Clinical trial NCT04143594
Conditions: HIV-1-infection
Sponsor: Gilead Sciences
Start date: 2019-11-22; Completion date: 2023-09-19
Enrollment: 183 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of lenacapavir (formerly GS-6207) containing regimens in people living with human immunodeficiency virus (HIV) (PLWH).

Detailed description:

Arms: arm 1: Induction phase: Participants will receive lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15.

Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80.

Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. arm 2: Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.

Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.

Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards. arm 3: Induction phase: Participants will receive LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15.

Maintenance phase: Participants will receive LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and will continue up to Week 80.

Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards. arm 4: Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80
Interventions: intervention 1: Oral Lenacapavir intervention 2: F/TAF intervention 3: Subcutaneous Lenacapavir intervention 4: TAF intervention 5: BIC intervention 6: B/F/TAF
Intervention descriptions: intervention 1: Tablets administered without regard to food intervention 2: Tablets administered without regard to food intervention 3: Administered in the abdomen via subcutaneous injections intervention 4: Tablets administered without regard to food intervention 5: Tablets administered without regard to food intervention 6: Tablets administered without regard to food

Protocol documents:
SAP_002.pdf: 
  
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2 Randomized, Open Label, Active Controlled Study 
Evaluating the Safety and Efficacy of Long-acting Capsid 
Inhibitor GS-6207 in Combination with Other Antiretroviral 
Agents in People Living with HIV
Name of Test Drug:
Lenacapavir (LEN; GS-6207) 
Study Number:
GS-US-200-4334
Protocol Version (Date):
Amendment 3 (01 September 2020)
Analysis Type:
Week 54 Interim Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
26 October 2021
Analysis Plan Author(s):
 
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
GILEAU 


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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ............................................................................................................................... 1 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ .4 
LIST OF ABBREVIATIONS ......................................................................................................................................... 5 
PHARMACOKINETICABBREVIATIONS ................................................................................................................. 6 
1. 
INTRODUCTION .................................................................................................................................................. 7 
1. 1. 
Study Objectives ........................................................................................................................................ 7 
1.2. 
Study Design ............................................................................................................................................. 7 
1.3. 
Sample Size and Power ........................................................................................................................... 10 
2. 
TYPE OF PLANNED ANALYSIS ...................................................................................................................... 11 
2.1. 
Interi1n Analyses ...................................................................................................................................... 11 
2.1. 1. 
Data Monitoring Committee Analysis ................................................................................... 11 
2.1.2. 
Week 28 Interim Analysis ..................................................................................................... 11 
2.1.3. 
Week 80 Interitn Analysis ..................................................................................................... 11 
2.2. 
Pri1nruy Analysis ..................................................................................................................................... 11 
2.3. 
Final Analysis .......................................................................................................................................... 11 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................. 12 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
Analysis Sets ........................................................................................................................................... 12 
3 .1. 1. 
All Randomized Analysis Set ................................................................................................ 12 
3.1.2. 
Full Analysis Set. ................................................................................................................... 12 
3.1.3. 
Per-Protocol Analysis Set ...................................................................................................... 13 
3.1.4. 
Safety Analysis Set ................................................................................................................ 13 
3.1.5. 
Pha1macokinetic Anal sis Set ............................................................................................... 13 
Subject Grouping ..................................................................................................................................... 14 
Strata and Covru'iates ............................................................................................................................... 14 
Examination of Subject Subgroups ......................................................................................................... 14 
3.4.1. 
Subject Subgroups for Efficacy Analyses ............................................................................. 14 
3.4.2. 
Subject Subgroups for Safety Analyses ................................................................................ 15 
Multiple Co1npa11sons ............................................................................................................................. 15 
Missing Data and Outliers ....................................................................................................................... 15 
3.6.1. 
Missing Data .......................................................................................................................... 15 
3. 6. 2. 
Outliers .................................................................................................................................. 15 
Data Handling Conventions and Transfo1mations .................................................................................. 15 
Analysis Visit Windows .......................................................................................................................... 17 
3.8.1. 
Definition of Key Dates and Study Day ................................................................................ 17 
3.8.2. 
Analysis Visit Windows ........................................................................................................ 18 
3.8.3. 
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window ................................................................................................................................. 19 
4. 
SUBJECT DISPOSITION ................................................................................................................................... 21 
4.1. 
Subject Enrollment and Disposition ........................................................................................................ 21 
4.2. 
Extent of Study Thug Exposme and Adherence ...................................................................................... 22 
4.2.1. 
Duration of Exposw·e to Study Dtug ..................................................................................... 22 
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4.2.2.
Adherence to Study Drug ......................................................................................................23
4.3.
Protocol Deviations .................................................................................................................................25
5.
BASELINE CHARACTERISTICS .....................................................................................................................26
5.1.
Demographics and Baseline Characteristics ...........................................................................................26
5.2.
Other Baseline Characteristics ................................................................................................................26
5.3.
Medical History.......................................................................................................................................26
6.
EFFICACY ANALYSES.....................................................................................................................................27
6.1.
Primary Efficacy Endpoint......................................................................................................................27
6.1.1.
US FDA-defined Snapshot Algorithm ..................................................................................27
6.1.2.
Primary Analysis of the Primary Efficacy Endpoint.............................................................28
6.1.3.
Secondary Analysis for the Primary Efficacy Endpoint........................................................29
6.2.
Secondary Efficacy Endpoints ................................................................................................................29
6.2.1.
Analysis of the Secondary Efficacy Endpoints .....................................................................29
6.3.
Other Efficacy Endpoints ........................................................................................................................30
6.3.1.
Proportion of Subjects with HIV-1 RNA < 50 copies/mL by 
Missing = Failure and Missing = Excluded Analyses...........................................................30
6.4.
Subgroup Analysis...................................................................................................................................31
6.5.
Changes from Protocol-Specified Efficacy Analyses .............................................................................31
7.
SAFETY ANALYSES.........................................................................................................................................32
7.1.
Adverse Events and Deaths.....................................................................................................................32
7.1.1.
Adverse Event Dictionary .....................................................................................................32
7.1.2.
Adverse Event Severity .........................................................................................................32
7.1.3.
Relationship of Adverse Events to Study Drug.....................................................................32
7.1.4.
Serious Adverse Events.........................................................................................................32
7.1.5.
Treatment-Emergent Adverse Events....................................................................................32
7.1.6.
Summaries of Adverse Events and Deaths............................................................................33
7.1.7.
Additional Analysis of Adverse Events ................................................................................35
7.2.
Laboratory Evaluations ...........................................................................................................................36
7.2.1.
Summaries of Numeric Laboratory Results ..........................................................................37
7.2.2.
Graded Laboratory Values ....................................................................................................37
7.3.
Body Weight and Vital Signs..................................................................................................................38
7.4.
Prior and Concomitant Medications........................................................................................................39
7.4.1.
Nonstudy Drug Antiretroviral Medications...........................................................................39
7.4.2.
Concomitant Non-ARV Medications....................................................................................39
7.5.
Electrocardiogram Results.......................................................................................................................40
7.5.1.
Investigator Electrocardiogram Assessment .........................................................................40
7.6.
Other Safety Measures ............................................................................................................................40
7.7.
Subject Subgroup for Safety Endpoints ..................................................................................................40
7.8.
Changes From Protocol-Specified Safety Analyses................................................................................40
8.
PHARMACOKINETIC (PK) ANALYSES.........................................................................................................41
8.1.
PK Sample Collection .............................................................................................................................41
8.2.
PK Analyses Related to Intensive PK Sampling.....................................................................................42
8.2.1.
Estimation of PK Parameters.................................................................................................42
8.2.2.
PK Parameters .......................................................................................................................42
8.2.3.
Statistical Analysis Methods .................................................................................................43
8.2.4.
Sensitivity Analyses ..............................................................................................................44
8.2.5.
Changes from Protocol-Specified Pharmacokinetic Analyses..............................................44
9.
REFERENCES.....................................................................................................................................................45
10.
SOFTWARE.........................................................................................................................................................46


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11.
SAP REVISION...................................................................................................................................................47
12.
APPENDICES......................................................................................................................................................48
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Visit Windows for HIV-1 RNA, CD4+ cell count, CD4 %, Hematology, 
Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, Urine Pregnancy Laboratory 
Tests, Vital Signs, and Weight for the LEN-containing Regimen Groups 
(Treatment Groups 1-3)...........................................................................................................18
Table 3-2.
Analysis Visit Windows for HIV-1 RNA, CD4+ cell count, CD4 %, Hematology, 
Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, Urine Pregnancy Laboratory 
Tests, Vital Signs, and Weight for the B/F/TAF Group (Treatment Group 4)........................19
Table 8-1.
Study TreatmentGroups and Associated Analytes ..................................................................42
Table 8-2.
PK Parameters for Each Analyte.............................................................................................43


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LIST OF ABBREVIATIONS
AE
adverse event
B/F/TAF
Bictegravir/Emtricitabine/Tenofovir Alafenamide
BIC
Bictegravir
BLQ
below the limit of quantitation
BMI
body mass index
CI
confidence interval
CSR
clinical study report
DMC
data monitoring committee
DAIDS
Division of AIDS
ECG
electrocardiogram
eCRF
electronic case report form
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
Full Analysis Set
GLPS
Gilead Global Patient Safety
Hb
hemoglobin
HLT
high-level term
IXRS
interactive web response system
LOQ
limit of quantitation
LPLV
last patient last visit
MedDRA
Medical Dictionary for Regulatory Activities
PK
pharmacokinetics
PP
per protocol
PT
preferred term
PWH
people with HIV
Q1, Q3
first quartile, third quartile
SAE
serious adverse events
SAP
statistical analysis plan
SC
subcutaneous 
SD
standard deviation
SE
standard error
SOC
system organ class
TAF
tenofovir alafenamide
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
TFV
tenofovir
TFV-DP
tenofovir diphosphate
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCtau
area under the concentration versus time curve over the dosing interval
Clast
last observed quantifiable concentration of the drug 
Cmax
maximum observed concentration of drug 
Ctau
observed drug concentration at the end of the dosing interval
CLss/F
apparent oral clearance after administration of the drug:
at steady state: CLss/F = Dose/AUCtau , where “Dose” is the dose of the drug
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 
2 by the terminal elimination rate constant (z)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination 
phase of the concentration of drug versus time curve


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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) of Week 54 interim analysis for 
Study GS-US-200-4334, the primary analysis of this study. A formal interim analysis will be 
performed when all subjects have completed Week 54 assessment or prematurely discontinued 
from study drug. The purpose of this interim analysis is to support the lenacapavir 
(LEN; GS-6207) regulatory filing for the indication in the heavily treatment experienced people 
with HIV (PWH).
This SAP is based on the study protocol amendment 3 dated 01 September 2020 and the 
electronic case report form (eCRF). The SAP will be finalized prior to data finalization for the 
Week 54 analysis. Any changes made after the finalization of the SAP will be documented in the 
clinical study report (CSR).
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate the efficacy of LEN containing regimens in PWH as determined by the 
proportion of subjects with HIV-1 RNA  50 copies/mL at Week 54
The secondary objectives of this study are as follows:

To evaluate the efficacy of LEN containing regimens in PWH as determined by the 
proportion of subjects with HIV-1 RNA  50 copies/mL at Weeks 28, 38, and 80

To evaluate the change from baseline in log10 HIV-1 RNA and in CD4+ cell count at 
Weeks 28, 38, 54, and 80

To evaluate the safety and tolerability of the LEN containing regimens through 28, 38, 54, 
and 80 weeks of treatment

To evaluate the pharmacokinetics (PK) of LEN, bictegravir (BIC), and tenofovir alafenamide 
(TAF)
1.2.
Study Design
Design Configuration and Subject Population
This is a Phase 2, randomized, open label, active controlled, multicenter study.
Approximately 175 treatment-naive PWH who meet all eligibility criteria will be randomized in 
a 2:2:2:1 ratio to 1 of the following 4 treatment groups. Randomization will be stratified by 
HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.


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Treatment Groups
Treatment Group 1 (n = 50)
Induction: Subjects will receive oral LEN 600 mg, 600 mg, and 300 mg, without regard to food, 
at Days 1, 2, and 8 respectively. Subjects will also begin oral daily emtricitabine (F)/TAF 
(200/25 mg), without regard to food from Day 1 onwards for a total of 28 weeks. On Day 15 
subjects will receive subcutaneous (SC) LEN 927 mg, without regard to food.
Maintenance: Subjects will receive SC LEN 927 mg at Week 28 and every 26 weeks thereafter. 
Subjects will discontinue oral daily F/TAF (200/25 mg) at Week 28 and begin taking oral daily 
TAF (25 mg), without regard to food.
Treatment Group 2 (n = 50)
Induction: Subjects will receive oral LEN 600 mg, 600 mg, and 300 mg, without regard to food 
at Days 1, 2, and 8 respectively. Subjects will also begin oral daily F/TAF (200/25 mg), without 
regard to food from Day 1 onward for a total of 28 weeks. On Day 15 subjects will receive SC 
LEN 927 mg, without regard to food.
Maintenance: Subjects will receive SC LEN 927 mg at Week 28 and every 26 weeks thereafter. 
Subjects will discontinue oral daily F/TAF (200/25 mg) at Week 28 and begin oral daily BIC 
(75 mg) without regard to food.
Treatment Group 3 (n = 50)
Subjects will receive oral LEN 600 mg and 600 mg without regard to food at Days 1 and 2, 
respectively. On Day 3, subjects will begin oral daily LEN 50 mg, without regards to food. 
Subjects will begin oral daily F/TAF (200/25 mg), without regard to food from Day 1 onwards.
Treatment Group 4 (n = 25)
Subjects will receive oral daily bictegravir/emtricitabine/TAF (B/F/TAF, 50/200/25 mg), without 
regard to food at Day 1 and throughout their participation in the study.
Key Eligibility Criteria
Treatment naive PWH who meet the following criteria:

Age ≥ 18 years of age at Screening

Plasma HIV-1 RNA  200 copies/mL at Screening

CD4+ cell count  200 cells/L at Screening

Antiretroviral (ARV) naive with no use of any ARV medications within one month of 
Screening. Use of pre-exposure prophylaxis (PrEP) (any duration), post-exposure 
prophylaxis (PEP) (any duration), or HIV-1 treatment (< 10 days therapy total) > 1 month 
prior to Screening is permitted.


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Schedule of Assessments
At screening, laboratory analyses (hematology, chemistry, and urinalysis, and serum pregnancy 
test [for women]), HIV-1 RNA, CD4+ cell count, vital signs, electrocardiogram (ECG), 
complete physical examination and estimated glomerular filtration rate (eGFR) will be 
performed, and hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies will be analyzed. 
Analysis of the subject’s HIV-1 resistance to support eligibility will be completed.
After screening procedures, eligible subjects will be randomized into 1 of the 4 treatment groups 
in a 2:2:2:1 ratio.
Subjects in Treatment Groups 1, 2, and 3 only, will have visits on Day 1, Day 2, 
 
 Day 8, and Day 15. All subjects will have a Week 4 visit and will continue to attend 
study visits every 6 weeks until Week 28.
Subjects in Treatment Groups 1 and 2 will need to have HIV-1 RNA results < 50 copies/mL at 
Weeks 16 and 22 to initiate treatment with a two agent regimen at Week 28; those with values 
≥ 50 copies/mL will discontinue the study drug at or prior to Week 28.
After Week 28, subjects will attend study visits on Week 38, Week 54, Week 64, and Week 80. 
After Week 80, subjects in Treatment Group 4 will complete the study and subjects in Treatment 
Groups 1, 2, and 3 will be given the option to receive further treatment and continue to attend 
visits alternating between every 10 weeks and every 16 weeks visits.
At each visit, adverse events (AEs), concomitant medications, laboratory tests, physical 
examinations, PK, and patient reported outcomes (PROs) will be performed in accordance with 
the Study Procedures Table.
More details for study procedures could be found in Section 12 (Appendix 1). 
Study Duration
Duration of treatment is at least 80 weeks. Subjects in Treatment Group 4 will complete the 
study at Week 80.
Following successful completion of Week 80 visit, subjects receiving LEN will be given the 
option to receive further treatment and continue to attend visits on Week 90, Week 106, 
Week 116, Week 132, Week 142, and will continue to alternate between every 10 weeks and 
every 16 weeks visits. Subjects willing to continue the study beyond Week 80 in Treatment 
Groups 1 and 2 will continue to receive SC LEN 927 mg every 6 months (26 weeks) from 
Week 80 onwards and subjects in Treatment Group 3 will receive oral LEN 50 mg daily from 
Week 80 until the product becomes accessible to subjects through an access program, or until 
Gilead elects to discontinue the study in the country. Subjects in Treatment Groups 1, 2, and 3 
will also receive TAF, F/TAF, or BIC as applicable.
Subjects who discontinue study drugs prior to Week 80 visit or prior to study completion may be 
required to complete 30-Day, 90-Day and/or 180-Day Follow Up visits after Early Termination 
Visit.
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1.3.
Sample Size and Power
A sample size of 50 subjects in Treatment Groups 1 to 3, respectively, was chosen to estimate 
the response rate of HIV-1 RNA < 50 copies/mL at Week 54. A total sample size of 75 subjects 
for each pair of comparisons (ie, between each of the LEN-containing regimen groups 
[Treatment Groups 1 to 3, n = 50] and the B/F/TAF [Treatment group 4, n = 25]) will provide 
39% power to evaluate non-inferiority with respect to the response rate of HIV-1 RNA 
 50 copies/mL at Week 54. In this sample size and power calculation, it is assumed a response 
rate is 90.9% (based on pooled data from Studies GS-US-380-1489 and GS-US-380-1490) for 
each treatment group and a non-inferiority margin is 0.12.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Data Monitoring Committee Analysis 
One external multidisciplinary Data Monitoring Committee (DMC) analysis was conducted after 
all subjects have completed their Week 16 visit or prematurely discontinued from study drug, all 
outstanding data queries had been resolved or adjudicated as unresolvable, and the data had been 
cleaned and finalized for the analysis. No formal stopping rules was used by the DMC for safety 
outcomes. Rather, a clinical assessment was made to determine if the nature, frequency, and 
severity of AEs associated with a study treatment warrant the early termination of the study in 
the best interest of the subjects. No alpha penalty will be applied for the primary analysis of the 
primary efficacy endpoint given that the study is not adequately powered for a formal efficacy 
evaluation. The purpose of the interim analysis was to provide the DMC with a statistical report 
for review. More details are documented in the DMC charter.
2.1.2.
Week 28 Interim Analysis
The Week 28 interim analysis was conducted after all subjects have completed the Week 28 visit 
or have prematurely discontinued the study drug, outstanding data queries had been resolved or 
adjudicated as unresolvable, and the data had been cleaned and finalized for the analysis. The 
analysis was used to support the LEN regulatory filing for the indication in the heavily treatment 
experienced PWH.
2.1.3.
Week 80 Interim Analysis
The Week 80 analysis will be conducted after all subjects either complete their Week 80 visit or 
prematurely discontinue from the study drug, outstanding data queries had been resolved or 
adjudicated as unresolvable, and the data had been cleaned and finalized for the analysis.
2.2.
Primary Analysis
The Week 54 interim analysis is a planned primary analysis and will be conducted after all 
subjects have completed Week 54 visit or have prematurely discontinued the study drug, 
outstanding data queries have been resolved or adjudicated as unresolvable, and the data have 
been cleaned and finalized for the analysis.
This SAP describes the analysis plan for the Week 54 interim analysis, the primary analysis of 
this study.
2.3.
Final Analysis
The final analysis will be performed after all subjects have completed the study or have 
prematurely discontinued the study drug, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized.


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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.
All statistical tests will be 2-sided and performed at the 5% significance level for descriptive 
purpose unless otherwise specified.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set and 
sorted by subject identification (ID) number, visit date, and time (if applicable). Data collected 
on log forms, such as AEs, will be presented in chronological order within the subject. The 
treatment group to which subjects were randomized will be used in the listings. Age, sex at birth, 
race, and ethnicity will be included in the listings, as space permits.
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. The analysis set will be identified and included as a subtitle of each 
table, figure, and listing.
For each analysis set, the number and percentage of subjects eligible for inclusion will be 
summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
All Randomized Analysis Set
All Randomized Analysis Set includes all subjects who were randomized in the study.
This is the primary analysis set for by-subject listings.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all randomized subjects who were randomized and 
received at least 1 dose of study drug. This is the primary analysis set for efficacy analyses.


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Per-Protocol Analysis Set 
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The Per-Protocol (PP) Analysis Set is defined for the prirmuy efficacy analysis. This analysis set 
includes all subjects in the FAS excluding subjects meeting any of the following criteria: 
• 
Subjects who do not have on-treatment HIV-1 RNA in the Week 54 analysis window, except 
when missing is due to discontinuation of study dmg for lack of efficacy. (Note: lack of 
efficacy is defined as having the check-box for Lack of Efficacy marked as the reason for 
premature study dmg discontinuation on the study chu g completion eCRF page.) 
• 
Subjects who meet the exclusion criterion that was known hypersensitivity to the study 
chug(s), the metabolites, or fonnulation excipient. 
• 
Subjects who meet the exclusion criterion for receiving ti·eatment within 3 months prior to 
screening, or anticipated ti·eatment during the study period with immunosuppressant 
therapies, hych·oxyurea, foscamet, radiation, or cytotoxic chemotherapeutic agents that listed 
in Table 5-3 in protocol Section 5.4. 
• 
Nonadherence to once daily (QD) study ch11g(s): subjects with adherence rate for active once 
daily study chug(s) up to the Week 54 Visit below the 2.5th percentile 
3.1.4. 
Safety Analysis Set 
The Safety Analysis Set includes all subjects who were randomized and received at least 1 dose 
of study chug. This is the primaiy analysis set for safety analyses. 
3.1.5. 
Pharmacokinetic Analysis Set 
The PK Analysis Set will include all subjects who (1) ai·e randomized into the study, (2) have 
received at least 1 dose of active study chug, and (3) have at least 1 nonmissing PK concenti·ation 
value for any analyte of interest repo1ted by the PK lab. The PK analysis set will be used for 
general PK analyses. 
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3.2.
Subject Grouping
For analyses based on the All Randomized Analysis Set or the FAS, subjects will be grouped 
according to the treatment group to which they were randomized. For all other analyses, subjects 
will be grouped according to the actual treatment received. The actual treatment received will 
differ from the randomized treatment only when their actual treatment differs from randomized 
treatment for the entire treatment duration.
Subjects will be grouped as follows for table summary:  

Treatment Group 1: SC LEN + (F/TAF → TAF) 

Treatment Group 2: SC LEN + (F/TAF → BIC)

Treatment Group 3: Oral LEN + F/TAF

Treatment Group 4: B/F/TAF

Treatment Groups 1 and 2: SC LEN (for all tables unless specified otherwise)

Treatment Groups 1, 2 and 3: LEN (for all tables unless specified otherwise)
3.3.
Strata and Covariates
Randomization was stratified by HIV-1 RNA level (≤ 100,000 copies/mL or 
> 100,000 copies/mL) at screening. 
Efficacy analyses will include HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) at 
baseline as a stratification factor. The HIV-1 RNA stratum will be reclassified using baseline 
HIV-1 RNA level for analysis purposes.
3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Efficacy Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 54 as determined by the 
United States (US) Food and Drug Administration (FDA)-defined snapshot algorithm {U. S. 
Department of Health and Human Services 2015} will be analyzed for the following subject 
subgroups based on FAS:

Age (years): (a) < 50 and (b) ≥ 50

Sex: (a) male and (b) female

Race: (a) black and (b) nonblack

Baseline HIV-1 RNA (copies/mL): (a) ≤ 100,000 and (b) > 100,000

Baseline CD4 Cell Count (/uL): (a) < 200 and (b)  ≥ 200


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3.4.2.
Subject Subgroups for Safety Analyses
Incidence of all treatment-emergent AEs (TEAEs) will be analyzed for the following subject 
subgroups: 

Age (years): (a) < 50 and (b) ≥ 50 

Sex: (a) male and (b) female 

Race: (a) black and (b) nonblack 
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be made in this Phase 2, non-confirmatory trial.
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
For missing last dose date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for 
prior and concomitant medications in Section 7.4.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
Only year of birth is collected in this study. The following conventions will be used for the 
imputation of date of birth when it is partially missing or not collected:

If only month and year of birth is collected, then “15” will be imputed as the day of birth

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed.
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, then age derived based on date of birth and the Day 1 
visit date will be used instead. If an enrolled subject was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (e.g., estimates of creatinine clearance, age 
at date of AE) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified.


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Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the lower LOQ at the same precision level of the originally 
reported value will be used to calculate descriptive statistics if the datum is reported in the 
form of “ x” (where x is considered the lower LOQ). For example, if the values are reported 
as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to calculate 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 to calculate 
summary statistics.

A value that is 1 unit above the upper LOQ will be used to calculate descriptive statistics if 
the datum is reported in the form of “> x” (where x is considered the upper LOQ). Values 
with decimal points will follow the same logic as above.

The lower or upper LOQ will be used to calculate descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the lower or upper LOQ, 
respectively).
Sparse PK concentration values that are below the limit of quantitation (BLQ) will be presented 
as “BLQ” in the data listing.
Logarithmic (base 10) transformations will be applied to HIV-1 RNA data for efficacy analysis. 
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “<20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purposes.
Natural logarithm transformation will be used for analyzing concentrations and PK parameters in 
intensive PK samples. Concentration values that are BLQ will be presented as “BLQ” in the 
concentration 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 
intensive 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 subjects 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 subjects 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 subjects 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 subjects 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.”


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3.8.
Analysis Visit Windows
3.8.1.
Definition of Key Dates and Study Day
Study Day 1 is defined as the day when the first dose of study drug was taken, as recorded on 
the Study Drug Administration eCRF. For subjects in Treatment Groups 1-3, the earliest of the 
first dose dates of any component (ie, LEN or F/TAF) is considered as the first dose date of the 
study drug.
Last Dose Date is defined as follows for subjects who prematurely discontinued study drug 
according to Study Drug Completion eCRF. 

For subjects who receive SC injection, the last dose date is defined as the latest nonmissing 
end date of the study drug used with LEN.

For subjects who do not receive SC injection, the last dose date is defined as the earliest of 
the last dose date of any study drug.

If the date of last dose is incomplete or missing (eg, due to lost to follow-up), the latest 
nonmissing study drug start dates and end dates, the clinic visit dates, and the laboratory visit 
dates excluding the dates of any follow-up visits will be used to impute the last dose date.
Study Days are calculated relative to Study Day 1 of study drug and derived as follows:

For postdose study days: Assessment Date – First Dose Date + 1

For days prior to the first dose: Assessment Date – First Dose Date
Baseline Value is defined as the last value obtained on or prior to the first dose of study drug.
Last Study Date is the latest nonmissing clinic visit dates, and/or the laboratory visit dates, 
and/or latest AE onset date and end date, whichever is latest, including the any follow-up visit 
dates, for subjects who prematurely discontinued study according to the Study Completion 
eCRF.
Last Exposure Date is defined as follows for subjects who prematurely discontinued study drug 
according to Study Drug Completion eCRF. This date is defined considering the prolonged 
exposure of LEN after the last dose date of LEN.

Treatment Groups 1 and 2:
For subjects who receive SC injection, last exposure date is defined as last study date.  
For subjects who do not receive SC injection, last exposure date is defined as the 
minimum of the last dose date plus 60 days and the last study date.


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
Treatment Group 3: last exposure date is defined as the minimum of the last dose date plus 
60 days and the last study date.

Treatment Group 4: last exposure date is defined as the minimum of the last dose date plus 
30 days and the last study date.
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 %, Hematology, Chemistry, Lipid 
Panel, Urinalysis, Urine Chemistry, Urine Pregnancy Laboratory Tests, Vital Signs, and Weight 
are provided in Table 3-1 and Table 3-2 for the LEN-containing regimen groups 
(Treatment Groups 1-3) and the B/F/TAF group (Treatment Group 4), respectively.
Table 3-1.
Analysis Visit Windows for HIV-1 RNA, CD4+ cell count, CD4 %, 
Hematology, Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, 
Urine Pregnancy Laboratory Tests, Vital Signs, and Weight for the 
LEN-containing Regimen Groups (Treatment Groups 1-3)
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Day 1
1
≤ 1
1
Day 2
2
2
5
Day 8
8
6
11
Day 15
15
12
21
Week 4
28
22
49
Week 10
70
50
91
Week 16 
112
92
133
Week 22
154
134
175
Week 28
196
176
231
Week 38
266
232
322
Week 54
378
323
413
Week 64
448
414
504
Week 80
560
505
595
Week 90
630
596
686
Week 106
742
687
777
I 
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Table 3-2.
Analysis Visit Windows for HIV-1 RNA, CD4+ cell count, CD4 %, 
Hematology, Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, 
Urine Pregnancy Laboratory Tests, Vital Signs, and Weight for the 
B/F/TAF Group (Treatment Group 4)
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Day 1
1
≤ 1
14
Week 4
28
15
49
Week 10
70
50
91
Week 16 
112
92
133
Week 22
154
134
175
Week 28
196
176
231
Week 38
266
232
322
Week 54
378
323
413
Week 64
448
414
504
Week 80
560
505
595
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 may be 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 1 value per analysis window.
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dose date of study drug will be 
selected, unless specified differently. If there are multiple records with the same time or no 
time recorded on the same day, the baseline value will be the average of the measurements 
for continuous data (except for HIV-1 RNA, see below), or the measurement with the lowest 
severity (eg, normal will be selected over abnormal for safety ECG findings) for categorical 
data.
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
For postbaseline values:
The record closest to the nominal day for that visit will be selected with the exception of 
CD4 cell counts and CD4% in which the latest record will be selected and HIV-1 RNA 
level (see below).
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken for 
continuous data (except for HIV-1 RNA, see below) and the worse severity will be taken 
for categorical data, unless otherwise specified.

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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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
Key study dates (i.e., first subject screened, first subject randomized, last subject randomized, 
last subject last visit for the primary endpoint, and last subject last visit for the CSR) will be 
provided.
A summary of subject enrollment will be provided by treatment group for each country, 
investigator within a country, and overall. The summary will present the number and percentage 
of subjects randomized. For each column, the denominator for the percentage calculation will be 
the total number of subjects analyzed for that column.
A similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of subjects in the stratum will be the total number of randomized subjects. If there are 
discrepancies in the value used for stratification assignment between the interactive web 
response system (IXRS) and the clinical database, the value collected in the clinical database will 
be used for the summary. A listing of subjects with discrepancies in the value used for 
stratification assignment between the IXRS and the clinical database at the time of data 
finalization will be provided. If there are differences between randomization stratum using 
screening HIV-1 RNA value and baseline HIV-1 RNA value, a listing of the differences will also 
be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group and total based on all 
screened subjects. This summary will present the number of subjects screened, the number of 
subjects who met all eligibility criteria but were not randomized with reasons subjects not 
randomized, the number of subjects randomized but never dosed (if applicable), the number of 
subjects randomized, and the number of subjects in each of the categories listed below:

Safety Analysis Set

Per-Protocol Analysis Set

Continuing study drug in the main phase

Completed study drug in the main phase

Did not complete study drug with reasons for premature discontinuation of study drug in the 
main phase (if applicable)

Entering and treated in the extension phase 

Continuing study drug in the extension phase


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
Completed study drug in the extension phase

Did not complete study drug with reasons for premature discontinuation of study drug in the 
extension phase (if applicable)

Continuing study 

Completed study 

Did not complete the study with reasons for premature discontinuation of study (if 
applicable)
Duration of treatment is at least 80 weeks. At Week 80, subjects in Treatment Group 4 will 
complete the study. Subjects in Treatment Groups 1, 2, and 3 will be given the option to receive 
further treatment and continue to attend visits beyond Week 80. Main phase data is defined as 
the data collected on/before Week 80 visit. Extension phase data is defined as the data collected 
after Week 80 visit. 
For the status of study drug and study completion and reasons for premature discontinuation, the 
number and percentage of subjects in each category will be provided. The denominator for the 
percentage calculation will be the total number of subjects in the Safety Analysis Set 
corresponding to that column in that study phase (if applicable). In addition, a flowchart will be 
provided to depict the disposition.
The following by-subject listings will be provided by subject ID number in ascending order to 
support the above summary tables:

Reasons for premature study drug or study discontinuation

Reasons for screen failure (will be provided by screening ID number in ascending order
4.2.
Extent of Study Drug Exposure and Adherence
Study drug administration and study drug dispensing information will be collected in the Study 
Drug Administration and Study Drug Accountability eCRFs. All data including lot number and 
kit ID (if applicable) will be listed. 
4.2.1.
Duration of Exposure to Study Drug
Due to long acting feature of LEN, duration of follow-up to study drug will consider the 
prolonged exposure of LEN after the last dose date of LEN. Duration of exposure to study drug 
will be defined as (the last exposure date – the first dose date + 1), and will be expressed in 
weeks using up to 1 decimal place (eg, 4.5 weeks). Last exposure date is defined in Section 3.8.1 
for subjects who prematurely discontinued study drug. For subjects who are still on study drug at 
the time of the data cut date of the Week 54 analysis, the data cut date will be used to impute the 
last exposure date.  


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Duration of exposure will be summarized using descriptive statistics (n, mean, SD, median, Q1, 
Q3, minimum, and maximum) and as the number and percentage of subjects exposed and 
remained through the following time periods: 1 day, 2 days, 8 days, 15 days, 4 weeks (28 days), 
10 weeks (70 days), 16 weeks (112 days), 22 weeks (154 days), 28 weeks (196 days), etc. 
Summaries will be provided based on the Safety Analysis Set. No inferential statistics will be 
provided.
4.2.2.
Adherence to Study Drug
4.2.2.1.
Adherence to SC LEN
The adherence to SC LEN will be assessed by adherence to the projected injection interval, 
which is 26 weeks (182 days) between 2 adjacent injection visits. The number of days from the 
projected injection visit date will be calculated for each injection visit (excluding the 1st injection 
visit) as the injection visit date – the previous injection visit date plus 1 day minus 182 days. The 
number of days from the projected injection visit date will be classified into the following 
categories: 

< -14 days

-14 to -8 days

 -7 to -3 days

± 2 days

3 to 7 days

8 to 14 days

> 14 days
The number and percentage of subjects in each category will be summarized for subjects in 
Treatment Groups 1 and 2 who receive SC injections for the injection visit of interest.
4.2.2.2.
Adherence to Once Daily Study Drug(s)
The adherence to once daily (QD) study drug(s) will be calculated based on 1 study drug for 
Treatment Groups 1, 2, and 4 (ie, F/TAF up to Week 28 and TAF or BIC from Week 28 onwards 
for Treatment Groups 1 and 2, and B/F/TAF for Treatment Group 4), and 2 study drugs for 
Treatment Group 3 (ie, oral QD LEN and F/TAF), excluding long acting LEN used for oral 
lead-in.


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Adherence (%) of QD study drug(s) will be calculated as follows:
Adherence (%) =  100 ×
𝑇𝑜𝑡𝑎𝑙 No. of pills taken
Total No. of pills prescribed
=  100 ×
∑∑No. of pills taken at each dispensing period  for each study drug[1]
∑∑No. of pills prescribed at each dispensing period for each study drug[2]
[1]
Number of pills taken at a distinct dispensing period for QD study drug(s) will be calculated as the minimum of (a) the daily 
number of pills prescribed multiplied by the duration of treatment of QD study drug(s) at the dispensing period of the same 
dispensing date, and (b) the number of pills taken (number of pills dispensed minus the number of pills returned). Total 
number of pills taken is determined by summing the number of pills taken from all evaluable dispensing periods for all QD 
study drug(s).
[2]
Number of pills prescribed at a distinct dispensing period for QD study drug(s) will be calculated as the daily number of 
pills prescribed multiplied by the duration of treatment of QD study drug(s) at the dispensing period of the same dispensing 
date. Total number of pills prescribed is determined by summing the number of pills prescribed from all evaluable 
dispensing periods for all QD study drug(s).
The duration of treatment of QD study drug(s) at a dispensing period for the study drug is 
calculated as the minimum of (a) the last returned date of the study drug at a dispensing period, 
(b) date of premature discontinuation of the study drug, and (c) next pill dispensing date of the 
study drug, minus dispensing date of the study drug.
The next pill dispensing date is the following dispensing date of the study drug regardless of the 
bottle return date. 
For a record where the number of pills returned was missing (with “Yes” answered for “Was 
Bottle returned?” question), it is assumed the number of pills returned was zero. If the number of 
pills dispensed was missing or any study drug bottle was not returned or the bottle return status 
was unknown, all records in that dispensing period for that study drug will be excluded from 
both denominator and numerator calculation.
Adherence will be calculated for each subject for the entire dosing period up to the date of 
permanent discontinuation of the study drug for subjects who prematurely discontinued study 
drug or using all available data for subjects ongoing on study drug by the data cut date. 
Descriptive statistics for adherence (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
along with the number and percentage of subjects belonging to adherence categories (eg, < 80%, 
≥ 80% to < 90%, ≥ 90% to < 95%, ≥ 95%) will be provided for subjects who return at least 
1 bottle of randomized QD study drug, and who have calculable adherence in the Safety Analysis 
Set. No inferential statistics will be provided.
A by-subject listing of study drug administration and drug accountability will be provided 
separately by subject ID number (in ascending order) and visit (in chronological order).


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4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry but enrolled in the study, will be 
summarized regardless of whether they were exempted by the sponsor or not. The summary will 
present the number and percentage of subjects who did not meet at least 1 eligibility criterion and 
the number of subjects who did not meet specific criteria by treatment group based on the All 
Safety Analysis Set. A by-subject listing will be provided for those subjects who did not meet at 
least 1 eligibility (inclusion or exclusion) criterion. The listing will present the eligibility criterion 
(or criteria if more than 1 deviation) that subjects did not meet and related comments, if collected.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations (e.g., at 
least 1, with 1, 2, 3 or more important protocol deviations), and the total number of important 
protocol deviations by deviation category (e.g., eligibility criteria, informed consent) will be 
summarized by treatment group for the Safety Analysis Set. A by-subject listing will be provided 
for those subjects with important protocol deviation. 


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic variables (ie, age, sex at birth, gender identity, sexual orientation, race, and 
ethnicity) and baseline characteristics (body weight [in kg], height [in cm], body mass index 
[BMI; in kg/m2]) will be summarized by treatment group and overall using descriptive statistics 
for continuous variables and using number and percentage of subjects for categorical variables. 
The summary of demographic data will be provided for the Safety Analysis Set.
Statistical comparison across treatment groups will be performed. For categorical data, the 
Cochran-Mantel-Haenszel (CMH) test will be used to compare across treatment groups except 
for gender identity and sexual orientation. For continuous data, the 2-sided Kruskal-Wallis test 
will be used to compare across treatment groups.
A by-subject demographic listing, including the informed consent date, will be provided by 
subject ID number in ascending order.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and overall 
using descriptive statistics for continuous variables and using number and percentage of subjects 
for categorical variables:  

HIV-1 RNA (log10 copies/mL)

HIV-1 RNA categories (copies/mL): (a) ≤ 100,000, (b) > 100,000

CD4 cell counts (/uL)

CD4 cell counts categories (/uL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, (d) ≥ 350 to 
< 500, and (e) ≥ 500

CD4 percentage (%)
The summary of these baseline disease characteristics will be provided for the Safety Analysis 
Set. Statistical comparison across treatment groups will be conducted similarly as described for 
the demographic and baseline characteristics.
A by-subject listing of other baseline characteristics will be provided by subject ID number in 
ascending order.
5.3.
Medical History
General medical history data will be collected at screening including HIV-1 disease-related 
events. General medical history data will be coded and listed.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA  50 copies/mL at 
Week 54 as determined by the United States (US) Food and Drug Administration (FDA)-defined 
snapshot algorithm {U. S. Department of Health and Human Services 2015}. The proportions 
are expressed as percentages for presentation purposes.
6.1.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 54 is defined as from Study Day 323 to Study Day 413, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, data collected up to 1 day after the last dose 
date) will be used in the US FDA-defined snapshot algorithm. Virologic outcome will be defined 
as the following categories:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 54 analysis window

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 54 
analysis window, or
Who do not have on-treatment HIV-1 RNA data in the Week 54 analysis window and
■
Who discontinue study drug prior to or in the Week 54 analysis window due to lack 
of efficacy, or
■
Who discontinue study drug prior to or in the Week 54 analysis window due to 
reasons other than AE, death, or lack of efficacy and have the last available 
on-treatment HIV-1 RNA ≥ 50 copies/mL

No Virologic Data in the Week 54 analysis window: this includes subjects who do not have 
on-treatment HIV-1 RNA data in the Week 54 analysis window because of the following:
Discontinuation of study drug prior to or in the Week 54 analysis window due to AE or 
death (regardless of whether the last available on-treatment HIV-1 RNA < 50 copies/mL 
or not) or,
Discontinuation of study drug prior to or in the Week 54 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
Missing data during the window but on study drug.
The flowchart of the US FDA-defined snapshot algorithm is provided in Section 12 
(Appendix 2).


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6.1.2.
Primary Analysis of the Primary Efficacy Endpoint
The proportion of subjects with HIV-1 RNA < 50 copies/mL as determined by the US 
FDA-defined snapshot algorithm at Week 54 will be based on the FAS. Point estimates (P1 – P2)  
and its 95% confidence interval (CI) for the difference in the response rates between each of the 
LEN-containing regimen groups (Treatment Groups 1 to 3) and the B/F/TAF group 
(Treatment Group 4) will be constructed using stratum-adjusted Mantel-Haenszel (MH) 
proportion as described as follows {Koch 1989}, stratified by baseline HIV-1 RNA level 
(≤ 100,000 copies/mL or > 100,000 copies/mL):
where 

(P1 – P2) = 

h
h
h
w
d
w
, is the stratum-adjusted MH proportion difference, 
where 
h
d  = 
h
h
p
p
2
1 
is the difference in the response rate between of the LEN-containing 
regimen groups (Treatment Groups 1 to 3) and the B/F/TAF group (Treatment Group 4) in 
stratum h (h=1 to 4).  

h
w =
h
h
h
h
n
n
n
n
2
1
2
1

, is the weight based on the harmonic mean of sample size per treatment group 
for each stratum where 
h
n1 and 
h
n2 are the sample sizes of the LEN-containing regimen 
groups (Treatment Groups 1 to 3) and the B/F/TAF group (Treatment Group 4) in stratum h.  

SE(P1 – P2) = 
2
2
*
2
*
2
1
*
1
*
1
2
)
(
1
)
1(
1
)
1(













h
h
h
h
h
h
h
h
w
n
p
p
n
p
p
w
, where 
1
5.0
1
1
*
1



h
h
h
n
m
p
and 
1
5.0
2
2
*
2



h
h
h
n
m
p
. 
h
m1  and 
h
m2 are the number of subjects with HIV-1 RNA < 50 copies/mL 
in the LEN-containing regimen groups (Treatment Groups 1 to 3) and the B/F/TAF group 
(Treatment Group 4) in stratum h.  

α = 0.05 for this study 

Z(1-α/2 ) = Z0.9750 = 1.96 is the 97.50th percentile of the normal distribution
Note that if the computed lower confidence bound is less than –1, the lower bound is defined 
as –1. If the computed upper confidence bound is greater than 1, the upper bound is defined as 1.


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The number and percentage of subjects with HIV-1 RNA < 50 copies/mL at Week 54 will be 
summarized. The associated p-values will be estimated based on the CMH test stratified by 
baseline HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL).
6.1.3.
Secondary Analysis for the Primary Efficacy Endpoint
A secondary analysis based on the Week 54 PP analysis set will also be performed to evaluate 
the robustness of the primary analysis of the primary endpoint. Subjects excluded from the 
Week 54 PP analysis set will be determined before database lock.
6.2.
Secondary Efficacy Endpoints
The secondary efficacy endpoints of this study are:

The proportion of subjects with HIV-1 RNA  50 copies/mL at Weeks 28, 38, and 80 as 
determined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and in CD4+ cell count at Weeks 28, 38, 54, 
and 80
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 28 as determined by the 
US FDA-defined snapshot algorithm has been performed in the Week 28 analyses and will not 
be repeated here. The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 38 as 
determined by the US FDA-defined snapshot algorithm will be analyzed using the same method 
as the primary analysis for the primary endpoint based on the FAS.
The proportion of subjects with HIV-1 RNA < 50 copies/mL as determined by the 
US FDA-defined snapshot algorithm at Week 80 will not be summarized for the Week 54 
interim analysis as the majority of subjects will not have reached the timepoints of interest.
6.2.1.
Analysis of the Secondary Efficacy Endpoints
The change from baseline in log10 HIV-1 RNA and in CD4+ cell counts will be based on the 
FAS and summarized up to the visits with available data using descriptive statistics. The 
differences in changes from baseline in log10 HIV-1 RNA and CD4+ cell count between each of 
the LEN-containing treatment groups (Treatment Groups 1-3) and the B/F/TAF group 
(Treatment Group 4) and the associated p-values and 95% CIs will be constructed using analysis 
of variance (ANOVA) models adjusting for the baseline HIV-1 RNA level (≤ 100,000 copies/mL 
or > 100,000 copies/mL).
Mean ± 95% CI and median (Q1, Q3) of the change from baseline in log10 HIV-1 RNA and 
CD4+ cell counts will be plotted by visit.


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6.3.
Other Efficacy Endpoints
6.3.1.
Proportion of Subjects with HIV-1 RNA < 50 copies/mL by Missing = Failure 
and Missing = Excluded Analyses
Number and percentage of subjects with HIV-1 RNA < 50 copies/mL by visit will be analyzed 
using the following 2 analyses:  

Missing = Failure (M = F): 
In this approach, missing data will be treated as virologic failure and summarized into the 
“missing” category (see list of HIV-RNA categories below). Results will be summarized by 
treatment group for all visits up to Week 54. 

Missing = Excluded (M = E): 
In this approach, missing data will be excluded in the computation of the percentages 
(ie, missing data points will be excluded from both the numerator and denominator in the 
computation). The denominator for percentages at a visit is the number of subjects in the 
FAS with nonmissing HIV-1 RNA value at that visit. Results will be summarized by 
treatment group for all visits up to Week 54.
For both M = F and M = E analyses, the number and percentage of subjects with HIV-1 RNA in 
the following categories will be summarized based on the FAS:

< 50 copies/mL 
< 20 copies/mL
■
< 20 copies/mL Not Detectable
■
< 20 copies/mL Detectable
20 to < 50 copies/mL 

50 to < 200 copies/mL 

200 to < 400 copies/mL 

400 to < 1000 copies/mL

≥ 1000 copies/mL 

Missing (only applicable to M = F analysis)
Statistical comparison between each of the LEN-containing treatment groups (Treatment Groups 
1-3) and the B/F/TAF group (Treatment Group 4) will be performed. Point estimates and its 
95% CIs will be estimated using stratum-adjusted MH proportion as described in Section 6.1.2. 
The associated p-values will be estimated based on the CMH test stratified by baseline HIV-1 
RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL).


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6.4.
Subgroup Analysis
Subgroups defined in Section 3.4.1 will be performed for the proportion of subjects with HIV-1 
RNA < 50 copies/mL at Week 54 as determined by the US FDA-defined snapshot algorithm. 
Subgroup analysis will be performed on subjects who have reached Week 54 at the time for the 
Week 54 analysis in the FAS for on-treatment data. Results will be descriptive and the associated 
95% CIs will be constructed using Exact method.
6.5.
Changes from Protocol-Specified Efficacy Analyses
No change from protocol-specified efficacy analysis is planned.


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7.
SAFETY ANALYSES
Safety data will be summarized for subjects in the Safety Analysis Set. All safety data collected 
up to the last exposure date for subjects who prematurely discontinued study drug or all available 
data for subjects who were still on study drug will be included in the table summary, unless 
specified otherwise. All collected data will be included in data listings.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of Medical Dictionary for 
Regulatory Activities (MedDRA). System organ class (SOC), high-level group term (HLGT), 
high-level term (HLT), preferred term (PT), and lower-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, 2, 3, 4, or 5 according to toxicity 
criteria specified in the protocol. The severity grade of events for which the investigator did not 
record severity will be categorized as “missing” for tabular summaries and data listings. The 
missing category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s 
choice, not that of the medical monitor. 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 the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs 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 leading to premature discontinuation of study drug, or

Any AEs with an onset date on or after the study drug start date and no later than the last 
exposure date after permanent discontinuation of the 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 dose 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 as follows:

Subjects who receive SC injection: the AE onset date is the same as or after the month and 
year (or year) of the first dose date of study drug

Subjects who do not receive SC injection: 
The AE onset is the same as or after the month and year (or year) of the first dose date of 
study drug, and
The AE onset date is the same as or before the month and year (or year) of the last 
exposure date
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dose 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 dose date of study drug will 
be considered treatment emergent.
When calculating the duration of event or time to onset, the following imputation rule will be 
used:
Missing start month/day: Jan 1/first day of the month will be used unless this is before the start 
date of study drug; in this case the study drug start date will be used;
Missing stop month/day: Dec 31/last day of the month will be used, unless this is after the last 
study date; in this case the last study date will be used.
Completely missing start or end dates will remain missing, with no imputation applied.
7.1.6.
Summaries of Adverse Events and Deaths
TEAEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE incidence in Combined Severity Grade Subsets 
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.


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The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by treatment group, SOC and PT, and by PT only for the following AE categories: 

TEAEs

TEAEs (by severity)

TEAEs with Grade 3 or higher (by severity)

TEAEs with Grade 2 or higher

TE treatment-related AEs

TE treatment-related AEs with Grade 3 or higher (by severity)

TE treatment-related AEs with Grade 2 or higher

TE SAEs

TE treatment-related SAEs 

TEAEs leading to premature discontinuation of study drug

TEAEs leading to premature discontinuation of study

TEAEs leading to death (by SOC and PT only)
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 then by PT in descending order of 
total frequency within each SOC. For summarizes by PT only, AEs will be summarized and 
listed by PT in descending order of total frequency. 
In addition, data listings will be provided for the following:

All AEs

All SAEs

All Deaths

 All AEs with severity of Grade 3 or higher

All AEs leading to premature discontinuation of study drug

All AEs leading to premature discontinuation of study
For each listing, whether the event is treatment emergent will be indicated.


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7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Study Drug Related Injection Site Reactions
Additional analysis of AEs will be performed for injection site reaction (ISR) related to study 
drug, which is defined as an AE related to study drug reported as any event within the MedDRA 
HLT of “Injection Site Reactions”. The following summaries will be provided for each SC 
injection visit (eg, Day 1, Week 28) and the overall for subjects in Treatment Groups 1 and 2.

Number of subjects that received SC injection(s) 

Number and percentage of subjects with study drug related ISRs 

Number and percentage of subjects with study drug related ISRs by grade 

Number and percentage of subjects with study drug related ISRs by PT 
The denominator for the percentage calculation for the by visit summary and the overall 
summary will be based on the total number of subjects who receive at least 1 SC injection at the 
visit of interest and the total number of subjects who receive at least 1 SC injection at any 
injection visit, respectively.
Duration of the ISR will also be calculated and summarized. Duration of a given ISR event is 
defined as the ISR stop date minus the ISR onset date plus 1 day. For ISRs with ongoing stop 
date, stop date will be imputed as last study date or data cut date, whichever is the earliest. 
Duration of ISR events in days will be summarized using descriptive statistics. 
A by-subject listing for study drug-related ISRs and the corresponding duration will be provided.
7.1.7.2.
Study Drug Related Injection Site Induration and Nodules
Percentage of ongoing and resolved study drug releated injection site induration will be 
summarized for each SC injection (eg, Day 15, Week 28, and Week 54) and the overall at both 
subject-level and event-level. 
For the subject-level summary, if a subject had more than one injection site indurations, the 
subject will be counted in the “Ongoing” category  unless all study drug releated injection site 
induration events have been resolved. 
For the event-level summary, duration of the resolved events will be summarized using 
descriptive statistics.
Study drug related injection site nodules will be summarized in the same manner as defined for 
study drug releated injection site induration.
A by-subject listing for study drug related injection site induration and nodules and the 
corresponding duration will be provided.


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7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last exposure date for subjects who 
have permanently discontinued study drug, or all available data at the time of the database 
snapshot for subjects who were ongoing at the time of an interim analysis. The analysis will be 
based on values reported in conventional units. When values are below the LOQ, they will be 
listed as such, and the closest imputed value will be used for the purpose of calculating summary 
statistics as specified in Section 3.7. Hemolyzed test results will not be included in the analysis, 
but they will be listed in by-subject laboratory listings.
Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 
Calcium corrected for albumin (mg/dL) = serum calcium (mg/dL) + 0.8 × (4.0 – albumin (g/dL))
Toxicity grading for calcium will be applied based on the corrected values.
Estimated Glomerular Filtration Rate
The following formulae will be used to calculate the estimated glomerular filtration rate using 
Cockcroft-Gault formula (eGFRCG):
eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / (SCr (mg/dL) × 72),
where weight is total body mass in kilograms and SCr is serum creatinine.
Low-Density Lipoprotein
The following formulae will be used to calculate the low-density lipoprotein (LDL) using 
Friedewald formula when cholesterol, high-density lipoprotein(HDL), and triglyceride for a 
given blood drawn are available: 
LDL (mg/dL) = total cholesterol (mg/dL)– HDL (mg/dL) – triglyceride (mg/dL)/5; 
The fourth generation LDL is calculated from above Friedewald formula. The third generation 
LDL is a direct measurement from blood drawn. Both generations of LDL will be listed in the 
listing. Only fourth generation LDL calculated from the Friedewald formula will be used for 
analysis.


