediatr·ic use in the country in which the subject is emolled or, c) Gilead Sciences 
elects to tenninate development of F/TAF in the applicable country. 
In the extension phase of the study, subjects will return for study visits eve1y 12 weeks. During 
these visits, subjects will be assessed at vaiying intervals for AEs and concomitant medications, 
Tanner Stage assessments, physical exams, vital signs, height measurements, 12-lead ECGs, 
urine collection, blood sampling, eGFR, CD4+ cell count and percentage, plasma HIV-I RNA, 
DXA scans, and study dmg dispensation and accountability. Refer to Section 6.6 for precise 
timing of the post Week 48 assessments. 
Figure 3-1. 
Screening 
$ 35 days prior 
to Day 1 
Screening 
Study Schema 
Baseline/ 
Dayl 
COHORT 1 
12 to < 18YR 
IPK 
(Week 2) 
PART A 
COHORT 2, 6 to < 12 YR 
GROUP 1, <! 25 kg 
COHORT 2, 2 to < 12 YR 
GROUP 2, 17 to< 25 kg 
Week48 
30 Day 
Follow-Up 
Extension 
Phase 
30 Day 
Follow-Up 
-or-
Extension 
Phase 
$ 35 days prior 
Baseline/ 
IPK 
Week48 
to Day 1 
Day 1 
(Week 2 or 4) 
Acceptable Week 4 
b 
PK & Safety Data 
a 
Screening 
PARTB 
COHORT 2, 6 to < 12 YR 
GROUP 1, <! 25 kg 
COHORT 2, 2 to < 12 YR 
GROUP 2, 17 to< 25 kg 
$ 35 days prior 
Baseline/ 
to Day 1 
Day 1 
Week48 
a 
Patt B screening will initiate after analysis of intensive PK samples and confumation ofTAF dose in corresponding age 
cohott in Patt A. 
b 
TI1e screening schema for Cohotts 3 and 4 will be specified in a future protocol amendment. 
3.3. 
Study Treatments 
In Coho1i 1, F/TAF will be administered orally, dosed once-daily in combination with their 
3rd ARV agent, at approximately the saine time each day, either with or without food, as 
determined by the subject's 3rd ARV agent. 
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In Cohorts 2, 3, and 4, F/TAF will be administered orally, dosed once-daily in combination with 
their 3rd ARV agent, at approximately the same time each day, either with or without food, as 
determined by the subject’s 3rd ARV agent. The F/TAF dose will be based on the subject’s 
weight and 3rd ARV agent.
On the morning of the IPK visit, subjects in Cohort 1 and in Part A of Cohorts 2, 3, and 4 will be 
administered their dose of study medication in combination with their 3rd ARV agent in the 
clinic, along with food, prior to IPK sampling. To prepare for the in-clinic dosing, subjects 
should begin taking study drug and their 3rd ARV agent in the morning starting at least 1 week 
prior to the IPK visit.
At the single observed dosing PK sampling visit, subjects will be administered their dose of 
study drug medication in combination with their 3rd ARV agent in the clinic. Prior to the single 
observed dosing PK sampling visit, subjects should take study drug at approximately the same 
time each day, regardless of the time of day, for at least 1 week prior to the PK sampling. 
Subjects will be required to report the time of the last dose during the visit. 
Prior to the single random PK sampling visit, subjects should take study drug in combination 
with their 3rd ARV agent at approximately the same time each day, regardless of the time of day, 
for at least 1 week prior to the PK sampling. Subjects will be required to report the time of the 
last dose at the time of the visit.
3.4.
Duration of Treatment
Subjects will receive their assigned treatment for 48 weeks. All subjects that complete 48 weeks
of treatment will be given the option to participate in an extension phase of the study where 
Gilead will provide F/TAF until a) the subject turns 18 years old and F/TAF is commercially 
available for use in adults in the country in which the subject is enrolled or b) F/TAF becomes 
commercially available for pediatric use in the country in which the subject is enrolled or 
c) Gilead Sciences elects to terminate development of F/TAF in the applicable country.
3.5.
Criteria for Discontinuation of Study Treatment
Study medication may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator.

Unacceptable toxicity or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest.

Therapeutic failure (i.e., virologic failure as per Section 6.10).

Subject request to discontinue for any reason.

Subject noncompliance.


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
Pregnancy during the study; refer to Appendix 5.

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC).


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
A minimum of 100 subjects who meet the eligibility criteria will be enrolled.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) HIV-1 infected male and female pediatric patients aged 1 month to < 18 years at 
Baseline/Day 1 (according to requirements of the enrolling cohort)
2) Subject able to give written assent prior to any screening evaluations if they have the ability 
to read and write
3) Parent or guardian able to give written informed consent prior to any screening evaluations 
and willing to comply with study requirements 
4) A negative serum β-HCG pregnancy test is required for female subjects of childbearing 
potential only (as defined in Appendix 5)
5) Body weight at screening as follows:
Age Range
Weight
Cohort 1
12 years to < 18 years
≥ 35 kg
Cohort 2: Group 1
6 years to < 12 years
≥ 25 kg
Cohort 2: Group 2 (able to swallow a tablet)
2 years to < 12 years
17 kg to < 25 kg
Cohort 3 (unable to swallow a tablet)
2 years to < 6 years
TBDa
Cohort 4
1 month to < 2 years
TBDb
a
Body weight cutoff at screening to be determined based upon analysis of short-term safety and PK data from Cohort 2 
Part A before initiating Cohort 3 Part A
b
Body weight cutoff at screening to be determined based upon analysis of short-term safety and PK data from Cohort 2 
Part A & Cohort 3 Part A
6) Currently on a stable 2-NRTI-containing regimen that includes a 3rd ARV agent for 
≥6 consecutive months prior to screening.
7) Plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 consecutive months preceding the 
screening visit (measured at least twice using the same assay) and not experienced 
two consecutive HIV-1 RNA above detectable levels after achieving a confirmed 
(two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year. 
a) To determine virologic suppression in the preceding 6 months prior to screening, the 
lower limit of quantification (LLOQ) by the local HIV-1 RNA assay may be used, only if 
its LLOQ is greater than 50 copies/mL (e.g. LLOQ of 75 copies/mL).


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8) Estimated glomerular filtration rate (eGFR) 90 mL/min/1.73m2 by (Schwartz) formula
9) All male subjects and those female subjects of childbearing potential or those who reach 
childbearing potential during study participation (as defined in Appendix 5) must agree to 
utilize highly effective contraception methods while on study treatment or agree to abstain 
from heterosexual intercourse throughout the study period and for 30 days following the last 
dose of study drug; highly effective methods normally utilize two separate forms of 
contraception, one of which must be an effective barrier contraceptive method. Pre-pubertal 
females (Tanner stages 1 and 2) are not considered to be of childbearing potential, unless 
onset of menarche has occurred. See Appendix 5 for definition of females of childbearing 
potential.
10) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least three months prior to study dosing. 
11) Adequate hematologic function defined as:
a) Absolute neutrophil count ≥500 cells/mm3 (Subjects with neutrophil count of < 500/mm3
documented at least twice within 6 months of screening, and in who, according to the 
investigator, there is no evidence of immunosuppression associated with low neutrophil
count, can enroll in the study contingent upon approval from the Gilead study Medical 
Monitor.)
b) Hemoglobin > 8.5 g/dL
c) Platelets ≥50,000/mm3
12) Hepatic transaminases (AST and ALT) 5 × upper limit of normal (ULN)
13) For subjects on all 3rd ARV agents except ATV, total bilirubin ≤1.5 mg/dL or normal direct 
bilirubin
14) For subjects on ATV, total bilirubin ≤ 3.0 mg/dL or normal direct bilirubin
15) Normal ECG (or if abnormal, determined by the investigator to be not clinically significant)
16) Must be willing and able to comply with all study requirements 
17) No opportunistic infection within 30 days of study entry (at Baseline/Day 1)
18) Subject is able to swallow a tablet


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4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. 
1) An acquired immunodeficiency syndrome (AIDS)-defining condition with onset within 
30 days prior to screening 
2) Life expectancy of < 2 years.
3) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Baseline/Day 1
4) Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of 
the screening visit 
5) Anticipated requirement for rifamycin treatment while participating in the study. 
Note: prophylactic isoniazid therapy for latent tuberculosis is allowed.
6) Active HCV infection defined as positive for HCV antibody and having detectable 
HCV RNA.
a) Note: subjects with positive HCV antibody and without detectable HCV RNA are 
permitted to enroll.
7) Positive hepatitis B surface antigen or other evidence of active HBV infection. 
a) Note: Subjects with positive HBV surface antibody and no evidence of active HBV
infection are permitted to enroll. 
8) Subjects with a historical genotype that have documented or suspected resistance to TFV or 
FTC, including, but not limited to, the presence of reverse transcriptase mutations K65R, 
K70E, M184V/I, or 3 or more thymidine analog-associated mutations (TAMs) that include 
M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R).
9) Have any serious or active medical or psychiatric illness which, in the opinion of the 
Investigator, would interfere with subject treatment, assessment, or compliance with the 
protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary 
(including chronic asthma or active tuberculosis), endocrine (e.g., diabetes), central nervous, 
gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), 
immunodeficiency disorders, active infection, or malignancy that are clinically significant or 
requiring treatment (within 30 days prior to Baseline/Day 1).
10) Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy).


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11) A history or ongoing malignancy other than cutaneous Kaposi’s sarcoma (KS), basal cell 
carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with 
biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic 
therapy for KS within 30 days of screening and are not anticipated to require systemic 
therapy during the study.
12) Pregnant or lactating subjects
13) Current alcohol or substance abuse judged by the Investigator to potentially interfere with 
subject compliance.
14) Have history of significant drug sensitivity or drug allergy.
15) Known hypersensitivity to the investigational medicinal product (IMP), the metabolites, or 
formulation excipient.
16) Have previously participated in an investigational trial involving administration of any 
investigational agent, other than TDF, within 30 days prior to the study dosing.
17) Participation in any other clinical trial without prior approval from sponsor is prohibited 
while participating in this trial.
18) Subjects receiving ongoing therapy with any of the following medications in the table below, 
including drugs not to be used with FTC, TAF or their 3rd ARV agent (refer to the individual 
agents Prescribing Information).
Table 4-1.
Prohibited Medication while on Study
Medication Class
Prohibited Medications
Anticonvulsants
carbamazepine, oxcarbazepine, phenobarbital, phenytoin
Antimycobacterials
rifapentine, rifabutin, rifampin
Antivirals
cidofovir, ganciclovir, valganciclovir
Herbal/Natural Supplements
St. John’s Wort, Echinacea, Milk thistle (i.e., silymarin), 
Chinese herb sho-saiko-to (or Xiao-Shai-Hu-Tang)
Other
probenecid
*
Administration of any of the above prohibited medications must be discontinued at least 30 days prior to the Baseline/Day 1 
visit and for the duration of the study.


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Enrollment 
This is an open-label study. 
It is the responsibility of the Investigator to ensure that the subject is eligible for the study prior
to enrollment.
Subjects will be assigned a screening number at the time of consent. 
The enrollment and Baseline/Day 1 visit cannot occur until subject eligibility has been 
confirmed. Once eligibility is confirmed, the study site will use the IWRS to assign a unique 
subject enrollment number. Once a subject number has been assigned to a subject it will not be 
reassigned to any other subject.
The subject number assignment and enrollment may be performed up to 7 days prior to the 
Baseline/Day1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed by the Sponsor.
All subjects will switch their current 2-NRTI-containing regimen to F/TAF while continuing 
their protocol-specified 3rd ARV agent.
IWRS will assign study drug bottle numbers for dispensing study drug at study visits. Initiation 
of treatment with the study drug must take place within 24 hours after the Baseline/Day 1 visit.
5.2.
Description and Handling 
5.2.1.
Formulations
5.2.1.1.
Emtricitabine/Tenofovir Alafenamide (F/TAF)
5.2.1.1.1.
Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg tablets
Emtricitabine 200 mg/Tenofovir Alafenamide 25 mg tablets are rectangular-shaped, film-coated 
blue tablets that are debossed with "GSI" on one side of the tablet and "225" on the other side of 
the tablet. The F/TAF tablet cores contain 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.


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5.2.1.1.2.
Emtricitabine 200 mg/Tenofovir Alafenamide 10 mg tablets
Emtricitabine 200 mg/Tenofovir Alafenamide 10 mg tablets are rectangular-shaped, film-coated 
gray tablets that are debossed with "GSI" on one side of the tablet and "210" on the other side of 
the tablet. The F/TAF tablet cores contain 200 mg of emtricitabine and 10 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 iron oxide black, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
5.2.1.1.3.
Emtricitabine 120 mg/Tenofovir Alafenamide 15 mg tablets
Emtricitabine 120 mg/Tenofovir Alafenamide 15 mg tablets are round, plain faced, film-coated 
white tablets. Alternatively F/TAF 120/15 mg tablets are round, debossed with “GSI” on one 
side of the tablet and “15” on the other side, film-coated white tablets. The F/TAF tablet cores 
contain 120 mg of emtricitabine and 15 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 polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.
5.2.2.
Packaging and Labeling
Emtricitabine/Tenofovir Alafenamide (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 capped with a white, continuous thread, child-resistant, 
polypropylene screw cap fitted with an induction-sealed, aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal 
Products), and/or other local regulations. All labels for study drug bottles to be distributed to 
centers in the US, EU and the rest of the countries will meet all applicable requirements of the 
US Food and Drug Administration (FDA) and Annex 13 of Good Manufacturing Practices: 
Manufacture of investigational medicinal products (February 2010) and/or other local regulations 
as applicable.
5.2.3.
Storage and Handling
Emtricitabine/Tenofovir Alafenamide (F/TAF) 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 subjects, all bottles of study 
drugs should be stored in a securely locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied. Consideration should be given to handling, 
preparation, and disposal through measures that minimize drug contact with the body. 
Appropriate precautions should be followed to avoid direct eye contact or exposure through 
inhalation when handling.


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5.3.
Dosage and Administration
All subjects in Cohort 1 will switch their current 2-NRTI-containing regimen to F/TAF while
continuing their 3rd ARV agent. All subjects in Cohorts 2, 3, and 4 will switch their current 
2-NRTI-containing regimen to F/TAF and must be on a boosted-PI or other agent as their 
3rd ARV agent as applicable per cohort.
5.3.1.
Cohort 1 (12 years to < 18 years, ≥ 35 kg)
F/TAF fixed-dose combination tablets will be provided by Gilead Sciences and will be 
administered orally, once daily as noted below in Table 5-1. The 3rd ARV agent will be 
prescribed by the Investigator and the subject will be responsible for obtaining the 3rd ARV agent 
prior to Baseline/Day 1 visit. 
During the study, investigators wishing to change a subject’s 3rd ARV agent for reasons other 
than virologic failure must discuss this change with the Gilead Medical Monitor. Refer to 
Section 6.10 for more information.
At the IPK and at the single observed dosing PK sampling visits at Weeks 4 and 12, subjects will 
be administered their dose of study medication and their 3rd ARV agent in the clinic with food 
prior to the PK sampling.
Subjects will receive their assigned treatment for 48 weeks. After completion of 48 weeks, all 
subjects will be given the option to participate in an extension phase of the study. Gilead will 
provide F/TAF until a) The subject turns 18 years old and F/TAF is commercially available for 
use in adults in the country in which the subject is enrolled or b), F/TAF becomes commercially 
available for pediatric use in the country in which the subject is enrolled or c), Gilead Sciences 
elects to terminate development of F/TAF in the applicable country. 
Table 5-1.
Cohort 1 Dosing Recommendation for F/TAF in combination with 
3rd ARV Agents
Cohort
Age and body weight
F/TAF dose (mg) with 3rd agent
1
12 to < 18 years, ≥ 35 kg
200/25 for unboosted 3rd agent
200/10 for boosted 3rd agent
5.3.2.
Cohorts 2, 3, and 4
F/TAF fixed-dose combination tablets will be provided by Gilead Sciences and will be 
administered orally, once daily as noted above in Table 5-1. The subject’s 3rd ARV agent will be 
prescribed by the Investigator and the subject will be responsible for obtaining the 3rd ARV agent 
prior to Baseline/Day 1 visit. 
For subjects in Part A of Cohorts 2, 3, and 4, at the IPK visit and at the single observed dosing 
PK sampling visits, subjects will be administered their dose of study medication and their 
3rd ARV agent in the clinic with food prior to the PK sampling.


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Table 5-2.
Cohorts 2, 3, and 4 Dosing Recommendations for F/TAF
Cohort
Age and body weight
F/TAF dose (mg) 
2, Group 1
6 to < 12 years, ≥ 25 kg
200/25
2, Group 2 (able to swallow a tablet)
2 to < 12 years, ≥ 17 to < 25 kg
120/15 
3 (unable to swallow a tablet)
2 to < 6 years, TBD
TBDa
4
1 month to < 2 years, TBD
TBDa
a
Dosage, using weight appropriate F/TAF dispersible tablets prepared as an oral suspension, will be specified by protocol 
amendment after clinical safety, efficacy, and PK data from Cohorts 1 and 2 are available to guide dose selection of F/TAF 
to be administered in Cohorts 3 and 4. Subjects under 6 years of age who cannot swallow tablets will be allowed to choose 
this formulation for treatment as well.
5.4.
Prior and Concomitant Medications
The use of medications for the treatment of HIV, other than the study treatment (i.e., F/TAF) and 
baseline 3rd ARV agent, is prohibited. Medications listed in Table 5-3 and use of herbal/natural 
supplements are excluded or should be used with caution while subjects are participating in the 
study due to potential drug-drug interactions with the study drugs. 
Should subjects have a need to initiate treatment with any excluded or prohibited concomitant 
medication, the Gilead Sciences Medical Monitor must be consulted 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 Sciences as soon as he/she is aware of the use of the 
prohibited medication.
Table 5-3.
List of Prohibited Medications and Medications That Are To Be Used 
With Caution
Medication Class
Prohibited Medications 
Medications To Be Used With Caution
Antiarrhythmics
amiodarone, quinidine: May increase 
concentration of TAF and/or TFV
Anticonvulsants
carbazepine, oxcarbazepine, 
phenobarbital, pheynytoin
Antimycobacterials
rifapentine, rifabutin, rifampin 
clarithromycin: may increase concentration of 
TAF and/or TFV
Antifungals
itraconazole, ketoconazole, voriconazole: may 
increase concentration of TAF and/or TFV
Antivirals
cidofovir, ganciclovir, valganciclovir 
acyclovir, valacyclovir
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, Echinaccea, Milk thistle 
(i.e. silymarin), Chinese herb sho-saiko-to 
(or Xiao-Shai-Hu-Tang
Others
Probenecid


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Medications listed in Table 5-4 are prohibited and should be discussed with the GSI Medical 
Monitor while subjects are participating in the study due to potential adverse skeletal effects. 
Table 5-4.
List of Prohibited Medications with Adverse Skeletal Effects
Medication Class
Prohibited Medications
Cyclophosphamides / Cytophosphanes
cytoxan, endoxan, neosar, procytox, revimmune
Ciclosporins
cyclosporine A, B, C, D, E, F, and G
Glucocorticoids
Chronic, systemic glucocorticoids
Medroxyprogesterones
Depo-Provera
Additionally, Investigators should refer to the product/package inserts of the other ARV
medications for age-related recommendations or contraindications related to their use.
5.5.
Accountability
The investigator is responsible for ensuring adequate accountability of all used and unused IMP. 
This includes acknowledgement of receipt of each shipment of IMP (quantity and condition). All 
used and unused IMP dispensed to subjects must be returned to the site.
F/TAF accountability records will be provided to each study site to:

Record the date received and quantity of IMP kits

Record the date, subject number, subject initials, the IMP kit number dispensed

Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information.
5.6.
Investigational Medicinal Product Return or Disposal
Refer to Section 9.1.7 for detailed instructions. 


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2, and also described in the text that follows.
Any deviation from protocol procedures should be noted in the subject’s clinical chart and
electronic Case Report Forms (eCRFs). In addition, the Sponsor or Contract Research 
Organization (CRO) should be promptly notified of any important protocol deviations.
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the Investigator to ensure that each subject is eligible for the study 
before enrollment.
Please refer to Section 5.1 for details about subject number and treatment assignment for each 
Cohort.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 35 days before Baseline/Day 1 to determine eligibility for 
participation in the study. The following activities will be performed and documented during
screening: 

Obtain written informed assent/consent
Each subject must sign an assent if they have the ability to read and write (and parent or legal 
guardian sign an informed consent form) prior to the conduct of any screening procedures. 
Subjects will be assigned a screening number at the time of assent/consent. Screening 
evaluations are used to determine the eligibility of each candidate for study enrollment. 

Obtain medical and medication history, including history of: 
Review of Concomitant Medications
■
Any ongoing medications within 30 days of the Screening visit
HIV-1 disease-related events 
Historical genotypes should be collected, if available.

Complete physical examination (urogenital/anorectal examination will be performed at the 
discretion of the investigator)

Vital signs (blood pressure, pulse, respiration rate, and temperature)


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
Weight and height/length

12-lead ECG performed supine 

Urine collection for the following laboratory procedures:
Urinalysis 

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (for females of childbearing potential in Cohorts 1 & 2 only). If 
the test is positive, the subject will not be enrolled.
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN)
Hematology profile: complete blood count (CBC) with differential and platelet count
Estimated Glomerular Filtration Rate (eGFR) using Schwartz Formula:
■
(mL/min/1.73 m2) = k × L/SCr (k is a proportionality constant, L is height in 
centimeters (cm) and SCr is serum creatinine (mg/dL)). 
○
The value of k is 0.55 for children (≥ 2 to < 12) and adolescent girls 
(≥12 years old) and 0.7 for adolescent boys (≥ 12 years old).
Plasma HIV-1 RNA 
CD4cell count and percentage
Hepatitis B virus (HBV) surface antigen serology (HBsAg)
Hepatitis C virus antibody (HCVAb) serology
■
Note: If the antibody test result is positive, HCV RNA test will be performed to 
confirm HCV viremia.

Record any serious adverse events and all adverse events related to protocol mandated 
procedures occurring after signing of the consent form.


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6.2.2.
Baseline/Day 1 Assessments
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 35 days after the Screening visit for the Baseline/Day 1visit.
Subjects with exclusionary screening laboratory results due to an acute clinical condition which 
resolves can be re-screened within 3 months of initial Screening. The decision to re-screen the 
subject will be made in consultation with the Medical Monitor, and written notice of eligibility 
from the Sponsor is required before a re-screened subject can be enrolled.
From the time of obtaining informed consent and subject assent through the first administration 
of investigational medicinal product, record all serious adverse events (SAEs), as well as any 
non-serious adverse events related to protocol-mandated procedures on the adverse events case 
report form (CRF/eCRF). All other untoward medical occurrences observed during the screening 
period, including exacerbation or changes in medical history are to be captured on the medical 
history CRF/eCRF. Refer to Section 7, Adverse Events and Toxicity Management, for additional 
details. 
The following items and evaluations are to be completed at the Baseline/Day 1 Visit. The subject 
must complete all Baseline/Day 1 procedures before being dispensed the study drug. Initiation of 
treatment with the study drug must take place within 24 hours after the Baseline/Day 1 visit.

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator) 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature)

Weight and height/length

Tanner Stage assessment

DXA Scan of the lumbar spine and of the total body for BMD:
The DXA scan will be performed on subjects once eligibility is confirmed and prior to 
study drug administration at the Baseline/Day 1 Visit. The scan may be performed on the 
morning of the Baseline/Day 1 Visit as long as it occurs before dosing.

Urine collection for the following laboratory procedures:
Urinalysis
Urine Chemistry


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Urine renal safety test ( collected fasted for Coho1is 1 and 2) including retinol binding 
protein and beta-2-microglobulin. If the subject has not fasted prior to the visit, the visit 
may continue; however, the subject must return within 72 hours in a fasted state to 
provide a urine sample for renal safety test. The fasting requirement for Cohorts 3 and 4 
will be specified in a future protocol amendment. 
-
Urine pregnancy test (females of childbearing potential in Cohorts 1 & 2 only). If the 
urine pregnancy test is positive at Baseline/Day 1, study dmg will not be dispensed. The 
positive result will be confomed with a sennn pregnancy test. If the semm pregnancy test 
is positive the subject will not be able to participate. 
• 
Blood sample collection for the following laborato1y analyses: 
-
Chemistiy profile: alkaline phosphatase, AST, ALT, total bilimbin, direct and indirect 
bilimbin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphoms, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is perfo1med in subjects with total amylase > 1.5 x ULN). 
-
Metabolic assessments: Fasting (no food or drinks, except water, at least 5 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
ti·iglycerides) for Coho1is 1 and 2 (all groups). If the subject has not fasted prior to the 
visit, the visit may continue; however, the subject must return within 72 hours in a fasted 
state to draw blood for the metabolic assessments. The fasting requirement for 
Coho1is 3 and 4 will be specified in a future protocol amendment. 
-
Hematology profile: complete blood count (CBC) with differential and platelet count 
-
Plasma HIV-1 RNA 
-
CD4+ cell count and percentage 
-
Whole blood sample storage for virology testing 
-
Semm will be collected for bone safety tests ( collected fasted), including bone specific 
alkaline phosphatase (BsAP), sennn phosphorous, PlNP, CTX, PTH, 1,25-0 H 
vitamin D, and 25-0H vitamin D. If the subject has not fasted prior to the visit, the visit 
may continue; however, the subject must return within 72 hours in a fasted state to draw 
blood for bone safety tests. 
-
eGFR using Schwa1iz Fo1mula 
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
Assign subject number:
The subject’s enrollment number can be assigned via IWRS up to 7 days prior to the 
Baseline/Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.

Study drug dispensation:
Study drug will be dispensed in an open-label fashion. Subjects and/or parent/guardian will 
be dispensed F/TAF based on cohort, their weight and their 3rd agent. Subjects should initiate 
dosing of study drug within 24 hours after the Baseline/Day 1 visit. Investigators will provide 
prescriptions to the subjects and/or parent/guardian for their 3rd ARV agent. The subjects
and/or parent/guardian are responsible for obtaining their 3rd ARV agent prior to the 
Baseline/Day 1 visit.
Subjects and/or parent/guardian should be instructed to take study drug along with the
subject’s 3rd ARV agent once daily with or without food as determined by the 3rd ARV agent
and at approximately the same time each day. The subject and/or parent/guardian should be 
counseled regarding the importance of adherence and taking all their ARV study medication 
at approximately the same time each day. Sites should consider individual subject study drug 
dosing schedules while scheduling study visits requiring collection of PK samples.

Study drug accountability:
Subjects and/or parent/guardian should be reminded to bring their drug bottles of the F/TAF
and their 3rd ARV agent with them for drug accountability at Week 1.
6.3.
Treatment Assessments through 48 Weeks (Weeks 1 (Day 7) −48)
The following evaluations are to be completed at the end of Weeks 1 (Day 7), 2, 4, 8, 12, 24, 36, 
and 48 unless otherwise specified.
All study visits are to be scheduled relative to when the Baseline/Day 1 visit was completed.
Thereafter all study visits through Week 8 are to be completed within ± 2 days of the protocol
specified visit date. Visits between Week 12 through Week 48 are to be completed within 
± 4 days of the protocol specified visit date, unless otherwise specified.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to
receive study drug.

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24 and 48) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed (Week(s) 1 (on Day 7), 2, 4, 8, 12, and 36)


F!TAF 
Protocol GS-US-311-1269 
Gilead Sciences, Inc. 
• 
Vital signs (blood pressure, pulse, respiration rate, and temperature) 
• 
Weight and height/length 
Final 
Amendment 2 
• 
Tanner Stage assessment (\Veeks 24 and 48 - except for subjects documented to have 
achieved Tanner Stage 5) 
• 
DXA Scan of the lumbar spine and the total body for BMD at Weeks 24 and 48 (± 10 days) 
• 
Urine collection for the following laborato1y procedures: 
-
Urinalysis 
-
Urine chemistry (\Veeks 2, 4, 8, 12, 24, and 48) 
-
Selected renal safety test ( collected fasted for Coho1is 1 and 2) including retinol binding 
protein and beta-2-microglobulin. If the subject has not fasted prior to the visit, the visit 
may continue; however, the subject must return within 72 hours in a fasted state to 
provide a urine sample for renal safety test (\Veeks 2, 4, 8, 12, 24, and 48). 
-
Urine pregnancy test (females of child bearing potential in Cohorts 1 & 2 only). If the 
urine pregnancy test is positive, study dmg will not be dispensed. The positive result will 
be confnmed with a sernm pregnancy test. If the sernm pregnancy test is positive the 
subject will be discontinued. 
• 
Blood collection for the following laborato1y procedures: 
-
Chemistiy profile: alkaline phosphatase, AST, ALT, total bilimbin, direct and indirect 
bilirnbin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorns, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is perfo1med in subjects with total amylase > 1.5 x ULN). 
-
Metabolic assessments: Fasting (no food or drinks, except water, at least 5 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
ti·iglycerides) for Coho1is 1 and 2. If the subject has not fasted prior to the visit, the visit 
may continue; however, the subject must return within 72 hours in a fasted state to draw 
blood for the metabolic assessments. Fasting requirement for Coho1is 3 and 4 will be 
specified in a future protocol amendment (\Veeks 24 and 48). 
-
Hematology profile: complete blood count (CBC) with differential and platelet count 
-
Plasma HIV-I RNA 
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Gilead Sciences, Inc. 
-
CD4+ cell count and percentage 
I 
Final 
Amendment2 
-
Sernm for bone safety tests ( collected fasted), including bone specific alkaline 
phosphatase (BsAP), sernm phosphorous, PlNP, CTX, PTH, 1,25-OH vitamin D, and 
25-OH vitamin D. If the subject has not fasted prior to the visit, the visit may continue; 
however, the subject must return within 72 hours in a fasted state to draw blood for bone 
safety tests (for Cohort 1: Weeks 4, 12, 24, and 48 (±6 days); for Cohorts 2,3, and 4: 
Weeks 8, 12, 24, and 48 (±6 days)) 
-
eGFR according to Schwaiiz fo1mula 
• 
Diaiy cai·d dispensation: 
-
Coho1i 1: Dispense subject diaiy cai·ds for subject to record administration of study mugs 
and their 3rd ARV agent for at least 3 days prior to the IPK visit (Week 2). 
-
Coho1is 2, 3, and 4, Paii A: Dispense subject diaiy cards for subject and/or 
pai·ent/guai·dian to record amninistration of study mugs and their 3rd ARV agent for at 
least 3 days prior to the IPK visit (Week 2 or 4). 
• 
Study mug dispensation: 
-
In-clinic dosing will occur at Weeks 2, 4, 8, and 12 
-
Document study mug dispensation for all study mugs dispensed (Weeks 4, 8, 12, 24, 36, 
and 48 [Week 48 study drug dispensing is for subjects that will continue post 
Week 48]). 
-
The subject should be counseled regai·ding the importance of adherence and taking their 
study medication and their 3rd ARV agent, once daily, at approximately the same time 
each day as directed by the Investigator. Sites should consider individual subject study 
mug dosing schedules while scheduling study visits requiring collection of PK samples. 
• 
Study mug accountability: 
-
Subjects and/or pai·ent/guai·dian should be reminded to bring their mug bottles of the 
F/TAF and their 3rd ARV agent with them to each visit for mug accountability 
(Weeks 1, 2, 4, 8, 12, 24, 36, and 48). 
• 
Subjects who meet the criteria for rebound should be managed according to Management 
Virologic Failure Section 6.10. 
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
PK Blood Collection:
Intensive PK: 
■
IPK samples will be collected for IPK evaluation for fasted subjects in Cohort 1
during the Week 2 visit and for fasted subjects in Cohort 2 Part A during either the 
Week 2 or the Week 4 visit or within 7 days after the completion of Week 2 or the 
Week 4 visit, as detailed in the PK manual. The protocol will be amended prior to 
Cohorts 3 and 4 screening. The IPK collection schedule and fasting requirement for 
Cohorts 3 and 4 will be specified in a future protocol amendment. 
■
Details of the IPK blood sampling procedures, and sample management will be 
documented in the Pharmacokinetic Sample Collection, Processing, Storage, and 
Shipment Manual (PK manual). Subject diary cards will be provided to subjects
and/or parent/guardian to record administration of study drugs and their
3rd ARV agent for at least 3 days prior to the PK visit. 
■
Subjects and/or parent/guardian should be instructed prior to the IPK visit that on the 
day of IPK evaluations they should be fasted and that their dose of F/TAF and their 
3rd ARV agent must not be taken prior to the visit. This is not applicable to the visits 
when the random PK sample is drawn.
■
If the subject has already dosed prior to the IPK evaluation visit or is not in a fasted 
state, the IPK assessments must not be completed. The subject should be instructed to 
return in a fasted state anytime within 7 days and to return completed Diary Cards.
■
If dosing non-compliance not related to AEs is identified on or prior to the IPK 
evaluation visit, the IPK assessments must not be completed. The subject should be 
counseled regarding proper dosing and be scheduled to return for the IPK evaluation 
visit no sooner than 3 days following compliant dosing and within 7 days and to 
return completed Diary Cards.
■
In both scenarios described above the subject and/or parent/guardian should be 
reminded again to be fasted and to not take the F/TAF or their 3rd ARV agent prior to 
arriving at the clinic on the day of the re-scheduled Intensive PK visit. 
■
Subject dosing diaries will be collected and reviewed on the day of the IPK study 
visit.


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Single PK: 
■
Cohort 1: A single random PK sample will be collected at Weeks 1 and 24, and a 
single observed PK dosing sample will be collected at any time between 15 min to 
4 hours post dose during Weeks 4 and 12 and a trough PK sample at 0 hours
(pre-dose, ≤ 30 minutes prior to dosing) during the Week 8 visit.
■
Cohorts 2, 3, and 4: A single random PK sample will be collected at Weeks 1 and 24,
and a single observed PK dosing sample will be collected at any time between 15 min 
to 4 hours post dose during Weeks 4 and 12 (Note: Single observed dosing PK 
sample does not need to be collected at Week 4 if Intensive PK is also collected at the 
Week 4 visit). Trough PK sampling will be performed at the Week 8 visit at 0 hours 
(pre-dose, ≤ 30 minutes prior to dosing).

Palatability and Acceptability Assessment:
Cohort 1: At the Week 2 visit palatability will be assessed 30 - 60 minutes after study 
drug dosing for all subjects undergoing IPK sampling. Acceptability will be assessed 
30 - 60 minutes after study drug dosing for active subjects at the next study visit 
immediately following approval of this protocol at the site.
Cohorts 2 Part A: Palatability and acceptability will be assessed at the Week 2 or Week 4 
visit, or within 7 days after the completion of the Week 2 or Week 4 visit,
30 - 60 minutes after study drug dosing for all subjects undergoing IPK sampling. 
Cohorts 3 and 4 Part A: Palatability and acceptability will be assessed for subjects 
undergoing IPK sampling. Assessment schedule will be specified in a future protocol
amendment.

PBMC Collection (at centers that have PBMC processing capability):
Cohorts 1 and 2: PBMC collection will be performed during the Week 8 visit only at 
study sites that can perform PBMC processing.
Cohorts 3 and 4: PBMC collection schedule will be specified in a future protocol
amendment.
For PK profiling in PBMCs, blood samples will be collected at 0 hours (≤30 minutes
pre-dose). Details of PBMC collection and processing will be documented in the PK 
manual.


F!TAF 
Protocol GS-US-311-1269 
Gilead Sciences, Inc. 
6.4. 
Early Study Drug Discontinuation (ESDD) 
Final 
Amendment2 
If a subject discontinues study drng prior to Week 48, the subject will be asked to return to the 
clinic within 72 hours of stopping study drngs for an ESDD Visit. Subjects will then be asked to 
continue attending all scheduled study visits. Subjects who are no longer taking study chug at 
Week 48 are not eligible to participate in the study extension. 
At the ESDD Visit, any evaluations showing abnormal results for which there is a possible 
or probable causal relationship with the study drug, should be repeated weekly ( or as often 
as deemed prudent by the investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained. 
The following evaluations are to be completed at the ESDD visit: 
• 
Review of AEs and concomitant medications 
• 
Complete physical examination (urogenital/anorectal exams will be perfo1med at the 
discretion of the Investigator) 
• 
Vital signs (blood pressure, pulse, respiration rate, and temperature) 
• 
Weight and height/length 
• 
12-lead ECG perfo1med supine 
• 
Urine collection for the following procedures: 
-
Urinalysis and urine chemistiy 
-
Urine pregnancy test (for females of childbearing potential in Coho1is 1 and 2 only). The 
positive result will be confomed with a sennn pregnancy test. 
-
Selected renal safety test, including retinol binding protein and beta-2-microglobulin 
(renal safety tests required if last test was acquired > 12 weeks from the date of the 
ESDD Visit (collected fasted for Coho1is 1 and 2). If the subject has not fasted prior to 
the visit, the visit may continue; however, the subject must return within 72 hours in a 
fasted state to provide a urine sample for renal safety test). 
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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN)
eGFR according to Schwartz formula
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4cell count and percentage
Plasma HIV-1 RNA 
Serum storage sample for possible additional testing
Serum will be collected for bone safety tests (collected fasted), including bone specific 
alkaline phosphatase (BsAP), serum phosphorous, P1NP, CTX, PTH, 1,25-OH vitamin 
D, and 25-OH vitamin D. If the subject has not fasted prior to the visit, the visit may 
continue, however the subject must return within 72 hours in a fasted state to draw blood 
for bone safety tests.

DXA scan (lumbar spine and total body) required if last scan was acquired > 12 weeks from 
the date of the ESDD Visit. DXA scan can occur up to 10 days after the ESDD Visit. 

Drug accountability
6.5.
30-Day Follow-Up Visit
Subjects who discontinue study drug prior to Week 48 will be required to return to the clinic 
30 days after completion of an ESDD visit for a 30-Day Follow-up visit. Those subjects who 
permanently discontinue study drug and continue in the study through at least one subsequent 
visit after the Early Study Drug Discontinuation Visit will not be required to complete the 
30-Day Follow-Up visit.
Subjects who complete 48 weeks on study drug and do not enroll in the extension phase of the 
study will be required to return to the clinic 30 days after completion of the Week 48 visit for a 
30-Day Follow-up visit.
For the purpose of scheduling a 30-Day Follow-Up visit, a ± 6 days window may be used.
CCI


F!TAF 
Protocol GS-US-311-1269 
Gilead Sciences, Inc. 
The following evaluations are to be completed at the 30-Day Follow-Up visit: 
• 
Review of AEs and concomitant medications 
• 
Symptom-directed physical examination 
• 
Vital signs (blood pressure, pulse, respiration rate, and temperature) 
• 
Weight and height/length 
• 
Urine collection for the following procedures: 
-
Urinalysis 
Final 
Amendment2 
-
Urine pregnancy test (for females of childbearing potential only for Coho1is 1 and 2). 
A positive result will be confnmed with a sernm pregnancy test. 
I 
• 
DXA scan (lumbar spine and total body) required if last scan was acquired > 12 weeks from 
the date of the 30 day follow-up Visit. DXA scan can occur up to 10 days after the 30 day 
follow-up Visit. 
• 
Blood sample collection for the following laborato1y analyses: 
-
Chemistiy profile: alkaline phosphatase, AST, ALT, total bilirnbin, direct and indirect 
bilirnbin, total protein, albumin, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorns, magnesium, potassium, and sodium, CPK, and uric acid 
-
eGFR according to Schwaiiz fo1mula 
-
Hematology profile: complete blood count (CBC) with differential and platelet count 
-
CD4+ cell count and percentage 
-
Plasma HIV-1 RNA 
-
Sernm storage sample for possible additional testing 
At the 30-Day Follow-Up visit, any evaluations showing abno1m al results for which there is a 
possible or probable causal relationship with the study diug. should be repeated weekly ( or as 
often as deemed prndent by the investigator) until the abno1mality is resolved, returns to 
baseline, or is othe1wise explained. 
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6.6.
Post Week 48 Assessments (every 12 weeks)
Subjects will receive their assigned treatment for 48 weeks. After completion of 48 weeks of 
study treatment, all subjects will be given the option to participate in an extension phase of the 
study. Gilead will provide F/TAF until a) the subject turns 18 years old and F/TAF is 
commercially available for use in adults in the country in which the subject is enrolled or
b) F/TAF becomes commercially available for pediatric use in the country in which the subject is 
enrolled or c) Gilead Sciences elects to terminate development of F/TAF in the applicable 
country. Subjects who are no longer taking study drug at Week 48 are not eligible to participate 
in the study extension. 
Subjects who choose to participate in the extension phase will return for study visits 
every 12 weeks (± 10 days).
The following evaluations are to be completed at each study visit unless otherwise specified:

Review of AEs and concomitant medications

Tanner Stage assessment (every 12 weeks except for subjects documented to have 
achieved Tanner Stage 5)

Either a symptom-directed physical examination every 12 weeks or a complete physical 
examination at every 48 weeks (urogenital/anorectal exams will be performed at the 
discretion of the Investigator).

Vital signs (blood pressure, pulse, respiration rate, and temperature) 

Weight and height/length

12 lead ECG performed supine every 48 weeks 

Urine collection for the following procedures:
Urinalysis Urine Chemistry (every 12 Weeks)
Urine pregnancy test (females of child bearing potential only). If the urine pregnancy test 
is positive, study drug will not be dispensed. The positive result will be confirmed with a 
serum pregnancy test. If the serum pregnancy test is positive the subject will be 
discontinued from the study.
Urine sample storage for possible additional testing (urine chemistry including urine 
phosphorus and urine creatinine)
Selected renal safety tests (collected fasted for Cohorts 1 and 2), including retinol binding 
protein and beta-2-microglobulin. If the subject has not fasted prior to the visit, the visit 
may continue; however, the subject must return within 72 hours in a fasted state to 
provide a urine sample for renal safety test (every 12 Weeks).