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A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events, Version 2.1 dated July 2017, will be flagged in the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for selected laboratory test as follows:

Baseline values 

Values at each postbaseline visit

Change from baseline at each postbaseline visit
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date/time of first dose of study drug. Change from baseline to a postbaseline visit will be defined 
as the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and maximum 
values will be displayed to the reported number of digits; SD values will be displayed to the 
reported number of digits plus 1.
Median (Q1, Q3) of the change from baseline values for these selected laboratory tests will be 
plotted by treatment group and visit.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
7.2.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 
dated July 2017, will be used to assign toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (i.e., increased, decreased) will be presented separately. 
For triglycerides, LDL (4th generation), and cholesterol, the toxicity grading scale is for fasting 
test values, so nonfasting lipid results (or lipid results without a known fasting status) will not be 
graded or summarized by toxicity grades.


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7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline visit, up to last exposure date for subjects who 
permanently discontinued study drug, or the last available date in the database snapshot for 
subjects who were still on treatment at the time of an interim analysis. If the relevant baseline 
laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame 
specified above will be considered treatment emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
subjects in the study with the given response at baseline and each scheduled postbaseline visit.
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Graded laboratory abnormalities

Grade 3 or 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values. 
A by-subject listing of treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities, respectively, will be provided by subject ID number and 
visit in chronological order. This listing will include all test results that were collected 
throughout the study for the lab test of interest, with all applicable severity grades and abnormal 
flags displayed.
7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI and vital signs 
as follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose date of study drug. Change from baseline to a postbaseline visit will be defined as 
the postbaseline value minus the baseline value.


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In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. Body weight, height, and BMI will be included in the vital signs listing, if 
space permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary. The WHO preferred name and drug 
code will be attached to the clinical database.
7.4.1.
Nonstudy Drug Antiretroviral Medications
Any nonstudy drug ARV medications are defined as any ARV medications taken prior to, 
during, or after the study (if collected). All nonstudy drug ARV medications will be listed. No 
inferential statistics will be provided.
7.4.2.
Concomitant Non-ARV Medications
Concomitant non-ARV medications are defined as non-ARV medications taken while a subject 
took study drug. Use of concomitant medications from Study Day 1 up to the last exposure date 
will be summarized (number and percentage of subjects) by treatment group, WHO drug class 
and preferred name. Multiple drug use (by preferred name) will be counted only once per 
subject. The summary will be sorted alphabetically by drug class and then by decreasing total 
frequency within a class. For drugs with the same frequency, sorting will be done alphabetically.
If the start or stop date of non-ARV medications is incomplete, the month and year (or year 
alone, if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARVs are concomitant or not. The medication is concomitant if the month and year of the 
start or stop (or year of the start or stop, if month is not recorded) of the medication does not 
meet either of the following criteria:

The month and year of start of the medication is after the last exposure date

The month and year of stop of the medication is before the first dose date of study drug
If the start and stop date of non-ARV medications are complete, the start date is not after last 
exposure date and the stop date is not before first dose date, or the non-ARV medications are 
marked as ongoing and start date is on or before last exposure date, the non-ARV medications 
are concomitant.
Summaries of non-ARV concomitant medications will be based on the Safety Analysis Set. No 
formal statistical testing is planned. A by-subject listing for all non-ARV concomitant 
medications will be listed and sorted by subject ID number and administration date in 
chronological order.


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7.5.
Electrocardiogram Results
7.5.1.
Investigator Electrocardiogram Assessment
The investigators’ assessment of ECG results (normal; abnormal, not clinically significant; 
abnormal, clinically significant) are collected at screening only. A by-subject listing for ECG 
assessment results will be provided by subject ID number.
7.6.
Other Safety Measures
A data listing will be provided for subjects experiencing pregnancy and subjects using/misusing 
any substances (eg, illicit drug) during the study, respectively. Physical examination was not 
collected in the eCRF. Therefore, it will not be included in the analysis.
7.7.
Subject Subgroup for Safety Endpoints
Incidence of all treatment-emergent AEs will be repeated within each subgroup defined in 
Section 3.4.2 using the Safety Analysis set. No formal statistical testing is planned.
7.8.
Changes From Protocol-Specified Safety Analyses
No change from protocol-specified safety analyses is planned.


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PHARMACOKINETIC (PK) ANALYSES 
8.1. 
PK Sample Collection 
Version 1.0 
Blood samples will be collected to detennine PK (and metabolites, if applicable) in plasma at the 
following timepoints: 
For Treatment Groups 1 and 2: 
Plasma PK sampling will occm relative to dosing of LEN at the following time points for all 
subjects: 
• 
Days 1, 2, and 8: 
-
Predose (within 30 minutes of dosing) 
-
A single timed PK sample between 1 and 6 homs postdose 
I 
• 
At Day 15 and at all visits with SC LEN injections: A single predose PK sample will be 
collected 
• 
Staiiing at Week 4 visit, at all visits without SC LEN injections: A single anytime PK sample 
will be collected. 
I 
I 
I 
For Treatment Group 3: 
• 
Staiiing at Day 1 visit, a single anytime PK sample will be collected at all study visits 
I 
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For Treatment Group 4:

Starting at Day 1 visit, a single anytime PK sample will be collected at all study visits.
Only plasma 
 samples collected through Week 54 last patient last visit (LPLV) 
date were analyzed and included in the Week 54 interim analysis.
8.2.
PK Analyses Related to Intensive PK Sampling
8.2.1.
Estimation of PK Parameters
PK parameters will be estimated using Phoenix WinNonlin® software using standard 
noncompartmental methods. The linear/log trapezoidal rule will be used in conjunction with the 
appropriate noncompartmental model, with input values for dose level, dosing time, 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 0.
For area under the curve (AUC), samples BLQ of the bioanalytical assays occurring prior to the 
achievement of the first quantifiable concentration will be assigned a concentration value of 0 to 
prevent overestimation of the initial AUC. Samples that are BLQ at all other time points will be 
treated as missing data in WinNonlin. The nominal time point for a key event or dosing 
interval (τ) may be used to permit direct calculation of AUC over specific time intervals. The 
appropriateness of this approach will be assessed by the PK scientist on a profile-by-profile 
basis.
Pharmacokinetic parameters such as AUCtau, λz and t1/2 are dependent on an accurate estimation 
of the terminal elimination phase of drug. The appropriateness of calculating these parameters 
will be evaluated upon inspection of PK data on a profile-by-profile basis by the PK scientist.
8.2.2.
PK Parameters
CCI
CCI


Lenacapavir 
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Statistical Analysis Plan - Week 54 Interim Analysis 
Table 8-2. 
PK Parameters for Each Analyte 
Analyte 
Parameters 
TAF 
AUCtau, AUC1as,, CL/F, t112, Az, V,IF, Cmax, Tmax, Ctast, T1as,, C,au 
TAF Week 38 
AUC1ast,ss, t112, /cz, Cmax,ss, Tmax,ss, C1as1,ss, Ttast,ss, AUCtau,ss, C,au,ss 
TFV 
AUCtau, AUC1as,, t112, Az, Cmax, Tmax, C1ash T1as1, Ctau 
BIC Week 38 
AUC1ast,ss, t112, /cz, Cmax,ss, Tmax,ss, C1as1,ss, Ttast,ss, AUCtau,ss, C,au,ss 
TFV-DP 
AUC1ast, Cmax, Tmax, Clash T1as, 
8.2.3. 
Statistical Analysis Methods 
Version 1.0 
I 
Plasma concentration for LEN, TAF, TFV, BIC, and TFV-DP will be li~d 
summarized b nominal time oint for subjects in the PK Analysis Set,_ 
by treatment group and analyte. 
arameters estimated for TAF, BIC, and TFV will be listed for all sub'ects. 
Summa1y statistics (n, mean, SD, coefficient of variation [%CV], median, min, max, Ql , and 
Q3) will be presented for both individual subject concentration data by time point and individual 
subject PK parameters by treatment group and analyte. Moreover, the geometric mean, 95% CI, 
and the mean and SD of the natural log-transfo1med values will be presented for individual 
subject PK parameter data. 
Individual concentration data listings and summaries will include all subjects with concentration 
data. The sample size for each time point will be based on the number of subjects with 
nonmissing concentration data at that time point. The number of subjects with concentration 
BLQ will be presented for each time point. For summaiy statistics, BLQ values will be treated as 
0 at predose and one-half of the lower LOQ for postdose time points. 
Individual PK pai·ameter data listings and summaries will include all subjects for whom PK 
pai·ameter(s) can be derived. The sample size for each PK pai·ameter will be based on the number 
of subjects with nonmissing data for that PK pai·ameter. 
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The following tables will be provided for each analyte by treatment group and visit:

Individual subject concentration data and summary statistics

Individual subject plasma PK parameters and summary statistics
The following figures may be provided for each analyte by treatment group:

Mean (± SD) concentration data versus time (on linear and semilogarithmic scales)

Median (Q1, Q3) concentration data versus time (on linear and semilogarithmic scales)
Individual, mean, and median postdose concentration values that are ≤ LOQ will not be 
displayed in the figures and remaining points connected.
PK sampling details by subject, including procedures, differences in scheduled and actual draw 
times, and sample age will be provided in listings.
The molecular weight of TFV-DP (447.17 g/mol) and the density of 5000 million cells/mL will 
be used in the conversion of concentration from ng/million cells to µmol/L; where the value in 
ng/million cells * (5000/447.17) results in the value in µmol/L or µM.  
𝑛𝑔
𝑚𝑖𝑙𝑙𝑖𝑜𝑛 𝑐𝑒𝑙𝑙𝑠×
1 𝑛𝑚𝑜𝑙
447.17 𝑛𝑔×
1 µ𝒎𝒐𝒍
1000 𝑛𝑚𝑜𝑙× 5000 𝑚𝑖𝑙𝑙𝑖𝑜𝑛 𝑐𝑒𝑙𝑙𝑠
1 𝑚𝐿
× 1000 𝑚𝐿
𝑳
=  µ𝑚𝑜𝑙
𝐿
=  µ𝑀
8.2.4.
Sensitivity Analyses
Sensitivity analysis may be conducted for the key PK analyses if the PK scientist identifies PK 
data as questionable. The sensitivity analysis will exclude specific data from analyses, if 
appropriate. If a sensitivity analysis is deemed necessary, a listing of the PK parameter(s) data 
being excluded, with associated reason(s) provided by the PK scientist, will be generated.
8.2.5.
Changes from Protocol-Specified Pharmacokinetic Analyses
No change from the protocol-specified PK analyses is planned.
CCII 


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9.
REFERENCES
Koch GG, Carr GJ, Amara IA, Stokes ME, Uryniak TJ. Categorical Data Analysis. Chapter 13 in 
Berry, D.A. (ed.).  Statistical Methodology in the Pharmaceutical Sciences. New 
York: Marcel Dekker, Inc., 1989:pp. 414-21. 
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
nQuery Advisor(R) Version 7.0. Statistical Solutions, Cork, Ireland.
Phoenix WinNonlin® 7.0 Pharsigh Corporation, Princeton, NJ, 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
Screeninga
Day 
1b
Day 
2
Day 
8
Day 
15
Every 
6 weeks 
from 
Week 4 
to 
Week 28 
±2 Days
Week 38 
±2 Days
Week 54 
±2 Days
Week 64 
±2 Days
Week 80 
±2 Days
Post 
Week 80 
Visitsc 
±6 Days
30, 90, 
180 Day 
Follow-Upd
Early 
Terminatione
Written Informed 
Consent
X
Obtain demographic 
information
X
Medical History 
X
Complete Physical 
Examination
X
X
X
Xf
X
X
X
Symptom-Directed 
Physical 
Examination
X
X
Xg
X
X
X
X
Vital Signsh 
(including weight)
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG 
(supine)
X
Height
X
Hematologyi, 
Chemistryj, Lipid 
panelk, Urinalysis 
and Urine 
Chemistryl, CD4+ 
Cell Count
X
X
X
X
X
X
X
X
X
X
X
X
X
CCI


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Statistical Analysis Plan - Week 54 Interim Analysis 
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Eveiy 
6weeks 
ti'Om 
Week4 
Post 
to 
Week8() 
30, 90, 
Day 
Day 
Week28 
Week38 
Week54 
Week64 
Week8() 
Visits' 
18()Day 
Early 
Scr'eel1ing" 
lb 
15 
±2 Days 
±2Days 
±2Days 
±2 Days 
±2 Days 
±6Days 
Follow-Upd 
Te11nination• 
Urine Storage 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Sample 
Serum Pregnancy 
X 
X 
Test"' 
SeiumFSH" 
X 
Urine Pregnancy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Test"' 
HBV,HCVTesting 
X 
IDV-1 Genotyping 
X 
Phenotyping 
PlasmaIDV-1 RNA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma Storage 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Sample 
PKPlasma 
X 
X 
X 
X 
X 
X 
X 
X 
Dispensation• 
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Screeninga
Day 
1b
Day 
2
Day 
8
Day 
15
Every 
6 weeks 
from 
Week 4 
to 
Week 28 
±2 Days
Week 38 
±2 Days
Week 54 
±2 Days
Week 64 
±2 Days
Week 80 
±2 Days
Post 
Week 80 
Visitsc 
±6 Days
30, 90, 
180 Day 
Follow-Upd
Early 
Terminatione
Subcutaneous 
GS-6207 
Administrationt
X
X
X
X
X
F/TAF Dispensationu
X
X
X
X
X
X
X
TAF Dispensationv
X
X
X
X
X
X
Bictegravir 
Dispensationw
X
X
X
X
X
X
B/F/TAF 
Dispensationx
X
X
X
X
X
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
QoL Administrationy
X
X
X
X
X
Injection Site 
Reaction Assessment 
Worksheetz
X
X
X
X
Adverse Events/ 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Screening evaluations must be completed within 30 days prior to Day 1
b
Day 1 tests and procedures must be completed prior to administration of the dose of study drug. Participants must begin dosing on the same day as Day 1
c
Assessments will be performed post Week 80 (Week 90, Week 106, Week 116, Week 132, Week 142) and will continue to alternate between every 10 weeks and every 
16 weeks with the visit window ±6 days.
d
Participants may be required to return to the clinic for a 30, 90 and 180-Day Follow-Up Visit after Early Termination visit. 
e
Within 72 hours of permanently discontinuing study. Counsel participant regarding the importance of continuing a complete ARV therapy in accordance to standard of care 
and refer participant to an appropriate HIV treatment facility.
f
Complete physical exam is only required at Week 28
g
Symptom directed physical to be completed at Weeks 4, 10, 16, and 22, as necessary
h
Vital signs – blood pressure, pulse, respiration rate, temperature, and weight
i
Hematology: CBC with differential and platelet count
CCI


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Statistical Analysis Plan - Week 54 Interim Analysis 
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Chemistries: Alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and indirect bilimbin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, lipase, magnesium, phosphoms, potassium, sodium, and uric acid. eGFR according to the Cockcroft-Gault formula 
k 
Fasting is not required for the lipid panel 
1 
Urinalysis and Urine Chemistry: including color & clarity, specific gravity, pH, glucose, ketones, bilimbin, m·obilinogen, blood, nitrite, leukocyte esterase and microscopic 
(if microscopic elements are seen), mine protein, albumin, creatinine, phosphate, calcium, magnesium and uric acid 
m 
Women will have a serum test pe1fo1med at Screening. U,ine pregnancy test will only be done for women of childbea,ing potential. In Treatment Groups 1 and 2, mine 
pregnancy tests should be confomed to be negative prior to subcutaneous GS-6207 administration. If any pregnancy test is positive, study dmg should be immediately 
intem1pted, and participant should come to the site for serum pregnancy test. 
n 
FSH test is required for women who are <54 years old and have stopped menstmating for :C:: 12 months but do not have documentation of ovarian honuonal failure. 
o 
PK collection: For Treatment Groups 1 and 2, plasma PK sam lino will occur relative to dosing ofGS-6207 at Da s 1, 2 and 8 redose (within 30 minutes of dosing) and a 
single timed PK sample between 1 and 6 hom·s postdose. 
At Day 15 and all visits with SC 
GS-6207, a single predose PK sample will be collected. tartrng at 
sample will be collected. PK sampling 
I' 
I 
I 
will continue at visits past Week 80. 
For Treatment Grou s 3 and 4 a,tici ants sta,ting at Da 1 a single an 
s 
Treatment Group 1 an 2 ora GS-6207 ea rn at Day 1, Day 2 an Day 8. Treatment Group 3 will receive oral GS-6207 lead in at Days 1 and 2 and will begin oral daily 
GS-6207 at Day 3. 
Treatment Group 1 and 2 Subcutaneous administration at Day 15 and every 26 weeks 
u 
Treatment Group 1, 2, and 3 F/TAF once daily for 28 weeks sta,ting at Day 1. Treatment Group 3 participants will continue F/TAF until study completion. 
v 
Treatment Group 1 daily oral TAF to be initiated at Week 28 
w 
Treatment Group 2 daily oral BIC to be initiated at Week 28 
x 
Treatment Group 4 daily oral B/F/TAF 
y 
Prior to completion of other study procedm·es, pa,ticipants will complete HIVTSQ12, HIVDQoL, and EQ-ED-5L at Day 1 (except HIVTSQ12), Day 15 (HIVTSQ12 only), 
Week 4, Week 28, Week 54, Week 80. Injection Acceptability Scale and Numeric Pain Rating Scale to be completed at Day 15, Weeks 28, 54 and 80 (for Treatment Groups 1 
and 2 pa,ticipants only) after SC GS-6207 administration and completion of other study procedures. 
z 
Provide Injection Site Reaction Assessment Worksheet and instmct the participants to measure and report injection site reactions following the administration of the 
subcutaneous injections (for Treatment Group 1 and 2 pa,ticipants only) 
CONFIDENTIAL 
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Lenacapavir 
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Statistical Analysis Plan - Week 54 Interim Analysis 
Version 1.0 
Appendix 2. 
Flowchart of US FDA-defined Snapshot Algorithm(for Nai've Trial) 
The following flowchaii for US FDA-defined snapshot algorithm is based on the US FDA 
Guidance on Human Immunodeficiency Virns-1 Infection: Developing Antiretroviral Drngs for 
Treatment {U. S. Depa1iment of Health and Human Services 2015} 
Yes 
Is there at least 1 on-
treatment* HIV-1 RNA 
collected in the Snapshot 
window? 
Is the last available on-treatment* 
HIV-1 RNA in the Snapshot 
window < 50 copies/mL? 
Yes 
No 
Is study dmg prematurely 
discontinued on or prior to the 
upper limit of the Snapshot 
window? 
Yes 
Is discontinuation of the study 
dmg due to Lack of Efficacy? 
HIV-1 RNA < 
50 copies/mL 
HIV-1 RNA ~ 
50 copies/mL 
No 
No 
Is discontinuation of the study 
ckug due to AE/Death? 
Is the last available 0 11-
treatment* HIV-1 RNA < 
50 copies/mL 
Yes 
No Virologic Data: 
Discontinued Study Drug 
Due to Other Reasons and 
Last HIV-1 RNA < 50 
copies/mL 
Yes 
No Virologic Data: 
Discontinued Study 
Drug Due to AE/Death 
No 
No Virologic Data: 
Missing Data dmi ng 
Window but on Study 
Drug 
* On-treatment data include all 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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Appendix 3.
Programming Specification
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
a) AGE (years) is calculated from the number of days between the DOB and Study Day 1,
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
AGE = the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened subjects refer to all subjects who are screened (ie, with non-missing screening 
date) and have a screening number. For summaries the same subject is counted only once.
3) Screen failure subjects are the subjects who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the subject was consent to.
4) Subjects in the randomized analysis set are defined as subjects randomized into the study. 
IXRSRAND is the source to determine whether the subject is randomized (ie, subject with 
non-missing RGMNDTN in the IXRSRAND dataset), and confirmed by the eCRF ENROLL 
dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) is derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if subject 
took at least 1 dose of study drug and assigned as blank if the subject was never dosed.
6) In the disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.
7) Body mass index (BMI) 
BMI will be calculated only at baseline as follows:
BMI = (weight [kg]) / (height [meters]2)
Baseline height and weight will be used for this calculation if available.


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8) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
CMH test for nominal variable (Y), the p-value from the general association test should be 
used for nominal variables:
proc freq;
tables trt * Y /cmh; /*general association test*/
run;
CMH test for ordinal variable (Y), the p-value from the row mean score test should be used 
for ordinal variables:
proc freq;
tables trt * Y / cmh2 ; /*row mean score test*/
run;
Kruskal-Wallis test for continuous variable (Y):
proc npar1way wilcoxon;
class trt; 
var Y;
run;
9) For race and ethnicity, “Not Permitted”, “Missing”, or “Other” will be excluded from 
percentage calculation and also excluded for p-value generation for categorical data analysis 
(eg, CMH test or Kruskal-Wallis test).
10) Study Day 1, Last Dose Date and Last Exposure Date
a) All the key dates were defined in Section 3.8.1. 
11) Study Day 1 and Last Dose Date
a) All the key dates were defined in Section 3.8.1.
b) Study Day 1 is defined as the earliest of the dose start dates from any Study Drug 
Administration eCRF (ie, EX, EX_ARV or EX_IV). 
c) Last Dose Date is defined for subjects who prematurely discontinued study drug 
according to Study Drug Completion eCRF(ie, SDRGCOMP). 
i)
For subjects who receive SC injection(ie, A subject has data in EX_IV.), the last dose 
date is defined as the latest nonmissing end date of the study drug used with LEN 
(ie, the last dose date in EX_ARV).
ii) For subjects who do not receive SC injection(ie, A subject has no data in EX_IV.), 
the last dose date is defined as the earliest of the last dose date of any study drug 
(ie, the earliest of last dose date in EX or EX_ARV).


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d) Study drug administration: Oral reload will be recorded as an “Unscheduled” visit in the 
Study Drug Administration eCRF. Subjects with oral reload prior to the 1st dose of SC 
have “Unscheduled” dosing visits occurred prior to Day 15 visit. Subjects who received a 
total of 5 tablets of LEN (300 mg) (ie, 2 x 300 mg LEN tablets each for the first 2 days 
and 1 x 300 mg LEN tablet on the 8th day) prior to “Unscheduled” dosing visits followed 
by Day 15 visit will be classified as oral reload due to missing scheduled SC dosing. 
Otherwise, subjects will be classified as oral reload due to missing scheduled oral dosing 
visit.
12) Adherence to QD Study Drug(s)
a) Adherence based on 1 study drug(Treatment Groups 1, 2, and 4):
Adherence (%) =  100 ×
𝑇𝑜𝑡𝑎𝑙 No. of pills taken
Total No. of pills prescribed
=  100 ×
∑No. of pills taken at each dispensing period  for each study drug[1]
∑No. of pills prescribed at each dispensing period for each study drug[2]
b) Adherence based on 2 study drugs(Treatment Group 3):






[2]
]1[
drug
each 
for 
period
dispensing
each 
at 
prescribed
pills
of
No.
drug
each 
for 
period
dispensing
each 
at 
 taken 
pills
of
No.
100
prescribed
pills
of
No.
Total
 taken
pills
of
No.
Total
100
(%)
Adherence
13) Efficacy Analysis
a) For categorical efficacy response (eg, Subjects with HIV-1 RNA < 50 copies/mL as 
determined by US FDA-defined snapshot algorithm, M=F, or M=E Analyses): the 
proportion difference between LEN-containing regimen groups (Treatment Groups 1 
to 3) and the B/F/TAF group (Treatment Group 4) and its 95% CIs are calculated based 
on the MH proportion adjusted by baseline HIV-1 RNA stratum ( 100,000 vs. 
 100,000 copies/mL) (see SAP Section 6.2 and 6.3 for details). The following SAS code 
will be used to compute p-value, where brnac is the baseline HIV-1 RNA stratum, trtgrp 
is the treatment, and response is the categorical efficacy response.
proc freq data=adeff;
tables brnac*trtgrp*response/cmh; /*p value from general 
association*/
run;


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b) All the ANOVA model for continuous efficacy variable (eg, CD4+): The differences in 
changes from baseline in log10 HIV-1 RNA and CD4+ cell count between treatment 
groups and the associated 95% CI will be constructed using an ANOVA, including 
baseline HIV-1 RNA stratum brnac, region stratum region, and treatment trtgrp as fixed 
effects in the model.
proc glm data=adeff;
class brnac region trtgrp;
model CD4=brnac region trtgrp;
lsmeans trtgrp /alpha=0.05 cl pdiff;
run;
14) Listing for US FDA-defined snapshot outcome:
In addition flag the values of HIV-1 RNA < 50 or ≥ 50 copies/mL for virologic outcomes.
Flag the last available HIV-1 RNA value while on treatment for the following categories:
a) HIV-1 RNA ≥ 50 copies/mL - Discontinued Study Drug Due to Other Reasons and 
Last Available HIV-1 RNA ≥ 50 copies/mL
b) No virologic Data - Discontinued Study Drug Due to Other Reasons and Last 
Available HIV-1 RNA < 50 copies/mL
15) Injection site reaction (ISR)
a) To summarize ISRs by injection visit, each study drug related ISR will be associated with 
one injection visit (eg, Day 15 SC injection, Week 28 SC Injection, Week 54 SC 
injection) based on the start date of the ISR. If the start date of the ISR is on or after a 
given injection visit date and prior to the next injection visit date, if available, the ISR 
will be associated with that injection visit.
b) For ISR summarized by PT:
i)
For the overall summary (ie, subjects received at least one injection), multiple ISRs 
with the same PT will only be counted once per subject for each PT.
ii) For by visit summary (ie, subjects received injection for a given injection visit), 
multiple ISRs associated with the injection visit of interest with the same PT will only 
be counted once per subject for each PT.
c) For ISR summarized by grade:
i)
For the overall summary (ie, subjects received at least one injection), the most severe 
grade based on all ISRs will be used.
ii) For by visit summary (subjects received injection for a given injection visit), the most 
severe grade from all ISRs associated with the injection visit of interest will be used.


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16) Concomitant nonstudy-drug ARV medications (ie, ARV medications other than study drug 
that are taken on or after first dose date) will be flagged in “Antiviral Medication” listings.
17) Graded Laboratory Abnormalities Summary 
18) The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Hemoglobin (Hb)
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
Hematology
WBC
Decrease
WBC (Decreased)
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
GGT
Increase
GGT (Increased)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Fasting)
Decrease
Serum Glucose (Fasting, Hypoglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Decrease
Serum Glucose (Nonfasting, Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Urea Nitrogen (BUN)
Increase
Urea Nitrogen (Increased)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Chemistry
Uric Acid
Decrease
Uric Acid (Hypouricemia)
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine Protein
Increase
Urine Protein (Proteinuria)
Urinalysis
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative)


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Page 58
26 October 2021
19) Clarification for “Pharmacokinetic Sampling Details and Concentrations” listings
“Sample age” will be added in this listing, defined as the duration in days between 
sample collection date and assay date, ie, sample age = assay date – sample collection 
date + 1. 
Scheduled PK sampling time for intensive PK samples at predose is 5 mins prior to 
dosing time. 
SAMTIME is calculated as the duration in hours between the dosing time before sample 
collected and sample collection time, except for intensive PK samples at predose. 
SAMTIME for intensive PK samples at predose is calculated as the duration in hours 
between the dose time on the same day (ie, right after the predose sample collection) and 
sample collection time.


GS-US-200-4334-Week54-SAP-v1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
26-Oct-2021
19:20:03
Clinical Pharmacology
eSigned
27-Oct-2021
02:47:41
Clinical Research eSigned
27-Oct-2021
05:36:46
PPD
PPD
PPD

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 Ra n d o mize d, O pe n La bel, Acti ve C o ntr olle d St u d y 
E val uati n g t he Safet y a n d Efficac y of L o n g-acti n g Ca psi d 
I n hi bit or G S- 6 2 0 7 i n C o m bi nati o n wit h Ot her A ntiretr o viral 
A ge nts i n Pe o ple Li vi n g wit h HI V
N a me of Test Dr u g: 
Le naca pa vir ( L E N; G S- 6 2 0 7)   
St u d y N u m ber:
G S- U S- 2 0 0- 4 3 3 4
Pr ot oc ol Versi o n ( D ate): 
A me n d me nt 4 ( 0 4 Fe br uar y 2 0 2 2)
A n al ysis T y pe:
Fi nal A nal ysis
A n al ysis Pl a n Versi o n: 
Versi o n 1. 0
A n al ysis Pl a n D ate: 
1 7 Ja n uar y 2 0 2 4
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
(r J GI L E A U 


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2
1 7 Ja n uar y 2 0 2 4
T A B L E O F C O N T E N T S
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 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........................................................................................................................................ 8
1. 2.  
St u d y Desi g n ............................................................................................................................................. 8
1. 3.  
Sa m ple Size a n d P o wer........................................................................................................................... 1 1
2.  
T Y P E O F P L A N N E D A N A L Y SI S...................................................................................................................... 1 2
2. 1.  
I nteri m A nal yses...................................................................................................................................... 1 2
2. 1. 1.   
D M C A nal ysis....................................................................................................................... 1 2
2. 1. 2.   
Wee k 2 8 I nteri m A nal ysis..................................................................................................... 1 2
2. 1. 3.   
Wee k 8 0 I nteri m A nal ysis..................................................................................................... 1 2
2. 2.  
Pri mar y A nal ysis..................................................................................................................................... 1 2
2. 3.  
Fi nal A nal ysis.......................................................................................................................................... 1 2
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 3
3. 1.   
A nal ysis Sets ........................................................................................................................................... 1 3
3. 1. 1.   
All Ra n d o mize d A nal ysis Set................................................................................................ 1 3
3. 1. 2.  
F ull A nal ysis Set.................................................................................................................... 1 3
3. 1. 3.  
Safet y A nal ysis Set................................................................................................................ 1 3
3. 1. 4.  
P har mac o ki netic A nal ysis Set............................................................................................... 1 4
3. 2.  
Partici pa nt Gr o u pi n g ............................................................................................................................... 1 4
3. 3.  
Strata a n d C o variates............................................................................................................................... 1 4
3. 4.  
E xa mi nati o n of Partici pa nt S u b gr o u ps.................................................................................................... 1 4
3. 4. 1.  
Partici pa nt S u b gr o u ps f or Safet y A nal yses........................................................................... 1 4
3. 5.   
M ulti ple C o m paris o ns............................................................................................................................. 1 5
3. 6.   
Missi n g Data a n d O utliers....................................................................................................................... 1 5
3. 6. 1.   
Missi n g Data.......................................................................................................................... 1 5
3. 6. 2.   
O utliers.................................................................................................................................. 1 5
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 5
3. 8.   
A nal ysis Visit Wi n d o ws.......................................................................................................................... 1 7
3. 8. 1.   
Defi niti o n of St u d y Da y ........................................................................................................ 1 7
3. 8. 2.   
A nal ysis Visit Wi n d o ws........................................................................................................ 1 8
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................................................................................................................................. 1 9
4.  
P A R TI CI P A N T  DI S P O SI TI O N ......................................................................................................................... 2 1
4. 1.  
Partici pa nt E nr oll me nt a n d Dis p ositi o n................................................................................................... 2 1
4. 2.  
St u d y Dr u g A d mi nistrati o n a n d A d here nce............................................................................................ 2 2
4. 2. 1.  
St u d y Dr u g A d mi nistrati o n ................................................................................................... 2 2
4. 2. 2.  
St u d y Dr u g A d here nce.......................................................................................................... 2 3
4. 2. 2. 1.   
A d here nce t o S C L E N..................................................................................... 2 3
4. 2. 2. 2.   
A d here nce t o O nce Dail y St u d y Dr u g(s)......................................................... 2 3
4. 3.  
St u d y D urati o n......................................................................................................................................... 2 5
4. 4.  
Pr ot oc ol De viati o ns................................................................................................................................. 2 5
5.  
B A S E LI N E C H A R A C T E RI S TI C S..................................................................................................................... 2 6


L e n a c a p av ir 
G S- U S- 2 0 0 -4 3 3 4 
St a tisti c al A n a ly si s  Pl a n  - Fi n a l A n a l ysi s 
V e rsio n  1. 0 
5. 1.  
D e m o gr a p hi c s  a n d B as eli n e  C h ar a c t eristics  ........................................................................................... 2 6 
5. 2.  
Ot h e r  Bas eli n e  C h ar a c t eristi cs  ................................................................................................................ 2 6 
5. 3.  
M e di c a l Hist o 1 y  ....................................................................................................................................... 2 6 
6.  
E F F IC A C Y  A N A L Y S E S  ..................................................................................................................................... 2 7 
6. 1. 
Pri 1 nr u y  Effi c a c y  E n d p oi n t ...................................................................................................................... 2 7 
6. 2.  
S e c o n dr u y  Effi c a c y  E n d p oi n ts ................................................................................................................ 2 7 
6. 2. 1.  
D efi ni ti o n of th e S e c o n d a 1y  Effi c a c y  E n d p oi nts  ................................................................... 2 7 
6. 2. 2.  
Pr i mr u y A n al y s i s f or t h e S e c o n d a 1 y  E n d p oi nt s ..................................................................... 2 7 
6. 2. 3.  
S e c o n dr u  A n al  s i s f or t h e S e c o n d a 1  E n d  oi nt s ................................................................. 2 7 
6. 4.  
C h a n g e s  fr o m P r ot o c ol-S p e cifi e d  Effi c a c y  A n al y s i s .............................................................................. 2 9 
7.  
S A F E T Y  A N A L Y S E S  ......................................................................................................................................... 3 0 
7 . 1.  
A d v ers e  E v e nt s  a n d  D e a th s ..................................................................................................................... 3 0 
7 . 1. 1.  
A d v ers e  E v e nt  Di c ti o n a 1 y ..................................................................................................... 3 0 
7. 1. 2.  
A d v ers e  E v e nt  S e v erit y ......................................................................................................... 3 0 
7. 1. 3 .  
R el ati o ns hi p of A d v er s e  E v e nt s t o  St u d y D m g ..................................................................... 3 0 
7 . 1. 4 .  
S eri o u s  A d v ers e  E v e nt s ......................................................................................................... 3 0 
7. 1. 5.    
Tr e ati n e nt -E m e rg e n t A d v er s e E v e nt s .................................................................................... 3 0 
7 . 1. 5. 1.  
D efi niti o n of Tr e ati n e nt -E m e rg e nt A d v er s e  E v e n t s ........................................ 3 0 
7 . 1. 5. 2.  
I n c o 1 n plet e D at es  ............................................................................................. 3 1 
7. 1. 6.  
S u m m a ri es of A d v er s e E v e nt s  a n d D e a t hs ............................................................................ 3 1 
7 . 1. 6. 1.  
S u m m ari e s of A E i n ci d e n c e i n C o m bi n e d  S e v er it y Gr a d e 
S u b s et s ............................................................................................................. 3 1 
7. 1. 7.  
A d di ti o n al A n a l ysi s of A d v er s e  E v e n t s ................................................................................ 3 3 
7 . 1.7 . 1.  
St u d y D m g R el at e d I nj e cti o n  Sit e  R e a cti o n s  .................................................. 3 3 
7 . 1.7 . 2.  
St u d y D m g R el at e d I nj e cti o n  Sit e  I n d m ati o n a n d N o d ul e s  ............................ 3 3 
7 . 2.  
L a b or at o 1y   E v al u ati o n s  ........................................................................................................................... 3 4 
7. 2. 1.  
S u m m ari e s of N u m eri c  L a b or at 0 1 y  R e s ul t s .......................................................................... 3 5 
7. 2. 2.    
Gr a d e d  L a b or at o 1 y V a lu e s  .................................................................................................... 3 5 
7 . 2. 2. 1.  
Tr e ati n e nt -E m e rg e nt  L a b o r at0 1 y A b n o n n aliti e s  ............................................. 3 5 
7 . 2. 2. 2.  
S m n m ari e s of L a b or a t0 1 y A b n o n n a liti es  ........................................................ 3 6 
7 . 3.  
B o d y  W ei g ht  a n d  Vi tal Si g n s  .................................................................................................................. 3 6 
7 . 4.  
Pri o r a n d  C o n c oi nit a nt  M e di c a ti o ns ........................................................................................................ 3 7 
7 . 4. 1.    
No n s t u d y D m g A nt ireti· ov ir al M e di c a ti o ns ........................................................................... 3 7 
7 . 4. 2.  
C o n c o 1 nit a nt  N o n -A R V  M e di c ati o ns  .................................................................................... 3 7 
7 . 5.  
El e ct ro cr u·di o gr a 1 n  R e s ult s ....................................................................................................................... 3 8 
7 . 5 . 1.  
I nv e sti g at or  El e cti· o c ar di o g ra m  A s s e ssm e nt  ......................................................................... 3 8 
7 . 6.  
Ot h e r S af et y  M e a sm e s  ............................................................................................................................ 3 8 
7. 7.  
P arti ci p a n t S u b gr o u p  f or S af et y  E n d p oi nt s ............................................................................................. 3 8 
7 . 8.  
C h a n g e s Fr o m  P r oto c ol -S p e cifi e d  S af et y  A n al y sis  ................................................................................ 3 8 
8.   P H A R M A C O KI N E T I C ( P K) A N A L Y S E S  ......................................................................................................... 3 9 
8. 1. 
P K S a m p l e C o lle cti o n  ............................................................................................................................. 3 9 
8. 2. 
P K A n a l ys es R e lat e d  t o  P K S a m pli n g .................................................................................................... . 4 0 
8. 2. 1.   
St ati sti c al  A n al ysi s  M et h o d s  ................................................................................................ . 4 0 
8. 2. 2.  
S e n s ativ e  A n a ly si s ................................................................................................................ . 4 1 
8. 3.  
C h a n g e s  Fr o m  P r oto c ol -S p e cifi e d  P K  A n a ly si s ..................................................................................... . 4 1 
9.  
R E F E R E N C E S  .................................................................................................................................................... . 4 2 
1 0 .  S O F T W A R E ........................................................................................................................................................ . 4 3 
C O N FI D E N TI A L 
P a g e 3 
1 7  J a n u a 1 y 2 0 2 4 


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4
1 7 Ja n uar y 2 0 2 4
1 1. 
S A P R E VI SI O N................................................................................................................................................... 4 4
1 2. 
A P P E N DI C E S...................................................................................................................................................... 4 5
LI S T O F I N- T E X T T A B L E S
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, Li pi d Pa nel, Uri nal ysis, Uri ne C he mistr y, Uri ne Pre g na nc y La b orat or y 
Tests, Vital Si g ns, a n d Wei g ht f or t he L E N-c o ntai ni n g Re gi me n Gr o u ps 
( Treat me nt Gr o u ps 1- 3)........................................................................................................... 1 8
Ta ble 3- 2.   
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, Li pi d Pa nel, Uri nal ysis, Uri ne C he mistr y, Uri ne Pre g na nc y La b orat or y 
Tests, Vital Si g ns, a n d Wei g ht f or t he B/ F/ T A F Gr o u p ( Treat me nt Gr o u p 4)........................ 1 9


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 5
1 7 Ja n uar y 2 0 2 4
LI S T O F A B B R E VI A TI O N S
A E
a d verse e ve nt
A L T
ala ni ne a mi n otra nsferase
A S T
as partate a mi n otra nsferase
B L Q
bel o w t he li mit of q ua ntitati o n
B MI
b o d y mass i n de x
C F R
C o de of Fe deral Re g ulati o ns
CI
c o nfi de nce i nter val
C K
creati ne ki nase
C R F
case re p ort f or m
C S R
cli nical st u d y re p ort
C T C A E 
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts
DI LI
dr u g-i n d uce d li ver i nj ur y
D M C 
data m o nit ori n g c o m mittee
E C G
electr ocar di o gra m
E T
earl y ter mi nati o n
F A S
F ull A nal ysis Set
H b
he m o gl o bi n
H L T
hi g h-le vel ter m
I C H
I nter nati o nal C o nfere nce o n Har m o nizati o n ( of Tec h nical Re q uire me nts f or Re gistrati o n of 
P har mace uticals f or H u ma n Use)
I T T
i nte nt t o treat
L T T
l o wer-le vel ter m
L O Q
li mit of q ua ntitati o n
Me d D R A 
Me dical Dicti o nar y f or Re g ulat or y Acti vities
P P
per pr ot oc ol
P T
preferre d ter m
Q 1, Q 3 
first q uartile, t hir d q uartile
Q R S
electr ocar di o gra p hic deflecti o n bet wee n t he be gi n ni n g of t he Q wa ve a n d ter mi nati o n of t he 
S wa ve re prese nti n g ti me f or ve ntric ular de p olarizati o n
Q T
electr ocar di o gra p hic i nter val bet wee n t he be gi n ni n g of t he Q wa ve a n d ter mi nati o n of t he 
T wa ve re prese nti n g t he ti me f or b ot h ve ntric ular de p olarizati o n a n d re p olarizati o n t o occ ur
Q Tc
Q T i nter val c orrecte d f or heart rate
Q Tc F 
Q T i nter val c orrecte d f or heart rate usi n g Fri dericia’s f or m ula
R R
electr ocar di o gra p hic i nter val re prese nti n g t he ti me meas ure me nt bet wee n t he R wa ve of o ne 
heart beat a n d t he R wa ve of t he prece di n g heart beat
S A P
statistical a nal ysis pla n
S D
sta n dar d de viati o n
SI ( u nits) 
i nter nati o nal s yste m of u nits
S O C
s yste m or ga n class


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6
1 7 Ja n uar y 2 0 2 4
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
U L N
u p per li mit of n or mal
V R
ve ntric ular rate
W H O
W orl d Healt h Or ga nizati o n


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7
1 7 Ja n uar y 2 0 2 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 last
area u n der t he c o nce ntrati o n vers us ti me c ur ve fr o m ti me zer o t o t he last q ua ntifia ble 
c o nce ntrati o n
A U C ta u
area u n der t he 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 c o nce ntrati o n of t he dr u g 
C ma x
ma xi m u m o bser ve d c o nce ntrati o n of dr u g 
C ta u
o bser ve d 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 Lss/ 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
t1/ 2
esti mate of t he ter mi nal eli mi nati o n half-life of t he dr u g, calc ulate d b y di vi di n g t he nat ural l o g of 
2 b y t he ter mi nal eli mi nati o n rate c o nsta nt ( z)
T last
ti me ( o bser ve d ti me p oi nt) of Clast
T ma x
ti me ( o bser ve d ti me p oi nt) of Cma x
z
ter mi nal eli mi nati o n rate c o nsta nt, esti mate d b y li near re gressi o n of t he ter mi nal eli mi nati o n 
p hase of t he c o nce ntrati o n of dr u g vers us ti me c ur ve


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 8
1 7 Ja n uar y 2 0 2 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 cli nical st u d y re p ort ( C S R) 
f or St u d y G S- U S- 2 0 0- 4 3 3 4. T his S A P is base d o n t he st u d y pr ot oc ol a me n d me nt 4 date d 
0 4 Fe br uar y 2 0 2 2  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
T he pri mar y o bjecti ve of t his st u d y is as f oll o ws:
•
T o e val uate t he efficac y of L E N c o ntai ni n g re gi me ns i n pe o ple li vi n g wit h HI V ( P L W H) as 
deter mi ne d b y t he pr o p orti o n of partici pa nts wit h HI V- 1 R N A  5 0 c o pies/ m L at Wee k 5 4
T he sec o n dar y o bjecti ves of t his st u d y are as f oll o ws:
•
T o e val uate t he efficac y of L E N c o ntai ni n g re gi me ns i n P L W H as deter mi ne d b y t he 
pr o p orti o n of partici pa nts wit h HI V- 1 R N A  5 0 c o pies/ m L at Wee ks 2 8, 3 8, a n d 8 0
•
T o e val uate t he c ha n ge fr o m baseli ne i n l o g 1 0 HI V- 1 R N A a n d i n C D 4 + cell c o u nt at 
Wee ks 2 8, 3 8, 5 4, a n d 8 0
•
T o e val uate t he safet y a n d t olera bilit y of t he L E N c o ntai ni n g re gi me ns t hr o u g h 2 8, 3 8, 5 4, 
a n d 8 0 wee ks of treat me nt
•
T o e val uate t he p har mac o ki netics ( P K) of L E N, bicte gra vir ( BI C), a n d te n of o vir alafe na mi de 
( T A F)
1. 2.  
St u d y Desi g n
Desi g n C o nfi g ur ati o n a n d P artici p a nt P o p ul ati o n
T his is a P hase 2, ra n d o mize d, o pe n la bel, acti ve c o ntr olle d, m ultice nter st u d y.
A p pr o xi matel y 1 7 5 treat me nt- nai ve P W H w h o meet all eli gi bilit y criteria will be ra n d o mize d i n 
a 2: 2: 2: 1 rati o t o 1 of t he f oll o wi n g 4 treat me nt gr o u ps. Ra n d o mizati o n will be stratifie d b y 
HI V- 1 R N A le vel ( ≤ 1 0 0, 0 0 0 c o pies/ m L or > 1 0 0, 0 0 0 c o pies/ m L) at scree ni n g.


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 9
1 7 Ja n uar y 2 0 2 4
Tre at me nt Gr o u ps
Tre at me nt Gr o u p 1 ( n = 5 0)
I n d ucti o n: Partici pa nts will recei ve oral L E N 6 0 0 m g, 6 0 0 m g, a n d 3 0 0 m g, wit h o ut re gar d t o 
f o o d, at Da ys 1, 2, a n d 8 res pecti vel y. Partici pa nts will als o be gi n oral dail y e mtricita bi ne 
( F)/ T A F ( 2 0 0/ 2 5 m g), wit h o ut re gar d t o f o o d fr o m Da y 1 o n war ds f or a t otal of 2 8 wee ks. O n 
Da y 1 5 partici pa nts will recei ve s u bc uta ne o us ( S C) L E N 9 2 7 m g, wit h o ut re gar d t o f o o d.
Mai nte na nce: Partici pa nts will recei ve S C L E N 9 2 7 m g at Wee k 2 8 a n d e ver y 2 6 wee ks 
t hereafter. Partici pa nts will disc o nti n ue oral dail y F/ T A F ( 2 0 0/ 2 5 m g) at Wee k 2 8 a n d be gi n 
ta ki n g oral dail y T A F ( 2 5 m g), wit h o ut re gar d t o f o o d.
Tre at me nt Gr o u p 2 ( n = 5 0)
I n d ucti o n: Partici pa nts will recei ve oral L E N 6 0 0 m g, 6 0 0 m g, a n d 3 0 0 m g, wit h o ut re gar d t o 
f o o d at Da ys 1, 2, a n d 8 res pecti vel y. Partici pa nts will als o be gi n oral dail y F/ T A F ( 2 0 0/ 2 5 m g), 
wit h o ut re gar d t o f o o d fr o m Da y 1 o n war d f or a t otal of 2 8 wee ks. O n Da y 1 5 partici pa nts will 
recei ve S C L E N 9 2 7 m g, wit h o ut re gar d t o f o o d.
Mai nte na nce: Partici pa nts will recei ve S C L E N 9 2 7 m g at Wee k 2 8 a n d e ver y 2 6 wee ks 
t hereafter. Partici pa nts will disc o nti n ue oral dail y F/ T A F ( 2 0 0/ 2 5 m g) at Wee k 2 8 a n d be gi n oral 
dail y BI C ( 7 5 m g) wit h o ut re gar d t o f o o d.
Tre at me nt Gr o u p 3 ( n = 5 0)
Partici pa nts will recei ve oral L E N 6 0 0 m g a n d 6 0 0 m g wit h o ut re gar d t o f o o d at Da ys 1 a n d 2, 
res pecti vel y. O n Da y 3, partici pa nts will be gi n oral dail y L E N 5 0 m g, wit h o ut re gar ds t o f o o d. 
Partici pa nts will be gi n oral dail y F/ T A F ( 2 0 0/ 2 5 m g), wit h o ut re gar d t o f o o d fr o m Da y 1 
o n war ds.
Tre at me nt Gr o u p 4 ( n = 2 5)
Partici pa nts will recei ve oral dail y bicte gra vir/e mtricita bi ne/ T A F ( B/ F/ T A F, 5 0/ 2 0 0/ 2 5 m g), 
wit h o ut re gar d t o f o o d at Da y 1 a n d t hr o u g h o ut t heir partici pati o n i n t he st u d y.
Ke y Eli gi bilit y Criteri a
Treat me nt nai ve P W H w h o meet t he f oll o wi n g criteria:
•
A ge ≥ 1 8 years of a ge at Scree ni n g
•
Plas ma HI V- 1 R N A  2 0 0 c o pies/ m L at Scree ni n g
•
C D 4 + cell c o u nt  2 0 0 cells/L at Scree ni n g
•
A ntiretr o viral ( A R V) nai ve wit h n o use of a n y A R V me dicati o ns wit hi n o ne m o nt h of 
Scree ni n g. Use of pre-e x p os ure pr o p h yla xis ( Pr E P) (a n y d urati o n), p ost-e x p os ure 
pr o p h yla xis ( P E P) (a n y d urati o n), or HI V- 1 treat me nt ( < 1 0 da ys t hera p y t otal) > 1 m o nt h 
pri or t o Scree ni n g is per mitte d.


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Sc he d ule of Assess me nts
At scree ni n g, la b orat or y a nal yses ( he mat ol o g y, c he mistr y, a n d uri nal ysis, a n d ser u m pre g na nc y 
test [f or w o me n]), HI V- 1 R N A, C D 4 + cell c o u nt, vital si g ns, electr ocar di o gra m ( E C G), 
c o m plete p h ysical e xa mi nati o n a n d esti mate d gl o mer ular filtrati o n rate (e G F R) will be 
perf or me d, a n d he patitis B vir us ( H B V) a n d he patitis C vir us ( H C V) ser ol o gies will be a nal yze d. 
A nal ysis of t he partici pa nt’s HI V- 1 resista nce t o s u p p ort eli gi bilit y will be c o m plete d.
After scree ni n g pr oce d ures, eli gi ble partici pa nts will be ra n d o mize d i nt o 1 of t he 4 treat me nt 
gr o u ps i n a 2: 2: 2: 1 rati o.
Partici pa nts i n Treat me nt Gr o u ps 1, 2, a n d 3 o nl y, will ha ve visits o n Da y 1, Da y 2,   
 
, Da y 8, a n d Da y 1 5. All partici pa nts will ha ve a Wee k 4 visit a n d will c o nti n ue t o 
atte n d st u d y visits e ver y 6 wee ks u ntil Wee k 2 8.
Partici pa nts i n Treat me nt Gr o u ps 1 a n d 2 will nee d t o ha ve HI V- 1 R N A res ults < 5 0 c o pies/ m L 
at Wee ks 1 6 a n d 2 2 t o i nitiate treat me nt wit h a t w o a ge nt re gi me n at Wee k 2 8; t h ose wit h val ues 
≥ 5 0 c o pies/ m L will disc o nti n ue t he st u d y dr u g at or pri or t o Wee k 2 8.
After Wee k 2 8, partici pa nts will atte n d st u d y visits o n Wee k 3 8, Wee k 5 4, Wee k 6 4, a n d 
Wee k 8 0. After Wee k 8 0, partici pa nts i n Treat me nt Gr o u p 4 will c o m plete t he st u d y a n d 
partici pa nts i n Treat me nt Gr o u ps 1, 2, a n d 3 will be gi ve n t he o pti o n t o recei ve f urt her treat me nt 
a n d c o nti n ue t o atte n d visits alter nati n g bet wee n e ver y 1 0 wee ks a n d e ver y 1 6 wee ks visits.
At eac h visit, a d verse e ve nts ( A Es), c o nc o mita nt me dicati o ns, la b orat or y tests, p h ysical 
e xa mi nati o ns, P K, a n d patie nt re p orte d o utc o mes ( P R Os) will be perf or me d i n acc or da nce wit h 
t he St u d y Pr oce d ures Ta ble.
M ore details f or st u d y pr oce d ures c o ul d be f o u n d i n Secti o n 1 2 ( A p pe n di x 1 ). 
St u d y D ur ati o n
D urati o n of treat me nt is at least 8 0 wee ks. Partici pa nts i n Treat me nt Gr o u p 4 will c o m plete t he 
st u d y at Wee k 8 0.
F oll o wi n g s uccessf ul c o m pleti o n of Wee k 8 0 visit, partici pa nts recei vi n g L E N will be gi ve n t he 
o pti o n t o recei ve f urt her treat me nt a n d c o nti n ue t o atte n d visits o n Wee k 9 0, Wee k 1 0 6, 
Wee k 1 1 6, Wee k 1 3 2, Wee k 1 4 2, a n d will c o nti n ue t o alter nate bet wee n e ver y 1 0 wee ks a n d 
e ver y 1 6 wee ks visits. Partici pa nts willi n g t o c o nti n ue t he st u d y be y o n d Wee k 8 0 i n Treat me nt 
Gr o u ps 1 a n d 2 will c o nti n ue t o recei ve S C L E N 9 2 7 m g e ver y 6 m o nt hs ( 2 6 wee ks) fr o m 
Wee k 8 0 o n war ds a n d partici pa nts i n Treat me nt Gr o u p 3 will recei ve oral L E N 5 0 m g dail y fr o m 
Wee k 8 0 u ntil t he pr o d uct bec o mes accessi ble t o partici pa nts t hr o u g h a n access pr o gra m, or u ntil 
Gilea d elects t o disc o nti n ue t he st u d y i n t he c o u ntr y. Partici pa nts i n Treat me nt Gr o u ps 1, 2, 
a n d 3 will als o recei ve T A F, F/ T A F, or BI C as a p plica ble.
Partici pa nts w h o disc o nti n ue st u d y dr u gs pri or t o Wee k 8 0 visit or pri or t o st u d y c o m pleti o n ma y 
be re q uire d t o c o m plete 3 0- Da y, 9 0- Da y a n d/ or 1 8 0- Da y F oll o w U p visits after Earl y 
Ter mi nati o n Visit.
C CI
-
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Or al Wee kl y Bri d gi n g of L E N f or Misse d S C I njecti o n
Partici pa nts recei vi n g S C L E N ma y miss t heir S C i njecti o n wi n d o w ( wit hi n 2 6 t o 2 8 wee ks of 
t he pre vi o us S C L E N d ose). If a misse d d ose is a ntici pate d, partici pa nts ma y recei ve oral 
bri d gi n g u ntil t he y ca n recei ve t heir ne xt S C i njecti o n.
1. 3.  
S a m ple Size a n d P o wer
A sa m ple size of 5 0 partici pa nts i n Treat me nt Gr o u ps 1 t o 3, res pecti vel y, was c h ose n t o esti mate 
t he res p o nse rate of HI V- 1 R N A < 5 0 c o pies/ m L at Wee k 5 4. A t otal sa m ple size of 
7 5 partici pa nts f or eac h pair of c o m paris o ns (ie, bet wee n eac h of t he L E N-c o ntai ni n g re gi me n 
gr o u ps [ Treat me nt Gr o u ps 1 t o 3, n = 5 0] a n d t he B/ F/ T A F [ Treat me nt gr o u p 4, n = 2 5]) will 
pr o vi de 3 9 % p o wer t o e val uate n o n-i nferi orit y wit h res pect t o t he res p o nse rate of HI V- 1 R N A 
 5 0 c o pies/ m L at Wee k 5 4. I n t his sa m ple size a n d p o wer calc ulati o n, it is ass u me d a res p o nse 
rate is 9 0. 9 % ( base d o n p o ole d data fr o m St u dies G S- U S- 3 8 0- 1 4 8 9 a n d G S- U S- 3 8 0- 1 4 9 0) f or 
eac h treat me nt gr o u p a n d a n o n-i nferi orit y mar gi n is 0. 1 2.


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2.  
T Y P E O F P L A N N E D A N A L Y SI S
2. 1.  
I nteri m A n al yses
2. 1. 1.   
D M C A n al ysis
O ne e xter nal m ulti disci pli nar y Data M o nit ori n g C o m mittee ( D M C) a nal ysis was c o n d ucte d after 
all partici pa nts ha ve c o m plete d t heir Wee k 1 6 visit or pre mat urel y disc o nti n ue d fr o m st u d y dr u g, 
all o utsta n di n g data q ueries ha d 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 d 
bee n clea ne d a n d fi nalize d f or t he a nal ysis. N o f or mal st o p pi n g r ules was use d b y t he D M C f or 
safet y o utc o mes. Rat her, a cli nical assess me nt was ma de t o deter mi ne if t he nat ure, fre q ue nc y, 
a n d se verit y of A Es ass ociate d wit h a st u d y treat me nt warra nt t he earl y ter mi nati o n of t he st u d y 
i n t he best i nterest of t he partici pa nts. N o al p ha pe nalt y will be a p plie d f or t he pri mar y a nal ysis 
of t he pri mar y efficac y e n d p oi nt gi ve n t hat t he st u d y is n ot a de q uatel y p o were d f or a f or mal 
efficac y e val uati o n. T he p ur p ose of t he i nteri m a nal ysis was t o pr o vi de t he D M C wit h a 
statistical re p ort f or re vie w. M ore details are d oc u me nte d i n t he D M C c harter.
2. 1. 2.   
Wee k 2 8 I nteri m A n al ysis
T he Wee k 2 8 i nteri m a nal ysis was c o n d ucte d after all partici pa nts ha ve c o m plete d t he Wee k 2 8 
visit or ha ve pre mat urel y disc o nti n ue d t he st u d y dr u g, o utsta n di n g data q ueries ha d 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 d bee n clea ne d a n d fi nalize d f or t he 
a nal ysis. T he a nal ysis was use d t o s u p p ort t he L E N re g ulat or y fili n g f or t he i n dicati o n i n t he 
hea vil y treat me nt e x perie nce d P W H.
2. 1. 3.   
Wee k 8 0 I nteri m A n al ysis
T he Wee k 8 0 i nteri m a nal ysis was c o n d ucte d after all partici pa nts ha ve c o m plete d t he Wee k 8 0 
visit or ha ve pre mat urel y disc o nti n ue d t he st u d y dr u g, o utsta n di n g data q ueries ha d 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 d bee n clea ne d a n d fi nalize d f or t he 
a nal ysis.
2. 2.  
Pri m ar y A n al ysis
T he Wee k 5 4 i nteri m a nal ysis was c o n d ucte d after all partici pa nts ha ve c o m plete d Wee k 5 4 visit 
or ha ve pre mat urel y disc o nti n ue d t he st u d y dr u g, 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 f or t he a nal ysis. T his is 
t he pri mar y a nal ysis of t his st u d y.
2. 3.  
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 ha ve c o m plete d t he st u d y, 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.
T his S A P descri bes t he a nal ysis pla n f or t he Fi nal A nal ysis.


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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, sta n dar d de viati o 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.
All statistical tests will be 2-si de d a n d perf or me d at t he 5 % si g nifica nce le vel u nless ot her wise 
s pecifie 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 Ra n d o mize d A nal ysis Set 
a n d s orte d b y partici pa nt I D n u m ber, visit date, a n d ti me (if a p plica ble). 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 wit hi n t he partici pa nt. T he 
treat me nt gr o u p t o w hic h partici pa nts were ra n d o mize 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 de ntifie d a n d i ncl u de d as a 
s u btitle of eac h ta ble, fi g ure, a n d listi n g.
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 treat me nt gr o u p.
A 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 b y partici pa nt.
3. 1. 1.   
All R a n d o mize d A n al ysis Set
All Ra n d o mize d  A nal ysis Set i ncl u des all partici pa nts w h o were ra n d o mize d i n t he st u d y.
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)  i ncl u des all ra n d o mize d partici pa nts w h o t o o k 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 i ncl u des all partici pa nts w h o t o o k 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.


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3. 1. 4.  
P h ar m ac o ki netic A n al ysis Set
T he P har mac o ki netic ( P K)  A nal ysis Set will i ncl u de all ra n d o mize d partici pa nts w h o t o o k at 
least 1 d ose of st u d y dr u g a n d ha ve at least 1 n o n missi n g c o nce ntrati o n val ue re p orte d b y t he P K 
la b orat or y. T his is t he pri mar y a nal ysis set f or all P K a nal yses. 
3. 2.  
P artici p a nt Gr o u pi n g
F or a nal yses base d o n t he All Ra n d o mize d A nal ysis Set or t he F A S , partici pa nts will be gr o u pe d 
acc or di n g t o t he treat me nt gr o u p t o w hic h t he y were ra n d o mize d. F or all ot her a nal yses, 
partici pa nts will be gr o u pe d acc or di n g t o t he act ual treat me nt recei ve d. T he act ual treat me nt 
recei ve d will differ fr o m t he ra n d o mize d treat me nt o nl y w he n t heir act ual treat me nt differs fr o m 
ra n d o mize d treat me nt f or t he e ntire treat me nt d urati o n.
Partici pa nts will be gr o u pe d as f oll o ws f or ta ble s u m mar y:  
•
Treat me nt Gr o u p 1: S C L E N + ( F/ T A F → T A F) 
•
Treat me nt Gr o u p 2: S C L E N + ( F/ T A F → BI C)
•
Treat me nt Gr o u p 3: Oral L E N + F/ T A F
•
Treat me nt Gr o u p 4: B/ F/ T A F
•
Treat me nt Gr o u ps 1 a n d 2: S C L E N (f or all ta bles u nless s pecifie d ot her wise)
•
Treat me nt Gr o u ps 1, 2, a n d 3: L E N (f or all ta bles u nless s pecifie d)
3. 3.  
Str at a a n d C o v ari ates
Ra n d o mizati o n was stratifie d b y HI V- 1 R N A le vel ( ≤ 1 0 0, 0 0 0 c o pies/ m L or 
> 1 0 0, 0 0 0 c o pies/ m L) at scree ni n g. 
Efficac y a nal yses will i ncl u de HI V- 1 R N A strat u m ( ≤ 1 0 0, 0 0 0 vs. > 1 0 0, 0 0 0 c o pies/ m L) at 
baseli ne as a stratificati o n fact or. T he HI V- 1 R N A strat u m will be reclassifie d usi n g baseli ne 
HI V- 1 R N A le vel f or a nal ysis p ur p oses.
3. 4.  
E x a mi n ati o n of P artici p a nt S u b gr o u ps
3. 4. 1.  
P artici p a nt S u b gr o u ps f or S afet y A n al yses
I nci de nce of all treat me nt-e mer ge nt A Es ( T E A Es) will be a nal yze d f or t he f oll o wi n g partici pa nt 
s u b gr o u ps: 
•
A ge ( years): (a) < 5 0 a n d ( b) ≥ 5 0 
•
Se x: (a) male a n d ( b) fe male 
•
Race: (a) blac k a n d ( b) n o n blac k 


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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 i n t his P hase 2, n o n-c o nfir mat or y trial.
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 o nset 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. 4 .
3. 6. 2.   
O utliers
O utliers 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
O nl y year of birt h is c ollecte d i n t his st u d y. 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 ra n d o mizati o n 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 
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.


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N o n- P K data t hat are c o nti n u o us i n nat ure b ut are 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 of 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 t he 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).
S parse P K c o nce ntrati o n val ues t hat are bel o w t he li mit of q ua ntitati o n ( B L Q) will be prese nte d 
as “ B L Q” i n t he data listi n g.
L o garit h mic ( base 1 0) tra nsf or mati o ns will be a p plie d t o HI V- 1 R N A data f or efficac y a nal ysis. 
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 p/ 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.
Nat ural l o garit h m tra nsf or mati o n will be use d f or a nal yzi n g c o nce ntrati o ns a n d P K para meters i n 
i nte nsi ve P K sa m ples. C o nce ntrati o n val ues t hat are B L Q will be prese nte d as “ B L Q” i n t he 
c o nce ntrati o n data listi n g. Val ues t hat are B L Q will be treate d as 0 at pre d ose ti me p oi nts, a n d 
o ne- half t he val ue of t he L O Q at p ost d ose ti me p oi nts f or s u m mar y p ur p oses.
T he f oll o wi n g c o n ve nti o ns will be use d f or t he prese ntati o n of s u m mar y a n d or der statistics f or 
i nte nsi ve P K c o nce ntrati o ns: 
•
If at least 1 partici pa nt has a c o nce ntrati o n val ue of B L Q f or t he ti me p oi nt, t he mi ni m u m 
val ue will be dis pla ye d as “ B L Q.”
•
If m ore t ha n 2 5 % of t he partici pa nts ha ve a c o nce ntrati o n data val ue of B L Q f or a gi ve n ti me 
p oi nt, t he mi ni m u m a n d Q 1 val ues will be dis pla ye d as “ B L Q.”
•
If m ore t ha n 5 0 % of t he partici pa nts ha ve a c o nce ntrati o n data val ue of B L Q f or a gi ve n ti me 
p oi nt, t he mi ni m u m, Q 1, a n d me dia n val ues will be dis pla ye d as “ B L Q.”
•
If m ore t ha n 7 5 % of t he partici pa nts ha ve a c o nce ntrati o n data val ue of B L Q f or a gi ve n ti me 
p oi nt, t he mi ni m u m, Q 1, me dia n, a n d Q 3 val ues will be dis pla ye d as “ B L Q.”
•
If all partici pa nts ha ve c o nce ntrati o n data val ues of B L Q f or a gi ve n ti me p oi nt, all or der 
statistics ( mi ni m u m, Q 1, me dia n, Q 3, a n d ma xi m u m) will be dis pla ye d as “ B L Q.”


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P K para meters t hat are B L Q will be i m p ute d as o ne- half L O Q bef ore l o g tra nsf or mati o n or 
statistical m o del fitti n g.
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 1 is defi ne d as t he da y w he n t he first d ose of st u d y dr u g was ta ke n, as 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. F or partici pa nts i n Treat me nt Gr o u ps 1- 3, t he earliest of 
t he first d ose dates of a n y c o m p o ne nt (ie, L E N or F/ T A F) is c o nsi dere d as t he first d ose date of 
t he st u d y dr u g.
L ast D ose D ate is defi ne d as f oll o ws 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 
i n Treat me nt Gr o u ps 1 t o 3, or c o m plete d st u d y dr u g at mai n p hase i n Treat me nt Gr o u p 4 
acc or di n g t o St u d y Dr u g C o m pleti o n e C R F (ie, “st u d y dr u g c o m pleti o n” b o x c hec ke d “ N o” f or 
partici pa nts w h o pre mat urel y disc o nti n ue d, or “st u d y dr u g c o m pleti o n” b o x c hec ke d “ Yes” f or 
partici pa nts w h o c o m plete d st u d y dr u g i n Treat me nt Gr o u p 4). 
•
F or partici pa nts w h o recei ve S C i njecti o n, t he last d ose date is defi ne d as t he latest 
n o n missi n g e n d date of t he st u d y dr u g use d wit h L E N.
•
F or partici pa nts w h o d o n ot recei ve S C i njecti o n, t he last d ose date is defi ne d as t he earliest 
of t he last d ose date of a n y st u d y dr u g.
•
If t he date of last d ose is i nc o m plete or missi n g (e g, d ue t o l ost t o f oll o w- u p), t he latest 
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, a n d t he la b orat or y visit 
dates e xcl u di n g t he dates of a n y f oll o w- u p visits will be use d t o i m p ute t he last d ose date.
St u d y D a ys  are calc ulate d relati ve t o St u d y Da y 1 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 ose Date + 1
•
F or da ys pri or t o t he first d ose: Assess me nt Date – First D ose Date
B aseli ne V al ue  is defi ne d as t he last val ue o btai ne d o n or pri or t o t he first d ose of st u d y dr u g.
L ast St u d y D ate  is t he latest n o n missi n g cli nic visit dates, a n d/ or t he la b orat or y visit dates, 
a n d/ or latest A E o nset date a n d e n d date, w hic he ver is latest, i ncl u di n g t he a n y f oll o w- u p visit 
dates, f or partici pa nts w h o pre mat urel y disc o nti n ue d 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.
L ast E x p os ure D ate  is defi ne d as f oll o ws 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 acc or di n g t o St u d y Dr u g C o m pleti o n e C R F. T his date is defi ne d c o nsi deri n g t he pr ol o n ge d 
e x p os ure of L E N after t he last d ose date of L E N.
•
Treat me nt Gr o u ps 1 a n d 2:

F or partici pa nts w h o recei ve S C i njecti o n, last e x p os ure date is defi ne d as last st u d y date.  

F or partici pa nts w h o d o n ot recei ve S C i njecti o n, last e x p os ure date is defi ne d as t he 
mi ni m u m of t he last d ose date pl us 6 0 da ys a n d t he last st u d y date.


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•
Treat me nt Gr o u p 3: last e x p os ure date is defi ne d as t he mi ni m u m of t he last d ose date pl us 
6 0 da ys a n d t he last st u d y date.
•
Treat me nt Gr o u p 4: last e x p os ure date is defi ne d as t he mi ni m u m of t he last d ose date pl us 
3 0 da ys a n d t he last st u d y date.
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, li pi d 
pa nel, uri nal ysis, uri ne c he mistr y, uri ne pre g na nc y la b orat or y tests, vital si g ns, a n d wei g ht are 
pr o vi de d i n Ta ble 3- 1  a n d Ta ble 3- 2  f or t he L E N-c o ntai ni n g re gi me n gr o u ps 
( Treat me nt Gr o u ps 1- 3) a n d t he B/ F/ T A F gr o u p ( Treat me nt Gr o u p 4), res pecti vel y.
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, Li pi d P a nel, Uri n al ysis, Uri ne C he mistr y, 
Uri ne Pre g n a nc y L a b or at or y Tests, Vit al Si g ns, a n d Wei g ht f or t he 
L E N-c o nt ai ni n g Re gi me n Gr o u ps ( Tre at me nt Gr o u ps 1- 3)
Visit Wi n d o w St u d y D a y
Visit
St u d y D a y
L o wer Li mit
U p per Li mit
Da y 1
1
≤ 1
1
Da y 2
2
2
5
Da y 8
8
6
1 1
Da y 1 5
1 5
1 2
2 1
Wee k 4
2 8
2 2
4 9
Wee k 1 0
7 0
5 0
9 1
Wee k 1 6 
1 1 2
9 2
1 3 3
Wee k 2 2
1 5 4
1 3 4
1 7 5
Wee k 2 8
1 9 6
1 7 6
2 3 1
Wee k 3 8
2 6 6
2 3 2
3 2 2
Wee k 5 4
3 7 8
3 2 3
4 1 3
Wee k 6 4
4 4 8
4 1 4
5 0 4
Wee k 8 0
5 6 0
5 0 5
5 9 5
Wee k 9 0
6 3 0
5 9 6
6 8 6
Wee k 1 0 6
7 4 2
6 8 7
7 7 7
Wee k 1 1 6
8 1 2
7 7 8
8 6 8
Wee k 1 3 2
9 2 4
8 6 9
9 5 9
Wee k 1 4 2
9 9 4
9 6 0
1 0 5 0
Wee k 1 5 8
1 1 0 6
1 0 5 1
1 1 4 1
Wee k 1 6 8
1 1 7 6
1 1 4 2
1 2 3 2
Wee k 1 8 4
1 2 8 8
1 2 3 3
≥ 1 2 8 8
I 
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T a ble 3- 2.   
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, Li pi d P a nel, Uri n al ysis, Uri ne C he mistr y, 
Uri ne Pre g n a nc y L a b or at or y Tests, Vit al Si g ns, a n d Wei g ht f or t he 
B/ F/ T A F Gr o u p ( Tre at me nt Gr o u p 4)
Visit Wi n d o w St u d y D a y
Visit
St u d y D a y
L o wer Li mit
U p per Li mit
Da y 1
1
≤ 1
1
Wee k 4
2 8
2
4 9
Wee k 1 0
7 0
5 0
9 1
Wee k 1 6
1 1 2
9 2
1 3 3
Wee k 2 2
1 5 4
1 3 4
1 7 5
Wee k 2 8
1 9 6
1 7 6
2 3 1
Wee k 3 8
2 6 6
2 3 2
3 2 2
Wee k 5 4
3 7 8
3 2 3
4 1 3
Wee k 6 4
4 4 8
4 1 4
5 0 4
Wee k 8 0
5 6 0
5 0 5
≥ 5 6 0
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 ose 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 (e xce pt f or HI V- 1 R N A, see bel o w), or t he meas ure me nt wit h t he l o west 
se verit y (e g, n or mal 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.
•
F or p ost baseli ne val ues:

T he rec or d cl osest t o t he n o mi nal da y f or t hat visit will be selecte d wit h t he e xce pti o n of 
C D 4 cell c o u nts a n d C D 4 % i n w hic h t he latest rec or d will be selecte d a n d HI V- 1 R N A 
le vel (see bel o w)

If t here are 2 rec or ds t hat are e q ui dista nt fr o m t he n o mi nal da y, t he later rec or d will be 
selecte d.
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
If t here is m ore t ha n 1 rec or d o n t he selecte d da y, t he a vera ge will be ta ke n f or 
c o nti n u o us data (e xce pt f or HI V- 1 R N A, see bel o w) a n d t he w orse se verit y will be ta ke n 
f or cate g orical data, u nless ot her wise s pecifie d.
•
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 test res ults (“ HI V R N A C o bas 6 8 0 0” or 
“ HI V R N A Ta q ma n 2. 0”) a n d re peate d HI V test res ults (“ HI V R N A C o bas 6 8 0 0 R P T” or 
“ 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 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 
C o bas 6 8 0 0” rec or ds wit h t he sa me c ollecti o n ti me, t he ge o metric mea n will be ta ke n f or 
a nal ysis p ur p oses.


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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 ra n d o mize d, last partici pa nt 
ra n d o mize d, last partici pa nt last visit f or t he pri mar y e n d p oi nt, 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 b y treat me nt gr o u p f or eac h  c o u ntr y, 
i n vesti gat or wit hi n a c o u ntr y, 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 ra n d o mize 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 si milar e nr oll me nt ta ble will be pr o vi de d b y ra n d o mizati o n strat u m. T he de n o mi nat or f or t he 
perce nta ge of partici pa nts i n t he strat u m will be t he t otal n u m ber of ra n d o mize d partici pa nts. If 
t here are discre pa ncies i n t he val ue use d f or stratificati o n assi g n me nt bet wee n t he i nteracti ve 
we b res p o nse s yste m (I X R S)  a n d t he cli nical data base, t he val ue c ollecte d i n t he cli nical 
data base will be use d f or t he s u m mar y. A listi n g of partici pa nts wit h discre pa ncies i n t he val ue 
use d f or stratificati o n assi g n me nt bet wee n t he I X R S a n d t he cli nical data base at t he ti me of data 
fi nalizati o n will be pr o vi de d. If t here are differe nces bet wee n ra n d o mizati o n strat u m usi n g 
scree ni n g HI V- 1 R N A val ue a n d baseli ne HI V- 1 R N A val ue, a listi n g of t he differe nces will als o 
be pr o vi de d.
T he ra n d o mizati o n sc he d ule use d f or t he st u d y was pr o vi de d as a n a p pe n di x t o t he Wee k 2 8 
C S R.
A s u m mar y of partici pa nt dis p ositi o n will be pr o vi de d b y treat me nt gr o u p a n d t otal base d o n all 
scree ne d partici pa nts. T his s u m mar y will prese nt t he n u m ber of partici pa nts scree ne d, t he 
n u m ber of partici pa nts w h o met all eli gi bilit y criteria b ut were n ot ra n d o mize d wit h reas o ns 
partici pa nts n ot ra n d o mize d, t he n u m ber of partici pa nts ra n d o mize d b ut ne ver d ose d (if 
a p plica ble), t he n u m ber of partici pa nts ra n d o mize d, a n d t he n u m ber of partici pa nts i n eac h of t he 
cate g ories liste d bel o w:
•
Safet y A nal ysis Set
•
C o nti n ui n g st u d y dr u g i n t he mai n p hase
•
C o m plete d st u d y dr u g i n t he mai n p hase
•
Di d n ot c o m plete st u d y dr u g 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 i n t he 
mai n p hase (if a p plica ble)
•
C o m plete d st u d y dr u g i n t he mai n p hase a n d n ot e nteri n g t he e xte nsi o n p hase
•
C o m plete d st u d y dr u g i n t he mai n p hase a n d e nteri n g i n t he e xte nsi o n p hase 


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•
E nteri n g a n d treate d i n t he e xte nsi o n p hase
•
C o nti n ui n g st u d y dr u g i n t he e xte nsi o n p hase
•
C o m plete d st u d y dr u g i n t he e xte nsi o n p hase
•
Di d n ot c o m plete st u d y dr u g 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 i n t he 
e xte nsi o n p hase (if a p plica ble)
•
C o nti n ui n g st u d y
•
C o m plete d st u d y 
•
Di d n ot c o m plete t he st u d y  wit h reas o ns f or pre mat ure disc o nti n uati o n of st u d y (if 
a p plica ble)
D urati o n of treat me nt is at least 8 0 wee ks. At Wee k 8 0, partici pa nts i n Treat me nt Gr o u p 4 will 
c o m plete t he st u d y. Partici pa nts i n Treat me nt Gr o u ps 1, 2, a n d 3 will be gi ve n t he o pti o n t o 
recei ve f urt her treat me nt a n d c o nti n ue t o atte n d visits be y o n d Wee k 8 0. Mai n p hase data is 
defi ne d as t he data c ollecte d o n/ bef ore Wee k 8 0 visit. E xte nsi o n p hase data is defi ne d as t he data 
c ollecte d after Wee k 8 0 visit.
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 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 i n t hat st u d y p hase (if a p plica ble). I n a d diti o n, a fl o wc hart will be 
pr o vi de d t o de pict t he dis p ositi o n.
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:
•
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
•
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)
4. 2.  
St u d y Dr u g A d mi nistr ati o n a n d A d here nce
St u d y dr u g a d mi nistrati o n a n d st u d y dr u g dis pe nsi n g i nf or mati o n will be c ollecte d i n t he St u d y 
Dr u g A d mi nistrati o n a n d St u d y Dr u g Acc o u nta bilit y e C R Fs. All data i ncl u di n g l ot n u m ber a n d 
kit I D (if a p plica ble) will be liste d.
4. 2. 1.  
St u d y Dr u g A d mi nistr ati o n
St u d y dr u g a d mi nistrati o n a n d st u d y dr u g dis pe nsi n g i nf or mati o n will be c ollecte d i n t he St u d y 
Dr u g A d mi nistrati o n a n d St u d y Dr u g Acc o u nta bilit y e C R Fs. N u m ber of partici pa nts recei vi n g 
oral lea d-i n L E N a n d S C L E N at eac h pr ot oc ol s pecifie d visit ( Da y 1, Da y 2, f or oral L E N a n d 
Da y 1 5, Wee k 2 8, Wee k 5 4, Wee k 8 0, Wee k 1 0 6, a n d etc. f or S C L E N) will be s u m marize d. 


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N u m ber of partici pa nts recei vi n g oral rel oa d bef ore t he first S C i njecti o n d ue t o misse d 
sc he d ule d oral d osi n g, a n d n u m ber of partici pa nts recei vi n g oral bri d gi n g after t he first S C 
i njecti o n will als o be pr o vi de d.
4. 2. 2.  
St u d y Dr u g A d here nce
A d here nce t o S C L E N a n d O nce Dail y St u d y Dr u g(s) will be deri ve d e xce pt f or oral lea d-i n 
L E N a n d oral bri d gi n g L E N i n Treat me nt Gr o u ps 1 a n d 2.
4. 2. 2. 1.   
A d here nce t o S C L E N
T he a d here nce t o S C L E N will be assesse d b y a d here nce t o t he pr ojecte d i njecti o n i nter val, 
w hic h is 2 6 wee ks ( 1 8 2 da ys) bet wee n 2 a djace nt i njecti o n visits. T he n u m ber of da ys fr o m t he 
pr ojecte d i njecti o n visit date will be calc ulate d f or eac h i njecti o n visit (e xcl u di n g t he 1 st i njecti o n 
visit) as t he i njecti o n visit date mi n us t he pre vi o us i njecti o n visit date mi n us 1 8 2 da ys mi n us oral 
bri d gi n g peri o d (ie, First D ose Date of Res u me d S C I njecti o n - First D ose Date of Oral Bri d gi n g) 
if a n y occ urre d bet wee n t hese 2 a djace nt i njecti o n visits. T he n u m ber of da ys fr o m t he pr ojecte d 
i njecti o n visit date will be classifie d i nt o t he f oll o wi n g cate g ories
•
< - 1 4 da ys
•
- 1 4 t o - 8 da ys
•
- 7 t o - 3 da ys
•
± 2 da ys
•
3 t o 7 da ys
•
8 t o 1 4 da ys
•
> 1 4 da ys
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 s u m marize d f or partici pa nts 
i n Treat me nt Gr o u ps 1 a n d 2 w h o recei ve S C i njecti o ns f or t he i njecti o n visit of i nterest.
4. 2. 2. 2.   
A d here nce t o O nce Dail y St u d y Dr u g(s)
T he a d here nce t o o nce dail y ( Q D) st u d y dr u g(s) will be calc ulate d base d o n 1 st u d y dr u g f or 
Treat me nt Gr o u ps 1, 2, a n d 4 (ie, F/ T A F u p t o Wee k 2 8 a n d T A F or BI C fr o m Wee k 2 8 o n war ds 
f or Treat me nt Gr o u ps 1 a n d 2, a n d B/ F/ T A F f or Treat me nt Gr o u p 4), a n d 2 st u d y dr u gs f or 
Treat me nt Gr o u p 3 (ie, oral Q D L E N a n d F/ T A F), e xcl u di n g l o n g acti n g L E N use d f or oral 
lea d-i n a n d oral bri d gi n g.


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A d here nce ( %) of Q D st u d y dr u g(s) will be calc ulate d as f oll o ws:
A d h er e nc e (%) 
=  1 0 0×
𝑇𝑜𝑡𝑎𝑙 N o . of pills t a k e n
T ot al N o. of pills pr escri b e d
=  1 0 0×
∑∑N o. of pills t a k e n at e ac h dis p e nsi n g p eri o d  f or e ac h st u d y dr u g [ 1]
∑∑N o. of pills pr escri b e d at e ac h dis p e nsi n g p eri o d f or e ac h st u d y dr u g [ 2]
[ 1] 
N u m ber of pills ta ke n at a disti nct dis pe nsi n g peri o d f or Q D st u d y dr u g(s) will be calc ulate d as t he mi ni m u m of (a) t he dail y 
n u m ber of pills prescri be d m ulti plie d b y t he d urati o n of treat me nt of Q D st u d y dr u g(s) at t he dis pe nsi n g peri o d of t he sa me 
dis pe nsi n g date, a n d ( b) t he n u m ber of pills ta ke n ( n u m ber of pills dis pe nse d mi n us t he n u m ber of pills ret ur ne d). T otal 
n u m ber of pills ta ke n is deter mi ne d b y s u m mi n g t he n u m ber of pills ta ke n fr o m all e val ua ble dis pe nsi n g peri o ds f or all Q D 
st u d y dr u g(s).
[ 2] 
N u m ber of pills prescri be d at a disti nct dis pe nsi n g peri o d f or Q D st u d y dr u g(s) will be calc ulate d as t he dail y n u m ber of 
pills prescri be d m ulti plie d b y t he d urati o n of treat me nt of Q D st u d y dr u g(s) at t he dis pe nsi n g peri o d of t he sa me dis pe nsi n g 
date. T otal n u m ber of pills prescri be d is deter mi ne d b y s u m mi n g t he n u m ber of pills prescri be d fr o m all e val ua ble 
dis pe nsi n g peri o ds f or all Q D st u d y dr u g(s).
T he d urati o n of treat me nt of Q D st u d y dr u g(s) at a dis pe nsi n g peri o d f or t he st u d y dr u g 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 st u d y dr u g at a dis pe nsi n g peri o d, 
( b) date of pre mat ure disc o nti n uati o n of t he st u d y dr u g, a n d (c) ne xt pill dis pe nsi n g date of t he 
st u d y dr u g, mi n us dis pe nsi n g date of t he st u d y dr u g.
T he ne xt pill 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 pills 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 pills ret ur ne d was zer o. If t he n u m ber of 
pills 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, all rec or ds i n t hat dis pe nsi n g peri o d f or t hat st u d y dr u g 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 n.
A d here nce will be calc ulate d f or eac h partici pa nt f or 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 or usi n g all a vaila ble data f or partici pa nts o n g oi n g o n st u d y dr u g b y t he data c ut date. 
Descri pti ve statistics f or 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 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 of ra n d o mize d Q D st u d y dr u g, a n d w h o ha ve calc ula ble a d here nce i n t he Safet y 
A nal ysis Set. N o i nfere ntial statistics will be pr o vi de d.
A b y- partici pa nt listi n g of st u d y dr u g a d mi nistrati o n a n d dr u g acc o u nta bilit y 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).


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4. 3.  
St u d y D ur ati o n
D ue t o l o n g acti n g feat ure of L E N, d urati o n of f oll o w- u p t o st u d y dr u g will c o nsi der t he 
pr ol o n ge d e x p os ure of L E N after t he last d ose date of L E N. 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 (t he last e x p os ure date – t he first d ose date + 1), 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). Last e x p os ure date is defi ne d i n Secti o n 3. 8. 1  
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. 
D urati o n of e x p os ure will be s u m marize d usi n g descri pti ve statistics ( 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) a n d as t he n u m ber a n d perce nta ge of partici pa nts e x p ose d a n d 
re mai ne d t hr o u g h t he f oll o wi n g ti me peri o ds: 1 da y, 2 da ys, 8 da ys, 1 5 da ys, 4 wee ks ( 2 8 da ys), 
1 0 wee ks ( 7 0 da ys), 1 6 wee ks ( 1 1 2 da ys), 2 2 wee ks ( 1 5 4 da ys), 2 8 wee ks ( 1 9 6 da ys), etc. 
S u m maries will be pr o vi de d base d o n t he Safet y A nal ysis Set. N o i nfere ntial statistics will be 
pr o vi de d.
4. 4.  
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 a n d t he n u m ber of partici pa nts w h o di d n ot meet s pecific criteria b y treat me nt gr o u p 
base d o n t he All Safet y 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 i m p orta nt pr ot oc ol de viati o ns (e g, at 
least 1, wit h 1, 2, 3 or m ore i m p orta nt pr ot oc ol de viati o ns), a n d t he t otal n u m ber of i m p orta nt 
pr ot oc ol de viati o ns b y de viati o n cate g or y (e g, eli gi bilit y criteria, i nf or me d c o nse nt) will be 
s u m marize d b y treat me nt gr o u p f or t he Safet y 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 wit h i m p orta nt pr ot oc ol de viati o n.


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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, se x at birt h, ge n der i de ntit y, se x ual orie ntati o n, 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], hei g ht [i n c m], b o d y mass i n de x 
[ B MI; i n k g/ m2]) will be s u m marize d b y treat me nt gr o u p 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 de m o gra p hic data will be pr o vi de d f or t he Safet y A nal ysis Set.
Statistical c o m paris o n acr oss treat me nt gr o u ps will be perf or me d. F or cate g orical data, t he 
C oc hra n- Ma ntel- Hae nszel ( C M H) test will be use d t o c o m pare acr oss treat me nt gr o u ps e xce pt 
f or ge n der i de ntit y a n d se x ual orie ntati o n. F or c o nti n u o us data, t he 2-si de d Kr us kal- Wallis test 
will be use d t o c o m pare acr oss treat me nt gr o u ps.
A b y- partici pa nt de m o gra p hic listi n g, i ncl u di n g t he i nf or me d c o nse nt date, 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
T he f oll o wi n g baseli ne disease c haracteristics will be s u m marize d b y treat me nt gr o u p 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:  
•
HI V- 1 R N A (l o g 1 0 c o pies/ m L)
•
HI V- 1 R N A cate g ories (c o pies/ m L): (a) ≤ 1 0 0, 0 0 0, ( b) > 1 0 0, 0 0 0
•
C D 4 cell c o u nts (/ u L)
•
C D 4 cell c o u nts cate g ories (/ u 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 ( %)
T he s u m mar y of t hese baseli ne disease c haracteristics will be pr o vi de d f or t he Safet y A nal ysis 
Set. Statistical c o m paris o n acr oss treat me nt gr o u ps will be c o n d ucte d si milarl y as descri be d f or 
t he de m o gra p hic a n d baseli ne c haracteristics.
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
Ge neral me dical hist or y data will be c ollecte d at scree ni n g i ncl u di n g HI V- 1 disease-relate d 
e ve nts. Ge neral me dical hist or y data will be c o de d a n d liste d.


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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 he pri mar y efficac y e n d p oi nt is t he pr o p orti o n of partici pa nts wit h HI V- 1 R N A  5 0 c o pies/ m L 
at Wee k 5 4 as deter mi ne d b y t he U nite d States ( U S) F o o d a n d Dr u g A d mi nistrati o n 
( F D A)- defi ne d s na ps h ot al g orit h m { U. S. De part me nt of Healt h a n d H u ma n Ser vices 2 0 1 5 }. T he 
pr o p orti o ns are e x presse d as perce nta ges f or prese ntati o n p ur p oses.
T he statistical a nal ysis met h o ds f or t he pri mar y efficac y e n d p oi nt were descri be d i n t he Wee k 5 4 
S A P a n d t he a nal ysis was perf or me d i n t he Wee k 5 4 a nal yses.
6. 2.  
Sec o n d ar y Effic ac y E n d p oi nts
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
T he sec o n dar y efficac y e n d p oi nts of t his st u d y are:
•
T he pr o p orti o n of partici pa nts wit h HI V- 1 R N A  5 0 c o pies/ m L at Wee ks 2 8, 3 8, a n d 8 0 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 l o g 1 0 HI V- 1 R N A a n d i n C D 4 + cell c o u nt at Wee ks 2 8, 3 8, 5 4, 
a n d 8 0
6. 2. 2.  
Pri m ar y A n al ysis f or t he Sec o n d ar y E n d p oi nts
T he pr o p orti o n of partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L at Wee ks 2 8, 3 8, a n d 8 0 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 has bee n perf or me d i n t he Wee ks 2 8, 5 4, 
a n d Wee k 8 0 a nal yses a n d will n ot be re peate d here.
6. 2. 3.  
Sec o n d ar y A n al ysis f or t he Sec o n d ar y E n d p oi nts
T he c ha n ge fr o m baseli ne i n l o g 1 0 HI V- 1 R N A a n d i n C D 4 + cell c o u nts will be base d o n t he 
F A S a n d s u m marize d u p t o t he visits wit h a vaila ble data usi n g descri pti ve statistics. T he 
differe nces i n c ha n ges fr o m baseli ne i n l o g 1 0 HI V- 1 R N A a n d C D 4 + cell c o u nt bet wee n eac h of 
t he L E N-c o ntai ni n g treat me nt gr o u ps ( Treat me nt Gr o u ps 1- 3) a n d t he B/ F/ T A F gr o u p 
( Treat me nt Gr o u p 4) a n d t he ass ociate d p- val ues a n d 9 5 % CIs will be c o nstr ucte d usi n g a nal ysis 
of varia nce ( A N O V A) m o dels a dj usti n g f or t he baseli ne HI V- 1 R N A le vel ( ≤ 1 0 0, 0 0 0 c o pies/ m L 
or > 1 0 0, 0 0 0 c o pies/ m L).
Mea n ± 9 5 % CI a n d me dia n ( Q 1, Q 3) of t he c ha n ge fr o m baseli ne i n l o g
1 0 HI V- 1 R N A a n d 
C D 4 + cell c o u nts will be pl otte d b y visit


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6. 3.   
Ot her Effic ac y E n d p oi nts
6. 3. 1.  
Pr o p orti o n of P artici p a nts wit h HI V- 1 R N A < 5 0 c o pies/ m L b y 
Missi n g = F ail ure a n d Missi n g = E xcl u de d A n al yses
N u m ber a n d perce nta ge of partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L b y visit will be 
a nal yze d usi n g t he f oll o wi n g 2 a nal yses:  
•
Missi n g = Fail ure ( M = F): 
I n t his a p pr oac h, missi n g data will be treate d as vir ol o gic fail ure a n d s u m marize d i nt o t he 
“ missi n g” cate g or y (see list of HI V- R N A cate g ories bel o w). 
•
Missi n g = E xcl u de d ( M = E): 
I n t his a p pr oac h, missi n g data will be e xcl u de d i n t he c o m p utati o n of t he perce nta ges 
(ie, missi n g data p oi nts will be e xcl u de d fr o m b ot h t he n u merat or a n d de n o mi nat or i n t he 
c o m p utati o n). T he de n o mi nat or f or perce nta ges at a visit is t he n u m ber of partici pa nts i n t he 
F A S wit h n o n missi n g HI V- 1 R N A val ue at t hat visit. 
F or b ot h M = F a n d M = E a nal yses, t he n u m ber a n d perce nta ge of partici pa nts wit h HI V- 1 R N A 
i n t he f oll o wi n g cate g ories will be s u m marize d base d o n t he F A S:
•
< 5 0 c o pies/ m L 

< 2 0 c o pies/ m L
■
< 2 0 c o pies/ m L N ot Detecta ble
■
< 2 0 c o pies/ m L Detecta ble

2 0 t o < 5 0 c o pies/ m L 
•
5 0 t o < 2 0 0 c o pies/ m L 
•
2 0 0 t o < 4 0 0 c o pies/ m L 
•
4 0 0 t o < 1 0 0 0 c o pies/ m L
•
≥ 1 0 0 0 c o pies/ m L 
•
Missi n g ( o nl y a p plica ble t o M = F a nal ysis)
Statistical c o m paris o n bet wee n eac h of t he L E N-c o ntai ni n g treat me nt gr o u ps ( Treat me nt 
Gr o u ps 1- 3) a n d t he B/ F/ T A F gr o u p ( Treat me nt Gr o u p 4) will be perf or me d. P oi nt esti mates a n d 
its 9 5 % CIs will be esti mate d usi n g strat u m-a dj uste d M H pr o p orti o n as descri be d i n 
Secti o n 6. 2. 3 . T he ass ociate d p- val ues will be esti mate d base d o n t he C M H test stratifie d b y 
baseli ne HI V- 1 R N A le vel ( ≤ 1 0 0, 0 0 0 c o pies/ m L or > 1 0 0, 0 0 0 c o pies/ m L).


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6. 4.   
C h a n ges fr o m Pr ot oc ol- S pecifie d Effic ac y A n al ysis
N o c ha n ge fr o m pr ot oc ol-s pecifie d efficac y a nal ysis is pla n ne d.


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7.  
S A F E T Y A N A L Y S E S
Safet y data will be s u m marize d f or partici pa nts i n t he Safet y A nal ysis Set. All safet y data 
c ollecte d u p t o t he last e x p os ure date 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. 
All c ollecte d data will be i ncl u de d i n data listi n gs.
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 dical Dicti o nar y f or 
Re g ulat or y Acti vities ( 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 wer-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, 2, 3, 4, or 5 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 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 d verse e ve nts ( 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. S 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 Gl o bal Patie nt Safet y 
( G L P S) 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 d verse e ve nts ( T E A Es) are defi ne d as 1 or b ot h of t he f oll o wi n g:
•
A n y 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, or


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A n y A Es wit h a n o nset date o n or after t he st u d y dr u g start date a n d n o later t ha n t he last 
e x p os ure date after per ma ne nt disc o nti n uati o n of t he st u d y dr u g.
7. 1. 5. 2.  
I nc o m plete Dates
If t he o nset 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 ose 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 o nset deter mi ne 
w het her a n A E is treat me nt e mer ge nt. T he e ve nt is c o nsi dere d treat me nt e mer ge nt as f oll o ws:
•
Partici pa nts w h o recei ve S C i njecti o n: t he A E o nset 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 date of st u d y dr u g
•
Partici pa nts w h o d o n ot recei ve S C i njecti o n: 

T he A E o nset 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 date of 
st u d y dr u g, a n d

T he A E o nset 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 last 
e x p os ure date
A n A E wit h c o m pletel y missi n g o nset a n d st o p dates, or wit h t he o nset date missi n g a n d a st o p 
date later t ha n t he first d ose date of st u d y dr u g, will be c o nsi dere d t o be treat me nt e mer ge nt. I n 
a d diti o n, a n A E wit h t he o nset 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 ose date of st u d y dr u g will 
be c o nsi dere d treat me nt e mer ge nt.
W he n calc ulati n g t he d urati o n of e ve nt or ti me t o o nset, t he f oll o wi n g i m p utati o n r ule will be 
use d:
Missi n g start m o nt h/ da y: Ja n 1/first da y of t he m o nt h will be use d u nless t his is bef ore t he start 
date of st u d y dr u g; i n t his case t he st u d y dr u g start date will be use d;
Missi n g st o p m o nt h/ da y: Dec 3 1/last da y of t he m o nt h will be use d, u nless t his is after t he last 
st u d y date; i n t his case t he last st u d y date will be use d.
C o m pletel y missi n g start or e n d dates will re mai n missi n g, wit h n o i m p utati o n a p plie d.
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 treat me nt gr o u p. 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.


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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 treat me nt gr o u p, S O C a n d P T, a n d b y P T o nl y f or t he f oll o wi n g A E 
cate g ories: 
•
T E A Es
•
T E A Es ( b y se verit y)
•
T E A Es wit h Gra de 3 or hi g her ( b y se verit y)
•
T E A Es wit h Gra de 2 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 3 or hi g her ( b y se verit y)
•
T E treat me nt-relate d A Es wit h Gra de 2 or hi g her
•
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 ( b y S O C a n d P T o nl 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 marizes b y P T o nl y, A Es will be s u m marize d a n d 
liste d b y P T i n desce n di n g or der of t otal fre q ue nc 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
•
All S A Es
•
All Deat hs
•
All A Es wit h se verit y of Gra de 3 or hi g her
•
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 pre mat ure disc o nti n uati o n of st u d y
F or eac h listi n g, w het her t he e ve nt is treat me nt e mer ge nt will be i n dicate d.


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7. 1. 7.   
A d diti o n al A n al ysis of A d verse E ve nts
7. 1. 7. 1.  
St u d y Dr u g Relate d I njecti o n Site Reacti o ns
A d diti o nal a nal ysis of A Es will be perf or me d f or i njecti o n site reacti o n (I S R) relate d t o st u d y 
dr u g, w hic h is defi ne d as a n A E relate d t o st u d y dr u g re p orte d as a n y e ve nt wit hi n t he Me d D R A 
H L T of “I njecti o n Site Reacti o ns”. T he f oll o wi n g s u m maries will be pr o vi de d f or eac h S C 
i njecti o n visit (e g, Da y 1, Wee k 2 8) a n d t he o verall f or partici pa nts i n Treat me nt Gr o u ps 1 a n d 2.
•
N u m ber of partici pa nts t hat recei ve d S C i njecti o n(s) 
•
N u m ber a n d perce nta ge of partici pa nts wit h st u d y dr u g relate d I S Rs 
•
N u m ber a n d perce nta ge of partici pa nts wit h st u d y dr u g relate d I S Rs b y gra de 
•
N u m ber a n d perce nta ge of partici pa nts wit h st u d y dr u g relate d I S Rs b y P T 
T he de n o mi nat or f or t he perce nta ge calc ulati o n f or t he b y visit s u m mar y a n d t he o verall 
s u m mar y will be base d o n t he t otal n u m ber of partici pa nts w h o recei ve at least 1 S C i njecti o n at 
t he visit of i nterest a n d t he t otal n u m ber of partici pa nts w h o recei ve at least 1 S C i njecti o n at a n y 
i njecti o n visit, res pecti vel y.
D urati o n of t he I S R will als o be calc ulate d a n d s u m marize d. D urati o n of a gi ve n I S R e ve nt is 
defi ne d as t he I S R st o p date mi n us t he I S R o nset date pl us 1 da y. F or I S Rs wit h o n g oi n g st o p 
date, st o p date will be i m p ute d as last st u d y date or data c ut date, w hic he ver is t he earliest. 
D urati o n of I S R e ve nts i n da ys will be s u m marize d usi n g descri pti ve statistics. 
A b y- partici pa nt listi n g f or st u d y dr u g-relate d I S Rs a n d t he c orres p o n di n g d urati o n will be 
pr o vi de d.
7. 1. 7. 2.  
St u d y Dr u g Relate d I njecti o n Site I n d urati o n a n d N o d ules
Perce nta ge of o n g oi n g a n d res ol ve d st u d y dr u g relate d i njecti o n site i n d urati o n will be 
s u m marize d f or eac h S C i njecti o n (e g, Da y 1 5, Wee k 2 8, Wee k 5 4, etc) a n d t he o verall at b ot h 
partici pa nt-le vel a n d e ve nt-le vel. 
F or t he partici pa nt-le vel s u m mar y, if a partici pa nt ha d m ore t ha n o ne i njecti o n site i n d urati o ns, 
t he partici pa nt will be c o u nte d i n t he “ O n g oi n g” cate g or y  u nless all st u d y dr u g relate d i njecti o n 
site i n d urati o n e ve nts ha ve bee n res ol ve d. 
F or t he e ve nt-le vel s u m mar y, d urati o n of t he res ol ve d e ve nts will be s u m marize d usi n g 
descri pti ve statistics.
St u d y dr u g relate d i njecti o n site n o d ules will be s u m marize d i n t he sa me ma n ner as defi ne d f or 
st u d y dr u g relate d i njecti o n site i n d urati o n.
A b y- partici pa nt listi n g f or st u d y dr u g relate d i njecti o n site i n d urati o n a n d n o d ules a n d t he 
c orres p o n di n g d urati o n will be pr o vi de d.


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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. 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 t he last e x p os ure date f or partici pa nts 
w h o ha ve per ma ne ntl y disc o nti n ue d st u d y dr u g, or all a vaila ble data at t he ti me of t he data base 
s na ps h ot f or partici pa nts w h o were o n g oi n g at t he ti me of a n i nteri m a nal ysis. 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 . He m ol yze d test res ults will n ot be i ncl u de d i n t he a nal ysis, 
b ut t he y wil l be liste d i n b y- partici pa nt la b orat or y listi n gs.
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 n 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 × ( 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.
Esti m ate d Gl o mer ul ar Filtr ati o n R ate
T he f oll o wi n g f or m ulae will be use d t o calc ulate t he esti mate d gl o mer ular filtrati o n rate usi n g 
C oc kcr oft- Ga ult f or m ula (e G F R C G ):
e G F R C G  ( m L/ mi n) = [( 1 4 0 – a ge ( yrs)) × wei g ht ( k g) × ( 0. 8 5 if fe male)] / ( S Cr ( m g/ d L) × 7 2),
w here wei g ht is t otal b o d y mass i n kil o gra ms a n d S Cr is ser u m creati ni ne.
L o w- De nsit y Li p o pr otei n
T he f oll o wi n g f or m ulae will be use d t o calc ulate t he l o w- de nsit y li p o pr otei n ( L D L) usi n g 
Frie de wal d f or m ula w he n c h olester ol, hi g h- de nsit y li p o pr otei n( H D L), a n d tri gl yceri de f or a 
gi ve n bl o o d dra w n are a vaila ble: 
L D L ( m g/ d L) = t otal c h olester ol ( m g/ d L) – H D L ( m g/ d L) – tri gl yceri de ( m g/ d L)/ 5; 
T he f o urt h ge nerati o n L D L is calc ulate d fr o m a b o ve Frie de wal d f or m ula. T he t hir d ge nerati o n 
L D L is a direct meas ure me nt fr o m bl o o d dra w n. B ot h ge nerati o ns of L D L will be liste d i n t he 
listi n g. O nl y f o urt h ge nerati o n L D L calc ulate d fr o m t he Frie de wal d f or m ula will be use d f or 
a nal ysis.


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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 o n 
t he Di visi o n of AI D S ( D AI D S) Ta ble f or Gra di n g t he Se verit y of A d ult a n d Pe diatric A d verse 
E ve nts, Versi o n 2. 1 date d J ul y 2 0 1 7, will be fla g ge d i n t he data listi n gs, as a p pr o priate.
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 treat me nt gr o u p f or selecte d la b orat or y test as f oll o ws:
•
Baseli ne val ues 
•
Val ues at eac h p ost baseli ne visit
•
C ha n ge fr o m baseli ne at eac h p ost baseli ne visit
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/ti me 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 visit 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.
Me dia n ( Q 1, Q 3) of t he c ha n ge fr o m baseli ne val ues f or t hese selecte d la b orat or y tests will be 
pl otte d b y treat me nt gr o u p a n d visit.
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 .
7. 2. 2.   
Gr a de d L a b or at or y V al ues
T he D AI D S Ta ble f or Gra di n g t he Se verit y of A d ult a n d Pe diatric A d verse E ve nts, Versi o n 2. 1 
date d J ul y 2 0 1 7, 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. 
F or tri gl yceri des, L D L ( 4 t h ge nerati o n), a n d c h olester ol, t he 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 a 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 visit, u p t o last e x p os ure date f or partici pa nts 
w h o per ma ne ntl y disc o nti n ue d st u d y dr u g, or t he last a vaila ble date i n t he data base s na ps h ot f or 


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partici pa nts w h o were still o n treat me nt at t he ti me of a n i nteri m a nal ysis. 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 treat me nt e mer ge nt.
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 treat me nt-e mer ge nt 
la b orat or y a b n or malities will be pr o vi de d b y la b test a n d treat me nt gr o u p; 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 test:
•
Gra de d la b orat or y a b n or malities
•
Gra de 3 or 4 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. 
A b y- partici pa nt listi n g of treat me nt-e mer ge nt la b orat or y a b n or malities a n d treat me nt-e mer ge nt 
Gra de 3 or 4 la b orat or y a b n or malities, res pecti vel y, 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 his listi n g 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 test of i nterest, wit h all a p plica ble se verit y gra des a n d a b n or mal 
fla gs dis pla ye d.
7. 3.  
B o d y Wei g ht a n d Vit al Si g ns
Descri pti ve statistics will be pr o vi de d b y treat me nt gr o u p f or b o d y wei g ht, B MI a n d vital si g ns 
as f oll o ws:
•
Baseli ne val ue
•
Val ues at eac h p ost baseli ne visit
•
C ha n ge fr o m baseli ne at eac h p ost baseli ne visit
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/ti me 
of first d ose date 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.