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Amendment 2
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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase > 1.5 × ULN).
Metabolic assessments: Fasting (no food or drinks, except water, at least 5 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and 
triglycerides) for Cohorts 1 and 2. If the subject has not fasted prior to the visit, the visit 
may continue; however, the subject must return within 72 hours in a fasted state to draw 
blood for the metabolic assessments (every 24 Weeks). Note that glucose analysis will be 
done as part of the fasting metabolic assessments and not as part of the chemistry profile, 
every 24 weeks post week 96
Serum will be collected for bone safety tests (collected fasted), including bone specific 
alkaline phosphatase (BsAP), serum phosphorous, P1NP, CTX, PTH, 1,25-OH vitamin 
D, and 25-OH vitamin D will be performed at every 12 weeks (±10 days) thereafter. If 
the subject has not fasted prior to the visit, the visit may continue; however, the subject 
must return within 72 hours in a fasted state to draw blood for bone safety tests
(every 24 Weeks)
Plasma sample storage for virology, safety, and/or PK testing (every 12 weeks)
eGFR according to Schwartz formula
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4cell count and percentage
Plasma HIV-1 RNA 

DXA scans of the lumbar spine and of the total body for BMD (every 24 Weeks ± 10 days)

Study drug dispensation:
Subjects and/or parent/guardian should be instructed to take study drugs with or without 
food as determined by their 3rd ARV agent. The subject and/or parent/guardian should be 
counseled regarding the importance of adherence and taking their study medication at 
approximately the same time each day as directed by the Investigator.

Study drug accountability:
Subjects and/or parent/guardian should be reminded to bring the required drug bottles of 
the F/TAF and their 3rd ARV agent with them for drug accountability.


F!TAF 
Protocol GS-US-311-1269 
Gilead Sciences, Inc. 
6.7. 
Bone Evaluations 
Final 
Amendment 2 
For all subjects DXA scans will be perfo1med prior to study diug adininistration at the 
Baseline/Day 1, at Weeks 24 and 48 (::1:10 days), followed by eve1y 24 weeks post Week 48 
(::1:10 days), and the Early Study Drng Discontinuation Visit (if applicable) up to 10 days after the 
ESDD visit date. Scans will cover the lumbar spine and total body to measure changes in bone 
mineral density (BMD). DXA scan results will be provided to study sites. 
A complete description of the procedures perfo1med for the DXA scans will be provided in a 
DXAmanual. 
6.8. 
Bone and Renal Safety Evaluations 
For subjects in Coho1i 1, the following bone safety tests will be collected (fasted) at 
Baseline/Day 1 and Weeks 4, 12, 24, and 48 (±6 days), followed by eve1y 24 weeks post 
Week 48 (::1:10 days): BsAP, PlNP, CTX, PTH, 1,25-OH vitamin D, and 25-OH vitamin. 
For subjects in Coho1i 2, 3, and 4, the following bone safety tests will be collected (fasted) at 
Baseline/Day 1 and Weeks 8, 12, 24, and 48 (±6 days), followed by eve1y 24 weeks post 
Week 48 (::1:10 days): BsAP, PlNP, CTX, PTH, 1,25-OH vitamin D, and 25-OH vitamin. 
For all subjects, urine will also be collected for selected renal safety tests, including urine 
chemistiy, retinol binding protein, and beta-2-inicroglobulin at the Baseline/Day 1 Visit, 
Weeks 2, 4, 8, 12, 24, and 48, followed by eve1y 12 weeks post Week 48 (::1:10 days). 
Bone and renal safety test assessments will be collected fasted. If the subject has not fasted prior 
to the visit, the visit may continue; however, the subject must return within 72 hours in a fasted 
state to di·aw blood for bone safety tests and provide a urine sample for renal safety tests. 
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6.10.
Virologic Failure and Management of Virologic Rebound
Subjects who experience virologic rebound (VR), as defined below, will be considered to have 
virologic failure. 
If the viral load is ≥ 50 copies/mL, HIV-1 RNA should be repeated at a scheduled or 
unscheduled visit (2-4 weeks after the date of the original test with HIV-1 RNA 
≥50 copies/mL).
Subjects will be considered to have virologic rebound if they have confirmed HIV-1 RNA 
≥50 copies/mL (two consecutive tests) at scheduled or unscheduled visits.
Upon confirmation of HIV-1 RNA ≥ 50 copies/mL, potential causes of virologic failure should 
be documented. Assessments should include:

Review treatment adherence with subject and/or parent/guardian

Review of AEs and concomitant medications

Comorbidities (eg, active substance abuse, depression, other intercurrent illnesses)
If virologic rebound is confirmed at the scheduled or unscheduled visit, and the HIV-1 RNA 
value is ≥ 400 copies/mL, the blood samples from the confirmation visit will be used for HIV-1 
genotype/phenotype testing.
If genotype/phenotype resistance to study drug is documented, study drugs should be 
discontinued. 
If no resistance is detected from genotype/phenotype testing, subject may remain on study drug 
and the HIV-1 RNA testing should be repeated (2-4 weeks from the date of confirmed test with 
viral load ≥ 50 copies/mL) until <50 copies/mL is achieved or the subject discontinues. 
Subjects experiencing virologic failure due to emergent resistance on study, but whose virus
remains sensitive to FTC and TFV will be permitted to switch to a new fully active 
3rd ARV agent and remain on their F/TAF-containing regimen. Subjects unable to tolerate 
current 3rd agents due to clinically significant toxicities will be permitted to switch after 
consultation with the medical monitor to a new fully active 3rd ARV agent and remain on their 
F/TAF-containing regimen.
Investigators should carefully evaluate the benefits and risks of remaining on study drug for each 
individual subject and document this assessment in the on site medical record. Investigators who 
opt to discontinue study drugs for an individual subject must discuss with the 
Gilead Medical Monitor prior to study drug discontinuation. 
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
rebound.


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Gilead Sciences, Inc.
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Figure 6-1.
Virologic Rebound Schema
a
If virologic rebound is not confirmed, the subject will remain on their current regimen
b
If virologic rebound is confirmed, and the HIV-1 RNA is ≥ 400 copies/mL, the HIV-1 genotype and phenotype 
(reverse transcriptase and protease) will be analyzed
c
Based on the results of the genotype/phenotype assays, the subject will remain on study drugs, or study drugs will be 
discontinued. If genotyping/phenotyping fails, a new ARV regimen may be configured at the discretion of the Investigator
d
If no resistance detected, HIV-1 RNA will be repeated (2-4 weeks later) until < 50 copies/mL is achieved or the subject 
discontinues. Investigator is to review and discuss study drug continuation/discontinuation options with Medical Monitor 
prior to study drug discontinuation
e
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study
6.10.1.
Subjects with ≥ 400 copies/mL of HIV-1 in Absence of Confirmed Virologic 
Failure
Subjects may also be analyzed for resistance that does not meet the virologic failure criteria. 
Subjects who have HIV-1 RNA ≥400 copies/mL at Weeks 24 or 48 or the last visit while 
receiving study drugs (within 72 hours of discontinuation of study treatment) will be analyzed 
for resistance.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 


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


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements. 
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (e.g., clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to IMP interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (e.g., electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (e.g., anemia), not the 
laboratory result (i.e., decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Appendix 3.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The Investigator or qualified Sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified sub-investigator is responsible for assessing the relationship to IMP 
therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an
alternative causality must be provided (e.g., pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.


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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 (e.g., invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures (e.g., venipuncture)
7.2.2.
Assessment of Severity
Severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4). For adverse events associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
Requirements for Collection Prior to Study Drug Initiation
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (CRF/eCRF): 

all serious adverse events (SAEs) 

adverse events related to protocol-mandated procedures.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 4 weeks after last administration of study IMP must be reported to the CRF/eCRF database 
as instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e., signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
CRF/eCRF database and Gilead Drug Safety and Public Health (DSPH) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed. Any SAEs and deaths that occur after the post treatment follow-up visit but 
within 30 days of the last dose of study IMP, regardless of causality, should also be reported. 


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All SAEs should be followed up until resolution if possible. If by the last day on study (including 
the off-study medication follow-up period) the SAE has not resolved, then the SAE will be 
followed up until the investigator and/or Gilead Sciences determine that the subject's condition is 
stable. However, Gilead Sciences may request that certain SAEs be followed until resolution.
Investigators are not obligated to actively seek SAEs after the follow up 30-day period. 
However, if the investigator learns of any SAEs that occur after study participation has 
concluded and the event is deemed relevant to the use of IMP, he/she should promptly document 
and report the event to Gilead DSPH.

All AEs and SAEs will be recorded in the CRF/eCRF database within the timelines 
outlined in the CRF/eCRF completion guideline. 

At the time of study start, SAEs will be reported using an electronic SAE (eSAE) system
using the Electronic Serious Adverse Event Reporting Process detailed below. Gilead will 
provide training and account information prior to implementing an eSAE system.

The Serious Adverse Event Paper Reporting Process is to be used only if the EDC System is 
not available.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel will record all SAE data in the eCRF database and from there transmit the 
SAE information to Gilead DSPH within 24 hours of the investigator’s knowledge of the 
event. Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, 
i.e., the eCRF database is not functioning, record the SAE on the paper serious adverse event 
reporting form and submit within 24 hours as described above.
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.

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, i.e., the 
eCRF database is not functioning, record the SAE on the paper serious adverse event 
reporting form and submit within 24 hours as described above.

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.


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• 
If an SAE has been reported via a paper fonn because the eCRF database has been locked, no 
further action is necessa1y. 
• 
For fatal or life-threatening events, copies of hospital case repo1ts, autopsy repo1ts, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the trnceability of a document to the subject identifiers. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
repo1ts. 
• 
Any medications necessaiy for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject's CRF/eCRF and the event description section of the SAE 
fo1m. 
Serious Adverse Event Paper Repo1ting Process 
SAEs will be recorded on the serious adverse event paper report fo1m and submitted by faxing or 
emailing the repo1t fo1m within 24 hours of the Investigator's knowledge of the event to the 
attention of Gilead DSPH and the medical monitor: 
Gilead Sciences Drng Safety 
Public Health (DSPH): 
Gilead Sciences Medical Monitor: 
Fax: 
E-mail: 
Name: 
Telephone: 
Mobile Phone: 
Fax: 
E-mail: 
7.4. 
Gilead Reporting Requirements 
IPIPD 
IPIPD 
IPIPD 
IPIPD 
IPIPD 
IPIPD 
IPIPD 
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 countiy-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulato1y agencies reports of SAEs, serious adverse drng reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulato1y 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
cmTent regulations. 
Assessment of expectedness for SAEs will be dete1mined by Gilead using reference safety 
info1mation specified in the investigator's brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR repo1ts. The 
investigator should notify the IRB or IEC of SUSAR reports as soon as is practical, where this is 
required by local regulato1y agencies, and in accordance with the local institutional policy. 
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7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
7.5.1.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 as outlined below.

All clinically significant Grade 3 and 4 laboratory abnormalities should be repeated
immediately to confirm toxicity grade. Confirmation of toxicity grade is required prior to the 
next dose of investigational medicinal product for any Grade 3 and 4 laboratory abnormality 
that in the opinion of the Investigator is clinically significant and may pose a risk to the 
subject’s safety.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
(Refer to Appendix 4).

Any questions regarding toxicity management should be directed to the 
Gilead Medical Monitor.
7.5.1.1.
Management of Bone Toxicity
As there is uncertainty surrounding the clinical significance and management of decreases in 
bone mineral density for HIV-1 infected children and adolescents, Gilead recommends that any 
subject who has a DXA scan that demonstrates a decrease from baseline or from the previous 
visit of ≥ 4% to have a repeat DXA within 7 calendar days to confirm the decrease. If the DXA 
is confirmed the investigator in consultation with the Gilead medical monitor may decide to 
discontinue the study drug but keep the subject on the study if feasible. 
7.5.2.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue investigational medicinal product at the discretion of the Investigator.
7.5.3.
Grades 3 Laboratory Abnormality or Clinical Event
For Grade 3 clinically significant laboratory abnormality or clinical event, investigational 
medicinal product may be continued if the event is considered to be unrelated to investigational 
medicinal product.
For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by repeat 
testing, that is considered to be related to investigational medicinal product, investigational 
medicinal product should be withheld until the toxicity returns to ≤Grade 2.


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If a laboratory abnormality recurs to ≥Grade 3 following rechallenge with investigational 
medicinal product and is considered related to investigational medicinal product, then 
investigational medicinal product should be permanently discontinued and the subject managed 
according to local practice. Recurrence of laboratory abnormalities considered unrelated to 
investigational medicinal product may not require permanent discontinuation.
7.5.4.
Grade 4 Laboratory Abnormality or Clinical Event
For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality confirmed 
by repeat testing that is considered related to investigational medicinal product, investigational 
medicinal product should be permanently discontinued and the subject managed according to 
local practice. The subject should be followed as clinically indicated until the laboratory 
abnormality returns to baseline or is otherwise explained, whichever occurs first. A clinically 
significant Grade 4 laboratory abnormality that is not confirmed by repeat testing should be 
managed according to the algorithm for the new toxicity grade.
Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant Grade 3-4 laboratory abnormality (e.g., CK elevation after strenuous exercise, or 
triglyceride elevation that is non-fasting or that can be medically managed) or a Grade 3-4 
clinical event considered unrelated to investigational medicinal product.
7.5.5.
Management of Hyperbilirubinemia in Patients Receiving Ritonavir Boosted 
Atazanavir
Most patients taking atazanavir sulfate experience asymptomatic elevations in indirect 
(unconjugated) bilirubin related to inhibition of UDP-glucuronyl transferase (UGT). In pediatric 
clinical trials, 58% of patients experienced Grade 3 to 4 elevations (≥ 3.2 mg/dL) in total 
bilirubin (Reyataz US Prescribing Information 2013). As subjects in this study who are taking 
ATV/r as their 3rd ARV agent may frequently have atazanavir-associated hyperbilirubinemia, the 
management of graded laboratory abnormalities described above in Section 7.5 is not applicable 
for the management of graded hyperbilirubinemia in these subjects.
However, repeat testing should be done and alternative etiologies (e.g. acute hepatitis B or C) 
should be sought in the following subjects:
1) In those with elevation in conjugated (direct) bilirubin > 1.5 × ULN (i.e. direct 
hyperbilirubinemia), regardless of the hyperbilirubinemia grade, liver labs (total bilirubin, 
direct bilirubin, AST, ALT) should be repeated within 7 days of the Investigator being 
notified of the elevated bilirubin level and be discussed with the Medical Monitor. 
Thereafter, the management of a subject who continues to have direct bilirubin > 1.5 × ULN, 
which is deemed as clinically not significant, should be followed according to the clinical 
judgment of the Investigator.
2) In those with hepatic transaminase elevation, the graded AST or ALT abnormalities should 
be managed according to Section 7.5


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Dose modification of atazanavir sulfate is not permitted. Subjects who experience unacceptable 
jaundice/scleral icterus due to atazanavir-associated hyperbilirubinemia can be discontinued 
from the study at the discretion of the Investigator.
7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, and 
pregnancy reports regardless of an associated AE. Also includes reports of adverse reactions in 
infants following exposure from breastfeeding, and reports of adverse reactions associated with 
product complaints and reports arising from occupational exposure.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer. 
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labeling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the Investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product. 
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The Investigator should report all pregnancies in the female subjects that are identified after 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to Gilead DSPH using the pregnancy report form within 24 hours of becoming aware of 
the pregnancy. Refer to Section 7.6.2 and 7.3 and the CRF/eCRF completion guidelines for full 
instructions on the mechanism of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.


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Any premature termination of pregnancy (e.g., a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: Email: 
and Fax: 
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH, fax number 
 or email 
Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Recommendations.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the Investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of medications prohibited by this protocol should not be reported as 
“misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.6.2 and the CRF/eCRF completion guidelines for full instructions on the 
mechanism of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE CRF/eCRF and/or the SAE report form. Details of the symptoms 
and signs, clinical management, and outcome will be reported, when available.
PPD
PPD
PPD
PPD


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objectives of this study are:

To evaluate the PK of TAF in HIV-1 infected children and adolescents virologically 
suppressed on 2-NRTI-containing regimen,

To evaluate the safety and tolerability of F/TAF through Week 24
The secondary objectives of this study are:

To evaluate the PK of TFV and FTC 

To evaluate the safety, tolerability, and efficacy of F/TAF through Week 48.
8.1.2.
Primary Endpoints
The primary endpoints are:

The PK parameter AUCtau for TAF

Incidence of treatment-emergent SAEs and all treatment-emergent adverse events through 
Week 24 
8.1.3.
Secondary Endpoints
The secondary endpoints are:

PK parameters of Cmax, Clast, Cl/F, and Vz /F for TAF, AUCtau, Cmax, and Ctau for FTC and 
TFV

Incidence of treatment-emergent SAEs and all treatment-emergent adverse events through 
Week 48 

The percentage of subjects with HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as defined 
by the US FDA-defined snapshot algorithm 

The change from baseline in CD4+ cell count (cells/μL) and CD4+ percentage at 
Weeks 24 and 48

The palatability and acceptability of the age-appropriate F/TAF formulation


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8.2. 
8.2.1. 
8.2.1.1. 
Analysis Conventions 
Analysis Sets 
All Enrolled 
The all enrolled analysis set includes all subjects who are enrolled into the study. 
All enrolled analysis set is the primaiy analysis set for by-subject listings. 
8.2.1.2. 
8.2.1.2.1. 
Efficacy 
Full Analysis Set 
Final 
Amendment2 
The full analysis set (FAS) will include all subjects who ai·e enrolled in the study and have 
received at least one dose of study medication. 
8.2.1.3. 
8.2.1.3.1. 
Safety 
Safety Analysis Set 
The safety analysis set will include all subjects who are enrolled in the study and have received 
at least one dose of study medication. 
8.2.1.4. 
8.2.1.4.1. 
DXA 
Total Body Less Head DXA Analysis Set 
The total body less head DXA analysis set will include all subjects who (1) are enrolled in the 
study, (2) have received at least one dose of study medication, and (3) have non-missing total 
body less head BMD value for the baseline visit. 
8.2.1.4.2. 
Spine DXA Analysis Set 
The spine DXA analysis set will include all subjects who (1) are enrolled in the study, 
(2) have received at least one dose of study medication and (3) have non-missing spine BMD 
value for the baseline visit. 
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8.2.1.5.
Pharmacokinetics
8.2.1.5.1.
IPK Analysis Set
The IPK analysis set will include all subjects who (1) are enrolled in Cohort 1 or Part A of 
Cohorts 2 (each group), 3, and 4 for IPK evaluation, (2) have received at least one dose of study 
medication and (3) have at least 1 non-missing PK concentration data for any analyte of interest 
(e.g., FTC, TAF, and TFV). The IPK analysis set will be used for analyses of intensive PK 
analytes of TAF, TFV, and FTC.
8.2.1.5.2.
PK Analysis Set
The PK analysis set will include all subjects who (1) are enrolled into the study, 
(2) have received at least one dose of study medication and (3) have at least 1 non-missing PK 
concentration data for any analyte of interest (e.g., FTC, TAF, and TFV). The PK analysis set 
will be used for analyses of general pharmacokinetics.
8.2.1.5.3.
PBMC PK Analysis Set
The PBMC PK analysis set will include all subjects who (1) are enrolled into the study, 
(2) have received at least one dose of study medication and (3) have at least 1 non-missing 
concentration data of TFV-DP. The PBMC PK analysis set will be used for pharmacokinetic 
analyses of TFV-DP.
8.3.
Data Handling Conventions
Natural logarithm transformation for PK parameters, such as Cmax, Clast, Ctau, AUClast, and 
AUCtau, will be applied for pharmacokinetic analysis.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized using standard descriptive 
methods.
Demographic summaries will include sex, race/ethnicity, and age.
Baseline data including body weight, height/length, body mass index, HIV-1 infection, and 
enrollment distribution will be summarized.
8.5.
Efficacy Analysis
Efficacy endpoints results from each group or cohort will be descriptive in nature. 
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA < 50 copies/mL at 
Week 24 as defined by the US FDA-defined snapshot algorithm using the full analysis set (FAS).
Virologic outcomes will be summarized using frequency counts and percentages. The 95% CI
for the percentage estimate for each group or cohort will be constructed using the Exact method. 


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8.5.2.
Secondary Analyses
The percentage of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the US 
FDA-defined snapshot algorithm will be summarized in the same manner as the primary efficacy 
endpoint.
The change from baseline in CD4+ cell count and CD4+ percentage will be summarized by visit, 
group, and cohort using descriptive statistics. 
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set.
All safety data collected on or after the date that the study drug was first administered up to the 
date of last dose of study drug plus 30 days, unless specified otherwise, will be summarized by 
group and cohort. Data for the pretreatment period and the period post the date of last dose of 
study drug plus 30 days will be included in data listings.
Safety results from each group and cohort will be descriptive in nature. F/TAF results from all
cohorts will be combined to describe the overall safety profile of F/TAF in subjects 1 month to 
< 18 years of age. 
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration data. Duration of exposure to study drug will be expressed as the number of 
weeks between the first and last dose of the study regimen, inclusive, regardless of temporary 
interruptions in study regimen administration. Exposure data will be summarized by group, 
cohort, and overall. Dosing information for individual subjects will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Treatment-emergent AEs are events that meet one of the following criteria up to 30 days after the 
permanent discontinuation of the study drug:

Events with onset dates on or after the first dose date of study drug,

Events that result in permanent study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC 
and PT) will be provided by group, cohort and overall. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing.


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On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Catego1y C events that are indicative of an AIDS-Defining Diagnoses. The Gilead medical 
personnel will review the possible Catego1y C events and approve the events that meet the 
definition. Those events that do meet the Catego1y C definition of an AIDS-Defining Diagnosis 
will be listed. A listing of Catego1y C, AIDS-Defining Diagnosis can be found in Appendix 6. 
8.6.3. 
Laboratory Evaluations 
Selected laborato1y data will be summarized using observed data. Absolute values and changes 
from baseline at all scheduled visits will be summarized. 
Graded laborato1y abnonnalities will be defined using the grading scheme defined in Grading of 
laborato1y abno1malities provided in Appendix 4. 
Incidence of treatment-emergent laborato1y abno1malities, defined as values that increase at least 
one toxicity grade from baseline at any time post baseline up to and including the date of last 
dose of study regimen plus 30 days, will be summarized by group, coho1t and overall. If baseline 
data are missing, then any graded abno1mality (i.e., at least a Grade 1) will be considered 
treatment emergent. The maximum toxicity grade will be summarized by laborato1y parameter. 
Laborato1y abno1malities that occm before the first dose of study regimen or after the subject has 
been discontinued from treatment plus 30 days will be included in a data listing. 
8.6.4. 
Bone Mineral Density 
Z-scores (standard Z-scores and adjusted Z-scores) for spine 
and total body less head BMD and change from baseline in Z-scores will also be summarized by 
visit, group and coho1t . The adjustment method will be specified in the Statistical Analysis Plan. 
8.6.5. 
Bone and Renal Safety Evaluations 
Selected bone safety tests, including BsAP, PlNP, CTX, PTH, 1,25-OH vitamin D, and 25-OH 
vitamin D, will be summarized by visit using descriptive statistics. 
For all subjects in all coho1ts, selected renal safety tests, including retinol binding protein, and 
beta-2-Inicroglobulin, will be summarized by visit, group, and coho1t using descriptive statistics. 
8.6.6. 
Tanner Stage Assessment 
The Tanner stage assessment score will be summarized by study visit, group, and coho1t . 
8.6.7. 
Acceptability and Palatability 
Acceptability and palatability will be summarized by study visit, group, and coho1t. 
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8.6.8. 
Other Safety Evaluations 
Final 
Amendment2 
Weight and height/length will be summarized by visit. Safety ECGs will be summarized. 
Number and percentage of subjects with abnonnal safety ECG will be summarized by visit, 
group, and cohort. 
8.7. 
Pharmacokinetic Analysis 
The concentrntion data ofTAF, FTC, and TFV (if applicable) over sampling time will be listed 
and SUilllllarized using descriptive statistics by group and cohort. PK parameters (e.g., AUC1au, 
AUC1ast, Cmax, Tmax, C1ast, T1ast, C1au, "-z., apparent CL, apparent V2, and T ½) will be listed and 
summarized for analytes TAF, FTC, and TFV (as applicable) using descriptive statistics 
(e.g., sample size, arithmetic mean, geometi·ic mean, coefficient of variation%, standard 
deviation, median, Ql , Q3, minimum, and maximum) by group and cohort. Plasma 
concenti·ations over time will be plotted in semilogarithmic and linear fo1mats as mean 
± standard deviation, and median (Ql , Q3). 
TAF exposure PK parameter (i.e., AUC1au) achieved in pediati·ic subjects from Cohort 1 and 
Pait A of Coho1is 2 (Groups 1 and 2), 3, 4 will be compared to historical adult data 
(ie, GS-US-311-1089). 
An analysis of variance will be canied out for log-ti·ansfonned TAF AUC1au as a prima1y 
pai·ameter while other pha1macokinetic pai·ameters such as Cmax will be explored. T AF data from 
each coho1i will be compai·ed to Study GS-US-311-1089 adult population PK T AF data by dose 
level and type of boosted PI ( eg, A TV /r or other Pis/r) if applicable. If the lower bound of the 
90% CI of the geometi·ic mean ratio (pediati·ic subjects vs adult subjects) is above 70% for TAF 
AUC1au, the TAF dose will be confnmed. 
In addition, the 95% CI of the geometi·ic mean estimate of apparent CL and apparent V z of T AF 
will be provided. 
8.8. 
Acceptability and Palatability 
Acceptability and palatability for the age-appropriate F/TAF FDC fo1mulation will be 
summarized. Treatinent adherence will also be summarized. 
8.9. 
Sample Size 
Cohort 1: Twenty-five subjects from Coho1i 1 in the TAF h'eatment aim will provide at least 
90% power to tai·get a 95% confidence interval within 60% and 140% of the geomeh'ic mean 
estimate of apparent CL and apparent V2 ofTAF, respectively, assuming a standai·d deviation of 
0.60 for CL and 0.58 for V2 (natural log scale) estimated from Study GS-US-292-0106 Coho1i 1 
PaiiA. 
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Cohort 2 (Group 1) Part A: At least 10 subjects on boosted ATV + F/TAF and 6 subjects on 
boosted LPV or DRV + F/TAF, compared with the population PK data from 44 adult subjects on 
boosted ATV + F/TAF and 87 adult subjects on boosted LPV or DRV + F/TAF in 
Study GS-US-311-1089, respectively, will each provide at least 80% power to show the lower 
bound of a 90% CI of geometric mean ratio (pediatric subjects vs. adult subjects) greater than 
70% for AUCtau of TAF, assuming that the expected geometric mean ratios of TAF AUCtau
between pediatric subjects and adult subjects are equal to 1 and the standard deviations are 0.40 
(with boosted ATV + F/TAF) and 0.33 (with boosted LPV or DRV + F/TAF) ng*hr/mL for TAF 
AUCtau (natural log scale) estimated from the population PK data in Study GS-US-311-1089.
Part A of Cohorts 2 (Group 2), 3, and 4: At least 10 subjects on boosted ATV + F/TAF and 
7 subjects on any other third agent + F/TAF in each group or cohort, compared with the 
population PK data from the 292 adults on any third agent + DVY in Study GS-US-311-1089, 
will provide 90% power to show the lower bound of a 90% CI of geometric mean ratio (pediatric 
subjects vs. adult subjects) greater than 70% for AUCtau of TAF, assuming that the expected 
geometric mean ratio of TAF AUCtau between pediatric subjects and adult subjects is equal to 1 
and the standard deviation is 0.48 ng*hr/mL for TAF AUCtau (natural log scale) estimated from 
the population PK data in Study GS-US-311-1089.
A total of at least 100 subjects receiving F/TAF from Cohort 1, and Parts A and B of Cohort 2 
(Groups 1 and 2), Cohort 3, and Cohort 4 combined will provide reasonable assessment of safety 
through Week 48 in pediatric subjects.
Sample size and power calculations were made using the statistical software package nQuery 
Advisor (Version 7.0) and R.
8.10.
Data Monitoring Committee
An external multidisciplinary independent data monitoring committee (IDMC) will review the 
progress of the study and perform interim reviews of safety, efficacy and PK data and provide 
recommendation to Gilead whether the nature, frequency, and severity of adverse effects 
associated with study treatment warrant the early termination of the study in the best interests of 
the participants, whether the study should continue as planned, or the study should continue with 
modifications. 
The IDMC’s specific activities will be defined in an approved charter, which will define the 
IDMC’s membership, conduct and meeting schedule.
While the IDMC will be asked to advise Gilead regarding future conduct of the study, including 
possible early study termination, Gilead retains final decision-making authority on all aspects of 
the study.


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8.11.
Analysis Schedule
Cohort 1
The Week 48 analysis of efficacy and safety will be conducted after the last subject completes 
Week 48 visit or prematurely discontinue from the study drug. Efficacy and safety endpoints at 
Week 24 for Cohort 1 will also be analyzed at the Week 48 analysis. A PK analysis will also be 
performed at the Week 48 analysis. 
Cohorts 2, 3 and 4
A PK analysis will be performed after all the subjects enrolled in Part A complete the IPK 
evaluation within each group (Cohort 2) or each cohort (Cohorts 3 and 4). After the confirmation 
of TAF dose and TAF safety acceptance among the subjects in Part A, enrollment in Part B will 
be initiated. 
The Week 24 analysis of efficacy and safety will be conducted after the last subject completes
Week 24 visit or prematurely discontinue from the study drug within each group (Cohort 2) or 
cohort (Cohorts 3 and 4). The Week 48 analysis of efficacy and safety will be conducted after the 
last subject completes Week 48 visit or prematurely discontinue from the study drug within each 
group (Cohort 2) or cohort (Cohorts 3 and 4).
Final analysis will be performed after all subjects complete the study or prematurely discontinue 
from the study.
8.12.
Endpoint Adjudication Committee
No formal endpoint adjudication committee is planned for this study.


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


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


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


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Prior to database lock (or any interim time points as described in the clinical data management 
plan), the investigator will use his/her log in credentials to confirm that the forms have been 
reviewed, and that the entries accurately reflect the information in the source documents.
System-generated or manual queries will be issued to the investigative site staff as data 
discrepancies are identified by the monitor or internal Gilead staff, who routinely review the data 
for completeness, correctness, and consistency. 
The site coordinator is responsible for responding to the queries in a timely manner, within the 
system, either by confirming the data as correct or updating the original entry, and providing the 
reason for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the 
site with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5
9.1.7.
Investigational Medicinal Product Accountability and Return
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 IMP disposal procedures and 
provide appropriate instruction for destruction of unused IMP supplies. If the site has an 
appropriate standard operating procedure (SOP) for drug destruction as determined by Gilead 
QA, the site may destroy used (empty or partially empty) and unused IMP supplies in accordance 
with that site’s approved SOP. A copy of the site’s approved SOP will be obtained for central 
files. 
If IMP is destroyed on site, the investigator must maintain accurate records for all IMP
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, or to regulatory authority or health authority inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.


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


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


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10.
REFERENCES
Capeau J. Premature Aging and Premature Age-Related Comorbidities in HIV-Infected Patients: 
Facts and Hypotheses. Clin Infect Dis 2011;53 (11):1127-9.
Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in Pediatric Infection. Available at http://aidsinfo.nih.gov/guidelines. 
Accessed: March 14 2014.
EMTRIVA®, Gilead Sciences Inc. EMTRIVA® (emtricitabine) capsule, for oral use. 
EMTRIVA® (emtricitabine) oral solution. US Prescribing Information. Foster 
City, CA. Revised November.  2012:
Gilead Sciences Inc. GENVOYA® (elvitegravir, cobicistat, emtricitabine, and tenofovir 
alafenamide) tablets, for oral use. US Prescribing Information. Foster City, CA 
Revised March.  2016:
Gilead Sciences International Limited. Genvoya 150mg/150mg/200mg/10mg film coated tablets. 
Summary of Product Characteristics.  Updated 07 March.  2016:
Ginsberg G, Hattis D, Miller R, Sonawane B. Pediatric pharmacokinetic data: implications for 
environmental risk assessment for children. Pediatrics 2004;113 (4 Suppl):973-83.
HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children with 
HIV. Guidelines for the use of Antiretroviral Agents in Pediatric HIV Infection. 
Revised: 27 April.  2017.
Joint United Nations Programme on HIV/AIDS (UNAIDS). Fact Sheet 2016. Available at: 
http://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf
.  2016.
McCarver DG. Applicability of the principles of developmental pharmacology to the study of 
environmental toxicants. Pediatrics 2004;113 (4 Suppl):969-72.
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of 
mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. 
Lancet 1998;352 (9142):1725-30.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60.


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Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children. Guidelines 
for the use of antiretroviral agents in pediatric HIV infection: Available at: 
http://aidsinfo.nih.gov/ContentFiles/PediactricGuidelines.pdf. Accessed 
September 9, 2012.  2011:1-279. 
Prejean J, Song R, Hernandez A, Ziebell R, Green T, Walker F, et al. Estimated HIV incidence 
in the United States, 2006-2009. PLoS ONE 2011;6 (8):e17502.
Robbins BL, Greenhaw JJ, Connelly MC, Fridland A. Metabolic pathways for activation of the 
antiviral agent 9-(2-phosphonylmethoxyethyl)adenine in human lymphoid cells. 
Antimicrob Agents Chemother 1995;39 (10):2304-8.
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84.
Welch S, Sharland M, Lyall EG, Tudor-Williams G, Niehues T, Wintergerst U, et al. PENTA 
2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. 
HIV Med 2009;10 (10):591-613.
World Health Organization (WHO). Developing Dosing Guidance For New And Upcoming 
Formulations Of Paediatric Antiretrovirals In Line With Treatment 2.0 Priorities. 
Presented at: Paediatric Antiretroviral Working Group.; 2011 25-26 October; 
Geneva, Switzerland. 


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


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 2/3, Open-Label, Multi-Cohort Switch Study to Evaluate Emtricitabine/Tenofovir 
Alafenamide (F/TAF) in HIV-1 Infected Children and Adolescents Virologically Suppressed on 
a 2-NRTI-Containing Regimen 
GS-US-311-1269, Amendment 2, 02 August 2017 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PPD 
PPD 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
infoimation provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 89 
02August2017 


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Appendix 2.
Study Procedures Table
Study Procedure
Screenc
Baseline/ 
Day 1d
End of Weeka
Post Week 48b
30 Day 
Follow-upe
ESDDf
1
2
4
8
12
24
36
48
Every 
12 Wks
Every 
24 Wks
Informed Consent/Assent
X
Medical Historyg
X
Concomitant Medications
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
Complete Physical Exam
X
X
X
X
Xh
X
Symptom-Directed Physical Exami
X
X
X
X
X
X
X
X
12-Lead ECG (performed supine)
X
Xj
X
Vital Signs 
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight and Height/Length
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Chemistry
X
X
X
X
X
X
X
X
X
Selected Renal Safety Testsk
X
X
X
X
X
X
X
X
Xl
Serum Pregnancy Testm
X
Urine Pregnancy Testn
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry Profile
X
X
X
X
X
X
X
X
X
X
X
X
X
Metabolic Assessments
X
X
X
X
Estimated GFR
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology Profile
X
X
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
CCI


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Study Procedure
Screenc
Baseline/ 
Day 1d
End of Weeka
Post Week 48b
30 Day 
Follow-upe
ESDDf
1
2
4
8
12
24
36
48
Every 
12 Wks
Every 
24 Wks
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
X
X
Whole Blood Sample Storage
X
Serum Storage Sample
X
X
HCV Serologyp
X
HBV Serology
X
Enrollmentq
X
Cohort 1 Dispense Diary Cards r
X
Cohorts 2, 3, & 4 Dispense Diary 
Cardsr
X
X
Single Random PK Samples
X
X
Cohorts 1 and 2 Fasted Prior to Visit
X
X
X
X
X
X
X
X
Cohort 1 IPK Samplingt
X
Cohort 2 Part A IPK Samplingt
Xt
Xt
Cohort 1 Palatability and 
Acceptability Assessmentu
X
Xu
Xu
Cohort 2 Part A Palatability and 
Acceptability Assessment
X
X
Single Observed Dosing PK Samplev
X
X
Trough PK Samples,w
X
PBMCs,x
X
DXA Scan (spine & total body)
X
X
X
X
Xy
Xy
CCI


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Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 92
02 August 2017
Study Procedure
Screenc
Baseline/ 
Day 1d
End of Weeka
Post Week 48b
30 Day 
Follow-upe
ESDDf
1
2
4
8
12
24
36
48
Every 
12 Wks
Every 
24 Wks
Cohort 1 Serum Bone Safety Testsz
X
X
X
X
X
X
Xaa
Cohorts 2, 3, and 4 Serum Bone 
Safety Testsz
X
X
X
X
X
X
Xaa
Tanner Stage Assessmentbb
X
X
X
X
In-Clinic Dosing 
X
X
X
X
Study Drug Dispensation 
X
X
X
X
X
X
X
Xcc
Study Drug Accountability
X
X
X
X
X
X
X
X
X
X
a
All study visits are to be scheduled relative to when the Baseline/Day 1 visit was completed. All study visits through Week 8 are to be completed within ± 2 days of the 
protocol-specified visit date. Visits between Week 12 through Week 48 are to be completed within ± 4 days of the protocol-specified visit date, unless otherwise specified.
b
Post Week 48 study visits are to be completed every 12 weeks (± 10 days) unless otherwise specified.
c
All screening evaluations are to be completed within 35 days prior to Baseline/Day 1 Visit.
d
Subjects will be dispensed study drug on the Baseline/Day 1 Visit. Initiation of treatment with the study drug must take place within 24 hours after the Baseline/Day 1 visit. 
F/TAF will be provided by the Sponsor unless prohibited by local regulations or upon request by the subject due to insurance restrictions.
e
30 Day Follow-Up only required for those subjects who do not wish to continue to participate after Week 48 or those subjects who permanently discontinue study drug and do 
not continue in the study through at least one subsequent visit after the Early Study Drug Discontinuation (ESDD) Visit. For the purpose of scheduling a 30-Day Follow-Up 
Visit, a ± 6 days window may be used.
f
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through 
Week 48 even if the subject discontinues study drug.
g
Medical history should include a history of HIV-1 disease-related events, ongoing medications within 30 days of Screening, and all information available on historical 
genotypes.
h
Complete physical examination every 48 weeks post 48 weeks (urogenital/anorectal exams will be performed at the discretion of the Investigator).
i
Symptom-directed physical examination, as needed.
j
12-lead ECG performed supine every 48 weeks post week 48.
k
Renal safety tests assessments will be collected fasted for Cohorts 1 and 2. If the subject has not fasted prior to the visit the subject must return within 72 hours in a fasted 
state to collect urine for renal safety tests. 
l
Required for ESDD visit if last test was > 12 weeks from ESDD visit.
m
Females of childbearing potential in Cohorts 1 and 2 only. Performed at screening and anytime during the study to confirm a positive urine pregnancy test.
n
Females of childbearing potential in Cohorts 1 and 2 only. Positive urine pregnancy tests anytime during the study will be confirmed with a serum test. 
 
p
If the antibody test result is positive, HCV RNA test will be performed to confirm HCV viremia.
q
Assignment of the subject’s enrollment number may occur up to 7 days prior to the Baseline/Day 1 visit.
CCI


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 93
02 August 2017
r
Diary Cards will be dispensed at Week 1 for all subjects in Cohort 1 to record administration of study drugs and their 3rd ARV agent for at least 3 days prior to the IPK visit at
the Week 2 visit. Diary Cards will be dispensed at Week 1 or Week 2 for all subjects in Part A of Cohorts 2, 3, and 4 to record administration of study drugs and their 
3rd ARV agent for at least 3 days prior to the IPK visit that is to occur during the Week 2 or 4 visit, or within 7 after the completion of the Week 2 or Week 4 visit. Diary 
Cards are to be collected and reviewed for protocol compliance prior to in-clinic dosing and IPK sampling. If the subject has already dosed or is not fasted prior to the IPK 
evaluation visit refer IPK instructions in Section 6.3 for details on how to proceed.
s
Subjects are allowed to take study drug at approximately the same time each day however at the time of the single random PK, trough PK, or PBMC sampling they are 
required to report the time of the last dose.
t
IPK will occur during the Week 2 visit for subjects in Cohort 1 and at either the Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits, for 
subjects in Cohort 2 Part A. For the purpose of scheduling the IPK visit, a +7 day window may be used. Subject dosing diary cards are to be collected and reviewed prior to 
in-clinic dosing and IPK sampling.
u
For Cohort 1, palatability will be assessed 30 - 60 minutes after study drug dosing for all subjects undergoing IPK sampling at Week 2. Acceptability will be assessed 
30 - 60 minutes after study drug dosing for active subjects at the next study visit immediately following approval of this protocol at the site.
v
A single observed dosing PK sample will be collected at Weeks 4 and 12 at any time between 15 min to 4 hours post observed in-clinic dose. For subjects in Cohort 2 Part A, 
a single observed dosing PK sample does not need to be collected at Week 4 if IPK is collected at the Week 4 visit.
w
For subjects in all Cohorts a trough PK sample will be collected during the Week 8 visit at 0 hours (pre-dose, ≤ 30 minutes prior to dosing) will be collected. 
x
For subjects in Cohorts 1 and 2, PBMC collection will be performed at the Week 8 visit only at study sites that can perform PBMC processing. For subjects in 
Cohorts 3 and 4, PBMC collection schedule will be specified in a future protocol amendment. All PBMC blood samples will be collected at 0 hours (≤30 minutes pre-dose).
y
DXA scan to be performed at the 30 Day Follow-up visit or the ESDD visit if the last scan was acquired > 12 weeks from the date of the ESDD Visit. DXA scan can occur up 
to 10 days after the ESDD visit date.
z
If the subject has not fasted prior to the blood draw for serum bone safety tests visit may continue however the subject must return within 72 hours after completion of the 
visit in a fasted state to draw blood for serum bone safety tests.
aa
Serum bone safety test is required at ESDD visit if last test was > 12 weeks from ESDD visit.
bb
Tanner assessments will be performed at Baseline/Day1, Weeks 24 and 48 and every 12 post week 48, or until subject reaches Tanner Stage 5
cc
Drug dispensation at Week 48 is only for subjects that are to continue in the study post Week 48.