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G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 7
1 7 Ja n uar y 2 0 2 4
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. B o d y wei g ht, hei g ht, a n d B MI  will be i ncl u de d i n t he vital si g ns listi n g, if 
s pace per mits. If n ot, t he y will be pr o vi de d se paratel y.
7. 4.  
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. T he W H O preferre d na me a n d dr u g 
c o de will be attac he d t o t he cli nical data base.
7. 4. 1.   
N o nst u d y Dr u g A ntiretr o vir al Me dic ati o ns
A n y n o nst u d y dr u g A R V me dicati o ns are defi ne d as a n y A R V me dicati o ns ta ke n pri or t o, 
d uri n g, or after t he st u d y (if c ollecte d). All n o nst u d y dr u g A R V me dicati o ns will be liste d. N o 
i nfere ntial statistics will be pr o vi de d. 
7. 4. 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 ta ke n w hile a 
partici pa nt t o o k st u d y dr u g. Use of c o nc o mita nt me dicati o ns fr o m St u d y Da y 1 u p t o t he last 
e x p os ure date will be s u m marize d ( n u m ber a n d perce nta ge of partici pa nts) b y treat me nt gr o u p, 
W H O dr u g class a n d 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 al p ha beticall y b y dr u g class a n d t he n b y 
decreasi n g t otal fre q ue nc y wit hi n a class. 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.
If t he start or st o p date of n o n- A R V me dicati o ns is i nc o m plete, 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 t he start or st o p date will be use d t o deter mi ne w het her t he 
n o n- A R Vs are c o nc o mita nt or n ot. T he me dicati o n is c o nc o mita nt if t he m o nt h a n d year of t he 
start or st o p ( or year of t he start or st o p, if m o nt h is n ot rec or de d) of t he me dicati o n d oes n ot 
meet eit her of t he f oll o wi n g criteria:
•
T he m o nt h a n d year of start of t he me dicati o n is after t he last e x p os ure date
•
T he m o nt h a n d year of st o p of t he me dicati o n is bef ore t he first d ose date of st u d y dr u g
If t he start a n d st o p date of n o n- A R V me dicati o ns are c o m plete, t he start date is n ot after last 
e x p os ure date a n d t he st o p date is n ot bef ore first d ose date, or t he n o n- A R V me dicati o ns are 
mar ke d as o n g oi n g a n d start date is o n or bef ore last e x p os ure date, t he n o n- A R V me dicati o ns 
are c o nc o mita nt.
S u m maries of n o n- A R V c o nc o mita nt me dicati o ns 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. A b y- partici pa nt listi n g f or all n o n- A R V c o nc o mita nt 
me dicati o ns will be liste 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.


Le naca pa vir
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Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 8
1 7 Ja n uar y 2 0 2 4
7. 5.  
Electr oc ar di o gr a m Res ults
7. 5. 1.  
I n vesti g at or Electr oc ar di o gr a m Assess me nt
T he i n vesti gat ors’ assess me nt of E C G res ults ( 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) are c ollecte d at scree ni n g o nl y. A b y- partici pa nt listi n g f or 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.
7. 6.   
Ot her S afet y Me as ures
A data listi n g will be pr o vi de d f or partici pa nts e x perie nci n g pre g na nc y a n d partici pa nts 
usi n g/ mis usi n g a n y s u bsta nces (e g, illicit dr u g) d uri n g t he st u d y, res pecti vel y. P h ysical 
e xa mi nati o n was n ot c ollecte d i n t he e C R F. T heref ore, it will n ot be i ncl u de d i n t he a nal ysis.
7. 7.  
P artici p a nt S u b gr o u p f or S afet y E n d p oi nts
I nci de nce of all treat me nt-e mer ge nt A Es will be re peate d wit hi n eac h s u b gr o u p defi ne d i n 
Secti o n 3. 4. 1 usi n g t he Safet y A nal ysis set. N o f or mal statistical testi n g is pla n ne d.
7. 8.   
C h a n ges Fr o m Pr ot oc ol- S pecifie d S afet y A n al ysis
N o c ha n ge fr o m pr ot oc ol-s pecifie d safet y a nal yses is pla n ne d.


L e n a c a p a vir 
G S- U S- 2 0 0 -4 3 3 4 
St ati sti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
8-
P H A R M A C O K I N E T I C  ( P K) A N A L Y S E S 
8. 1. 
P K S a m pl e  C oll e cti o n 
V er si o n  1. 0 
Bl o o d  s a m pl e s  wi ll b e  c oll e ct e d t o d et e n ni n e P K ( a n d m et a b oli tes, if a p pli c a b le)  i n pl a s m a  at  t h e 
f ollo w i ng  ti m e p oi nts: 
F or  T r e at m e nt Gr o u p s 1 a n d 2: 
Pl a s m a P K s a m pli n g wi ll o c c m  rel ati v e  t o d os i ng of G S- 6 2 0 7  at  t h e f oll o wi n g ti m e p oi nt s  f or  a ll 
p aiii ci p a nt s: 
•  D a y s  1,  2,  a n d 8: 
- 
Pr e d o s e  ( withi n  3 0  mi n u t es of d os i ng) 
-   
A si ngl e  ti m e d P K s a m pl e  b et w e e n  1  a n d  6  h o m s  p o st d o s e 
I 
•  At  D a y 1 5 a n d  at  all  vi si ts wit h  S C  G S 6 2 0 7  i nj e cti o ns: A  s i ngl e  pr e d o s e  P K  s a m p l e wi ll b e 
c oll e ct e d 
•  St aiii n g  at  W e e k  4  vi sit , at  all  vi si ts wit h o ut  S C  G S- 6 2 0 7  i nje cti o ns:  A s i ngl e  a n yti m e P K 
s a m pl e  wi ll b e  c oll e ct e d 
I 
I 
F or  T r e at m e nt Gr o u p 3: 
St aiii n g  at  D a y  1  vi sit ,  a si ngl e  a n yti m e P K s a m pl e w ill b e  c o lle ct e d  at  all  st u d y vi sit s . 
C O N FI D E N TI A L 
P a g e  3 9 
1 7 J a n u a 1 y 2 0 2 4 


L e n a c a p av ir 
G S- U S - 20 0 -4 3 3 4 
St a tis tic a l A n al ysis  Pl a n  - Fi n a l A n al ysis 
I 
F or  Tr e at m e nt  Gr o u p  4: 
V ersi on 1. 0 
•  St aiii n g  at D a y 1 vi s it,  a si ngl e  a n yt im e P K sa m pl e  wi ll b e  c o lle ct e d  at  all st u dy  vis its. 
8. 2. 
P K A n al y s e s  R el at e d  t o P K  S a m pli n g 
8. 2 . 1. 
S t atisti c al A n al y s i s M e t h o ds 
Pl as m a c o n c e n tr nti o n f or L E N  a n d  o t h er a p pr o p riat e  a n al yt es  wi ll b e list e d f or  a ll p aiii c ip a nt s 
a n d  s Uilllll ai ·iz e d  b y  n o mi n a l ti m e p o i nt f or p ait ici p a nt s  i n t h e P K  A n al y sis  S et  b y  tr e at m ent 
g r o u p. 
S u m m a 1y  s t atis ti cs  ( n, m e a n ,  9 0 % CI , S D , c o effi ci e nt  of  v ai ·iat i o n [ %C V] , m e d i a n,  mi n, m a x, 
Ql ,  a n d  Q 3)  wi ll b e pr es e nt e d  f or  b ot h i ndi vi d u al  p aiii c ip a nt  c o n c e n tr atio n  d at a  b y ti m e  p o i nt  b y 
tr e at m e nt g i-o u p  a n d  a n a l yt e. M or e o v er,  t h e g e o m etr i c m e a n,  9 5 %  CI,  a n d  t h e m e a n  a n d  S D  of 
t h e  nat ur al  lo g -tr a ns f on n e d v al u e s  wi ll b e  pr e s e n t e d. 
T h e s a m p l e si z e f or e a c h  ti m e p o i nt wi ll b e  b a s e d  o n  t h e n u m b e r  of p a 1t ici p a nt s  wit h  n o n mi s s i ng 
c o n c e ntr at i o n d at a  at  t hat  ti m e p o i nt. T h e  n u m b e r  of p aiii c ip a nt s  wit h  c o n c e ntr at i o n B L Q  wi ll b e 
pr e s e n t e d f or e a c h  ti m e p o i nt. F or  s u m m ai y  st ati sti cs,  B L Q v a l ue s  wi ll b e  tr e at e d as O at pr e d os e 
a n d  o n e - half  of t h e l o w er  L O Q  f or p o st d os e ti m e p o i nt s. 
T h e  f ollo w i ng  t a bl e s  will b e  pr o v i d e d f or e ac h  a n a lyt e  b y  tr e at m e nt g r ou p  a n d  vi sit: 
•  I n di vi du al  p a 1t i ci p a nt  c o n c e n tr ati o n d a t a a n d S llilll n aty  st ati sti cs 
T h e  f ollo w i ng  fig ur es  m a y b e pr o vi d e d  f or e a c h  a n al yt e  b y  tr ea t m ent  g r ou p: 
•  M e a n ( ± S D)  c o n c e n tr ati o n d a t a v er s u s tim e  (o n li ne ai· a n d  s e m ilo g ai·it h mi c s c a l e s) 
•  M e d i a n ( Ql, Q 3 )  c o nc e ntr at i o n d at a  v ers u s  ti m e ( on  li n e ai· an d se mi lo g arit h mi c  sc al e s) 
I n di vi du al,  m e a n,  a n d  m e di a n  p o st d os e  c o n c e ntr at i o n  val u e s t h at  ar e : S L O Q  wi ll n ot b e 
di s pl a y e d i n t h e fig ur e s  a n d  r e m ai ni ng  p o i nt s c o n n e c t e d. 
P K s am pli n g  d et a ils  b y  p aiii c ip a nt, i ncl u di ng  pr o c e d ur e s,  di ff ere n c e s  i n sc h e d ul e d  a n d  a c t u al 
dr a w  ti m es, a n d  s am pl e  a g e  wi ll b e  pr o vi d e d  i n lis ti n gs. 
C O N F I DE N TI A L 
P a g e 4 0 
1 7 J a n ua 1y  2 0 2 4 


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 1
1 7 Ja n uar y 2 0 2 4
T he m olec ular wei g ht of T F V- D P ( 4 4 7. 1 7 g/ m ol) a n d t he de nsit y of 5 0 0 0 milli o n cells/ m L will 
be use d i n t he c o n versi o n of c o nce ntrati o n fr o m n g/ milli o n cells t o µ m ol/ L; w here t he val ue i n 
n g/ milli o n cells * ( 5 0 0 0/ 4 4 7. 1 7) res ults i n t he val ue i n µ m ol/ L or µ M.  
𝑇𝑜
𝑡𝑎𝑙𝑙𝑖𝑜𝑛 𝑐𝑒𝑙𝑙𝑠×
1 𝑛𝑚𝑜𝑙
4 4 7. 1 7 𝑛𝑔×
1 µ 𝒎𝒐𝒍
1 0 0 0 𝑛𝑚𝑜𝑙× 5 0 0 0 𝑚𝑖𝑙𝑙𝑖𝑜𝑛 𝑐𝑒𝑙𝑙𝑠
1 𝑚𝐿
× 1 0 0 0 𝑚𝐿
𝑳
=  µ 𝑚𝑜𝑙
𝐿
=  µ𝑀
8. 2. 2.  
Se ns ati ve A n al ysis
Se nsiti vit y a nal ysis ma y be c o n d ucte d f or t he ke y P K a nal yses if t he P K scie ntist i de ntifies P K 
data as q uesti o na ble or w ort h e xcl u di n g. T he se nsiti vit y a nal ysis will e xcl u de s pecific data fr o m 
a nal yses, if a p pr o priate.
8. 3.   
C h a n ges Fr o m Pr ot oc ol- S pecifie d P K A n al ysis
N o c ha n ge fr o m pr ot oc ol-s pecifie d P K a nal yses is pla n ne d.


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 2
1 7 Ja n uar y 2 0 2 4
9.   
R E F E R E N C E S
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.


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 3
1 7 Ja n uar y 2 0 2 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( R) Versi o n 7. 0. Statistical S ol uti o ns, C or k, Irela n d.


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G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 4
1 7 Ja n uar y 2 0 2 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


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 5
1 7 Ja n uar y 2 0 2 4
1 2.   
A P P E N DI C E S
A p pe n di x 1.  
Sc he d ule of Assess me nts
Scree ni ng a
Day 
1 b
Day 
2
Day 
8
Day 
15
Every 
6 wee ks 
fro m 
Wee k 4 
to 
Wee k 28 
±2 Days
Wee k 38 
±2 Days
Wee k 54 
±2 Days
Wee k 64 
±2 Days
Wee k 80 
±2 Days
Post 
Wee k 80 
Visits c 
±6 Days
Oral 
Bri dgi ng 
Visits d
30, 90, 
180 Day 
Follo w- U p e
Early 
Ter mi natio n f
Written Infor med 
Consent
X
Obtain de mographic 
infor mation
X
Medical History 
X
Co mplete Physical 
Exa mination
X 
X
X 
X g
X
X
X
Sy mpto m- Directed 
Physical Exa mination
X
X
X h
X
X
X 
X
X
Vital Signs i 
(including weight)
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
12-lead E C G (supine) 
X
Height
X
He matology j, 
Che mistry k, Lipid 
panel l, Urinalysis and 
Urine Che mistry m , 
C D4 + Cell Count
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
Urine Storage Sa mple
X 
X
X 
X 
X 
X 
X 
X 
X 
X
X
Seru m Pregnancy Test n
X
X
Seru m F S H o
X
Urine Pregnancy Test n
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
H B V, H C V Testing 
X
HI V-1 Genotyping/
Phenotyping
X
Plas ma HI V-1 R N A 
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
Plas ma Storage 
Sa mple
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X
X
X
P K Plas ma Collection p
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X
C CI


L e n a c a p a vir 
G S- U S- 2 0 0 -4 3 3 4 
St ati sti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
E v er y 
6 w e e k s 
fro m 
W e e k 4 
P o.st 
W e e k 8 0 
V er si o n  1. 0 
I   
I 
I   
I   
··• ; • ·
; • · 
• • · 
,. • · 
; 1 - - -
:-'1 ;I 
: 
......... 
, 1,, 
·
1 1
1 1  ,  1  1  1 
t  
• I 
•
..... , .. . 11 .,  ., 
S u b c ut m e o us 
G S- 6' 2JJ 7 
A d mi ni. 5tr a 1i o n" 
F/f A F Dis p ells ali c n v 
T A F Di < J p e n s ati c n W 
Bi ct e gr a vir 
f)j ~ 
Bi F/f A F 
f)j ~ 
Sr u d y Dr u g 
A c cr u nl a bilit y 
Q >l, A dr n ms 1i ati o n' 
I nj e di m Si kl R e a c b o n 
A = n e nt 
W a ks b e et "' 
A d v ers e E v e ms/ 
C o o:: a uit a ut 
M e di c ati o os 
X 
- - 1 
1 - -
X 
X 
X 
X    
X 
X 
X    
X 
1•• 
I 
I 
I 
I 
I 
I 
I 
I   I 
LJ 
X 
X    
X 
X 
X 
X    
X 
a  
S cr e e ni n g  e v al u ati o n s  m ust  b e  c o m pl et e d  wit hi n  3 0  d a y s pri or  t o D a y  I 
X 
X    
X    
X    
X    
X    
X 
X 
X 
X    
X 
X    
X    
X    
X    
X    
X 
X    
X    
X    
X    
X    
X 
X    
X    
X    
X    
X    
X 
X    
X    
X    
X 
X    
X    
X    
X    
X    
X 
X 
X 
X 
X 
X 
X 
X    
X    
X    
X    
X    
X    
X 
X 
b  
D a y  I  t ests a n d  pr o c e d m· es m u st  b e  c o m pl et e d  pri or  t o a d mi nistr ati o n of t h e d o s e of s t u d y dr u g . P a 1ti ci p a n ts m u st  b e gi n  d o si n g o n  t h e s a m e  d a y as D a y  I 
X 
c  
Ass ess m e nts  will  b e  p erf or m e d  p o st  W e e k  8 0  ( W e e k 9 0 , W e e k  1 0 6 , W e e k  I 1 6, W e e k  1 3 2 , W e e k  1 4 2)  a n d  will  c o nti n u e  t o alt er n at e  b et w e e n  e v er y I O w e e ks  a n d e v er y 
1 6 w e e ks  w it h t h e visit  wi n d o w ± 6 d a y s. 
d  
O nl y  a p pli c a bl e  t o p arti ci p a nts  w h o  r e q uir e o r al w e e kl y  bri d gi n g if a n S C  i nj e cti o n of G S- 6 2 0 7  c a n n ot b e  a d mi nist er e d  f or a n y r e as o n wit hi n  t h e pr ot o c ol  vi sit  wi n d o w . 
e  
P a 1ti ci p a nts  m a y  b e  r e q uir e d t o r et ur n t o t h e cli ni c f or a  3 0 , 9 0  a n d  1 8 0 -D a y  F oll o w- U p  Vi sit  aft er  E arl y  T e mti n ati o n  vis it. 
f  
Wit hi n  7 2 h o m·s of p e 1 m a n e ntl y  di sc o nti n ui n g  st u d y . C o u n sel p arti ci p a nt  r e g ar di n g t h e ir n p o 1t a n c e of c o nti n ui n g a  c o m pl et e  A R V  t h er a p y i n a c c or d a n c e  t o sta n d ar d of c ar e 
a n d  r ef er p a 1ti ci p a nt  t o a n a p pr o pri at e  HI V  tr e at m e nt f a cilit y. 
g  
C o m pl et e  p h y si c al e x a m is o nl y  r e q uir e d at W e e k 2 8 
C O N FI D E N TI A L 
P a g e 4 6 
1 7 J a n u a 1 y 2 0 2 4 


L e n a c a p a vir 
G S- U S- 2 0 0 -4 3 3 4 
St ati sti c al  A n al ysis  Pl a n  - Fi n al  A n al ysis 
h  
S y m pt o m  dir e ct e d  p h y si c al  t o b e  c o m pl et e d  at W e e k s  4, 1 0 , 1 6 , a n d 2 2 , a s  n e c ess a 1 y 
Vit al  s i g ns - bl o o d  pr ess m· e, p ul s e , r es pir ati o n r at e, t e m p er at ur e, a n d  w e i g ht 
J 
H e m at ol o g y : C B C  w it h diff er e nti al  a n d  pl at el et  c o u nt 
V er si o n  1. 0 
k  
C h e mistri es : Al k ali n e  p h os p h at as e , A S T , A L T , G G T , t ot al bili m bi n , dir e ct  a n d i n dir e ct bili m bi n , t ot al pr ot ei n , al b u mi n , L D H , C P K , bi c ar b o n at e ,  BU N , c al ci u m , c hl ori d e , 
cr e ati ni n e , gl u c os e , li p as e, m a g n esi u m , p h o s p h o m s , p ot a s si u m , s o di u m, a n d  uri c  a ci d . e G F R a c c or di n g  t o t h e C o c k cr oft -G a ult  f or m ul a 
F asti n g  is n ot  r e q uir e d f or t h e li pi d p a n el 
m  
Uri n al ysis  a n d  Uri n e  C h e mistr y:  i n cl u di n g c ol or  &  cl arit y , sp e cifi c  gr a vit y , p H , gl u c os e , k et o n es , bili m bi n , m· o bili n o g e n,  bl o o d,  nitrit e,  l e u k o c yt e es t er as e a n d  mi cr o sc o pi c 
(if mi cr o sc o pi c  el e m e nts ar e  s e e n) , mi n e  pr ot ei n , al b u mi n , cr e ati ni n e , p h o sp h at e , c al ci u m, m a g n e si u m a n d  uri c  a ci d 
n  
W o m e n  will  h a v e  a  s er u m t est p e 1f o 1 m e d at S cr e e ni n g . U 1i n e  pr e g n a n c y t est will  o nl y  b e  d o n e  f or w o m e n of c hil d b e a 1i n g  p ot e nti al . I n Tr e at m e nt  Gr o u ps  1  a n d 2, mi n e 
pr e g n a n c y  t ests  s h o ul d b e  c o nf o m e d t o b e  n e g ati v e  pri or  t o s u b c ut a n e o us G S -6 2 0 7  a d mi nistr ati o n . If a n y pr e g n a n c y  t est is  p o siti v e, st u d y d m g s h o ul d  b e  i m m e di at el y 
i nt e m 1 pt e d, a n d  p arti ci p a nt  s h o ul d c o m e  t o t h e sit e f or ser u m pr e g n a n c y  t est. 
o  
F S H  t est is r e q uir e d f or w o m e n  w h o  ar e  < 5 4  y e ar s  ol d a n d  h a v e sto p p e d  m e n s t m ati n g f or : C:: 1 2  m o nt h s b ut  d o  n ot  h a v e  d o c u m e nt ati o n of o v ari a n  h o n u o n al  f ail ur e . 
p  
P K  c oll e cti o n:  F or  Tr e at m e nt Gr o u ps 1 a n d 2,  pl a s m a  P K  sa m  li n o w ill o c c ur  r el ativ e  t o d osi n g  of G S- 6 2 0 7 at D a  s 1, 2  a n d  8  r e d os e ( wit hi n 3 0  mi n ut e s of d o si n g) a n d a 
si n gl e ti m e d P K  sa m pl e  b et w e e n 1 a n d 6 h o m·s p o s t d os e. 
. At D a y 1 5 a n d all vi sits wit h  S C 
G S- 6 2 0 7 ,  a si n gl e pr e d o s e  P K  s a m pl e will  b e  c oll e ct e d . St art m g  at W e e  
4  a n  at a 
VI Slts w 1 
o ut S C  G S -6 2 0 7 , 6 2 0 7  m c  u  m g  
e  Or al  Bri d gi n g  vis its, if a p pli c a bl e , a 
si n gl e a n yti m e  P K  sa m pl e  w ill b e  c oll e ct e d . P K  sa m pli n g  w ill c o nti n u e  at vis its  p a st  W e e k  8 0 . 
F or  Tr e at m e nt Gr o n  s  3  a n d  4  a 1ti ci  a nts  st a1ti n g at D a 
1 a  si n gl e a n  i m e P K  sa m  l e w ill b e  c oll e ct e d at all  s t u d  vi sits. 
q 
I 
s 
Tr e at m e nt Gr o u p  1  a n  2  or a  G S- 6 2 0 7  e a m at D a y 1, D a y  2  a n  D a y  8.  Tr e at m e nt Gr o u p  3  will  r e c ei v e or al  G S -6 2 0 7  l e a d i n at D a y s  1 a n d 2  a n d  will  b e gi n  or al  d ail y 
G S- 6 2 0 7 at D a y  3. 
u  
T r eat m e nt Gr o u p  1 a n d  2  S u b c ut a n e o u s  a d mi nistr ati o n at D a y 1 5 a n d e v er y 2 6  w e e ks 
v  
Tr e at m e nt  Gr o u p  1,  2,  a n d 3 F / TA F o n c e  d ail y  f or 2 8  w e e ks  st a1ti n g at D a y 1. Tr e at m e nt Gr o u p  3  p a 1ti ci p a n ts will  c o nti n u e  F/ T A F u ntil s t u d y c o m pl eti o n. 
w    T r eat m e nt Gr o u p  1 d ail y  o r al T A F  t o b e  i niti at e d at W e e k  2 8 
x    
T r eat m e nt Gr o u p  2  d ail y  o r al  BI C t o b e  i niti at e d at W e e k  2 8 
y  
Tr e at m e nt  Gr o u p  4  d ail y  o r al B/ F/ T A F 
z  
Pri or  t o c o m pl eti o n of ot h er s t u d y pr o c e d m· es, p a 1ti ci p a nts  will  c o m pl et e HI V T S Q 1 2 , HI V D Q o L , a n d  E Q- E D -5 L at D a y 1 (e x c e p t HI V T S Q 1 2) , D a y  1 5  (HI V T S Q 1 2  o nl y) , 
W e e k  4,  W e e k  2 8 , W e e k  5 4 , W e e k  8 0 . I nj e cti o n A c c e pt a bilit y  S c al e  a n d  N m u eri c  P ai n  R ati n g  S c al e  t o b e  c o m pl et e d at D a y 1 5 , W e e ks  2 8 , 5 4  a n d  8 0  (f or Tr e at m e nt  Gr o u ps  1 
a n d 2  p a 1ti ci p a nts  o nl y ) aft er S C  G S- 6 2 0 7  a d mi nistr ati o n  a n d c o m pl eti o n of ot h er  st u d y pr o c e d ur e s. 
a a  
Pr o vi d e  I nj e cti o n S it e R e a cti o n  Ass ess m e nt  W or k s h e et  a n d i ns t m ct t h e p arti ci p a nts  t o m e as ur e  a n d  r e p ort i nj e cti o n sit e r e a cti o ns f oll o wi n g t h e a d mi nistr ati o n of t h e 
s u b c ut a n e o us i nj e cti o ns  (f or  Tre at m e nt Gr o u p 1 a n d 2  p a 1ti ci p a nts  o nl y ) 
C O N FI D E N TI A L 
P a g e  4 7 
1 7  J a n u a1 y  2 0 2 4 


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 8
1 7 Ja n uar y 2 0 2 4
A p pe n di x 2.  
Pr o gr a m mi n g S pecific ati o n
1) If t he a ge fr o m t he Da y 1 e C R F is n ot a vaila ble, a ge will be calc ulate d as f oll o ws:
O nl y year is pr o vi de d f or t he date of birt h ( D O B). Use J ul y 1 f or t he m o nt h a n d da y.
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 D O B a n d St u d y Da y 1,
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,
A G E = t he i nte ger of t he res ult i n (c),
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)
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.
3)
Scree n fail ure partici pa nts are t he 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 criteria or “ Yes” f or a n y e xcl usi o n criteria re gar dless of w hic h versi o n of pr ot oc ol 
t he partici pa nt was c o nse nt t o.
4)
Partici pa nts i n t he ra n d o mize d a nal ysis set are defi ne d as partici pa nts ra n d o mize d i nt o 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 t he partici pa nt is ra n d o mize d 
(ie, partici pa nt wit h n o n- missi n g R G M N 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 C R F 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).
5)
Ra n d o mize d treat me nt (ie, T R T 0 1 P i n A D S L) is deri ve d fr o m I X R S R A N D, w hile act ual 
treat me nt recei ve d (ie, T R T 0 1 A i n A D S L) is assi g ne d as t he ra n d o mize d treat me nt if 
partici pa nt t o o k at least 1 d ose of st u d y dr u g a n d assi g ne d as bla n k if t he partici pa nt was 
ne ver d ose d.
6) I n t he 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 
as t he y a p pear o n t he e C R F.
7)
B o d y mass i n de x ( B MI) 
B MI will be calc ulate d o nl y at baseli ne as f oll o ws:

B MI = ( wei g ht [ k g]) / ( hei g ht [ meters] 2)
Baseli ne hei g ht a n d wei g ht will be use d f or t his calc ulati o n if a vaila ble.


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 9
1 7 Ja n uar y 2 0 2 4
8)
S A S c o des f or t he treat me nt c o m paris o n f or de m o gra p hics a n d baseli ne c haracteristics ta bles.
C M H test f or n o mi nal varia ble ( Y), t he p- val ue fr o m t he ge neral ass ociati o n test s h o ul d be 
use d f or n o mi nal varia bles:
p r o c  f r e q ;
t a b l e s  t r t  *  Y  / c m h ;  / * g e n e r a l  a s s o c i a t i o n  t e s t * /
r u n ;
C M H test f or or di nal varia ble ( Y), t he p- val ue fr o m t he r o w mea n sc ore test s h o ul d be use d 
f or or di nal varia bles:
p r o c  f r e q ;
t a b l e s  t r t  *  Y  /  c m h 2  ;  / * r o w  m e a n  s c o r e  t e s t * /
r u n ;
Kr us kal- Wallis test f or c o nti n u o us varia ble ( Y):
p r o c  n p a r 1 w a y  w i l c o x o n ;
c l a s s  t r t ;  
v a r  Y ;
r u n ;
9)
F or race a n d et h nicit y, “ N ot Per mitte d”, “ Missi n g”, or “ Ot her” will be e xcl u de d fr o m 
perce nta ge calc ulati o n a n d als o e xcl u de d f or p- val ue ge nerati o n f or cate g orical data a nal ysis 
(e g, C M H test or Kr us kal- Wallis test).
1 0) St u d y Da y 1, Last D ose Date a n d Last E x p os ure Date
a)
All t he ke y dates were defi ne d i n Secti o n 3. 8. 1 . 
1 1) St u d y Da y 1 a n d Last D ose Date
a)
All t he ke y dates were defi ne d i n Secti o n 3. 8. 1 .
b)
St u d y Da y 1 is defi ne d as t he earliest of t he d ose start dates fr o m a n y St u d y Dr u g 
A d mi nistrati o n e C R F (ie, E X, E X _ A R V or E X _I V). 
c)
Last D ose Date is defi ne 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 i n 
Treat me nt Gr o u ps 1 t o 3, or c o m plete d st u d y dr u g at mai n p hase i n Treat me nt Gr o u p 4 
acc or di n g t o St u d y Dr u g C o m pleti o n e C R F(ie, S D R G C O M P). 
i)
F or partici pa nts w h o recei ve S C i njecti o n(ie, A partici pa nt has data i n E X _I V.) a n d 
t o o k a n y oral bri d gi n g L E N(ie, A partici pa nt has data i n E X. E X T R T =” Oral G S-
6 2 0 7” a n d E X. E X D O S F R Q _ S T D =” 1 TI M E P E R W E E K”), t he last d ose date is 
defi ne d as earliest of t he last d ose date of oral bri d gi n g L E N(ie, t he last d ose date of 
E X. E X T R T =” Oral G S- 6 2 0 7” a n d E X. E X D O S F R Q _ S T D =” 1 TI M E P E R W E E K”) or 
oral Q D dr u g(ie, t he last d ose date i n E X _ A R V),


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 5 0
1 7 Ja n uar y 2 0 2 4
ii)
F or partici pa nts w h o recei ve S C i njecti o n(ie, A partici pa nt has data i n E X _I V.) a n d 
di d n ot ta ke a n y oral bri d gi n g L E N, t he last d ose date is defi ne d as t he latest 
n o n missi n g e n d date of t he st u d y dr u g use d wit h L E N (ie, t he last d ose date i n 
E X _ A R V).
iii) F or partici pa nts w h o d o n ot recei ve S C i njecti o n(ie, A partici pa nt has n o data i n 
E X _I V.), t he last d ose date is defi ne d as t he earliest of t he last d ose date of a n y st u d y 
dr u g (ie, t he earliest of last d ose date i n E X or E X _ A R V).
d)
St u d y dr u g a d mi nistrati o n: Oral rel oa d will be rec or de d as a n “ U nsc he d ule d” visit i n t he 
St u d y Dr u g A d mi nistrati o n e C R F. Partici pa nts wit h oral rel oa d pri or t o t he 1 st d ose of S C 
ha ve “ U nsc he d ule d” d osi n g visits occ urre d pri or t o Da y 1 5 visit. Partici pa nts w h o 
recei ve d a t otal of 5 ta blets of L E N ( 3 0 0 m g) (ie, 2 x 3 0 0 m g L E N ta blets eac h f or t he 
first 2 da ys a n d 1 x 3 0 0 m g L E N ta blet o n t he 8t h da y) pri or t o “ U nsc he d ule d” d osi n g 
visits f oll o we d b y Da y 1 5 visit will be classifie d as oral rel oa d d ue t o missi n g sc he d ule d 
S C d osi n g. Ot her wise, partici pa nts will be classifie d as oral rel oa d d ue t o missi n g 
sc he d ule d oral d osi n g visit.
1 2) A d here nce t o Q D St u d y Dr u g(s): (e xcl u di n g oral lea d-i n L E N a n d oral bri d gi n g L E N)
a)
A d here nce base d o n 1 st u d y dr u g( Treat me nt Gr o u ps 1, 2, a n d 4):
A d h er e nc e (%) 
=  1 0 0×
𝑇𝑜𝑡𝑎𝑙 N o . of pills t a k e n
T ot al  N o. of pills pr escri b e d
=  1 0 0×
∑N o . of pills t a k e n at e ac h dis p e nsi n g p eri o d f or e ac h st u d y dr u g [ 1]
∑N o . of pills pr escri b e d at e ac h dis p e nsi n g p eri od f o r e ac h st u d y dr u g [ 2]
b)
A d here nce base d o n 2 st u d y dr u gs( Treat me nt Gr o u p 3):






[ 2]
]1[
dr u g
eac h 
f or 
peri o d
dis pe nsi n g
eac h 
at 
prescri be d
pills
of
N o.
dr u g
eac h 
f or 
peri o d
dis pe nsi n g
eac h 
at 
 ta ke n 
pills
of
N o.
1 0 0
prescri be d
pills
of
N o.
T otal
 ta ke n
pills
of
N o.
T otal
1 0 0
( %)
A d here nce


Le naca pa vir
G S- U S- 2 0 0- 4 3 3 4
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 5 1
1 7 Ja n uar y 2 0 2 4
1 3) Efficac y A nal ysis
a)
F or cate g orical efficac y res p o nse (e g, Partici pa nts wit h HI V- 1 R N A < 5 0 c o pies/ m L as 
deter mi ne d b y U S F D A- defi ne d s na ps h ot al g orit h m, M = F, or M = E A nal yses): t he 
pr o p orti o n differe nce bet wee n L E N-c o ntai ni n g re gi me n gr o u ps ( Treat me nt Gr o u ps 1 
t o 3) a n d t he B/ F/ T A F gr o u p ( Treat me nt Gr o u p 4) a n d its 9 5 % CIs are calc ulate d base d 
o n t he M H pr o p orti o n a dj uste d b y baseli ne HI V- 1 R N A strat u m (  1 0 0, 0 0 0 vs. 
 1 0 0, 0 0 0 c o pies/ m L) (see S A P Secti o n 6. 2  a n d Secti o n 6. 3  f or details). T he f oll o wi n g 
S A S c o de will be use d t o c o m p ute p- val ue, w here br n ac  is t he baseli ne HI V- 1 R N A 
strat u m, trt gr p is t he treat me nt, a n d res p o nse is t he cate g orical efficac y res p o nse.
p r o c  f r e q  d a t a = a d e f f ;
t a b l e s  b r n a c * t r t g r p * r e s p o n s e / c m h ;  / * p  v a l u e  f r o m  g e n e r a l  
a s s o c i a t i o n * /
r u n ;
b)
All t he A N O V A m o del f or c o nti n u o us efficac y varia ble (e g, C D 4 +): T he differe nces i n 
c ha n ges fr o m baseli ne i n l o g 1 0 HI V- 1 R N A a n d C D 4 + cell c o u nt bet wee n treat me nt 
gr o u ps a n d t he ass ociate d 9 5 % CI will be c o nstr ucte d usi n g a n A N O V A, i ncl u di n g 
baseli ne HI V- 1 R N A strat u m br n ac , re gi o n strat u m re gi o n, a n d treat me nt trt gr p as fi xe d 
effects i n t he m o del.
p r o c  g l m  d a t a = a d e f f ;
c l a s s  b r n a c  r e g i o n  t r t g r p ;
m o d e l  C D 4 = b r n a c  r e g i o n  t r t g r p ;
l s m e a n s  t r t g r p  / a l p h a = 0 . 0 5  c l  p d i f f ;
r u n ;


G S- U S- 2 0 0- 4 3 3 4- Fi n al- 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 8- J a n- 2 0 2 4
0 4: 3 1: 3 2
Cli ni c al P h ar m a c ol o g y
e Si g n e d
1 8- J a n- 2 0 2 4
2 2: 5 0: 2 3
Cli ni c al D e v el o p m e nt
e Si g n e d
1 8- J a n- 2 0 2 4
2 3: 0 8: 0 8
P P D
P P D
P P D

Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 2 Randomized, Open Label, Active Controlled Study 
Evaluating the Safety and Efficacy of Long-acting Capsid Inhibitor 
GS-6207 in Combination with Other Antiretroviral Agents in 
People Living with HIV
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
136260 
Not Applicable
NCT04143594
Indication:
HIV-1 Infection
Protocol ID:
GS-US-200-4334
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List
Protocol Version/Date:
Original:
02 October 2019
Amendment 1:
05 November 2019
Amendment 2:
24 January 2020
Amendment 3:
01 September 2020
Amendment 4:
04 February 2022
This study will be conducted under US Food and Drug Administration IND regulations 
(21 CFR Part 312); however, sites located in the European Economic Area and Switzerland are 
not included under the IND and are considered non-IND sites.
GILEAU 


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.


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Final 
Amendment4 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................................................ 3 
LIST OF IN-TEXT TABLES ......................................................................................................................................... 6 
LIST OF IN-TEXT FIGURES ........................................................................................................................................ 7 
PROTOCOL SYNOPSIS ................................................................................................................................................ 8 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 15 
1. 
INTRODUCTION ................................................................................................................................................ 19 
1.1. 
Backgrowid .............................................................................................................................................. 19 
1.2. 
GS-6207 ................................................................................................................................................... 19 
1. 2 .1. 
General Infonnation .............................................................................................................. 19 
1.2.2. 
Clinical Studies of GS-6207 .................................................................................................. 20 
1.3. 
Info1mation About Bictegravir ................................................................................................................ 57 
1.3.1. 
General Infonnation .............................................................................................................. 57 
1.4. 
Info1mation About Tenofovir Alafenamide ............................................................................................ 58 
1.4.1. 
General Infonnation .............................................................................................................. 58 
1.5. 
Info1mation About Emtricitabine/Tenofovir Alafenamide ..................................................................... 58 
1.5.1. 
General Infonnation .............................................................................................................. 58 
1.6. 
Info1mation About Bictegravir/Emti·icitabine/Tenofovir Alafenamide .................................................. 59 
1.6.1. 
General Infonnation .............................................................................................................. 59 
1.7. 
Rationale for This Study .......................................................................................................................... 59 
1.8. 
Rationale for Dose Selection ................................................................................................................... 59 
1.8.1. 
GS-6207 ................................................................................................................................. 59 
1.8.2. 
F/TAF and TAF ..................................................................................................................... 61 
1.8.3. 
BIC ........................................................................................................................................ 61 
1.8.4. 
B/F/TAF ................................................................................................................................ 61 
1.9. 
Rationale for Oral Weekly Bridging of GS-6207 for Missed SC Injection ............................................ 61 
1.10. 
Risk/Benefit Assessment for the Study ................................................................................................... 62 
1.11. 
Co1npliance .............................................................................................................................................. 63 
2. 
OBJECTIVES ....................................................................................................................................................... 64 
3. 
STUDY DESIGN ................................................................................................................................................. 65 
3.1. 
3.2. 
3.3. 
3.4. 
Endpoints ................................................................................................................................................. 65 
Study Design ........................................................................................................................................... 65 
Study Treatlnents ..................................................................................................................................... 65 
Duration ofTreatlnent ............................................................................................................................. 66 
4. 
PARTICIPANTPOPULATION .......................................................................................................................... 68 
4.1. 
Number of Participants and Part icipant Selection ................................................................................... 68 
4.1.1. 
Participant Replacement ........................................................................................................ 68 
4.2. 
Inclusion Criteria ..................................................................................................................................... 68 
4.3. 
Exclusion Criteria .................................................................................................................................... 68 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS ............................................................................................. 70 
5.1. 
Randomization, Blinding, and Treatment Codes Access ........................................................................ 70 
5.1.1. 
Randoinization ....................................................................................................................... 70 
5.1.2. 
Blinding ................................................................................................................................. 70 
5.2. 
Description and Handling ofLenacapavir (GS-6207) Injection, Lenacapavir (GS-6207) 
Tablets, TAF, F/TAF, B/F/TAF, and Bictegravir ................................................................................... 70 
CONFIDENTIAL 
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GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Final 
Amendment4 
5.2.1. 
Fo1mulation ........................................................................................................................... 70 
5.2.2. 
Packaging and Labeling ........................................................................................................ 71 
5.2.3. 
Storage and Handling ............................................................................................................ 72 
5.3. 
Dosage and Administrntion of Study Dmgs ............................................................................................ 73 
5 .4. 
Dosing and Administration of Oral Weekly Bridging of GS-6207 ......................................................... 7 4 
5.5. 
Prior and Concomitant Medications ........................................................................................................ 76 
5.6. 
Accountability for Investigational Medicinal Product ............................................................................ 78 
5.6.1. 
Investigational Medicinal Product Return or Disposal of GS-6207, TAF, 
F/TAF, BIC, and B/F/TAF .................................................................................................... 78 
6. 
STUDY PROCEDURES ...................................................................................................................................... 80 
6.1. 
6.2. 
6.3. 
6.4. 
6.5. 
6.6. 
6.8. 
6.9. 
Participant Enrollment and Treatment Assignment ................................................................................ 80 
Preti·eatinent Assessments ....................................................................................................................... 80 
6.2.1. 
Screening Visit ...................................................................................................................... 80 
Treatinent Assessments ........................................................................................................................... 81 
6.3.1. 
Day 1 ..................................................................................................................................... 81 
6.3.2. 
Day 2,1111 Day 8, and Day 15 .......................................................................................... 82 
6.3.3. 
Treatment Assessments (Week 4 - Week 28) ....................................................................... 83 
6.3.4. 
Post Week 28 Assessments ................................................................................................... 84 
Post-ti·eatment Assessments .................................................................................................................... 86 
6.4.1. 
Early Te1mination Visit Assessments ................................................................................... 86 
6.4.2. 
30-Day, 90-Day and 180-Day Follow-up Visits ................................................................... 88 
Clinical Laborato1y Assessments ............................................................................................................ 89 
6.5.1. 
Blood Samples ....................................................................................................................... 89 
6.5.2. 
Pha1macokinetic Assessments: .............................................................................................. 90 
6.5.3. 
Blood Storage Samples .......................................................................................................... 91 
6.5.4. 
Urine Samples ....................................................................................................................... 92 
Criteria for Discontinuation of Stud Treatment. .................................................................................... 92 
End of Study ............................................................................................................................................ 94 
Post Study Care ....................................................................................................................................... 94 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ................................................................................ 95 
7.1. 
Definitions of Adverse Events and Serious Adverse Events ................................................................... 95 
7.1.1. 
Adverse Events ...................................................................................................................... 95 
7 .1. 2. 
Serious Adverse Events ......................................................................................................... 9 5 
7.2. 
Assessment of Adverse Events and Serious Adverse Events .................................................................. 96 
7.2.1. 
Assessment of Causality for Study Thugs and Procedw-es ................................................... 96 
7.2.2. 
Assess1nent of Severity .......................................................................................................... 96 
7.3. 
Investigator Requirements and Instrnctions for Reporting Adverse Events and Serious 
Adverse Events ........................................................................................................................................ 97 
7.3.1. 
Adverse Events ...................................................................................................................... 97 
7.3.2. 
Serious Adverse Events ......................................................................................................... 97 
7.4. 
Gilead Reporting Requirements .............................................................................................................. 98 
7.5. 
Clinical Laborat01y Abnonnalities and Other Abno1mal Assessments as Adverse Events or 
Serious Adverse Events ........................................................................................................................... 99 
7.6. 
Toxicity Manageinent .............................................................................................................................. 99 
7.6.1. 
Grades 1 and 2 Laborat01y Abnonnality or Clinical Event .................................................. 99 
7.6.2. 
Grade 3 Laborato1y Abno1mality or Clinical Event .............................................................. 99 
7.6.3. 
Grade 4 Laborato1y Abno1mality or Clinical Event.. .......................................................... 100 
CONFIDENTIAL 
Page4 
04 Febma1y 2022 


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 5
04 February 2022
7.6.4.
Management of Adverse Events of Injection Site Reactions of Grade 3 or 
Higher, or Persisting for More Than 26 Weeks ..................................................................100
7.7.
Special Situations Reports.....................................................................................................................101
7.7.1.
Definitions of Special Situations.........................................................................................101
7.7.2.
Instructions for Reporting Special Situations......................................................................102
7.8.
Safety Monitoring Committee...............................................................................................................103
8.
STATISTICAL CONSIDERATIONS...............................................................................................................104
8.1.
Analysis Objectives and Endpoints.......................................................................................................104
8.1.1.
Analysis Objectives.............................................................................................................104
8.1.2.
Primary Endpoint.................................................................................................................104
8.1.3.
Secondary Endpoint.............................................................................................................104
8.2.
Planned Analyses...................................................................................................................................105
8.2.1.
Interim Analysis ..................................................................................................................105
8.2.2.
Primary Analysis .................................................................................................................105
8.2.3.
Final Analysis......................................................................................................................105
8.3.
Analysis Conventions............................................................................................................................106
8.3.1.
Analysis Sets .......................................................................................................................106
8.3.2.
Data Handling Conventions ................................................................................................106
8.4.
Demographic and Baseline Characteristics Analysis............................................................................106
8.5.
Efficacy Analysis...................................................................................................................................107
8.5.1.
Primary Analysis .................................................................................................................107
8.5.2.
Secondary Analyses.............................................................................................................107
8.6.
Safety Analysis......................................................................................................................................107
8.6.1.
Extent of Exposure ..............................................................................................................107
8.6.2.
Adverse Events....................................................................................................................108
8.6.3.
Laboratory Evaluations .......................................................................................................108
8.6.4.
Other Safety Evaluations.....................................................................................................108
8.7.
Adjustments for Multiplicity .................................................................................................................108
8.8.
Pharmacokinetic Analysis .....................................................................................................................109
8.9.
Biomarker Analysis...............................................................................................................................109
8.10.
Sample Size ...........................................................................................................................................109
8.11.
Data Monitoring Committee..................................................................................................................109
9.
RESPONSIBILITIES.........................................................................................................................................110
9.1.
Investigator Responsibilities .................................................................................................................110
9.1.1.
Good Clinical Practice.........................................................................................................110
9.1.2.
Financial Disclosure ............................................................................................................110
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval..............................................................................................................................110
9.1.4.
Informed Consent ................................................................................................................110
9.1.5.
Confidentiality.....................................................................................................................111
9.1.6.
Study Files and Retention of Records .................................................................................111
9.1.7.
Case Report Forms ..............................................................................................................113
9.1.8.
Investigator Inspections.......................................................................................................113
9.1.9.
Protocol Compliance ...........................................................................................................113
9.2.
Sponsor Responsibilities .......................................................................................................................113
9.2.1.
Protocol Modifications ........................................................................................................113
9.2.2.
Study Report and Publications ............................................................................................114
9.3.
Joint Investigator/Sponsor Responsibilities ..........................................................................................114
9.3.1.
Payment Reporting ..............................................................................................................114
9.3.2.
Access to Information for Monitoring.................................................................................114
9.3.3.
Access to Information for Auditing or Inspections .............................................................115
9.3.4.
Study Discontinuation .........................................................................................................115


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 6
04 February 2022
10.
REFERENCES...................................................................................................................................................116
11.
APPENDICES....................................................................................................................................................117
Appendix 1.
Investigator Signature Page...................................................................................................118
Appendix 2.
Study Procedures Table.........................................................................................................119
Appendix 3.
Management of Clinical and Laboratory Adverse Events.....................................................123
Appendix 4.
Pregnancy Precautions, Definition for Women of Childbearing Potential, and 
Contraceptive Requirements..................................................................................................124
Appendix 5.
Pandemic Risk Assessment and Mitigation Plan ..................................................................127
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-200-4071: GS-6207 Formulations and Doses Evaluated............................................21
Table 1-2.
GS-US-200-4071: Preliminary Plasma Pharmacokinetic Parameters of GS-6207 
Following Single Dose Oral Administration of 50 mg/mL Solution in Capsule (N = 
8 per cohort).............................................................................................................................22
Table 1-3.
GS-US-200-4071: Preliminary Plasma Pharmacokinetic Parameters of GS-6207 
Following Multiple Dose Oral Administration of 30 mg and 100 mg Solution in 
Capsule (50 mg/mL) (N = 8 per cohort)..................................................................................23
Table 1-4.
GS-US-200-4071: Preliminary Plasma Pharmacokinetic Parameters Following 
Single Dose Oral Administration of GS-6207 Tablets, Fasted, or Following a High 
or Low Fat Meal (N = 8 per cohort) ........................................................................................25
Table 1-5.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters of GS-6207 
300 mg Oral Capsule Following Administration Alone or with DRV/COBI 
(800/150 mg QD) or COBI (150 mg QD) [N = 29-30 per cohort]..........................................29
Table 1-6.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters of GS-6207 
300 mg Tablet Following Administration Alone or with RIF (600 mg QD) or FAM 
(40 mg) [N = 25-27 per cohort]...............................................................................................30
Table 1-7.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters of PIT (2 mg) 
Following Administration Alone or with GS-6207 (N = 30-31).............................................31
Table 1-8.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters of ROS (5 mg) 
Following Administration Alone or with GS-6207 (N = 30) ..................................................31
Table 1-9.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters of TAF (25 mg) 
and its Metabolite, TFV, Following Administration Alone or with GS-6207 
(N = 28-30) ..............................................................................................................................32
Table 1-10.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters of MDZ (2.5 
mg) and its Metabolite, 1-OH-MDZ, Following Administration Alone or with 
GS-6207 (N = 30-31)...............................................................................................................33
Table 1-11.
Preliminary Pharmacokinetic Parameters for GS-6207 Injection, 309 mg/mL.......................35
Table 1-12.
GS-US-200-4538: Summary of Adverse Events in > 2 Participants by Preferred 
Term.........................................................................................................................................36
Table 1-13.
GS-US-200-5709: Summary Statistics of GS-6207 Plasma Pharmacokinetic 
Parameters (Cohort 1) (GS-6207 PK Analysis Set) ................................................................38
Table 1-14.
GS-US-200-5709: Summary Statistics of GS-6207 Plasma Pharmacokinetic 
Parameters (Cohort 2) (GS-6207 PK Analysis Set) ................................................................40
Table 1-15.
GS-US-200-5709: Summary Statistics of GS-6207 Plasma Pharmacokinetic 
Parameters (Cohort 3) (GS-6207 PK Analysis Set) ................................................................41
Table 1-16.
GS-US-200-4334: Study Treatments.......................................................................................49
Table 5-1.
GS-6207 Dosing for Treatment Group 1 and 2 .......................................................................73
Table 5-2.
GS-6207 Dosing for Treatment Group 3.................................................................................74


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 7
04 February 2022
Table 5-3.
Dosing Schedule for Oral Weekly Bridging and Resumption of SC GS-6207 
Injection...................................................................................................................................75
Table 5-4.
Missed Dose Recommendations for GS-6207 During Oral Weekly Bridging........................76
Table 5-5.
List of Representative Medications that are Prohibited or To Be Used with Caution 
due to the Potential for Drug-Drug Interaction with GS-6207................................................77
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-200-4071: Preliminary Mean (SD) GS-6207 Plasma Concentration-Time 
Profiles Following Single-Dose Administration of Oral GS-6207 Solution in 
Capsule (50 mg/mL; N = 8/cohort) .........................................................................................22
Figure 1-2.
GS-US-200-4071: Preliminary Mean (SD) GS-6207 Plasma Concentration-Time 
Profiles Following Single-Dose Oral Administration of GS-6207 Tablets, Fasted (N 
= 8/cohort) ...............................................................................................................................24
Figure 1-3.
GS-US-200-4071: Preliminary Mean (SD) GS-6207 Plasma Concentration-Time 
Profiles Following Single-Dose Administration of Oral GS-6207 300 mg Tablets, 
Administered Fasted or with a High Fat or Low Fat Meal (N = 8/cohort)..............................24
Figure 1-4.
GS-US-200-4072: Mean and 95% CIs Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (Full Analysis Set)......................................................................................27
Figure 1-5.
GS-US-200-4538: Preliminary Mean (SD) GS-6207 Plasma Concentration-Time 
Profiles Following Single-Dose Administration of GS-6207 Injection, 309 mg/mL 
(N = 8 per cohort) ....................................................................................................................34
Figure 1-6.
GS-US-200-5709: Mean (SD) GS-6207 Plasma Concentration Versus Time (Cohort 
1: Through Day 225) (GS-6207 PK Analysis Set)..................................................................37
Figure 1-7.
GS-US-200-5709: Mean (SD) GS-6207 Plasma Concentration Versus Time (Cohort 
2: Through Day 85) (GS-6207 PK Analysis Set)....................................................................39
Figure 1-8.
GS-US-200-4334: Study Design .............................................................................................50
Figure 1-9.
Simulated Pharmacokinetic Profile of Oral Weekly Bridging of GS-6207 (300 mg) 
(A) Prior to and (B) After Resuming SC Injection..................................................................62
Figure 3-1.
Study Schema ..........................................................................................................................67