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 94
02 August 2017
Appendix 3.
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
Repe t lab t  
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
 Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator
 
  
 
 
 
 
 
 
----l --
 
 
 
 
 
 
 
 
 


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 95
02 August 2017
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Version: 18 June 2012
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 7 Days
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Infant, 2 – 7 Days
1250 to 1500/mm3
1.25 to 1.50 GI/L
1000 to 1250/mm3
1.00 to < 1.25 GI/L
750 to 1000/mm3
0.75 to < 1.00 GI/L
750/mm3
< 0.75 GI/L
Infant, 1 Day
4000 to 5000/mm3
4.00 to 5.00 GI/L
3000 to 4000/mm3
3.00 to < 4.00 GI/L
1500 to 3000/mm3
1.50 to < 3.00 GI/L
1500/mm3
< 1.50 GI/L


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Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 96
02 August 2017
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0%


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 97
02 August 2017
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
146  to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
146  to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
3.0 to 3.4 mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Hyperkalemia 
5.6 to 6.0 mEq/L
6.0 to 6.5 mEq/L
6.5 to 7.0 mEq/L
7.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mmol/L
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
40 to 55 mg/dL
30 to 40 mg/dL
30 mg/dL
3.03 to 3.58 mmol/L
2.20 to 3.03 mmol/L
1.64 to 2.20 mmol/L
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
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
7 Days
7.8 to 8.4  mg/dL
7.0 to 7.8 mg/dL
6.1 to 7.0 mg/dL
6.1 mg/dL
1.94 to 2.10 mmol/L
1.74 to 1.94 mmol/L
1.51 to 1.74 mmol/L
1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia (corrected 
for albumin if appropriate*)
Adult and Pediatric
7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 98
02 August 2017
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to   1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
1.5 to 2.0 mg/dL
1.0 to 1.5 mg/dL
1.0 mg/dL
0.63  to LLN mmol/L
0.47 to 0.63 mmol/L
0.31 to 0.47 mmol/L
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to 3.5 mg/dL
0.96 to 1.12 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 4.5 mg/dL
1.12 to 1.46 mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia 
Adult and Pediatric 
> 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia
1.5 mg/dL to LLN
1.0 to 1.5 mg/dL
0.5 to 1.0 mg/dL
0.5 mg/dL
87 μmol/L to LLN
57 to 87 μmol/L
27 to 57 μmol/L
27 μmol/L
Creatinine 
1.50 to 2.00 mg/dL
2.00 to 3.00 mg/dL
3.00 to 6.00 mg/dL 
6.00 mg/dL
133 to 177 μmol/L
177 to 265 μmol/L
265 to 530 μmol/L
530 μmol/L


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 99
02 August 2017
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Bicarbonate
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
750 to 1200 mg/dL
1200 mg/dL
5.64–8.47 mmol/L
8.47–13.55 mmol/L
13.55 mmol/L
LDL
(Fasting)
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to  4.92 mmol/L
>4.92 mmol/L
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
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
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
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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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
                              Females
>ULN - 10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
                              Males
6-10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 h
>1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
>499 to 799 mg/m2/24 h
>799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes: 

Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by Covance Laboratory, however for other laboratories, toxicity grades will only be assigned to 
Dipstick Hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.

If the severity of a clinical AE could fall under either one of two grades (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.


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Amendment 2
CONFIDENTIAL
Page 101
02 August 2017
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 
(e.g., 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 
(e.g., malignant hypertension) 
OR Hospitalization indicated 
(other than emergency room 
visit)
Hypotension
NA
Symptomatic, corrected with 
oral fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure
Pericardial Effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, moderate or 
larger effusion requiring no 
intervention
Effusion with non-life-
threatening physiologic 
consequences OR Effusion 
with non-urgent intervention 
indicated
Life-threatening consequences 
(e.g., tamponade) OR Urgent 
intervention indicated


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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 102
02 August 2017
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV 
block OR Ventricular pause 
3.0 sec
Complete AV block 
Pediatric 16 Years
1st degree AV block
(PR > normal for age and 
rate)
Type I 2nd degree AV block 
Type II 2nd degree AV 
block 
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc interval 
0.50 sec OR Increase in 
interval 0.06 sec above 
baseline
Life-threatening 
consequences, e.g., 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, e.g., Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated 
(e.g., anticoagulation, lysis 
filter, invasive procedure) 
Deep vein thrombosis AND 
Intervention indicated (e.g., 
anticoagulation, lysis filter, 
invasive procedure) 
Embolic event (e.g., 
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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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 103
02 August 2017
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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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 104
02 August 2017
SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by 
study participant or  
caregiver (for disabled 
adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or morbilliform 
rash with vesicles or limited 
number of bullae OR 
Superficial ulcerations of 
mucous membrane limited to 
one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson syndrome 
OR Ulceration of mucous 
membrane involving two 
or more distinct mucosal 
sites OR Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 105
02 August 2017
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 [e.g., tube feeding or 
total parenteral nutrition]
Ascites
Asymptomatic
Symptomatic AND Intervention 
indicated (e.g., 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 
(e.g., sepsis or perforation) 
Constipation 
NA
Persistent constipation requiring 
regular use of dietary 
modifications, laxatives, or
enemas 
Obstipation with manual 
evacuation indicated
Life-threatening consequences 
(e.g., 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 
(e.g., 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


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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 106
02 August 2017
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Dysphagia-Odynophagia 
Symptomatic but able to eat 
usual diet
Symptoms causing altered 
dietary intake without medical 
intervention indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention indicated
Life-threatening reduction in 
oral intake
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, 
Dysphagia-Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal bleeding 
OR Life-threatening 
consequences (e.g., 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 (e.g., 
IV fluids)
Life-threatening consequences 
(e.g., hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening consequences 
(e.g., 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 
(e.g., 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 
(e.g., hypotensive shock)


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Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 107
02 August 2017
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Alteration in Personality-
Behavior or in Mood (e.g., 
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 (e.g., 
suicidal/homicidal ideation or 
attempt, acute psychosis) OR 
Causing inability to perform 
basic self-care functions
Altered Mental Status 
For Dementia, see Cognitive 
and Behavioral/Attentional 
Disturbance (including 
dementia and ADD)
Changes causing no or 
minimal interference with 
usual social & functional 
activities
Mild lethargy or somnolence 
causing greater than minimal 
interference with usual social 
& functional activities
Confusion, memory 
impairment, lethargy, or 
somnolence causing inability 
to perform usual social & 
functional activities
Delirium OR obtundation, OR 
coma
Ataxia 
Asymptomatic ataxia 
detectable on exam OR 
Minimal ataxia causing no 
or minimal interference with 
usual social & functional 
activities
Symptomatic ataxia causing 
greater than minimal 
interference with usual social 
& functional activities
Symptomatic ataxia causing 
inability to perform usual 
social & functional activities 
Disabling ataxia causing 
inability to perform basic self-
care functions
Cognitive and 
Behavioral/Attentional 
Disturbance (including 
dementia and Attention 
Deficit Disorder) 
Disability causing no or 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources not indicated
Disability causing greater than 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources on part-time basis 
indicated
Disability causing inability to 
perform usual social & 
functional activities OR 
Specialized resources on a 
full-time basis indicated
Disability causing inability to 
perform basic self-care 
functions OR 
Institutionalization indicated
CNS Ischemia
(acute)
NA
NA
Transient ischemic attack
Cerebral vascular accident 
(CVA, stroke) with 
neurological deficit 
Developmental delay –
Pediatric 16 Years
Mild developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate 
for the setting
Moderate developmental 
delay, either motor or 
cognitive, as determined by 
comparison with a 
developmental screening tool 
appropriate for the setting 
Severe developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting 
Developmental regression, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting


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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 108
02 August 2017
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Headache 
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference with 
usual social & functional 
activities
Symptoms causing inability to 
perform usual social & 
functional activities
Symptoms causing inability to 
perform basic self-care 
functions OR Hospitalization 
indicated (other than ER visit) 
OR Headache with significant 
impairment of alertness or 
other neurologic function 
Insomnia
NA
Difficulty sleeping causing 
greater than minimal 
interference with usual 
social/functional activities
Difficulty sleeping causing 
inability to perform usual 
social & functional activities
Disabling insomnia causing 
inability to perform basic self-
care functions
Neuromuscular Weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength on exam 
OR Minimal muscle weak-
ness causing no or minimal 
interference with usual 
social & functional activities
Muscle weakness causing 
greater than minimal 
interference with usual social 
& functional activities
Muscle weakness causing 
inability to perform usual 
social & functional activities 
Disabling muscle weakness 
causing inability to perform 
basic self-care functions OR 
Respiratory muscle weakness 
impairing ventilation
Neurosensory Alteration 
(including paresthesia and 
painful neuropathy)
Asymptomatic with sensory 
alteration on exam or 
minimal paresthesia causing 
no or minimal interference 
with usual social & 
functional activities 
Sensory alteration or 
paresthesia causing greater 
than minimal interference with 
usual social & functional 
activities 
Sensory alteration or 
paresthesia causing inability to 
perform usual social & 
functional activities
Disabling sensory alteration or 
paresthesia causing inability to 
perform basic self-care 
functions
Seizure: (new onset) 
NA
1 seizure 
2–4 seizures 
Seizures of any kind that are 
prolonged, repetitive (e.g., 
status epilepticus), or difficult 
to control (e.g., refractory 
epilepsy)


F/TAF
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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 109
02 August 2017
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Seizure: (pre-existing) 
For Worsening of Existing 
Epilepsy the Grades Should 
Be Based on an Increase 
from Previous Level of 
Control to Any of These 
Levels
NA
Increased frequency of pre-
existing seizures (non-
repetitive) without change in 
seizure character OR 
infrequent breakthrough 
seizures while on stable meds 
in a previously controlled 
seizure disorder
Change in seizure character 
from baseline either in 
duration or quality (e.g., 
severity or focality) 
Seizures of any kind that are 
prolonged, repetitive (e.g., 
status epilepticus), or difficult 
to control (e.g., 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


F/TAF
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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 110
02 August 2017
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


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 111
02 August 2017
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 [e.g., 
tube feeding or total parenteral 
nutrition]


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 112
02 August 2017
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 (e.g., upper 
arm/thigh)
Erythema OR Induration 
OR Edema involving 50% 
surface area of the extremity 
segment (e.g., 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


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 113
02 August 2017
ENDOCRINE/METABOLIC
Grade 1
Grade 2
Grade 3
Grade 4
Lipodystrophy (e.g., 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 
(e.g., 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
(e.g., 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 
(e.g., myxedema coma)
Lipoatrophy (e.g., 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


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 114
02 August 2017
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 (e.g., stone)
NA
Signs or symptoms of urinary 
tract obstruction without 
hydronephrosis or renal 
dysfunction
Signs or symptoms of urinary 
tract obstruction with 
hydronephrosis or renal 
dysfunction
Obstruction causing 
life-threatening 
consequences
INFECTION
Grade 1
Grade 2
Grade 3
Grade 4
Infection (any other 
than HIV infection)
Localized, no systemic antiμbial 
treatment indicated AND 
Symptoms causing no or 
minimal interference with usual 
social & functional activities
Systemic antiμbial treatment 
indicated OR Symptoms 
causing greater than minimal 
interference with usual social 
& functional activities
Systemic antiμbial treatment 
indicated AND Symptoms 
causing inability to perform 
usual social & functional 
activities OR Operative 
intervention (other than simple 
incision and drainage) indicated
Life-threatening 
consequences (e.g., 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.


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 115
02 August 2017
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Pregnancy and Contraception Requirements for Males and Females of Childbearing 
Potential 
The risks of treatment with the study drug during pregnancy have not been evaluated. Pregnancy 
must be excluded before the start of treatment with study drug and prevented thereafter by 
reliable contraceptive methods. Pregnancy tests will be performed regularly throughout this 
study (Refer to Appendix 2). If females are using hormonal agents for contraception, the safety 
and/or efficacy may be affected by possible drug-drug interaction. However, it is recommended 
that the hormonal agent be continued and that a non-hormonal method (or methods) be used 
concurrently.
If females utilize hormonal agents as one of their contraceptive methods, it is required that the 
same hormonal method be used for at least 3 months before study dosing. Please refer to the 
latest version of the Investigator’s Brochure for additional information.
2) Definition of Female of Childbearing Potential
For the purposes of this study, a female subject of childbearing potential is a nonmenopausal 
female who has not had a hysterectomy, bilateral oophorectomy, or medically documented 
ovarian failure. A woman who has had a tubal sterilization is considered to be of childbearing 
potential. This definition also includes a pubertal female who has not yet started menstruating. 
A female subject may be considered menopausal in either of the following conditions:

Surgical menopause: Appropriate medical documentation of prior complete bilateral 
oophorectomy (i.e., surgical removal of the ovaries and occurring at the age at which the 
procedure was performed)

Spontaneous menopause: Permanent cessation of previously occurring menses as a result of 
ovarian failure with documentation of hormonal deficiency by a certified health care 
provider. The worldwide mean age of spontaneous menopause is 49.24 (SD 1.73) years
3) Contraceptive Requirements 
Female subjects of childbearing potential who engage in intercourse must agree to utilize 
protocol specified methods of contraception from the screening visit throughout the study period 
and for 30 days following the last dose of study drug. Male subjects of childbearing potential 
who engage in intercourse must agree to utilize protocol specified methods of contraception from 
the enrollment visit throughout the study period and for 30 days following the last dose of study 
drug. 
Female study subjects who are not heterosexually active must provide periodic confirmation of 
continued abstinence from heterosexual intercourse and regular pregnancy testing while taking 
any study medication. The investigator will counsel subjects on the protocol specified method(s) 
for avoiding pregnancy in case the subject chooses to engage in heterosexual intercourse.


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Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 116
02 August 2017
Protocol specified contraceptive methods are as follows: 
1) a combination of one hormonal method and one barrier method; 
2) two barrier methods where one method is the male condom; 
3) use of an intrauterine device (IUD) or tubal sterilization; 
See Appendix Table 1 below. Acceptable hormonal methods include injectable progesterone, 
progesterone implants, combination oral contraceptives, transdermal contraceptive patch, and 
vaginal ring. Acceptable barrier methods include diaphragm with spermicide, cervical cap with 
spermicide, and the male condom. 
Female subjects must use either a hormonal method or a barrier method if the partner has a 
vasectomy. If a subject has undergone tubal sterilization or has had a Copper T 380A IUD or 
LNg 20 IUD inserted, no other contraception is needed.
If tubal sterilization is via the Essure procedure, verification of tubal blockage by 
hysterosalpingogram (HSP) must be performed approximately 3 months after microinsertion. 
Prior to verification, Essure is not considered a reliable form of contraception and the 
contraception methods described below must be used. Female subjects who utilize hormonal 
contraceptives as one of their birth control methods must have used the same method for at least 
3 months before study dosing.
Female subjects of childbearing potential must have a negative serum pregnancy test at screening 
and a negative urine pregnancy test at Baseline/Day 1 prior to receiving the first dose of study 
drug. Lactating females must discontinue nursing before IMP administration.
Appendix Table 1.
Protocol Specified Contraceptive Methods
Methods to Use by Themselves
Combination Methods
Hormone Methods
(choose one and use with a 
barrier method)
Barrier Methods
(use both OR choose one and use 
with a hormone method)
Intrauterine Devices (IUDs)

Copper T 380A IUD

LNg 20 IUD
Tubal Sterilization
Estrogen and Progesterone

Oral contraceptives

Transdermal patch

Vaginal ring
Progesterone

Injection

Implant

Diaphragm with spermicide
OR

Cervical cap with spermicide

Male condom (without 
spermicide)
Partner’s vasectomy must be used with a hormone or barrier method.


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Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 117
02 August 2017
The investigator will counsel all subjects on the most effective method(s) for avoiding pregnancy 
during the study.
Male subjects must agree to use condoms during heterosexual intercourse and avoid sperm 
donation while enrolled in the study and for at least 30 days after administration of the last dose 
of study medication
Use of condoms, except for lambskin, has been proven to decrease the risk of transmission of 
HIV and other sexually transmitted diseases. The use of spermicide is not recommended if the 
subject or subject’s partner is infected with HIV.
4) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose.
Subjects who become pregnant or who suspect that they are pregnant during the study must 
report the information to the investigator and seek the investigator’s advice regarding action 
required with the study drug immediately. 
Instructions for reporting pregnancy and pregnancy outcome are outlined in Section 7.6.2.1.


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 118
02 August 2017
Appendix 6.
Definitions of HIV-1 Related Disease
CDC Classification Systems, Category C: AIDS-Indicator Conditions

Bacterial pneumonia, recurrent (two or more episodes in 12 months)

Candidiasis of bronchi, trachea, or lungs

Candidiasis, esophageal

Cervical carcinoma, invasive, confirmed by biopsy

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (1 month duration)

Cytomegalovirus disease (other than liver, spleen or nodes)

Encephalopathy, HIV-related

Herpes simplex: chronic ulcers (1 month duration), or bronchitis, pneumonitis or 
esophagitis

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (1-month duration)

Kaposi’s sarcoma

Lymphoma, Burkitt, immunoblastic, or primary central nervous system

Mycobacterium avium complex (MAC) or Myobacterium kansasii, disseminated or 
extrapulmonary

Mycobacterium tuberculosis, pulmonary or extrapulmonary 

Mycobacterium, other species or unidentified species, disseminated or extrapulmonary

Pneumocystis jirovecii (formerly carinii) pneumonia (PCP)

Progressive multifocal leukoencephalopathy (PML)

Salmonella septicemia, recurrent (nontyphoid)


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Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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
Toxoplasmosis of brain

Wasting syndrome caused by HIV (involuntary weight loss > 10% of baseline weight) 
associated with either chronic diarrhea (two or more loose stools per day for ≥1 month) or 
chronic weakness and documented fever for ≥ 1 month
U.S Department of Health and Human Services (DHHS). Guide for HIV/AIDS Clinical Care. -
2014 {Department of Health and Human Services (DHHS) 2014}


F/TAF
Protocol GS-US-311-1269
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 120
02 August 2017
Appendix 7.
Tanner Stages
1. Pubic hair (male and female)
Tanner I
no pubic hair at all (prepubertal Dominic state)
Tanner II
small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum 
(males) or on the labia majora (females)
Tanner III
hair becomes more coarse and curly, and begins to extend laterally
Tanner IV
adult-like hair quality, extending across pubis but sparing medial thighs
Tanner V
hair extends to medial surface of the thighs
2. Genitals (male) (One standard deviation around mean age)
Tanner I
Testes, scrotum, and penis about same size and proportion as in early childhood
Tanner II
Enlargement of scrotum and testes; skin of scrotum reddens and changes in texture; little or no 
enlargement of penis (10.5-12.5)
Tanner III
Enlargement of penis, first mainly in length; further growth of testes and scrotum (11.5-14)
Tanner IV
Increased size of penis with growth in breadth and development of glans; further enlargement of 
testes and scrotum and increased darkening of scrotal skin (13.5-15)
Tanner V
Genitalia adult in size and shape
3. Breasts (female)
Tanner I
no glandular tissue: areola follows the skin contours of the chest
Tanner II
breast bud forms, with small area of surrounding glandular tissue; areola begins to widen
Tanner III
breast begins to become more elevated, and extends beyond the borders of the areola, which 
continues to widen but remains in contour with surrounding breast
Tanner IV
increased breast size and elevation; areola and papilla form a secondary mound projecting from 
the contour of the surrounding breast
Tanner V
breast reaches final adult size; areola returns to contour of the surrounding breast, with a 
projecting central papilla.

SAP_003.pdf: 
S T A TI S TI C A L A N A L Y SI S P L A N
St u d y Title:
A P hase 2/ 3, O pe n- La bel, M ulti- C o h ort S witc h St u d y t o 
E val uate E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F) i n 
HI V- 1 I nfecte d C hil dre n a n d A d olesce nts Vir ol o gicall y 
S u p presse d o n a 2- N R TI- C o ntai ni n g Re gi me n
N a me of Test Dr u g: 
E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
St u d y N u m ber:
G S- U S- 3 1 1- 1 2 6 9
Pr ot oc ol Versi o n ( D ate): 
A me n d me nt 2 ( 0 2 A u g ust 2 0 1 7);
S o ut h Africa A me n d me nt 2. 1 ( 1 0 A u g ust 2 0 1 7);
U K A d de n d u m 2. 0 ( 1 5 A u g ust 2 0 1 7)
A n al ysis T y pe:
Fi nal A nal ysis
A n al ysis Pl a n Versi o n: 
1. 0
A n al ysis Pl a n D ate: 
1 9 Fe br uar y 2 0 2 5
A n al ysis Pl a n A ut h or(s):
C O N FI D E N TI A L A N D P R O P RI E T A R Y I N F O R M A TI O N
P P D
GI L E A U 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 of 6 4
T A B L E O F C O N T E N T S
S T A TI S TI C A L A N A L Y SI S P L A N............................................................................................................................... 1
T A B L E O F C O N T E N T S................................................................................................................................................ 2
LI S T O F I N- T E X T T A B L E S......................................................................................................................................... 4
LI S T O F I N- T E X T FI G U R E S........................................................................................................................................ 4
LI S T O F A B B R E VI A TI O N S......................................................................................................................................... 5
P H A R M A C O KI N E TI C A B B R E VI A TI O N S................................................................................................................. 7
1.  
I N T R O D U C TI O N.................................................................................................................................................. 8
1. 1.  
St u d y O bjecti ves a n d E n d p oi nts................................................................................................................ 8
1. 2.  
St u d y Desi g n ............................................................................................................................................. 9
1. 3.  
Sa m ple Size a n d P o wer........................................................................................................................... 1 2
2.  
T Y P E O F P L A N N E D A N A L Y SI S...................................................................................................................... 1 4
2. 1.  
C o h ort 1 Wee k 4 8 I nteri m A nal ysis........................................................................................................ 1 4
2. 2.  
C o h ort 2 Wee k 2 4 I nteri m A nal ysis........................................................................................................ 1 4
2. 3.  
I nteri m 2 A nal ysis ................................................................................................................................... 1 4
2. 4.  
Fi nal A nal ysis.......................................................................................................................................... 1 4
2. 5.   
Data M o nit ori n g C o m mittee ( D M C) A nal yses....................................................................................... 1 4
2. 6.  
C ha n ges Fr o m Pr ot oc ol- S pecifie d Pla n ne d A nal yses............................................................................. 1 5
3.   
G E N E R A L C O N SI D E R A TI O N S F O R D A T A A N A L Y S E S............................................................................. 1 6
3. 1.   
A nal ysis Sets ........................................................................................................................................... 1 6
3. 1. 1.   
All E nr olle d A nal ysis Set...................................................................................................... 1 6
3. 1. 2.  
F ull A nal ysis Set.................................................................................................................... 1 6
3. 1. 3.  
Safet y A nal ysis Set................................................................................................................ 1 6
3. 1. 4.   
D X A A nal ysis Set ................................................................................................................. 1 7
3. 1. 5.  
P har mac o ki netic A nal ysis Set............................................................................................... 1 7
3. 2.  
Partici pa nt Gr o u pi n g ............................................................................................................................... 1 7
3. 3.  
Strata a n d C o variates............................................................................................................................... 1 8
3. 4.  
E xa mi nati o n of Partici pa nt S u b gr o u ps.................................................................................................... 1 8
3. 5.   
M ulti ple C o m paris o ns............................................................................................................................. 1 8
3. 6.   
Missi n g Data a n d O utliers....................................................................................................................... 1 8
3. 6. 1.   
Missi n g Data.......................................................................................................................... 1 8
3. 6. 2.   
O utliers.................................................................................................................................. 1 8
3. 7.   
Data Ha n dli n g C o n ve nti o ns a n d Tra nsf or mati o ns.................................................................................. 1 8
3. 8.   
A nal ysis Visit Wi n d o ws.......................................................................................................................... 1 9
3. 8. 1.   
Defi niti o n of St u d y Da y ........................................................................................................ 1 9
3. 8. 2.   
A nal ysis Visit Wi n d o ws........................................................................................................ 2 0
3. 8. 3.  
Selecti o n of Data i n t he E ve nt of M ulti ple Rec or ds i n a n A nal ysis Visit 
Wi n d o w................................................................................................................................. 2 4
4.  
P A R TI CI P A N T DI S P O SI TI O N .......................................................................................................................... 2 6
4. 1.  
Partici pa nt E nr oll me nt a n d Dis p ositi o n................................................................................................... 2 6
4. 2.  
E xte nt of St u d y Dr u g E x p os ure a n d A d here nce...................................................................................... 2 7
4. 2. 1.   
D urati o n of E x p os ure t o St u d y Dr u g..................................................................................... 2 7
4. 2. 2.   
A d here nce t o St u d y Dr u g...................................................................................................... 2 8
4. 3.  
Pr ot oc ol De viati o ns................................................................................................................................. 2 9
4. 4.   
Assess me nt of C O VI D- 1 9 I m pact........................................................................................................... 2 9
4. 4. 1.  
St u d y Dr u g or St u d y Disc o nti n uati o n D ue t o C O VI D- 1 9..................................................... 2 9


E mtri cit a bi n e/f e n of o v ir Al af e n a mi d e  (F/f A F ; D e s c o v y®) 
G S- U S- 3 1 1 - 1 2 6 9 
St ati sti c al  A n al ysi s  Pl a n - Fi n al  A n al y si s 
V ersi o n  1. 0 
4. 4 . 2.  
Pr ot o c ol  D e vi ati o n s  D u e  t o C O VI D- 1 9  ................................................................................ 3 0 
4. 4 . 3.  
Mi s s e d  a n d Viit u al  Vi sit s  d u e  t o C O VI D- 1 9  ........................................................................ 3 0 
4. 4. 4 .  
A d v ers e  E v e nts  D u e  t o C O VI D -1 9 ....................................................................................... 3 0 
5.  
B A S E LI N E  C H A R A C T E RI S TI C S  ..................................................................................................................... 3 1 
5. 1. 
D e m o gr a p hi cs  a n d B a s eli n e  C h ar a ct eristi cs  ........................................................................................... 3 1 
5. 2.  
Ot h er  B a s eli n e  C h ar a ct eristi cs  ................................................................................................................ 3 1 
5. 3.  
M e di c al  Hi st oi y  ....................................................................................................................................... 3 2 
6.  
E F FI C A C Y  A N A L Y S E S  ..................................................................................................................................... 3 3 
6. 1. 
Pri 1 nr u y  Effi c a c y  E n d p oi nt  ...................................................................................................................... 3 3 
6. 2.  
S e c o n dr u y  Effi c a c y  E n d p oi nts  ................................................................................................................ 3 3 
6. 2. 1.  
D efi niti o n of t h e S e c o n d a 1 y  Effi c a c y  E n d p oi nts  ................................................................... 3 3 
6. 2. 2.  
A n al  si s of S e c o n dr u  Effi c a c  E n d  oi nts  ........................................................................... 3 3 
6. 4.  
C h a n g es  Fr o m  Pr ot o c ol -S p e cifi e d  Effi c a c y  A n al ys es  ............................................................................ 3 5 
7.  
S A F E T Y  A N A L Y S E S  ......................................................................................................................................... 3 6 
7. 1.  
A d v ers e  E v e nts  a n d  D e at hs  ..................................................................................................................... 3 6 
7. 1. 1.  
A d v ers e  E v e nt  Di cti o n a 1 y  ..................................................................................................... 3 6 
7. 1. 2.  
A d v ers e  E v e nt  S e v erit y  ......................................................................................................... 3 6 
7. 1. 3 .  
R el ati o ns hi p of A d v er s e  E v e nts  t o St u d y D m g ..................................................................... 3 6 
7. 1. 4 .  
S eri o u s  A d v ers e  E v e nts  ......................................................................................................... 3 6 
7. 1. 5.  
Tr e ati n e nt -E m er g e nt  A d v er s e  E v e nts  .................................................................................... 3 6 
7. 1. 6. 
S Ullllll ari es of A d v er s e  E v e nts  a n d D e at h s  ............................................................................ 3 7 
7. 1. 7.  
A d diti o n al  A n al ysis of A d v er s e  E v e nts  ................................................................................ 3 9 
7. 2.  
L a b or a to 1 y E v al u ati o ns  ........................................................................................................................... 3 9 
7. 2. 1.  
S Ullllll ari es of N u m eri c  L a b or at 0 1 y  R es ults  ......................................................................... . 4 0 
7. 2. 2.  
Gr a d e d  L a b or at o 1 y  V al u e s  ................................................................................................... . 4 1 
7. 2. 3.  
Li v er -r el at e d L a b or at 0 1 y  E v al u ati o ns  ................................................................................... . 4 2 
7. 2. 4 .  
M et a b oli c  L a b or a to 1 y E v al u ati o ns  ....................................................................................... . 4 2 
7. 2. 5.  
R e n al  S af et y  E v al u ati o ns  ...................................................................................................... . 4 3 
7. 2. 6.  
B o n e  S af et y  E v al u ati o ns  ....................................................................................................... . 4 3 
7. 3.  
T a n n er  St a g e  A s s e s s m e nt  ....................................................................................................................... . 4 5 
7. 4.  
A c c e pt a bilit y  a n d  P al at a bilit y  A s s e s s m e nt  ............................................................................................. . 4 5 
7 . 5.  
B o d y  W ei g ht , H ei g ht , a n d Vit al  Si g n s  ................................................................................................... . 4 5 
7. 6.  
Pri or  a n d C o n c oi nit a nt  M e di c ati o ns  ....................................................................................................... . 4 6 
7 . 6. 1.  
N o n st u d y -D m g A ntir etr n vir al  M e di c ati o ns  ......................................................................... . 4 6 
7. 6. 2.  
C o n c o 1 nit a nt  N o n -A R V  M e di c ati o ns  ................................................................................... . 4 7 
7. 7.  
El e ctr o cr u· di o gr a 1 n  R es ults  ...................................................................................................................... . 4 7 
7. 8. 
Ot h er  S af et y  M e a s ur e s  ........................................................................................................................... . 4 7 
7 . 9.  
C h a n g es  Fr o m  Pr ot o c ol -S p e cifi e d  S af et y  A n al ys es  ............................................................................... . 4 7 
8.  
P H A R M A C O KI N E TI C  ( P K) A N A L Y S E S  ........................................................................................................ . 4 8 
8. 1. 
P K S a m pl e  C oll e cti o n  ............................................................................................................................ . 4 8 
8. 2. 
P K A n al ys es  R el at e d  t o I nt e nsi v e/S pr u·s e P K S a m pli n g  ........................................................................ . 4 8 
8. 2. 1.  
P K/ P D  A n al y s e s  ................................................................................................................... . 4 8 
8. 3.  
C h a n g es Fr o m  Pr ot o c ol -S p e cifi e d P K A n al y s e s  .................................................................................... . 4 8 
9.  
R E F E R E N C E S  .................................................................................................................................................... . 4 9 
1 0 .  S O F T W A R E ......................................................................................................................................................... 5 0 
1 1 .  S A P  R E VI SI O N  ................................................................................................................................................... 5 1 
1 9 F e br u ar y  2 0 2 5 
GI L E A D  C O N FI D E N TI A L  I N F O R M A TI O N 
P a g e  3 of 6 4 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 of 6 4
1 2. 
A P P E N DI C E S...................................................................................................................................................... 5 2
1 2. 1.  
Sc he d ule of Assess me nts......................................................................................................................... 5 2
1 2. 2.   
Data C ollecti o n of C O VI D- 1 9 Data........................................................................................................ 5 6
1 2. 2. 1.   
Data C ollecti o n...................................................................................................................... 5 6
1 2. 2. 2.   
Deter mi nati o n of Misse d a n d Virt ual Visits.......................................................................... 5 6
1 2. 3.   
U S F D A- Defi ne d S na ps h ot Al g orit h m ................................................................................................... 5 7
1 2. 4.  
Pr o gra m mi n g S pecificati o n..................................................................................................................... 5 9
LI S T O F I N- T E X T T A B L E S
Ta ble 1- 1.  
C o h ort 2 Part A.......................................................................................................................... 9
Ta ble 3- 1.   
A nal ysis Visit Wi n d o ws f or HI V- 1 R N A, C D 4 cell c o u nt, C D 4 %, He mat ol o g y, 
C he mistr y, a n d Uri nal ysis La b orat or y Tests, e G F R Sc h wartz , Vital Si g ns, Hei g ht, a n d 
Wei g ht ..................................................................................................................................... 2 1
Ta ble 3- 2.   
A nal ysis Visit Wi n d o ws f or Fasti n g Gl uc ose, Uri ne C he mistr y a n d Uri ne Re nal 
Safet y Tests a ............................................................................................................................ 2 2
Ta ble 3- 3.   
A nal ysis Visit Wi n d o ws f or Meta b olic Assess me nts a a n d B M D Assess me nts...................... 2 2
Ta ble 3- 4.   
A nal ysis Visit Wi n d o ws f or C o h ort 1 Ser u m B o ne Safet y Assess me nts a............................... 2 3
Ta ble 3- 5.   
A nal ysis Visit Wi n d o ws f or C o h ort 2 Ser u m B o ne Safet y Assess me nts a............................... 2 3
Ta ble 3- 6.   
A nal ysis Visit Wi n d o ws f or 1 2-lea d E C G .............................................................................. 2 4
Ta ble 3- 7.   
A nal ysis Visit Wi n d o ws f or Ta n ner Sta ge Assess me nts......................................................... 2 4
Ta ble 1 2- 1.  
E xa m ple Searc h Ter ms f or “ C O VI D- 1 9” a n d “ Virt ual” Use d t o I de ntif y 
Misse d/ Virt ual Visits............................................................................................................... 5 6
LI S T O F I N- T E X T FI G U R E S
Fi g ure 1 2- 1.  
Fl o wc hart of U S F D A- Defi ne d S na ps h ot Al g orit h m.............................................................. 5 8


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 of 6 4
LI S T O F A B B R E VI A TI O N S
1, 2 5- O H vita mi n D 
1, 2 5- di h y dr o x y vita mi n D
2 5- O H vita mi n D 
2 5- h y dr o x y vita mi n D
A B C/ 3 T C
a baca vir/la mi v u di ne
A E
a d verse e ve nt
AI D S
ac q uire d i m m u n o deficie nc y s y n dr o me
A L P
al kali ne p h os p hatase
A L T
ala ni ne a mi n otra nsferase
A R V
a ntiretr o viral
A S T
as partate a mi n otra nsferase
A T V
ataza na vir
B L Q
bel o w t he li mit of q ua ntitati o n
B M D
b o ne mi neral de nsit y
B MI
b o d y mass i n de x
B S A
b o d y s urface area
Bs A P
b o ne-s pecific al kali ne p h os p hatase
B U N
bl o o d urea nitr o ge n
C B C
c o m plete bl o o d c o u nt
C D C
Ce nters f or Disease C o ntr ol a n d Pre ve nti o n
CI
c o nfi de nce i nter val
C O VI D- 1 9
c or o na vir us disease 2 0 1 9
C P K
creati ne p h os p h o ki nase
C S R
cli nical st u d y re p ort
C T X
C-t y pe c olla ge n se q ue nce
D M C
data m o nit ori n g c o m mittee
D O B
date of birt h
D R V
dar u na vir
D X A
d ual-e ner g y x-ra y a bs or pti o metr y
E C G
electr ocar di o gra m
e C R F 
electr o nic case re p ort f or m
e G F R
esti mate d gl o mer ular filtrati o n rate
E S D D
earl y st u d y dr u g disc o nti n uati o n
F A S
F ull A nal ysis Set
F/ T A F
e mtricita bi ne/te n of o vir alafe na mi de (c of or m ulate d; Desc o v y ® )
F T C or F
e mtricita bi ne
H Bs A g
he patitis B s urface a nti ge n 
H B V
he patitis B vir us
H C V
he patitis C vir us
H D L
hi g h- de nsit y li p o pr otei n
HI V- 1
h u ma n i m m u n o deficie nc y vir us (t y pe 1)
H L G T
hi g h-le vel gr o u p ter m


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 6 of 6 4
H L T
hi g h-le vel ter m
I P K
i nte nsi ve p har mac o ki netic(s)
I R T
i nteracti ve res p o nse tec h n ol o g y
L D L
l o w- de nsit y li p o pr otei n
L L T
l o wer-le vel ter m
L O Q
li mit of q ua ntitati o n
M = E 
missi n g = e xcl u de d
M = F 
missi n g = fail ure
M C H
mea n c or p usc ular he m o gl o bi n
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
mea n c or p usc ular v ol u me
Me d D R A
Me dical Dicti o nar y f or Re g ulat or y Acti vities
M S T
Me d D R A searc h ter m
N L P
nat ural la n g ua ge pr ocessi n g
N R TI
n ucle osi de re verse tra nscri ptase i n hi bit or
O L E
o pe n-la bel e xte nsi o n
P 1 N P
pr oc olla ge n t y pe I N-ter mi nal pr o pe pti de
PI
pr otease i n hi bit or
P K
p har mac o ki netic(s)
P B M C
peri p heral bl o o d m o n o n uclear cell
P T
preferre d ter m
P T H
parat h yr oi d h or m o ne
Q 1, Q 3
first q uartile, t hir d q uartile
Q D
o nce dail y
R B C
re d bl o o d cell
R B P
reti n ol- bi n di n g pr otei n
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S D
sta n dar d de viati o n
S E
sta n dar d err or
S M Q
Sta n dar dise d Me d D R A Q uer y
S O C
s yste m or ga n class
T A F
te n of o vir alafe na mi de ( Ve mli d y® )
T B L H
t otal b o d y less hea d
T E A E
treat me nt-e mer ge nt a d verse e ve nt
T F Ls
ta bles, fi g ures, a n d listi n gs
T F V, T F V- D P  
te n of o vir, te n of o vir- di p h os p hate
U L N
u p per li mit of n or mal
W B C
w hite bl o o d cell
W H O
W orl d Healt h Or ga nizati o n


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 7 of 6 4
P H A R M A C O KI N E TI C A B B R E VI A TI O N S
A U C ta u
area u n der t he plas ma dr u g c o nce ntrati o n vers us ti me c ur ve o ver t he d osi n g i nter val
C last
last o bser ve d q ua ntifia ble plas ma dr u g c o nce ntrati o n 
C ma x
ma xi m u m o bser ve d plas ma dr u g c o nce ntrati o n 
C ta u
o bser ve d plas ma dr u g c o nce ntrati o n at t he e n d of t he d osi n g i nter val
C L/ F 
a p pare nt oral cleara nce after a d mi nistrati o n of t he dr u g:
at stea d y state: C Lss/ F = D ose/ A U C ta u , w here “ D ose” is t he d ose of t he dr u g
V z 
v ol u me of distri b uti o n


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 8 of 6 4
1.  
I N T R O D U C TI O N
T his statistical a nal ysis pla n ( S A P) descri bes t he statistical a nal ysis met h o ds a n d data 
prese ntati o ns t o be use d i n ta bles, fi g ures, a n d listi n gs ( T F Ls) i n t he fi nal cli nical st u d y re p ort 
( C S R) f or St u d y G S- U S- 3 1 1- 1 2 6 9. T his S A P is base d o n st u d y pr ot oc ol a me n d me nt 2 
( date d 0 2 A u g ust 2 0 1 7), S o ut h Africa a me n d me nt 2. 1 ( date d 1 0 A u g ust 2 0 1 7), U K 
a d de n d u m 2. 0 ( date d 1 5 A u g ust 2 0 1 7),  a n d t he electr o nic case re p ort f or m (e C R F). T he S A P will 
be fi nalize d bef ore data base fi nalizati o n. A n y c ha n ges ma de after t he fi nalizati o n of t he S A P will 
be d oc u me nte d i n t he C S R.
1. 1.  
St u d y O bjecti ves a n d E n d p oi nts
T he pri mar y o bjecti ves of t his st u d y are:
•
T o e val uate t he p har mac o ki netics ( P K) of te n of o vir alafe na mi de ( T A F) a n d c o nfir m t he T A F 
d ose i n HI V- 1 i nfecte d c hil dre n a n d a d olesce nts vir ol o gicall y s u p presse d o n a 
2 n ucle osi de/ n ucle oti de re verse tra nscri ptase i n hi bit or ( N R TI)-c o ntai ni n g re gi me n
•
T o e val uate t he safet y, t olera bilit y of F/ T A F t hr o u g h Wee k 2 4
T he pri mar y e n d p oi nts are:
•
T he P K para meter A U C ta u f or T A F
•
I nci de nce of treat me nt-e mer ge nt seri o us a d verse e ve nts ( S A Es) a n d all treat me nt-e mer ge nt 
a d verse e ve nts ( T E A Es) t hr o u g h Wee k 2 4
T he sec o n dar y o bjecti ves are:
•
T o e val uate t he P K of T F V a n d F T C
•
T o e val uate t he safet y, t olera bilit y, a n d efficac y of F/ T A F t hr o u g h Wee k 4 8
T he sec o n dar y e n d p oi nts are:
•
P K para meters C ma x , Clast, C L/ F, a n d Vz / F f or T A F, A U Cta u, Cma x , a n d Cta u f or F T C a n d T F V
•
I nci de nce of treat me nt-e mer ge nt S A Es a n d all treat me nt-e mer ge nt a d verse e ve nts t hr o u g h 
Wee k 4 8
•
T he perce nta ge of partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L at Wee ks 2 4 a n d 4 8 as 
defi ne d b y t he U S F D A- defi ne d s na ps h ot al g orit h m
•
T he c ha n ge fr o m baseli ne i n C D 4 cell c o u nt (cells/ μ L) a n d C D 4 perce nta ge at Wee ks 2 4 a n d 
4 8
•
T he palata bilit y a n d acce pta bilit y of t he a ge-a p pr o priate F/ T A F f or m ulati o n


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 9 of 6 4
T he tertiar y e n d p oi nts are:
•
T he perce nta ge c ha n ge fr o m baseli ne i n s pi ne a n d t otal- b o d y-less- hea d ( T B L H) b o ne mi neral 
de nsit y ( B M D) at Wee ks 2 4 a n d 4 8
•
T he perce nta ge c ha n ge fr o m baseli ne i n b o ne safet y tests at Wee ks 1 2, 2 4, a n d 4 8
•
T he perce nta ge c ha n ge fr o m baseli ne i n re nal safet y tests at Wee ks 1 2, 2 4, a n d 4 8
1. 2.  
St u d y Desi g n
T his is a n o pe n-la bel, m ultic o h ort s witc h st u d y t o e val uate t he P K, safet y, a n d efficac y of F/ T A F 
i n HI V- 1 i nfecte d c hil dre n ( 1 m o nt h t o < 1 2 years) a n d a d olesce nts ( 1 2 t o < 1 8 years) w h o are 
vir ol o gicall y s u p presse d ( HI V- 1 R N A < 5 0 c o pies/ m L f or at least 6 c o nsec uti ve m o nt hs) o n a 
sta ble 2- N R TI-c o ntai ni n g re gi me n.
A mi ni m u m of 1 0 0 c hil dre n a n d a d olesce nt partici pa nts, 1 m o nt h t o < 1 8 years of a ge of eit her 
se x, were pla n ne d t o be e nr olle d t o recei ve F/ T A F. T he st u d y was pla n ne d t o pr ocee d i n 
se q ue ntial c o h orts as f oll o ws:
C o h ort 1 ( A d olesce nts 1 2 t o < 1 8 ye ars, ≥ 3 5 k g):
All partici pa nts i n C o h ort 1 ( n = 2 5) s witc he d t heir c urre nt 2- N R TI-c o ntai ni n g re gi me n t o 
o pe n-la bel F/ T A F w hile c o nti n ui n g o n t heir t hir d a ntiretr o viral ( A R V) a ge nt t hr o u g h 4 8 wee ks. 
A n i nte nsi ve P K (I P K) e val uati o n was c o n d ucte d at t he Wee k 2 visit t o c o nfir m t he d ose of T A F 
a n d t o c haracterize T F V a n d F T C e x p os ures. F oll o wi n g c o m pleti o n of t he Wee k 2 I P K visit, all 
partici pa nts c o nti n ue d t o recei ve F/ T A F pl us t heir t hir d A R V a ge nt a n d ret ur ne d f or st u d y visits 
t hr o u g h Wee k 4 8.
C o h ort 2:
Partici pa nts i n C o h ort 2 ha d t o be o n a b o oste d pr otease i n hi bit or ( PI) or a n y ot her 3r d A R V 
a ge nt a n d s witc he d t heir c urre nt 2- N R TI-c o ntai ni n g re gi me n t o o pe n-la bel F/ T A F w hile 
c o nti n ui n g t heir b o oste d PI or 3r d a ge nt t hr o u g h 4 8 wee ks.
C o h ort 2 pla n ne d t o e nr oll b y treat me nt gr o u p i nt o a 2- part st u d y ( Parts A a n d B). Ta ble 1- 1  
liste d Part A as bel o w.
P art A
T a ble 1- 1.   
C o h ort 2 P art A
N u m ber of P artici p a nts
C o h ort 2
A ge R a n ge
Wei g ht
R a n ge at 
Scree ni n g
A T V +
F/ T A F
L P V or
D R V
+ F/ T A F
Ot her t hir d
A R V A ge nt
+ F/ T A F
Gr o u p 1
6 t o  1 2 years
 2 5 k g
n  1 0
n  6
n/a
Gr o u p 2 
( partici pa nts a ble 
t o s wall o w a 
ta blet)
2 t o < 1 2 years 
1 7 k g t o < 2 5 k g 
n ≥ 1 0
n ≥ 7


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 1 0 of 6 4
All partici pa nts i n Part A u n der we nt a n I P K e val uati o n at eit her t he Wee k 2 or Wee k 4 visit 
( + 7 da ys) t o c o nfir m t he d ose of T A F a n d t o c haracterize t he e x p os ure of T F V. F oll o wi n g 
c o m pleti o n of t he I P K visit, all partici pa nts c o nti n ue d t o recei ve F/ T A F pl us t heir t hir d A R V 
a ge nt a n d ret ur ne d f or st u d y visits t hr o u g h Wee k 4 8.
P art B
After c o nfir mati o n of T A F d ose i n Part A, a p pr o xi matel y 1 0 a d diti o nal partici pa nts were pla n ne d 
t o be e nr olle d i n Part B, t o recei ve F/ T A F w hile c o nti n ui n g t heir t hir d A R V a ge nt t hr o u g h 
4 8 wee ks. 
E nr oll me nt i nt o t he st u d y has c o ncl u de d a n d o nl y Part A was e nr olle d. Wit h t he i ntr o d ucti o n of 
F/ T A F t o St u d y G S- U S- 2 1 6- 0 1 2 8 via St u d y G S- U S- 2 1 6- 0 1 2 8 pr ot oc ol a me n d me nt 7, 
partici pa nts i n t his st u d y c o ul d r oll o ver t o G S- U S- 2 1 6- 0 1 2 8 a n d n o f urt her e nr oll me nt i n t his 
st u d y was re q uire d. T his mea nt t hat pla n ne d C o h ort 2 Part B f or t his st u d y was n ot o pe ne d f or 
e nr oll me nt a n d n o f urt her partici pa nts were e nr olle d i nt o C o h ort 2 Part A. Details ca n be f o u n d 
i n Secti o n 2. 6 .
C o h ort 3 a n d 4
T he details of C o h ort 3 a n d 4 are i n Secti o n 3. 2. 2 of st u d y pr ot oc ol a me n d me nt 2. T he 
e nr oll me nt of C o h ort 3 a n d 4 were n ot i nitiate d d ue t o st u d y e nr oll me nt pa use (as i n C o h ort 2 
Part B a b o ve). A d diti o nal details ca n be f o u n d i n Secti o n 2. 6 .
St u d y Pr oce d ure/ Fr e q ue nc y:
At scree ni n g, H B V a n d H C V ser ol o g y were a nal yze d.
At t he Scree ni n g, Baseli ne/ Da y 1, a n d all s u bse q ue nt st u d y visits, vital si g ns, wei g ht a n d 
hei g ht/le n gt h, la b orat or y a nal yses ( he mat ol o g y, c he mistr y, a n d uri nal ysis), plas ma HI V- 1 R N A, 
C D 4 cell c o u nt, c o m plete or s y m pt o m  directe d p h ysical e xa mi nati o ns, a n d e G F R usi n g t he 
Sc h wartz f or m ula were perf or me d. Ser u m (scree ni n g) or uri ne (all ot her visits) pre g na nc y tests 
were perf or me d o n fe male partici pa nts of c hil d beari n g p ote ntial.
Partici pa nts ret ur ne d f or st u d y visits at Wee ks 1, 2, 4, 8, 1 2, 2 4, 3 6, a n d 4 8. After c o m pleti o n of 
4 8 wee ks of treat me nt i n t he st u d y, all eli gi ble partici pa nts were gi ve n t he o pti o n t o partici pate i n 
a n e xte nsi o n p hase of t he st u d y i n w hic h visits occ urre d e ver y 1 2 wee ks. A d verse e ve nts a n d 
c o nc o mita nt me dicati o ns were assesse d at eac h visit.
Ta n ner sta ge assess me nts were perf or me d f or partici pa nts ≥ 6 years of a ge at t he ti me of t he visit 
at Baseli ne/ Da y 1, Wee ks 2 4, 4 8, a n d e ver y 1 2 wee ks t hereafter, or u ntil partici pa nts reac he d 
Ta n ner Sta ge 5, after w hic h p oi nt Ta n ner assess me nts were n o l o n ger perf or me d.
D ual e ner g y x-ra y a bs or pti o metr y ( D X A) sca ns of t he l u m bar s pi ne a n d t otal b o d y were 
perf or me d at Baseli ne/ Da y 1, Wee ks 2 4 a n d 4 8, a n d e ver y 2 4 wee ks t hereafter t o meas ure s pi ne 
B M D a n d T B L H B M D.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 1 1 of 6 4
Ser u m was c ollecte d f or b o ne safet y tests (c ollecte d faste d), i ncl u di n g b o ne s pecific al kali ne 
p h os p hatase ( Bs A P), ser u m p h os p h or us, pr oc olla ge n t y pe I N-ter mi nal pr o pe pti de ( P 1 N P), 
C-t y pe c olla ge n se q ue nce ( C T X), parat h yr oi d h or m o ne ( P T H), 1, 2 5- O H vita mi n D, a n d 2 5- O H 
vita mi n D. T he assess me nt sc he d ules differe d f or differe nt c o h orts:
•
C o h ort 1 o nl y: Baseli ne/ Da y 1, Wee ks 4, 1 2, 2 4 a n d 4 8, a n d e ver y 2 4 wee ks t hereafter.
•
C o h ort 2: Baseli ne/ Da y 1, Wee ks 8, 1 2, 2 4 a n d 4 8, a n d e ver y 2 4 wee ks t hereafter.
F or b ot h c o h orts, uri ne was c ollecte d f or uri ne c he mistr y a n d selecte d re nal safet y tests, 
i ncl u di n g reti n ol bi n di n g pr otei n a n d beta- 2- micr o gl o b uli n, at Baseli ne/ Da y 1, Wee ks 2, 4, 8, 1 2, 
2 4 a n d 4 8, a n d e ver y 1 2 wee ks t hereafter.
F or C o h orts 1 a n d 2 ( b ot h gr o u ps), meta b olic assess me nts were c ollecte d f or fasti n g gl uc ose a n d 
li pi d pa nel (t otal c h olester ol, H D L, direct L D L, a n d tri gl yceri des) at Baseli ne/ Da y 1, Wee ks 2 4 
a n d 4 8, a n d e ver y 2 4 wee ks ( ± 1 0 da ys) t hereafter. 
F or P K sa m pli n g:
•
Si n gle P K sa m ples were c ollecte d f or b ot h c o h orts
o
Wee ks 1 a n d 2 4: a si n gle ra n d o m P K sa m ple.
o
Wee ks 4 a n d 1 2: a si n gle o bser ve d d osi n g P K sa m ple at a n y ti me bet wee n 1 5 mi n utes t o 
4 h o urs p ost d ose. ( N ote: f or C o h ort 2 Part A, a si n gle o bser ve d d osi n g P K sa m ple di d 
n ot nee d t o be c ollecte d at Wee k 4 if I P K was als o c ollecte d at t he Wee k 4 visit)
•
Wee k 8: a tr o u g h sa m ple at 0 h o urs ( pre d ose, ≤ 3 0 mi n utes pri or t o d osi n g) at Wee k 8.
•
I nte nsi ve P K (I P K) sa m pli n g
o
C o h ort 1 partici pate d i n a n I P K e val uati o n at t he Wee k 2 visit as detaile d i n t he P K 
ma n ual.
o
C o h ort 2 Part A partici pate d i n a n I P K e val uati o n d uri n g eit her t he Wee k 2 or Wee k 4 
visit or wit hi n 7 da ys after t he c o m pleti o n of Wee k 2 or Wee k 4 visit as detaile d i n t he 
P K ma n ual.
Peri p heral bl o o d m o n o n uclear cell ( P B M C) c ollecti o n was perf or me d at st u d y sites t hat c o ul d 
perf or m P B M C pr ocessi n g.
•
C o h orts 1 a n d 2: P B M C c ollecti o n was perf or me d at t he Wee k 8 visit.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
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Versi o n 1. 0
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Pa ge 1 2 of 6 4
Palata bilit y a n d Acce pta bilit y Assess me nt:
•
C o h ort 1: At t he Wee k 2 visit, palata bilit y a n d acce pta bilit y were assesse d 3 0 t o 6 0 mi n utes 
after st u d y dr u g d osi n g f or all partici pa nts u n der g oi n g I P K sa m pli n g. Acce pta bilit y was als o 
assesse d 3 0 t o 6 0 mi n utes after st u d y dr u g d osi n g f or acti ve partici pa nts at t he ne xt st u d y 
visit.
•
C o h ort 2 Part A: Palata bilit y a n d acce pta bilit y were assesse d at t he Wee k 2 or Wee k 4 visit, 
or wit hi n 7 da ys after t he c o m pleti o n of t he Wee k 2 or Wee k 4 visit, 3 0 t o 6 0 mi n utes after 
st u d y dr u g d osi n g f or all partici pa nts u n der g oi n g I P K sa m pli n g.
Partici pa nts w h o pre mat urel y disc o nti n ue d fr o m t he st u d y or di d n ot partici pate i n t he e xte nsi o n 
p hase were re q uire d t o ret ur n t o t he cli nic f or a 3 0- Da y F oll o w- u p Visit.
A d diti o nal details of sc he d ule d assess me nts ca n be f o u n d i n Secti o n 1 2. 1 .
1. 3.  
S a m ple Size a n d P o wer
C o h ort 1: T we nt y-fi ve partici pa nts fr o m C o h ort 1 i n t he T A F treat me nt gr o u p were a ntici pate d 
t o pr o vi de at least 9 0 % p o wer t o tar get a 9 5 % c o nfi de nce i nter val ( CI) wit hi n 6 0 % a n d 1 4 0 % of 
t he ge o metric mea n esti mate of a p pare nt C L a n d a p pare nt Vz of T A F, ass u mi n g a sta n dar d 
de viati o n ( S D) of 0. 6 0 f or C L a n d 0. 5 8 f or V z ( nat ural l o g scale) esti mate d fr o m St u d y 
G S- U S- 2 9 2- 0 1 0 6 C o h ort 1 Part A.
C o h ort 2 ( Gr o u p 1) P art A: At least 1 0 partici pa nts o n b o oste d A T V + F/ T A F a n d 6 
partici pa nts o n b o oste d L P V or D R V + F/ T A F, c o m pare d wit h t he p o p ulati o n P K ( P o p P K) data 
fr o m 4 4 a d ult partici pa nts o n b o oste d A T V + F/ T A F a n d 8 7 a d ult partici pa nts o n b o oste d L P V 
or D R V + F/ T A F i n St u d y G S- U S- 3 1 1- 1 0 8 9, res pecti vel y, eac h was a ntici pate d t o pr o vi de at 
least 8 0 % p o wer t o s h o w t he l o wer b o u n d of a 9 0 % CI of ge o metric mea n rati o ( pe diatric 
partici pa nts vs. a d ult partici pa nts) greater t ha n 7 0 % f or A U C ta u of T A F, ass u mi n g t hat t he 
e x pecte d ge o metric mea n rati os of T A F A U C ta u bet wee n pe diatric partici pa nts a n d a d ult 
partici pa nts are e q ual t o 1 a n d t he S Ds are 0. 4 0 ( wit h b o oste d A T V + F/ T A F) a n d 0. 3 3 ( wit h 
b o oste d L P V or D R V + F/ T A F) n g∙h/ m L f or T A F A U C ta u ( nat ural l o g scale) esti mate d fr o m t he 
P o p P K data i n St u d y G S- U S- 3 1 1- 1 0 8 9.
P art A of C o h orts 2 ( Gr o u p 2), 3, a n d 4:  At least 1 0 partici pa nts o n b o oste d A T V + F/ T A F a n d 
7 partici pa nts o n a n y ot her t hir d a ge nt + F/ T A F i n eac h gr o u p or c o h ort, c o m pare d wit h t he 
P o p P K data fr o m t he 2 9 2 a d ults o n a n y t hir d a ge nt + D V Y i n St u d y G S- U S- 3 1 1- 1 0 8 9, were 
a ntici pate d t o pr o vi de 9 0 % p o wer t o s h o w t he l o wer b o u n d of a 9 0 % CI of ge o metric mea n rati o 
( pe diatric partici pa nts vs. a d ult partici pa nts) greater t ha n 7 0 % f or A U C ta u of T A F, ass u mi n g t hat 
t he e x pecte d ge o metric mea n rati o of T A F A U Cta u bet wee n pe diatric partici pa nts a n d a d ult 
partici pa nts is e q ual t o 1, a n d t he S D is 0. 4 8 n g∙h/ m L f or T A F A U C ta u ( nat ural l o g scale) 
esti mate d fr o m t he P o p P K data i n St u d y G S- U S- 3 1 1- 1 0 8 9.
I nitiall y, a t otal of at least 1 0 0 partici pa nts recei vi n g F/ T A F fr o m C o h ort 1, a n d Parts A a n d B of 
C o h ort 2 ( Gr o u ps 1 a n d 2), C o h ort 3, a n d C o h ort 4 c o m bi ne d were a ntici pate d t o pr o vi de 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
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Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
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Pa ge 1 3 of 6 4
reas o na ble assess me nt of safet y t hr o u g h Wee k 4 8 i n pe diatric partici pa nts. H o we ver, C o h ort 2 
Part B, C o h ort 3 a n d 4 were n ot e nr olle d, a n d details ca n be f o u n d i n Secti o n 2. 6 .
Sa m ple size a n d p o wer calc ulati o ns were ma de usi n g t he statistical s oft ware pac ka ge n Q uer y 
A d vis or ( Versi o n 7. 0) a n d R.


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Pa ge 1 4 of 6 4
2.  
T Y P E O F P L A N N E D A N A L Y SI S
2. 1.   
C o h ort 1 Wee k 4 8 I nteri m A n al ysis
A C o h ort 1 Wee k 4 8 a nal ysis was pla n ne d t o be c o n d ucte d after all partici pa nts i n C o h ort 1 ha d 
eit her c o m plete d t heir Wee k 4 8 visit or pre mat urel y disc o nti n ue d st u d y dr u g. 
T his a nal ysis was n ot perf or me d. T he res ults f or C o h ort 1 t hr o u g h Wee k 4 8 were later i ncl u de d 
as part of t he I nteri m A nal ysis 2 C S R. 
2. 2.   
C o h ort 2 Wee k 2 4 I nteri m A n al ysis
A C o h ort 2 Wee k 2 4 a nal ysis was pla n ne d t o be c o n d ucte d after all partici pa nts i n C o h ort 2 ha d 
eit her c o m plete d t heir Wee k 2 4 visit or pre mat urel y disc o nti n ue d st u d y dr u g. 
T his a nal ysis was n ot perf or me d. T he res ults f or C o h ort 2 Part A ( Gr o u ps 1 a n d 2) t hr o u g h 
Wee k 2 4 were later i ncl u de d as part of t he I nteri m A nal ysis 2 C S R. 
2. 3.  
I nteri m 2 A n al ysis
T his a nal ysis i ncl u de d data fr o m C o h ort 1 a n d C o h ort 2 Part A ( Gr o u ps 1 a n d 2). It was 
c o n d ucte d after partici pa nts e nr olle d i n C o h ort 1 a n d C o h ort 2 Part A ( Gr o u ps 1 a n d 2) ha d 
c o m plete d t heir Wee k 4 8 visit or pre mat urel y disc o nti n ue d st u d y dr u g.
2. 4.  
Fi n al A n al ysis
T he fi nal a nal ysis will be perf or me d after all partici pa nts (ie, partici pa nts i n C o h ort 1 a n d C o h ort 
2 Part A [ Gr o u ps 1 a n d 2]) ha ve c o m plete d t he st u d y or pre mat urel y disc o nti n ue d, o utsta n di n g 
data q ueries ha ve bee n res ol ve d or a dj u dicate d as u nres ol va ble, a n d t he data ha ve bee n clea ne d 
a n d fi nalize d. 
2. 5.   
D at a M o nit ori n g C o m mittee ( D M C) A n al yses
A n e xter nal m ulti disci pli nar y Data M o nit ori n g C o m mittee ( D M C) was pla n ne d t o re vie w t he 
pr o gress of t he st u d y a n d perf or m i nteri m re vie ws of t he safet y data i n or der t o pr otect 
partici pa nt welfare a n d preser ve st u d y i nte grit y. 
D M C re vie w was n ot perf or me d f or t he st u d y.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
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Pa ge 1 5 of 6 4
2. 6.   
C h a n ges Fr o m Pr ot oc ol- S pecifie d Pl a n ne d A n al yses
Wit h t he i ntr o d ucti o n of F/ T A F t o St u d y G S- U S- 2 1 6- 0 1 2 8 via t he St u d y G S- U S- 2 1 6- 0 1 2 8 
pr ot oc ol a me n d me nt 7, it was a gree d t hat partici pa nts i n St u d y G S- U S- 3 1 1- 1 2 6 9 c o ul d r oll o ver 
t o G S- U S- 2 1 6- 0 1 2 8 a n d n o f urt her e nr oll me nt i n t his st u d y was re q uire d. T his mea nt t hat 
C o h orts 2 Part B, 3, a n d 4 f or t his st u d y were n ot o pe ne d f or e nr oll me nt a n d n o f urt her 
partici pa nts were e nr olle d i nt o C o h ort 2 Part A. T he e nr oll me nt was cl ose d, a n d t he last 
partici pa nt was e nr olle d o n 2 2- Ma y- 2 0 1 9.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
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Versi o n 1. 0
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Pa ge 1 6 of 6 4
3.   
G E N E R A L C O N SI D E R A TI O N S F O R D A T A A N A L Y S E S
A nal ysis res ults will be prese nte d usi n g descri pti ve statistics. F or cate g orical varia bles, t he 
n u m ber a n d perce nta ge of partici pa nts i n eac h cate g or y will be prese nte d; f or c o nti n u o us 
varia bles, t he n u m ber of partici pa nts ( n), mea n, S D or sta n dar d err or ( S E), me dia n, first q uartile 
( Q 1), t hir d q uartile ( Q 3), mi ni m u m, a n d ma xi m u m will be prese nte d.
B y- partici pa nt listi n gs will be prese nte d f or all partici pa nts i n t he All E nr olle d A nal ysis Set 
u nless s pecifie d ot her wise, a n d s orte d b y partici pa nt i de ntificati o n (I D) n u m ber i n asce n di n g 
or der, visit date, a n d ti me (if a p plica ble), u nless ot her wise s pecifie d. Data c ollecte d o n l o g f or ms, 
s uc h as A Es, will be prese nte d i n c hr o n ol o gical or der f or eac h partici pa nt. T he c o h ort (a n d 
gr o u p, w here a p plica ble) t o w hic h partici pa nts were i nitiall y assi g ne d will be use d i n t he listi n gs. 
A ge, se x at birt h, race, a n d et h nicit y will be i ncl u de d i n t he listi n gs, as s pace per mits.
3. 1.   
A n al ysis Sets
A nal ysis sets defi ne t he partici pa nts t o be i ncl u de d i n a n a nal ysis. A nal ysis sets a n d t heir 
defi niti o ns are pr o vi de d i n t his secti o n. T he a nal ysis set will be i ncl u de d as a s u btitle of eac h 
ta ble, fi g ure, a n d listi n g ( T F L).
F or eac h a nal ysis set, t he n u m ber a n d perce nta ge of partici pa nts eli gi ble f or i ncl usi o n will be 
s u m marize d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall.
A b y- partici pa nt listi n g of reas o ns f or e xcl usi o n fr o m a nal ysis sets will be pr o vi de d.
3. 1. 1.   
All E nr olle d A n al ysis Set
T he All E nr olle d A nal ysis Set will i ncl u de all partici pa nts w h o are e nr olle d i nt o t he st u d y (ie, 
recei ve d a st u d y partici pa nt i de ntificati o n n u m ber i n t he st u d y after scree ni n g).
T his is t he pri mar y a nal ysis set f or b y- partici pa nt listi n gs.
3. 1. 2.  
F ull A n al ysis Set
T he F ull A nal ysis Set ( F A S) will i ncl u de all e nr olle d partici pa nts w h o recei ve d at least 1 d ose of 
st u d y dr u g. T his is t he pri mar y a nal ysis set f or efficac y a nal yses.
3. 1. 3.  
S afet y A n al ysis Set
T he Safet y A nal ysis Set will i ncl u de all e nr olle d partici pa nts w h o recei ve d at least 1 d ose of 
st u d y dr u g. T his is t he pri mar y a nal ysis set f or safet y a nal yses.


E mtri cit a bi n e/f e n of o vir  Al af e n a mi d e ( F/f A F; D e s c o v y ®) 
G S- U S- 3 1 1 - 1 2 6 9 
St ati sti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
3. 1. 4. 
3. 1. 4. 1. 
D X A  A n al ysis  S et 
T ot a l  Bo d y  L e ss  H e a d D X A  A n al ysis  S e t 
V ersi o n  1. 0 
T h e  T B L H  D X A  A n al y si s  S et  w ill i ncl u d e  all  p arti ci p a nts  w h o  ar e  e m oll e d  a n d h a v e  re c ei v e d  at 
le as t  1 d os e of st u d y d m g  an d h a v e  a  n o n mi ss i ng  T B L H  B M D  v al u e  at  t h e b as eli n e  vi si t. 
3. 1. 4. 2. 
3. 1. 5. 
3. 1. 5. 1. 
S pi n e  D X A  A n al y sis  S et 
P h a r m a c o ki n eti c  A n al y si s  S et 
I P K A n al y sis  S et 
T h e  I P K A n al y si s  S et  w ill i n cl u d e all  p a 1ti ci p ant s  w h o  e m oll e d  i n C o h o 1t 1  or  P ai t A of C o h o 1t 2 
( e a c h  gr o u p)  f or I P K e v a l u atio n  a n d r ec e iv e d  at  l e ast  o n e  d os e  of s t u d y m e di c ati o n  a n d h a v e  at 
le as t  1 n o n mi ss i ng  P K  c o n c e nt r ati o n d at a  f or a n y  a n al yt e of i nt erest  ( e g, F T C ,  TA F,  a n d  T F V) . 
T h e  I P K a n al ysis  s et i s  us e d f or a n al ys es  o fI P K a n al yt e s of T A F , T F V,  a n d  F T C. 
3. 1. 5. 2. 
P K A n al y sis  S et 
T h e P K A n al y si s  S et  w ill i n cl u d e all  p a 1ti ci p ant s w h o  ar e  e m oll e d  a n d h a v e  re c ei v e d  at  l e ast  o n e 
d os e of st u dy  dr n g  a n d h a v e  at  l e ast 1 n o n mi ss i n g P K c o n c e ntr ati o n  d at a  f or a n y  a n al yt e of 
i nt ere st  (i e, F T C , T A F,  a n d  T F V) . T h e  P K  a n al ysis  s e t is u s e d f or  a n al ys es of g e n e r al P K. 
3. 1. 5. 3.  
P B M C  P K  A n al ysis  S e t 
T h e  P B M C P K a n al y si s s et w ill i n cl u d e all  p a 1ti ci p ant s w h o  ar e  e m oll e d  an d h a v e  re c ei v e d  at 
le as t o n e  d o s e of st u dy  m e di c ati o n  a n d  h a v e  at  l e ast 1  n o n mi ss i ng  c o n c e n tr ati o n d at a of T F V - D P. 
T h e  P B M C P K a n al y si s s et w ill b e  u s e d f or P K  a n al ys es of T F V - D P. 
3. 2. 
P a rti ci p a nt  G r o u pi n g 
P aiti c i p a nts wi ll b e  a n al y z e d b as e d o n  t he  c o h o rt (a n d gr o u p , if a p pli c a bl e)  t o w hi c h t h e y  w er e 
i niti ally  ass i g ne d as  w e ll as  o v er a ll. 
F or  t h e P K  A n al ysis  S e t, p aiti ci p a nt s wi ll b e  gr o u p e d  a c c or di n g  t o t h e a ct u al  tr e at m e nt t he y 
r e c ei v e d. 
P aiti c i p a nts wi ll b e  gr o u p e d  i nto  t he  f oll o wi n g: 
•  C o h o 1t  1 :  A g e  1 2 t o  < 1 8 y e ai·s an d w ei g ht  3 5  k g 
•  C o h o 1t  2  Gr o u p  1 :  A g e  6  t o < 1 2 y e ars  a n d  w e i g ht  2 5  k g 
•  C o h o 1t  2  Gr o u p 2: A g e  2  t o < 1 2 y e ars  a n d  w e i g ht  1 7 t o  < 2 5  k g 
1 9 F e br u ar y  2 0 2 5 
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P a g e 1 7 of 6 4 


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Pa ge 1 8 of 6 4
3. 3.  
Str at a a n d C o v ari ates
T his is n ot a ra n d o mize d st u d y. T heref ore, a stratifie d ra n d o mizati o n sc he d ule is n ot a p plica ble 
w he n e nr olli n g partici pa nts. N o c o variates will be i ncl u de d i n efficac y or safet y a nal yses.
3. 4.  
E x a mi n ati o n of P artici p a nt S u b gr o u ps
T here are n o pres pecifie d partici pa nt s u b gr o u pi n gs f or efficac y a n d safet y a nal yses.
3. 5.   
M ulti ple C o m p aris o ns
A dj ust me nts f or m ulti plicit y will n ot be ma de, beca use n o f or mal statistical testi n g will be 
perf or me d i n t his st u d y.
3. 6.   
Missi n g D at a a n d O utliers
3. 6. 1.   
Missi n g D at a
I n ge neral, missi n g data will n ot be i m p ute d u nless met h o ds f or ha n dli n g missi n g data are 
s pecifie d. E xce pti o ns are prese nte d i n t his d oc u me nt.
F or missi n g last d osi n g date of st u d y dr u g, i m p utati o n r ules are descri be d i n Secti o n 3. 8. 1 . T he 
ha n dli n g of missi n g or i nc o m plete dates f or A E start is descri be d i n Secti o n 7. 1. 5. 2 , a n d f or pri or 
a n d c o nc o mita nt me dicati o ns i n Secti o n 7. 6 .
3. 6. 2. 
O utliers
O utliers of n o n- P K data will be i de ntifie d d uri n g t he data ma na ge me nt a n d data a nal ysis pr ocess, 
b ut n o se nsiti vit y a nal yses will be c o n d ucte d. All data will be i ncl u de d i n t he data a nal ysis.
3. 7.   
D at a H a n dli n g C o n ve nti o ns a n d Tr a nsf or m ati o ns
T he f oll o wi n g c o n ve nti o ns will be use d f or t he i m p utati o n of date of birt h w he n it is partiall y 
missi n g or n ot c ollecte d:
•
If o nl y m o nt h a n d year of birt h is c ollecte d, t he n “ 1 5” will be i m p ute d as t he da y of birt h
•
If o nl y year of birt h is c ollecte d, t he n “ 0 1 J ul y” will be i m p ute d as t he da y a n d m o nt h of birt h
•
If year of birt h is missi n g, t he n date of birt h will n ot be i m p ute d.
I n ge neral, a ge c ollecte d at Da y 1 (i n years) will be use d f or a nal yses a n d prese nte d i n listi n gs. If 
a ge at Da y 1 is n ot a vaila ble f or a partici pa nt, t he n a ge deri ve d base d o n date of birt h a n d t he 
Da y 1 visit date will be use d i nstea d. If a n e nr olle d partici pa nt was n ot d ose d wit h a n y st u d y 
dr u g, t he e nr oll me nt date will be use d i nstea d of t he Da y 1 visit date. F or scree n fail ures, t he date 
t he first i nf or me d c o nse nt was si g ne d will be use d f or t he a ge deri vati o n. A ge re q uire d f or 
l o n git u di nal a n d te m p oral calc ulati o ns a n d a nal yses (e g, esti mates of creati ni ne cleara nce, a ge at 
start date of A E) will be base d o n a ge deri ve d fr o m date of birt h a n d t he date of t he meas ure me nt 
or e ve nt, u nless ot her wise s pecifie d.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
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1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 1 9 of 6 4
N o n- P K data ( ot her t ha n HI V- 1 R N A) t hat are c o nti n u o us i n nat ure b ut less t ha n t he l o wer li mit 
of q ua ntitati o n ( L O Q) or a b o ve t he u p per L O Q will be i m p ute d as f oll o ws:
•
A val ue t hat is 1 u nit less t ha n t he l o wer L O Q at t he sa me precisi o n le vel as t he ori gi nall y 
re p orte d val ue will be use d t o calc ulate descri pti ve statistics if t he dat u m is re p orte d i n t he 
f or m of “ < x” ( w here x is c o nsi dere d l o wer L O Q). F or e xa m ple, if t he val ues are re p orte d as 
< 5 0 a n d < 5. 0, val ues of 4 9 a n d 4. 9, res pecti vel y, will be use d t o calc ulate s u m mar y 
statistics. A n e xce pti o n t o t his r ule is a n y val ue re p orte d as < 1 or < 0. 1, etc. F or val ues 
re p orte d as < 1 or < 0. 1, a val ue of 0. 9 or 0. 0 9, res pecti vel y, will be use d t o calc ulate 
s u m mar y statistics.
•
A val ue t hat is 1 u nit a b o ve t he u p per L O Q will be use d t o calc ulate descri pti ve statistics if 
t he dat u m is re p orte d i n t he f or m of “ > x” ( w here x is c o nsi dere d t he u p per L O Q). Val ues 
wit h deci mal p oi nts will f oll o w t he sa me l o gic as a b o ve.
•
T he l o wer or u p per L O Q will be use d t o calc ulate descri pti ve statistics if t he dat u m is 
re p orte d i n t he f or m of “ ≤ x” or “ ≥ x” ( w here x is c o nsi dere d t he l o wer or u p per L O Q, 
res pecti vel y).
HI V- 1 R N A res ults of “ N o HI V- 1 R N A detecte d” a n d “ < 2 0 c o pies/ m L HI V- 1 R N A Detecte d” 
will be i m p ute d as 1 9 c o pies/ m L f or a nal ysis p ur p oses.
If met h o ds base d o n t he ass u m pti o n t hat t he data are n or mall y distri b ute d are n ot a de q uate, 
a nal yses ma y be perf or me d o n tra nsf or me d data or n o n para metric a nal ysis met h o ds ma y be use d, 
as a p pr o priate.
3. 8.   
A n al ysis Visit Wi n d o ws
3. 8. 1.   
Defi niti o n of St u d y D a y
St u d y d a y  will be calc ulate d fr o m t he first d osi n g date of st u d y dr u g a n d deri ve d as f oll o ws:
•
F or p ost d ose st u d y da ys: Assess me nt Date – First D osi n g Date + 1
•
F or da ys pri or t o t he first d ose: Assess me nt Date – First D osi n g Date
T heref ore, St u d y D a y 1  is t he da y of first d ose of st u d y dr u g a d mi nistrati o n.
L ast D ose D ate  is t he earliest of t he last d osi n g dates of F/ T A F a n d t he t hir d a ge nt i n a 
partici pa nt’s st u d y re gi me n. 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 0 of 6 4
F or F/ T A F, t he last d osi n g date is t he latest n o n missi n g e n d date rec or de d o n t he St u d y Dr u g 
A d mi nistrati o n e C R F wit h “ St u d y Dr u g Per ma ne ntl y Wit h dra w n” b o x c hec ke d f or partici pa nts 
w h o pre mat urel y disc o nti n ue d st u d y dr u g, or w h o c o m plete d st u d y dr u g acc or di n g t o t he St u d y 
Dr u g C o m pleti o n e C R F ( or St u d y Dr u g C o m pleti o n ( P ost- Wee k 4 8 E xte nsi o n P hase) e C R F if 
a p plica ble). If t he date of last d ose is missi n g (e g, d ue t o l ost t o f oll o w- u p) f or partici pa nts w h o 
pre mat urel y disc o nti n ue d st u d y dr u g, t he latest of n o n missi n g st u d y dr u g start dates a n d e n d 
dates, t he cli nic visit dates, la b orat or y visit dates a n d vital si g ns assess me nts dates e xcl u di n g t he 
date of t he 3 0- da y f oll o w- u p visit will be use d t o i m p ute t he last d osi n g date. F or ot her partial 
missi n g last d ose date, please see t he A p pe n di x 1 2. 4  f or i m p utati o n r ule details.
T he t hir d a ge nt i n a partici pa nt’s e xisti n g treat me nt re gi me n is t he A R V me dicati o n 
(e xcl u di n g a baca vir ( A B C) a n d la mi v u di ne ( 3 T C)) t hat a partici pa nt was ta ki n g i m me diatel y 
pri or t o t he first d ose date (ie, A R V start date bef ore t he first d ose date of st u d y dr u g a n d A R V 
e n d date after t he first d ose date of st u d y dr u g mi n us 1). T he last d osi n g date of t he t hir d a ge nt is 
rec or de d o n t he N o n- St u d y A R V Me dicati o n e C R F. If t he t hir d a ge nt is o n g oi n g, t he n t he last 
d ose date of t he st u d y re gi me n will be t he last d osi n g date of F/ T A F. 
F or a n A R V w hic h is mar ke d as c urre nt b ut n ot o n g oi n g o n t he N o n- St u d y A R V Me dicati o n 
e C R F, if t he A R V e n d date is missi n g (e g, d ue t o l ost t o f oll o w- u p), t he latest of n o n missi n g 
st u d y dr u g start date a n d e n d date, t he cli nic visit dates, a n d la b orat or y visit dates e xcl u di n g t he 
date of t he 3 0 da y f oll o w- u p visit will be use d t o i m p ute t he e n d date of t he A R V.
L ast St u d y D ate  is t he latest of t he n o n missi n g st u d y dr u g start dates, st u d y dr u g e n d dates, a n d 
t he cli nic visit, a n d la b orat or y visit dates, i ncl u di n g t he 3 0- da y f oll o w- u p visit date f or 
partici pa nts w h o a) pre mat urel y disc o nti n ue d st u d y fr o m mai n p hase or b) c o m plete d st u d y i n t he 
mai n p hase b ut di d n ot partici pate i n t he e xte nsi o n p hase acc or di n g t o t he St u d y C o m pleti o n 
e C R F or c) disc o nti n ue d st u d y fr o m t he e xte nsi o n p hase acc or di n g t o t he St u d y C o m pleti o n 
e C R F. 
B aseli ne v al ue  is defi ne d as t he last n o n missi n g val ue o btai ne d o n or pri or t o St u d y Da y 1 f or all 
assess me nts, e xce pt f or t he B M D data, w hic h is t he last n o n missi n g val ue o btai ne d pri or t o or u p 
t o St u d y Da y 2 1 (i ncl usi ve). 
3. 8. 2.   
A n al ysis Visit Wi n d o ws
Partici pa nt visits mi g ht n ot occ ur o n pr ot oc ol-s pecifie d da ys. T heref ore, f or t he p ur p ose of 
a nal ysis, o bser vati o ns will be assi g ne d t o a nal ysis wi n d o ws.
T he a nal ysis wi n d o ws f or HI V- 1 R N A, C D 4 cell c o u nt, C D 4 %, he mat ol o g y, c he mistr y, a n d 
uri nal ysis la b orat or y tests, e G F R Sc h wartz , vital si g ns, hei g ht, a n d wei g ht are prese nte d i n Ta ble 3- 1  
bel o w.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 1 of 6 4
T a ble 3- 1.   
A n al ysis Visit Wi n d o ws f or HI V- 1 R N A, C D 4 cell c o u nt, C D 4 %, 
He m at ol o g y, C he mistr y, a n d Uri n al ysis L a b or at or y Tests, 
e G F R Sc h w artz , Vit al Si g ns, Hei g ht, a n d Wei g ht
Visit Wi n d o w St u d y D a y
Visit
N o mi n al St u d y D a y
L o wer Li mit
U p per Li mit
Baseli ne
1
( n o ne)
1
Wee k 1
7
2
1 0
Wee k 2
1 4
1 1
2 1
Wee k 4
2 8
2 2
4 2
Wee k 8
5 6
4 3
7 0
Wee k 1 2
8 4
7 1
1 2 6
Wee k 2 4
1 6 8
1 2 7
2 1 0
Wee k 3 6
2 5 2
2 1 1
2 9 4
Wee k 4 8
3 3 6
2 9 5
3 7 8
He mat ol o g y pr ofile i ncl u des c o m plete bl o o d c o u nt ( C B C) ( he m o gl o bi n, mea n c or p usc ular he m o gl o bi n ( M C H), mea n 
c or p usc ular he m o gl o bi n c o nce ntrati o n ( M C H C), he mat ocrit, mea n c or p usc ular v ol u me ( M C V), re d bl o o d cells ( R B C) a n d w hite 
bl o o d cells ( W B C) wit h differe ntial (a bs ol ute bas o p hils, e osi n o p hils, l y m p h oc ytes, m o n oc ytes, ne utr o p hils) a n d platelet c o u nt.
C he mistr y pr ofile i ncl u des al b u mi n, al kali ne p h os p hatase ( A L P), as partate a mi n otra nsferase ( A S T), ala ni ne a mi n otra nsferase 
( A L T), direct a n d i n direct bilir u bi n, t otal bilir u bi n, bicar b o nate, bl o o d urea nitr o ge n ( B U N), calci u m (al b u mi n c orrecte d), 
c hl ori de, creati ne ki nase, ser u m gl uc ose, ser u m creati ni ne, ma g nesi u m, p h os p h or us, p otassi u m, t otal pr otei n, s o di u m, uric aci d, 
a m ylase, a n d li pase.
Vital si g ns i ncl u des bl o o d press ure, te m perat ure, heart rate, a n d res pirati o n rate.
Uri nal ysis d oes n ot i ncl u de uri ne c he mistr y a n d uri ne re nal safet y.
T he a nal ysis wi n d o ws f or fasti n g gl uc ose, uri ne c he mistr y a n d uri ne re nal safet y tests are 
prese nte d i n Ta ble 3- 2  bel o w.
C CI
C CI