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Study Title: 
IND Number: 
EudraCT Number: 
ClinicalTrials.gov 
Identifier: 
Study Centers 
Planned: 
Objectives: 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
Final 
Amendment4 
A Phase 2 Randomized, Open Label, Active Contrnlled Study 
Evaluating the Safety and Efficacy of Long-acting Capsid Inhibitor 
GS-6207 in Combination with Other Antiretrnviral Agents in 
People Living with HIV 
136260 
Not Applicable 
NCT04143594 
Approximately 75 centers in North America and Latin America 
The primaiy objective of this study is: 
• 
To evaluate the efficacy of GS-6207 (Lenacapavir, LEN) 
containing regimens in people living with HIV (PL WH) as 
determined by the proportion of paiticipants with HIV-1 RNA 
< 50 copies/mL at Week 54 
The secondaiy objectives of this study are: 
• 
To evaluate the efficacy of GS-6207 containing regimens in 
PL WH as determined by the proportion of paiticipants with 
HIV-1 RNA < 50 copies/mL at Weeks 28, 38, and 80 
• 
To evaluate the change from baseline in log10 HIV-1 RNA and 
in CD4+ cell count at Weeks 28, 38, 54, and 80 
• 
To evaluate the safety and tolerability of the GS-6207 
containing regimens through 28, 38, 54, and 80 weeks of 
treatment 
• 
To evaluate the phannacokinetics (PK) of GS-6207, BIC, and 
TAF 
Page8 
04 Febrna1y 2022 


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Study Design: 
Number of 
Paiiicipants 
Planned: 
Tai·get Population: 
CONFIDENTIAL 
I 
Final 
Amendment4 
This is a Phase 2, randomized, open label, active controlled, 
multicenter study. 
Treatment-naive PL WH who meet all eligibility criteria will be 
randomized in a 2:2:2:1 ratio to 1 of the 4 treatment groups. 
Randomization will be stratified by HIV-I RNA level 
(~ 100,000 copies/mL or > 100,000 copies/mL) at Screening. 
Treatment Group 1 (n = 50) 
Induction: GS-6207 600 mg oral on Day 1 and Day 2, GS-6207 
300 mg oral on Day 8, then subcutaneous (SC) GS-6207 927 mg on 
Day 15 + oral daily emti·icitabine/tenofovir alafenamide (F/TAF) 
(200/25 mg) from Day 1 onwai·ds for a total of28 weeks 
Maintenance: SC GS-6207 927 mg on Week 28 and eve1y 26 weeks 
+ oral daily T AF (25 mg) 
Treatment Group 2 (n = 50) 
Induction: GS-6207 600 mg oral on Day 1 and Day 2, GS-6207 
300 mg oral on Day 8, then SC GS-6207 927 mg on Day 15 + oral 
daily F/TAF (200/25 mg) from Day 1 onwards for a total of 
28 weeks 
Maintenance: SC GS-6207 927 mg on Week 28 and eve1y 26 weeks 
+ oral daily bictegravir (BIC) (75 mg) from Week 28 onwai·ds 
Treatment Group 3 (n = 50) 
GS-6207 600 mg oral on Day 1 and Day 2 then oral daily GS-6207 
50 mg+ oral daily FffAF (200/25 mg) from Day 1 onwai·ds 
Treatment Group 4 (n = 25) 
Oral daily B/F/TAF (50/200/25 mg) 
Approximately 175 paiiicipants will be emolled in this study. 
50 paiiicipants may be emolled in Treatment Group 1 
50 paiiicipants may be emolled in Treatment Group 2 
50 paiiicipants may be emolled in Treatment Group 3 
25 paiiicipants may be emolled in Treatment Group 4 
Treatment nai've PL WH 
18 yeai·s of age. 
Page9 
04 Febrna1y 2022 


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Duration of 
Treatment: 
Diagnosis and Main 
Eligibility Criteria: 
Study Procedures/ 
Frequency: 
CONFIDENTIAL 
Final 
Amendment4 
Duration of tr·eatment is at least 80 weeks. Participants in Treatment 
Group 4 will complete the study at Week 80. 
Following successful completion of Week 80 visit, participants 
receiving GS-6207 will be given the option to receive further 
tr·eatment and continue to attend visits on Week 90, Week 106, 
Week 116, Week 132, Week 142, and will continue to alternate 
between eve1y 10 weeks and eve1y 16 weeks visits. Paiticipants 
willing to continue the study beyond Week 80 in Treatment 
Groups 1 and 2 will continue to receive SC GS-6207 927 mg eve1y 
6 months (26 weeks) from Week 80 onwards and paiticipants in 
Treatment Group 3 will receive oral GS-6207 50 mg daily from 
Week 80 until the product becomes accessible to participants 
through an access program, or until Gilead elects to discontinue the 
study in the country . Pa1ticipants in Treatment Groups 1, 2, and 
3 will also receive TAF, F/TAF, or BIC as applicable. 
Paiticipants who discontinue study dmgs prior to Week 80 visit or 
prior to study completion may be required to complete 30-Day, 90-
Day and/or 180-Day Follow Up visits after Eai·ly Tennination Visit. 
Treatment naive PL WH who meet the following criteria: 
• 
Age :::: 18 yeai·s of age at Screening 
• 
Plasma HIV-1 RNA 
200 copies/mL at Screening 
• 
CD4+ cell count ~ 200 cells/µL at Screening 
• 
Antiretr·oviral naive with no use of any ARV within one month 
of Screening. Use of pre-exposure prophylaxis (PrEP) ( any 
duration), post-exposure prophylaxis (PEP) (any duration), or 
HIV-1 h'eatment ( < 10 days therapy total) > 1 month prior to 
Screening is permitted. 
At Screening, laborato1y analyses (hematology, chemistry and 
urinalysis and sennn pregnancy test [ for women]), HIV-1 RNA, 
CD4+ cell count, vital signs, elech'ocai·diograin (ECG), complete 
physical examination and estimated glomemlar filtr·ation rate 
(eGFR) will be perfo1med, and hepatitis B vims (HBV) and 
hepatitis C vims (HCV) serologies will be analyzed 
After screening procedures, eligible paiticipants will be randomized 
into one of the four tr·eatment groups in a 2:2:2:1 ratio. 
Paiticipants in Treatment Groups 1, 2, and 3 only, will have visits 
on Day 1, Day 2, 
Day 8, and Day 15. All 
Page 10 
04 Febrna1y 2022 


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
CONFIDENTIAL 
Final 
Amendment4 
paiiicipants will have a Week 4 visit and will continue to attend 
study visits eve1y 6 weeks until Week 28. 
Paiiicipants in Treatment Groups 1 and 2 will need to have 
HIV-1 RNA results < 50 copies/mL at Weeks 16 and 22 to initiate 
treatment with a two-agent regimen at Week 28; those with values 
:::: 50 copies/mL will discontinue the study drng at or prior to 
Week 28. 
After Week 28, paiticipants will attend study visits on Week 38, 
Week 54, Week 64, and Week 80. After Week 80, paiiicipants in 
Treatment Group 4 will complete the study and paiiicipants in 
Treatment Groups 1, 2, and 3 will be given the option to receive 
fmther treatment and continue to attend visits alternating between 
eve1y 10 weeks and eve1y 16 weeks visits. 
At each visit, adverse events (AEs), concoinitant medications, 
laborato1y tests and physical examinations will be perfo1med in 
accordance with the Study Procedmes Table (Appendix 2). 
Pharmacokinetic Assessments: 
For Treatment Groups 1 and 2: 
Plasma PK sampling will occm relative to dosing of GS-6207 at the 
following time points for all pa1ticipants: 
• 
Days 1, 2, and 8: 
-
Predose (within 30 minutes of dosing) 
-
A single timed PK sample between 1 and 6 homs postdose 
I 
• 
At Day 15 and at all visits with SC GS-6207 injections: A single 
predose PK sample will be collected 
• 
Staiiing at Week 4 visit, at all visits without SC GS-6207 
injections: A single anytime PK sample will be collected 
I 
Page 11 
04 Febrna1y 2022 


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Test Product, Dose, 
and Mode of 
Administration: 
Reference Therapy, 
Dose, and Mode of 
Administration: 
CONFIDENTIAL 
For Treatment Group 3: 
Final 
Amendment4 
• 
Staiiing at Day 1 visit, a single anytime PK sample will be 
collected at all study visits 
For Treatment Group 4: 
• 
Staiiing at Day 1 visit, a single anytime PK sample will be 
collected at all study visits. 
Patient Reported Outcomes (PROs) (if available): 
• 
HIV Dependent Quality of Life (HIVDQoL) and EQ-ED-5L at 
Day 1, Weeks 4, 28, 54 and 80 
• 
HIV Treatment Satisfaction Questionnaire (HIVTSQ12) at 
Day 15, Weeks 4, 28, 54 and 80 
• 
The Injection Acceptability Scale and Numeric Pain Rating 
Scale at Day 15, Weeks 28, 54 and 80 (for Treatment Groups 1 
and 2 pa1i icipants only) 
Treatment Group 1 
Induction: Oral GS-6207, SC GS-6207, and oral F/TAF 
Maintenance: SC GS-6207 and oral TAF 
Treatment Group 2 
Induction: Oral GS-6207, SC GS-6207, and oral F/TAF 
Maintenance: SC GS-6207 and oral BIC 
Treatment Group 3 
Oral GS-6207 and oral F/TAF 
Paiiicipants in Group 1 and Group 2 may require oral weekly 
bridging 300 mg if a SC injection of GS-6207 cannot be 
administered for any reason within the protocol visit window. 
Treatment Group 4 
Oral B/F/TAF 
None after Week 80 
Page 12 
04 Febrna1y 2022 


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Criteria for 
Evaluation: 
Safety: 
Efficacy: 
Phannacokinetics: 
Statistical Methods: 
CONFIDENTIAL 
Final 
Amendment4 
Incidence ofti·eatment-emergent adverse events (TEAEs) and 
ti·eatment-emergent clinical laborato1y abno1malities 
The prima1y endpoint of this study is: 
• 
The proportion of participants with HIV-1 RNA < 50 copies/mL 
at Week 54 as detennined by the Food and Drng Adminisu-ation 
(FDA)-defined snapshot algorithm 
The secondaiy endpoints of this study are: 
• 
The proportion of paiticipants with HIV-1 RNA < 50 copies/mL 
at Weeks 28, 38, and 80 as detennined by the FDA-defined 
snapshot algorithm 
• 
The change from baseline in log10 HIV-1 RNA and in CD4+ cell 
count at Weeks 28, 38, 54, and 80 
The following PK pai·ameters will be calculated for GS-62O7, T AF, 
and BIC (and metabolites, as appropriate) in plasma, as appropriate. 
AUCo-t, AUCtau, AUC1as1, CL/F, t112, Az, VzlF, Cmax, Tmax, Ciast, T1ast, 
Ctau, Ct 
The prima1y efficacy analysis is to compare the propo1tion of 
paiticipants with HIV-1 RNA < 50 copies/mL at Week 54 as 
dete1mined by the US FDA-defined snapshot algorithm. Point 
estimates and 95% confidence interval (CI) for the difference in the 
response rates between each of the GS-62O7-containing regimen 
groups (Treatment Groups 1 to 3) and the B/F/TAF group 
(Treatment Group 4) will be constructed using n01mal 
approximation method, sti·atified by baseline HIV-1 RNA level 
(~ 100,000 copies/mL or > 100,000 copies/mL). The percentage of 
paiticipants with HIV-1 RNA < 50 copies/mL at Weeks 28, 38, and 
80 respectively, as dete1mined by the US FDA-defined snapshot 
algorithm will be analyzed using the saine methods as for the 
primaiy efficacy endpoint. Baseline HIV-1 RNA level 
(~ 100,000 copies/mL or > 100,000 copies/mL) adjusted differences 
in change from baseline in log10 HIV-1 RNA and CD4+ cell count 
at Weeks 28, 38, 54, and 80 between each of the 
GS-62O7-containing regimen groups (Treatment Groups 1 to 3) and 
the B/F/TAF group (Treatment Groups 4) and the associated 
Page 13 
04 Febrna1y 2022 


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 14
04 February 2022
95% CIs will be constructed using analysis of variance (ANOVA) 
models. 
Incidence of TEAEs and treatment-emergent laboratory 
abnormalities will be summarized using descriptive statistics.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
λz
terminal elimination rate constant, estimated by linear regression of the terminal elimination 
phase of the log concentration versus time curve of the drug
%AUCexp
percentage of AUC extrapolated between AUClast and AUCinf
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ALT
alanine aminotransferase 
ANOVA
analysis of variance
ART
antiretroviral therapy
ARV
antiretroviral
AST
aspartate aminotransferase 
AUC
area under the concentration versus time curve
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as 
AUClast + (Clast/λz)
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCtau
area under the concentration versus time curve over the dosing interval
BIC
BCRP
Bictegravir, B
breast cancer resistance protein
B/F/TAF
bictegravir/emtricitabine/tenofovir alafenamide 
BMI
BLQ
body mass index
below the limit of quantitation 
bpm
beats per minute
BUN
blood urea nitrogen
BVY
bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®)
CAI
capsid inhibitor
CBC
complete blood count
CFR
Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
CL/F
apparent oral clearance after administration of the drug:
CL/F = Dose/AUCinf, where “Dose” is the dose of the drug 
Clast
last observed quantifiable concentration of the drug
CLcr
creatinine clearance
Cmax
maximum observed concentration of drug
CMH
Cochran-Mantel-Haenszel
COBI
cobicistat
CPK
creatine phosphokinase
CRF
case report form
CRO
contract (or clinical) research organization 
CSR
clinical study report


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Ct
observed drug concentration
Ctau
observed drug concentration at the end of the dosing interval
CYP
cytochrome P450
DAIDS
DDI
Division of AIDS
Drug-Drug Interaction
DMC
Data monitoring committee
DNA
deoxyribonucleic acid
DRV
darunavir
EC
ethics committee
ECG
EFV
Electrocardiogram
Efavirenz
eCRF
electronic case report form
EDC
electronic data capture
eGFR
Estimated glomerular filtration rate
EudraCT
European Clinical Trials Database
eSAE
electronic serious adverse event
ET
early termination
eTMF
Electronic trial master file
EU
FAM
European Union
famotidine
FAS
Full Analysis Set
FDA
Food and Drug Administration
FDC
fixed-dose combination
FSH
follicle-stimulating hormone
F/TAF
emtricitabine/tenofovir alafenamide
FTC
Emtricitabine
GD
Gestation Day
GGT
gamma-glutamyltransferase
GCP
Good Clinical Practice
Gilead
Gilead Sciences, Inc.
GLSM
geometric least-squares mean
HBV
hepatitis B virus
HCV
hepatitis C virus
HDL
high-density lipoprotein
HDPE
high-density polyethylene
HIV, HIV-1
human immunodeficiency virus, type 1
HIVDQoL
HIV Dependent Quality of Life
HIVTSQ12
HIV Treatment Satisfaction Questionnaire
HLGT
high-level group term
HLT
high-level term


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IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
IEC
Independent ethics committee
IND
investigational new drug (application)
INSTI
Integrase strand transfer inhibitor
IQ
inhibitory quotient
IRB
institutional review board
IV
intravenous
IWRS
Interactive Web Response System
LDH
lactate dehydrogenase
LDL
low-density lipoprotein
LLT
lower-level term
LLOQ
MDZ
lower limit of quantitation
midazolam
MedDRA
NaS
NOAEL
NOEL
Medical Dictionary for Regulatory Activities
Sodium Salt
No-Observed-Adverse-Effect Level 
No-Observed-Effect Level
NNRTI
nonnucleoside reverse transcriptase inhibitor
NRTI
PIT
Nucleoside reverse transcriptase inhibitors
pitavastatin
PBMC
Peripheral blood mononuclear cell
PD
pharmacodynamic(s)
PEP
Post-exposure prophylaxis
PI
protease inhibitor
PopPK
population pharmacokinetic
PrEP
PRO
Pre-exposure prophylaxis
Patient Reported Outcomes
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PLWH
people living with HIV
PPI
proton pump inhibitors
PT
Preferred Term
GLPS
Global Patient Safety (formerly Pharmacovigilance and Epidemiology)
QD
once daily
RIP
rifampin
ROS
rosuvastatin
RAL
raltegravir
SAC
Safety Assessment Committee


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SADR
serious adverse drug reaction
SAE
serious adverse event 
SC
Subcutaneous
SD
standard deviation
SOC
system organ class
SOP
standard operating procedure
SUSAR
SSR
SVR
suspected unexpected serious adverse reaction
special situation report
suboptimal virologic response
TAF
tenofovir alafenamide
TDF
tenofovir disoproxil fumarate
TEAE
treatment-emergent adverse event
Tlast
time (observed time point) of Clast
Tmax
the time (observed time point) of Cmax
TFV
Tenofovir
TFV-DP
tenofovir diphosphate
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log 
of 2 by the terminal elimination rate constant (λz)
ULN
upper limit of normal
US, USA
United States, United States of America
VORI
Voriconazole
VR
virologic rebound
WHO
World Health Organization


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1.
INTRODUCTION
1.1.
Background
Human Immunodeficiency Virus (HIV)-1 infection is a life-threatening and serious disease of 
major public health significance, with approximately 37 million people living with HIV (PLWH) 
worldwide including approximately 16 million on antiretroviral (ARV) treatment {UNAIDS 
2018}. Advances in combination antiretroviral therapy (ART) for HIV have led to significant 
improvements in morbidity and mortality by suppressing viral replication, preserving 
immunologic function, and averting disease progression to acquired immunodeficiency 
syndrome (AIDS). Standard-of-care for the treatment of HIV-1 infection involves the use of a 
combination of oral ARV drugs (ie, 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a 
third agent) to suppress viral replication to below detectable limits, increase CD4 cell counts, and 
delay disease progression.
While combination ART for the treatment of HIV-1 infection is efficacious and well tolerated, 
these agents need to be taken every day and require near perfect adherence to minimize the 
emergence of drug resistant variants. In addition, “treatment fatigue” can occur, which is defined 
as “decreased desire and motivation to maintain vigilance in adhering to a treatment regimen” 
among PLWH prescribed chronic or life-long treatment {Claborn 2015}, which can lead to 
nonadherence and treatment failure. As such, there remains a significant medical need for ARVs 
that can be administered less frequently (ie, long acting drug products), thereby providing an 
alternative treatment option for PLWH. In addition, some PLWH may benefit from combination 
HIV therapy using GS-6207.
1.2.
GS-6207
GS-6207 is a novel, first-in-class, selective inhibitor of HIV-1 capsid function, which has potent 
antiviral activity, low human clearance, and physicochemical properties well suited for 
extended-release parenteral or oral formulations. GS-6207 has been assigned the International 
Nonproprietary Name Lenacapavir (LEN).
1.2.1.
General Information
For further information on GS-6207, please refer to the Investigator’s Brochure (IB). Information 
in the IB includes:

Nonclinical pharmacokinetic (PK) and in vitro metabolism

Nonclinical pharmacology and toxicology

Clinical experience


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1.2.2.
Clinical Studies of GS-6207
A summary of the relevant available data from studies not yet included in the IB is presented. 
These data are from four Phase 1 clinical studies in healthy volunteers (GS-US-200-4071, 
GS-US-200-4333, and GS-US-200-4538) and one study in PLWH (GS-US-200-4072). 
Participants in study GS-US-200-4072 received injections of a subcutaneous (SC) GS-6207 
suspension formulation that will not be used in this protocol. Studies GS-US-200-4071 and 
GS-US-200-4538 used the tablet and SC solution formulations, respectively, that will be used in 
this study.
1.2.2.1.
GS-US-200-4071
GS-US-200-4071 is an ongoing, Phase 1 study in healthy volunteers evaluating the safety, 
tolerability, and PK of single and multiple ascending doses of oral GS-6207 as an oral liquid 
(solution)-filled capsule (50 mg/mL or 100 mg/mL) or tablet (50 mg or 300 mg). As of 
03 September 2019, a total of 50 unique participants have received GS-6207 or placebo capsules 
and 46 unique participants have received GS-6207 or placebo tablets. Single and multiple dose 
PK data from the 50 mg/mL solution filled capsule, and single dose PK data from the tablets are 
presented below. To reduce pill burden, the GS-6207 tablet will be the oral form used in this 
study.
This study was originally designed as a SAD/MAD evaluation of solution in capsule 
formulations, with 10 days of washout between the single dose and multiple dose periods 
(Cohorts 1 and 2). Following receipt of PK data from these 2 cohorts suggesting the t1/2 was 
longer than predicted, the study design was altered to be single ascending dose.
Within each cohort, participants were randomized to receive GS-6207 (N = 8) or placebo 
(N = 2); all treatments were administered under fasted conditions, unless otherwise specified. In 
Cohorts 1, 2 and 5, capsules containing 50 mg/mL solution were evaluated at doses of 30, 100, 
and 300 mg, respectively. Following development of a tablet formulation, 50 mg and 300 mg 
tablets were assessed in which participants were randomized to receive GS-6207 (N = 8) or 
placebo (N = 2) under fasted conditions. In addition, two cohorts received open-label 300 mg 
GS-6207 tablets (N = 8) given with a high fat, high calorie meal or with a low fat, low calorie 
meal. A brief description of all cohorts is presented in Table 1-1.


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Table 1-1.
GS-US-200-4071: GS-6207 Formulations and Doses Evaluated
Formulation Description
Dose (# capsules/fasting status)
Single dose solution in capsule
50 mg/mL
30 mg (1 capsule, fasted)
100 mg (3 capsules, fasted)
300 mg (8 capsules, fasted)
Multiple dose solution in capsule
50 mg/mL
30 mg (1 capsule, fasted)
100 mg (3 capsules, fasted)
Single dose tablet
50 mg
50 mg (1 tablet, fasted)
300 mg
300 mg (1 tablet, fasted)
900 mg (3 tablets, fasted)
1800 mg (6 tablets, fasted)
300 mg (1 tablet, high fat)a
300 mg (1 tablet, low fat)a
a
high fat meal included high calorie count (~1000 kcal, ~50% fat), low fat meal included low calorie count (~400 kcal, 
~25% fat)
Pharmacokinetic Results
GS-6207 concentration-time profiles and preliminary PK parameters after administration of 
single oral doses of GS-6207 oral solution in capsules are presented in Figure 1-1 and Table 1-2, 
respectively. Maximum plasma concentrations of GS-6207 (Cmax) occurred between 7 and 
29 hours (median Tmax), and the median t1/2 of GS-6207 was approximately 12 days. Within each 
increase in dose, the increase in Cmax was less than dose proportional, suggesting GS-6207 
exhibits solubility-limited absorption. 


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Gilead Sciences, Inc. 
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Figure 1-1. 
GS-US-200-4071: Preliminary Mean (SD) GS-6207 Plasma 
Concentration-Time Profiles Following Single-Dose Administration of 
Oral GS-6207 Solution in Capsule (50 mg/mL; N = 8/cohort) 
10 
...... 300 mg (50 mg/ml ) 
100 mg (50 mg/ml ) 
-
..J 
-e-
30 mg (50 mg/ml) 
E -
C> 
C -" 
1 
0 
N 
(0 
I en 
(!) 
Mean (SD) 
0.1 
0 
7 
14 
21 
28 
35 
42 
49 
56 
Days post dose 
Table 1-2. 
GS-US-200-4071: Preliminary Plasma Pharmacokinetic Parameters 
of GS-6207 Following Single Dose Oral Administration of 50 mg/mL 
Solution in Capsule (N = 8 per cohort) 
Cohort 1; 30 mg 
Cohort 2; 100 mg 
Cohort 5; 300 mg 
Parameter 
(N =8) 
(N =8) 
(N =8) 
Cmax (ng/mL) 
1.16 (23.9) 
2.70 (55.4) 
4.75 (52.4) 
tmax (hr)t 
29.0 
26.0 
7.00 
(4.00, 90.0) 
(4.00, 96.0) 
(4.00, 18.00) 
AUC1as1 (hr*ng/mL)• 
147 (29.0) 
319 (46.0) 
1990 (52.0) 
AUCinf (hr*ng/mL) 
ND 
ND 
2280 (53.1) 
AUC %Extrapolated 
ND 
ND 
11.6 (61.0) 
(%) 
AUC0_24 (hr*ng/mL) 
17.6 (19.7) 
34.8 (47.3) 
75.7 (61.3) 
t112t(days) 
ND 
ND 
12.3 (10.7, 13.8) 
PK parameters are presented as Mean (%CV), and shown to 3 significant digits; SD = single dose; ND = not detennined due to 
insufficient PK sampling; tMedian (Ql,Q3); • AUC1as1 calculated through Day 7 post dose for Coho1t s 1 and 2 and through last 
ctm·ently available tiniepoint for Coho1t 5; AUC0.24hr= AUC from tinie zero through 24 hom·s post dose 
CONFIDENTIAL 
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04 Febrna1y 2022 


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GS-6207 preliminary PK parameters after 10 daily oral doses of GS-6207 (50 mg/mL solution in 
capsule) are presented in Table 1-3. Consistent with its half-life, following 10 days of multiple 
dosing, the mean GS-6207 Cmax and AUC0-24 were at least 10-fold higher than those after a 
single dose (Table 1-2 and Table 1-3).
Table 1-3.
GS-US-200-4071: Preliminary Plasma Pharmacokinetic Parameters 
of GS-6207 Following Multiple Dose Oral Administration of 30 mg 
and 100 mg Solution in Capsule (50 mg/mL) (N = 8 per cohort)
Parameter
Cohort 1; 30 mg (N = 8)
Cohort 2; 100 mg (N = 8)
50 mg/mL solution in capsule
Cmax (ng/mL)
12.2 (17.1)
41.3 (53.8)
tmax (hr)†
3.50 (1.89, 10.0)
4.00 (4.00, 10.5)
AUC0-24hr (hr*ng/mL)
232 (17.9)
843 (56.5)
%CV = percentage coefficient of variation; Q1 = first quartile; Q3 = third quartile
Pharmacokinetic parameters are presented as Mean (%CV), and shown to 3 significant digits
†Median (Q1, Q3)
GS-6207 concentration-time profiles and preliminary PK parameters after administration of 
single doses of GS-6207 oral tablets administered either under fasted conditions, or with a high 
fat or low fat meal, are presented in Figure 1-2 and Figure 1-3, and Table 1-4. Interim safety and 
PK data are available through at least 8 days postdose. Based on preliminary PK data, GS-6207 
exposures increased in a less than dose-proportional manner over the dose range of 50 mg to 
1800 mg. Maximal concentrations (Cmax) of GS-6207 were achieved approximately 4 to 8 h 
postdose (Tmax), and GS-6207 half-life (t1/2) is estimated to be approximately 12 days (Table 1-4).
Exposure (Cmax and AUC0-D8) and time to maximal exposure (Tmax) were comparable following 
administration of GS-6207 300 mg tablets under fasted conditions or with a high or low fat meal; 
thereby, supporting dosing of GS-6207 tablets with or without food in future clinical trials (Table 1-4).


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Figure 1-2. 
GS-US-200-4071: Preliminary Mean (SD) GS-6207 Plasma 
Concentration-Time Profiles Following Single-Dose Oral 
Administration of GS-6207 Tablets, Fasted (N = 8/cohort) 
100 
::; 
E 10 
-e, 
C -
..... 
0 
"' 
1 
(!) 
-+- 50 mg fasted 
-a- 300 mg fasted 
-+- 900 mg fasted 
-e- 1800 mg fasted 
0,1..._...,.._,.....,...._._._.....,,......_._.._.....,...,..__..,......_....,.._.....,,...._.,....M_ea .. 
n..,<S--iDJ 
Figure 1-3. 
100 
-
..J 
-E 10 
C) 
C -
..... 
0 
N 
: 
1 
(!) 
0 
' 
J 
I 
I 
I 
•t 
7 
14 
21 
28 
35 
Days post dose 
GS-US-200-4071: Preliminary Mean (SD) GS-6207 Plasma 
Concentration-Time Profiles Following Single-Dose Administration of 
Oral GS-6207 300 mg Tab lets, Administered Fasted or with a 
High Fat or Low Fat Meal (N = 8/cohort) 
--e- 300 mg fasted 
--- 300 mg high fat 
--- 300 mg low fat 
,. 
0.1---------------------------M 
... ean
,iii,i,,i--.
so 
0 
CONFIDENTIAL 
7 
Days post dose 
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Table 1-4.
GS-US-200-4071: Preliminary Plasma Pharmacokinetic Parameters 
Following Single Dose Oral Administration of GS-6207 Tablets, 
Fasted, or Following a High or Low Fat Meal (N = 8 per cohort)
Parameter
50 mg
(N = 8)
300 mg
(N = 8)
900 mg
(N = 8)
1800 mg
(N = 8)
300 mg + 
High Fat 
Meal
(N = 8)
300 mg + 
Low Fat 
Meal
(N = 8)
AUCinf 
(hr*ng/mL)
NC
7990 (56.1)
9900 (44.9)
NC
NC
NC
AUC0-D8 
(hr*ng/mL)a
694 (56.0)
2790 (81.5)
3900 (67.2)
5080 (56.3)
2540 (33.6)
2060 (55.7)
Cmax (ng/mL)
8.24 (48.3)
33.7 (96.3)
43.9 (73.3)
53.8 (48.0)
35.0 (33.0)
28.1 (60.6)
Tmax (hr)
4.00
(4.00, 5.50)
4.00
(4.00, 6.00)
4.00
(2.50, 20.0)
8.00
(5.00, 8.00)
5.00
(4.00, 6.00)
6.00
(4.00, 8.00)
T1/2 (h) [days]
NC
265 (223, 349) 
[11.0]
322 (237, 333) 
[13.4]
NC
NC
NC
PK parameters are presented as Mean (%CV) except Tmax and T1/2 which are presented as median (Q1,Q3) and shown to 
3 significant digits; NC = not calculated due to insufficient PK sampling; 
a
AUC0-D8 calculated through Day 8 postdose
Safety Results
Safety data as of 03 September 2019 are available for 56 participants who have received oral 
GS-6207 tablets or matched placebo in one of 6 dosing cohorts.
GS-6207 tablets were generally safe and well tolerated across all treatment groups. A total of 
9 of 56 participants (16.1%) had at least 1 adverse event (AE) reported. The most commonly 
reported AEs were headache (n = 3, 5.4%) and back pain (n = 2, 3.6%). No other AEs were 
reported by more than one participant. No Grade 3 or 4 AEs, deaths, serious adverse events 
(SAEs), pregnancy, or AEs leading to permanent discontinuation of study drug were reported in 
any treatment group.
In a preliminary blinded review of safety data as of 03 September 2019, when all participants 
who had received GS-6207 solution in capsules or placebo-to-match had completed or 
discontinued the study, the safety profile was similar to that observed with the tablets. The only 
AE reported for > 1 participant was headache (6.7%, 2 participants).
1.2.2.2.
GS-US-200-4072
GS-US-200-4072 is an ongoing, Phase 1b, randomized, double-blinded, placebo-controlled, 
multi-cohort dose-ranging study evaluating the safety, tolerability, PK, and short-term antiviral 
activity of monotherapy with SC doses of a GS-6207 free acid suspension (100 mg/mL) in 
PLWH who are either ART naive or ART experienced but capsid inhibitor (CAI) naive.


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This study will enroll 5 cohorts of approximately 8 unique participants per cohort to receive 
GS-6207 or placebo. Within each Cohort (n = 8), participants are randomized in a 3:1 ratio to 
receive active GS-6207 (n = 6) or placebo (n = 2). A single dose of GS-6207 or placebo is 
administered as SC injection(s) in the abdomen on Day 1.
As of 25 July 2019, 32 participants have been administered SC GS-6207 or placebo (3:1 ratio) at 
doses of 20 mg, 50 mg, 150 mg, and 450 mg. Enrollment of a fifth cohort to receive GS-6207 
750 mg is ongoing. Interim blinded data for participants who received GS-6207 20 mg to 450 mg 
are presented below.
Disposition and Baseline Characteristics
As of 25 July 2019, 32 participants have been randomized and received a single dose of SC 
GS-6207 or placebo. All participants are continuing in study follow up. The median duration of 
follow-up (number of days between Day 1 and the last study date) ranged from 38 to 199 days 
across the 4 cohorts.
The majority of participants were male (93.8%), white (56.3%), and not Hispanic or Latino 
(90.6%). The median age was 34 years (range: 19−59 years). The median (Q1, Q3) baseline 
HIV-1 RNA was 4.48 (4.27, 4.68) log10 copies/mL, and the median (Q1, Q3) CD4 cell count was 
458 (361, 594) cells/μL. The majority of participants were ART naive (78.1%).
Efficacy Results
As of 25 July 2019, 32 participants have been randomized and received a single dose of SC 
GS-6207 or placebo. HIV-1 RNA levels decreased following initiation of study drug Figure 1-4). 
The mean (SD) maximum HIV-1 RNA reductions from baseline through Day 10 were 1.35 
(0.318), 1.79 (0.476), 1.76 (0.203), and 2.20 (0.468) log10 copies/mL at doses of GS-6207 20 mg, 
50 mg, 150 mg, and 450 mg, respectively. All participants who received ≥ 50 mg GS-6207 had a 
> 1 log10 copies/mL reduction in their HIV-1 RNA through Day 10. Overall, antiviral activity 
was comparable across the dose range of 50 mg to 450 mg but lower at the 20 mg dose.


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Figure 1-4.
GS-US-200-4072: Mean and 95% CIs Change from Baseline in 
HIV-1 RNA (log10 copies/mL) (Full Analysis Set)
Pharmacokinetic Results
Preliminary PK data show that following 50, 150, and 450 mg doses of GS-6207 SC suspension 
mean GS-6207 concentrations on Day 10 are 1.1- to 9.9-fold higher than the protein adjusted 
(pa)EC95 for wild type HIV-1 based on the EC50 in MT-4 cells (inhibitory quotient [IQ] = 1.1, 
3.3, and 9.9, for the 50, 150, and 450 mg doses, respectively).
Safety Results
As of 25 July 2019, no deaths, Grade 4 AEs, or AEs leading to study drug discontinuation have 
been reported to date. One participant experienced a Grade 3 SAE of atrial fibrillation which 
occurred following methamphetamine use and was not considered related to study drug by the 
investigator. No other serious or Grade 3 AEs were reported. Most (24 of 32, 75%) participants 
reported an AE. The most frequent AEs were injection site pain (40.6%), injection site erythema 
(28.1%), and injection site induration (21.9%).
Six participants (18.8%) had a Grade 3 or Grade 4 laboratory abnormality reported. 
One participant had a Grade 4 laboratory abnormality reported; a Grade 4 creatine kinase 
elevation with a concurrent Grade 3 aspartate aminotransferase (AST) elevation both attributed 
to exercise. The Grade 3 or 4 abnormalities reported for more than one participant were: transient 
creatine kinase elevations, both attributed to recent exercise, (n = 2).
No notable changes from predose in vital signs (systolic blood pressure, diastolic blood pressure, 
pulse, temperature, and respiration rate) have been observed in the study. No clinically 
significant ECG abnormalities have been reported.
---
-1 
-1 
• 
- GS-6207 150 mg 
0 
• GS-6207 50 mg 
/:, - G -6207 :150 mg 
-2 8 
• GS-6207 20 mg 
- Placebo 
-2 
.3 '--,-----~-----~----~----~----------~----~----------"-) 
GS-6207 150 mg (n• ), 
GS-6207 50 mg (n=): 
GS-6207 450 mg (n• ), 
GS-6207 20 mg (n=): 
Placebo (R"'): 
BL 
10 
Day 


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1.2.2.3.
GS-US-200-4329
GS-US-200-4329 is an ongoing Phase 1 study in healthy volunteers evaluating the safety, 
tolerability, PK, metabolism, and excretion of a single intravenous dose (IV) of GS-6207. As of 
17 November 2019, a total of 21 unique participants have received GS-6207 or placebo as a 
1-hour IV infusion. In Cohort 1, 11 participants received 10 mg GS-6207 or placebo (unlabeled; 
N = 8 GS-6207 and N = 3 placebo), and in Cohort 2, 10 participants received 20 mg GS-6207 
containing a mixture of unlabeled GS-6207 and a [14C]-GS-6207 (equivalent to ~200 uCi). 
Safety, PK, and radioactivity analysis is ongoing.
Preliminary radioactivity data through Day 78 postdose in Cohort 2 indicate < 1% of the total 
dose is recovered in the urine and > 80% of the total dose is recovered in the feces, suggesting 
renal elimination is a minor pathway for GS-6207.
1.2.2.4.
GS-US-200-4333
GS-US-200-4333 is an ongoing, Phase 1, open-label, parallel-design, single- and multiple-dose, 
multiple-cohort study in healthy volunteers evaluating the drug-drug interaction (DDI) potential 
of GS-6207. Available preliminary data of administration of GS-6207 capsules administered in 
combination with known strong cytochrome P450 enzyme (CYP)3A/P-glycoprotein (P-gp) 
inhibitors, darunavir (DRV)/cobicistat (COBI) and COBI, or GS-6207 tablets in combination 
with a strong CYP3A/UGT/P-gp inducer, rifampin (RIF), an acid reducing agent, famotidine 
(FAM), and organic anion transporting polypeptide (OATP), breast cancer resistance protein 
(BCRP), P-gp or CYP3A substrates, pitavastatin, rosuvastatin (ROS), TAF and midazolam 
(MDZ), respectively are presented below. Evaluation of GS-6207 PK following co-
administration with voriconazole (VORI), atazanavir/COBI (ATV/co), or efavirenz (EFV) has 
not yet been completed.
Cohort 1 served as a reference arm for Cohorts 2 and 3; participants received a single dose of 
GS-6207 300 mg alone (N = 30). Participants in Cohorts 2 and 3 received up to 90 days of COBI 
150 mg QD, or DRV/COBI 800/150 mg QD, respectively, with a single dose of GS-6207 
300 mg coadministered in the morning on Day 11 (N = 29 per cohort). All doses were 
administered in the morning under fed conditions. Pharmacokinetic samples were obtained up to 
Day 63 (Cohort 1) and up to Day 35 (Cohorts 2 and 3) to characterize the PK of GS-6207 in each 
treatment. Safety data analysis is ongoing.
Preliminary PK data are presented below (Table 1-5). Median maximum plasma concentrations 
of GS-6207 (Cmax) occurred between 6 to 8 hours (Tmax), and the median t1/2 of GS-6207 
administered alone was 12.3 days, and ranged from 16.8 to 18.8 days following administration 
with DRV/co or COBI. Coadministration of DRV/COBI or COBI with GS-6207 resulted in an 
approximate 2-fold increase in Cmax and AUCinf. This 2-fold increase in GS-6207 exposure was 
not deemed clinically relevant, based on safety data from ongoing Phase 1 studies at or above 
exposures anticipated to be achieved following administration of GS-6207 with strong 
CYP3A/P-gp inhibitors. Accordingly, the use of strong CYP3A and P-gp inhibitors is permitted 
with GS-6207.


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Table 1-5.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters 
of GS-6207 300 mg Oral Capsule Following Administration Alone or 
with DRV/COBI (800/150 mg QD) or COBI (150 mg QD) [N = 29-
30 per cohort]
Parameter
GS-6207 Alone 300 mg
(N = 30)
GS-6207 300 mg + 
COBI (N = 29)
GS-6207 300 mg + 
DRV/COBI
(N = 29)
Cmax (ng/mL)
30.6 (74.4)
57.8 (53.6)
61.5 (43.4)
AUClast (h*ng/mL)
10,400 (77.7)
16,100 (61.3)
14,200 (47.3)
AUCinf (h*ng/mL)
10,700 (76.8)
22,700 (62.5)
19,500 (48.7)
Tmax (hours)
8.00 (6.00, 48.0)
8.00 (6.00, 48.0)
6.00 (6.00, 8.00)
t1/2 (days) 
 12.3 (9.97, 15.9)
18.8 (15.9, 24.2)
16.8 (14.5, 19.3)
%CV = percentage coefficient of variation; COBI = cobicistat; DRV = darunavir; Q1 = first quartile; Q3 = third quartile
Pharmacokinetic parameters are presented as Mean (%CV) except Tmax, t1/2, and Tlast, which are presented as median (Q1, Q3), 
and shown to 3 significant digits 
Cohort 4 served as a reference arm for Cohorts 8 and 10; in Cohort 4, participants received a 
single dose of GS-6207 300 mg tablet alone (N = 27). Participants in Cohort 8 received 25 days 
of RIF (600 mg QD), with GS-6207 administered on Day 14, and participants in Cohort 
10 received a single dose of FAM (40 mg) 2 hours prior to a GS-6207 on Day 1 (N = 25 per 
cohort). All GS-6207 doses were administered in the morning under fasted conditions. 
Pharmacokinetic samples were obtained up to Day 23 post GS-6207 dose (Cohorts 4 and 10) and 
up to Day 12 post dose (Cohort 8) to characterize the PK of GS-6207 in each treatment. Safety 
data analysis is ongoing.
The median t1/2 of GS-6207 administered alone was 13.4 days (Table 1-6). Following 
co-administration with RIF, GS-6207 Cmax and AUCinf were approximately 2.5-fold and 5-fold 
lower, respectively, with a corresponding ~5-fold decrease in t1/2. These data support the existing 
recommendations to disallow use of strong inducers with GS-6207. 
Following co-administration with FAM, no change in GS-6207 exposure or t1/2 was observed; 
accordingly, use of famotidine and other acid reducing agents is permitted with GS-6207. 


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Table 1-6.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters 
of GS-6207 300 mg Tablet Following Administration Alone or with 
RIF (600 mg QD) or FAM (40 mg) [N = 25-27 per cohort]
Parameter
GS-6207 Alone 300 mg
(N = 27)
GS-6207 300 mg +RIF
(N = 25)
GS-6207 300 mg +FAM
(N = 25)
Cmax (ng/mL)
20.4 (102)
8.17 (59.6)
18.6 (60.2)
AUClast (h*ng/mL)
3880 (65.3)a
745 (48.1)b
4610 (58.3)
AUCinf (h*ng/mL)
5430 (58.0)a
786 (47.7)b
6360 (52.9)
%AUCexp
30.0 (24.6)a
5.20 (50.7)
28.5 (24.7)
Tmax (hours)
4.00 (4.00, 6.00)
24.0 (24.0, 48.0)
10.0 (4.00, 48.0)
t1/2 (hours)[days] 
321 (261, 374) [13.4]a
63.8 (59.5, 71.1) [2.66]b
270 (250, 331) [11.3]
Tlast (days) 
23.0 (23.0, 23.0)
12.0 (12.0, 12.0)
23.0 (23.0, 23.0)
a N= 25; b = N=24; %CV = percentage coefficient of variation; FAM = famotidine; RIF = rifampin; Q1 = first quartile; Q3 = third 
quartile
Pharmacokinetic parameters are presented as mean (%CV) except Tmax, t1/2, and Tlast, which are presented as median (Q1, Q3), 
and shown to 3 significant digits.
In Cohort 11, participants received PIT, ROS, TAF and MDZ alone, or co-administered with oral 
GS-6207. Agents were either co-dosed with oral GS-6207 to evaluate the worst-case 
(co-administration; PIT, ROS, TAF and MDZ), or up to 3 days after the last dose of GS-6207 
(PIT, MDZ) to evaluate the systemic drug interaction liability of GS-6207. Mean concentrations 
of GS-6207 were at, or above clinically relevant Cmax concentrations (> 100 ng/mL) throughout 
the drug interaction evaluation (data not shown). Preliminary PK data are presented in Table 1-7, 
Table 1-8, Table 1-9 and Table 1-10; Safety data analysis is ongoing.


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Table 1-7.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters 
of PIT (2 mg) Following Administration Alone or with GS-6207 
(N = 30-31)
Parameter
PIT Alone
(N = 31)
PIT+ GS-6207 
(Day 15; 
Co-administration)
(N = 30)
PIT + GS-6207 
(Day 27; 3 Days Post 
GS-6207 Dose)
(N = 30)
Cmax (ng/mL)
31.4 (52.8)
31.0 (48.1)
26.8 (50.5)
AUClast (h*ng/mL)
85.7 (44.9)a
96.8 (47.8)
76.2 (37.7)b
AUCinf (h*ng/mL)
90.9 (43.7)a
102 (46.9)
81.5 (36.1)b
Tmax (hours)
1.00 (1.00, 1.00)
1.00 (1.00, 2.00)
1.00 (1.00, 2.00)
t1/2 (hours)
11.7 (8.56, 13.5)a
10.9 (7.41, 14.7)
14.1 (10.2, 16.5)b
Tlast (hours) 
36.0 (24.0, 48.0)
36.0 (24.0, 48.0)
36.0 (24.0, 48.0)
a N=30; b N=26; %CV = percentage coefficient of variation; PIT = pitavastatin; Q1 = first quartile; Q3 = third quartile
Pharmacokinetic parameters are presented as mean (%CV) except Tmax, t1/2, and Tlast, which are presented as median (Q1, Q3), 
and shown to 3 significant digits.
Table 1-8.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters 
of ROS (5 mg) Following Administration Alone or with GS-6207 
(N = 30)
Parameter
ROS Alone
(N = 33)
ROS+ GS-6207 
(Day 18; Co-administration)
(N = 28)
Cmax (ng/mL)
1.06 (39.5)
1.87 (65.8)
AUClast (h*ng/mL)
10.8 (34.2)a
14.2 (48.1)b
AUCinf (h*ng/mL)
12.3 (33.9)a
16.1 (43.8)b
Tmax (hours)
5.00 (5.00, 5.00)
4.00 (2.00, 4.00)
t1/2 (hours)
13.1 (9.13, 17.8)a
17.3 (13.9, 20.8)b
Tlast (hours) 
36.0 (24.0, 48.0)
48.0 (36.0, 48.0)
a N=30; b N=26; %CV = percentage coefficient of variation; ROS = rosuvastatin; Q1 = first quartile; Q3 = third quartile
Pharmacokinetic parameters are presented as mean (%CV) except Tmax, t1/2, and Tlast, which are presented as median (Q1, Q3), 
and shown to 3 significant digits.


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Table 1-9.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters 
of TAF (25 mg) and its Metabolite, TFV, Following Administration 
Alone or with GS-6207 (N = 28-30)
Parameter
TAF Alone
(N = 30)
TAF+ GS-6207 
(Day 21; Co-administration)
(N = 28)
TAF
 
Cmax (ng/mL)
248 (52.5)
322 (52.6)
AUClast (h*ng/mL)
256 (54.3)
328 (35.3)
AUCinf (h*ng/mL)
262 (54.4)a
361 (27.8)b
Tmax (hours)
1.00 (0.50, 1.13)
1.00 (0.50, 1.50)
t1/2 (hours)
0.38 (0.34, 0.42) a
0.41 (0.35, 0.43) b
TFV
Cmax (ng/mL)
6.29 (30)
7.97 (34.2)
AUClast (h*ng/mL)
171 (26.3)
259 (22.2) c
AUCinf (h*ng/mL)
206 (25.9)
322 (21)
%CV = percentage coefficient of variation; TAF = tenofovir alafenamide; TFV = tenofovir; Q1 = first quartile; Q3 = third 
quartile
a 
N=28
b
N=22
c
N=27
Pharmacokinetic parameters are presented as mean (%CV) except Tmax, and t1/2, which are presented as median (Q1, Q3), and 
shown to 3 significant digits.


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Table 1-10.
GS-US-200-4333: Preliminary Plasma Pharmacokinetic Parameters 
of MDZ (2.5 mg) and its Metabolite, 1-OH-MDZ, Following 
Administration Alone or with GS-6207 (N = 30-31)
Parameter
MDZ Alone
(N = 31)
MDZ+ GS-6207 
(Day 24; Co-administration)
(N = 30)
MDZ + GS-6207 
(Day 25; 1 Day Post GS-6207 
Dose)
(N = 30)
MDZ
Cmax (ng/mL)
9.46 (29.1)
17.7 (22.7)
19.7 (23.8)
AUClast (h*ng/mL)
50.5 (35.1)
129 (24.9)
171 (27.7)
AUCinf (h*ng/mL)
52.9 (36.3)
170 (30.6)
208 (34.5)
Tmax (hours)
2.00 (1.00, 2.00)
2.00 (1.25, 4.00)
2.00 (1.00, 2.00)
t1/2 (hours)
5.18 (3.96, 7.2)
7.05 (6.06, 9.05)
9.38 (7.04, 11.4)
1-OH-MDZ
Cmax (ng/mL)
2.64 (44.4)
1.39 (34.9)
1.33 (36.5)
AUClast (h*ng/mL)
13.1 (39.2)
8.12 (28.6)
9.7 (35.9)
AUCinf (h*ng/mL)
13.9 (38.9)
9.56 (30)
11.5 (43)
%CV = percentage coefficient of variation; MDZ = midazolam; Q1 = first quartile; Q3 = third quartile
Pharmacokinetic parameters are presented as mean (%CV) except Tmax, and t1/2, which are presented as median (Q1, Q3), and 
shown to 3 significant digits.
PIT AUC and Cmax were not affected following administration with GS-6207, suggesting 
GS-6207 does not inhibit OATP transporters (Table 1-7). ROS AUC and Cmax were 
approximately 1.3 to 1.6-fold higher following co-administration with GS-6207 (Table 1-8), 
suggesting GS-6207 inhibits BCRP transporters. TAF and TFV AUC and Cmax were 1.2 to 
1.6-fold higher following co-administration with GS-6207 (Table 1-9), suggesting GS-6207 is a 
weak inhibitor of P-gp transporters. MDZ AUC and Cmax were approximately 2- to 4-fold higher, 
and 1-OH-MDZ AUC and Cmax were correspondingly lower following co-administration with 
GS-6207 (Table 1-10), suggesting GS-6207 is a moderate inhibitor of CYP3A.
1.2.2.5.
GS-US-200-4538
GS-US-200-4538 is an ongoing, blinded Phase 1 study in healthy volunteers evaluating the 
safety, tolerability, and PK of single ascending SC doses of GS-6207 solution formulations. As 
of 28 August 2019, 30 unique participants across 3 dosing cohorts have received single doses of 
either SC GS-6207 injection, 309 mg/mL or placebo (4:1 ratio). Analysis of other formulations is 
ongoing.
Based on the PK data available to date, the GS-6207 injection, 309 mg/mL was selected for use 
in this study. This formulation has been administered as single SC doses of either 309 mg 
(1  1.0 mL) or 927 mg (3  1.0 mL or 2  1.5 mL) in study GS-US-200-4538; these selected 
data are summarized below.