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 2 of 6 4
T a ble 3- 2.   
A n al ysis Visit Wi n d o ws f or F asti n g Gl uc ose, Uri ne C he mistr y a n d 
Uri ne Re n al S afet y Tests a
Visit Wi n d o w St u d y D a y
Visit
N o mi n al St u d y D a y
L o wer Li mit
U p per Li mit
Baseli ne
1
( n o ne)
1
Wee k 2
1 4
2
2 1
Wee k 4
2 8
2 2
4 2
Wee k 8
5 6
4 3
7 0
Wee k 1 2
8 4
7 1
1 2 6
Wee k 2 4
1 6 8
1 2 7
2 5 2
Wee k 4 8
3 3 6
2 5 3
3 7 8
a   
Uri ne c he mistr y tests i ncl u de creati ni ne, p h os p hate, uric aci d, al b u mi n, calci u m, ma g nesi u m, pr otei n, N-tel o pe pti de a n d 
N-tel o pe pti de/creati ni ne; Uri ne re nal safet y tests (c ollecte d faste d) i ncl u de reti n ol bi n di n g pr otei n ( R B P), 
beta- 2- micr o gl o b uli n, uri ne R B P t o uri ne creati ni ne rati o, uri ne beta- 2- micr o gl o b uli n t o uri ne creati ni ne rati o, a n d uri ne 
pr otei n t o creati ni ne rati o.
T he a nal ysis wi n d o ws f or meta b olic a n d B M D assess me nts are prese nte d i n Ta ble 3- 3  bel o w.
T a ble 3- 3.   
A n al ysis Visit Wi n d o ws f or Met a b olic Assess me nts a a n d B M D 
Assess me nts
Visit Wi n d o w St u d y D a y
Visit
N o mi n al St u d y D a y
L o wer Li mit
U p per Li mit
Baseli ne
1
( n o ne)
1
Wee k 2 4
1 6 8
2
2 5 2
Wee k 4 8
3 3 6
2 5 3
4 2 0
a   
Meta b olic assess me nts i ncl u de li pi d pa nel (t otal c h olester ol, hi g h- de nsit y li p o pr otei n [ H D L], direct l o w- de nsit y li p o pr otei n 
[ L D L], a n d tri gl yceri des). 
T he a nal ysis wi n d o ws f or ser u m b o ne safet y assess me nts f or C o h ort 1 are prese nte d i n Ta ble 3- 4  
bel o w.
C CI
C CI


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 3 of 6 4
T a ble 3- 4.   
A n al ysis Visit Wi n d o ws f or C o h ort 1 Ser u m B o ne S afet y Assess me nts a 
Visit Wi n d o w St u d y D a y
Visit
N o mi n al St u d y D a y
L o wer Li mit
U p per Li mit
Baseli ne
1
( n o ne)
1
Wee k 4
2 8
2
5 6
Wee k 1 2
8 4
5 7
1 2 6
Wee k 2 4
1 6 8
1 2 7
2 5 2
Wee k 4 8
3 3 6
2 5 3
4 2 0
a  
B o ne safet y tests (c ollecte d faste d) i ncl u de b o ne s pecific al kali ne p h os p hatase ( Bs A P), P 1 N P, C T X, P T H, 1, 2 5- O H vita mi n 
D, a n d 2 5- O H vita mi n D.
T he a nal ysis wi n d o ws f or ser u m b o ne safet y assess me nts f or C o h ort 2 are prese nte d i n Ta ble 3- 5  
bel o w.
T a ble 3- 5.   
A n al ysis Visit Wi n d o ws f or C o h ort 2 Ser u m B o ne S afet y Assess me nts a 
Visit Wi n d o w St u d y D a y
Visit
N o mi n al St u d y D a y
L o wer Li mit
U p per Li mit
Baseli ne
1
( n o ne)
1
Wee k 8
5 6
2
7 0
Wee k 1 2
8 4
7 1
1 2 6
Wee k 2 4
1 6 8
1 2 7
2 5 2
Wee k 4 8
3 3 6
2 5 3
4 2 0
a  
B o ne safet y tests (c ollecte d faste d) i ncl u de b o ne s pecific al kali ne p h os p hatase ( Bs A P), P 1 N P, C T X, P T H, 1, 2 5- O H vita mi n 
D, a n d 2 5- O H vita mi n D.
T he a nal ysis wi n d o ws f or 1 2-lea d Electr ocar di o gra m ( E C G) are prese nte d i n Ta ble 3- 6  bel o w.
C CI
C CI


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 4 of 6 4
T a ble 3- 6.   
A n al ysis Visit Wi n d o ws f or 1 2-le a d E C G
Visit Wi n d o w St u d y D a y
Visit
N o mi n al St u d y D a y
L o wer Li mit
U p per Li mit
Baseli ne
1
( n o ne)
1
T he a nal ysis wi n d o ws f or Ta n ner Sta ge assess me nts are prese nte d i n Ta ble 3- 7  bel o w.
T a ble 3- 7.   
A n al ysis Visit Wi n d o ws f or T a n ner St a ge Assess me nts
Visit Wi n d o w St u d y D a y
Visit
N o mi n al St u d y D a y
L o wer Li mit
U p per Li mit
Baseli ne
1
( n o ne)
1
Wee k 2 4
1 6 8
2
2 5 2
Wee k 4 8
3 3 6
2 5 3
3 7 8
F or Ta n ner sta ge, assess me nt is perf or me d f or partici pa nts ≥ 6 years of a ge at t he ti me of t he visit at Baseli ne/ Da y 1, Wee ks 2 4 
a n d 4 8, a n d e ver y 1 2 wee ks t hereafter, or u ntil partici pa nts reac h Ta n ner Sta ge 5.
3. 8. 3.  
Selecti o n of D at a i n t he E ve nt of M ulti ple Rec or ds i n a n A n al ysis Visit 
Wi n d o w
De pe n di n g o n t he statistical a nal ysis met h o d, si n gle val ues ma y be re q uire d f or eac h a nal ysis 
wi n d o w. F or e xa m ple, c ha n ge fr o m baseli ne b y visit us uall y re q uires a si n gle val ue, w hereas a 
ti me-t o-e ve nt a nal ysis w o ul d n ot re q uire 1 val ue per a nal ysis wi n d o w.
If m ulti ple vali d, n o n missi n g meas ure me nts e xist i n a n a nal ysis wi n d o w, rec or ds will be c h ose n 
base d o n t he f oll o wi n g r ules if a si n gle val ue is nee de d:
•
F or baseli ne, t he last n o n missi n g val ue o n or pri or t o t he first d osi n g date of st u d y dr u g will 
be selecte d, u nless s pecifie d differe ntl y. If t here are m ulti ple rec or ds wit h t he sa me ti me or 
n o ti me rec or de d o n t he sa me da y, t he baseli ne val ue will be t he a vera ge of t he 
meas ure me nts f or c o nti n u o us data, or t he meas ure me nt wit h t he l o west se verit y (e g, n or mal 
C CI
C CI


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 5 of 6 4
will be selecte d o ver a b n or mal f or safet y E C G fi n di n gs) f or cate g orical data. T he e xce pti o n 
is f or HI V- 1 R N A (see bel o w).
•
F or p ost baseli ne visits:
•
F or C D 4 cell c o u nt a n d C D 4 % data, t he rec or d(s) c ollecte d o n t he latest da y i n t he wi n d o w 
will be selecte d f or a nal ysis.
•
F or D X A data, i ncl u di n g s pi ne or T B L H B M D b o ne l oss w here b o ne l oss is ≥ 4 % fr o m 
baseli ne, a re peat meas ure me nt is t o be ta ke n t o c o nfir m t he res ult ( b o ne l oss re peat visit). 
F or re peat res ults, t he latest meas ure me nt (ie, t he b o ne l oss re peat visit) will be selecte d f or 
a nal ysis. I n a d diti o n, it s h o ul d be n ote d t hat s o me para meters at a visit will ha ve t w o 
meas ure me nts a n d ot hers f or t he sa me partici pa nt will o nl y ha ve o ne.
•
F or ot her n u meric o bser vati o ns (ie, e xce pt HI V- 1 R N A, C D 4 cell c o u nt, C D 4 %, s pi ne or 
T B L H B M D w here a b o ne l oss re peat visit occ urs), t he rec or d(s) c ollecte d o n t he da y cl osest 
t o t he n o mi nal da y f or t hat visit will be selecte d. If t here are 2 da ys e q ui dista nt fr o m t he 
n o mi nal da y, t he later da y will be selecte d.
o
F or a n y n u meric o bser vati o ns e xce pt HI V- 1 R N A, if t here are m ulti ple rec or ds o n t he 
selecte d da y, t he a vera ge will be ta ke n. F or cate g orical o bser vati o ns, if t here are m ulti ple 
rec or ds wit hi n a n a nal ysis wi n d o w, t he rec or d(s) c ollecte d o n t he da y cl osest t o t he 
n o mi nal da y f or t hat visit will be selecte d. If t here are t w o da ys e q ui dista nt fr o m t he 
n o mi nal da y, t he later da y will be selecte d. If t here are m ulti ple rec or ds o n t he selecte d 
da y, t he w orst se verit y will be ta ke n.
•
F or baseli ne a n d p ost baseli ne HI V- 1 R N A, t he latest (c o nsi deri n g b ot h date a n d ti me) 
rec or d(s) i n t he wi n d o w will be selecte d. If b ot h “ HI V R N A Ta q ma n 2. 0” or “ C O B A S 6 8 0 0” 
a n d “ HI V R N A Re peat” (ie, t he HI V- 1 R N A res ult o btai ne d fr o m a n a d diti o nal ali q u ot of t he 
ori gi nal sa m ple) are a vaila ble wit h t he sa me c ollecti o n date/ti me, t he res ults fr o m t he “ HI V 
R N A Re peat” will be selecte d f or a nal ysis p ur p oses; ot her wise, if t here are m ulti ple: “ HI V 
R N A Ta q ma n 2. 0” or “ C O B A S 6 8 0 0” rec or ds wit h t he sa me c ollecti o n date/ti me, t he 
ge o metric mea n will be ta ke n f or a nal ysis p ur p oses.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 6 of 6 4
4.  
P A R TI CI P A N T DI S P O SI TI O N
4. 1.  
P artici p a nt E nr oll me nt a n d Dis p ositi o n
Ke y st u d y dates (ie, first partici pa nt scree ne d, first partici pa nt e nr olle d, last partici pa nt e nr olle d 
a n d last partici pa nt last visit f or t he cli nical st u d y re p ort) will be pr o vi de d.
A s u m mar y of partici pa nt e nr oll me nt will be pr o vi de d f or eac h  c o u ntr y, a n d i n vesti gat or wit hi n 
t he c o u ntr y, b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall. T he s u m mar y will prese nt t he 
n u m ber a n d perce nta ge of partici pa nts e nr olle d. F or eac h c ol u m n, t he de n o mi nat or f or t he 
perce nta ge calc ulati o n will be t he t otal n u m ber of partici pa nts a nal yze d f or t hat c ol u m n.
A s u m mar y of partici pa nt dis p ositi o n will be pr o vi de d b y c o h ort (a n d gr o u p, w here a p plica ble) 
a n d o verall. T his s u m mar y will prese nt t he n u m ber of partici pa nts scree ne d, scree ne d 
partici pa nts w h o were n ot e nr olle d, i ncl u di n g t h ose scree n faile d, a n d w h o met all eli gi bilit y 
criteria b ut were n ot e nr olle d, partici pa nts e nr olle d, partici pa nts e nr olle d b ut ne ver treate d, a n d 
partici pa nts i n eac h of t he cate g ories liste d bel o w:
•
Safet y A nal ysis Set 
•
F A S 
•
F or t he 4 8- wee k treat me nt p hase:
o
C o m plete d st u d y dr u g
o
Pre mat urel y disc o nti n ue d st u d y dr u g pri or t o Wee k 4 8 wit h reas o ns f or pre mat ure 
disc o nti n uati o n of st u d y dr u g
o
C o m plete d st u d y 
o
Pre mat urel y disc o nti n ue d t he st u d y pri or t o Wee k 4 8 wit h reas o ns f or pre mat ure 
disc o nti n uati o n of st u d y
•
F or t he e xte nsi o n p hase:
o
E ntere d t he e xte nsi o n p hase
o
C o m plete d st u d y dr u g i n t he e xte nsi o n p hase 
o
Pre mat urel y disc o nti n ue d st u d y dr u g i n t he e xte nsi o n p hase wit h reas o ns f or pre mat ure 
disc o nti n uati o n of st u d y dr u g
o
C o m plete d st u d y i n t he e xte nsi o n p hase
o
Pre mat urel y disc o nti n ue d fr o m t he st u d y i n t he e xte nsi o n p hase wit h reas o ns f or 
disc o nti n uati o n


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 7 of 6 4
F or t he stat us of st u d y dr u g a n d st u d y c o m pleti o n a n d reas o ns f or pre mat ure disc o nti n uati o n, t he 
n u m ber a n d perce nta ge of partici pa nts i n eac h cate g or y will be pr o vi de d. T he de n o mi nat or f or 
t he perce nta ge calc ulati o n i n t he mai n p hase will be t he t otal n u m ber of partici pa nts i n t he Safet y 
A nal ysis Set c orres p o n di n g t o t hat c ol u m n. T he de n o mi nat or f or t he perce nta ge calc ulati o n i n t he 
e xte nsi o n p hase will be t he t otal n u m ber of partici pa nts e nteri n g e xte nsi o n p hase c orres p o n di n g 
t o t hat c ol u m n.
I n a d diti o n, t he t otal n u m ber of partici pa nts w h o were scree ne d, scree n faile d, e nr olle d, a n d t he 
n u m ber of partici pa nts i n eac h of t he dis p ositi o n cate g ories liste d a b o ve will be dis pla ye d i n a 
fl o wc hart.
T he f oll o wi n g b y- partici pa nt listi n gs will be pr o vi de d b y partici pa nt I D n u m ber i n asce n di n g 
or der t o s u p p ort t he a b o ve s u m mar y ta bles:
•
E nr oll me nt i nf or mati o n, i ncl u di n g c o h ort, treat me nt gr o u p, date of i nf or me d c o nse nt si g ne d, 
e nr oll me nt pr ot oc ol versi o n, c o u ntr y, a n d if t he y ha ve met all eli gi bilit y criteria.
•
Scree n fail ures, wit h reas o ns f or scree n fail ure ( will be pr o vi de d b y scree ni n g I D n u m ber i n 
asce n di n g or der)
•
Partici pa nt dis p ositi o n, i ncl u di n g c o h ort, t hir d a ge nt, treat me nt gr o u p, date of e nr oll me nt, 
first d ose date, last d ose date a n d da y, e n d of st u d y date a n d da y, st u d y dr u g disc o nti n uati o n 
a n d st u d y disc o nti n uati o n f or t he mai n p hase a n d t heir c orres p o n di n g reas o ns, if e ntere d 
e xte nsi o n p hase, st u d y dr u g disc o nti n uati o n a n d st u d y disc o nti n uati o n f or t he e xte nsi o n 
p hase a n d t heir c orres p o n di n g reas o ns.
•
Partici pa nt pr ofiles, i ncl u di n g c o h ort, treat me nt gr o u p, date of e nr oll me nt, first d ose date, last 
d ose date a n d da y, last visit date a n d da y, last la b orat or y date a n d da y, a n d last st u d y date a n d 
da y.
4. 2.  
E xte nt of St u d y Dr u g E x p os ure a n d A d here nce
E xte nt of e x p os ure t o st u d y dr u g will be e xa mi ne d b y assessi n g t he t otal d urati o n of e x p os ure t o 
st u d y dr u g a n d t he le vel of a d here nce relati ve t o t he st u d y dr u g re gi me n s pecifie d i n t he pr ot oc ol.
4. 2. 1.   
D ur ati o n of E x p os ure t o St u d y Dr u g
T otal d urati o n of e x p os ure t o st u d y dr u g will be defi ne d as last d osi n g date mi n us first d osi n g 
date pl us 1, re gar dless of a n y te m p orar y i nterr u pti o ns i n st u d y dr u g a d mi nistrati o n, a n d will be 
e x presse d i n wee ks usi n g u p t o 1 deci mal place (e g, 4. 5 wee ks). If t he last st u d y dr u g d osi n g date 
is missi n g, refer t o Secti o n 3. 8. 1  f or i m p utati o n met h o d. 
T he t otal d urati o n of e x p os ure t o st u d y dr u g will be s u m marize d usi n g descri pti ve statistics, a n d 
usi n g t he n u m ber (ie, c u m ulati ve c o u nts) a n d perce nta ge of partici pa nts e x p ose d t hr o u g h t he 
f oll o wi n g ti me peri o ds: ≥ 1 Wee k ( 7 da ys), ≥ 2 wee ks ( 1 4 da ys), ≥ 4 wee ks ( 2 8 da ys), ≥ 8 wee ks 
( 5 6 da ys), ≥ 1 2 wee ks ( 8 4 da ys), ≥ 2 4 wee ks ( 1 6 8 da ys), ≥ 3 6 weeks ( 2 5 2 da ys), ≥ 4 8 wee ks 
( 3 3 6 da ys), ≥ 6 0 wee ks ( 4 2 0 da ys), a n d e ver y 1 2 wee ks ( 8 4 da ys) t hereafter.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 8 of 6 4
S u m maries will be pr o vi de d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall f or t he Safet y 
A nal ysis Set.
N o f or mal statistical testi n g is pla n ne d.
4. 2. 2.   
A d here nce t o St u d y Dr u g
St u d y dr u g a d here nce is calc ulate d base d o n ta blet c o u nts. T he pres u me d t otal n u m ber of ta blets 
a d mi nistere d t o a partici pa nt is deter mi ne d b y t he data c ollecte d o n t he St u d y Dr u g 
Acc o u nta bilit y e C R F. A d here nce ( %) t o t he st u d y dr u g will be calc ulate d as f oll o ws:
A d h er e nc e (% ) = 1 0 0 ×
N u m b er of t a bl ets t a k e n
N u m b er of t a bl ets pr escri b e d
= 1 0 0 ×  
S u m of  n um b er of  t a bl ets t a k e n at e ac h dis p e nsi n g p eri o d [ 1]
S u m of n u m b er  of t abl ets pr escri b e d at e ac h dis p e nsi n g p eri o d [ 2]
[ 1] N u m ber of t a blets  t a ke n at e ac h disti nct dis pe nsi n g peri o d is calc ulate d as t he mi ni m u m of a) t he dail y 
n u m ber of ta blets prescri be d m ulti plie d b y t he d ur ati o n of tre at me nt at e ac h dis pe nsi n g peri o d , a n d b) 
n u m ber of ta blets ta ke n ( n u m ber of ta blets dis pe nse d mi n us t he n u m ber of ta blets ret ur ne d). T otal n u m ber of 
ta blets ta ke n is deter mi ne d b y s u m mi n g t he n u m ber of ta blets ta ke n fr o m all e val ua ble dis pe nsi n g peri o ds.
[ 2] N u m ber of t a blets  prescri be d at e ac h disti nct dis pe nsi n g peri o d  is calc ulate d as t he dail y n u m ber of ta blets 
prescri be d m ulti plie d b y t he d ur ati o n of tre at me nt at e ac h dis pe nsi n g peri o d . T otal n u m ber of ta blets 
prescri be d is deter mi ne d b y s u m mi n g t he n u m ber of ta blets prescri be d fr o m all e val ua ble dis pe nsi n g peri o ds.
T he d urati o n of treat me nt at eac h dis pe nsi n g peri o d is calc ulate d as t he mi ni m u m of (a) t he last 
ret ur ne d date of t he sa me dis pe nsi n g peri o d, ( b) t he date of per ma ne nt disc o nti n uati o n of st u d y 
dr u g, a n d (c) ne xt st u d y dr u g dis pe nsi n g date, mi n us t he dis pe nsi n g date of t he st u d y dr u g. 
T he ne xt st u d y dr u g dis pe nsi n g date is t he f oll o wi n g dis pe nsi n g date of t he st u d y dr u g re gar dless 
of t he b ottle ret ur n date.
F or a rec or d w here t he n u m ber of ta blets ret ur ne d was missi n g ( wit h “ Yes” a ns were d f or 
“ Was B ottle ret ur ne d?” q uesti o n), it is ass u me d t he n u m ber of ta blets ret ur ne d was 0. If t he 
n u m ber of ta blets dis pe nse d was missi n g or a n y st u d y dr u g b ottle was n ot ret ur ne d or t he b ottle 
ret ur n stat us was u n k n o w n f or t he sa me dis pe nsi n g date, all rec or ds f or t he sa me dis pe nsi n g date 
will be e xcl u de d fr o m b ot h de n o mi nat or a n d n u merat or calc ulati o ns.
Treat me nt a d here nce will be calc ulate d usi n g all data fr o m t he e ntire d osi n g peri o d u p t o t he date 
of per ma ne nt disc o nti n uati o n of t he st u d y dr u g f or partici pa nts w h o pre mat urel y disc o nti n ue d 
st u d y dr u g.
Descri pti ve statistics b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall f or treat me nt 
a d here nce ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, a n d ma xi m u m) al o n g wit h t he n u m ber a n d 
perce nta ge of partici pa nts bel o n gi n g t o treat me nt a d here nce cate g ories (e g, < 8 0 %, ≥ 8 0 % t o 
< 9 0 %, ≥ 9 0 % t o < 9 5 %, ≥ 9 5 %) will be pr o vi de d f or partici pa nts w h o ret ur n at least 1 b ottle a n d 
ha ve calc ula ble treat me nt a d here nce d uri n g t he st u d y usi n g t he Safet y A nal ysis Set. 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 2 9 of 6 4
N o f or mal statistical testi n g is pla n ne d.
Dr u g acc o u nta bilit y a n d treat me nt a d here nce data will be liste d.
A b y- partici pa nt listi n g of st u d y dr u g a d mi nistrati o n will be pr o vi de d se paratel y b y partici pa nt 
I D n u m ber (i n asce n di n g or der) a n d visit (i n c hr o n ol o gical or der).
4. 3.  
Pr ot oc ol De vi ati o ns 
Partici pa nts w h o di d n ot meet t he eli gi bilit y criteria f or st u d y e ntr y b ut e nr olle d i n t he st u d y, will 
be s u m marize d re gar dless of w het her t he y were e xe m pte d b y t he s p o ns or or n ot. T he s u m mar y 
will prese nt t he n u m ber a n d perce nta ge of partici pa nts w h o di d n ot meet at least 1 eli gi bilit y 
criteri o n b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall, base d o n t he All E nr olle d A nal ysis 
Set. 
A b y- partici pa nt listi n g will be pr o vi de d f or t h ose partici pa nts w h o di d n ot meet at least 1 
eli gi bilit y (i ncl usi o n or e xcl usi o n) criteri o n. T he listi n g will prese nt t he eli gi bilit y criteri o n ( or 
criteria if m ore t ha n 1 de viati o n) t hat partici pa nts di d n ot meet a n d relate d c o m me nts, if 
c ollecte d.
Pr ot oc ol de viati o ns occ urri n g after partici pa nts e ntere d t he st u d y are d oc u me nte d d uri n g r o uti ne 
m o nit ori n g. T he n u m ber a n d perce nta ge of partici pa nts wit h at least 1 i m p orta nt pr ot oc ol 
de viati o n will be s u m marize d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall as well as b y 
de viati o n cate g or y f or t he All E nr olle d A nal ysis Set . A d diti o nall y, t he n u m ber a n d perce nta ge of 
partici pa nts wit h at least 1, 2, or 3 or m ore i m p orta nt pr ot oc ol de viati o ns will be s u m marize d. 
T he t otal n u m ber of i m p orta nt pr ot oc ol de viati o ns will be s u m marize d b y de viati o n cate g or y. 
A b y- partici pa nt listi n g will be pr o vi de d f or t h ose partici pa nts wit h pr ot oc ol de viati o ns, 
i ncl u di n g a c ol u m n s pecif yi n g w het her t he pr ot oc ol de viati o n is i m p orta nt.
4. 4.   
Assess me nt of C O VI D- 1 9 I m p act
T his st u d y was o n g oi n g d uri n g t he n o vel c or o na vir us ( C O VI D- 1 9) pa n de mic w hic h has a n 
i m pact o n t he st u d y c o n d uct. S o me partici pa nts were u na ble t o atte n d o nsite visits d ue t o s helter 
i n place g ui deli nes, site cl os ures, or ot her reas o ns. T his secti o n descri bes h o w s pecial sit uati o ns 
d ue t o C O VI D- 1 9 will be ha n dle d i n t he a nal ysis. Please refer t o A p pe n di x 1 2. 2  f or data 
c ollecti o n a n d deter mi nati o n of C O VI D- 1 9 i m pact Data.
4. 4. 1.  
St u d y Dr u g or St u d y Disc o nti n u ati o n D ue t o C O VI D- 1 9
A b y- partici pa nt listi n g of reas o ns f or pre mat ure st u d y dr u g or st u d y disc o nti n uati o n d ue t o 
C O VI D- 1 9 will be pr o vi de d if a p plica ble.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 0 of 6 4
4. 4. 2.  
Pr ot oc ol De vi ati o ns D ue t o C O VI D- 1 9
A s u m mar y of i m p orta nt pr ot oc ol de viati o ns d ue t o C O VI D- 1 9 will be pr o vi de d, si milar t o t he 
s u m mar y descri be d i n t he pr ot oc ol de viati o ns secti o n ( Secti o n 4. 3 ).
T he n u m ber a n d perce nta ge of partici pa nts wit h n o ni m p orta nt pr ot oc ol de viati o ns relate d t o 
C O VI D- 1 9 b y n u m ber of de viati o ns (e g, at least 1, wit h 1, 2, 3 or m ore de viati o ns) will be 
s u m marize d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall.
A b y- partici pa nt listi n g will be pr o vi de d f or partici pa nts wit h i m p orta nt a n d n o ni m p orta nt 
pr ot oc ol de viati o ns relate d t o C O VI D- 1 9 se paratel y, if a p plica ble.
4. 4. 3.   
Misse d a n d Virt u al Visits d ue t o C O VI D- 1 9
A b y- partici pa nt listi n g of partici pa nts wit h misse d or virt ual visits d ue t o C O VI D- 1 9 will be 
pr o vi de d b y partici pa nt I D n u m ber i n asce n di n g or der.
I nf or mati o n re gar di n g misse d or virt ual visits d ue t o C O VI D- 1 9 will be c ollecte d as free te xt i n 
t he C R F c o m me nt fiel ds. T he deter mi nati o n of misse d or virt ual visits d ue t o C O VI D- 1 9 will be 
d o ne usi n g Nat ural La n g ua ge Pr ocessi n g ( N L P) t o searc h t he C R F c o m me nt fiel ds. A detaile d 
e x pla nati o n of t he al g orit h m is gi ve n i n A p pe n di x 1 2. 2. 2 .
4. 4. 4.   
A d verse E ve nts D ue t o C O VI D- 1 9
A d verse e ve nts of C O VI D- 1 9 will be i ncl u de d i n a nal yses of A Es if a p plica ble, w hic h will be 
deter mi ne d t hr o u g h C O VI D- 1 9 Sta n dar dize d Me d D R A Q uer y ( S M Q) narr o w searc h fr o m 
sta n dar dize d Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) q uer y. A b y- partici pa nt 
listi n g of A Es of C O VI D- 1 9 will be pr o vi de d if a p plica ble.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 1 of 6 4
5.  
B A S E LI N E C H A R A C T E RI S TI C S
5. 1.   
De m o gr a p hics a n d B aseli ne C h ar acteristics
Partici pa nt de m o gra p hic varia bles (ie, a ge, a ge gr o u p, se x at birt h, race, a n d et h nicit y) a n d 
baseli ne c haracteristics ( b o d y wei g ht [i n k g], b o d y wei g ht Z-sc ore, hei g ht [i n c m], hei g ht 
Z-sc ore, b o d y mass i n de x [ B MI; i n k g/ m 2], B MI Z-sc ore, b o d y s urface area [i n m2], a n d Ta n ner 
sta ge) will be s u m marize d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall usi n g descri pti ve 
statistics f or c o nti n u o us varia bles, a n d usi n g n u m ber a n d perce nta ge of partici pa nts f or 
cate g orical varia bles. A d diti o nall y, Ta n ner Sta ge will be s u m marize d se paratel y f or ge n der 
( breasts a n d p u bic hair f or fe male; ge nitalia a n d p u bic hair f or male). T he ma xi m u m Ta n ner 
Sta ge will be s u m marize d f or eac h ge n der se paratel y.
T he s u m mar y of de m o gra p hic data will be pr o vi de d f or t he Safet y A nal ysis Set. Missi n g val ues 
(i ncl u di n g n ot per mitte d) will n ot be i ncl u de d i n t he de n o mi nat or w he n calc ulati n g perce nta ges.
A b y- partici pa nt de m o gra p hic listi n g will be pr o vi de d b y partici pa nt I D n u m ber i n asce n di n g 
or der.
5. 2.   
Ot her B aseli ne C h ar acteristics
Ot her baseli ne c haracteristics i ncl u de:
•
T hir d a ge nt i n a partici pa nt’s pre-e xisti n g treat me nt re gi me n: (a) A T V + R T V, ( b) C O BI + 
D R V, (c) D R V + R T V, ( d) D T G, (e) E F V, a n d (f) L P V/r
•
HI V- 1 R N A cate g ories (c o pies/ m L): (a) < 5 0, a n d ( b) ≥ 5 0 
•
C D 4 cell c o u nt (cells/ μ L) 
•
C D 4 cell c o u nt cate g ories (cells/ μ L): (a) < 5 0, ( b) ≥ 5 0 t o < 2 0 0, (c) ≥ 2 0 0 t o < 3 5 0, ( d) ≥ 
3 5 0 t o < 5 0 0, a n d (e) ≥ 5 0 0 
•
C D 4 perce nta ge ( %)
•
Years dia g n ose d wit h HI V (calc ulate d as ti me pri or t o first d ose date)
•
M o de of i nfecti o n ( HI V ris k fact or): (a) Heter ose x ual Se x, ( b) H o m ose x ual Se x, (c) I V Dr u g 
Use, ( d) Tra nsf usi o n, (e) Vertical Tra ns missi o n, (f) Ot her, a n d ( g) U n k n o w n
•
HI V disease stat us: (a) AI D S, ( b) As y m pt o matic, (c) S y m pt o matic HI V I nfecti o n, a n d ( d) 
U n k n o w n
•
H B V s urface a nti ge n: (a) Ne gati ve, a n d ( b) P ositi ve


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 2 of 6 4
•
H B V s urface a nti b o d y: (a) Ne gati ve, a n d ( b) P ositi ve
•
H C V a nti b o d y: (a) Ne gati ve, a n d ( b) P ositi ve
•
e G F R calc ulate d usi n g t he Sc h wartz F or m ula ( m L/ mi n/ 1. 7 3 m 2)
•
Pr otei n uria b y uri nal ysis ( di pstic k): (a) Gra de 0, ( b) Gra de 1, (c) Gra de 2, a n d ( d) Gra de 3
T hese baseli ne c haracteristics will be s u m marize d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d 
o verall usi n g descri pti ve statistics f or c o nti n u o us varia bles a n d usi n g n u m ber a n d perce nta ge of 
partici pa nts f or cate g orical varia bles. T he s u m mar y of t hese baseli ne c haracteristics will be 
pr o vi de d f or t he Safet y A nal ysis Set. N o f or mal statistical testi n g is pla n ne d.
A b y- partici pa nt listi n g of ot her baseli ne c haracteristics will be pr o vi de d b y partici pa nt I D 
n u m ber i n asce n di n g or der.
5. 3.   
Me dic al Hist or y
Me dical hist or y will be c ollecte d at scree ni n g f or HI V- 1 disease-relate d e ve nts. Me dical hist or y 
will be c o de d usi n g t he c urre nt Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) 
dicti o nar y. 
T he me dical hist or y data will be c ollecte d at scree ni n g a n d liste d o nl y.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 3 of 6 4
6.  
E F FI C A C Y A N A L Y S E S
6. 1.  
Pri m ar y Effic ac y E n d p oi nt
T here is n o pri mar y efficac y e n d p oi nt i n t his st u d y.
6. 2.  
Sec o n d ar y Effic ac y E n d p oi nts
T he sec o n dar y efficac y e n d p oi nts are:
•
Perce nta ge of partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L at Wee ks 2 4 a n d 4 8 as 
deter mi ne d b y t he U S F D A- defi ne d s na ps h ot al g orit h m
•
T he c ha n ge fr o m baseli ne i n C D 4 cell c o u nt (cells/ μ L) a n d C D 4 perce nta ge at Wee ks 2 4 a n d 
4 8
6. 2. 1.   
Defi niti o n of t he Sec o n d ar y Effic ac y E n d p oi nts
6. 2. 1. 1.  
Perce nta ge of Partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L at Wee k 2 4 as 
Deter mi ne d b y t he U S F D A- defi ne d S na ps h ot Al g orit h m
T he defi niti o n of a b o ve e n d p oi nt ca n be referre d t o i n t he I nteri m A nal ysis 2 S A P.
6. 2. 1. 2.  
Perce nta ge of Partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L at Wee k 4 8 as 
Deter mi ne d b y t he U S F D A- defi ne d S na ps h ot Al g orit h m
T he defi niti o n of a b o ve e n d p oi nt ca n be referre d t o i n t he I nteri m A nal ysis 2 S A P.
6. 2. 2.   
A n al ysis of Sec o n d ar y Effic ac y E n d p oi nts
T he F A S will be t he pri mar y a nal ysis set f or t he sec o n dar y efficac y e n d p oi nts. N o f or mal 
statistical testi n g is pla n ne d.
6. 2. 2. 1.  
Perce nta ge of Partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L at Wee k 2 4 as 
Deter mi ne d b y t he U S F D A- defi ne d S na ps h ot Al g orit h m
All re q uire d a nal yses f or t his e n d p oi nt ha ve alrea d y bee n re p orte d as part of I nteri m A nal ysis 2.
6. 2. 2. 2.  
Perce nta ge of Partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L at Wee k 4 8 as 
Deter mi ne d b y t he U S F D A- defi ne d S na ps h ot Al g orit h m
All re q uire d a nal yses f or t his e n d p oi nt ha ve alrea d y bee n re p orte d as part of I nteri m A nal ysis 2.


E mtri cit a bi n e/f e n of o v ir Al af e n a mi d e  (F/f A F ; D es c o v y®) 
G S- U S- 3 1 1 - 1 2 6 9 
St atisti c al  A n al ysi s  Pl a n  - Fi n al  A n al y si s 
6. 2. 2. 3.  
C h a n g e fro m  B a s eli n e  i n C D 4  C e ll C o u n ts a n d  P er c e n t a g es 
V ersi o n  1. 0 
C D 4  c ell c ou n t a n d  C D 4 %  d at a  wi ll b e su m m ar i z e d u s i ng  o b s e rv e d,  o n- ti· e at m ent  d at a  (i e,  dat a 
c oll e c te d u p  t o 1 d a y  aft er p e n n a n e nt  dis c o nt i n uati o n  or  c o m pl eti o n of st u dy di u g). 
A b s ol ut e  v al u e s  a n d  c h a n g es  fr o m  b a s e li ne  i n C D 4  c ell c o u n t ( c ells/ µ L )  a n d C D 4 %  at  e a c h  vi si t 
wi ll b e  su m m ar i z e d b y  c o h o 1i  ( an d  gr o u p,  w h er e  a p p li c a ble)  a n d  o v er a ll a n d  b y  vi sit 
d e s c ri ptiv el y  ( s a mp l e si z e,  m e a n,  S D,  m e di a n , Ql , Q 3,  mi ni m u m ,  a n d m a xi m u m)  a n d  wi ll al s o 
i ncl u d e  t h e 9 5 % CI b a s e d  o n t h e  t-dis u-i b uti o n. 
T h e  m e a n  a n d  9 5 % CI of c h a n g e  fr o m  b a s e li ne  o v e r ti m e b y  c o h o 1i ( an d  gr o u p,  w h er e 
a p p li c a bl e) a n d  o v er all  wi ll b e  pl ot te d. 
T h e  a bs ol ut e v a l ues of C D 4  c e ll c o u nt  ( c ells/ µ L)  a n d  C D 4 % at  e a c h  vi sit  wi ll al s o b e list e d . 
--
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1 9 F e b r u ar y 2 0 2 5 
GI L E A D  C O N FI D E N TI A L  I N F O R M A TI O N 
P a g e  3 4 of 6 4 


E mtri ci t a bi n e/f e n of o vir Al af e n a mi d e  (F/f A F; D es c ov y ®) 
G S- U S- 3 1 1 - 1 2 6 9 
St a tisti c a l A n al ysi s  Pl a n  - Fi n a l A n a lysis 
I 
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I 
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6. 4.  
C h a n g e s  F r o m  P r ot o c ol- S p e cifi e d  Effi c a c y  A n al y s e s 
T h er e  ar e  n o  d e v i atio n s  fr o m t h e  pr ot o c o l-s p e c ifie d e ffic a c y  a n al ys es. 
1 9 F e br u ar y  2 0 2 5 
G I L E A D C O N FI D E N TI A L  I N F O R M A TI O N 
V e rsi o n 1. 0 
P a g e  3 5 of 6 4 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 6 of 6 4
7.  
S A F E T Y A N A L Y S E S
7. 1.   
A d verse E ve nts a n d De at hs
7. 1. 1.   
A d verse E ve nt Dicti o n ar y
Cli nical a n d la b orat or y A Es will be c o de d usi n g t he c urre nt versi o n of Me d D R A. S yste m or ga n 
class ( S O C), hi g h-le vel gr o u p ter m ( H L G T), hi g h-le vel ter m ( H L T), preferre d ter m ( P T), a n d 
l o west-le vel ter m ( L L T) will be pr o vi de d i n t he A E dataset.
7. 1. 2.   
A d verse E ve nt Se verit y
A d verse e ve nts are gra de d b y t he i n vesti gat or as Gra de 1 ( mil d), 2 ( m o derate), 3 (se vere), 4 
(life-t hreate ni n g) acc or di n g t o t o xicit y criteria s pecifie d i n t he pr ot oc ol. T he se verit y gra de of 
e ve nts f or w hic h t he i n vesti gat or di d n ot rec or d se verit y will be cate g orize d as “ missi n g” f or 
ta b ular s u m maries a n d data listi n gs. T he missi n g cate g or y will be liste d last i n s u m mar y 
prese ntati o n.
7. 1. 3.   
Rel ati o ns hi p of A d verse E ve nts t o St u d y Dr u g
Relate d A Es are t h ose f or w hic h t he i n vesti gat or selecte d “ Relate d” o n t he A E e C R F t o t he 
q uesti o n of “ Relate d t o St u d y Treat me nt.” Relate d ness will al wa ys defa ult t o t he i n vesti gat or’s 
c h oice, n ot t hat of t he me dical m o nit or. E ve nts f or w hic h t he i n vesti gat or di d n ot rec or d 
relati o ns hi p t o st u d y dr u g will be c o nsi dere d relate d t o st u d y dr u g f or s u m mar y p ur p oses. 
H o we ver, b y- partici pa nt data listi n gs will s h o w t he relati o ns hi p as missi n g.
7. 1. 4.  
Seri o us A d verse E ve nts
Seri o us A Es ( S A Es) will be i de ntifie d a n d ca pt ure d as S A Es if t he A Es met t he defi niti o ns of 
S A Es t hat were s pecifie d i n t he st u d y pr ot oc ol. Seri o us A Es ca pt ure d a n d st ore d i n t he cli nical 
data base will be rec o ncile d wit h t he S A E data base fr o m t he Gilea d Patie nt Safet y De part me nt 
bef ore data fi nalizati o n.
7. 1. 5.  
Tre at me nt- E mer ge nt A d verse E ve nts 
7. 1. 5. 1.   
Defi niti o n of Treat me nt- E mer ge nt A d verse E ve nts
Treat me nt-e mer ge nt A Es ( T E A Es) are defi ne d as e ve nts t hat meet o ne of t he f oll o wi n g criteria:
•
A n y A Es wit h a start date o n or after t he date of t he first d ose of st u d y dr u g a n d u p t o 3 0 da ys 
after t he per ma ne nt disc o nti n uati o n of t he st u d y dr u g
•
A n y A Es t hat res ult i n per ma ne nt st u d y dr u g disc o nti n uati o n