GS-6207 
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Amendment4 
Pharmacokinetic Results 
PK samples will be collected for up to 450 days; PK analysis is ongoing. Data available to date 
after administration of single doses of GS-6207 SC injection, 309 mg/mL are presented below 
(Figure 1-5, Table 1-11). Based on available PK data, a slow initial release of GS-6207 is 
observed; however, concentrations exceeding an IQ of 4 (4-fold higher than the paEC95 from 
MT-4 cells; 3.87 ng/mL) are observed for at least 26 weeks following a single 927 mg dose. 
Preliminaiy PK data through 20 weeks postdose suggest similai· PK profiles following SC 
administration of a 927 mg dose administered as either 3 x 1.0 mL or 2 x 1.5 mL SC injections. 
Figure 1-5. 
100 
:::; 
E 
c, 10 
C -
...... 
0 N 
<9 
Cl) 
c., 
1 
0.1 
0 
4 
GS-US-200-4538: Preliminary Mean (SD) GS-6207 Plasma 
Concentration-Time Profiles Following Single-Dose Administration of 
GS-6207 Injection, 309 mg/mL (N = 8 per cohort) 
•• 
4-fold paEC!6 (IQ4) 
......... t 
•••••••••••••••••••••••••••••••••••• 
-e- 309 mg (1x1ml; 309 mg/ml NaS) 
.....- 927 mg (3x1 ml; 309 mg/ml NaS) 
·-A·- 927 mg (2x1 .5 ml ; 309 mg/ml NaS) 
Mean (SD) 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
56 
Weeks post dose 
paEC95= protein adjusted EC95 from MT-4 cells; 3.87 ng/mL 
CONFIDENTIAL 
Page 34 
04 Febrna1y 2022 


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Table 1-11.
Preliminary Pharmacokinetic Parameters for GS-6207 Injection, 
309 mg/mL 
PK parameter*
(Mean %CV)
309 mg (1  1.0 mL)
(N = 8)
927 mg (3  1.0 mL)
N = 8
927 mg (2  1.5 mL)
N = 8
AUCinf (hr*ng/mL)
68700 (29.4)
256000 (28.8)
NC
AUClast (hr*ng/mL)
49400 (28.8)
147000 (56.9)
NC
%AUCexp (%)
28.6 (64.5)
30.3 (55.1)
NC
Cmax (ng/mL)
17.7 (50.3)
67.0 (54.8)
NC
Tmax (hr)
[days]
2350 (1340, 3360)
[98]
1850 (1680, 2020)
[77]
NC
T1/2 (hr)
[days]
2550 (929, 3000)
[106]
NC
NC
%CV = percentage coefficient of variation; NC = not calculated due to insufficient data at this time; Q1 = first quartile; Q3 
= third quartile
Pharmacokinetic parameters presented to 3 significant figures as mean (%CV), except Tmax and T1/2: median (Q1, Q3).
Safety Results
In a preliminary blinded review of safety data as of 28 August 2019 of the 30 participants who 
received SC GS-6207 injection, 309 mg/mL, no deaths or Grade 4 AEs have been reported. One 
participant was hospitalized for SAE of Grade 3 abscess, which occurred at their ankle; it was 
considered not related to the study medication. No other serious or Grade 3 AEs have been 
reported.
The most frequently reported AEs were injection site induration (21 participants, 70.0%), 
injection site pain (14 participants, 46.7%), and headache and injection site erythema 
(both 10 participants, 33.3%). Adverse events reported for > 2 participants are presented in 
Table 1-12.
Overall, 7 of 30 participants (23.3%) had Grade 3 or 4 laboratory abnormalities. One participant 
had a Grade 4 creatine kinase elevation attributed to exercise.
No notable changes from predose in vital signs (systolic blood pressure, diastolic blood pressure, 
pulse, temperature, and respiration rate) have been observed in the study. No clinically 
significant ECG abnormalities have been reported during the study.


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Table 1-12.
GS-US-200-4538: Summary of Adverse Events in > 2 Participants by 
Preferred Term
Preferred Term
GS-6207
309 mg / 
placebo
N = 10
GS-6207
927 mg / 
placebo
(3  1.0 mL)
N = 10
GS-6207
927 mg / 
placebo
(2  1.5 mL)
N = 10
Total
GS-6207 
927 mg / 
placebo
N = 20
Total
N = 30
Number (%) of Participants with 
Any Treatment-Emergent AE
7 (70%)
10 (100)
10 (100)
20 (100)
27 (90)
Injection site induration
3 (30)
8 (80)
10 (100)
18 (90)
21 (70)
Injection site pain
-
6 (60)
8 (80)
14 (70)
14 (47)
Headache
3 (30)
4 (40)
3 (30)
7 (35)
10 (33)
Injection site erythema
1 (10)
5 (50)
4 (40)
9 (45)
10 (33)
Injection site swelling
-
4 (40)
4 (40)
8 (40)
8 (27)
Injection site nodule
2 (20)
3 (30)
-
3 (14)
5 (17)
Injection site bruising
-
3 (30)
1 (10)
4 (20)
4 (13)
Upper respiratory tract injection
1 (10)
1 (10)
1 (10)
2 (10)
3 (10)
AE = adverse event
1.2.2.6.
GS-US-200-5709
GS-US-200-5709 is an ongoing Phase 1, open-label, multiple-cohort study in healthy 
participants assessing the safety, tolerability, and PK of multiple-dose oral (tablet) and SC 
(309 mg/mL NaS) GS-6207.
In Cohorts 1 and 2 of this study, safety and PK of potential clinical regimens will be evaluated. 
Study conduct is ongoing.
Cohort 3 of this study characterized the safety and PK of GS-6207 administered at clinically 
relevant therapeutic and supratherapeutic exposures; this regimen included oral GS-6207 600 mg 
administered twice daily for 11 days, with the last dose given in the morning on the 11th day. 
Preliminary Pharmacokinetic Results
Interim PK data through Day 225 for Cohort 1 after administration of oral GS-6207 600 mg on 
Days 1 and 2, oral GS-6207 300 mg on Day 8, and SC GS-6207 927 mg on Day 15, are 
presented in Figure 1-6. Intensive PK sampling was conducted on Days 1, 2, 8, and 15, and 
single anytime PK samples were collected at prespecified study visits through Day 225. The 
GS-6207 PK parameters for Days 1, 2, 8, and 15 are summarized in Table 1-13. Mean GS-6207 
plasma concentrations and their lower bound 90% CIs achieved IQ4 (4-fold higher than paEC95) 
within 2 hours postdose on Day 2, and this was maintained through Week 30.


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Figure 1-6.
GS-US-200-5709: Mean (SD) GS-6207 Plasma Concentration Versus 
Time (Cohort 1: Through Day 225) (GS-6207 PK Analysis Set)
BLQ = below the limit of quantitation; IQ4 = inhibitory quotient of 4; GS-6207 = lenacapavir; LLOQ = lower limit of 
quantitation; PK = pharmacokinetic(s); SC = subcutaneous; SD = standard deviation
Cohort 1 dosing was oral GS-6207 600 mg on Days 1 and 2, oral GS-6207 300 mg on Day 8, and SC GS-6207 927 mg on 
Day 15.
Values BLQ were treated as 0 for predose and one-half the LLOQ for postdose summaries. 
LLOQ was defined as 0.5 ng/mL for GS-6207.
Postdose concentration values ≤ LLOQ were not presented on the figure.
Figures on the semi-log scale were set to include all lower bar and mean/median values > 0 on the Y-axis. 
Reference lines indicate IQ4 (15.5 ng/mL) and LLOQ (0.5 ng/mL)
, ... 
t mi-Log calt 
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, .. 
, .. 
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eek 
ohonl (a-) 
31 
29 
23 
22 
19 
20 


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Table 1-13.
GS-US-200-5709: Summary Statistics of GS-6207 Plasma 
Pharmacokinetic Parameters (Cohort 1) (GS-6207 PK Analysis Set)
GS-6207
PK Parameter
Mean (%CV)
Day 1
600 mg oral GS-
6207
(2  300 mg 
tablets)
(N = 31)
Day 2
600 mg oral GS-
6207
(2  300 mg tablets) 
(N = 31)
Day 8
300 mg oral GS-
6207 (1  300 mg 
tablet) 
(N = 31)
Day 15
927 mg SC GS-
6207 (2  1.5 mL 
309 mg/mL NaS) 
(N = 30)
Cmax (ng/mL)
22.0 (45.5)
40.4 (43.4)
39.3 (44.7)
58.7 (58.1)
Tmax (h)a
[days]
4.00 (4.00, 6.00)
[0.17]
6.00 (4.00, 8.00)
[0.25]
6.00 (4.00, 8.00)
[0.25]
2028.04 
(1682.45, 2688.23)
[84.5]
Clast (ng/mL)
11.2 (60.8)
19.2 (40.8)
20.6 (43.1)
25.0 (81.7)
Tlast (h)a
[days]
12.00 
(12.00, 12.00)
[0.5]
120.00
(120.00, 120.00)
[5.0]
144.00 
(144.00, 144.00)
[6.0]
5037.95 
(4032.00, 5042.33)
[209.9]
%CV = percentage coefficient of variation; BLQ = below the limit of quantitation; GS-6207 = lenacapavir; LLOQ = lower limit 
of quantitation; NaS = sodium salt; PK = pharmacokinetics; Q1 = first quartile; Q3 = third quartile; SC = subcutaneous
Median (Q1, Q3).
Values BLQ were treated as 0 for predose and one-half of the LLOQ for postdose summaries.
LLOQ was defined as 0.5 ng/mL for GS-6207.
Interim PK data through Day 85 for Cohort 2 after administration of SC GS-6207 927 mg and 
oral GS-6207 600 mg on Day 1, followed by oral GS-6207 600 mg on Day 2, are presented in 
Figure 1-7. Intensive PK sampling was conducted on Days 1 and 2, and single anytime PK 
samples were collected at prespecified study visits through Day 85. The GS-6207 PK parameters 
for Days 1 and 2 are summarized in Table 1-14. Mean GS-6207 plasma concentrations and their 
lower bound 90% CIs achieved IQ4 within 2 hours postdose on Day 2, and this was maintained 
through Day 85. From Days 0 to 85, mean AUC0-85d (%CV) of 83,082.9 h•ng/mL (43.6%), was 
generally comparable to Cohort 1 (68,364.8 h•ng/mL [49.8%]).


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Figure 1-7.
GS-US-200-5709: Mean (SD) GS-6207 Plasma Concentration Versus 
Time (Cohort 2: Through Day 85) (GS-6207 PK Analysis Set)
BLQ = below the limit of quantitation; IQ4 = inhibitory quotient of 4; GS-6207 = lenacapavir; LLOQ = lower limit of 
quantitation; PK = pharmacokinetic(s); SC = subcutaneous; SD = standard deviation
Cohort 2 dosing was SC GS-6207 927 mg and oral GS-6207 600 mg on Day 1 and oral GS-6207 600 mg on Day 2.
Values BLQ were treated as 0 for predose and one-half the LLOQ for postdose summaries. 
LLOQ was defined as 0.5 ng/mL for GS-6207.
Postdose concentration values ≤ LLOQ were not presented on the figure.
Figures on the semi-log scale were set to include all lower bar and mean/median values > 0 on the Y-axis. 
Reference lines indicate IQ4 (15.5 ng/mL) and LLOQ (0.5 ng/mL)
, ... 
emi-Log cale 
, ... 
, .. 
, .. 
,. 
10 
., 
0 I 
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,. 
., 
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71 
" 
Days 
--b--
... al 
ohort.2 (n•t 
14 
14 
14 
14 
14 
12 
12 
12 
12 


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Table 1-14.
GS-US-200-5709: Summary Statistics of GS-6207 Plasma 
Pharmacokinetic Parameters (Cohort 2) (GS-6207 PK Analysis Set)
GS-6207
PK Parameter
Mean (%CV)
Day 1
927 mg SC GS-6207 (2  1.5 mL 
309 mg/mL NaS)
600 mg Oral GS-6207 (2  300 mg 
Tablets)
(N = 14)
Day 2
600 mg Oral GS-6207
(2  300 mg Tablets) 
(N = 14)
Cmax (ng/mL)
19.9 (35.5)
64.7 (45.0)
Tmax (h)a
[days]
6.00 (4.00, 8.00)
[0.25]
1653.74 (12.00, 1653.98)
[68.9]
Clast (ng/mL)
13.6 (36.5)
53.8 (54.2)
Tlast (h)a
[days]
12.0 (12.0, 12.0) 
[0.50]
1991.16 (1990.70, 1991.18)
[83.0]
%CV = percentage coefficient of variation; BLQ = below the limit of quantitation; GS-6207 = lenacapavir; LLOQ = lower limit 
of quantitation; NaS = sodium salt; PK = pharmacokinetics; Q1 = first quartile; Q3 = third quartile; SC = subcutaneous
Median (Q1, Q3).
Values BLQ were treated as 0 for predose and one-half of the LLOQ for postdose summaries.
LLOQ was defined as 0.5 ng/mL for GS-6207.
Final PK data from Cohort 3 after administration of oral GS-6207 600 mg twice daily 
(Days 1 through 10), followed by an oral GS-6207 600 mg dose in the morning on Day 11, are 
presented in Table 1-15. Intensive PK sampling (from 0 to 12 hours) was conducted on Days 1, 
2, and 11 with sparse sampling on Days 3, 4, 8, 9, and 10. As shown, GS-6207 exhibited 
significant accumulation over the course of 11 days of dosing, which is consistent with its 
long t1/2. 


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Table 1-15.
GS-US-200-5709: Summary Statistics of GS-6207 Plasma 
Pharmacokinetic Parameters (Cohort 3) (GS-6207 PK Analysis Set)
GS-6207
600 mg oral GS-6207 (2  300 mg tablets; AM dose) and
600 mg oral GS-6207 (2  300 mg tablets; PM dose)
600 mg 
oral 
GS-6207 
(2  300 m
g tablets; 
AM dose)
PK 
Parameter
Mean (%CV)
Day 1
(N = 15)
Day 2
(N = 15)
Day 3
(N = 15)
Day 4
(N = 15)
Day 8
(N = 15)
Day 9
(N = 15)
Day 10
(N = 15)
Day 11
(N = 15)
AUC0-12h 
(h•ng/mL)
135.4 (30.7)
894.4 
(47.2)
NC
NC
NC
NC
NC
9706.9 
(28.2)
Cmax (ng/mL)
19.0
(24.0)
96.4 
(49.5)
NC
NC
NC
NC
NC
1012.1 
(26.2)
Tmax (h)a
5.00
(4.00, 5.00)
8.00
(5.00, 
11.97)
NC
NC
NC
NC
NC
4.00 (4.00, 
5.00)
Clast (ng/mL)
11.1 (39.9)
88.4
(45.2)
241.6 
(41.2)
376.9 
(31.7)
604.8
(32.6)
680.5
(28.2)
751.9
(25.7)
787.7 
(31.3)
Tlast (h)a
11.97
(11.97, 
11.97)
11.97
(11.97, 
11.97)
11.97
(11.97, 
11.97)
11.97
(11.97, 
11.97)
11.97
(11.97, 
11.97)
11.97
(11.97, 
11.97)
11.97
(11.97, 
11.97)
11.97
(11.97, 
11.97)
C0 (ng/mL)
BLQ
(BLQ)
42.0
(47.2)
152.6 
(49.7)
342.4 
(39.6)
558.5
(36.8)
699.9
(33.2)
693.1
(35.0)
788.8
(32.1)
BLQ = below the limit of quantitation; %CV = percentage coefficient of variation; GS-6207 = lenacapavir; LLOQ = lower limit 
of quantitation; NC = not calculated due to insufficient PK sampling; PK = pharmacokinetics; Q1 = first quartile; Q3 = third 
quartile
a
Median (Q1, Q3).
C0 represents concentration at time 0 hours.
Values BLQ were treated as 0 for predose and one-half the LLOQ for postdose summaries.
LLOQ was defined as 0.5 ng/mL for GS-6207.
Preliminary Safety Results
Interim safety data through 25 June 2021 for Cohorts 1 and 2 and final safety data for Cohort 3 
are summarized below. 
A total of 31 participants were enrolled into Cohort 1 and received at least 1 dose of study drug. 
Overall, GS-6207 was generally safe and well tolerated. No Grade 3 or 4 AEs, SAEs, deaths, or 
pregnancies were reported. One participant (3.2%) prematurely discontinued study drug and the 
study due to a Grade 1 AE of SARS-CoV-2 test positive. Five participants (16.1%) had 
Grade 3 laboratory abnormalities (increased fasting triglycerides [2 participants] and increases in 


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creatinine kinase (CK), fasting urine glucose, and fasting creatinine [1 participant each]), and 1 
participant (3.2%) had a Grade 4 laboratory abnormality (increased fasting triglycerides). 
A total of 14 participants were enrolled into Cohort 2 and received at least 1 dose of study drug. 
Overall, GS-6207 was generally safe and well tolerated. No Grade 3 or 4 AEs, SAEs, AEs 
leading to study drug or study discontinuation, deaths, or pregnancies were reported. No 
participant had Grade 4 laboratory abnormalities. Three participants (21.4%) had Grade 3 
laboratory abnormalities (increased fasting cholesterol and LDL cholesterol [1 participant] and 
increases in CK and fasting triglycerides [1 participant each]).
No participant in Cohort 1 or 2 had notable changes in vital signs (systolic blood pressure, 
diastolic blood pressure, pulse, and temperature) or clinically significant electrocardiogram 
(ECG) abnormalities. 
A total of 15 participants were enrolled in Cohort 3 and completed GS-6207 600 mg twice daily 
dosing for 11 days, with the last dose given in the morning on the 11th day. Overall, GS-6207 
was generally safe and well tolerated at clinically relevant therapeutic and supratherapeutic 
exposures. Despite the supratherapeutic exposures observed, no Grade 3 or 4 AEs, SAEs, AEs 
leading to study drug or study discontinuation, deaths, or pregnancies were reported. One 
participant (6.7%) experienced an AE of dyspepsia (Grade 1), which was not considered related 
to study drug. No participant had Grade 4 laboratory abnormalities. One participant (6.7%) had 
Grade 3 increased fasting triglycerides. No participant had notable changes in vital signs 
(systolic blood pressure, diastolic blood pressure, pulse, and temperature) or clinically significant 
ECG abnormalities. Specifically, no participant had postbaseline QTcF exceeding 
450 milliseconds.
1.2.2.7.
GS-US-200-4625
Study GS-US-200-4625 is a Phase 2/3, placebo-controlled, multicenter study of GS-6207 
together with an optimized background regimen (OBR) in heavily treatment-experienced (HTE) 
people with HIV-1 (PWH) with multidrug resistant infection.
Herein is a summary from the 2 clinical study reports of interim analysis at Week 26 (after all 
participants in Cohort 1 completed the Week 26 visit) and the Week 52 addendum (after all 
participants in Cohort 1 completed the Week 26 visit and all participants in Cohort 2 completed 
Week 26 visit).
Participants in Cohort 1 were randomized to receive either oral GS-6207 or placebo, while also 
continuing their failing regimen during a 14-day Functional Monotherapy Period. After this 
period, participants who received oral GS-6207 switched to SC GS-6207 (972 mg; 309 mg/mL; 
2  1.5 mL) and OBR, and participants who had received placebo then received oral GS-6207 
and OBR for 14 days prior to switching to SC GS-6207 (972 mg; 309 mg/mL; 2  1.5 mL) and 
OBR. Participants in Cohort 2 received oral GS-6207 and OBR for 14 days before switching to 
SC GS-6207 and OBR. Cohort 2 includes participants that did not meet the criteria for 
randomization in Cohort 1 or who joined the study after Cohort 1 was fully enrolled.


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Disposition and Baseline Characteristics
Overall in Cohorts 1 and 2, 72 participants were enrolled in the study and were included in the 
Safety Analysis Set (Cohort 1: GS-6207, 24 participants; placebo, 12 participants; 
Cohort 2: GS-6207 + OBR, 36 participants). All 72 participants completed the Functional 
Monotherapy (Cohort 1, 36 participants) or oral Lead-in Period (Cohort 2, 36 participants), and 
all received Day 1 SC GS-6207.
Of the 72 participants who received Day 1 SC GS-6207, 32 participants (all from Cohort 2) are 
continuing study drug in the Main Phase, and 37 participants completed study drug in the Main 
Phase (Week 52). Three participants discontinued study drug during the Main Phase. Reasons for 
premature discontinuation were lost to follow-up, investigator’s discretion, and death 
(1 participant each, 1.4%). One participant who decided not to receive SC GS-6207 at Week 52 
and not to continue the study completed the study at the Week 52 visit. Thirty-six participants 
entered into the Extension Phase (Cohort 1: 34 participants; Cohort 2: 2 participants). Of the 
36 participants who entered the Extension Phase, 34 participants are continuing study drug. 
Two participants discontinued study drug during the Extension Phase. Reasons for premature 
discontinuation were AE and lost to follow-up (1 participant each, 2.8%).
Cohort 1
In Cohort 1, demographic and baseline characteristics were generally similar between the 
GS-6207 and placebo groups. The majority of participants were male (72.2%; 26 of 
36 participants), White (45.7%, 16 participants) or Black (45.7%, 16 participants), and not 
Hispanic or Latino (71.4%, 25 participants). Median age was 54 years (range: 24−71 years).
Baseline disease characteristics were consistent with the profile of the HTE population, with a 
median (range) number of prior ARV medications of 9 (2, 24), and 75% of participants with 
CD4 cell count < 200 cells/μL (a hallmark of severe immune suppression and the criterion to 
diagnose AIDS). Differences were seen between the GS-6207 and placebo groups in HIV-1 
RNA (log10 copies/mL), HIV-1 RNA categories, and CD4 cell counts and CD4 percentage.
The most common prior ARV medications were as follows: INSTI (97.2%), NRTI (94.4%), 
nonnucleoside reverse transcriptase inhibitor (NNRTI;  (88.9%), and protease inhibitor (PI; 
(83.3%). Known resistance to ≥ 2 drugs in class was as follows: NRTI (97.2%), NNRTI (94.4%), 
PI (77.8%), and INSTI (75.0%).
The median number of ARVs in the failing regimen for Cohort 1 was 3 (range: 1−7). The 
composition of participants’ failing regimens were characteristic of those of PWH with 
multidrug resistance, for example, PI (boosted darunavir twice daily), INSTI (dolutegravir twice 
daily), chemokine receptor 5 entry inhibitor (maraviroc), CD4-directed post attachment 
(ibalizumab), attachment inhibitor (fostemsavir, which was investigational at the time of 
enrollment), and fusion inhibitor (enfuvirtide).


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The median number of ARVs in the OBR was 4 (range: 2−7). The composition of participants’ 
failing regimens and OBRs were similar, suggesting that they had few remaining treatment 
options prior to enrolling. Specifically, 6 out of 36 (16.7%) of participants continued their failing 
regimens as OBRs, suggesting there were no viable agents that could have further optimized the 
regimen.
The percentage of participants by number of fully active ARV agents in the OBR were as 
follows: 16.7% (0 fully active ARV agents), 38.9% (1 fully active ARV agent), 25.0% (2 fully 
active ARV agents), and 19.4% (≥ 3 fully active ARV agents).
Cohort 2
In Cohort 2, the majority of participants were male (77.8%; 28 of 36 participants), White (36.1%, 
13 participants) or Asian (33.3%, 12 participants), and not Hispanic or Latino (86.1%, 
31 participants). Median age was 49 years (range: 23−78 years). 
The baseline disease characteristics, prior ARVs, failing regimens, OBR regimen, and resistance 
characteristics for Cohort 2 were consistent with the profile of the HTE population. 
Efficacy Results: 
Primary efficacy end point: Reduction in HIV 1 RNA of ≥ 0.5 log10 copies/mL
A significantly greater percentage of participants receiving GS-6207 had a reduction in HIV-1 
RNA of ≥ 0.5 log10 copies/mL from baseline at the end of the Functional Monotherapy Period 
compared than those receiving placebo (87.5% vs 16.7%; P < 0.0001). To address the imbalance 
in baseline HIV-1 RNA between the GS-6207 and placebo groups, a post hoc analysis of the 
primary efficacy end point with adjustment for baseline HIV-1 RNA using rank analysis of 
covariance was conducted. Results from this post hoc analysis confirmed that the difference 
between the groups remained statistically significant: 87.5% versus 16.7%; P = 0.0003. To 
address the imbalance in baseline CD4 cell count between the GS-6207 and placebo groups, post 
hoc analyses of the primary efficacy end point were conducted in participants with comparable 
or clinically relevant CD4 cell counts. These analyses showed that the difference between groups 
remained statistically significant for the comparison between participants in the GS-6207 group 
with a low baseline CD4 cell count (median: 98.5 cells/μL; n = 12) and participants in the 
placebo group (median: 84.5 cells/μL; n = 12) (P = 0.0008) and between participants in the 
GS-6207 and placebo groups with a baseline CD4 cell count < 200 cells/μL (P < 0.0001).


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Secondary Efficacy End Points
Week 26
The percentages of participants in Cohort 1 with HIV 1 RNA < 50 and < 200 copies/mL at Week 
26 using the United States (US) Food and Drug Administration (FDA) defined snapshot 
algorithm were 80.6% (29 of 36 participants) and 88.9% (32 of 36 participants), respectively. 
The percentages of participants in Cohort 2 with HIV 1 RNA < 50 and < 200 copies/mL at Week 
26 using the US FDA defined snapshot algorithm were 66.7% (4 of 6 participants) and 66.7% (4 
of 6 participants), respectively.
Week 52
The percentages of participants in Cohort 1 with HIV 1 RNA < 50 and < 200 copies/mL at 
Week 52 using the US FDA defined snapshot algorithm were 83.3% (30 of 36 participants) and 
86.1% (31 of 36 participants), respectively.
HIV-1 RNA < 50 Copies/mL and < 200 Copies/mL
At Week 26, the percentages of participants in Cohorts 1 and 2 with HIV-1 RNA < 50 and 
< 200 copies/mL using the US FDA-defined snapshot algorithm were 80.6% (58 of 
72 participants) and 87.5% (63 of 72 participants), respectively. 
At Week 52, the percentages of participants in Cohorts 1 and 2 with HIV-1 RNA < 50 and 
< 200 copies/mL using the US FDA-defined snapshot algorithm were 77.8% (35 of 
45 participants) and 82.2% (37 of 45 participants), respectively.
Change From Baseline in HIV-1 RNA
Mean (SD) baseline HIV-1 RNA values of participants in Cohorts 1 and 2 was 
4.12 (1.028) log10 copies/mL. The mean (SD) change from baseline in HIV-1 RNA at Weeks 26 
and 52 was −2.53 (1.184) log10 copies/mL, and −2.50 (1.145) log10 copies/mL, respectively.
Change From Baseline in CD4 Cell Count
Mean (SD) baseline CD4 cell count value of participants in Cohorts 1 and 2 at baseline was 
212 (226.2) cells/μL. At Week 26, mean (SD) change from baseline was 89 (106.7) cells/μL. At 
Week 52, mean (SD) change from baseline was 94 (121.5) cells/μL.
Preliminary Pharmacokinetic Results
A population PK (PopPK) model was developed from multiple Phase 1/2 studies to 
simultaneously describe IV, oral, and SC routes of administration for the GS-6207 treatment 
program. Data from Study GS-US-200-4625 up to Week 13 (interim PK data cut) were utilized 
in the PopPK model to derive posthoc exposure parameters. Following a dosing schedule of 
GS-6207 SC (927 mg or 2 x 1.5 mL of 309 mg/mL, administered every 26 weeks), preceded by a 


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14-day oral Lead-in Period, mean (%CV) GS-6207 post hoc Cmax and CWeek26 were 136.2 (75.2) 
ng/mL and 35.1 (59.2) ng/mL, respectively.
Adverse Events
Functional Monotherapy Period
During the Functional Monotherapy Period, the percentages of participants who experienced 
AEs were: GS-6207 37.5% (9 of 24 participants); placebo 25.0% (3 of 12 participants). Nausea 
was the only AE reported in > 1 participant (GS-6207 12.5%, 3 participants).
Adverse event considered related to study drugs that was reported in > 1 participant was as 
follows: nausea (8.3%, 2 participants; GS-6207 group). 
No deaths, SAEs, AEs leading to discontinuation of study drug, or Grade 3 or higher AEs, were 
reported in either the GS-6207 or placebo group.
All GS-6207 Analysis
The percentage of participants who received GS-6207 in Cohorts 1 and 2 and experienced AEs 
was 93.1% (67 of 72 participants). The 3 most commonly reported AEs were injection site pain 
(37.5%, 27 of 72 participants), injection site swelling (33.3%, 24 participants), and injection site 
erythema (27.8%, 20 participants). Some injection site reactions (ISRs) were attributed to 
enfuvirtide.
The majority of AEs were Grade 1 or 2 in severity. Grade 3 or higher AEs were reported for 
16 participants (22.2%). Grade 3 or higher AEs that were reported for ≥ 2 participants were 
injection site erythema (5.6%, 4 participants), injection site edema, injection site pain, and 
injection site swelling (2.8%, 2 participants each). Four participants experienced Grade 3 or 
higher AEs that were considered related to study drug: rash and abdominal abscess, injection site 
swelling and injection site erythema, injection site pain, and immune reconstitution inflammatory 
syndrome (1 participant each). The AE of abdominal abscess was an abscess at the injection site 
due to secondary infection most likely because the participant scratched the injection site.
Overall, 66.7% (48 of 72 participants) experienced treatment-related AEs. The most commonly 
reported treatment-related AEs were injection site pain and injection site swelling (30.6%, 
22 participants), injection site erythema (25.0%, 18 participants), and injection site nodule 
(23.6%, 17 participants)
SAEs were reported for 11.1% (8 of 72 participants). The only SAE that was reported for more 
than 1 participant was COVID-19. None of these events led to discontinuation of study drug. No 
SAEs were considered related to study drug. One SAE of cancer resulted in death which was 
also reported as an AE leading to premature discontinuation from the study. This participant in 
Cohort 2 died on Study Day 90, and the cause of death was reported as cancer. The event was 
previously reported in the Week 26 analysis and was considered not related to study drug.


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While no participant discontinued study drug due to AE at the Week 26 analysis, 1 participant 
(1.4%) in Cohort 1 experienced a Grade 1 AE of injection site nodule during the Extension 
Phase, leading to premature discontinuation from the study after receiving the Week 52 GS-6207 
SC injection. The event was considered related to study drug.
Overall, 45 participants (62.5%) experienced a study drug-related ISR. All were Grade 1 or 
2 with the exception of 2 participants (2.8%) who experienced a Grade 3 ISR which resolved 
after a few days. No Grade 3 or 4 ISRs were reported beyond Week 26. The median (Q1, Q3) 
total duration of any study drug-related ISR was 8 (3, 67) days. The most frequently reported 
study drug-related ISRs (reported in ≥ 10% of participants overall) and duration in median (Q1, 
Q3) days were as follows:

Injection site swelling (30.6%, 22 participants), 12 (6, 30) days

Injection site pain (30.6%, 22 participants), 3 (2, 7) days

Injection site nodule (23.6%, 17 participants), 180 (111, 330) days

Injection site erythema (25%, 18 participants), 6 (3, 8) days

Injection site induration (15.3%, 11 participants), 118 (15, 182) days
A numerically lower percentage of participants had ISRs after the second GS-6207 injection 
compared with the first injection.
Overall, 17 participants experienced study drug-related injection site nodule, and 11 participants 
experienced study drug-related injection site induration. All events were Grade 1 or 2.
The injection site nodules and indurations reported due to Day 1 SC injection were as follows:

Participant level analysis:
Nodules: Ongoing (9/16 [56.3%]); Resolved (7/16 [43.8%])
Indurations: Ongoing (1/8 [12.5%]); Resolved (7/8 [87.5%])

Event level analysis:
Nodules: Ongoing (9/23 [39.1%]); Resolved (14/23 [60.9%])
Indurations: Ongoing (1/8 [12.5%]); Resolved (7/8 [87.5%])
The median (Q1, Q3) duration of resolved injection site nodule and injection site induration due 
to Day 1 SC injection was 107 (70, 227) days and 43 (15, 196) days, respectively.


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The injection site nodules and indurations reported due to the second GS-6207 injection at 
Week 26 were as follows:

Participant level analysis:
Nodules: Ongoing (6/8 [75.0%%]); Resolved (2/8 [25.0%])
Indurations: Ongoing (3/7 [42.9%]); Resolved (4/7 [57.1%])

Event level analysis:
Nodules: Ongoing (12/14 [85.7%]); Resolved (2/14 [14.3%])
Indurations: Ongoing (3/7 [42.9%]); Resolved (4/7 [57.1%])
The median (Q1, Q3) duration of resolved injection site nodule and injection site induration due 
to the second GS-6207 injection at Week 26 was 92 (3, 180) Days and 38 (9, 123) Days, 
respectively.
CONCLUSIONS:
The conclusions from the Week 52 interim analysis of Study GS-US-200-4625 are as follows:

Consistent with the data reported in the Study GS-US-200-4625 Interim Week 26 CSR, high 
rates of virologic suppression continued to be maintained through Week 52. These results 
were consistent even in participants who had suboptimal baseline OBR (eg, low OSS, no or 
1 fully active agent, INSTI resistance, no dolutegravir or darunavir), demonstrating a 
clinically meaningful contribution of GS-6207 towards virologic suppression.

Consistent with the data reported in the Study GS-US-200-4625 Interim Week 26 CSR, there 
were clinically meaningful increases in CD4 cell count from baseline to Week 52.
GS-6207 remained generally safe and well tolerated. No participant experienced a study 
drug-related SAE. The majority of ISRs were Grade 1 or 2 in severity. One participant 
discontinued GS-6207 at Week 52 (after the Week 26 interim analysis) due to an AE of Grade 1 
injection site nodule.
1.2.2.8.
GS-US-200-4334
Study GS-US-200-4334 is an ongoing, Phase 2, randomized, open-label, active-controlled, 
multicenter study evaluating the safety and efficacy of GS-6207 in combination with other ARV 
agents in ARV-naive PWH. Participants were randomized in a 2:2:2:1 ratio to 1 of 4 treatment 
groups (Table 1-16, Figure 1-8).
Participants are treated for at least 80 weeks. Participants in Treatment Group 4 will complete the 
study at Week 80.


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Herein is a summary from the two clinical study reports of interim analysis at Week 28 and the 
Week 54 addendum.
Table 1-16.
GS-US-200-4334: Study Treatments
Treatment Group
Time Period
Study Treatments
Induction (Day 1 
through Week 27)

Oral GS-6207 600 mg (2  300 mg tablet) on Days 1 and 
2; 300 mg (1  300 mg tablet) on Day 8

Oral daily F/TAF (200/25 mg) from Day 1 onwards for a 
total of 28 weeksa

SC GS-6207 927 mg (3 mL of 309 mg/mL) on Day 15
1
Maintenance (Week 28 
through Week 80)

SC GS-6207 927 mg (3 mL of 309 mg/mL) at Week 28 
and every 26 weeks thereafter

Oral daily TAF (25 mg)
Induction (Day 1 
through Week 27)

Oral GS-6207 600 mg (2  300 mg tablet) on Days 1 and 
2; 300 mg (1  300 mg tablet) on Day 8

Oral daily F/TAF (200/25 mg) from Day 1 onwards for a 
total of 28 weeksb

SC GS-6207 927 mg (3 mL of 309 mg/mL) on Day 15
2
Maintenance (Week 28 
through Week 80)

SC GS-6207 927 mg (3 mL of 309 mg/mL) at Week 28 
and every 26 weeks thereafter

Oral daily BIC (75 mg)
3
Day 1 through Week 80

Oral GS-6207 600 mg (2  300 mg tablet) on Days 1 and 
2; 50 mg (1  50 mg tablet) daily from Day 3 onwards

Oral daily F/TAF (200/25 mg)
4
Day 1 through Week 80

Oral daily B/F/TAF (50/200/25 mg)
BIC, B = bictegravir; F = emtricitabine; F/TAF = emtricitabine/tenofovir alafenamide (coformulated; Descovy®); GS-6207 = 
lenacapavir; SC = subcutaneous; TAF = tenofovir alafenamide
a
Treatment Group 1 participants with < 50 copies/mL of HIV-1 RNA at Week 16 and Week 22 stopped F/TAF at Week 28 
and initiated oral daily TAF.
b
Treatment Group 2 participants with < 50 copies/mL of HIV-1 RNA at Week 16 and Week 22 stopped F/TAF at Week 28 
and initiated oral daily BIC. 


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Figure 1-8.
GS-US-200-4334: Study Design
BIC, B = bictegravir; B/F/TAF = bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®, BVY); 
BL = baseline; F/TAF = emtricitabine/tenofovir alafenamide (coformulated; Descovy®); GS-6207 = lenacapavir, LEN; 
PK = pharmacokinetic; QD = once daily; Q6M = every 6 months; SC = subcutaneous; TAF = tenofovir alafenamide; 
Tx-naive = treatment naive; Wk = week
Disposition and Baseline Characteristics
Of the 249 participants screened, 183 were randomized, and 182 received at least 1 dose of study 
drug. Of these 182 participants, 22 participants (12.1%) prematurely discontinued the study drug 
during the Main Phase (ie, data collected on or before Week 80): 17 of 105 participants (16.2%) 
in the SC GS-6207 total group, 4 of 52 participants (7.7%) in the oral GS-6207 group, and 
1 of 25 participants (4.0%) in the bictegravir/emtricitabine/tenofovir alafenamide (coformulated; 
Biktarvy®; BVY) group. The reasons for premature study drug discontinuation in the SC GS-
6207 total group were participant decision and lost to follow-up (each 4 participants [3.8%]), 
investigator’s discretion, lack of efficacy, and AE (each 3 participants [2.9%]). The reasons for 
premature study drug discontinuation in the oral GS-6207 group were lost to follow-up 
(3 participants [5.8%]) and participant decision (1 participant [1.9%]) and in the BVY group it 
was participant decision (1 participant [4.0%]).
As of the Week 54 data cut date, 8 participants entered into the Extension Phase (SC GS-6207 
total group, 5 participants; oral GS-6207 group, 3 participants) and were continuing study drug.
Demographics, general baseline characteristics, and baseline disease characteristics are described 
in the Interim Week 28 CSR.
Demographic and baseline characteristics were similar across the treatment groups. Most 
participants were male (93.4%), cisgender (92.3%), and gay (69.8%). Median age was 29 years 
(range: 19−72 years). Race was balanced between Black versus non-Black (52.2% vs 47.8%, 
respectively), as was ethnicity between Hispanic or Latino versus not Hispanic or Latino 
(45.1% vs 54.9%, respectively).
Tx-Na'ive 
n=175 
BL 
Induction 
F/TAF (oral QD) 
Wk28 
Maintenance 
*GS-6207 (SC Q6M) 
**TAF (oral QD) 
*GS-6207 (SC Q6M) 
.. BIC (oral QD) 
*GS-6207 (oral QD) 
F/TAF (oral QD) 
Wk54 
Wk80 
.............. 
.............. 
'Treatment Groups 1 2 and 3 will have oral PK loading doses 
" Participants in Trea\ment Groups 1 and 2 will need to have HJV.1 RNA results < 50 copies/ml at Weeks 16 and 22 to initiate 
treatment with a two-agent regimen at Week 28; those with values :? 50 copies/ml will discontinue the study at Week 28. 


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Baseline disease characteristics were similar across the treatment groups. Overall, the median 
(Q1, Q3) baseline HIV-1 RNA value was 4.37 (3.86, 4.74) log10 copies/mL, and the median (Q1, 
Q3) baseline CD4 cell count was 437 (332, 599) cells/μL. Among the 182 participants, most had 
HIV-1 RNA ≤ 100,000 copies/mL (85.2%, 155 participants) and a CD4 cell count range of ≥ 350 
to < 500 cells/µL (31.9%, 58 participants) or ≥ 500 cells/µL (37.4%, 68 participants).
Efficacy Results:
Primary Efficacy End Point
HIV-1 RNA < 50 copies/mL at Week 54 Using the US FDA-Defined Snapshot Algorithm
The primary analysis at Week 54 demonstrated similar results in each treatment group, with no 
significant difference between each of the GS-6207-containing groups and the BVY group, as 
follows:

GS-6207 total: 136 of 157 participants (86.6%)

SC GS-6207 + (DVY → TAF): 47 of 52 participants (90.4%)

SC GS-6207 + (DVY → BIC): 45 of 53 participants (84.9%)

Oral GS-6207 + DVY: 44 of 52 participants (84.6%)

BVY: 23 of 25 participants (92.0%) 
For participants with HIV-1 RNA < 50 copies/mL at Week 28, the proportion with HIV-1 RNA 
< 50 copies/mL at Week 54 using the US FDA-defined snapshot algorithm were also similar in 
each treatment group, with no significant difference between each of the GS-6207-containing 
groups and the BVY group, as follows:

GS-6207 total: 135 of 147 participants (91.8%)

SC GS-6207 + (DVY → TAF): 46 of 49 participants (93.9%)

SC GS-6207 + (DVY → BIC): 45 of 49 participants (91.8%)

Oral GS-6207 + DVY: 44 of 49 participants (89.8%)

BVY: 23 of 25 participants (92.0%)


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Secondary Efficacy End Points
Week 28
Results from the secondary efficacy analysis of Week 28 data of Study GS-US-200-4334 
demonstrated similar results in each treatment group, with no significant difference between each 
of the GS-6207-containing treatment groups and the BVY treatment group with respect to the 
proportion of participants with HIV-1 RNA  50 copies/mL using the US FDA-defined snapshot 
algorithm, the change from baseline in log10 HIV-1 RNA, and the change from baseline in CD4 
cell count.
HIV-1 RNA  50 copies/mL using the US FDA-defined snapshot algorithm

GS-6207 total: 147 of 157 participants (93.6%)

SC GS-6207 + (DVY → TAF): 49 of 52 participants (94.2%)

SC GS-6207 + (DVY → BIC): 49 of 53 participants (92.5%)

Oral GS-6207 + DVY: 49 of 52 participants (94.2%)

BVY: 25 of 25 participants (100.0%) 
Week 38
HIV-1 RNA  50 copies/mL at Week 38 Using the US FDA-defined snapshot algorithm

GS-6207 total: 140 of 157 participants (89.2%)

SC GS-6207 + (DVY → TAF): 47 of 52 participants (90.4%)

SC GS-6207 + (DVY → BIC): 47 of 53 participants (88.7%)

Oral GS-6207 + DVY: 46 of 52 participants (88.5%)

BVY: 24 of 25 participants (96.0%) 
Change from Baseline in HIV-1 RNA at Weeks 28, 38 and 54
Week 28

GS-6207 total: −2.99 (0.666) log10 copies/mL

SC GS-6207 + (DVY → TAF): −2.92 (0.649) log10 copies/mL 

SC GS-6207 + (DVY → BIC): −3.04 (0.638) log10 copies/mL 


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
Oral GS-6207 + DVY: −3.01 (0.716) log10 copies/mL 
Week 38

GS-6207 total: −3.01 (0.681) log10 copies/mL

SC GS-6207 + (DVY → TAF): −2.96 (0.639) log10 copies/mL

SC GS-6207 + (DVY → BIC): −3.06 (0.641) log10 copies/mL

Oral GS-6207 + DVY: −3.02 (0.771) log10 copies/mL

BVY: −3.04 (0.760) log10 copies/mL
Week 54

GS-6207 total: −2.98 (0.700) log10 copies/mL

SC GS-6207 + (DVY → TAF): −2.95 (0.636) log10 copies/mL

SC GS-6207 + (DVY → BIC): −3.12 (0.589) log10 copies/mL

Oral GS-6207 + DVY: −2.85 (0.840) log10 copies/mL

BVY: −3.08 (0.787) log10 copies/mL
Change from Baseline in CD4 Cell Count at Weeks 38 and 54
Week 28

GS-6207 total: 179 (166.0) cells/μL

SC GS-6207 + (DVY → TAF): 172 (178.2) cells/μL

SC GS-6207 + (DVY → BIC): 158 (164.1) cells/μL

Oral GS-6207 + DVY: 206 (154.6) cells/μL

BVY: 163 (157.7) cells/μL
Week 38

GS-6207 total: 208 (172.7) cells/μL

SC GS-6207 + (DVY → TAF): 195 (164.6) cells/μL

SC GS-6207 + (DVY → BIC): 219 (187.4) cells/μL


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
Oral GS-6207 + DVY: 210 (167.1) cells/μL

BVY: 232 (209.3) cells/μL
Week 54

GS-6207 total: 213 (182.1) cells/μL

SC GS-6207 + (DVY → TAF): 206 (187.0) cells/μL

SC GS-6207 + (DVY → BIC): 212 (187.1) cells/μL

Oral GS-6207 + DVY: 220 (175.5) cells/μL

BVY: 193 (191.1) cells/μL
Results from the secondary efficacy analysis at Weeks 38 and 54 demonstrated similar results in 
each treatment group, with no significant difference between each of the GS-6207-containing 
treatment groups and the BVY treatment group with respect to the proportion of participants with 
HIV-1 RNA < 50 copies/mL (Week 38), the change from baseline in log10 HIV-1 RNA, and the 
change from baseline in CD4 cell count (Weeks 38 and 54).
Preliminary Pharmacokinetic Results
As per the PopPK modeling summarized in Section 1.2.2.7, the mean (%CV) GS-6207 post hoc 
Cmax and CWeek26 in Study GS-US-200-4334 were 93.1 (61.9) ng/mL and 22.5 (63.4) ng/mL, 
respectively.
Safety Results:
GS-6207 and BVY were well tolerated. By Week 54, 89.2% of participants in the GS-6207 total 
group (140 of 157 participants) and 96.0% of those in the BVY group (24 of 25 participants) had 
been exposed to study drug for at least 54 weeks.
Adverse Events
Similar percentages of participants in the GS-6207 total (total of 157 participants) and BVY 
(total of 25 participants) groups had any AE by Week 54 (GS-6207 total 87.9%, 138 participants; 
BVY 84.0%, 21 participants).
The most commonly reported AEs were as follows:

GS-6207 total (157 participants), excluding ISRs: headache and nausea (each 13.4%, 
21 participants), COVID-19 (9.6%, 15 participants), and syphilis and lymphadenopathy (each 
8.9%, 14 participants)


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
SC GS-6207 total (105 participants), only ISRs: injection site erythema (31.4%, 
33 participants), injection site swelling (27.6%, 29 participants), and injection site pain 
(23.8%, 25 participants)

Oral GS-6207 + DVY (52 participants): headache (13.5%, 7 participants), nausea and 
lymphadenopathy (each 11.5%, 6 participants) and COVID-19, syphilis, diarrhea, and 
influenza (each 9.6%, 5 participants)

BVY (25 participants): syphilis and arthralgia (each 16.0%, 4 participants) and headache, 
COVID-19, back pain, weight increased, upper respiratory tract infection, and insomnia 
(each 12.0%, 3 participants)
The majority of the AEs reported in the 4 treatment groups were Grade 1 or 2 in severity. The 
percentage of participants with AEs of Grade 3 or higher was 8.3% (13 of 157 participants) in 
the GS-6207 total group and 8.0% (2 of 25 participants) in the BVY group. No AEs of Grade 
3 or higher were reported for > 1 participant in any treatment group.
Since the Week 28 analysis, 2 additional AEs of Grade 3 or higher were reported in the GS-6207 
total group (SC GS-6207 + [DVY → TAF] group: 1 participant; SC GS-6207 + [DVY → BIC] 
group: 1 participant]) and 1 additional AE of Grade 3 or higher was reported in the BVY group 
(1 participant).
The percentages of participants with treatment-related AEs were as follows:

GS-6207 total (157 participants): 43.9% (69 participants)

SC GS-6207 total (105 participants): 58.1% (61 participants)

Oral GS-6207 + DVY (52 participants): 15.4% (8 participants)

BVY (25 participants): 16.0% (4 participants)
The higher frequency of treatment-related AEs in the SC GS-6207 total group was mainly 
because of ISRs, as reflected in the most common AEs considered related to study drugs:

GS-6207 total group (157 participants), excluding ISRs: nausea (5.1%, 8 participants), 
diarrhea and headache (each 2.5%, 4 participants), and fatigue (1.9%, 3 participants)

SC GS-6207 total group (105 participants), only ISRs: injection site erythema (26.7%, 
28 participants), injection site swelling (22.9%, 24 participants), injection site pain (19.0%, 
20 participants) 

Oral GS-6207 + DVY (52 participants): nausea and diarrhea (each 3.8%, 2 participants), 
fatigue, headache, dyspepsia, flatulence, vomiting, weight increased, influenza, overdose, 
and hot flush (each 1.9%, 1 participant)


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
BVY (25 participants): dyspepsia, salivary hypersecretion, insomnia, and weight increased 
(4.0%, 1 participant)
Overall, 57 of 103 participants (55.3%) who received SC GS-6207 had a study drug-related ISR; 
all were Grade 1 or Grade 2, except for 1 participant with a Grade 3 injection site nodule. There 
were no new Grade 3 or higher ISRs reported since the Week 28 analysis. The most frequently 
reported ISRs (≥ 10% in SC GS-6207 total group) and their duration in median (Q1, Q3) days 
were as follows:

Injection site erythema (27.2%, 28 participants), 5 (2, 11) days 

Injection site swelling (23.3%, 24 participants), 11 (6, 29) days

Injection site pain (19.4%, 20 participants), 4 (1, 9) days

Injection site nodule (14.6%, 15 participants), 195 (122, 301) days

Injection site inflammation (13.6%, 14 participants), 3 (1, 8) days

Injection site induration (12.6%, 13 participants), 202 (101, 361) days
Overall, 15 of 103 participants had an AE of injection site nodule and 13 of 103 participants had 
an AE of injection site induration. All were Grade 1 or Grade 2, except for 1 participant with a 
Grade 3 injection site nodule. Ongoing and resolved injection site indurations and nodules were 
as follows:
ISRs after the first SC GS-6207 injection at Day 15:
Participant-level analysis:

Nodules: Ongoing (1 of 11 [9.1%]); Resolved (10 of 11 [90.9%])

Indurations: Ongoing (6 of 9 [66.7%]); Resolved (3 of 9 [33.3%])
Event-level analysis:

Nodules: Ongoing (1 of 13 [7.7%]); Resolved (12 of 13 [92.3%])

Indurations: Ongoing (6 of 9 [66.7%]); Resolved (3 of 9 [33.3%])
The median (Q1, Q3) duration of resolved injection site nodule and injection site induration was 
278 (136, 366) days and 202 (101, 213) days, respectively.


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ISRs after the second SC GS-6207 injection at Week 28:
Participant-level analysis:

Nodules: Ongoing (5 of 8 [62.5%]); Resolved (3 of 8 [37.5%])

Indurations: Ongoing (3 of 6 [50.0%]); Resolved (3 of 6 [50.0%])
Event-level analysis:

Nodules: Ongoing (5 of 8 [62.5%]); Resolved (3 of 8 [37.5%])

Indurations: Ongoing (3 of 6 [50.0%]); Resolved (3 of 6 [50.0%])
The median (Q1, Q3) duration of resolved injection site nodule and injection site induration was 
152 (123, 240) days and 145 (4, 258) days, respectively.
CONCLUSIONS: 
The conclusions from the Week 54 interim analysis of Study GS-US-200-4334 are as follows:

High rates of virologic suppression continued to be maintained through Week 54. For the 
primary efficacy end point, overall, 136 of 157 participants (86.6%) who received SC or oral 
GS-6207 and 23 of 25 participants (92.0%) who received BVY had HIV-1 RNA < 50 
copies/mL at Week 54.

For participants with HIV-1 RNA < 50 copies/mL at Week 28, high rates of virologic 
suppression continued to be maintained through Week 54.

Subcutaneously and orally administered GS-6207 remained generally safe and well tolerated.
1.3.
Information About Bictegravir
Bictegravir (BIC, B) is a potent integrase strand transfer inhibitor (INSTI) that has been 
evaluated for the treatment of HIV-1 infection and that has demonstrated a terminal half-life 
suitable for once daily administration without a boosting agent.
1.3.1.
General Information
For further information on BIC, please refer to the IB. Information in the IB includes:

Nonclinical PK and in vitro metabolism

Nonclinical pharmacology and toxicology

Clinical experience


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1.4.
Information About Tenofovir Alafenamide 
Tenofovir (TFV) is a nucleotide analog with limited oral bioavailability that as its intracellular 
active moiety, tenofovir diphosphate (TFV-DP), inhibits HIV-1 reverse transcription. Tenofovir 
alafenamide (TAF) is an oral phosphonamidate prodrug of TFV. Tenofovir alafenamide is more 
stable in plasma than tenofovir disoproxil fumarate (TDF), provides higher intracellular levels of 
the active phosphorylated metabolite TFV-DP to target cells.
1.4.1.
General Information
For further information on TAF, please refer to the IB. Information in the IB includes:

Nonclinical PK and in vitro metabolism

Nonclinical pharmacology and toxicology

Clinical experience
1.5.
Information About Emtricitabine/Tenofovir Alafenamide 
Tenofovir is a nucleotide analog with limited oral bioavailability that as its intracellular active 
moiety, TFV-DP, inhibits HIV-1 reverse transcription. Tenofovir alafenamide is an oral 
phosphonamidate prodrug of TFV. Tenofovir alafenamide is more stable in plasma than TDF, 
provides higher intracellular levels of the active phosphorylated metabolite TFV-DP to target 
cells. TAF in combination with emtricitabine (FTC) (F/TAF) forms an N(t)RTI backbone that 
can be combined with different third agents for the treatment of PLWH.
In 2016, US and international guidelines for the treatment of HIV infection were updated to 
include F/TAF as part of several recommended regimens for initial treatment of ART-naive, 
PLWH {Panel on Antiretroviral Guidelines for Adults and Adolescents 2016, Saag 2018}. In 
both current guidelines ({Department of Health and Human Services (DHHS) 2011, European 
AIDS Clinical Society (EACS) 2018}), F/TAF is recommended for initial therapy in most 
PLWH in combination with an INSTI, specifically dolutegravir or BIC (available as 
BIKTARVY® [BVY, B/F/TAF]), or raltegravir (RAL).
1.5.1.
General Information
For further information on F/TAF, please refer to the IB. Information in the IB includes:

Nonclinical PK and in vitro metabolism

Nonclinical pharmacology and toxicology

Clinical experience


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1.6.
Information About Bictegravir/Emtricitabine/Tenofovir Alafenamide 
Bictegravir/F/TAF is a fixed-dose combination (FDC) tablet for the treatment for HIV-1 
infection. The B/F/TAF FDC tablet is a safe and highly effective INSTI-based treatment 
regimen, offering minimal pill burden, once-daily dosing, and excellent tolerability. The 
B/F/TAF FDC is a recommended initial treatment for PLWH {Department of Health and Human 
Services (DHHS) 2013}.
1.6.1.
General Information
For further information on B/F/TAF, please refer to the IB. Information in the IB includes:

Nonclinical PK and in vitro metabolism

Nonclinical pharmacology and toxicology

Clinical experience
1.7.
Rationale for This Study
Advances in ART have led to significant improvements in morbidity and mortality among 
people living with HIV by suppressing viral replication, preserving immunologic function, and 
averting disease progression to AIDS. While combination ARV therapy for the treatment of 
HIV-1 infection has been largely successful in reducing the morbidity and mortality associated 
with HIV disease, there remains a significant medical need for new well-tolerated therapies that 
take into consideration HIV genetic variability, ARV resistance, and new options for regimen 
simplification.
The goal of this study is to systematically evaluate potential combination regimens containing 
the novel capsid inhibitor, GS-6207, in treatment-naïve PLWH as an induction regimen and in 
virologically-suppressed people as a maintenance regimen. Participants who do not meet criteria 
for viral suppression will not be permitted to initiate a maintenance regimen using fewer agents 
than the induction regimen. The data are intended to support the ongoing clinical development of 
SC and oral GS-6207 for PLWH. The regimen of oral GS-6207+F/TAF will provide a positive 
control for the dual agent maintenance groups as well as support this combination for further 
development. An active control group of B/F/TAF is included as a current standard-of-care 
comparator.
1.8.
Rationale for Dose Selection 
1.8.1.
GS-6207
The dose selection for GS-6207 in this study is supported by antiviral activity, PK, and safety 
data from the ongoing Phase 1b POC (study GS-US-200-4072) in treatment-naive and treatment 
experienced but CAI-naïve PLWH, as well as PK and safety data from the two Phase 1 studies in 
healthy volunteers (Studies GS-US-200-4538 and GS-US-200-4071).