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 7 of 6 4
7. 1. 5. 2.  
I nc o m plete Dates
If t he start date of t he A E is i nc o m plete a n d t he A E st o p date is n ot pri or t o t he first d osi n g date 
of st u d y dr u g, t he n t he m o nt h a n d year ( or year al o ne if m o nt h is n ot rec or de d) of start deter mi ne 
w het her a n A E is treat me nt-e mer ge nt ( T E). T he e ve nt is c o nsi dere d T E if b ot h of t he f oll o wi n g 2 
criteria are met:
•
T he A E start date is t he sa me as or after t he m o nt h a n d year ( or year) of t he first d osi n g date 
of st u d y dr u g, a n d
•
T he A E start date is t he sa me as or bef ore t he m o nt h a n d year ( or year) of t he date 
c orres p o n di n g t o 3 0 da ys after t he date of t he last d ose of st u d y dr u g 
A n A E wit h c o m pletel y missi n g start a n d st o p dates, or wit h t he start date missi n g a n d a st o p 
date later t ha n t he first d osi n g date of st u d y dr u g, will be c o nsi dere d t o be T E. I n a d diti o n, a n A E 
wit h t he start date missi n g a n d i nc o m plete st o p date wit h t he sa me or later m o nt h a n d year ( or 
year al o ne if m o nt h is n ot rec or de d) as t he first d osi n g date of st u d y dr u g will be c o nsi dere d T E.
7. 1. 6.  
S u m m aries of A d verse E ve nts a n d De at hs
Treat me nt-e mer ge nt A Es will be s u m marize d base d o n t he Safet y A nal ysis Set.
7. 1. 6. 1.  
S u m maries of A E i nci de nce i n C o m bi ne d Se verit y Gra de S u bsets 
A brief, hi g h-le vel s u m mar y of t he n u m ber a n d perce nta ge of partici pa nts w h o e x perie nce d at 
least 1 T E A E i n t he cate g ories descri be d bel o w will be pr o vi de d b y c o h ort (a n d gr o u p, w here 
a p plica ble) a n d o verall. All deat hs o bser ve d i n t he st u d y will als o be i ncl u de d i n t his s u m mar y.
I n a d diti o n, a brief, hi g h-le vel s u m mar y of T E A Es u p t o t he n o mi nal Wee k 2 4 visit will als o be 
pr o vi de d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall. S u m maries of A Es u p t o n o mi nal 
Wee k 2 4 will i ncl u de a n y A E wit h start date o n or bef ore t he n o mi nal Wee k 2 4 visit date. T he 
sa me a nal ysis will be re peate d f or t he n o mi nal Wee k 4 8 visit. 
T he n u m ber a n d perce nta ge of partici pa nts w h o e x perie nce d at least 1 T E A E will be pr o vi de d 
a n d s u m marize d b y S O C, P T, c o h ort (a n d gr o u p, w here a p plica ble), a n d o verall as f oll o ws: 
•
T E A Es
•
T E A Es wit h Gra de 2 or hi g her 
•
T E A Es wit h Gra de 3 or hi g her
•
T E treat me nt-relate d A Es
•
T E treat me nt-relate d A Es wit h Gra de 2 or hi g her 
•
T E treat me nt-relate d A Es wit h Gra de 3 or hi g her 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 8 of 6 4
•
T E S A Es
•
T E treat me nt-relate d S A Es 
•
T E A Es lea di n g t o pre mat ure disc o nti n uati o n of st u d y dr u g
•
T E A Es lea di n g t o pre mat ure disc o nti n uati o n of st u d y
•
T E A Es lea di n g t o deat h (ie, o utc o me of deat h)
M ulti ple e ve nts will be c o u nte d o nl y o nce per partici pa nt i n eac h s u m mar y. A d verse e ve nts will 
be s u m marize d a n d liste d first i n al p ha betic or der of S O C a n d t he n b y P T i n desce n di n g or der of 
t otal fre q ue nc y wit hi n eac h S O C. 
I n a d diti o n, all T E A Es a n d T E treat me nt-relate d A Es will be s u m marize d b y P T o nl y, i n 
desce n di n g or der of t otal fre q ue nc y. All T E A Es u p t o n o mi nal Wee k 2 4 visit a n d n o mi nal 
Wee k 4 8 visit will als o be s u m marize d b y P T o nl y.
I n a d diti o n, data listi n gs will be pr o vi de d f or t he f oll o wi n g:
•
All A Es, i n dicati n g w het her t he e ve nt is T E
•
All A Es u p t o n o mi nal Wee k 2 4 visit, i n dicati n g w het her t he e ve nt is T E
•
All A Es u p t o n o mi nal Wee k 4 8 visit, i n dicati n g w het her t he e ve nt is T E
•
All A Es wit h se verit y of Gra de 3 or hi g her
•
All S A Es
•
All treat me nt-relate d S A Es
•
All deat hs
•
All A Es lea di n g t o pre mat ure disc o nti n uati o n of st u d y dr u g
•
All A Es lea di n g t o deat h 
•
All A Es lea di n g t o pre mat ure disc o nti n uati o n of st u d y


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 3 9 of 6 4
7. 1. 6. 2.  
S u m maries of A E I nci de nce b y Se verit y 
T he n u m ber a n d perce nta ge of partici pa nts w h o e x perie nce d at least 1 T E A E will be pr o vi de d 
a n d s u m marize d b y S O C a n d P T, b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall.
•
T E A Es b y ma xi m u m se verit y 
•
T E treat me nt-relate d A Es b y ma xi m u m se verit y 
M ulti ple e ve nts will be c o u nte d o nl y o nce per partici pa nt i n eac h s u m mar y. A d verse e ve nts will 
be s u m marize d a n d liste d first i n al p ha betic or der of S O C a n d t he n b y P T i n desce n di n g or der of 
t otal fre q ue nc y wit hi n eac h S O C. F or s u m maries b y se verit y gra de, t he w orst se verit y gra de will 
be use d f or t h ose A Es t hat occ urre d m ore t ha n o nce i n a gi ve n partici pa nt d uri n g t he st u d y.
7. 1. 7.   
A d diti o n al A n al ysis of A d verse E ve nts
7. 1. 7. 1.  
Cate g or y C E ve nts i n HI V
O n a n o n g oi n g basis A Es will be re vie we d f or e ve nts t hat mi g ht meet t he defi niti o n of 
Cate g or y C e ve nts t hat are i n dicati ve of a n ac q uire d i m m u ne deficie nc y s y n dr o me 
( AI D S)- defi ni n g dia g n osis. T he Gilea d me dical m o nit or will re vie w p ossi ble Cate g or y C e ve nts 
a n d a p pr o ve t he e ve nts t hat meet t he defi niti o n. T h ose e ve nts t hat d o meet t he Cate g or y C 
defi niti o n of a n AI D S- defi ni n g dia g n osis will be liste d. A list of Cate g or y C AI D S- Defi ni n g 
Dia g n osis ca n be f o u n d i n A p pe n di x 6 of st u d y pr ot oc ol a me n d me nt 2.
7. 1. 7. 2.  
Fract ure E ve nts
S u m maries of t he f oll o wi n g T E A Es of i nterest will be pr o d uce d t o e n ha nce t he a nal ysis of safet y 
data.
•
A Es of fract ure e ve nts, utilizi n g a Me d D R A searc h ter m ( M S T) list de vel o pe d b y Gilea d
T he n u m ber a n d perce nta ge of partici pa nts w h o ha d a n y of t he a b o ve e ve nts will be s u m marize d 
f or eac h c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall b y A E of i nterest cate g or y a n d P T. A 
b y- partici pa nt listi n g of fract ure e ve nts will be pr o vi de d.
7. 2.  
L a b or at or y E v al u ati o ns
La b orat or y data c ollecte d d uri n g t he st u d y will be a nal yze d a n d s u m marize d usi n g b ot h 
q ua ntitati ve a n d q ualitati ve met h o ds. T he a nal ysis will be base d o n val ues re p orte d i n 
c o n ve nti o nal u nits. W he n val ues are bel o w t he L O Q, t he y will be liste d as s uc h, a n d t he cl osest 
i m p ute d val ue will be use d f or t he p ur p ose of calc ulati n g s u m mar y statistics as s pecifie d i n 
Secti o n 3. 7 . 
S u m maries of la b orat or y data will be pr o vi de d f or t he Safet y A nal ysis Set a n d will i ncl u de data 
c ollecte d u p t o 3 0 da ys after per ma ne nt disc o nti n uati o n of st u d y dr u g.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 0 of 6 4
A b y- partici pa nt listi n g f or la b orat or y test res ults will be pr o vi de d b y partici pa nt I D n u m ber a n d 
visit i n c hr o n ol o gical or der f or he mat ol o g y, ser u m c he mistr y, a n d uri nal ysis se paratel y. Val ues 
falli n g o utsi de of t he rele va nt refere nce ra n ge a n d/ or ha vi n g a se verit y gra de of 1 or hi g her will 
be fla g ge d i n t he data listi n gs, as a p pr o priate.
A listi n g will prese nt la b orat or y test refere nce ra n ges f or he mat ol o g y, ser u m c he mistr y 
(i ncl u di n g li ver-relate d a n d b o ne-relate d e val uati o ns), uri nal ysis, C D 4 cell c o u nt a n d perce nta ge.
N o f or mal statistical testi n g is pla n ne d.
7. 2. 1.  
S u m m aries of N u meric L a b or at or y Res ults
Descri pti ve statistics will be pr o vi de d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall f or 
eac h la b orat or y test s pecifie d i n t he st u d y pr ot oc ol as f oll o ws:
•
Baseli ne val ues 
•
Val ues at eac h p ost baseli ne a nal ysis wi n d o w
•
C ha n ge fr o m baseli ne at eac h p ost baseli ne a nal ysis wi n d o w
•
Perce nta ge c ha n ge fr o m baseli ne at eac h p ost baseli ne a nal ysis wi n d o w (if s pecifie d)
A baseli ne la b orat or y val ue will be defi ne d as t he last meas ure me nt o btai ne d o n or pri or t o t he 
date of first d ose of st u d y dr u g. C ha n ge fr o m baseli ne t o a p ost baseli ne visit will be defi ne d as 
t he p ost baseli ne val ue mi n us t he baseli ne val ue. T he mea n, me dia n, Q 1, Q 3, mi ni m u m, a n d 
ma xi m u m val ues will be dis pla ye d t o t he re p orte d n u m ber of di gits; S D val ues will be dis pla ye d 
t o t he re p orte d n u m ber of di gits pl us 1.
I n t he case of m ulti ple val ues i n a n a nal ysis wi n d o w, data will be selecte d f or a nal ysis as 
descri be d i n Secti o n 3. 8. 3 .
C alci u m C orrecte d f or Al b u mi n:
Calci u m c orrecte d f or al b u mi n will be calc ulate d a n d s u m marize d f or t he st u d y. T he f oll o wi n g 
f or m ula will be use d w he n b ot h ser u m calci u m a n d al b u mi n res ults f or a gi ve n bl o o d dra w are 
a vaila ble a n d ser u m al b u mi n val ue is < 4. 0 g/ d L.
•
Calci u m c orrecte d f or al b u mi n ( m g/ d L) = ser u m calci u m ( m g/ d L) + 0. 8 x ( 4. 0 - al b u mi n 
[ g/ d L]).
T o xicit y gra di n g f or calci u m will be a p plie d base d o n t he c orrecte d val ues.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 1 of 6 4
7. 2. 2.   
Gr a de d L a b or at or y V al ues
T he Gilea d Gra di n g Scale f or Se verit y of A d verse E ve nts a n d La b orat or y A b n or malities will be 
use d t o assi g n t o xicit y gra des ( 0 t o 4) t o la b orat or y res ults f or a nal ysis. Gra de 0 i ncl u des all 
val ues t hat d o n ot meet t he criteria f or a n a b n or malit y of at least Gra de 1. F or la b orat or y tests 
wit h criteria f or b ot h i ncrease d a n d decrease d le vels, a nal yses f or eac h directi o n (ie, i ncrease d, 
decrease d) will be prese nte d se paratel y. 
If t here is a n y la b orat or y t o xicit y gra di n g scale o verla p pi n g wit h t he n or mal refere nce ra n ges 
(ie, gra de 1 scale o verla ps wit h n or mal refere nce ra n ges), la b orat or y val ues t hat are wit hi n t he 
n or mal ra n ge will be gra de 0 e xce pt f or li pi d tests.
F or tri gl yceri des, L D L, a n d c h olester ol, t he pr ot oc ol-s pecifie d t o xicit y gra di n g scale is f or 
fasti n g test val ues, s o n o nfasti n g li pi d res ults ( or li pi d res ults wit h o ut k n o w n fasti n g stat us) will 
n ot be gra de d or s u m marize d b y t o xicit y gra des.
7. 2. 2. 1.  
Treat me nt- E mer ge nt La b orat or y A b n or malities
Treat me nt-e mer ge nt la b orat or y a b n or malities are defi ne d as val ues t hat i ncrease at least 
1 t o xicit y gra de fr o m baseli ne at a n y p ost baseli ne ti me p oi nt d uri n g t he ti me peri o d s pecifie d i n 
Secti o n 7. 2 . If t he rele va nt baseli ne la b orat or y val ue is missi n g, a n y a b n or malit y of at least 
Gra de 1 o bser ve d wit hi n t he ti me fra me s pecifie d a b o ve will be c o nsi dere d T E.
Fasti n g gl uc ose a n d n o nfasti n g gl uc ose (i ncl u di n g gl uc ose res ults wit h o ut a k n o w n fasti n g 
stat us) are gra de d base d o n differe nt gra di n g scales as s pecifie d i n t he pr ot oc ol.
7. 2. 2. 2.  
S u m maries of La b orat or y A b n or malities
La b orat or y data t hat are cate g orical will be s u m marize d usi n g t he n u m ber a n d perce nta ge of 
partici pa nts i n t he st u d y wit h t he gi ve n res p o nse at baseli ne a n d eac h sc he d ule d p ost baseli ne 
visit.
T he f oll o wi n g s u m maries ( n u m ber a n d perce nta ge of partici pa nts) f or T E la b orat or y 
a b n or malities will be pr o vi de d b y la b orat or y test a n d b y c o h ort (a n d gr o u p, w here a p plica ble) 
a n d o verall; partici pa nts will be cate g orize d acc or di n g t o t he m ost se vere p ost baseli ne 
a b n or malit y gra de f or a gi ve n la b orat or y test:
•
Gra de d T E la b orat or y a b n or malities
•
Gra de 3 or 4 T E la b orat or y a b n or malities
F or all s u m maries of la b orat or y a b n or malities, t he de n o mi nat or is t he n u m ber of partici pa nts 
wit h n o n missi n g p ost baseli ne val ues d uri n g t he ti me peri o d s pecifie d i n Secti o n 7. 2 .
A b y- partici pa nt listi n g of gra de d la b orat or y a b n or malities, as well as Gra de 3 or 4 la b orat or y 
a b n or malities will be pr o vi de d b y partici pa nt I D n u m ber a n d visit i n c hr o n ol o gical or der. T hese 
listi n gs will i ncl u de all test res ults t hat were c ollecte d t hr o u g h o ut t he st u d y f or t he la b orat or y test 
of i nterest, wit h all a p plica ble se verit y gra des dis pla ye d a n d T E la b orat or y a b n or malities fla g ge d.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 2 of 6 4
7. 2. 3.  
Li ver-rel ate d L a b or at or y E v al u ati o ns
Li ver-relate d a b n or malities after baseli ne will be e xa mi ne d a n d s u m marize d usi n g t he n u m ber 
a n d perce nta ge of partici pa nts w h o were re p orte d t o ha ve t he f oll o wi n g la b orat or y test val ues f or 
p ost baseli ne meas ure me nts:
•
As partate a mi n otra nsferase ( A S T): (a) > 3 ti mes t he u p per li mit of refere nce ra n ge ( U L N); 
( b) > 5 x U L N; (c) > 1 0 x U L N; ( d) > 2 0 x U L N
•
Ala ni ne a mi n otra nsferase ( A L T): (a) > 3 x U L N; ( b) > 5 x U L N; (c) > 1 0 x U L N; ( d) > 2 0 x 
U L N
•
A S T or A L T: (a) > 3 x U L N; ( b) > 5 x U L N; (c) > 1 0 x U L N; ( d) > 2 0 x U L N
•
T otal bilir u bi n: (a) > 1 x U L N; ( b) > 2 x U L N
•
Al kali ne p h os p hatase ( A L P): > 1. 5 x U L N
•
A S T or A L T > 3 x U L N a n d t otal bilir u bi n: (a) > 1. 5 x U L N; ( b) > 2 x U L N
•
A S T or A L T > 3 x U L N, t otal bilir u bi n > 2 x U L N, a n d A L P < 2 x U L N
T he s u m mar y will i ncl u de data fr o m all p ost baseli ne visits d uri n g t he ti me peri o d s pecifie d i n 
Secti o n 7. 2 . F or i n di vi d ual la b orat or y tests, partici pa nts will be c o u nte d o nce base d o n t he m ost 
se vere p ost baseli ne val ues. F or b ot h t he c o m p osite e n d p oi nt of A S T or A L T a n d t otal bilir u bi n, 
a n d t he c o m p osite e n d p oi nt of A S T or A L T, t otal bilir u bi n, a n d A L P, partici pa nts will be 
c o u nte d o nce w he n t he criteria are met at t he sa me p ost baseli ne visit date. T he de n o mi nat or is 
t he n u m ber of partici pa nts i n t he Safet y A nal ysis Set w h o ha ve n o n missi n g p ost baseli ne val ues 
of all rele va nt tests at t he sa me p ost baseli ne visit date. A listi n g of partici pa nts w h o met at least 1 
of t he a b o ve criteria will be pr o vi de d.
Partici pa nts wit h A S T or A L T > 3 x U L N, T otal bilir u bi n > 1 x U L N, or A L P > 1. 5 x U L N will 
als o be liste d.
7. 2. 4.   
Met a b olic L a b or at or y E v al u ati o ns
F or meta b olic assess me nts, i ncl u di n g fasti n g gl uc ose a n d t he li pi d pa nel (ie, t otal c h olester ol, 
tri gl yceri des, direct L D L, H D L, t otal c h olester ol t o H D L rati o), o nl y t h ose meas ure me nts u n der 
fasti n g stat us will be s u m marize d a n d liste d base d o n t he Safet y A nal ysis Set.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 3 of 6 4
7. 2. 5.   
Re n al S afet y E v al u ati o ns
7. 2. 5. 1.  
Ser u m Creati ni ne a n d e G F R Sc h wartz
T he Sc h wartz f or m ula will be use d t o calc ulate e G F R:
o
e G F R ( m L/ mi n/ 1. 7 3 m 2) = k × L/ SCr , w here k is t he pr o p orti o nalit y c o nsta nt ( 0. 5 5 f or 
c hil dre n [ ≥ 2 t o < 1 2 years] a n d a d olesce nt fe males ≥ 1 2 years; 0. 7 0 f or a d olesce nt males 
≥ 1 2 years, L is hei g ht (c m), S Cr is ser u m creati ni ne ( m g/ d L)
Baseli ne, p ost baseli ne, a n d c ha n ge fr o m baseli ne i n ser u m creati ni ne a n d e G F R Sc h wartz  will be 
s u m marize d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall b y visit usi n g descri pti ve 
statistics. 
Me dia n ( Q 1, Q 3)  of t he c ha n ge fr o m baseli ne val ues f or ser u m creati ni ne a n d e G F R Sc h wartz  will 
be pl otte d usi n g a li ne pl ot  b y c o h ort (a n d gr o u p, w here a p plica ble), b y a nal ysis wi n d o w.
7. 2. 5. 2.  
Re nal Safet y Tests
Re nal safet y tests, i ncl u di n g reti n ol bi n di n g pr otei n ( R B P), beta- 2- micr o gl o b uli n, uri ne 
creati ni ne, uri ne R B P t o uri ne creati ni ne rati o, uri ne beta- 2- micr o gl o b uli n t o uri ne creati ni ne 
rati o, a n d uri ne pr otei n t o creati ni ne rati o, will be s u m marize d b y visit usi n g descri pti ve statistics 
a n d liste d.
7. 2. 6.  
B o ne S afet y E v al u ati o ns 
7. 2. 6. 1.  
B o ne Mi neral De nsit y
B o ne mi neral de nsit y data c ollecte d d uri n g t he st u d y will be a nal yze d a n d s u m marize d usi n g 
b ot h q ua ntitati ve a n d q ualitati ve met h o ds. S u m maries of B M D data will be pr o vi de d f or t he 
s pi ne usi n g t he S pi ne D X A A nal ysis Set a n d T B L H usi n g t he T B L H D X A A nal ysis Set.
Descri pti ve statistics will be pr o vi de d b y c o h ort a n d o verall a n d b y visit f or s pi ne a n d T B L H 
B M D as f oll o ws:
•
Baseli ne val ue
•
Val ue at eac h p ost baseli ne a nal ysis wi n d o w
•
C ha n ge fr o m baseli ne t o eac h p ost baseli ne a nal ysis wi n d o w (if s pecifie d)
•
Perce nta ge c ha n ge fr o m baseli ne t o eac h p ost baseli ne a nal ysis wi n d o w (if s pecifie d)
I n a d diti o n, descri pti ve statistics will be pr o vi de d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d 
o verall a n d b y visit f or t he s pi ne a n d T B L H B M D Z-sc ores (sta n dar d Z-sc ore a n d hei g ht-a ge 
Z-sc ore) as f oll o ws:


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 4 of 6 4
•
Baseli ne val ue
•
Val ue at eac h p ost baseli ne a nal ysis wi n d o w
•
C ha n ge fr o m baseli ne t o eac h p ost baseli ne a nal ysis wi n d o w
S hift ta bles of cli nical B M D stat us at baseli ne vers us p ost baseli ne visits will be prese nte d f or 
b ot h s pi ne a n d T B L H B M D. Cli nical B M D stat us will be classifie d i nt o t w o cate g ories usi n g 
B M D Z-sc ores (sta n dar d Z-sc ore a n d hei g ht-a ge Z-sc ore): Z-sc ores > −2 vers us Z-sc ores ≤ −2 
{ G or d o n 2 0 0 8 } . T he s hift will be fr o m > −2 t o ≤ −2.
T he n u m be r a n d perce nta ge of partici pa nts wit h at least 4 % decli ne i n B M D fr o m baseli ne t o 
eac h p ost baseli ne visit will be s u m marize d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall 
a n d b y visit f or b ot h s pi ne a n d T B L H B M D.
B y- partici pa nt listi n gs of B M D, Z-sc ores (sta n dar d Z-sc ore a n d hei g ht-a ge Z-sc ore) will be 
pr o vi de d f or s pi ne a n d T B L H B M D se paratel y.
A b y- partici pa nt listi n g will pr o vi de partici pa nts wit h at least 4 % decli ne i n B M D fr o m baseli ne 
t o a n y p ost baseli ne visit i n eit her b o d y site (ie, s pi ne or T B L H). T he B M D val ues, sta n dar d 
Z-sc ores, hei g ht-a ge Z-sc ores, hei g ht, a n d b o d y wei g ht will be prese nte d.
B y- partici pa nt listi n gs of partici pa nts wit h s pi ne a n d/ or T B L H B M D Z-sc ore t hat s hifts fr o m 
> −2 at baseli ne t o ≤ −2 at a n y p ost baseli ne visit will als o be pr o vi de d, fr o m sta n dar d Z-sc ores 
a n d hei g ht-a ge Z-sc ores, se paratel y. 
7. 2. 6. 2.  
B o ne Safet y Tests
Ser u m b o ne safet y tests i ncl u de: Bs A P, P 1 N P, C T X, P T H, 1, 2 5- O H vita mi n D, a n d 2 5- O H 
vita mi n D.
Descri pti ve statistics will be pr o vi de d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall a n d 
b y visit f or b o ne tests a b o ve as f oll o ws:
•
Baseli ne val ue
•
Val ue at eac h p ost baseli ne a nal ysis wi n d o w
•
C ha n ge fr o m baseli ne t o eac h p ost baseli ne a nal ysis wi n d o w (if s pecifie d)
•
Perce nta ge c ha n ge fr o m baseli ne t o eac h p ost baseli ne a nal ysis wi n d o w (if s pecifie d)
A b y- partici pa nt listi n g will be pr o vi de d f or b o ne safet y test res ults a b o ve, as well as 
N-tel o pe pti de a n d N-tel o pe pti de/creati ni ne fr o m uri ne c he mistr y tests.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 5 of 6 4
7. 3.  
T a n ner St a ge Assess me nt
Ta n ner Sta ges will be use d t o e val uate t he o nset a n d pr o gressi o n of p u bertal c ha n ges f or c hil dre n 
w h o are 6 years or ol der. Fe males will be rate d f or p u bic hair gr o wt h a n d breast de vel o p me nt, 
a n d males will be rate d f or p u bic hair gr o wt h a n d ge nitalia de vel o p me nt. T he s hift i n Ta n ner 
Sta ges ( breasts or p u bic hair f or fe male; ge nitalia or p u bic hair f or male) fr o m baseli ne at all 
p ost baseli ne visits will be s u m marize d b y se x, b y c o h ort (a n d gr o u p, w here a p plica ble) a n d 
o verall usi n g fre q ue nc y c o u nt a n d perce nta ge. T he ma xi m u m Ta n ner Sta ge will als o be 
prese nte d.
Ta n ner Sta ge res ults at Da y 1 a n d d uri n g t he st u d y, if a vaila ble, will be liste d.
7. 4.   
Acce pt a bilit y a n d P al at a bilit y Assess me nt
Acce pta bilit y assess me nts will be s u m marize d usi n g fre q ue nc y c o u nt a n d perce nta ge b y c o h ort 
(a n d gr o u p, w here a p plica ble) a n d o verall. Palata bilit y assess me nts will be s u m marize d usi n g 
fre q ue nc y c o u nt a n d perce nta ge b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall, b y visit.
A b y- partici pa nt listi n g will als o be pr o vi de d f or acce pta bilit y a n d palata bilit y details.
7. 5.  
B o d y Wei g ht, Hei g ht, a n d Vit al Si g ns
A n a ge- a n d se x-s pecific Z-sc ore will be deri ve d f or eac h b o d y wei g ht, hei g ht, a n d B MI 
meas ure me nt acc or di n g t o t he d o w nl oa da ble S A S pr o gra m a vaila ble o n t he Ce nters f or Disease 
C o ntr ol a n d Pre ve nti o n ( C D C) we bsite usi n g t he year 2 0 0 0 gr o wt h c harts. T he met h o ds a n d S A S 
pr o gra m p u blis he d o n t he f oll o wi n g C D C we bsites will be a p plie d t o calc ulate t he Z-sc ore:
•
htt p:// w w w.c dc. g o v/ ncc d p h p/ d n pa o/ gr o wt hc harts/res o urces/i n de x. ht m
•
htt p:// w w w.c dc. g o v/ ncc d p h p/ d n pa o/ gr o wt hc harts/res o urces/sas. ht m
Descri pti ve statistics will be pr o vi de d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall f or 
b o d y wei g ht, b o d y wei g ht Z-sc ore, b o d y hei g ht, b o d y hei g ht Z-sc ore, B MI a n d B MI Z-sc ore as 
f oll o ws:
•
Baseli ne val ue
•
Val ues at eac h p ost baseli ne a nal ysis wi n d o w
•
C ha n ge fr o m baseli ne at eac h p ost baseli ne a nal ysis wi n d o w
A baseli ne val ue will be defi ne d as t he last a vaila ble val ue c ollecte d o n or pri or t o t he date of 
first d ose of st u d y dr u g. C ha n ge fr o m baseli ne t o a p ost baseli ne visit will be defi ne d as t he 
p ost baseli ne val ue mi n us t he baseli ne val ue. 
I n t he case of m ulti ple val ues i n a n a nal ysis wi n d o w, data will be selecte d f or a nal ysis as 
descri be d i n Secti o n 3. 8. 3 . N o f or mal statistical testi n g is pla n ne d.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 6 of 6 4
A b y- partici pa nt listi n g of b o d y wei g ht, b o d y wei g ht Z-sc ore, b o d y hei g ht, b o d y hei g ht Z-sc ore, 
B MI, B MI Z-sc ore, a n d B S A will be pr o vi de d.
A b y- partici pa nt listi n g of vital si g ns will be pr o vi de d b y partici pa nt I D n u m ber a n d visit i n 
c hr o n ol o gical or der.
7. 6.  
Pri or a n d C o nc o mit a nt Me dic ati o ns
Me dicati o ns c ollecte d at scree ni n g a n d d uri n g t he st u d y will be c o de d usi n g t he c urre nt versi o n 
of t he W orl d Healt h Or ga nizati o n ( W H O) Dr u g dicti o nar y.
F or t he p ur p oses of a nal ysis, a n y me dicati o ns wit h a start date pri or t o or o n t he first d osi n g date 
of st u d y dr u g c o nti n ue d t o be ta ke n after t he first d osi n g date, or w hic h are starte d after t he first 
d osi n g date b ut pri or t o or o n t he last d osi n g date of st u d y dr u g will be c o nsi dere d c o nc o mita nt 
me dicati o ns. Me dicati o ns starte d a n d st o p pe d o n t he sa me da y as t he first d osi n g date or t he last 
d osi n g date of st u d y dr u g will als o be c o nsi dere d c o nc o mita nt. Me dicati o ns wit h a st o p date pri or 
t o t he date of first d osi n g date of st u d y dr u g or a start date after t he last d osi n g date of st u d y dr u g 
will be e xcl u de d fr o m t he c o nc o mita nt me dicati o n s u m mar y.
If a partial st o p date is e ntere d, a n y me dicati o n wit h t he m o nt h a n d year (if da y is missi n g) or 
year (if da y a n d m o nt h are missi n g) pri or t o t he date of first st u d y dr u g a d mi nistrati o n will be 
e xcl u de d fr o m t he c o nc o mita nt me dicati o n s u m mar y. If a partial start date is e ntere d, a n y 
me dicati o n wit h t he m o nt h a n d year (if da y is missi n g) or year (if da y a n d m o nt h are missi n g) 
after t he st u d y dr u g st o p date will be e xcl u de d fr o m t he c o nc o mita nt me dicati o n s u m mar y. 
Me dicati o ns wit h c o m pletel y missi n g start a n d st o p dates will be i ncl u de d i n t he c o nc o mita nt 
me dicati o n s u m mar y, u nless ot her wise s pecifie d. S u m maries will be base d o n t he Safet y 
A nal ysis Set. N o f or mal statistical testi n g is pla n ne d.
7. 6. 1.   
N o nst u d y- Dr u g A ntiretr o vir al Me dic ati o ns
N o nst u d y- dr u g me dicati o ns are defi ne d as a n y A R V me dicati o ns ot her t ha n st u d y dr u g t hat are 
ta ke n pri or t o, d uri n g or after t he st u d y (if c ollecte d).
N o nst u d y- dr u g A R V me dicati o n wit h a n e n d date o n or 1 da y bef ore t he first d ose date of st u d y 
dr u g will be c o nsi dere d as n o nst u d y- dr u g A R V me dicati o n recei ve d pri or t o t he first d ose date of 
st u d y dr u g ( or pres witc h A R V use d).
N o nst u d y- dr u g A R V me dicati o n recei ve d pri or t o t he first d ose date of st u d y dr u g will be 
s u m marize d b y A R V dr u g class a n d ge neric na me f or partici pa nts i n t he Safet y A nal ysis Set. 
M ulti ple dr u g use ( b y dr u g class or ge neric na me) will be c o u nte d o nl y o nce per partici pa nt. 
Dr u g classes will be prese nte d al p ha beticall y a n d ge neric na mes wit hi n eac h dr u g class will be 
prese nte d i n desce n di n g or der of t he t otal fre q ue nc y. N o i nfere ntial statistics will be pr o vi de d.
All n o nst u d y- dr u g A R V me dicati o ns will be pr o vi de d i n a b y- partici pa nt listi n g s orte d b y 
partici pa nt I D n u m ber a n d a d mi nistrati o n date i n c hr o n ol o gical or der.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 7 of 6 4
7. 6. 2.   
C o nc o mit a nt N o n- A R V Me dic ati o ns
C o nc o mita nt n o n- A R V me dicati o ns are defi ne d as n o n- A R V me dicati o ns ot her t ha n st u d y dr u g 
ta ke n w hile a partici pa nt recei vi n g t he st u d y dr u g. 
All c o nc o mita nt n o n- A R V me dicati o ns will be s u m marize d b y c o h ort (a n d gr o u p, w here 
a p plica ble) a n d o verall, b y preferre d na me. M ulti ple dr u g use ( b y preferre d na me) will be 
c o u nte d o nl y o nce per partici pa nt. T he s u m mar y will be s orte d b y decreasi n g t otal fre q ue nc y. 
F or dr u gs wit h t he sa me fre q ue nc y, s orti n g will be d o ne al p ha beticall y. 
A b y- partici pa nt listi n g will als o be pr o vi de d a n d s orte d b y partici pa nt I D n u m ber a n d 
a d mi nistrati o n date i n c hr o n ol o gical or der.
7. 7.  
Electr oc ar di o gr a m Res ults
S u m maries of i n vesti gat or assess me nt of E C G rea di n gs will be pr o vi de d as bel o w f or t he Safet y 
A nal ysis Set f or eac h sc he d ule d ti me p oi nt. N o f or mal statistical testi n g is pla n ne d. 
A s hift ta ble of t he i n vesti gat ors’ assess me nt of E C G res ults at eac h visit c o m pare d wit h baseli ne 
val ues will be prese nte d b y c o h ort (a n d gr o u p, w here a p plica ble) a n d o verall usi n g t he f oll o wi n g 
cate g ories: n or mal; a b n or mal, n ot cli nicall y si g nifica nt; a b n or mal, cli nicall y si g nifica nt; or 
missi n g. T he n u m ber a n d perce nta ge of partici pa nts i n eac h cr oss-classificati o n gr o u p of t he s hift 
ta ble will be prese nte d. Partici pa nts wit h a missi n g val ue at baseli ne or p ost baseli ne will n ot be 
i ncl u de d i n t he de n o mi nat or f or perce nta ge calc ulati o n.
A b y- partici pa nt listi n g of E C G assess me nt res ults will be pr o vi de d b y partici pa nt I D n u m ber 
a n d visit i n c hr o n ol o gical or der.
7. 8.   
Ot her S afet y Me as ures
A b y- partici pa nt listi n g of partici pa nt pre g na ncies d uri n g t he st u d y will be pr o vi de d b y 
partici pa nt I D n u m ber.
Alt h o u g h n ot necessaril y relate d t o safet y, a b y- partici pa nt listi n g of all c o m me nts recei ve d 
d uri n g t he st u d y o n t he Ge neral C o m me nts e C R F will be pr o vi de d b y partici pa nt I D n u m ber, a n d 
f or m f or w hic h t he c o m me nt a p plies.
7. 9.   
C h a n ges Fr o m Pr ot oc ol- S pecifie d S afet y A n al yses
T here are n o de viati o ns fr o m t he pr ot oc ol-s pecifie d safet y a nal yses.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 8 of 6 4
8.  
P H A R M A C O KI N E TI C ( P K) A N A L Y S E S
8. 1.  
P K S a m ple C ollecti o n
B ot h i nte nsi ve a n d s parse P K were c ollecte d f or all partici pa nts t hr o u g h o ut t he st u d y. Refer t o 
A p pe n di x 2 i n t he st u d y pr ot oc ol a me n d me nt 2 f or sc he d ule details f or P K sa m ple c ollecti o n. 
8. 2.  
P K A n al yses Rel ate d t o I nte nsi ve/ S p arse P K S a m pli n g
A b y- partici pa nt listi n g will list t he a vaila ble P B M C P K sa m ples f or T F V- D P c o nce ntrati o ns a n d 
t he ass ociate d res ults. All ot her a nal yses relate d t o I P K a n d s parse P K ha ve bee n c o m plete d i n 
I nteri m A nal ysis 2. Please refer t o t he S A P f or I nteri m A nal ysis 2 f or details.
8. 2. 1.  
P K/ P D A n al yses
P K/ P D relati o ns hi ps are n ot a p plica ble f or t he st u d y.
8. 3.   
C h a n ges Fr o m Pr ot oc ol- S pecifie d P K A n al yses
T here are n o de viati o ns fr o m t he pr ot oc ol-s pecifie d P K a nal yses.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 4 9 of 6 4
9.   
R E F E R E N C E S
G or d o n C M, Bac hrac h L K, Car pe nter T O, Cra btree N, El- Hajj F ulei ha n G, K utile k S, et al. D ual 
E ner g y X-ra y A bs or pti o metr y I nter pretati o n a n d Re p orti n g i n C hil dre n a n d 
A d olesce nts: T he 2 0 0 7 I S C D Pe diatric Official P ositi o ns. J Cli n De nsit o m 
2 0 0 8; 1 1 ( 1): 4 3- 5 8.
U. S. De part me nt of Healt h a n d H u ma n Ser vices, F o o d a n d Dr u g A d mi nistrati o n ( F D A), Ce nter 
f or Dr u g E val uati o n a n d Researc h ( C D E R). H u ma n I m m u n o deficie nc y Vir us- 1 
I nfecti o n: De vel o pi n g A ntiretr o viral Dr u gs f or Treat me nt. G ui da nce f or I n d ustr y. 
Sil ver S pri n g, M D. N o ve m ber, 2 0 1 5.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 0 of 6 4
1 0.  
S O F T W A R E
S A S ®  S oft ware Versi o n 9. 4. ( S A S I nstit ute I nc., Car y, N C, U S A.)
n Q uer y A d vis or ®  Versi o n 7. 0. ( Statistical S ol uti o ns, C or k, Irela n d.)


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 1 of 6 4
1 1.  
S A P R E VI SI O N
Re visi o n D ate
( D D M M M Y Y Y Y) 
Secti o n 
S u m m ar y of Re visi o n
Re as o n f or Re visi o n


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 2 of 6 4
1 2.   
A P P E N DI C E S
1 2. 1.  
Sc he d ule of Assess me nts
E n d of Wee k a
P ost Wee k 4 8 b
St u d y Pr oce d ure
Scree n c
B aseli ne/ 
D a y 1 d
1 
2 
4 
8
1 2 
2 4 
3 6 
4 8
E ver y
1 2 W ks
E ver y
2 4 W ks
3 0 D a y
F oll o w- u p e
E S D D f
I nf or me d C o nse nt/ Asse nt
X
Me dical Hist or y g
X
C o nc o mita nt Me dicati o ns
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
A d verse E ve nts
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
C o m plete P h ysical E xa m
X 
X
X
X
X h
X
S y m pt o m- Directe d P h ysical E x a m i
X 
X 
X 
X 
X
X
X
X
1 2- Lea d E C G ( perf or me d s u pi ne)
X
X j
X
Vital Si g ns
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
Wei g ht a n d Hei g ht/ Le n gt h
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
Uri nal ysis
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
Uri ne C he mistr y
X
X 
X 
X 
X 
X
X 
X
X
Selecte d Re nal Safet y Tests k
X
X 
X 
X 
X 
X
X 
X
X l
Ser u m Pre g na nc y Test m
X
Uri ne Pre g na nc y Test n
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
C he mistr y Pr ofile
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
Meta b olic Assess me nts
X
X
X
X
C CI


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 3 of 6 4
E n d of Wee k a
P ost Wee k 4 8 b
St u d y Pr oce d ure
Scree n c
B aseli ne/ 
D a y 1 d
1 
2 
4 
8
1 2 
2 4 
3 6 
4 8
E ver y
1 2 W ks
E ver y
2 4 W ks
3 0 D a y
F oll o w- u p e
E S D D f
Esti mate d G F R
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
He mat ol o g y Pr ofile
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
Plas ma HI V- 1 R N A
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
C D 4 Cell C o u nt
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
W h ole Bl o o d Sa m ple St ora ge
X
Ser u m St ora ge Sa m ple
X
X
H C V Ser ol o g y p
X
H B V Ser ol o g y
X
E nr oll me nt q
X
C o h ort 1 Dis pe nse Diar y Car ds r
X
C o h orts 2, 3, & 4 Dis pe nse Diar y
Car ds r
X 
X
Si n gle Ra n d o m P K Sa m ple s
X
X
C o h orts 1 a n d 2 Faste d Pri or t o Visit
X
X 
X 
X 
X 
X
X
X
C o h ort 1 I P K Sa m pli n g t
X
C o h ort 2 Part A I P K Sa m pli n g t
X t
X t
C o h ort 1 Palata bilit y a n d
Acce pta bilit y Assess me nt u
X
u
X
X u
C o h ort 2 Part A Palata bilit y a n d
C CI


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 4 of 6 4
E n d of Wee k a
P ost Wee k 4 8 b
St u d y Pr oce d ure
Scree n c
B aseli ne/  
D a y 1 d
1 
2 
4 
8
1 2 
2 4 
3 6 
4 8
E ver y
1 2 W ks
E ver y
2 4 W ks
3 0 D a y
F oll o w- u p e
E S D D f
Acce pta bilit y Assess me nt
X 
X
Si n gle O bser ve d D osi n g P K Sa m ple v
X
X
Tr o u g h P K Sa m ple s, w
X
P B M C s, x
X
D X A Sca n (s pi ne & t otal b o d y)
X
X
X
X
X y
X y
C o h ort 1 Ser u m B o ne Safet y Tests z
X
X
X 
X
X
X
X aa
C o h orts 2, 3, a n d 4 Ser u m B o ne
Safet y Tests z
X
X 
X 
X
X
X
X aa
Ta n ner Sta ge Assess me nt b b
X
X
X 
X
I n- Cli nic D osi n g
X 
X 
X 
X
St u d y Dr u g Dis pe nsati o n
X
X 
X 
X 
X 
X 
X
X cc
St u d y Dr u g Acc o u nta bilit y
X 
X 
X 
X 
X 
X 
X 
X 
X
X
a   
All st u d y visits are t o be sc he d ule d relati ve t o w he n t he Baseli ne/ Da y 1 visit was c o m plete d. All st u d y visits t hr o u g h Wee k 8 are t o be c o m plete d wit hi n ± 2 da ys of t he 
pr ot oc ol-s pecifie d visit date. Visits bet wee n Wee k 1 2 t hr o u g h Wee k 4 8 are t o be c o m plete d wit hi n ± 4 da ys of t he pr ot oc ol-s pecifie d visit date, u nless ot her wise s pecifie d.
b  
P ost Wee k 4 8 st u d y visits are t o be c o m plete d e ver y 1 2 wee ks ( ± 1 0 da ys) u nless ot her wise s pecifie d. 
c   
All scree ni n g e val uati o ns are t o be c o m plete d wit hi n 3 5 da ys pri or t o Baseli ne/ Da y 1 Visit.
d  
Partici pa nts will be dis pe nse d st u d y dr u g o n t he Baseli ne/ Da y 1 Visit. I nitiati o n of treat me nt wit h t he st u d y dr u g m ust ta ke place wit hi n 2 4 h o urs after t he Baseli ne/ Da y 1 
visit. F/ T A F will be pr o vi de d b y t he S p o ns or u nless pr o hi bite d b y l ocal re g ulati o ns or u p o n re q uest b y t he partici pa nt d ue t o i ns ura nce restricti o ns.
e  
3 0 Da y F oll o w- U p o nl y re q uire d f or t h ose partici pa nts w h o d o n ot wis h t o c o nti n ue t o partici pate after Wee k 4 8 or t h ose partici pa nts w h o per ma ne ntl y disc o nti n ue st u d y dr u g 
a n d d o n ot c o nti n ue i n t he st u d y t hr o u g h at least o ne s u bse q ue nt visit after t he Earl y St u d y Dr u g Disc o nti n uati o n ( E S D D) Visit. F or t he p ur p ose of sc he d uli n g a 3 0- Da y 
F oll o w- U p Visit, a ± 6 da ys wi n d o w ma y be use d.
f  
Earl y St u d y Dr u g Disc o nti n uati o n visit t o occ ur wit hi n 7 2 h o urs of last d ose of st u d y dr u g. Partici pa nts will be as ke d t o c o nti n ue atte n di n g t he sc he d ule d st u d y visits t hr o u g h 
Wee k 4 8 e ve n if t he partici pa nt disc o nti n ues st u d y dr u g.
g   
Me dical hist or y s h o ul d i ncl u de a hist or y of HI V- 1 disease-relate d e ve nts, o n g oi n g me dicati o ns wit hi n 3 0 da ys of Scree ni n g, a n d all i nf or mati o n a vaila ble o n hist orical 
ge n ot y pes.
h  
C o m plete p h ysical e xa mi nati o n e ver y 4 8 wee ks p ost 4 8 wee ks ( ur o ge nital/a n orectal e xa ms will be perf or me d at t he discreti o n of t he I n vesti gat or).