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In the ongoing Phase 1b POC study (GS-US-200-4072), potent antiviral activity of GS-6207 has 
been demonstrated; the mean maximum HIV-1 RNA decline over 10-day monotherapy after 
single SC doses of 50 mg to 450 mg was 1.8 to 2.2 log10 copies/mL, respectively. All participants 
achieved at least 1 log10 copies/mL decline in their HIV-1 RNA at Day 10. Day 10 antiviral 
activity was comparable across a single dose range of 50 mg to 450 mg. At these doses, mean 
(% CV) GS-6207 concentrations on Day 10 were 1.1- to 9.9-fold higher (ie, IQ 1.1 to 9.9) than 
the protein adjusted (pa)EC95 for wild type HIV-1 (paEC95 = 3.87 ng/mL in MT-4 cells) 
(see Section 1.2.2.2).
Based on these data and the safety data available to date, a concentration target of at least 
15.5 ng/mL for Ctrough (corresponding to IQ4 based on paEC95 from MT-4 cells) has been 
selected to ensure adequate antiviral activity would be achieved throughout dosing. GS-6207 
formulations and doses to be evaluated in this study are informed by PK and safety data from 
Phase 1 studies, GS-US-200-4071 and GS-US-200-4538, in healthy volunteers.
In Treatment Groups 1, 2 and 3, the proposed GS-6207 regimens target an exposure whereby the 
lower bound of the 90% CI of the Ctrough is at least 4-fold higher than the paEC95 (ie, IQ4; 
15.5 ng/mL) starting within a few days of dosing initiation and maintained throughout the dosing 
interval.
In Treatment Groups 1 and 2, participants will receive a SC GS-6207 regimen (every 26 weeks), 
preceded by an oral PK loading regimen. As described in Section 1.2.2.5, GS-6207 SC Injection 
(309 mg/mL) exhibits a slow initial release necessitating oral PK loading prior to the first SC 
injection to achieve IQ4 within a few days of initiation of dosing, participants will receive oral 
tablet doses of GS-6207 600 mg on Days 1 and 2, and 300 mg on Day 8. Participants will then 
receive GS-6207 927 mg SC on Day 15, followed by GS-6207 927 mg SC administered every 
6 months (every 26 weeks). This regimen is projected to achieve target exposures within a few 
days of initiation, and to maintain throughout the 26 weeks SC dosing interval.
In Treatment Group 3, participants will receive an oral daily regimen of GS-6207. Participants 
will receive oral tablet doses of GS-6207 600 mg on Days 1 and 2, as a PK load, and 50 mg once 
daily, starting from Day 3. This regimen is projected to achieve target exposures within a few 
days of initiation. Based on available PK data (GS-US-200-4071), GS-6207 50 mg once daily is 
predicted to achieve a similar Cmax as GS-6207 927 mg SC, administered every 26 weeks in 
Treatment Groups 1 and 2.
Safety data from studies GS-US-200-4071 and GS-US-200-4538 demonstrated favorable safety 
and tolerability profile of GS-6207 administered as single oral doses of up to 1800 mg, multiple 
oral daily doses of up to 100 mg or single SC doses of up to 927 mg. GS-6207 exposures in this 
study are predicted to be within the range of those shown to be safe and well tolerated; thereby, 
supporting further evaluation of this regimen in this study.


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1.8.2.
F/TAF and TAF
In Cohorts 1, 2 and 3, participants will receive F/TAF once daily (during the induction phase for 
Cohorts 1 and 2, and throughout Cohort 3), and in Cohort 1, participants will receive oral 
once daily TAF 25 mg during the maintenance period in combination with SC GS-6207. Both 
the F/TAF FDC containing F (200 mg) and TAF (25 mg), and TAF 25 mg single agent have 
been approved by the US Food and Drug Administration (FDA) as a component of several 
regimens, for use once daily for the treatment of HIV-1 infection in adults, or for treatment of 
hepatitis B virus (HBV) {BIKTARVY 2019, DESCOVY® 2017, VEMLIDY® 2019}.
1.8.3.
BIC
In the maintenance period of Cohort 2, participants will receive oral once daily BIC (75 mg) in 
combination with SC GS-6207. The PK of BIC 75 mg has been evaluated previously at this 
dose: BIC exposure is similar to that observed in the B/F/TAF Phase 2/3 clinical program, where 
it was shown to be safe and well tolerated {BIKTARVY 2019}.
1.8.4.
B/F/TAF
In Cohort 4, participants will receive B/F/TAF. The B/F/TAF FDC containing B (50 mg), 
F (200 mg), and TAF (25 mg), has been approved by the US-FDA for use once daily for the 
treatment of HIV-1 infection in adults {BIKTARVY 2019}.
1.9.
Rationale for Oral Weekly Bridging of GS-6207 for Missed SC Injection
Participants receiving SC GS-6207 may miss their SC injection window (within 26 to 28 weeks 
of the previous SC GS-6207 dose [Section 5.3]). If a missed dose is anticipated, participants may 
receive oral bridging until they can receive their next SC injection. 
Oral bridging of GS-6207 is supported by antiviral activity, PK, and safety data from a Phase 1b 
proof of concept study (GS-US-200-4072) and 2 ongoing Phase 2 and 2/3 studies 
(GS-US-200-4334 and GS-US-200-4625), as well as PK and safety data from 2 Phase 1 studies 
in healthy volunteers (GS-US-200-4071 and GS-US-200-4333). Phenotypic analyses and PK/PD 
modeling indicate that a GS-6207 plasma concentration of 15.5 ng/mL, corresponding to IQ of 4 
or higher, would provide near maximal antiviral activity (GS-US-200-4072). 
The oral bridging dose of GS-6207 is 300 mg administered once weekly starting 26 to 28 weeks 
after the last GS-6207 SC injection. This oral weekly bridging dose, even when started as late as 
28 weeks after the last GS-6207 SC injection, is predicted to immediately maintain the lower 
bound of the 90% CI of arithmetic mean for GS-6207 Ctau above IQ4 (ie, even before reaching 
steady state) (Figure 1-9A). As long as the oral weekly bridging is initiated between 26 to 
28 weeks after the last GS-6207 SC injection, the PK profile upon resuming SC injection is 
predicted to be comparable with that of the prior SC dose and within the target range regardless 
of when SC injection is resumed (Figure 1-9B).


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GS-6207 has been administered orally at doses up to 1800 mg (Study GS-US-200-4071). Safety 
data from all completed and ongoing clinical studies indicate that GS-6207 is generally safe and 
well tolerated at the intended exposures. 
Figure 1-9. 
Simulated Pharmacokinetic Profile of Oral Weekly Bridging of 
GS-6207 (300 mg) (A) Prior to and (B) After Resuming SC Injection 
SC 
26 2ll 
36 
Study-
P0300n,g QW 
Line= Geo. Mean 
eo Alea= 90% Cl 
SC 
2628 
36 
Study 
SC 927 n,g 
CI = confidence interval; IQ = inhibitory quotient; LEN = lenacapavir (GS-6207); PD = phannacodynamic; PK = 
pha1macokinetic; PO = oral; SC = subcutaneous; QW = once weekly 
62 
70 
TI1e solid line and the shaded region correspond to the geometric mean and 90% CI, respectively. IQ is calculated as trough 
concentration/in vitro protein-adjusted EC95 (paEC95) against wild-type vims. Horizontal dashed lines co!l'espond to target IQ 
values of 4 based on phenotypic analyses and PK/PD modeling. 
1.10. 
Risk/Benefit Assessment for the Study 
Potential risks associated with the study include unknown AEs, including injection site reaction, 
general risks associated with frequent clinic visits and laborato1y blood draws, and the associated 
pain and discomfo1t of multiple phlebotomies. Strategies to mitigate these risks include close 
monitoring of lab values as well as AEs. Parameters for monitoring of AEs will be well defined 
and closely followed. 
In addition, potential risks to PL WH include prolonged exposure to sub therapeutic 
concentrations of GS-6207 if it is discontinued which could lead to HIV-1 developing resistance 
to GS-6207. Strategies to mitigate any potential risks include use of a regimen with at least three 
ARVs during the induction phase and with at least two ARVs during the maintenance phase. In 
addition, all participants will have regular monitoring of their HIV-I level to allow early 
selection of alternative therapies in the event of inadequate response. Paiticipants will be advised 
to initiate alternative therapy for HIV if they discontinue from the study. 
Given the above, the benefit-risk balance for this study is considered positive. 
During the period of a pandemic ( such as COVID-19), additional potential risks to paiticipants 
may include intenuptions to study visit schedule, inadequate study drng availability, and 
unrecognized safety issues due to inte1n1ptions in adherence to protocol-specified safety 
monitoring or laborato1y assessments. Refer to Appendix 5 for finther details on the risks and 
risk mitigation strategy. 
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1.11.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


GS-6207 
Protocol GS-US-200-4334 
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2_ 
OBJECTIVES 
The prima1y objective of this study is: 
Final 
Amendment4 
• 
To evaluate the efficacy of GS-6207 (Lenacapavir, LEN) containing regimens in people 
living with HIV (PL WH) as detennined by the propo1iion of paiiicipants with HIV-1 RNA 
< 50 copies/mL at Week 54 
The secondaiy objectives of this study are: 
• 
To evaluate the efficacy of GS-6207 containing regimens in PL WH as detennined by the 
propo1iion of paiiicipants with HIV-1 RNA < 50 copies/mL at Weeks 28, 38, and 80 
• 
To evaluate the change from baseline in log10 HIV-1 RNA and in CD4+ cell count at 
Weeks 28, 38, 54, and 80 
• 
To evaluate the safety and tolerability of GS-6207 containing regimens through 28, 38, 54, 
and 80 weeks of treatment 
• 
To evaluate the PK of GS-6207, BIC, and T AF 
I 
I 
I 
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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

The proportion of participants with HIV-1 RNA  50 copies/mL at Week 54 as determined 
by the FDA-defined snapshot algorithm
The secondary endpoints of this study are:

The proportion of participants with HIV-1 RNA  50 copies/mL at Weeks 28, 38, and 80 as 
determined by the FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and in CD4+ cell count at Weeks 28, 38, 54, 
and 80
3.2.
Study Design
This is a Phase 2, randomized, open label, active controlled, multicenter study.
Treatment-naïve PLWH who meet all eligibility criteria will be randomized in a 2:2:2:1 ratio to 
1 of the 4 treatment groups. Randomization will be stratified by HIV-1 RNA level 
(≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.
3.3.
Study Treatments
Approximately 175 participants who meet all eligibility criteria may be enrolled in this study in 
one of the following treatment groups:
Treatment Group 1
Induction: Participants will receive oral GS-6207 600 mg, 600 mg, and 300 mg, without regard 
to food, at Days 1, 2, and 8 respectively. Participants will also begin oral daily F/TAF 
(200/25 mg), without regard to food from Day 1 onwards for a total of 28 weeks. On Day 15 
participants will receive SC GS-6207 927 mg, without regard to food.
Maintenance: Participants will receive SC GS-6207 927 mg at Week 28 and every 26 weeks 
thereafter. Participants will discontinue oral daily F/TAF (200/25 mg) at Week 28 and begin 
taking oral daily TAF (25 mg), without regard to food.
Treatment Group 2
Induction: Participants will receive oral GS-6207 600 mg, 600 mg, and 300 mg, without regard 
to food at Days 1, 2, and 8 respectively. Participants will also begin oral daily F/TAF 
(200/25 mg), without regard to food from Day 1 onward for a total of 28 weeks. On Day 15 
participants will receive SC GS-6207 927 mg, without regard to food.


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Maintenance: Participants will receive SC GS-6207 927 mg at Week 28 and every 26 weeks 
thereafter. Participants will discontinue oral daily F/TAF (200/25 mg) at Week 28 and begin oral 
daily BIC (75 mg) without regard to food.
Treatment Group 3
Participants will receive oral GS-6207 600 mg, and 600 mg without regard to food at Days 1 and 
2, respectively. On Day 3, participants will begin oral daily GS-6207 50 mg, without regards to 
food. Participants will begin oral daily F/TAF (200/25 mg), without regard to food from Day 1 
onwards.
Treatment Group 4
Participants will receive oral daily B/F/TAF (50/200/25 mg), without regard to food at Day 1 and 
throughout their participation in the study.
Randomization will be stratified as defined in Section 5.1.
3.4.
Duration of Treatment
Participants will be treated for at least 80 weeks. Participants in Treatment Group 4 will 
complete the study at Week 80.
At Week 80, participants receiving GS-6207 will be given the option to receive further treatment 
and continue to attend visits on Week 90, Week 106, Week 116, Week 132, Week 142, and will 
continue to alternate between every 10 weeks and every 16 weeks visits. Participants willing to 
continue the study beyond Week 80 in Treatment Groups 1 and 2 will continue to receive SC 
GS-6207 927 mg every 6 months (26 weeks) from Week 80 onwards and participants in 
Treatment Group 3 will continue to receive oral GS-6207 50 mg (daily) from Week 80 until 
product becomes accessible to participants through an access program, or until Gilead elects to 
discontinue the study in the country. Participants in Treatment Groups 1, 2, and 3 will also 
receive TAF, F/TAF, or BIC as applicable.
Participants who discontinue study drugs prior to Week 80 visit or prior to study completion may 
be required to complete 30-Day, 90 Day and/or 180-Day Follow Up visits after Early 
Termination Visit as described in Section 6.4.2.


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Figure 3-1. 
Study Schema 
BL 
Induction 
Wk28 
Maintenance 
n=50 
.. GS-6207 (SC Q6M) 
n=50 
•GS-6207 (SC Q6M) 
Tx-Na'ive 
n=175 
F/TAF (oral QD) 
""BIC (oral QD) 
n=50 
"GS-6207 (oral QD) 
F/TAF (oral QD) 
Wk54 
Wk80 
............... 
............... 
.............. 
•Treatment GrouJ)s 1, 2 and 3 will have oral PK loading doses 
.. Participants in Treatment Groups 1 and 2 will need to have HIV-1 RNA results < 50 copies/ml at Weeks 16 and 22 to initiate 
treatment with a two-agent regimen at Week 28; those with values 
50 copies/ml will discontinue the study at Week 28. 
BIC, B = bictegravir; BL = baseline; F = emtricitabine; HIV-1 = human immunodeficiency vims type 1; PK = phanuacokinetic; 
QD = once daily; Q6M = every 6 months; SC = subcutaneous; TAF = tenofovir alafenamide; Tx-nai:Ve = treatment nai:ve; Wk = 
week. 
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4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection
Approximately 175 PLWH who meet the eligibility criteria will be enrolled in one of 4 treatment 
groups.
4.1.1.
Participant Replacement
Participants who discontinue prior to the end of study will not be replaced.
4.2.
Inclusion Criteria
Participants must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Willing and able to provide written informed consent prior to performing study procedures
2) Aged ≥ 18 years
3) Antiretroviral naïve with no use of any ARV within one month of Screening. Use of 
pre-exposure prophylaxis (PrEP) (any duration), post-exposure prophylaxis (PEP) 
(any duration), or HIV-1 treatment (< 10 days therapy total) > 1 month prior to Screening is 
permitted
4) Plasma HIV-1 RNA  200 copies/mL at Screening
5) CD4+ cell count  200 cells/L at Screening
6) A negative serum pregnancy test is required for all women at screening
7) Participants of childbearing potential who engage in heterosexual intercourse must agree to 
use protocol-specified method(s) of contraception as defined in Appendix 4.
8) Lactating women must agree to discontinue nursing before the study drug(s) is administered
4.3.
Exclusion Criteria
Participants who meet any of the following exclusion criteria are not to be enrolled in this study:
1) An opportunistic illness requiring acute therapy within 30 days prior to screening
2) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days before screening
3) Active tuberculosis infection
4) Acute hepatitis within 30 days prior to screening


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5) HBV infection, defined as screening results showing either or both of:
a) Positive HBV surface antigen
b) Positive HBV core antibody and negative HBV surface antibody 
6) Hepatitis C virus (HCV) antibody positive and HCV RNA > lower limit of quantitation 
(LLOQ)
7) A history of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or 
variceal bleeding)
8) Treatment within 3 months prior to screening, or anticipated treatment during the study 
period with immunosuppressant therapies, hydroxyurea, foscarnet, radiation, or cytotoxic 
chemotherapeutic agents without prior approval from sponsor prior to randomization. Agents 
disallowed in Table 5-5 may not be considered for approval
9) Active malignancy requiring acute therapy (with the exception of local cutaneous 
Kaposi's sarcoma)
10) Current alcohol or substance use judged by the investigator to potentially interfere with the 
participant’s study compliance
11) Clinically significant abnormal ECG at the screening visit
12) Any of the following laboratory values at screening
a) Estimated glomerular filtration rate (eGFR) ≤ 50 mL/min according to the 
Cockcroft-Gault formula for creatinine clearance {Cockcroft 1976}
b) Alanine aminotransferase (ALT) > 5  upper limit of normal (ULN)
c) Direct bilirubin > 1.5  ULN
d) Platelets < 50,000/mm3
e) Hemoglobin < 8.0 g/dL
13) Participation or planned participation in any other clinical trial (including observational 
trials) without prior approval from the sponsor throughout the study
14) Prior use of, or exposure to, GS-6207
15) Known hypersensitivity to the study drug(s), the metabolites, or formulation excipient
16) Use or planned use of exclusionary medications, refer to Section 5.4
17) Any other clinical condition or prior therapy that, in the opinion of the investigator, would 
make the participant unsuitable for the study or unable to comply with dosing requirements


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding, and Treatment Codes Access
5.1.1.
Randomization
Participants will be assigned a screening number using the Interactive Web Response System 
(IWRS) on the day of the screening visit. Randomization and Day 1 visits must not occur 
until participant eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day 1 visit, the investigator or 
designee will randomize the participant using IWRS. Once a participant number has been 
assigned to a participant, it will not be reassigned to any other participant.
Randomization or enrollment may occur approximately 3 days prior to Day 1 visit provided that 
all screening procedures have been completed and participant eligibility has been confirmed.
Participants who meet eligibility criteria will be randomized in a 2:2:2:1 ratio to 1 of 4 treatment 
groups starting on Day 1. Randomization will be stratified by HIV-1 RNA level 
(≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.
5.1.2.
Blinding
Blinding of treatment assignments or data will not be performed in this study.
5.2.
Description and Handling of Lenacapavir (GS-6207) Injection, Lenacapavir 
(GS-6207) Tablets, TAF, F/TAF, B/F/TAF, and Bictegravir
5.2.1.
Formulation
GS-6207 injection, 309 mg/mL, is a clear, yellow to brown solution for SC injection. In addition 
to the active ingredient (GS-6207 sodium salt), GS-6207 injection, 309 mg/mL, contains the 
following inactive ingredients: polyethylene glycol 300 and water for injection.
GS-6207 tablets, 300 mg are capsule-shaped, film-coated, beige tablets, debossed with “GSI” on 
one side of the tablet and “62L” on the other side of the tablet. Each tablet core contains the 
equivalent of 300 mg GS-6207 free acid in the form of GS-6207 sodium salt. In addition to the 
active ingredient, GS-6207 tablets 300 mg contain the following inactive ingredients: 
microcrystalline cellulose, mannitol, poloxamer 407, copovidone, croscarmellose sodium, 
magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, iron oxide 
red, iron oxide black, and iron oxide yellow.
GS-6207 tablets, 50 mg are capsule-shaped, film-coated green tablets, debossed with “GSI” on 
one side of the tablet and “07S” on the other side of the tablet. Each tablet core contains the 
equivalent of 50 mg GS-6207 free acid in the form of GS-6207 sodium salt. In addition to the 
active ingredient, GS-6207 tablets 50 mg contain the following inactive ingredients: 
microcrystalline cellulose, mannitol, poloxamer 407, copovidone, croscarmellose sodium, 
magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, iron oxide 
black, and iron oxide yellow.


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TAF tablets, 25 mg are round, biconvex, film-coated yellow tablets, debossed with "GSI" on one 
side of the tablet and "25" on the other side of the tablet. Each tablet core contains 25 mg of 
TAF. In addition to the active ingredient, TAF tablets contain the following inactive ingredients: 
lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, 
polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide yellow.
F/TAF (200/25 mg) tablets are rectangular-shaped, film-coated blue tablets, debossed with 
“GSI” on one side of the tablet and “225” on the other side of the tablet. Each tablet core 
contains 200 mg of FTC and 25 mg of TAF. In addition to the active ingredients, F/TAF tablets 
contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The tablet 
cores are film-coated with blue #2/indigo carmine aluminum lake, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.
B/F/TAF (50/200/25 mg) tablets are capsule-shaped, film-coated, purplish-brown tablets, 
debossed with "GSI" on one side of the tablet and "9883" on the other side of the tablet. Each 
tablet core contains 50 mg of BIC, 200 mg of FTC, and 25 mg of TAF. In addition to the active 
ingredients, B/F/TAF tablets contain croscarmellose sodium, magnesium stearate, and 
microcrystalline cellulose. The tablet cores are film-coated with iron oxide red, iron oxide black, 
polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
Bictegravir tablets, 75 mg are yellow, round, plain-faced, film-coated tablets. In addition to BIC, 
each tablet contains lactose monohydrate, microcrystalline cellulose, crospovidone, sodium 
stearyl fumarate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc and iron oxide 
yellow.
5.2.2.
Packaging and Labeling
GS-6207 injection, 309 mg/mL, is supplied as a sterile solution packaged in a single use, clear 
vial fitted with a rubber stopper and an aluminum flip-off seal.
GS-6207 tablets, 300 mg are packaged in white, high-density polyethylene (HDPE) bottles. Each 
bottle contains 4 or 5 tablets, silica gel desiccant, and polyester packing material. Each bottle is 
enclosed with a white, continuous thread, child-resistant polypropylene screw cap fitted with an 
induction-sealed and aluminum-faced liner.
GS-6207 tablets, 50 mg are packaged in white, HDPE bottles. Each bottle contains 30 tablets, 
silica gel desiccant, and polyester packing material. Each bottle is enclosed with a white, 
continuous thread, child-resistant polypropylene screw cap fitted with an induction-sealed and 
aluminum-faced liner.
TAF tablets, 25 mg are packaged in white, HDPE bottles. Each bottle contains 30 tablets, silica 
gel desiccant, and polyester packing material. Each bottle is enclosed with a white, continuous 
thread, child-resistant polypropylene screw cap fitted with an induction-sealed and 
aluminum-faced liner.


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F/TAF tablets, 200/25 mg are packaged in white, HDPE bottles. Each bottle contains 30 tablets, 
silica gel desiccant, and polyester packing material. Each bottle is enclosed with a white, 
continuous thread, child-resistant polypropylene screw cap fitted with an induction-sealed and 
aluminum-faced liner. 
B/F/TAF tablets, 50/200/25 mg are packaged in white, HDPE bottles. Each bottle contains 
30 tablets, silica gel desiccant, and polyester packing material. Each bottle is enclosed with a 
white, continuous thread, child-resistant polypropylene screw cap fitted with an induction-sealed 
and aluminum-faced liner. 
Bictegravir tablets, 75 mg are packaged in white, HDPE bottles with polyester coil in each bottle. 
Each bottle contains 30 tablets and polyester packing material, continuous thread, child-resistant 
polypropylene screw cap fitted with an induction-sealed and aluminum-faced liner.
Study drugs to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US-FDA and/or other local regulations.
5.2.3.
Storage and Handling
GS-6207 injection, 309 mg/mL should be stored below 30°C (86°F), protected from light. 
Storage conditions are specified on the label.
GS-6207, 300 mg tablets should be stored below 30°C (86°F). Storage conditions are specified 
on the label.
GS-6207, 50 mg tablets should be stored below 30°C (86°F). Storage conditions are specified on 
the label.
TAF tablets should be stored at controlled room temperature of 25°C (77°F); excursions are 
permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label.
F/TAF tablets should be stored at controlled room temperature of 25°C (77°F); excursions are 
permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label.
B/F/TAF tablets should be stored at controlled room temperature of 25°C (77°F); excursions are 
permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label.
Bictegravir, 75 mg tablets should be stored at controlled room temperature of 25°C (77°F); 
excursions are permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are 
specified on the label.
Until dispensed to the participants, all study drugs should be stored in a securely locked area, 
accessible only to authorized site personnel. To ensure the stability and proper identification, 
study drugs should not be stored in a container other than the container in which they were 
supplied. Consideration should be given to handling, preparation, and disposal through measures 
that minimize drug contact with the body. Appropriate precautions should be followed to avoid 
direct eye contact or exposure when handling.


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5.3.
Dosage and Administration of Study Drugs
All study drugs (Oral GS-6207, GS-6207 injection for SC administration, TAF, F/TAF, BIC, 
B/F/TAF) will be provided by Gilead.
Treatment Group 1 and 2 participants will be administered oral GS-6207 on Days 1, 2, and 8. 
GS-6207 will be administered without regards to food. The oral GS-6207 (300 mg) bottle will 
remain at investigator site and will not be given to the participants. Oral and SC dosing is 
presented in Table 5-1.
Table 5-1.
GS-6207 Dosing for Treatment Group 1 and 2
Study Visits
GS-6207
Day 1 
600 mg oral
Day 2 
600 mg oral
Day 8 
300 mg oral
Day 15 
927 mg SC
Week 28 and every 26 weeks thereafter
927 mg SC
GS-6207 927 mg injection will be administered in the abdomen via SC injections on Day 15, 
Week 28, and every 6 months (26 weeks) thereafter. GS-6207 should be administered as multiple 
injections at different abdominal sites no more than 15 minutes apart when possible.
In addition to GS-6207, Treatment Group 1 and 2 participants will take oral daily F/TAF from 
Day 1 onwards approximately at the same time. F/TAF will be administered on-site on Day 1. 
The F/TAF bottle(s) can be kept on-site for Day 2 administration and should be given to 
participants at the end of Day 2 visit to take at home from Day 3 onwards. Treatment Group 1 
participants with < 50 copies/mL of HIV-1 RNA at Week 16 and Week 22 will stop F/TAF at 
Week 28 and will initiate oral daily TAF. Treatment Group 2 participants with < 50 copies/mL 
of HIV-1 RNA at Week 16 and Week 22 will stop F/TAF at Week 28 and will initiate oral daily 
BIC.
Oral dosing on Day 1, Day 2, and Day 8 and all SC GS-6207 administrations will occur on site 
and without regard to food (for Oral Bridging Period, see 5.4).
If participants in Treatment Groups 1 and 2 are not dosed within the protocol visit windows, and 
the investigator believes that it is in the participant’s medical interest to continue to receive 
GS-6207, Gilead should be contacted immediately, and the participant may continue to receive 
GS-6207 with the approval of the Gilead medical monitor. Additional oral GS-6207 doses may 
be needed prior to subsequent SC dosing (Section 5.4).


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Table 5-2.
GS-6207 Dosing for Treatment Group 3
Study Visits
GS-6207
Day 1
600 mg oral
Day 2
600 mg oral
Day 3 onwards
50 mg oral daily
Participants in Treatment Group 3 will be administered oral GS-6207, 600 mg, on Days 1 and 2. 
GS-6207 will be administered without regards to food. The oral GS-6207 (300 mg) bottle will 
remain at the investigator site and will not be given to the participants. 
In addition to oral GS-6207, participants in Treatment Group 3 will take oral F/TAF daily from 
Day 1 onwards approximately at the same time. Dosing of GS-6207 and F/TAF will occur 
on-site on Day 1. The GS-6207 50 mg bottle(s) and F/TAF bottle(s) can be kept on-site and 
should be given to the participants by end of Day 2 visit. Participants will take 50 mg of 
GS-6207 oral daily and F/TAF oral daily together at approximately the same time from Day 3 
onwards. Oral GS-6207 dosing is presented in Table 5-2.
Treatment Group 4 participants will take B/F/TAF orally daily at approximately the same time. 
Administration of dose on Day 1 will occur on-site and without regard to food.
For participants in all treatment groups, the date and time of the last meal prior to dosing will be 
collected. 
5.4.
Dosing and Administration of Oral Weekly Bridging of GS-6207
Participants in Treatment Groups 1 and 2 may require oral weekly bridging if an SC injection of 
GS-6207 cannot be administered for any reason within the protocol visit window.

If 26 to 28 weeks elapses since the last SC injection and if clinically appropriate to continue 
GS-6207, start oral GS-6207 300 mg (1 tablet) once a week at Oral Bridging visits and 
continue weekly dosing on the same day of the week. 

If more than 28 weeks elapse since the last SC injection and if clinically appropriate to 
continue GS-6207, restart the oral lead-in at the Oral Bridging visits and continue oral 
weekly dosing on the same day of the week, until SC GS-6207 is administered (Table 5-3). 


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Table 5-3.
Dosing Schedule for Oral Weekly Bridging and Resumption of SC 
GS-6207 Injection
26 to 28 weeks of elapse
since the last SC injection
More than 28 weeks of elapse 
since the last SC injection
GS-6207 Dose
Treatment time from oral start
Dose
N/A
Day 1a
Oral 600 mg
(2 x 300 mg tablets)
N/A
Day 2
Oral 600 mg
(2 x 300 mg tablets)
Day 1a
Day 8; 
continue oral weekly GS-6207 on 
the same day of the week as first 
dose until GS-6207 SC is 
administered
Oral 300 mg
(1 x 300 mg tablet)
Day 8;
continue oral weekly GS-6207 on 
the same day of the week as first 
dose until GS-6207 SC is 
administered
Not applicable
Oral 300 mg
(1 x 300 mg tablet)
once a week
SC administration restart
(within one week of the oral weekly 
300 mg dose [as early as after Day 
1 dosing])
SC administration restart
(within one week of the oral weekly 
300 mg dose [as early as after Day 
8 dosing])
SC 927 mg
every 6 monthsa
N/A = not applicable; SC = subcutaneous
a
Day 1 oral dosing and SC GS-6207 will be administered on site, otherwise, all other oral dosing will be administered at 
home, but can be done on site at the investigator’s discretion.

For oral weekly bridging, the administration of the first dose will occur on-site and up to 
2 bottles of GS-6207 will be given to the participant to take oral GS-6207 at home; further 
on-site oral dosing may occur at investigator’s discretion. Up to 2 additional bottles may be 
given to the participant as needed upon completion of previously dispensed bottles.

Participants may continue receiving oral weekly GS-6207 300 mg until they can receive their 
next SC GS-6207 injection. 

If oral weekly GS-6207 administration is expected to be needed beyond 12 consecutive 
weeks, Gilead should be contacted and further additional oral weekly doses can be provided 
after assessment unless other guidance is provided by Gilead.

Monitoring of participants should continue according to the study protocol. Oral Bridging 
visit should be completed every 10-12 weeks. Additional visits during the oral weekly 
administration may be conducted per investigator’s discretion 

Missed dose recommendations for oral weekly bridging are provided in Table 5-4. The 
scheduled dosing day of the week should not change due to the missed dose of GS-6207.


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Table 5-4.
Missed Dose Recommendations for GS-6207 During Oral Weekly 
Bridging
Number of days since initial 
missed schedule dose
Recommendation
Example
1 to 6 days
(1 missed dose)
Take 1 dose as soon as possible, 
then resume normal schedule, 
taking 1 dose on the next scheduled 
day
Participant forgets to take dose on 
Monday (scheduled) but 
remembers before the next 
scheduled dose day (ie, 
Tuesday-Sunday). Take 1 dose as 
soon as possible, then take 1 dose 
on the following Monday as 
scheduled.
7 to 14 days
(1 - 2 missed doses)
Take 2 doses as soon as possible, 
then resume normal schedule on 
scheduled day. If participant 
remembers on scheduled dosing 
day, then take 2 doses only. Never 
take 3 doses on the same day.
Participant forgets to take dose on 
Monday (scheduled) but 
remembers the following Monday. 
Take 2 doses on the second 
Monday and resume dosing 
schedule (1 dose on Mondays).
Participant forgets to take dose on 
2 consecutive Mondays (scheduled) 
but remembers a few days later 
(ie, Tuesday-Sunday following 
second missed dose) before the 
third Monday. Take 2 doses as soon 
as possible, then take 1 dose the 
next Monday as scheduled.
Participant forgets to take dose on 
2 consecutive Mondays (scheduled) 
but remembers on the third 
Monday. Take 2 doses on the third 
Monday and resume dosing 
schedule (1 dose on Mondays). 
Never take 3 doses on the same 
day.
More than 14 days
(3 or more missed doses)
Assess whether clinically 
appropriate to continue oral weekly 
bridging. 
Consider checking HIV-1 RNA.
Participant forgets to take dose on 
3 consecutive Mondays 
(scheduled). Clinical assessment 
needed.
5.5.
Prior and Concomitant Medications
Clinical data indicate GS-6207 is a substrate of P-gp transporters and an inhibitor of CYP3A 
(moderate), BCRP and P-gp. In vitro data suggest GS-6207 is also a substrate of CYP3A and 
UGT1A1 enzymes. Concomitant use of GS-6207 with some medications or herbal/natural 
supplements that are inhibitors and inducers of CYP3A, UGT1A1 or P-gp may result in 
increased or decreased exposure of GS-6207 respectively. 


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Concomitant use of GS-6207 with some medications or herbal/natural supplements that are 
substrates of CYP3A, P-gp or BCRP may result in increased exposure of these medications.
Representative medications listed Table 5-3 and herbal/natural supplements are currently 
excluded or should be used with caution while participating in this study; this table is not 
exhaustive. For medications that may be substrates of Pgp, CYP3A, UGT1A1 or BCRP, or those 
that may be inducers, the investigator should reach out to Gilead for guidance.
Participants should discontinue disallowed concomitant medications 30 days prior to initiation of 
study drug, unless otherwise specified.
Table 5-5.
List of Representative Medications that are Prohibited or To Be Used 
with Caution due to the Potential for Drug-Drug Interaction with 
GS-6207
Medication Class
Disallowed Medications
Use Discouraged and To Be Used With Caution
Anti-coagulants
Dabigatran etexilate: monitoring and/or dose 
reduction may be needed for certain populations per 
prescribing information
Anti-convulsants
Carbamazepine, Oxcarbazepine, 
Phenobarbital, Phenytoin
Anti-mycobacterials
Rifampin, Rifabutin, Rifapentine
Anti-retroviral agents
Any ARV not part of the study treatment 
regimen
Digoxin
Digoxin: Concomitant use may result in increased 
levels of digoxin; use with caution and with 
appropriate monitoring of serum digoxin levels
Ergot derivatives
Ergotamine, Ergonovine, 
Dihydroergotamine, Methylergonovine, 
Ergometrine
Herbal/Natural 
Supplements
St. John’s Wort, Echinaccea, Milk thistle 
(i.e., silymarin), Chinese herb sho-saiko-to 
(or Xiao-Shai-Hu-Tang)
3-Hydroxy-3-
methylglutaryl-
coenzyme A (HMG-
CoA) Reductase 
Inhibitors
Concentrations of some statins may increase with 
GS-6207. Start with the lowest dose and titrate to 
clinical response. For each of the following statins, 
the maximum allowed dose is:
Simvastatin: 10 mg
Lovastatin: 20 mg
Atorvastatin: 40 mg
Careful monitoring for signs and symptoms of 
muscle weakness or myopathy, 
including rhabdomyolysis.
Phosphodiesterase-5 
Inhibitors
Sildenafil, Vardenafil, Tadalafil: It is recommended 
that a single dose of Sildenafil no more than 25 mg 
in 48 hours, Vardenafil no more than 2.5 mg in 72 
hours, or Tadalafil no more than 10 mg in 72 hours 
be coadministered.
Sedatives/Hypnotics
Midazolam, Triazolam


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Medication Class
Disallowed Medications
Use Discouraged and To Be Used With Caution
Systemic 
Corticosteroids
All agents, including dexamethasone
For participants in Treatment Groups 1, 2, and 3, physicians should also refer to the most current 
package insert for F/TAF for guidance on concomitant medications while participants are 
receiving treatments containing TAF (TAF single agent or F/TAF).
For participants in Treatment Groups 2 and 4, physicians should also refer to the most current 
package insert for B/F/TAF for guidance on concomitant medications while the participants are 
receiving BIC.
Medications to treat disease conditions excluded from the protocol are not listed under this 
Concomitant Medication section and are disallowed in the study. Medications for malignancy are 
not included in the table.
Should participants have a need to initiate treatment with any disallowed concomitant 
medication, the medical monitor must be consulted prior to initiation of the new medication. In 
instances where disallowed medication is initiated prior to discussion with the sponsor, the 
investigator must notify Gilead as soon as they are aware of the use of the medication.
5.6.
Accountability for Investigational Medicinal Product 
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug. This includes acknowledgment of receipt of each shipment of study drug (quantity and 
condition). All used and unused study drug dispensed to participants must be returned to the site.
Each study site must keep accountability records that capture:

the date received and quantity of study drug kits 

the date, participant number, and the study drug kit number dispensed

the date, quantity of used and unused study drug returned, along with the initials of the 
person recording the information
5.6.1.
Investigational Medicinal Product Return or Disposal of GS-6207, TAF, 
F/TAF, BIC, and B/F/TAF
Gilead recommends that used and unused study drug supplies be destroyed at the site. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead, the site may destroy used (empty or partially empty) and unused study drug supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for electronic trail master file (eTMF). If study drug is destroyed on-site, the investigator must 
maintain accurate records for all study drugs destroyed. Records must show the identification 
and quantity of each unit destroyed, the method of destruction, and the person who disposed of 
the study drug. Upon study completion, copies of the study drug accountability records must be 
filed at the site. Another copy will be returned to Gilead.


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If the site does not have an appropriate SOP for drug destruction, used and unused study drug 
supplies are to be sent to the designated disposal facility for destruction. The study monitor will 
provide instructions for return.
The study monitor will review study drug supplies and associated records at periodic intervals.
For both disposal options listed above, the study monitor must first perform drug accountability 
during an on-site monitoring visit, unless otherwise agreed with the sponsor and documented.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each participant enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.
The investigator must document any deviation from the protocol procedures and notify Gilead or 
the contract research organization (CRO).
6.1.
Participant Enrollment and Treatment Assignment
Entry into screening does not guarantee enrollment into the study. In order to manage the total 
study enrollment, Gilead, at its sole discretion, may suspend screening and/or enrollment at any 
site or study-wide at any time.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Participants will be screened within 30 days before randomization to determine eligibility for 
participation in the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain demographic information, including gender at birth, sexual orientation, and gender 
identity

Obtain medical history including HIV-1 disease-related events, available historical 
genotype/phenotype reports and prior medications within 30 days of the screening visit. 
Samples for genotype reports will be collected at screening but results are not required to 
determine eligibility.

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the investigator) including, vital signs (blood pressure, pulse, respiration rate, 
and temperature, body weight, and height)

12-lead ECG performed supine

Obtain blood and urine samples as noted in Section 6.5

Record any SAEs and all AEs related to protocol-mandated procedures occurring after 
signing of the consent form.
Participants meeting all of the inclusion criteria and none of the exclusion criteria will return to 
the clinic within 30 days after screening for randomization into the study.


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Participants not meeting one or more inclusion criteria and/or meeting one or more exclusion 
criteria may be rescreened on a case-by-case basis upon written approval from Gilead Medical 
Monitor or Study Director.
 From the time of obtaining informed consent through the first administration of study drug, 
record all SAEs, as well as any AEs related to protocol-mandated procedures on the AEs 
electronic case report form (eCRF). All other untoward medical occurrences observed during the 
screening period, including exacerbation or changes in medical history are to be considered 
medical history. See Section 7 Adverse Events and Toxicity Management for additional details.
6.3.
Treatment Assessments
6.3.1.
Day 1
The following evaluations are to be completed at the Day 1 visit. The investigator must have 
confirmed eligibility before proceeding with randomization and the Day 1 visit. Participants 
must complete all study procedures before being administered study drug:

Prior to the completion of other study procedures, participants will read the questionnaires by 
themselves and provide answers directly onto the questionnaires (if available)
HIV dependent quality of life (HIVDQoL) and EQ-ED-5L

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs (blood pressure, pulse, respiration rate, and temperature), including weight

Obtain blood and urine samples as described in Section 6.5

Dispense study drug(s) based on participant’s treatment assignment at randomization:
Participants randomized to Treatment Group 1, 2, and 3 will be dispensed PK loading 
doses of oral GS-6207 (600 mg) and F/TAF (200/25 mg). Bottle of 300 mg GS-6207 will 
remain at site for in-clinic observed dosing. Bottle of F/TAF can remain at site on Day 1 
and Day 2 for in-clinic observed dosing and then will be given to participant at the end of 
Day 2 visit for subsequent daily dosing at home.
Participants randomized to Treatment Group 3 will be dispensed oral GS-6207 (50 mg). 
Participants may be given bottle of oral GS-6207 (50 mg) at the end of Day 2 visit to 
initiate dosing from Day 3 onwards only.
Participants randomized to Treatment Group 4 will be dispensed oral daily B/F/TAF 
(50/200/25 mg)


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
Observed first dose administration of the assigned study drugs as described in Section 5.3
Participants randomized to Treatment Group 1, 2, and 3 will be administered PK loading 
doses of oral GS-6207 (600 mg) and F/TAF (200/25 mg)
Participant randomized to Treatment Group 4 will be administered oral daily B/F/TAF 
(50/200/25 mg)
6.3.2.
Day 2, 
 Day 8, and Day 15
The following evaluations are to be completed at Day 2,
 (± 1 day) 
 
, Day 8, and Day 15 for participants only 
in Treatment Groups 1, 2, and 3. Participants in Treatment Group 4 will have visits starting at 
Week 4 after Day 1.

Prior to the completion of other study procedures, participants will read the questionnaires by 
themselves and provide answers directly onto the questionnaires (if available)
HIV Treatment Satisfaction Questionnaire (HIVTSQ12) (Day 15)

Review of AEs and changes in concomitant medications

Complete physical examination (Day 15), (urogenital/anorectal exams will be performed at 
the discretion of the Investigator) or symptom-directed physical examination as needed 

Vital signs (blood pressure, pulse, respiration rate, and temperature), including weight 

Obtain blood and urine samples as described in Section 6.5

Document dispensation and accountability for GS-6207 

Observed dose administration of the assigned study drugs as described in Section 5.3 
(Days 2, 8, and 15 for Treatment Groups 1 and 2 only)
Day 2: Participants randomized to Treatment Groups 1, 2, and 3 will be administered PK 
loading doses of oral GS-6207 (600 mg).
Day 8: Participants randomized to Treatment Groups 1 and 2 will be administered PK 
loading doses of oral GS-6207 (300 mg).

Instruct participant to initiate dosing of GS-6207 50 mg from Day 3 onwards 
(Treatment Group 3 only)

GS-6207 SC injection for Treatment Group 1 and 2 participants only (Day 15)
Provide Injection Site Reaction Assessment Worksheet and instruct the participants to 
measure and report injection site reactions following the administration of the SC 
injections
CCI
CCI
CCI
CCI
CCI
CCI
-
-


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
After administration of SC GS-6207 and completion of other study procedures, participants 
will read the questionnaires by themselves and provide answers directly onto the 
questionnaires (if available) (Day 15)
Injection Acceptability Questionnaire and Numeric Pain Rating Scale for participants 
randomized to Treatment Groups 1 and 2 only
6.3.3.
Treatment Assessments (Week 4 – Week 28)
The following evaluations are to be completed at Week 4 and every 6 weeks until Week 28, 
unless otherwise specified.
All study visits are to be completed within ± 2 days of the protocol-specified visit date (based on 
the Day 1 visit), unless otherwise specified.
Regularly scheduled evaluations will be made on all participants whether or not they continue to 
receive their study regimen.

Prior to completion of other study procedures, participants will read the questionnaires by 
themselves and provide answers directly onto the questionnaires (if available) (Week 4, 
Week 28)
HIV Treatment Satisfaction Questionnaire status (HIVTSQ12s), HIVDQoL, and 
EQ-ED-5L

Review of AEs and changes in concomitant medications

Complete physical examination (Week 28) (urogenital/anorectal exams will be performed at 
the discretion of the Investigator) or symptom-directed physical examination, as needed

Vital signs (blood pressure, pulse, respiration rate, and temperature), including weight

Obtain blood and urine samples as described in Section 6.5

Document bottle dispensation for study drug(s) for all visits
Participants randomized to Treatment Groups 1 and 2 will be dispensed F/TAF 
(200/25 mg) (Week 4, Week 10, Week 16, Week 22) 
Participants in Treatment Group 1 will discontinue F/TAF and will be dispensed TAF 
(25 mg) (Week 28)
Participants in Treatment Group 2 will discontinue F/TAF and will be dispensed BIC 
(75 mg) (Week 28)
Participants randomized to Treatment Group 3 will be dispensed GS-6207 (50 mg) and 
F/TAF (200/25 mg)
Participant randomized to Treatment Group 4 will be dispensed B/F/TAF (50/200/25 mg)


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
Document accountability for study drug(s) for all visit

GS-6207 SC injection for Treatment Group 1 and 2 participants only (Week 28)
Provide Injection Site Reaction Assessment Worksheet and instruct the participants to 
measure and report injection site reactions following the administration of the SC 
injections

Participants who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.7

Participants in Treatment Groups 1 and 2 will need to have HIV-1 RNA results 
< 50 copies/mL at Weeks 16 and 22 to initiate treatment with a two-agent regimen at 
Week 28; HIV-1 RNA results ≥ 50 copies/mL will be assessed for virologic rebound as 
described in Section 6.7.2. Participants with confirmed HIV-1 RNA values ≥ 50 copies/mL 
will discontinue the study drug at or prior to Week 28

After administration of SC GS-6207 and completion of other study procedures, participants 
will read the questionnaires by themselves and provide answers directly onto the 
questionnaires (if available)
Injection Acceptability Questionnaire and Numeric Pain Rating Scale for participants 
randomized to Treatment Groups 1 and 2 only (Week 28 only)
6.3.4.
Post Week 28 Assessments
The following evaluations are to be completed at Week 38, Week 54, Week 64, and Week 80. At 
Week 80, participants in Treatment Group 4 will complete the study. Participants in Treatment 
Groups 1, 2, and 3 will be given the option to receive further treatment and continue to attend 
visits on Week 90, Week 106, Week 116, Week 132, Week 142, and will continue to alternate 
between every 10 weeks and every 16 weeks.
Week 28 through Week 80 study visits are to be completed within ± 2 days of the 
protocol-specified visit date (based on the Day 1 visit). Following the completion of the Week 80 
visit, visits are to be completed within ± 6 days of the protocol-specified visit date. Each SC 
GS-6207 dosing should occur within 26 and 28 weeks of the previous SC GS-6207 dosing 
(unless there is no intervening Oral Bridging Period).
Participants in Treatment Groups 1 and 2 may require Oral Bridging if an SC injection of 
GS-6207 cannot be administered within the protocol visit window. In case of oral bridging 
initiation, participants will receive oral GS-6207 as specified in Section 5.4 and complete Oral 
Bridging visits. An Oral Bridging visit should be completed every 10-12 weeks. Additional visits 
during the oral weekly administration may be conducted per investigator’s discretion. Upon 
restarting GS-6207 SC injection, a SC dosing visit will restart (ie, Week 80, Week 106), with 
follow-up visits in between occurring as specified in this protocol.


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
Prior to the completion of other study procedures, participants will read the questionnaires by 
themselves and provide answers directly onto the questionnaires (if available) (Week 54)
HIV Treatment Satisfaction Questionnaire change (HIVTSQ12c), HIVDQoL, and 
EQ-ED-5L 

Prior to the completion of other study procedures, participants will read the questionnaires by 
themselves and provide answers directly onto the questionnaires (if available) (Week 80)
HIVTSQ12s, HIVDQoL, and EQ-5D-5L

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 54, 80) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination, as 
needed

Vital signs (blood pressure, pulse, respiration rate, and temperature), including weight

Obtain blood and urine samples as described in Section 6.5

Document dispensation and accountability for study drug(s) for all visits
Participants in Treatment Group 1 will be dispensed TAF (25 mg) 
Participants in Treatment Group 2 will be dispensed BIC (75 mg) 
Participants randomized to Treatment Group 3 will be dispensed oral daily GS-6207 
(50 mg) and F/TAF (200/25 mg)
Participant randomized to Treatment Group 4 will be dispensed oral daily B/F/TAF 
(50/200/25 mg) (Week 38, Week 54, Week 64)

GS-6207 SC injection for Treatment Group 1 and 2 participants only (Week 54 and every 
26 weeks thereafter)
Provide Injection Site Reaction Assessment Worksheet and instruct the participants to measure 
and report injection site reactions following the administration of the SC injections

For all participants on oral weekly bridging, the first dose of oral GS-6207 will be 
administered at the study center without regard to food and up to two bottles will be provided 
to the participant with instructions to take the remaining doses at home once a week 
(1  300 mg GS-6207) without regard to food on the same day of the week that the first dose 
was given.

After administration of SC GS-6207 and completion of other study procedures, participants 
will read the questionnaires by themselves and provide answers directly onto the 
questionnaires (if available) (Week 54, Week 80)


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Injection Acceptability Questionnaire and Numeric Pain Rating Scale for participants 
randomized to Treatment Groups 1 and 2 only 

Document study drug administration

Document study drug accountability

Participants who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.7
6.4.
Post-treatment Assessments
6.4.1.
Early Termination Visit Assessments
6.4.1.1.
Early Termination Visit Assessments - Treatment Group 1 and 2
6.4.1.1.1.
Early Termination visit after Day 1 and prior to Day 15
If a participant discontinues oral GS-6207 or decides not to initiate SC GS-6207 at Day 15, an 
Early Termination Visit should be performed within 72 hours of the decision to discontinue the 
study drug. Participants will be asked to continue to attend study visits until completion of the 
Day 15 visit. Participants will be required to complete 90-Day Follow up Visit. Refer to 
Section 6.4.2
6.4.1.1.2.
Early Termination visit after Day 15 and prior to Week 80
If a participant decides to discontinue GS-6207 (SC and oral) prior to Week 80, an Early 
Termination Visit should be performed within 72 hours of decision to discontinue study drug.
The participant will be asked to continue attending the scheduled study visits through the Week 
80 visit. 

If the participant decides to discontinue SC GS-6207 but continues to attend study visits 
through Week 80, no follow up visits are required. 

If the participant decides to discontinue SC GS-6207 and does not continue to attend study 
visits through Week 80, the 30-Day, 90-Day and 180-Day Follow Up Visits are required. 
Refer to Section 6.4.2. The 180-Day follow up may be conducted via a phone call per the 
investigator’s discretion.

If a participant discontinues oral GS-6207 during the Oral Bridging Period and does not 
continue to attend study visits through their next SC dosing visit, the participant will be 
required to complete the 90-Day Follow up-Visit (see Section 6.4.2).


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6.4.1.1.3.
Early Termination visit after Week 80
If a participant continues the study after completing the Week 80 visit, but discontinues GS-6207 
(SC and oral) prior to study completion, an Early Termination Visit should be performed within 
72 hours of decision to discontinue study drug. 