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 5 of 6 4
i  
S y m pt o m- directe d p h ysical e xa mi nati o n, as nee de d.
j  
1 2-lea d E C G perf or me d s u pi ne e ver y 4 8 wee ks p ost wee k 4 8.
k  
Re nal safet y tests assess me nts will be c ollecte d faste d f or C o h orts 1 a n d 2. If t he partici pa nt has n ot faste d pri or t o t he visit t he partici pa nt m ust ret ur n wit hi n 7 2 h o urs i n a 
faste d state t o c ollect uri ne f or re nal safet y tests.
l  
Re q uire d f or E S D D visit if last test was > 1 2 wee ks fr o m E S D D visit.
m  
Fe males of c hil d beari n g p ote ntial i n C o h orts 1 a n d 2 o nl y. Perf or me d at scree ni n g a n d a n yti me d uri n g t he st u d y t o c o nfir m a p ositi ve uri ne pre g na nc y test. 
n  
Fe males of c hil d beari n g p ote ntial i n C o h orts 1 a n d 2 o nl y. P ositi ve uri ne pre g na nc y tests a n yti me d uri n g t he st u d y will be c o nfir me d wit h a ser u m test.
p  
If t he a nti b o d y test res ult is p ositi ve, H C V R N A test will be perf or me d t o c o nfir m H C V vire mia.
q
Assi g n me nt of t he partici pa nt’s e nr oll me nt n u m ber ma y occ ur u p t o 7 da ys pri or t o t he Baseli ne/ Da y 1 visit.
r   
Diar y Car ds will be dis pe nse d at Wee k 1 f or all partici pa nts i n C o h ort 1 t o rec or d a d mi nistrati o n of st u d y dr u gs a n d t heir 3 r d A R V a ge nt f or at least 3 da ys pri or t o t he I P K 
visit at t he Wee k 2 visit. Diar y Car ds will be dis pe nse d at Wee k 1 or Wee k 2 f or all partici pa nts i n Part A of C o h orts 2, 3, a n d 4 t o rec or d a d mi nistrati o n of st u d y dr u gs a n d 
t heir 3r d A R V a ge nt f or at least 3 da ys pri or t o t he I P K visit t hat is t o occ ur d uri n g t he Wee k 2 or 4 visit, or wit hi n 7 after t he c o m pleti o n of t he Wee k 2 or Wee k 4 visit. 
Diar y Car ds are t o be c ollecte d a n d re vie we d f or pr ot oc ol c o m plia nce pri or t o i n-cli nic d osi n g a n d I P K sa m pli n g. If t he partici pa nt has alrea d y d ose d or is n ot faste d pri or t o 
t he I P K e val uati o n visit refer I P K i nstr ucti o ns i n t he st u d y pr ot oc ol a me n d me nt 2 Secti o n 6. 3 f or details o n h o w t o pr ocee d.
s  
Partici pa nts are all o we d t o ta ke st u d y dr u g at a p pr o xi matel y t he sa me ti me eac h da y h o we ver at t he ti me of t he si n gle ra n d o m P K, tr o u g h P K, or P B M C sa m pli n g t he y are 
re q uire d t o re p ort t he ti me of t he last d ose.
t  
I P K will occ ur d uri n g t he Wee k 2 visit f or partici pa nts i n C o h ort 1 a n d at eit her t he Wee k 2 or Wee k 4 visit, or wit hi n 7 da ys after t he c o m pleti o n of Wee k 2 or Wee k 4 visits, 
f or partici pa nts i n C o h ort 2 Part A. F or t he p ur p ose of sc he d uli n g t he I P K visit, a + 7 da y wi n d o w ma y be use d. Partici pa nt d osi n g diar y car ds are t o be c ollecte d a n d re vie we d 
pri or t o i n-cli nic d osi n g a n d I P K sa m pli n g.
u  
F or C o h ort 1, palata bilit y will be assesse d 3 0 - 6 0 mi n utes after st u d y dr u g d osi n g f or all partici pa nts u n der g oi n g I P K sa m pli n g at Wee k 2. Acce pta bilit y will be assesse d 3 0 - 
6 0 mi n utes after st u d y dr u g d osi n g f or acti ve partici pa nts at t he ne xt st u d y visit i m me diatel y f oll o wi n g a p pr o val of t his pr ot oc ol at t he site.
v   
A si n gle o bser ve d d osi n g P K sa m ple will be c ollecte d at Wee ks 4 a n d 1 2 at a n y ti me bet wee n 1 5 mi n t o 4 h o urs p ost o bser ve d i n-cli nic d ose. F or partici pa nts i n C o h ort 2 Part 
A, a si n gle o bser ve d d osi n g P K sa m ple d oes n ot nee d t o be c ollecte d at Wee k 4 if I P K is c ollecte d at t he Wee k 4 visit.
w  
F or partici pa nts i n all C o h orts a tr o u g h P K sa m ple will be c ollecte d d uri n g t he Wee k 8 visit at 0 h o urs ( pre- d ose, ≤ 3 0 mi n utes pri or  t o d osi n g) will be c ollecte d.
x  
F or partici pa nts i n C o h orts 1 a n d 2, P B M C c ollecti o n will be perf or me d at t he Wee k 8 visit o nl y at st u d y sites t hat ca n perf or m P B M C pr ocessi n g. All P B M C bl o o d sa m ples 
will be c ollecte d at 0 h o urs ( ≤ 3 0 mi n utes pr e- d ose).
y   
D X A sca n t o be perf or me d at t he 3 0 Da y F oll o w- u p visit or t he E S D D visit if t he last sca n was ac q uire d > 1 2 wee ks fr o m t he date of t he E S D D Visit. D X A sca n ca n occ ur u p 
t o 1 0 da ys after t he E S D D visit date.
z  
If t he partici pa nt has n ot faste d pri or t o t he bl o o d dra w f or ser u m b o ne safet y tests visit ma y c o nti n ue h o we ver t he partici pa nt m ust ret ur n wit hi n 7 2 h o urs after c o m pleti o n of 
t he visit i n a faste d state t o dra w bl o o d f or ser u m b o ne safet y tests.
aa  Ser u m b o ne safet y test is re q uire d at E S D D visit if last test was > 1 2 wee ks fr o m E S D D visit.
b b  Ta n ner assess me nts will be perf or me d at Baseli ne/ Da y 1, Wee ks 2 4 a n d 4 8 a n d e ver y 1 2 p ost wee k 4 8, or u ntil partici pa nt reac hes Ta n ner Sta ge 5 
cc   
Dr u g dis pe nsati o n at Wee k 4 8 is o nl y f or partici pa nts t hat are t o c o nti n ue i n t he st u d y p ost Wee k 4 8.
C CII 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 6 of 6 4
1 2. 2.   
D at a C ollecti o n of C O VI D- 1 9 D at a
T his a p pe n di x descri bes t he cli nical trial site c ollecti o n of C O VI D- 1 9 data pertai ni n g t o 
misse d/ virt ual visits a n d t he data pr ocessi n g al g orit h m t hat will be use d t o deter mi ne w hic h visits 
are missi n g a n d w hic h visits are virt ual.
1 2. 2. 1.   
D at a C ollecti o n
A C O VI D- 1 9 s u p ple me nt t o t he e C R F C o m pleti o n G ui deli nes was pr o vi de d b y Cli nical Data 
Ma na ge me nt t o i nstr uct cli nical trial sites wit h data e ntr y e x pectati o ns pertai ni n g t o sce nari os 
relate d t o t he C O VI D- 1 9 pa n de mic. If a visit was misse d, sites were i nstr ucte d t o e nter “ Visit 
misse d d ue t o C O VI D- 1 9” a n d if a n i n- pers o n visit was c o n d ucte d virt uall y, sites were i nstr ucte d 
t o e nter “ Virt ual visit d ue t o C O VI D- 1 9”.
1 2. 2. 2.   
Deter mi n ati o n of Misse d a n d Virt u al Visits
Nat ural la n g ua ge pr ocessi n g will be use d t o searc h t he C R F c o m me nt fiel ds t o i de ntif y i nsta nces 
of “ C O VI D- 1 9”, “ Virt ual”, or s y n o n y ms (see Ta ble 1 2- 1 ). T he searc h ter ms will be mai ntai ne d 
i n a gl o bal l o o k u p ta ble a n d ca n be m o difie d t o t u ne t he N L P m o del. A n y c o m me nts wit h 
C O VI D- 1 9 searc h ter ms, “ Misse d visit” or “ Virt ual visit will be assi g ne d as f oll o ws:
•
If C O VI D- 1 9 ter ms are i de ntifie d t hr o u g h N L P a n d t he visit date is missi n g, t he n res ult is 
” Misse d Visit”
•
If C O VI D- 1 9 a n d Virt ual ter ms are i de ntifie d t hr o u g h N L P f or a visit, t he n res ult is “ Virt ual 
Visit”. W he n t here are m ulti ple rec or ds f or t he sa me partici pa nt a n d t he sa me visit, if o ne 
rec or d c o ul d be cate g orize d as “ Virt ual Visit”, all rec or ds ass ociate d wit h t his partici pa nt a n d 
t his visit will be cate g orize d as “ Virt ual Visit”
•
Ot her wise, t he res ult is missi n g
T a ble 1 2- 1 . 
E x a m ple Se arc h Ter ms f or “ C O VI D- 1 9 ” a n d “ Virt u al ” Use d t o 
I de ntif y Misse d/ Virt u al Visits
Se arc h Ter ms f or “ C O VI D- 1 9 ”
Se arc h Ter ms f or “ Virt u al ”
C O VI D 1 9
VI R T U A L
C O R O N A
T E L E M E D
C O R O N A VI R U S
T E L E H E A L T H
P A N D E MI C
T E L E P H O N E
O U T B R E A K
R E M O T E
C RI SI S
T E L E M E DI CI N E
L O C K D O W N
T E L E C O N S U L T A TI O N
Q U A R A N TI N E
T E L E P H O NI C A L L Y


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 7 of 6 4
Se arc h Ter ms f or “ C O VI D- 1 9 ”
Se arc h Ter ms f or “ Vir t u al ”
S H E L T E R
P H O N E
H O M E VI SI T
Z O O M
S K Y P E
1 2. 3.   
U S F D A- Defi ne d S n a ps h ot Al g orit h m
T he fl o wc hart of t he U S F D A- defi ne d s na ps h ot al g orit h m base d o n t he U S F D A G ui da nce o n 
H u ma n I m m u n o deficie nc y Vir us- 1 I nfecti o n: De vel o pi n g A ntiretr o viral Dr u gs f or Treat me nt 
{ U. S. De part me nt of Healt h a n d H u ma n Ser vices 2 0 1 5 } is pr o vi de d i n Fi g ure 1 2- 1 .


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 8 of 6 4
Fi g ure 1 2- 1.  
Fl o wc h art of U S F D A- Defi ne d S n a ps h ot Al g orit h m 
*   
O n-treat me nt data i ncl u de all data c ollecte d u p t o 1 da y after t he last d ose of st u d y dr u g f or partici pa nts w h o pre mat urel y 
disc o nti n ue or c o m plete st u d y dr u g.
I t h e n.: ill I · ~I I n-
------ 1 tr c: 1t m m• HI 
- 1 R 1 A d a m 
1 1 
l e d i n 1 h 
n a p h  1 1---- ... ·o 
I· t h· I t a, ai la b l  o n-tr e at m e nt• 
HI 
- 1 Ill 
i n I 
I 
\ i n d W < 0 C 
C 
Ill - 1 R N 
< 
0 c o pi 
ml , 
i n d w ? 
I r u d dr u g p 
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ir ol gi D at n 
g O I d urir 
b ut o n 
t u 
Dr u g 


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 5 9 of 6 4
1 2. 4.  
Pr o gr a m mi n g S pecific ati o n
Ge ner al C o n ve nti o ns
1)
A G E calc ulate d as f oll o ws:
a)
A G E ( years) is calc ulate d fr o m t he n u m ber of da ys bet wee n t he date of birt h ( D O B) a n d 
Da y 1 (first d ose date),
b)
Use t he S A S I N T C K f u ncti o n t o deter mi ne t he n u m ber of “ 1st- of- m o nt h da ys” 
(e g, Ja n uar y 1st, Fe br uar y 1st, Marc h 1st) bet wee n D O B a n d Da y 1 (i ncl usi ve),
c)
Di vi de t he res ult i n ( b) b y 1 2,
d)
A G E = t he i nte ger of t he res ult i n (c),
e) If t he D O B a n d Da y 1 ha ve t he m o nt h i n c o m m o n a n d t he birt h da y is later i n t he m o nt h 
t ha n t he date of St u d y Da y 1, t he n s u btract o ne fr o m t he A G E res ult a b o ve.
F or partici pa nts e nr olle d a n d ne ver d ose d wit h st u d y dr u g, a ge will be calc ulate d fr o m t he 
date of e nr oll me nt. 
A ge f or la b orat or y test refere nce ra n ge will be base d o n t he a ge at t he sa m ple c ollecti o n date.
2)
Years si nce partici pa nt dia g n ose d wit h HI V
First D ose Year – Year Partici pa nt Dia g n ose d wit h HI V (if HI V was prese nt at birt h, years 
si nce partici pa nt was dia g n ose d will be e q ual t o a ge of partici pa nt).
3)
All scree ne d partici pa nts refer t o all partici pa nts w h o are scree ne d (ie, wit h n o n missi n g 
scree ni n g date) a n d ha ve a scree ni n g n u m ber. F or s u m maries t he sa me partici pa nt is c o u nte d 
o nl y o nce. Date of birt h a n d ot her de m o gra p hic i nf or mati o n s uc h as se x, race, et h nicit y, 
c o u ntr y, a n d i nitials will be use d t o i de ntif y u ni q ue scree ne d partici pa nts.
4)
Scree n fail ure partici pa nts are t h ose partici pa nts w h o were scree ne d a n d a ns were d “ N o” f or 
a n y i ncl usi o n criteri o n or “ Yes” f or a n y e xcl usi o n criteri o n re gar dless of w hic h versi o n of 
pr ot oc ol t he partici pa nt was c o nse nte d t o. I n a d diti o n, f or partici pa nts w h o “ Met All 
Eli gi bilit y Criteria” ie, t h ose w h o were scree ne d b ut n ot e nr olle d, t hese are partici pa nts w h o 
a ns were d “ N o” t o “ Was t he partici pa nt e nr olle d” i n t he E nr oll me nt e C R F.
5)
Partici pa nts i n t he All E nr olle d A nal ysis Set are defi ne d as partici pa nts e nr olle d i n t he st u d y. 
I X R S R A N D is t he s o urce t o deter mi ne w het her a partici pa nt is e nr olle d (ie, partici pa nt wit h 
n o n missi n g E N R D T N i n t he I X R S R A N D dataset), a n d c o nfir me d b y t he E N R O L L dataset 
(ie, E N R O L L Y N = “ Yes” i n E N R O L L dataset).
6) I n dis p ositi o n ta ble, t he reas o ns f or pre mat ure disc o nti n uati o n are dis pla ye d i n t he or der t he y 
a p pear o n t he e C R F.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 6 0 of 6 4
7)
B MI a n d B S A
B MI a n d B S A will be calc ulate d o nl y at baseli ne as f oll o ws:
a)
B MI = ( wei g ht [ k g])/ ( hei g ht [ meters] 2)
b)
B S A ( m 2) = S Q R T( [ Hei g ht(c m) x Wei g ht( k g) ]/ 3 6 0 0 )
B MI a n d B S A are deri ve d o nl y at visits w here b ot h wei g ht a n d hei g ht are c ollecte d. F urt her, 
if hei g ht is at scree ni n g a n d wei g ht is at Da y 1 a n d scree ni n g, t he deri vati o ns w o ul d be base d 
o n t he sa me visit (i n t his case scree ni n g)
Baseli ne is defi ne d as t he last val ue o n or pri or t o St u d y 1 f or all assess me nts, u nless 
ot her wise s pecifie d. E xa m ples bel o w:
a) If hei g ht is c ollecte d at b ot h scree ni n g a n d Da y 1, t he n Da y 1 val ues w o ul d be use d.
b) If hei g ht is c ollecte d at scree ni n g o nl y t he n scree ni n g w o ul d be use d.
8)
“ N ot Per mitte d”, “ U n k n o w n”, or missi n g cate g ories will be e xcl u de d f or perce nta ge 
calc ulati o n; e xce pt f or m o de of i nfecti o n ( HI V Ris k Fact ors), w here “ U n k n o w n” will be 
i ncl u de d f or perce nta ge calc ulati o n, si nce a partici pa nt ma y fit m ore t ha n 1 HI V ris k fact or, 
a n d t heref ore perce nta ge ma y a d d t o m ore t ha n 1 0 0 %.
9)
Last D ose Date a n d Last St u d y Date
a)
Last d ose date (ie, T R T E D T C or T R T E D T) i n A D S L was defi ne d i n Secti o n 3. 8. 1 .
F or partici pa nts wit h a partial last d osi n g date (ie, m o nt h a n d year of last d ose are 
k n o w n), t he latest of t he dis pe nsi n g dates of st u d y dr u g b ottles, st u d y dr u g start dates a n d 
e n d dates, a n d t he i m p ute d last d ose date [ da y i m p ute d as 1 5] will be use d as t he fi nal 
i m p ute d last d ose date. H o we ver, if dis pe nsi n g date’s m o nt h is after last d ose date’s 
m o nt h, a data q uer y is nee de d.
b)
Last st u d y date is t he latest of t he st u d y dr u g start a n d e n d dates, t he cli nic visit dates, a n d 
t he la b orat or y visit dates, i ncl u di n g t he 3 0- da y f oll o w- u p visit date f or partici pa nts w h o 
pre mat urel y disc o nti n ue d st u d y or w h o c o m plete d t he st u d y acc or di n g t o t he St u d y 
C o m pleti o n e C R F. If st u d y dr u g start or e n d date is partiall y missi n g (ie, o nl y year a n d 
m o nt h are k n o w n), t he da y will be i m p ute d as 1 5 f or t he p ur p ose of t his a nal ysis.
1 0) F or HI V- 1 R N A M = F, 
M = F w he n
a)
T he partici pa nt has a visit after t he missi n g val ue.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 6 1 of 6 4
b)
T he partici pa nt is missi n g HI V- 1 R N A beca use he/s he has alrea d y disc o nti n ue d t he st u d y 
dr u g.
c)
T he partici pa nt ca me f or a la b orat or y visit f or t hat visit, b ut t he HI V- 1 R N A val ue is 
missi n g (e g, sa m ple iss ue).
Missi n g is e xcl u de d fr o m t he de n o mi nat or w he n
d)
T his partici pa nt has neit her baseli ne n or p ost baseli ne la b orat or y data.
1 1) T E A E
E ve nts wit h Missi n g St art D a y a n d/ or M o nt h
A n A E is T E if t he f oll o wi n g 3 criteria are met:
1.
T he m o nt h a n d year ( or year) of start date is t he sa me as or after t he m o nt h a n d year 
( or year) of t he first d ose of st u d y dr u g, a n d
2.
T he m o nt h a n d year ( or year) of t he start date is t he sa me as or bef ore t he m o nt h a n d year 
( or year) of t he 3 0t h da y after t he date of t he last d ose of st u d y dr u g, a n d
3.
E n d date is as f oll o ws:
a.
T he (c o m plete) e n d date is o n or after t he first d ose date, or
b.
T he m o nt h a n d year ( or year) of e n d date is t he sa me or after t he m o nt h a n d year 
( or year) of t he first d ose of st u d y dr u g, or
c.
E n d date is c o m pletel y missi n g
E ve nts wit h C o m pletel y Missi n g St art D ate
A n A E wit h a c o m pletel y missi n g start date is defi ne d as T E A E if e n d date meets a n y of t he 
criteria s pecifie d i n 3) a b o ve.
1 2) Gra de d La b orat or y A b n or malities S u m mar y


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 6 2 of 6 4
T he f oll o wi n g la bels will be use d f or T E la b orat or y a b n or malities a n d Gra de 3 or 4 T E 
la b orat or y a b n or malities s u m mar y ta bles a n d listi n gs:
B atter y
L a b or at or y Test L a bel
Use d i n l-l a bt o x Listi n g
T o xicit y 
Directi o n
L a b or at or y Test L a bel
Use d i n t-l a bt o x T a ble
He mat ol o g y
He m o gl o bi n
Decrease
He m o gl o bi n ( Decrease d)
 
Ne utr o p hils
Decrease
Ne utr o p hils ( Decrease d)
 
Platelets
Decrease
Platelets ( Decrease d)
 
W B C
Decrease
W B C ( Decrease d)
C he mistr y
Al b u mi n
Decrease
Al b u mi n ( Decrease d)
 
Al kali ne P h os p hatase
I ncrease
Al kali ne P h os p hatase (I ncrease d)
 
A L T
I ncrease
A L T (I ncrease d)
 
A m ylase
I ncrease
A m ylase (I ncrease d)
 
A S T
I ncrease
A S T (I ncrease d)
 
Bicar b o nate
Decrease
Bicar b o nate ( Decrease d)
 
C orrecte d Calci u m
I ncrease
C orrecte d Calci u m ( H y percalce mia)
 
C orrecte d Calci u m
Decrease
C orrecte d Calci u m ( H y p ocalce mia)
 
Creati ne Ki nase ( C K)
I ncrease
Creati ne Ki nase (I ncrease d)
 
Creati ni ne
I ncrease
Creati ni ne (I ncrease d)
 
Li pase
I ncrease
Li pase (I ncrease d)
 
Ma g nesi u m
Decrease
Ma g nesi u m ( H y p o ma g nese mia)
 
P h os p hate
Decrease
P h os p hate ( H y p o p h os p hate mia)
 
Ser u m Gl uc ose ( Fasti n g) 
I ncrease
Ser u m Gl uc ose ( Fasti n g, H y per gl yce mia)
 
Ser u m Gl uc ose ( Fasti n g) 
Decrease
Ser u m Gl uc ose ( Fasti n g, H y p o gl yce mia)
 
Ser u m Gl uc ose ( N o nfasti n g) 
I ncrease
Ser u m Gl uc ose ( N o nfasti n g, H y per gl yce mia)
 
Ser u m Gl uc ose ( N o nfasti n g) 
Decrease
Ser u m Gl uc ose ( N o nfasti n g, H y p o gl yce mia)
 
Ser u m P otassi u m
I ncrease
Ser u m P otassi u m ( H y per kale mia)
 
Ser u m P otassi u m
Decrease
Ser u m P otassi u m ( H y p o kale mia)
 
Ser u m S o di u m
I ncrease
Ser u m S o di u m ( H y per natre mia)
 
Ser u m S o di u m
Decrease
Ser u m S o di u m ( H y p o natre mia)
 
T otal Bilir u bi n
I ncrease
T otal Bilir u bi n ( H y per bilir u bi ne mia)
 
T otal C h olester ol ( Fasti n g) 
I ncrease 
T otal C h olester ol ( Fasti n g, H y perc h olester ole mia)
 
Tri gl yceri des ( Fasti n g) 
I ncrease
Tri gl yceri des ( Fasti n g, I ncrease d)
 
L D L ( Fasti n g)
I ncrease
L D L ( Fasti n g, I ncrease d)
 
Urea Nitr o ge n ( B U N)
I ncrease
Urea Nitr o ge n (I ncrease d)
 
Uric Aci d
I ncrease
Uric Aci d ( H y per urice mia)
 
Uric Aci d
Decrease
Uric Aci d ( H y p o urice mia)
Uri nal ysis
Uri ne Gl uc ose
I ncrease
Uri ne Gl uc ose ( Gl yc os uria)
 
Uri ne Pr otei n
I ncrease
Uri ne Pr otei n ( Pr otei n uria)
 
Uri ne R B C
I ncrease
Uri ne R B C ( He mat uria, Q ua ntitati ve)


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 6 3 of 6 4
1 3) F or fi g ures, if at a visit w here n (sa m ple size) ≤ 5, data will n ot be dis pla ye d at t he visit i n 
fi g ure (e xce pt t he Ka pla n- Meier fi g ure), b ut all data will be i ncl u de d i n t he c orres p o n di n g 
ta ble s u m mar y.
1 4) L D L: C o n versi o ns bet wee n sec o n d a n d t hir d ge nerati o ns
L D L was a nal yze d b y 2 differe nt assa ys i n t he st u d y: sec o n d ge nerati o n (i ncl u di n g 
R C T 2 3 9 4, R C T 2 3 1 2, a n d R C T 2 8 1 1) a n d t hir d ge nerati o n ( R C T 3 8 7 0). Sa m ples c ollecte d at 
earlier visits were a nal yze d usi n g L D L sec o n d ge nerati o n assa y. Sa m ples c ollecte d at later 
visits were a nal yze d usi n g L D L t hir d ge nerati o n assa y. T he c o n versi o n f or m ulas are as 
f oll o w:
a)
sec o n d ge nerati o n ( m m ol/ L) = (t hir d ge nerati o n − 0. 0 6 2 6)/ 0. 8 8 2
b) t hir d ge nerati o n ( m m ol/ L) = ( 0. 8 8 2 x sec o n d ge nerati o n) + 0. 0 6 2 6
F or t his a nal ysis, si nce L D L sa m ples were a nal yze d b y sec o n d ge nerati o n assa y at Baseli ne, 
o nl y c o n versi o n fr o m t hir d ge nerati o n t o sec o n d ge nerati o n was re q ueste d.
F or t he a nal ysis of c ha n ge fr o m baseli ne i n fasti n g direct L D L: t he sa m ple a nal yze d b y L D L 
t hir d ge nerati o n assa y will be c o n verte d t o sec o n d ge nerati o n as a ne w rec or d wit h test c o des 
of LI P. L D L. 0 0. 0 2 i n ra w data. D uri n g A Da M sta ge, a deri ve d para meter c o de ( F L D L 2) f or 
“ Fasti n g L D L C h olester ol 2 N D G E N C o m bi ne d” will be ge nerate d t o p o ol t he rec or ds fr o m 
b ot h ori gi nal (i ncl u di n g test c o des R C T 2 3 9 4, R C T 2 3 1 2, a n d R C T 2 8 1 1) a n d c o n verte d 
( LI P. L D L. 0 0. 0 2) sec o n d ge nerati o n res ults t o calc ulate t he c ha n ge fr o m baseli ne i n fasti n g 
direct L D L.
F or t he a nal ysis of t o xicit y gra de f or fasti n g direct L D L: t o xicit y gra de will be base d o n t he 
Gilea d gra di n g res ults (ie, t o x gr g) fr o m ori gi nal val ues bef ore c o n versi o n. I n ot her w or ds, 
d uri n g A Da M sta ge, a deri ve d para meter c o de ( F L D L T O X) f or “ Fasti n g L D L C h olester ol 
f or T o xicit y” will be ge nerate d t o p o ol t he rec or ds fr o m sec o n d ge nerati o n (i ncl u di n g 
R C T 2 3 9 4, R C T 2 3 1 2, a n d R C T 2 8 1 1) a n d t hir d ge nerati o n (ie, R C T 3 8 7 0) t o deri ve 
treat me nt-e mer ge nt t o xicit y gra des, ma xi m u m p ost baseli ne t o xicit y gra des, etc.
1 5) Pre vi o usl y, f or t he la b test of “ U R. N- T E L O/ C R E A T R A TI O”, it ca me fr o m L B T E S T C D = 
I M T 1 6 1 9, w hic h ha d t he u nit val ue of “ n m ol B C E/ m m ol Creat”. D ue t o a La b C or p assa y 
u p date, a ne w test I D has bee n use d wit h a L B T E S T C D = I M T 3 0 1 9, w hic h has a ne w u nit 
val ue of “' n m ol B C E/ m m ol C”. T he discre pa nc y of u nit u n der t he sa me test na me will ca use 
a n P 2 1 Err or “( S D 0 0 0 7 – I nc o nsiste nt val ue f or Sta n dar d U nits)”. La b C or p was n ot a ble t o 
u p date t he u nit na me t o matc h t he pre vi o us u nit na me, b ut c o nfir me d b ot h tests meas ure d t he 
sa me para meter a n d res ults were i nterc ha n gea ble. T h us, t he u nit was u p date d i n S D T M le vel, 
f or C O V L A B. L B T E S T C D = I M T 3 0 1 9 t he u nit was u p date d as “ n m ol B C E/ m m ol Creat” t o 
matc h t he pre vi o us u nit val ue.


E mtricita bi ne/ Te n of o vir Alafe na mi de ( F/ T A F; Desc o v y ® )
G S- U S- 3 1 1- 1 2 6 9
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
1 9 Fe br uar y 2 0 2 5 
GI L E A D C O N FI D E N TI A L I N F O R M A TI O N
Pa ge 6 4 of 6 4
1 6) I n C O V L A B ra w data, L B T E S T C D t hat are L A T 1 9 3 9 a n d E R T 7 8 6 are b ot h i m m u n oassa y 
perf or me d o n Ser u m, testi n g t he sa me para meter “car b o x yter mi nal tel o pe pti de t y pe 1 
c olla ge n”, t he test na me was gi ve n differe ntl y de pe n di n g o n t he re gi o n t hat is usi n g t he test 
(ie, A mericas vers us E ur o pe). L A T 1 9 3 9 was u p date d t o E R T 7 8 6 i n Oct o ber 2 0 1 8 as 
L A T 1 9 3 9 test was disc o nti n ue d i n La b C or p ( E R T 7 8 6 is perf or me d b y a n e xter nal 
la b orat or y).
1 7) I n C O V L A B, t he alert fla g ( A L R T F L) f or la b test “ Beta 2 Micr o gl o b uli n” ( L B T E S T C D = 
S C T 3 0 9 4) is a ge de pe n de nt. Partici pa nts fr o m 0 Y t o < 1 8 Y has n o refere nce ra n ge, a n d 
partici pa nts fr o m > = 1 8 Y t o < 1 5 0 Y wit h res ults > 0. 3 m g/ L is fla g ge d as “ H”.
1 8) T he f oll o wi n g c ol u m ns hea ders will be use d f or ta bles:
a)
C o h ort 1 ( 1 2 t o < 1 8 years a n d ≥ 3 5 k g)
b)
C o h ort 2 Gr o u p 1 ( 6 t o < 1 2 years a n d ≥ 2 5 k g)
c)
C o h ort 2 Gr o u p 2 ( 2 t o < 1 2 years a n d 1 7 t o < 2 5 k g)
d)
T otal
1 9) F or rescree ne d partici pa nts, t he later rec or ds will be use d.
2 0) F or D X A a nal ysis, 
a)
Varia ble C O R C C B M D w he n Re gi o n = “ S pi ne T otal A de q uate” f or s pi ne a n d 
Re gi o n = “ B o d y T otal N o Hea d” f or T B L H B M D a nal ysis.
b)
Varia ble C O R C C Z C R w he n Re gi o n = “ S pi ne T otal A de q uate” f or s pi ne a n d 
Re gi o n = “ B o d y T otal N o Hea d” f or T B L H sta n dar d Z-sc ore a nal ysis.
c)
Varia ble C O R C C H A Z w he n Re gi o n = “ S pi ne T otal A de q uate” f or s pi ne a n d 
Re gi o n = “ B o d y T otal N o Hea d” f or T B L H hei g ht-a ge Z-sc ore a nal ysis.
F or c), c orrecte d cr oss cali brate d hei g ht-a ge Z-sc ore will o nl y be a vaila ble w he n refere nce is 
a vaila ble f or e xtra p olati o n.
2 1) F or H B V s urface a nti ge n/a nti b o d y, a n d H C V a nti b o d y, o nl y dis pla y missi n g cate g or y w he n 
a p plica ble i n t he data.
2 2) F or P B M C re p orti n g, fr o m s o urce P K data t here were t w o differe nt t y pes of c o nce ntrati o ns: 
V O L C O N C a n d C O N C C. F or re p orti n g, o nl y re p ort t he i ntracell ular c o nce ntrati o n, w hic h is 
C O N C C (i n n g/ milli o n cells). I ntracell ular c o nce ntrati o n s h o ul d be re p orte d i n b ot h 
n g/ milli o n cells a n d f m ol/ milli o n cells. T he c o n versi o n bet wee n t he t w o is: f m ol/ milli o n cells 
= n g/ milli o n cells × 1 0 0 0 0 0 0/ 4 4 7. 1 7.


G S- U S- 3 1 1- 1 2 6 9- Fi n al- A n al y si s- S A P- v 1. 0
E L E C T R O NI C SI G N A T U R E S
Si g n e d b y
M e a ni n g of Si g n at ur e 
S er v er D at e
( d d- M M M-
y y y y h h: m m: s s)
Bi o st ati sti c s e Si g n e d 
1 9- F e b- 2 0 2 5
2 3: 0 1: 0 1
Cli ni c al P h ar m a c ol o g y
e Si g n e d
2 1- F e b- 2 0 2 5
0 5: 1 5: 2 1
Gl o b al D e v el o p m e nt
L e a d ( G D L) e Si g n e d
2 2- F e b- 2 0 2 5
0 0: 1 3: 2 3
P P D
P P D
P P D

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2/3, Open-Label, Multi-Cohort Switch Study to 
Evaluate Emtricitabine/Tenofovir Alafenamide (F/TAF) in 
HIV-1 Infected Children and Adolescents Virologically 
Suppressed on a 2-NRTI-Containing Regimen
Name of Test Drug:
Emtricitabine/Tenofovir Alafenamide (F/TAF)
Study Number:
GS-US-311-1269
Protocol Version (Date):
Amendment 2: 02 Aug 2017
Analysis Type:
For CT.gov Posting
Analysis Plan Version:
1.0
Analysis Plan Date:
06 October 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(rJ GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF ABBREVIATIONS........................................................................................................................................4
1.
INTRODUCTION ................................................................................................................................................7
1.1.
Study Objectives ......................................................................................................................................7
1.2.
Study Design............................................................................................................................................7
1.3.
Sample Size and Power..........................................................................................................................11
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................12
2.1.
Cohort 1 Interim Analysis......................................................................................................................12
2.2.
Cohort 2 Interim Analysis......................................................................................................................12
2.3.
Analysis for CT.gov...............................................................................................................................12
2.4.
Final Analysis ........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................13
3.1.
Analysis Sets..........................................................................................................................................13
3.1.1.
All Enrolled Analysis Set.....................................................................................................13
3.1.2.
Full Analysis Set ..................................................................................................................13
3.1.3.
Safety Analysis Set...............................................................................................................14
3.1.4.
DXA Analysis Set ................................................................................................................14
3.1.4.1.
Spine DXA Analysis Set.................................................................................14
3.1.4.2.
Total Body Less Head DXA Analysis Set......................................................14
3.1.5.
PK Analysis Sets ..................................................................................................................14
3.2.
Subject Grouping ...................................................................................................................................14
3.3.
Strata and Covariates..............................................................................................................................14
3.4.
Examination of Subject Subgroups........................................................................................................14
3.5.
Multiple Comparisons............................................................................................................................14
3.6.
Missing Data and Outliers......................................................................................................................15
3.6.1.
Missing Data ........................................................................................................................15
3.6.2.
Outliers.................................................................................................................................15
3.7.
Data Handling Conventions and Transformations .................................................................................15
3.8.
Analysis Visit Windows.........................................................................................................................16
3.8.1.
Definition of Study Day .......................................................................................................16
3.8.2.
Analysis Visit Windows.......................................................................................................17
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window................................................................................................................................18
4.
SUBJECT DISPOSITION ..................................................................................................................................20
4.1.
Subject Enrollment and Disposition.......................................................................................................20
4.1.1.
Subject Enrollment...............................................................................................................20
4.1.2.
Subject Disposition ..............................................................................................................20
4.2.
Extent of Study Drug Exposure .............................................................................................................21
5.
BASELINE CHARACTERISTICS....................................................................................................................22
5.1.
Demographics and Baseline Characteristics ..........................................................................................22
5.2.
Baseline Disease Characteristics............................................................................................................22
6.
EFFICACY ANALYSES ...................................................................................................................................23
6.1.
Definition of the Efficacy Endpoints......................................................................................................23
6.1.1.
Efficacy Endpoints ...............................................................................................................23
6.1.2.
US FDA-Defined Snapshot Algorithm ................................................................................23


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6.1.3.
Analysis Methods for Efficacy Endpoints............................................................................24
7.
SAFETY ANALYSES........................................................................................................................................25
7.1.
Adverse Events and Deaths....................................................................................................................25
7.1.1.
Adverse Event Dictionary ....................................................................................................25
7.1.2.
Adverse Event Severity........................................................................................................25
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................25
7.1.4.
Serious Adverse Events........................................................................................................25
7.1.5.
Treatment-Emergent Adverse Events...................................................................................25
7.1.5.1.
Definition of Treatment-Emergent Adverse Events .......................................25
7.1.5.2.
Incomplete Dates ............................................................................................26
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................26
7.2.
Renal Safety Analysis ............................................................................................................................27
7.3.
Bone Safety Analyses ............................................................................................................................27
7.4.
Palatability/Acceptability Assessment ...................................................................................................27
8.
PHARMACOKINETICS ANALYSIS ...............................................................................................................28
8.1.
PK Endpoints .........................................................................................................................................28
8.2.
Estimation of Pharmacokinetic Parameters............................................................................................28
8.3.
Analysis for PK Parameters ...................................................................................................................28
8.3.1.
Statistical Comparative Analysis..........................................................................................29
9.
REFERENCES ...................................................................................................................................................31
10.
SOFTWARE.......................................................................................................................................................32
11.
SAP REVISION..................................................................................................................................................33
12.
APPENDICES ....................................................................................................................................................34
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Windows for HIV-1 RNA, CD4 cell count, CD4 %, Hematology, 
Chemistry, and Urinalysis Laboratory Tests, eGFRSchwartz, Vital Signs, Height, 
and Weight .............................................................................................................................17
Table 3-2.
Analysis Windows for BMD Assessments.............................................................................18


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LIST OF ABBREVIATIONS
ABC/3TC
abacavir (ABC)/lamivudine (3TC)
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ARV 
antiretroviral 
AST
aspartate aminotransferase
ATV
atazanavir
ATV/r
ritonavir boosted atazanavir
AUC
area under curve for concentration over time
BIC
bictegravir
B/F/TAF
fixed dose combination of bictegravir (BIC; B) 50 mg / emtricitabine (FTC; F) 200 
mg / tenofovir alafenamide (TAF) 25 mg
BLQ
below limit of quantitation
BMD
bone mineral density
BMI
body mass index
BSA
body surface area
CDC
Centers for Disease Control
CDER
Center for Drug Evaluation and Research
CL/F
the apparent oral clearance after administration of the drug: 
CL/F Dose/AUCinf
where “Dose” is the dose of the drug
CL
volume of plasma cleared of drug per unit time
CI
confidence interval 
CPK
creatine phosphokinase
CRF
case report form
CSR
clinical study report
CV
coefficient of variation
DC
study drug discontinuation
DRV
darunavir
DXA
dual-energy X-ray absorptiometry
DSPH
Drug Safety and Public Health
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eGFRSchwartz
estimated glomerular filtration rate calculated using the Schwartz formula
FAS
full analysis set
FDA
Food and Drug Administration
FDC
fixed-dose combination
FTC, F
emtricitabine
GFR
glomerular filtration rate


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Gilead
Gilead Sciences, Inc.
GS-9883
bictegravir
h
hour
HBV
hepatitis B Virus
HCV
hepatitis C Virus
HIV-1
human immunodeficiency virus (Type 1) 
HDL
high-density lipoprotein
HLGT
high-level group term
HLT
high-level term
IDMC
independent data monitoring committee
IPK
intensive pharmacokinetics
kg
kilogram
LDL
low-density lipoprotein
LLOQ
lower limit of quantitation
LLT
lowest level term
LPV
lopinavir
MedDRA
Medical Dictionary for Regulatory Activities
NDA
New Drug Application
ng
nanogram
NRTI
nucleoside reverse transcriptase inhibitor
PBMC
peripheral blood mononuclear cell
PI
protease inhibitor
PT
preferred term
PK
pharmacokinetics
Q
quartile
Q1
first quartile
Q3
third quartile
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SCr
serum creatinine
SD
standard deviation
SE
standard error
SMQ
standardized MedDRA query
SOC
system organ class
SQRT
square root, √
TAF
tenofovir alafenamide 
TEAE
treatment-emergent adverse events
TFL
tables, figures, and listings
TFV
tenofovir


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ULN
upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-311-1269. This SAP is based on the study protocol amendment 2 dated 
02 August 2017 and the electronic case report form (eCRF). The SAP will be finalized before 
database finalization. Any changes made after the finalization of the SAP will be documented in 
the CSR.
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate the pharmacokinetics (PK) of tenofovir alafenamide (TAF) and confirm the TAF 
dose in HIV-1 infected children and adolescents virologically suppressed on a 
2 NRTI-containing regimen.

To evaluate the safety and tolerability of F/TAF through Week 24.
The secondary objectives of this study are as follows:

To evaluate the PK of tenofovir (TFV) and emtricitabine (FTC).

To evaluate the safety, tolerability, and efficacy of F/TAF through Week 48.
1.2.
Study Design
This is an open-label, multi-cohort switch study to evaluate the PK, safety, and efficacy of 
F/TAF in HIV-1 infected children (1 month to < 12 years) and adolescents (12 to <18 years) who 
are virologically suppressed (HIV-1 RNA < 50 copies/mL for at least 6 consecutive months) on a 
stable 2-NRTI-containing regimen.
A minimum of 100 subjects aged 1 month to < 18 years of either sex will be enrolled as follows:
Cohort 1 (adolescents 12 to < 18 years, ≥ 35 kg): All subjects in Cohort 1 (n  25) will switch 
their current 2-NRTI-containing regimen to F/TAF while continuing their 3rd antiretroviral 
(ARV) agent through 48 weeks. An intensive PK (IPK) evaluation will be conducted at the 
Week 2 visit. TAF dose confirmation will be established if the exposure is comparable to that 
associated with efficacy in adults. All subjects in Cohort 1 will continue to receive F/TAF plus 
their 3rd ARV agent and return for study visits through Week 48.
Cohorts 2, 3, and 4: Cohorts 2, 3, and 4 will be enrolled by cohort into two parts (Parts A and 
B). Cohort 2 consists of 2 groups: Group 1 weighing ≥ 25 kg and Group 2 weighing 17 kg to 
< 25 kg.


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All subjects in Cohort 2 Group 1 must be on a boosted protease inhibitor (PI) as their 3rd ARV 
agent and will switch their current 2-NRTI-containing regimen to open-label F/TAF while 
continuing their boosted PI through 48 weeks.
All subjects in Cohort 2, Group 2 and Cohorts 3 and 4 will be on a boosted PI or other 
protocol-specified 3rd agents and will switch their current 2-NRTI-containing regimen to 
open-label F/TAF while continuing their 3rd agents through 48 weeks.
A minimum of 10 subjects who are on boosted- atazanavir (ATV) as their 3rd ARV agent will be 
enrolled into Part A of each group of Cohort 2, as well as Cohorts 3 and 4.
Cohorts 2, 3, and 4 will be enrolled as follows:
Cohort
Age Range
Weight
Range
Number of Subjects
ATV +
F/TAF
LPV or
DRV
+ F/TAF
Other 3rd
ARV Agents
+ F/TAF
2, Group 1
6 to < 12 years
≥ 25 kg
n ≥ 10
n ≥ 6
n/a
2, Group 2
(subjects able to 
swallow a
tablet)
2 to < 12 years
17 kg to
< 25 kg
n ≥ 10
n ≥ 7
3b (subjects
unable to
swallow a
tablet)
2 to < 6 years
TBD
n ≥ 10
n ≥ 7
4a,b
1 month to
< 2 years
TBD
n ≥ 10
n ≥ 7
a
DRV is not approved for Cohort 4
b
Formulation, dosing, and population specific details for Cohorts 3 and 4 will be added via a protocol amendment after data 
is obtained from Cohort 2.
All subjects in Part A will undergo an IPK evaluation at either the Week 2 or Week 4 visit 
(+7 days) to confirm the dose of TAF.
Part B
Screening will be initiated for Part B following confirmation of TAF dose in Part A for each 
group of Cohort 2 and Cohorts 3 and 4. Approximately 10 additional total subjects will be 
enrolled in Part B and will receive F/TAF while continuing their 3rd ARV agent through 
48 weeks.


F!TAF 
GS-US-311- 1269 
Statistical Analysis Plan (For CT.gov Posting) 
Study Procedure/Frequency: 
Version 1.0 
At the Screening, Baseline/Day 1, and all subsequent study visits, laboratory analyses 
(hematology, chemistry, and urinalysis), HIV-1 RNA, CD4+ cell com1t, complete or symptom 
directed physical examinations, and estimated glomerular filtration rate ( eGFR) using the 
Schwartz fonnula will be perfonned. Serum (screening) or urine (all other visits) pregnancy tests 
will be perfonned on female subjects of childbearing potential. 
Adverse events and concomitant medications will be assessed at each visit. 
Serum will be collected for bone safety tests (collected fasted): 
• 
Cohort 1 only: Baseline/Day 1, Weeks 4, 12, 24, and 48 
• 
Cohorts 2, 3, and 4: Baseline/Day 1, Weeks 8, 12, 24, 48, 
For all Cohorts, urine will be collected for urine chemistry and selected renal safety tests, 
includin retinol bindin 
rotein and beta-2-microglobulin, at Baseline/Day 1, Weeks 2, 4, 8, 12, 
24, 48, 
For Cohorts 1 and 2 (all groups), metabolic assessments will be collected for fasting glucose and 
lipid anel total cholesterol HDL direct LDL, and triglycerides) at Baseline/Day 1, Weeks 24, 
48, 
The fasting requirement for Cohorts 3 and 4 will 
be spec1 1e 
Ta1mer stage assessment will be erfonned for sub ·ects 2: 6 ears of age at the time of the visit at 
Baseline/Day 1, Weeks 24, 48, 
, or until subjects reach Ta1mer 
Stage 5, after which point Tanner assessments will no longer be perfonned. 
For all Cohorts, dual energy x-ray absorptiometry (DXA) scans of the lumbars 
body will be perfonned at Baseline/Day 1, Weeks 24, 48, 
measure spine bone mineral density (BMD) and total body BMD. 
PK sampling: 
Single PK samples will be collected at the following visits for all cohorts: 
• 
Weeks 1 and 24: a single random PK sample. 
to 
• 
Weeks 4 and 12: a single observed dosing PK sample at any time between 15 min to 4 hours 
post dose. (Note: Single observed dosing PK sample does not need to be collected at Week 4 
if IPK is also collected at the Week 4 visit). 
• 
Week 8: a trough sample at O hours (pre-dose, :S 30 minutes prior to dosing) at Week 8. 
CONFIDENTIAL 
Page 9 
06 October 2020 


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CONFIDENTIAL
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Intensive PK sampling:

Cohort 1 will participate in an IPK evaluation at the Week 2 visit as detailed in the PK 
manual.

Cohort 2 Part A will participate in an IPK evaluation during either the Week 2 or Week 4 
visit or within 7 days after the completion of Week 2 or Week 4 visit as detailed in the PK
manual. The IPK collection schedule and fasting requirement for Cohorts 3 and 4 will be 
specified in a future protocol amendment.
Peripheral Blood Mononuclear Cell (PBMC) collection:

PBMC collection will be performed at study sites that canperform PBMC processing.

Cohorts 1 and 2: PBMC collection will be performed at the Week 8 visit.

Cohort 3, and 4: PBMC collection schedule will be specified in a future protocol amendment.
Palatability and Acceptability Assessment:

Cohort 1: At the Week 2 visit, palatability and acceptability will be assessed 30 - 60 minutes 
after study drug dosing for all subjects undergoing IPK sampling. Acceptability will also be 
assessed 30 - 60 minutes after study drug dosing for active subjects at the next study visit 
immediately following approval of this protocol at the site.

Cohort 2 Part A: Palatability and acceptability will be assessed at the Week 2 or Week 4 
visit, or within 7 days after the completion of the Week 2 or Week 4 visit, 30 - 60 minutes 
after study drug dosing for all subjects undergoing IPK sampling.

Cohorts 3 and 4 Part A: Palatability and acceptability will be assessed for subjects 
undergoing IPK sampling. Assessment schedule will be specified in a future protocol 
amendment.
Subjects who prematurely discontinue from the study 
 
will be required to return to the clinic for a 30-Day Follow-up Visit.
The additional details of Schedule of Assessments can be found in Appendix 1.
Test Product, Dose, and Mode of Administration:
F/TAF tablets administered orally once daily (QD) in combination with a 3rd ARV agent, with or 
without food (as determined by the 3rd ARV agent), dosed as follows:
CCI


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Cohort
Age Range
Weight
Range
F/TAF dose (mg) with 3rd agent
1
12 to <18 years
≥ 35 kg
200/25 for unboosted 3rd agent
200/10 for boosted 3rd agent
2, Group 1
6 to < 12 years
≥ 25 kg
200/25
2, Group 2 (subjects able
to swallow a tablet)
2 to < 12 years
17 kg to
< 25 kg
120/15
3 (subjects unable to swallow a
tablet)
2 to < 6 years
TBD
TBD
4
1 month to
< 2 years
TBD
TBD
1.3.
Sample Size and Power
Cohort 1: Twenty-five subjects from Cohort 1 in the TAF treatment arm will provide at least
90% power to target a 95% confidence interval within 60% and 140% of the geometric mean
estimate of apparent volume of plasma cleared of drug per unit time (CL) and apparent Vz of 
TAF, respectively, assuming a standard deviation of 0.60 for CL and 0.58 for Vz (natural log 
scale) estimated from Study GS-US-292-0106 Cohort 1 Part A.
Cohort 2 (Group 1) Part A: At least 10 subjects on boosted ATV + F/TAF and 6 subjects on 
boosted lopinavir (LPV) or darunavir (DRV) + F/TAF, compared with the population PK data 
from 44 adult subjects on boosted ATV + F/TAF and 87 adult subjects on boosted LPV or DRV 
+ F/TAF in Study GS-US-311-1089, respectively, will each provide at least 80% power to show 
the lower bound of a 90% CI of geometric mean ratio (pediatric subjects vs. adult subjects) 
greater than 70% for AUCtau of TAF, assuming that the expected geometric mean ratios of TAF 
AUCtau between pediatric subjects and adult subjects are equal to 1 and the standard deviations 
are 0.40 (with boosted ATV + F/TAF) and 0.33 (with boosted LPV or DRV + F/TAF) ng*hr/mL 
for TAF AUCtau (natural log scale) estimated from the population PK data in Study 
GS-US-311-1089.
Part A of Cohorts 2 (Group 2), 3, and 4: At least 10 subjects on boosted ATV + F/TAF and 
7 subjects on any other third agent + F/TAF in each group or cohort, compared with the 
population PK data from the 292 adults on any third agent + DVY in Study GS-US-311-1089, 
will provide 90% power to show the lower bound of a 90% confidence interval (CI) of geometric 
mean ratio (pediatric subjects vs. adult subjects) greater than 70% for AUCtau of TAF, assuming 
that the expected geometric mean ratio of TAF AUCtau between pediatric subjects and adult 
subjects is equal to 1 and the standard deviation is 0.48 ng*hr/mL for TAF AUCtau (natural log 
scale) estimated from the population PK data in Study GS-US-311-1089. A total of at least 
100 subjects receiving F/TAF from Cohort 1, and Parts A and B of Cohort 2 (Groups 1 and 2), 
Cohort 3, and Cohort 4 combined will provide reasonable assessment of safety through Week 48 
in pediatric subjects.
Sample size and power calculations were made using the statistical software package nQuery 
Advisor (Version 7.0) and R.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Cohort 1 Interim Analysis
A Cohort 1 Week 48 analysis was planned to be conducted after all subjects in Cohort 1 either 
complete their Week 48 visit or prematurely discontinue from the study drug. This analysis was 
not done as this study was not needed to support the new drug application (NDA) for F/TAF for 
pediatrics.
2.2.
Cohort 2 Interim Analysis
A Cohort 2 Week 24 analysis was planned to be conducted after all subjects in Cohort 2 either 
complete their Week 24 visit or prematurely discontinue from the study drug. This analysis was 
not done as this study was not needed to support the NDA for F/TAF for pediatrics.
2.3.
Analysis for CT.gov
The Food and Drug Administration (FDA) Amendment Act of 2007 requires that the results for 
the primary endpoint be posted on ClinicalTrials.gov within one year of the last patient last visit 
of the primary endpoint.
This statistical analysis plan describes the analysis planned to be posted on CT.gov. Only the 
primary and secondary endpoints are included in this analysis.
2.4.
Final Analysis
Final Analysis will be conducted after all subjects (Cohorts 1 and 2) either complete the study or 
prematurely discontinue from the study. The Cohorts 3 and 4 were not enrolled.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, 
first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all subjects in the All Enrolled analysis set unless 
otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). Data 
collected on log forms, such as AEs, will be presented in chronological order within a subject.
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. For enrolled but never dosed subjects, age on the date of enrollment will 
be used. For screen failures, age on the date the informed consent was signed will be used. If 
only birth year is collected on the eCRF, “01 January” will be used for the unknown birth day 
and month for the purpose of age calculation, similarly, if only birth year and month are 
collected on the eCRF, “01” will be used for the unknown birth day for the purpose of age 
calculation.
In general, permanent discontinuation of study drug refers to premature discontinuation of study 
drug or completion of study drug.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. Subjects included in each analysis set will be determined before data 
finalization. The analysis set will be included as a subtitle of each table, figure, and listing. A 
summary of the number and percentage of subjects in each analysis set will be provided.
3.1.1.
All Enrolled Analysis Set
The All Enrolled Analysis Set will include all subjects who are enrolled into the study. This is 
the primary analysis set for by-subject listings.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) will include all subjects who (1) are enrolled into the study and 
(2) have received at least 1 dose of study drug. For the FAS, all efficacy data, including data 
collected after the last dose of study drug, will be included, unless specified otherwise. This is 
the primary analysis set for efficacy analyses.


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3.1.3.
Safety Analysis Set
The Safety Analysis Set will include all subjects who (1) are enrolled into the study and (2) have 
received at least 1 dose of study drug. All the data collected up to 30 days after permanent 
discontinuation of the study drug will be included in the safety summaries, unless specified 
otherwise. This is the primary analysis set for safety analyses.
3.1.4.
DXA Analysis Set
3.1.4.1.
Spine DXA Analysis Set
The spine DXA analysis set will include all subjects who are enrolled and have received at least 
1 dose of study drug, and have non-missing spine BMD value at baseline visit.
3.1.4.2.
Total Body Less Head DXA Analysis Set
The total body less head DXA analysis set will include all subjects who are enrolled and have 
received at least 1 dose of study drug, and have non-missing total body less head BMD value at 
baseline visit.
3.1.5.
PK Analysis Sets
The PK analysis set for each analyte of interest will include all subjects who (1) are enrolled into 
Cohort 1 or Cohort 2 for PK evaluation, (2) have received at least one dose of study medication 
and (3) have at least 1 non-missing IPK concentration data for that analyte (eg, TAF, TFV, and 
FTC).
3.2.
Subject Grouping
For Cohort 1, subjects will be grouped into 1 treatment group (ie, F/TAF) for efficacy and safety 
analyses. For Cohort 2, subjects will be grouped into 2 groups: Group 1: Age 6 to < 12 years and 
weight ≥25 kg and Group 2: Age 2 to < 12 years and weight 17 to < 25 kg.
3.3.
Strata and Covariates
Not applicable.
3.4.
Examination of Subject Subgroups
Not applicable.
3.5.
Multiple Comparisons
Not applicable.


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


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Natural logarithm transformation will be used for analyzing concentrations and PK parameters. 
Concentration and PK parameter values that are below the limit of quantitation (BLQ) will be 
presented as “BLQ” in the data listing. Values that are BLQ will be treated as 0 at predose time 
points, and one-half the value of the LOQ at postdose time points for summary purposes.
The following conventions will be used for the presentation of summary and order statistics for 
PK concentrations:

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the participants have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the participants have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the participants have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all participants have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study Day 1 is defined as the day when the first dose of study drug F/TAF was taken, as 
recorded on the Study Drug Administration eCRF form.
Study Days are calculated relative to Study Day 1. For events that occurred on or after the Study 
Day 1 date, study days are calculated as (visit date minus Study Day 1 plus 1). For events that 
occurred prior to Study Day 1, study days are calculated as (visit date minus Study Day 1).
Last Dose Date is the earliest of the last dosing dates of F/TAF and the third agent in a subject’s 
study regimen.
For F/TAF, the last dosing date is the latest nonmissing end date recorded on the Study Drug 
Administration eCRF form with “Study Drug Permanently Withdrawn” box checked for subjects 
who prematurely discontinued study drug or who completed study drug according to Study Drug 
Completion eCRF. If the date of last dose is missing (eg, due to lost to follow-up) for subjects 
who prematurely discontinued study drug or who are still on study drug, the latest of nonmissing 
study drug start dates and end dates, the clinic visit dates, and the laboratory visit dates excluding 
the date of 30-day follow-up visit will be used to impute the last dosing date.


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The third agent in a subject’s existing treatment regimen is the ARV medications 
(excluding ABC and 3TC) that a subject was taking immediately prior to the first dose date 
(ie, ARV start date < the first dose date of study drug and ARV end date ≥ the first dose date of 
study drug  1). The last dosing date of the third agent is recorded on the ARV eCRF form. If the 
third agent is ongoing, then the last dose date of the study regimen will be the last dosing date of 
F/TAF.
For an ARV which is marked as current but not ongoing on the ARV eCRF form, if the ARV 
end date is missing (eg, due to lost to follow-up), the latest of nonmissing study drug start dates 
and end dates, the clinic visit dates, and the laboratory visit dates excluding the date of 30-day 
follow-up visit will be used to impute the end date of this ARV.
Baseline value is defined as the last value obtained on or prior to Study Day 1 for all 
assessments, exept for the BMD data, which is the last value on or prior to Study Day 21.
3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
The analysis windows for HIV-1 RNA, CD4 cell count, CD4 %, hemotology, chemistry, and 
urinalysis laboratory test, eGFRSchwartz, vital signs, height, and weight are presented in Table 3-1.
Table 3-1.
Analysis Windows for HIV-1 RNA, CD4 cell count, CD4 %, 
Hematology, Chemistry, and Urinalysis Laboratory Tests, 
eGFRSchwartz, Vital Signs, Height, and Weight
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
Week 1
7
2
10
Week 2
14
11
21
Week 4
28
22
42
Week 8
56
43
70
Week 12
84
71
126
Week 24
168
127
210
Week 36
252
211
294
Week 48
336
295
378
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The analysis windows for DXA assessments are presented in Table 3-2.
Table 3-2.
Analysis Windows for BMD Assessments
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
21
Week 24
168
22
252
Week 48
336
253
420
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values are required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time to event analysis would not require one value per analysis window. When a single value is 
needed, the following rule(s) will be used.
If multiple nonmissing numeric observations exist in a window, then records will be chosen as 
follows:

For baseline, the latest available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, average will be used for the baseline value, except for HIV-1 RNA (see below).

For postbaseline visits:
For CD4 cell count and CD4% data, the record(s) collected on the latest day in the 
window will be selected for analysis.
For other numeric observations (ie, except HIV-1 RNA, CD4 cell count, and CD4%), the 
record(s) collected on the day closest to the nominal day for that visit will be selected. If 
there are 2 days equidistant from the nominal day, the later day will be selected.
For any numeric observations except HIV-1 RNA, if there are multiple records on the 
selected day, the average will be taken.

For baseline and postbaseline HIV-1 RNA, the latest (considering both date and time) 
record(s) in the window will be selected. If both “HIV RNA Taqman 2.0” and “HIV RNA 
Repeat” (ie, the HIV-1 RNA result obtained from an additional aliquot of the original 
sample) are available with the same collection time, the results from the “HIV RNA Repeat” 
will be selected for analysis purposes; otherwise, if there are multiple “HIV RNA Taqman 
2.0” records with the same collection time, the geometric mean will be taken for analysis 
purposes.
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If multiple valid nonmissing categorical observations exist in a window, records will be chosen 
as follows:

For baseline, the last available record on or prior to the first dose date of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected (eg, normal will be selected over 
abnormal).

For postbaseline visits, the most conservative value within the window will be selected (eg, 
abnormal will be selected over normal).


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
4.1.1.
Subject Enrollment
The number and percentage of subjects enrolled at each country and investigator will be 
summarized using the safety analysis set.
4.1.2.
Subject Disposition
The summary of subject disposition will be provided for all screened subjects. This summary 
will include the number of subjects screened, screen failure subjects who were not enrolled, 
subjects who met all eligibility criteria and were not enrolled, subjects enrolled, subjects enrolled 
but never treated, subjects in the safety analysis set, DXA Analysis set, IPK analysis set, and 
subjects in the FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:
For the 48-Week treatment phase (up to Week 48):

Completed study drug

Still on study drug

Prematurely discontinuing study drug prior to Week 48 (with summary of reasons for 
discontinuing study drug)

Completed Study

Still on Study

Prematurely discontinuing study prior to Week 48 (with summary of reasons for 
discontinuing study)
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The denominator for the percentages of subjects in each category will be the nmnber of subjects 
in the safety analysis set. 
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided. 
4.2. 
Extent of Study Drug Exposure 
Duration of exposure to study drug will be defined as (the last dose date 
the first dose 
date + 1 ), regardless of temporary interruptions in study drug administration, and will be 
expressed in weeks using up to 1 decimal place (eg, 4.5 weeks). For the calculation of the 
duration of exposure to study drug, the data cut date will be used to impute the last dose date for 
subjects who have not pennanently discontinued study drug at the time of the data cut date. 
Duration of exposure to study drug will be summarized using descriptive statistics (n, mean, SD, 
median, Q 1, Q3, minimum, and maximum) and as the number and percentage of subjects 
exposed for specified periods, eg, 
4 weeks (28 days),~ 8 weeks (56 days),~ 12 weeks 
(84 days),~ 24 weeks (168 days),~ 36 weeks (252 days), etc. 
Summaries will be provided for subjects in the safety analysis set. No inferential statistics will be 
provided. 
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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, race, and ethnicity) and baseline characteristics 
(eg, body weight, weight Z-score, height, height Z-score, body surface area [BSA], 
body mass index [BMI], and Tanner Stage) will be summarized using descriptive statistics for all
subjects in the safety analysis set. The percentage of subjects who reach Tanner Stage 4 or 5 will 
also be summarized. The sample size, mean, SD, median, Q1, Q3, minimum, and maximum will 
be provided for continuous data, and the number and percentage of subjects will be provided for 
categorical data. Age is calculated as age in years at first dose of study drug. The definition of 
baseline value is provided in Section 3.8.1.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized:

Third agent in a subject’s pre-existing treatment regimen

HIV-1 RNA categories (copies/mL): (a) < 50, (b) ≥50

CD4+ cell count (/µL)

CD4+ cell count categories (/µL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, (d) ≥350 to 
< 500, and (e) ≥500

CD4 percentage (%)

Mode of infection (HIV risk factor)

HIV disease status

eGFR calculated using the Schwartz Formula

Years diagnosed with HIV (to be calculated as time prior to first dose date)

HBV surface antigen

HCV antibody


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6.
EFFICACY ANALYSES
6.1.
Definition of the Efficacy Endpoints
6.1.1.
Efficacy Endpoints
The efficacy endpoints include:

The percentage of subjects with plasma HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as 
defined by the US FDA-defined snapshot algorithm

The change from baseline in CD4 cell counts and percentages at Weeks 24 and 48
The analyses for the efficacy endpoints will be conducted using the FAS
6.1.2.
US FDA-Defined Snapshot Algorithm
The analysis window at Week 24 is defined as from Study Day 127 to Study Day 210, inclusive. 
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378, inclusive. 
The All HIV-1 RNA data collected on-treatment (ie, data collected up to 1 day after the last dose 
date of study drug) will be used in the US FDA-defined snapshot algorithm. Virologic outcome 
at Week 24 will be defined as the following categories:
HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 24 analysis window
HIV-1 RNA ≥50 copies/mL: this includes subjects
1) Who have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 24 
analysis window, or
2) Who do not have on-treatment HIV-1 RNA data in the Week 24 analysis window and 
a) Who discontinue study drug prior to or in the Week 24 analysis window due to lack of 
efficacy, or
b) Who discontinue study drug prior to or in the Week 24 analysis window due to AE or 
death and have the last available on-treatment HIV-1 RNA ≥ 50 copies/mL or
c) Who discontinue study drug prior to or in the Week 24 analysis window due to reasons 
other than AE, death, or lack of efficacy and have the last available on-treatment HIV-1 
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No Virologic Data (in the Week 24 analysis window): this includes subjects who do not have 
on-treatment HIV-1 RNA data in the Week 24 analysis window because of the following:
1) Discontinuation of study drug prior to or in the Week 24 analysis window due to AE or death 
and the last available on-treatment HIV-1 RNA < 50 copies/mL or
2) Discontinuation of study drug prior to or in the Week 24 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA is 
< 50 copies/mL, or
3) Missing data during the window but on study drug
Virologic outcome at week 48 will be defined similarly by using the Week 48 anlaysis window.
6.1.3.
Analysis Methods for Efficacy Endpoints
For the virologic outcome at Weeks 24 and 48 as defined by the US FDA defined snapshot 
algorithm, respectively, the numbers and percentages of subjects with HIV 1 RNA 
< 50 copies/mL, HIV 1 RNA ≥ 50 copies/mL (including subcategories), and no virological data 
(including reasons) will be summarized. The 95% confidence interval for the percentage estimate 
will be constructed using the Exact method.
Baseline values and changes from baseline in CD4 cell count (cells/μL) and CD4% at each visit 
will be summarized descriptively (sample size, mean, SD, 95% CI, median, Q1, Q3, minimum, 
and maximum) using observed, on-treatment data (ie, data collected up to 1 day after permanent 
discontinuation of study drug or all available data for subjects who were still on study drug).


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7.
SAFETY ANALYSES
Safety data will be summarized for the subjects in the safety analysis set. All safety data 
collected up to 30 days after permanent discontinuation of study drug or all available data for 
subjects who were still on study drug will be summarized, unless specified otherwise.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the MedDRA Version 22.1. System organ class 
(SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and lowest-
level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe) or Grade 4 (life threatening) according to toxicity criteria specified in the protocol. The 
severity grade of events for which the investigator did not record severity will not be imputed 
and will be left as “missing” for data listings.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Global Patient Safety (GLPS)
Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of the study drug, or

Any AEs leading to premature discontinuation of study drug.


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The month and year (or year) of the AE onset is the same as or after the month and year 
(or year) of the first dosing date of study drug, and

The month and year (or year) of the AE onset is the same as or before the month and year 
(or year) of the date corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date on or after the first dosing date of study drug, will be considered to be treatment emergent. 
In addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
A brief, high-level summary of the number and percentage of subjects who experienced at least 
1 TEAE in the categories described below will be provided by treatment group. All deaths 
observed in the study will also be included in this summary.
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC and PT for the following categories:

TEAEs

TESAEs

TEAEs with grade 3 or higher

TE treatment-related AEs

TEAEs leading to premature discontunaton of study drug

Death
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC (and HLT within each SOC if applicable), 
and then by PT in descending order of total frequency within each SOC.
TEAEs and TESAEs will also be summarized up to Week 24. The AEs with onset date after the 
Week 24 nominal visit date will not be included in the analysis.
In addition, a data listing for all AEs, indicating whether the event is treatment emergent or not,
will be provided.


F!TAF 
GS-US-311- 1269 
Statistical Analysis Plan (For CT.gov Posting) 
7.2. 
Renal Safety Analysis 
The following fonn ula will be used to calculate eGFR: 
Schwartz Formula: 
eGFR (ml/min/1.73m2) = k x L/SCr, 
where 
Version 1.0 
k is the proportionality constant (0.55 for children~ 2 to <12 years old and adolescent girls 
12 years old; and 0.70 for adolescent boys~ 12 years old); 
L is height (cm); 
SCr is serum creatinine (mg/dL ). 
Baseline, postbaseline, and change from baseline in serum creatinine and eGFRSchwartz will be 
summarized by visit using descriptive statistics. 
7.3. 
Bone Safety Analyses 
The BMD will be evaluated in 2 body sites: spine and total body less head. BMD standard 
Z-score will be computed based on the chronological age-matched population of the same sex 
and ethnicity. BMD height-age Z-score will be generated by substituting height-age for 
chronological age, where height-age will be detennined as the age at which the child's height is 
the median on the stature-for-age Centers for Disease Control (CDC) Year 2000 growth chart 
published on the following CDC website: 
http://www.cdc.gov/nccdphp/dnpao/growthcharts/resources/index.htm 
If a subject's height was greater than the median height for a 20-year-old according to the growth 
chart, both height-age and height-age Z-score will not be calculated. The BMD Z-scores 
(standard Z-score and height-age Z-score) will be calculated for the 2 body sites (ie, spine and 
total body less head). 
Descriptive summaries for the BMD Z-scores (standard Z-score and height-age Z-score) and the 
change from baseline in Z-scores (standard Z-score and height-age Z-score) will be presented by 
visit for the spine and total body less head DXA Analysis Sets. 
7.4. 
Palatability/ Acceptability Assessment 
Palatability and acceptability assessments will be summarized by visit and cohorts using 
frequency count and percentage. 
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8.
PHARMACOKINETICS ANALYSIS
8.1.
PK Endpoints
The primary PK endpoints include:

The PK parameter AUCtau for TAF
The secondary PK endpoints include:

Additional PK parameters including AUClast, Cmax, Tmax, Clast, Tlast, Ctau, λz, apparent CL, 
apparent Vz, and T½)
The PK analysis for Cohort 1 was done in 2017 and will not be repeated in this analysis. Only 
IPK concentrations and parameters from Cohort 2 will be included in this analysis.
8.2.
Estimation of Pharmacokinetic Parameters
Pharmacokinetic parameters from the intensive PK sampling will be estimated using 
WinNonlinsoftware using standard noncompartmental method. The linear/log trapezoidal rule 
will be used in conjunction with the appropriate noncompartmental model with input values for 
dose level, time of dose, plasma concentration, and corresponding real time values, based on 
drug dosing times whenever possible.
All predose sample times before time zero will be converted to zero. Samples below the limit of 
quantitation of the bioanalytical assays that occur prior to the achievement of the first 
quantifiable concentration will be assigned a concentration value of zero to prevent 
overestimation of the initial AUC. Samples that are BLQ at all other time points will be treated 
as missing data. The nominal time point for a key event or dosing interval (tau) may be used to 
permit direct calculation of AUC over specific time intervals. The appropriateness of this 
approach will be assessed by the pharmacokineticist on a profile-by-profile basis.
Accurate estimation of several PK parameters, such as λz and t1/2, are dependent on the accurate 
estimation of the terminal elimination phase of the drug. The appropriateness of calculating these 
parameters will be evaluated upon inspection of PK data on a profile-by-profile basis by the 
pharmacokineticist.
8.3.
Analysis for PK Parameters
Plasma concentration will be listed for all subjects and summarized by nominal time point for 
subjects in each PK analysis set for Cohort 2 by groups (ie. Group 1 with F/TAF 200/25 mg and 
Group 2 with F/TAF 120/15 mg).


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PK parameters estimated for each analyte will be listed for all subjects and summarized for 
subjects in each PK analysis set for cohort 2 by groups (ie. Group 1 with F/TAF 200/25 mg and 
Group 2 with F/TAF 120/15 mg).
The descriptive statistics (n, mean, SD, coefficient of variation [%CV], minimum, median, 
maximum, Q1, Q3, geometric mean, and its 95% CI) will be presented for plasma concentration 
and parameter data. For concentration values BLQ, the number of subjects with values of BLQ 
will be presented. For PK parameter data, the geometric mean, its 95% CI, and the mean and SD 
of the natural-log transformed values will be presented in addition to the summaries mentioned 
above.
8.3.1.
Statistical Comparative Analysis
To determine whether the adult dose in adolescents achieves similar systemic exposure to that in 
adults, statistical comparisons will be performed to compare the PK data from the current study 
with adult data from HIV-1 infected, F/TAF-treated subjects in Study GS-US-311-1089. The 
comparisons will be conducted in subgroup of subjects by the dose of F/TAF received 
(ie. 200/25 mg vs 120/15 mg).
For TAF, a one-way analysis of variance (ANOVA) model will be fitted to the natural 
logarithmic transformed values of AUCtau (as the primary endpoint) and Cmax (as the secondary 
endpoint), respectively, with treatment group as a fixed effect. The treatment groups are defined 
as the test treatment (adolescents in this study) and reference treatment (adults from Study 
GS-US-311-1089).
The PK parameters AUCtau, Cmax, and Ctau for TFV will be analyzed similarly.
The ANOVA model will be carried out using the PROC MIXED procedure in SAS. An example 
SAS code is provided below:
Proc Mixed;
by analyte paramcd; 
class group subjid;
model lnest = group;
repeated  / group = group;
lsmeans group / e  diff cl alpha = 0.1;
estimate ‘Test  versus Reference’  group  1 1 / cl alpha = 0.10; 
Run;
The geometric least-squares means (LS-means) of each treatment group, mean ratio 
(test/reference) and corresponding 90% CI for each PK parameter of the analytes will be 
reported.
The LSMEANS statement computes LS-means for each treatment group on the natural log scale. 
These values will then be exponentiated to produce the geometric LS-means on the original 
linear scale.


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The ESTIMATE statement will produce the point estimate and 90% CI on the natural-log scale 
for the difference between treatments. The test/reference exposure ratio and associated 90% CIs 
will be calculated by exponentiation of the natural-log scale point estimate and the associated 
90% CI lower and upper limits.
For each analyte, 90% CIs for the ratio of the geometric LS (GLS) means of the test (adolescents 
in this study) and reference (adults from Study GS-US-311-1089) treatments will be calculated 
for AUCtau, Cmin(if applicable), and Cmax, consistent with the two 1-sided tests each performed at 
an alpha level of 0.05 {U.S. Department of Health and Human Services Food and Drug 
Administration Center for Drug Evaluation and Research (CDER) 2001, U.S. Department of 
Health and Human Services Food and Drug Administration Center for Drug Evaluation and 
Research (CDER) 2003}. Equivalency in PK will be concluded if the 90% CI are within the 
equivalence boundaries of 70% to 143%.


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9.
REFERENCES
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER). Guidance for Industry. Statistical Approaches 
to Establishing Bioequivalence.  January, 2001.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER). Guidance for Industry. Bioavailability and 
Bioequivalence Studies for Orally Administered Drug Products - General 
Considerations (Revision 1).  March, 2003.


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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11.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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12.
APPENDICES
Appendix 1.
Schedule of Assessments


F!TAF 
GS-US-311- 1269 
Statistical Analysis Plan (For CT.gov Posting) 
Version 1.0 
Appendix 1. 
Schedule of Assessments 
End of Week• 
Baseline/ 
30 Day 
Study Procedure 
Screen< 
Day Id 
I 
2 
4 
8 
12 
24 
36 
48 
Follow-up• 
ESDD' 
Informed Consent/ Assent 
X 
Medical Historyg 
X 
Concomitant Medications 
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 
Complete Physical Exam 
X 
X 
X 
X 
X 
Symptom-Directed Physical Exam; 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG (performed supine) 
X 
X 
Yitai Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight and Height/Length 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Pregnancy Test" 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry Profile 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Metabolic Assessments 
X 
X 
X 
Estimated GFR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology Profile 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma HJ V- 1 RNA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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F!TA F 
GS-US-311- 1269 
Statistical Analysis Plan (For CT.gov Posting) 
Baseline/ 
Study Procedure 
Screen< 
Day I d 
I 
Serum Storage Sample 
HCV Serology!' 
X 
HBV Serology 
X 
Enrollmentq 
X 
Cohort I Dispense Diary Cards ' 
X 
Cohorts 2, 3, & 4 Dispense Diary 
X 
Cards' 
Single Random PK Sample' 
X 
Cohorts I and 2 Fasted Prior to Visit 
X 
Cohort I lPK Sampling1 
Cohort 2 Part A IPK Sampling1 
Cohort I Palatability and 
Acceptability Assessment
0 
Cohort 2 Part A Palatability and 
Acceptability Assessment 
Single Observed Dosing PK Samplev 
Trough PK Sampte•,w 
PBMC',x 
DXA Scan (spine & total body) 
X 
CONFIDENTIAL 
2 
X 
X 
X 
x 1 
X 
X 
Version 1.0 
End of Week• 
30 Day 
4 
8 
12 
24 
36 
48 
Follow-up• 
ESDD' 
X 
X 
X 
X 
X 
X 
X 
X 
x
1 
X 
X 
X 
X 
X 
X 
X 
XY 
XY 
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Study Procedure
Screenc
Baseline/ 
Day 1d
End of Weeka
30 Day 
Follow-upe
ESDDf
1
2
4
8
12
24
36
48
Cohort 1 Serum Bone Safety Testsz
X
X
X
X
X
Xaa
Cohorts 2, 3, and 4 Serum Bone 
Safety Testsz
X
X
X
X
X
Xaa
Tanner Stage Assessmentbb
X
X
X
In-Clinic Dosing 
X
X
X
X
Study Drug Dispensation 
X
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
X
a
All study visits are to be scheduled relative to when the Baseline/Day 1 visit was completed. All study visits through Week 8 are to be completed within ± 2 days of the 
protocol specified visit date. Visits between Week 12 through Week 48 are to be completed within ± 4 days of the protocol specified visit date, unless otherwise specified.
c
All screening evaluations are to be completed within 35 days prior to Baseline/Day 1 Visit.
d
Subjects will be dispensed study drug on the Baseline/Day 1 Visit. Initiation of treatment with the study drug must take place within 24 hours after the Baseline/Day 1 visit. 
F/TAF will be provided by the Sponsor unless prohibited by local regulations or upon request by the subject due to insurance restrictions.
e
30 Day Follow Up only required for 
 or those subjects who permanently discontinue study drug and do 
not continue in the study through at least one subsequent visit after the Early Study Drug Discontinuation (ESDD) Visit. For the purpose of scheduling a 30 Day Follow Up 
Visit, a ± 6 days window may be used.
f
Early Study Drug Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through 
Week 48 even if the subject discontinues study drug.
g
Medical history should include a history of HIV 1 disease related events, ongoing medications within 30 days of Screening, and all information available on historical 
genotypes.
i
Symptom directed physical examination, as needed.
k
Renal safety tests assessments will be collected fasted for Cohorts 1 and 2. If the subject has not fasted prior to the visit the subject must return within 72 hours in a fasted 
state to collect urine for renal safety tests. 
l
Required for ESDD visit if last test was > 12 weeks from ESDD visit.
m
Females of childbearing potential in Cohorts 1 and 2 only. Performed at screening and anytime during the study to confirm a positive urine pregnancy test.
n
Females of childbearing potential in Cohorts 1 and 2 only. Positive urine pregnancy tests anytime during the study will be confirmed with a serum test. 
  
p
If the antibody test result is positive, HCV RNA test will be performed to confirm HCV viremia.
q
Assignment of the subject’s enrollment number may occur up to 7 days prior to the Baseline/Day 1 visit.
CCI
CCI
CCI
CCI
CCI
CCI
I 
I 
I 
I 


F!TAF 
GS-US-311- 1269 
Statistical Analysis Plan (For CT.gov Posting) 
Version 1.0 
r 
Diary Cards will be dispensed at Week I for all subjects in Cohort I to record administration of study dmgs and their 3rd ARV agent for at least 3 days prior to the IPK visit at 
the Week 2 visit. Diary Cards will be dispensed at Week I or Week 2 for all subjects in Part A of Cohorts 2, 3, and 4 to record administration of study dmgs and their 
3rd ARV agent for at least 3 days prior to the IPK visit that is to occur during the Week 2 or 4 visit, or within 7 after the completion of the Week 2 or Week 4 visit. Diary 
Cards are to be collected and reviewed for protocol compliance prior to in clinic dosing and IPK sampling. If the subject has already dosed or is not fasted prior to the IPK 
evaluation visit refer IPK instmctions in protocol Section 6.3 for details on how to proceed. 
s 
Subjects are allowed to take study dmg at approximately the same time each day however at the time of the single random PK, trough PK, or PBMC sampling they are 
re.quired to report the time of the last dose. 
IPK will occur during the Week 2 visit for subjects in Cohort I and at either the Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits, for 
subjects in Cohort 2 Part A. For the purpose of scheduling the IPK visit, a +7 day window may be used. Subject dosing diary cards are to be collected and reviewed prior to 
in clinic dosing and IPK sampling. 
u 
For Cohort I, palatability will be assessed 30 60 minutes after study dmg dosing for all subjects undergoing IPK sampling at Week 2. Acceptability will be assessed 
30 60 minutes after study dmg dosing for active subjects at the next study visit immediately following approval of this protocol at the site. 
v 
A single observed dosing PK sample will be collected at Weeks 4 and 12 at any time between 15 min to 4 hours post observed in clinic dose. For subjects in Cohort 2 Part A, 
a single observed dosing PK sample does not need to be collected at Week 4 if IPK is collected at the Week 4 visit. 
w 
For subjects in all Cohorts a trough PK sample will be collected during the Week 8 visit at O hours (pre dose, ::S 30 minutes prior to dosing) will be collected. 
x 
For subjects in Cohorts I and 2, PBMC collection will be perfom1ed at the Week 8 visit only at study sites that can perfom1 PBMC processing. For subjects in 
Cohorts 3 and 4, PBMC collection schedule will be specified in a future protocol amendment. All PBMC blood samples will be collected at O hours (::S 30 minutes pre dose). 
y 
DXA scan to be perfom1ed at the 30 Day Follow up visit or the ESDD visit if the last scan was acquired > 12 weeks from the date of the ESDD Visit. DXA scan can occur up 
to IO days after the ESDD visit date. 
z 
If the subject has not fasted prior to the blood draw for semm bone safety tests visit may continue however the subject must return within 72 hours after completion of the 
visit in a fasted state to draw blood for semm bone safety tests. 
aa 
Semm bone safety test is re.quired at ESDD visit if last test was > 12 weeks from ESDD visit. 
bb Tanner assessments will be erfom1ed at Baseline/Da I Weeks 24 and 48 
I 
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