If the participant decides to discontinue SC GS-6207 but continues to attend the scheduled 
study visits through their next SC dosing visit, they will complete all assessments except SC 
dosing at the last visit and complete the study. No further follow up visits are required.

If the participant decides to discontinue SC GS-6207 and does not continue to attend the 
scheduled study visits through their next SC dosing visit, the 30-Day, 90-Day and 180-Day 
Follow Up Visits are required. Refer to Section 6.4.2. The 180-Day Follow Up may be 
conducted via a phone call per the investigator’s discretion.

If a participant discontinues oral GS-6207 during the Oral Bridging Period and does not 
continue to attend study visits through their next SC dosing visit, the participant will be 
required to complete the 90-Day Follow up Visit (see Section 6.4.2).
6.4.1.2.
Early Termination Visit Assessments - Treatment Group 3
If the participant discontinues their study regimen prior to Week 64 visit, the participant will be 
asked to return to the clinic within 72 hours of stopping study treatment for an Early Termination 
visit. The participant will be asked to continue to attend study visits through Week 80.

If the participant agrees to continue to attend study visits through Week 80, no follow up 
visits are required. 

If the participant does not agree to continue to attend study visits through Week 80, the 
30-Day and 90-Day Follow Up Visits are required. Refer to Section 6.4.2
If a participant discontinues the study drug between Week 64 and Week 80 OR after completing 
the Week 80 visit but prior to study completion, the Early Termination visit should be 
performed. The participant will complete the 30-Day and 90-Day follow-up visits after 
completion of the Early Termination visit.
6.4.1.3.
Early Termination Visit Assessments - Treatment Group 4
If the participant discontinues their study regimen prior to Week 64 visit, the participant will be 
asked to return to the clinic within 72 hours of stopping study drug for an Early Termination 
visit. The participant will be asked to continue to attend study visits through Week 80.

If the participant agrees to continue to attend study visits through Week 80, no follow up 
visits are required. 


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
If the participant does not agree to continue to attend study visits through Week 80, the 
30-Day Follow Up Visit is required. Refer to Section 6.4.2
If a participant discontinues the study drug between Week 64 and Week 80, the Early 
Termination visit should be performed. The participant will complete the 30-Day Follow-Up 
visit after completion of the Early Termination visit.
If there are any abnormal laboratory results with a possible or probable causal relationship with 
the study drug, every attempt should be made to keep the participant in the study and repeat 
those laboratory tests weekly (or as often as deemed prudent by the investigator) until the 
abnormality is resolved, returns to baseline, or is otherwise explained. If this is not possible or 
acceptable to the participant or investigator, the participant may be withdrawn from the study.
If there are any AEs, every attempt should be made to keep the participant in the study and 
should be followed up until the AE is resolved or stable. Gilead may request that certain AEs be 
followed beyond the protocol-defined follow-up period. If this is not possible or acceptable to 
the participant or investigator, the participant may be withdrawn from the study.
The following evaluations should be performed at the Early Termination visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Obtain blood and urine samples as noted in Section 6.5

Counsel participant regarding the importance of continuing a complete ARV therapy in 
accordance to standard of care, and refer participant to an appropriate HIV treatment facility
6.4.2.
30-Day, 90-Day and 180-Day Follow-up Visits
The assessments below will be completed for participants who are required to complete the 
30-Day, 90-Day and 180-Day Follow-up visits as noted in Section 6.4.1. 
Follow-up visits will be scheduled based on the date of the Early Termination Visit. For the 
purpose of scheduling the follow-up visits, a ±6 day window may be used.
The following evaluations are to be completed at the follow-up visits:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination


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
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Obtain blood and urine samples as noted in Section 6.5
At the 30-Day, 90-Day or 180-Day Follow-Up Visit, as applicable, if there are any abnormal 
laboratory results indicating that there is a possible or probable causal relationship with the study 
drug(s), every attempt should be made to repeat those laboratory tests weekly (or as often as 
deemed prudent by the investigator) until the abnormality is resolved, returns to baseline, or is 
otherwise explained. If this is not possible or acceptable to the participant or investigator, the 
participant may be withdrawn from the study.
If there are any AEs, every attempt should be made to keep the participant in the study and 
should be followed up until resolution or until the AE is stable, if possible. Gilead may request 
that certain AEs be followed beyond the protocol-defined follow-up period.
6.5.
Clinical Laboratory Assessments 
Blood and urine samples will be collected throughout the study as outlined below, within 
Section 6, and in Appendix 2 Study Procedures Table.
6.5.1.
Blood Samples
Blood sample collection for the following laboratory analyses will be performed at every visit, 
unless specified:

Serum pregnancy test for all women (Screening only)

Serum follicle-stimulating hormone (FSH) test (FSH test is required for women who are 
< 54 years old and have stopped menstruating for ≥ 12 months but do not have 
documentation of ovarian hormonal failure) (Screening only)

Chemistry profile: alkaline phosphatase, AST, ALT, gamma-glutamyltransferase (GGT), 
total bilirubin, direct and indirect bilirubin, total protein, albumin, lactate dehydrogenase 
(LDH), creatine phosphokinase (CPK), bicarbonate, blood urea nitrogen (BUN), calcium, 
chloride, creatinine, glucose, lipase, magnesium, phosphorus, potassium, sodium, uric acid 

Nonfasting lipid panel: total cholesterol, high-density lipoprotein (HDL), direct low-density 
lipoprotein (LDL), and triglycerides 

Estimated GFR 
 according to:
Cockcroft-Gault formula for Creatinine clearance for participants  18 years of age
Male:
(140 – age in years)  (weight in kg)  CLcr (mL/min)
72  (serum creatinine in mg/dL)
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Female: 
(140 - age in years) x (weight in kg) x 0.85 = CLcr (mL/min) 
72 x (semm creatinine in mg/dL) 
Final 
Amendment4 
rofile: complete blood count (CBC) with differential and platelet count 
• 
CD4+ cell count 
• 
Plasma HIV-1 RNA 
• 
HIV-1 genotype and phenotype at Screening visit and any subsequent visit with virologic 
failure (described in Section 6.7) 
• 
HBV serologies (HBV surface antigen, HBV core antibody, HBV surface antibody) 
(Screening only) 
• 
HCV antibody serology (Screening only) 
I 
• 
Plasma stor~itional safety and virology testing (HIV-1 genotype and 
phenotype)-
6.5.2. 
Pharmacokinetic Assessments: 
For Treatment Groups 1 and 2: 
Plasma PK sampling will occur relative to dosing of GS-6207 at the following time points for all 
paiiicipants: 
• 
Days 1, 2, and 8: 
-
Predose (within 30 minutes of dosing) 
-
A single timed PK sample between 1 and 6 hours postdose 
I 
• 
At Day 15 and at all visits with GS-6207 SC injections, including when GS-6207 SC 
injection is resumed after the Oral Bridging Visits, if applicable: A single predose PK sample 
will be collected 
• 
Staiiing at Week 4 visit, at all visits without GS-6207 SC injections, including the Oral 
Bridging visits, if applicable: A single anytime PK sample will be collected 
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I 
I 
I 
For Treatment Group 3: 
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• 
Staiiing at Day 1 visit, a single anytime PK sample will be collected at all study visits 
I 
For Treatment Group 4: 
• 
Staiiing at Day 1 visit, a single anytime PK sample will be collected at all study visits. 
6.5.3. 
Blood Storage Samples 
Any residual blood and mine samples collected at all visits 
Tennination Visits will be frozen and stored. 
uman genetic 
testing will be perfo1med using these samples without consent of study paiiicipants. 
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Gilead Sciences, Inc.
Amendment 4
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6.5.4.
Urine Samples
Urine samples will be collected for the following laboratory analyses at every study visit, unless 
otherwise specified:

Urinalysis and urine chemistry: including color & clarity, specific gravity, pH, glucose, 
ketones, bilirubin, urobilinogen, blood, nitrite, leukocyte esterase and microscopic 
(if microscopic elements are seen), urine protein, albumin, creatinine, phosphate, calcium, 
magnesium, and uric acid

Urine pregnancy test for women of childbearing potential (except at Screening 
 
visits)
If the test is positive, confirmatory serum test should be performed and study drug dosing 
should be delayed until results obtained
For participants in Treatment Groups 1 and 2, a confirmatory negative urine pregnancy 
test prior to subcutaneous GS-6207 administration must be completed.

Urine storage for possible additional clinical testing (except at Screening, 
 and 30-Day, 
90-Day, and 180-Day Follow-up visits, as applicable).
6.6.
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 
participant 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 participant’s 
best interest

Lack of efficacy

Participant request to discontinue for any reason

Participant noncompliance

Pregnancy during the study; refer to Appendix 4.

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board (IRB) or independent ethics committee (IEC)
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Paiiicipants in Treatment Groups 1 and 2 will need to have HIV-1 RNA results 
I 
< 50 copies/mL at Weeks 16 and 22 to initiate ti·eatment with a two-agent regimen at 
Week 28; those with values ~ 50 copies/mL will discontinue the study dmg at or prior to 
Week 28. If data are missing at either Weeks 16 or 22 the paiiicipants discontinuation should 
be discussed with the medical monitor. 
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6.8. 
End of Study 
The end of the study will be the last paiiicipant's last observation (or visit). 
6.9. 
Post Study Care 
Final 
Amendment4 
After the paiiicipant has completed/tenninated their participation in the study, long-te1m cai·e of 
the paiiicipant will remain the responsibility of their primaiy treating physician. 
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events and Serious Adverse Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study participant administered an 
investigational 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 an investigational product, whether or not considered related to the 
investigational product. AEs may also include pre- or post-treatment complications that occur as 
a result of protocol-specified procedures or special situations (Section 7.7). 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 AE and must be reported.

Preexisting diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (Section 7.7.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be preexisting and should be documented as medical history.
7.1.2.
Serious Adverse Events
An SAE is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the participant was at risk of death at the time of the event; it does not refer to 
an event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity


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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to study 
drug using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the study drug. For SAEs, an 
alternative causality must be provided (eg, preexisting condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study drug.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures, (eg, venipuncture)
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale.
The DAIDS scale is available at the following location: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf


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7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events 
Requirements for Collection Prior to Study Drug Initiation
After informed consent, but prior to initiation of study medication, the following types of events 
must be reported on the applicable electronic case report forms (eCRFs): all SAEs and AEs 
related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, all AEs, regardless of cause or relationship, throughout 
the duration of the study, including the protocol-defined follow-up period, must be reported on 
the eCRFs as instructed.
All AEs should be followed up until resolution or until the AE is stable, if possible. Gilead may 
request that certain AEs be followed beyond the protocol-defined follow-up period.
7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occur after the participant first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-defined follow-up period, must be reported on the applicable 
eCRFs and submitted to Gilead Global Patient Safety (GLPS) (formerly known as 
Pharmacovigilance an Epidemiology (PVE)) as instructed below in this section. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period. 
However, if the investigator learns of any SAEs that occur after the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study drug(s), the 
investigator should promptly document and report the event to Gilead GLPS.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guidelines.
7.3.2.1.
Electronic Serious Adverse Event (eSAE) Reporting Process 

Site personnel record all SAE data on the applicable eCRFs and from there transmit the SAE 
information to Gilead GLPS within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study start), record the 
SAE on the paper serious adverse event reporting form and submit within 24 hours to:


GS-6207 
Protocol GS-US-200-4334 
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Gilead GLPS: 
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or 
Final 
Amendment 4 
• 
As soon as it is possible to do so, any SAE repo1ied via paper must be transcribed on the 
applicable eCRFs according to instructions and within the timelines outlined in the eCRF 
completion guidelines. 
• 
If an SAE has been repo1ied via a paper fonn because the eCRF database has been locked, 
no fmther action is necessaiy. 
• 
For fatal or life-threatening events, copies of hospital case repo1is, autopsy repo1is, and other 
doclllllents are also to be submitted by email or fax when requested and applicable. 
Transmission of such doclllllents should occm without personal paiiicipant identification, 
maintaining the tr·aceability of a document to the paiiicipant identifiers. 
• 
Additional infonnation may be requested to ensm e the timely completion of accm ate safety 
repo1is. 
• 
Any medications necessaiy for u-eatment of the SAE must be recorded onto the concomitant 
medication section of the paiiicipant's eCRF and the event description of the SAE f01m. 
7.4. 
Gilead Reporting Requirements 
Depending on relevant local legislation or regulations, including the applicable US-FDA Code of 
Federal Regulations, the Em opean Union (EU) Clinical Trials Directive (2001/20/EC) and 
relevant updates, and other country-specific legislation or regulations, Gilead may be required to 
expedite to worldwide regulato1y agencies repo1is of SAEs, which may be in the f01m of 
line-listings, serious adverse diug 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 IB or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR repo1is associated 
with any study di11g. 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
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to study drug interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, ECG, x-rays, vital signs) that are associated with 
signs and/or symptoms must be recorded as an AE or SAE if they meet the definition of an AE 
or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory abnormality is part of a 
syndrome, record the syndrome or diagnosis (eg, anemia), not the laboratory result 
(ie, decreased hemoglobin).
Severity should be recorded and graded according to the DAIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For AEs associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
7.6.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 and as outlined below. 
Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results and before investigational medicinal product 
discontinuation, unless such a delay is not consistent with good medical practice. If repeat testing 
is not possible within 3 calendar days of receipt of results, it may be completed within 
14 calendar days of receipt of results per the Investigator’s discretion.
The Gilead medical monitor should be consulted prior to study drug discontinuation when 
medically feasible. 
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug(s) at the discretion of the investigator.
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event
For a Grade 3 clinically significant laboratory abnormality or clinical event, study drug(s) may 
be continued if the event is considered to be unrelated to study drug(s).
For a Grade 3 clinically significant laboratory abnormality or clinical event confirmed by repeat 
testing, that is considered to be related to study drug(s), then study drug(s) should be withheld 
until the toxicity returns to ≤ Grade 2.


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If a clinically significant laboratory abnormality or clinical event recurs to ≥ Grade 3 following 
re-challenge with study drug(s) and is considered to be related to study drug(s), then study 
drug(s) should be permanently discontinued, and the participant managed according to local 
practice, including switching to an effective alternative ARV regimen with consideration of the 
long duration of exposure of GS-6207 
. Recurrence of 
laboratory abnormalities considered unrelated to study drug(s) may not require permanent 
discontinuation but requires discussion with the Gilead medical monitor.
7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event
For a Grade 4 clinically significant laboratory abnormality or clinical event confirmed by repeat 
testing, that is considered to be related to study drug(s), then study drug(s) should be 
permanently discontinued, and the participant managed according to local practice, including 
switching to an effective alternative ARV regimen with consideration of the long duration of 
exposure of GS-6207 
. The participant should be followed as 
clinically indicated until the laboratory abnormality returns to baseline or is otherwise explained, 
whichever occurs first. A clinically significant Grade 4 laboratory abnormality that is not 
confirmed by repeat testing should be managed according to the algorithm for the new toxicity 
grade.
Study drug(s) may be continued without dose interruption for a clinically non-significant 
Grade 4 laboratory abnormality (eg, Grade 4 creatine kinase elevation after strenuous exercise or 
triglyceride elevation that is nonfasting or that can be medically managed) or a clinical event 
considered unrelated to study drug(s).
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the Gilead medical monitor, and the appropriate course of action will be discussed and decided.
Whether or not considered treatment-related, all participants experiencing AEs must be 
monitored periodically until symptoms subside, any abnormal laboratory values have resolved or 
returned to baseline levels or they are considered irreversible, or until there is a satisfactory 
explanation for the changes observed.
Any questions regarding toxicity management should be directed to the Gilead medical monitor.
7.6.4.
Management of Adverse Events of Injection Site Reactions of Grade 3 or 
Higher, or Persisting for More Than 26 Weeks
In clinical studies of SC GS-6207, Grade 3 or higher AEs of injections site reactions (ISRs) were 
uncommon. Some participants experienced AEs of injection site nodule and induration, which 
decreased in size over 6 months or longer. For AEs of ISRs related to SC GS-6207 administered 
from a borosilicate vial that are Grade 3 or higher or persisting for more than 26 weeks, 
particularly nodule and/or induration, the investigator must contact the medical monitor and 
obtain consultation with an independent dermatologist to evaluate the ISRs. 
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If clinically indicated as determined by the independent dermatologist, a biopsy of the SC 
injection site may be performed. The histopathology should be reviewed by an independent 
dermatopathologist; if a dermatopathologist is not locally available, the histopathology may be 
reviewed by an otherwise medically qualified person. 
Photographic documentation of the ISRs that meets the criteria above is recommended, if 
possible, but is not mandatory. If obtained, the documentation may be shared by the investigator 
with the independent dermatologist or dermatopathologist and may be requested by the sponsor.
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports (SSRs) include all reports of medication error, abuse, misuse, overdose, 
occupational exposure with AE, AE in an infant following exposure via breastfeeding, product 
complaints with AE, and pregnancy regardless of an associated AE.
Medication error is any unintentional error in the prescribing, dispensing, preparation for 
administration or administration of an investigational product while the medication is in the 
control of a health care professional, patient, or consumer. Medication errors may be classified as 
a medication error without an AE, which includes situations of missed dose; medication error 
with an AE; intercepted medication error; or potential medication error.
Abuse is defined as persistent or sporadic intentional excessive use of an investigational product 
by a participant.
Misuse is defined as any intentional and inappropriate use of an investigational 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 an 
investigational 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 
participant in question). In cases of a discrepancy in drug accountability, overdose will be 
established only when it is clear that the participant has taken the excess dose(s). Overdose 
cannot be established when the participant cannot account for the discrepancy except in cases in 
which the investigator has reason to suspect that the participant has taken the additional dose(s).
Occupational exposure is defined as exposure to an investigational product as a result of one’s 
professional or non-professional occupation.
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the investigational product. 


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7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study participants and female partners of 
male study participants that are identified after initiation of study drug and throughout the study, 
including the protocol-defined follow-up period, to the Gilead GLPS using the pregnancy report 
form within 24 hours of becoming aware of the pregnancy. Refer to Appendix 4 for further 
information regarding protocol-defined follow-up periods.
If the investigator learns of any pregnancy or pregnancy outcomes that occur after the 
protocol-defined follow-up period has concluded but within 700 days following the last dose of 
SC GS-6207 (Treatment Groups 1 and 2), or within 60 days following the last oral dose of 
GS-6207, the investigator should promptly document and report the event to Gilead GLPS. 
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to the Gilead GLPS.
The participant should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to the Gilead GLPS 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 GLPS (Treatment Groups 1-4). If the pregnancy occurs 
after the study has been completed, but within 700 days following the last dose of SC GS-6207, 
the pregnancy/outcome should be reported directly to Gilead GLPS (Treatment Groups 1-2). 
Gilead GLPS contact information is as follows: email: 
 and fax: 
Pregnancies of female partners of male study participants exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to the Gilead GLPS using 
the pregnancy and pregnancy outcome forms within 24 hours. If the end of the pregnancy occurs 
after the study has been completed, the outcome should be reported directly to Gilead GLPS: 
fax number 
 or email 
 
Refer to Appendix 4. for Pregnancy Precautions, Definition for Women of Childbearing 
Potential, and Contraceptive Requirements.
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7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to the Gilead GLPS within 24 hours of the investigator becoming aware of the 
situation. These reports must consist of situations that involve study drug and/or Gilead 
concomitant medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications do not need to be reported on 
the special situations report form; however, special situations that result in AEs due to a 
non-Gilead concomitant medication, must be reported as an AE. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3 and the eCRF completion guidelines for instructions on special situation 
reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
7.8.
Safety Monitoring Committee
Gilead teams periodically review accumulating safety data across completed and ongoing studies 
within the GS-6207 development program to detect unexpected suspected adverse reactions and 
clinically important increased rates of AEs, laboratory abnormalities, and previously recognized 
adverse reactions. If, during the periodic review of safety data from clinical studies, a significant 
numerical imbalance is observed for an AE across treatment groups based on predefined 
reporting thresholds, a safety monitoring committee will request to review unblinded safety data 
and, in collaboration with other safety committees (in line with Gilead’s signal management 
process and unblinding process), determine if any actions are necessary to protect participants 
involved in the GS-6207 development program. If appropriate and available, the safety 
monitoring committee would be a data monitoring committee (DMC). If an appropriate DMC is 
not available, an internal Safety Assessment Committee (SAC), comprised of Gilead employees 
not involved in the conduct of the study, reviews the data. The membership, responsibilities, 
conduct, specific activities, and meeting schedule of the unblinded internal SAC will be 
described in a charter. The blind will be maintained for persons responsible for the ongoing 
conduct of the study and those responsible for data analysis and interpretation of results at the 
conclusion of the study. 


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STATISTICAL CONSIDERATIONS 
8.1. 
Analysis Objectives and Endpoints 
8.1.1. 
Analysis Objectives 
The prirmuy objective of this study is: 
Final 
Amendment4 
• 
To evaluate the efficacy of regimens in PL WH as determined by the propo1i ion of 
paii icipants with HIV-1 RNA < 50 copies/mL at Week 54 
The secondaiy objectives of this study ai·e: 
• 
To evaluate the efficacy of regimens in PL WH as determined by the propo1i ion of 
paii icipants with HIV-1 RNA < 50 copies/mL at Weeks 28, 38, and 80 
• 
To evaluate the change from baseline in log10 HIV-1 RNA and in CD4+ cell count at 
Weeks 28, 38, 54, and 80 
• 
To evaluate the safety and tolerability ofregimens through 28, 38, 54, and 80 weeks of 
treatment 
• 
To evaluate the PK of GS-6207, BIC, and T AF 
I 
I 
I 
8.1.2. 
Primary Endpoint 
The prima1y endpoint is the propo1i ion of paii icipants with HIV-1 RNA < 50 copies/mL at 
Week 54 as detennined by the US-FDA-defined snapshot algorithm. 
8.1.3. 
Secondary Endpoint 
The secondaiy endpoints ai·e: 
• 
The propo1iion of pa1iicipants with HIV-1 RNA < 50 copies/mL at Weeks 28, 38, and 80 as 
detennined by the US-FDA-defined snapshot algorithm 
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
The change from baseline in log10 HIV-1 RNA and in CD4+ cell count at Weeks 28, 38, 54, 
and 80
8.2.
Planned Analyses
8.2.1.
Interim Analysis 
Prior to the final analysis, interim analyses may be conducted for DMC analysis, for data to be 
submitted to regulatory agencies to seek guidance for the overall clinical development program, 
and to support regulatory filings, etc.
8.2.1.1.
Planned Internal Analysis 
Prior to the primary analysis (defined in Section 8.2.2), there will be two planned internal 
analyses. One analysis will be performed after all participants have completed their Week 28 
visit or prematurely discontinued study drug. The other analysis will be conducted after all 
participants have completed their Week 38 visit or prematurely discontinued study drug. Both 
analyses will be used to support the GS-6207 regulatory filing and the planning of other studies.
After the primary analysis, the Week 80 analysis will be conducted after all participants have 
completed their Week 80 visit or prematurely discontinued study drug.
8.2.1.2.
DMC Analysis
There will be one planned DMC analysis conducted after all participants have completed their 
Week 16 visit. No formal stopping rules will be used by the DMC for safety outcomes. Rather, a 
clinical assessment will be made to determine if the nature, frequency, and severity of AEs 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants. No alpha penalty will be applied for the primary analysis of the primary efficacy 
endpoint given that the study is not adequately powered for a formal efficacy evaluation. Data 
from this analysis may be used to support the GS-6207 regulatory filing and the planning of 
other studies.
8.2.2.
Primary Analysis
The primary analysis will be conducted after all participants have completed the Week 54 visit or 
have prematurely discontinued study drug, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized for the analysis. This 
analysis of the primary endpoint will serve as the final analysis for this endpoint.
8.2.3.
Final Analysis
The final analysis will be performed after all participants have completed the study, outstanding 
data queries have been resolved or adjudicated as unresolvable, and the data have been cleaned 
and finalized.


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8.3.
Analysis Conventions
8.3.1.
Analysis Sets
8.3.1.1.
Efficacy
The primary analysis set for efficacy analyses is defined as Full Analysis Set (FAS), which 
includes all participants who are randomized and receive any dose of study drug. Participants 
will be grouped according to the treatment to which they are randomized.
8.3.1.2.
Safety
The primary analysis set for safety analyses is defined as Safety Analysis Set, which includes all 
participants who are randomized and receive any dose of study drug. Participants who receive 
treatment other than that intended will be analyzed according to treatment received. All data 
collected during treatment will be included in the safety summaries.
8.3.1.3.
Pharmacokinetics
The primary analysis set for PK analyses is defined for each analyte, which includes all 
participants who are randomized, receive any dose of study drug, and have at least 1 non-missing 
postbaseline concentration value for the analyte of interest.
8.3.2.
Data Handling Conventions
Logarithm (base 10) transformation will be applied to HIV-1 RNA levels for efficacy analysis. 
Natural logarithm transformation for all PK parameters of GS-6207, TAF, and BIC (and any 
metabolites, as applicable) (eg, Cmax, Ct, and AUC0-t, as applicable) will be applied for 
pharmacokinetic analysis.
For summary statistics, PK concentration values below the limit of quantitation (BLQ) will be 
treated as zero at predose and one-half of the LLOQ for postdose time points.
Laboratory data that are continuous in nature but are less than the LLOQ or above the upper limit 
of quantitation will be imputed to the value of the lower or upper limit minus or plus 1 
significant digit, respectively (eg, if the result of a continuous laboratory test is < 20, a value of 
19 will be assigned; if the result of a continuous laboratory test is < 20.0, a value of 19.9 will be 
assigned).
8.4.
Demographic and Baseline Characteristics Analysis
Demographic and baseline measurements will be summarized using standard descriptive 
methods.
Demographic summaries will include age, race, ethnicity, sex, sexual orientation, gender 
identity, and randomization stratification group.


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Baseline data will include a summary of body weight, height, and BMI.
For categorical demographic and baseline characteristics, the Cochran-Mantel-Haenszel (CMH) 
test will be used to compare across treatment groups. For continuous demographic and baseline 
characteristics, the 2-sided Kruskal-Wallis test will be used to compare across treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary efficacy endpoint is the proportion of participants with HIV-1 RNA  50 copies/mL 
at Week 54 as determined by the US-FDA-defined snapshot algorithm. The primary analysis of 
the efficacy endpoint will be based on the FAS.
The point estimates and 95% CI for the difference in the response rates between each of the 
GS-6027-containing regimen groups (Treatment Groups 1 to 3) and the B/F/TAF group 
(Treatment Group 4) will be constructed using normal approximation method, stratified by 
baseline HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL). The nominal 
p-values will be provided for above mentioned treatment group comparisons using the 2-sided 
CMH test stratified by the baseline HIV-1 RNA level.
8.5.2.
Secondary Analyses
The proportion of participants with HIV-1 RNA < 50 copies/mL at Weeks 28, 38, and 80, 
respectively, will be analyzed using the same methods as for the primary efficacy endpoint. 
The changes from baseline in log10 HIV-1 RNA and CD4+ cell count will be summarized using 
descriptive statistics. The differences in changes from baseline in log10 HIV-1 RNA and 
CD4+ cell count between treatment groups and the associated 95% CIs will be constructed using 
analysis of variance (ANOVA) models adjusting for the baseline HIV-1 RNA level.
8.6.
Safety Analysis
For Treatment Groups 1 and 2, all safety data collected on or after the first dose date will be 
included. For participants who discontinue from the oral GS-6207, only data collected up to 
60 days (approximately 5 times the GS-6207 oral dose half-life) after the last dose of the oral 
GS-6207 will be included. For Treatment Groups 3 and 4, all safety data collected on or after the 
first dose date and up to 60 days and 30 days, respectively, after the last dose date will be 
included. All data will be summarized by treatment according to the study drug received. All 
collected data will be included in data listings.
8.6.1.
Extent of Exposure
A participant’s extent of exposure to study drug data will be generated from the study drug 
administration data. Exposure data will be summarized.


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8.6.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), 
High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to 
the clinical database.
Events will be summarized on the basis of the date of onset for the event. For Treatment Groups 
1 and 2, a treatment-emergent adverse event (TEAE) will be defined as any AE that begins on or 
after the date of first dose of study drug. For participants in Treatment Groups 1 and 2 who 
discontinue from the oral GS-6207, only AEs collected up to 60 days (approximately 5 times the 
GS-6207 oral dose half-life) after the last dose of the oral GS-6207 will be considered treatment 
emergent. For Treatment Groups 3 and 4, a TEAE will be defined as any adverse event that 
begins on or after the date of first dose of study drug and up to 60 days and 30 days, respectively, 
after the last dose date; or any AE leading to study drug discontinuation.
Summaries (number and percentage of participants) of TEAEs (by SOC and PT) will be 
provided by treatment group. Additional summaries will include summaries for AEs by grade, 
investigator’s assessment of relationship to study drug, and effect on study drug dosing.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Data and change from baseline at all scheduled time points will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme in DAIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
Incidence of treatment-emergent laboratory abnormalities will be summarized by treatment 
group. For Treatment Groups 1 and 2, treatment-emergent laboratory abnormalities are defined 
as values that increase at least 1 toxicity grade from baseline at any time post baseline (and up to 
60 days after the last dose date if participants discontinue from the oral GS-6207). For Treatment 
Groups 3 and 4, treatment-emergent laboratory abnormalities are defined as values that increase 
at least 1 toxicity grade from baseline at any time post baseline up to and including the date of 
last dose of study drug plus 60 days and 30 days, respectively. If baseline data are missing, any 
graded abnormality (ie, at least a Grade 1) will be considered treatment emergent. The post 
baseline maximum toxicity grade will be summarized by laboratory parameter.
8.6.4.
Other Safety Evaluations
Vital sign and safety ECG data will be summarized and/or listed as appropriate.
8.7.
Adjustments for Multiplicity
Not applicable.


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8.8.
Pharmacokinetic Analysis 
Plasma concentrations of GS-6207, TAF, and BIC (and metabolites, as applicable) will be 
summarized by nominal sampling time and treatment using descriptive statistics. 
Pharmacokinetic parameters will be listed and summarized using descriptive statistics 
(eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard 
deviation, median, minimum, and maximum) by treatment group. The concentrations of the 
study drug in plasma over time will be plotted in semi-logarithmic and linear formats as mean 
 standard deviation and median (Q1, Q3), respectively.
8.9.
Biomarker Analysis
Not applicable.
8.10.
Sample Size
A sample size of 50 participants in Treatment Groups 1 to 3, respectively, was chosen to estimate 
the response rate of HIV-1 RNA  50 copies/mL at Week 54. A total sample size of 
75 participants for each pair of comparisons (ie, between each of the GS-6207-containing 
regimen groups [Treatment Groups 1 to 3, n = 50] and the B/F/TAF [Treatment group 4, n = 25]) 
will provide 39% power to evaluate non-inferiority with respect to the response rate of HIV-1 
RNA  50 copies/mL at Week 54. In this sample size and power calculation, it is assumed a 
response rate is 90.9% (based on pooled data from studies GS-US-380-1489 and 
GS-US-380-1490) for each treatment group and a non-inferiority margin is 0.12.
8.11.
Data Monitoring Committee 
An external multidisciplinary DMC will review the progress of the study and perform interim 
reviews of efficacy and safety data, and provide recommendation to Gilead whether the nature, 
frequency, and severity of AEs 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 DMC’s specific activities will be defined by a mutually agreed charter, which will define the 
DMC’s membership, conduct, and meeting schedule.
While the DMC 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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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with International Council 
for Harmonisation (ICH) E6(R2) addendum to its guideline for GCP and applicable laws and 
regulations.
9.1.2.
Financial Disclosure
The investigator and subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with Gilead, or proprietary interests in the investigational drug 
during the course of a clinical study. This documentation must be provided prior to the 
investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last participant completes the protocol-defined activities.
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval
The investigator (or Gilead as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the 
participant (such as advertisements, participant information sheets, or descriptions of the study 
used to obtain informed consent) to an IRB/IEC. The investigator will not begin any study 
participant activities until approval from the IRB/IEC has been documented and provided as a 
letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the participant after initial IRB/IEC approval, with the exception of those necessary 
to reduce immediate risk to study participants.
9.1.4.
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 before undertaking any study-related procedures. The investigator 
must use the most current IRB- or IEC-approved consent form for documenting written informed 
consent. Each informed consent (or assent as applicable) will be appropriately signed and dated 
by the participant or the participant’s legally authorized representative and the person conducting 
the consent discussion, and also by an impartial witness if required by IRB or IEC or local 
requirements. 


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Confidentiality 
Final 
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The investigator must assure that paiiicipants' anonymity will be sti·ictly maintained and that 
their identities ai·e protected from unauthorized paiiies. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as year of bi1ih) will be recorded on any fo1m 
or biological sample submitted to Gilead, IRB, or laborato1y. Laborato1y specimens must be 
labeled in such a way as to protect paiiicipant identity while allowing the results to be recorded 
to the proper pa1iicipant. Refer to specific laborato1y instructions. NOTE: The investigator must 
keep a screening log with details for all paiiicipants screened and emolled in the study, in 
accordance with the site procedures and regulations. Paiiicipant data will be processed in 
accordance with all applicable regulations. 
The investigator agrees that all info1mation received from Gilead, including but not limited to the 
IB, this protocol, CRF/eCRF, the study diug, and any other study infonnation, remain the sole 
and exclusive prope1iy of Gilead during the conduct of the study and thereafter. This info1mation 
is not to be disclosed to any third paiiy ( 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 fmiher agrees to take all reasonable precautions to prevent the disclosure by any 
employee or agent of the study site to any third pa1iy or othe1wise into the public domain. 
9.1.6. 
Study Files and Retention of Records 
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following 2 categories: (1) investigator's study file, and 
(2) paiiicipant clinical source documents. 
The investigator's study file will contain the protocol/amendments, paper or electi·onic 
completed paiiicipant CRFs, IRB and governmental approval with con espondence, info1med 
consent, dmg records, staff cuniculum vitae and authorization fo1ms, and other appropriate 
documents and con espondence. 
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The required source data should include sequential notes containing at least the following 
information for each participant:

Participant identification;

Documentation that participant meets eligibility criteria, ie, medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented participant is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol-specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of study drug, including dates of dispensing and 
return;

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, US, Europe, or Japan) and until there are no pending or planned marketing 
applications in an ICH region; or, if no application is filed or if the application is not approved 
for such indication, until 2 years after the investigation is discontinued and regulatory authorities 
have been notified. Investigators may be required to retain documents longer if specified by 
regulatory requirements, by local regulations, or by an agreement with Gilead. The investigator 
must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
participant, appropriate copies should be made for storage away from the site.


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9.1.7.
Case Report Forms
For each participant consented, an eCRF casebook will be completed by an authorized study 
staff member whose training for this function is completed in the electronic data capture 
(EDC) system. The eCRF casebook will only capture the data required per the protocol schedule 
of events and procedures. The inclusion/exclusion criteria and enrollment eCRFs should be 
completed only after all data related to eligibility have been received. Data entry should be 
performed in accordance with the CRF completion guidelines provided by the sponsor. 
Subsequent to data entry, a study monitor will perform source data verification within the EDC 
system. System-generated or manual queries will be issued in the EDC system as data 
discrepancies are identified by the monitor or Gilead staff, who routinely review the data for 
completeness, correctness, and consistency. The site investigator or site coordinator or other 
designee is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry and providing the reason 
for the update (eg, data entry error). Original entries as well as any changes to data fields will be 
stored in the audit trail of the system. At a minimum, prior to any interim time points or database 
lock (as instructed by Gilead), the investigator will use his/her log in credentials to confirm that 
the forms have been reviewed, and that the entries accurately reflect the information in the 
source documents. At the conclusion of the study, Gilead will provide the site investigator 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 9.1.6.
9.1.8.
Investigator Inspections
The investigator will make available all source documents and other records for this study to 
Gilead’s appointed study monitors, to IRBs/IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study participants, 
may be made only by Gilead. The investigator must submit all protocol modifications to the IRB 
in accordance with local requirements and receive documented IRB approval before 
modifications can be implemented.


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9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared. Gilead will ensure that the report meets the 
standards set out in the ICH Guideline for Structure and Content of CSRs (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 9.1.5).
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 (eg, attendance at investigator meetings). If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
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 participant records 
needed to verify the entries in 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.


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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 Gilead 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 participants, 
appropriate regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the 
investigator will assure that adequate consideration is given to the protection of the participants’ 
interests.


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10.
REFERENCES
BIKTARVY, Gilead Sciences Inc. BIKTARVY® (bictegravir, emtricitabine, and tenofovir 
alafenamide) Tablets, for Oral Use. U. S. Prescribing Information. Foster City, 
CA. Revised: June.  2019:
Claborn KR, Meier E, Miller MB, Leffingwell TR. A Systematic Review Of Treatment Fatigue 
Among HIV-Infected Patients Prescribed Antiretroviral Therapy. Psychology, 
health & medicine 2015;20 (3):1-11.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 
January 10, 2011. http://AIDSinfo.nih.gov. Accessed July 25, 2011.
Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents. Developed by the HHS Panel 
on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of 
the Office of AIDS Research Advisory Council (OARAC). Revised 12 February 
2013. Available at: http://aidsinfo.nih.gov/guidelines. Accessed: 2013 February 
12.  2013.
DESCOVY®, Gilead Sciences Inc. DESCOVY® (emtricitabine and tenofovir alafenamide) 
tablets, for oral use. U. S. Prescribing Information. Foster City, CA. Revised: 
September.  2017:
European AIDS Clinical Society (EACS). Guidelines Version 9.1 English.  2018:
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of 
Antiretroviral Agents in HIV-1 Infected Adults and Adolescents.  Developed by 
the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents - A 
Working Group of the Office of AIDS Research Advisory Council (OARAC). 
Downloaded from 
https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf on 
2/03/2016. Last Updated 28 January.  2016.
Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, et al. Antiretroviral 
Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 
Recommendations of the International Antiviral Society-USA Panel. JAMA 
2018;320 (4):379-96.
UNAIDS. 2017 Global HIV Statistics. Fact Sheet - July.  2018.
VEMLIDY®, Gilead Sciences Inc. VEMLIDY® (tenofovir alafenamide) Tablets, for Oral Use. 
U. S. Prescribing Information. Foster City, CA. Revised: February.  2019:


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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.
Pregnancy Precautions, Definition for Women of Childbearing Potential, and 
Contraceptive Requirements
Appendix 5.
Pandemic Risk Assessment and Mitigation Plan


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Appendix 1.
Investigator Signature Page
GILEAD SCIENCES, INC.
333 LAKESIDE DRIVE
FOSTER CITY, CA 94404
STUDY ACKNOWLEDGMENT
A Phase 2 Randomized, Open Label, Active Controlled Study Evaluating the Safety and 
Efficacy of Long-acting Capsid Inhibitor GS-6207 in Combination with Other Antiretroviral 
Agents in People Living with HIV
GS-US-200-4334, Amendment 4 04 February 2022
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval.
[See appended electronic signature]
Name (Printed)
Executive Director, Clinical Research
Signature
[See appended electronic signature]
Date
INVESTIGATOR STATEMENT
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated.
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I 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


Prot GS-US-200-4334 amd-4
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
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GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 119
04 February 2022
Appendix 2.
Study Procedures Table
Screeninga
Day 
1b
Day 
2
Day 
8
Day 
15
Every 
6 weeks 
from 
Week 4 
to 
Week 2
8 
±2 Days
Week 
38 ±2 
Days
Week 5
4 
±2 Days
Week 6
4 ±2 
Days
Week 8
0 
±2 Days
Post 
Week 8
0 Visitsc 
±6 Days
Oral 
Bridging 
Visitsd
30, 90, 
180 Day 
Follow-Upe
Early 
Terminationf
Written 
Informed 
Consent
X
Obtain 
demographic 
information
X
Medical 
History 
X
Complete 
Physical 
Examination
X
X
X
Xg
X
X
X
Symptom-
Directed 
Physical 
Examination
X
X
Xh
X
X
X
X
X
Vital Signsi 
(including wei
ght)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG 
(supine)
X
Height
X
Hematologyj, 
Chemistryk, 
Lipid panell, 
Urinalysis and 
Urine 
Chemistrym, 
CD4+ Cell 
Count
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Storage 
Sample
X
X
X
X
X
X
X
X
X
X
X
CCI


GS-6207 
Protocol GS-US-200-4334 
Final 
Gilead Sciences, Inc. 
Amendment4 
Eve1-y 
6 weeks 
from 
Week4 
to 
Post 
Week2 
Week 
WeekS 
Week6 
Week8 
Week8 
Oral 
30, 90, 
Day 
Day 
8 
38±2 
4 
4±2 
0 
0 Visits' 
Bridging 
180 Day 
Early 
Screening' 
lb 
15 
±2 Days 
Days 
±2 Days 
Days 
±2 Days 
±6Days 
Visits• 
Follow-Up• 
Terminationf 
Serum 
Pregnancy 
X 
X 
Test" 
Se 
FSH0 
X 
Urine 
Pregnancy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Test" 
HBV, HCV 
X 
Testing 
IITV-1 
Genotyping/ 
X 
Phenotyping 
Plasma IITV-1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RNA 
Plasma 
X 
Storage 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Sample 
PK Plasma 
Dispensation' 
CONFIDENTIAL 
Page 120 
04 Febrna1y 2022 


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 121
04 February 2022
Screeninga
Day 
1b
Day 
2
Day 
8
Day 
15
Every 
6 weeks 
from 
Week 4 
to 
Week 2
8 
±2 Days
Week 
38 ±2 
Days
Week 5
4 
±2 Days
Week 6
4 ±2 
Days
Week 8
0 
±2 Days
Post 
Week 8
0 Visitsc 
±6 Days
Oral 
Bridging 
Visitsd
30, 90, 
180 Day 
Follow-Upe
Early 
Terminationf
Subcutaneous 
GS-6207 
Administratio
nu
X
X
X
X
X
F/TAF 
Dispensationv
X
X
X
X
X
X
X
TAF 
Dispensationw
X
X
X
X
X
X
Bictegravir 
Dispensationx
X
X
X
X
X
X
B/F/TAF 
Dispensationy
X
X
X
X
X
Study Drug 
Accountabilit
y
X
X
X
X
X
X
X
X
X
X
QoL 
Administratio
nz
X
X
X
X
X
Injection Site 
Reaction 
Assessment 
Worksheetaa
X
X
X
X
Adverse 
Events/ 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Screening evaluations must be completed within 30 days prior to Day 1
b
Day 1 tests and procedures must be completed prior to administration of the dose of study drug. Participants must begin dosing on the same day as Day 1
c
Assessments will be performed post Week 80 (Week 90, Week 106, Week 116, Week 132, Week 142) and will continue to alternate between every 10 weeks and every 
16 weeks with the visit window ±6 days.
d
Only applicable to participants who require oral weekly bridging if an SC injection of GS-6207 cannot be administered for any reason within the protocol visit window.
e
Participants may be required to return to the clinic for a 30, 90 and 180-Day Follow-Up Visit after Early Termination visit as noted in Section 6.4.1
CCI


GS-6207 
Protocol GS-US-200-4334 
Gilead Sciences, Inc. 
Final 
Amendment4 
f 
Within 72 hom·s of pe1manently discontinuing study. Counsel participant regarding the impo1tance of continuing a complete ARV therapy in accordance to standard of care 
and refer pa1ticipant to an appropriate HIV treatment facility. 
g 
Complete physical exam is only required at Week 28 
h 
Symptom directed physical to be completed at Weeks 4, 10, 16, and 22, as necessa1y 
Vital signs - blood pressm·e, pulse, respiration rate, temperature, and weight 
J 
Hematology: CBC with differential and platelet count 
k 
Chemistries: Alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and indirect bilimbin, total protein, albmnin, LDH, CPK, bicaibonate, BUN, calcium, chloride, 
creatinine, glucose, lipase, magnesium, phosphoms, potassium, sodium, and uric acid. eGFR according to the Cockcroft-Gault formula 
Fasting is not required for the lipid panel 
m 
Urinalysis and Urine Chemistry: including color & clarity, specific gravity, pH, glucose, ketones, bilimbin, m·obilinogen, blood, nitrite, leukocyte esterase and microscopic 
(if microscopic elements aie seen), mine protein, albumin, creatinine, phosphate, calcium, magnesium and uric acid 
n 
Women will have a semm test pe1fo1med at Screening. U1ine pregnancy test will only be done for women of childbea1ing potential. In Treatment Groups 1 and 2, mine 
pregnancy tests should be confomed to be negative prior to subcutaneous GS-6207 administration. If any pregnancy test is positive, study dmg should be innnediately 
intem1pted, and participant should come to the site for serum pregnancy test. 
o 
FSH test is required for women who aie <54 years old and have stopped menstmating for:;:: 12 months but do not have documentation of ovarian honuonal failure. 
p 
PK collection: For Treatment Groups 1 and 2, plasma PK sam lino will occur relative to dosing ofGS-6207 at Da s 1, 2 and 8 redose (within 30 minutes of dosing) and a 
single timed PK sample between 1 and 6 hom·s postdose. 
At Day 15 and all visits with SC 
GS-6207, a single predose PK sample will be collected. Startmg at Wee 4 an at a VISlts w1 out SC GS-6207, 6207 mc u mg e Oral Bridging visits, if applicable, a 
single anytime PK sample will be collected. PK sampling will continue at visits past Week 80. 
r 
I 
I 
For Treatment Grou s 3 and 4 a1tici ants, sta1ting at Da 1, a single an ime PK sam le will be collected at all stud visits. 
Treatment Group 1 an 2 era GS-6207 ea mat Day 1, Day 2 an Day 8. Treatment Group 3 will receive oral GS-6207 lead in at Days 1 and 2 and will begin oral daily 
GS-6207 at Day 3. 
u 
Treatment Group 1 and 2 Subcutaneous administration at Day 15 and every 26 weeks 
v 
Treatment Group 1, 2, and 3 F/TAF once daily for 28 weeks sta1ting at Day 1. Treatment Group 3 participants will continue F/TAF until study completion. 
w 
Treatment Group 1 daily oral TAF to be initiated at Week 28 
x 
Treatment Group 2 daily oral BIC to be initiated at Week 28 
y 
Treatment Group 4 daily oral B/F/TAF 
z 
Prior to completion of other study procedm·es, pa1ticipants will complete HIVTSQ12, HIVDQoL, and EQ-ED-5L at Day 1 (except HIVTSQ12), Day 15 (HIVTSQ12 only), 
Week 4, Week 28, Week 54, Week 80. Injection Acceptability Scale and Nmueric Pain Rating Scale to be completed at Day 15, Weeks 28, 54 and 80 (for Treatment Groups 1 
and 2 pa1ticipants only) after SC GS-6207 administration and completion of other study procedures. 
aa 
Provide Injection Site Reaction Assessment Worksheet and instmct the participants to measure and report injection site reactions following the administration of the 
subcutaneous injections (for Treatment Group 1 and 2 pa1ticipants only) 
CONFIDENTIAL 
Page 122 
04 Febrna1y 2022 


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 123
04 February 2022
Appendix 3.
Management of Clinical and Laboratory Adverse Events
I 
Grade 1 
I 
Grade 2 
I 
I 
Grade 3 
I 
I 
Grade 4 
I 
\I 
May continue dosing 
Repeat lab to 
Repeat lab to 
If confirmed, and 
at the discretion of 
confirm toxicity 
confirm toxicity 
f-------;i possibly or probably 
the investigator 
grade 
grade 
related to 
investigational 
products, discontinue 
,v 
'" 
investigational 
If confirmed, and possibly or probably related to investigational 
If confirmed, and unrelated to 
medicinal products 
products: 
investigational medical 
dosing permanently, 
I. Withhold investigational medicinal products until ::o Grade 2 
products, dosing may continue 
and manage 
2. Restart all investigational medicinal products at full dose 
at the discretion of the 
participant according 
upon discussion with the Gilead Sciences Medical Monitor 
investigator 
to local practice. 
J 
Participant should be 
followed as clinically 
indicated until the 
If Grade 3 or 4 recurrence is 
If Grade 3 or 4 recurrence is 
laboratory 
confirmed, and possibly or 
confinned, and unrelated to 
abnormality returns 
probably related to 
investigational medical 
to baseline, or is 
investigational products, 
products, continue all 
otherwise explained 
discontinue all investigational 
investigational medicinal 
medicinal products dosing 
products at the same dose, at 
permanently, and manage the 
the discretion of the 
participant according to local 
investigator 
practice 


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 124
04 February 2022
Appendix 4.
Pregnancy Precautions, Definition for Women of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born participant is considered a woman of childbearing 
potential following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, 
unless permanently sterile or with medically documented ovarian failure. No documentation of 
Tanner stage will be required unless the participant is considered to be prepubescent.
Women are considered to be in a postmenopausal state when they are ≥ 54 years of age with 
cessation of previously occurring menses for ≥ 12 months without an alternative cause. In 
addition, women of < 54 years of age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
For the purpose of this study, permanent sterilization is hysterectomy, bilateral oophorectomy, or 
bilateral salpingectomy in a woman of any age. Tubal ligation is not considered permanent 
sterilization.
b. Definition of Male Fertility
For the purposes of this study, a male born participant is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Born Participants
a. Study Drug Effects on Pregnancy and Hormonal Contraception
Nonclinical toxicity studies of GS-6207 have demonstrated no adverse effect on fertility or 
embryo-fetal development. However, there are no clinical studies of GS-6207 in pregnant 
women. Based on in vitro and in vivo drug–drug interaction liability assessments, a clinically 
significant drug-drug interaction with GS-6207 and hormonal contraceptives is not expected; an 
oral contraception drug-drug interaction study was not done. 
No adequate and well-controlled study of F/TAF, FTC, or TAF has been conducted in pregnant 
women. There is an ongoing clinical study of B/F/TAF in pregnant women. Non-clinical toxicity 
studies of BIC, FTC, and TAF have demonstrated no adverse effect on fertility or embryo-fetal 
development. Neither BIC, FTC nor TAF are considered to be genotoxic. Please refer to the 
latest version of the investigator’s brochures for additional information.


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 125
04 February 2022
b. Contraception Requirements for Female Born Participants of Childbearing Potential
The inclusion of female born participants of childbearing potential requires using at least an 
acceptable effective contraceptive. They must have a negative serum pregnancy test at screening 
and a negative pregnancy test at the Day 1 visit prior to the dose of study drug. Pregnancy tests 
will be performed as defined by the study procedures in Appendix 2.In the event of a delayed 
menstrual period (over one month between menstruations), a pregnancy test must be performed 
to rule out pregnancy. This is also applicable for female born participants of childbearing 
potential with infrequent or irregular periods. 
Duration of contraception for female born participants of childbearing potential enrolled in this 
clinical trial should start from Screening visits until 60 days after the last dose of oral study drug 
or 700 days following the last dose of subcutaneous study drug, whichever is later, as applicable.
Female born participants of childbearing potential must agree to 1 of the following contraceptive 
methods: 

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the participant’s preferred and usual 
lifestyle.
Or

Consistent and correct use of 1 of the following methods of birth control listed below: 
Hormonal and non-hormonal intrauterine device (IUD) 
Bilateral tubal occlusion (upon medical assessment of surgical success)
Vasectomy in the male born partner (upon medical assessment of surgical success)
Or
Female born participants who initiate use of a hormonal contraceptive > 7 days after onset of 
menses as one of their birth control methods should use additional back-up contraception (eg, 
condoms) or avoid sexual intercourse for 7 days. Hormonally-based contraceptives and barrier 
methods permitted for use in this protocol are as follows:
Hormonal Methods 
o
Oral contraceptives (either combined or progesterone only)
o
Injectable progesterone
o
Subdermal contraceptive implant
o
Transdermal contraceptive patch
o
Contraceptive vaginal ring
Barrier methods 


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 126
04 February 2022
o
Male condom (with or without spermicide)
o
Female condom (with or without spermicide)
o
Diaphragm with spermicide
o
Cervical cap with spermicide
o
Sponge with spermicide
Inclusion of methods of contraception in this list of permitted methods does not imply that the 
method is approved in any country or region. Methods should only be used if locally approved.
Female born participants must also refrain from egg donation and in vitro fertilization during 
treatment and until the end of contraception requirement.
3) Contraception Requirements for Male Born Participants
No contraception measures are needed.
Condoms should be used for all sexual activity including oral, vaginal, and anal sexual contact to 
decrease the risk of transmission of HIV and other sexually transmitted diseases.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg. calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM). A female condom and a male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Female born participants who are pregnant or suspect they are pregnant will be instructed to 
notify the investigator at any time during the study, including the protocol-defined follow-up 
period (Treatment Groups 1-4), and if they become pregnant within 700 days following the 
last dose of SC GS-6207 (Treatment Groups 1 and 2) or within 60 days following last dose of 
oral GS-6207. Participants who become pregnant or who suspect that they are pregnant during 
the study should discontinue study drug(s) immediately. 
Male participants whose partner has become pregnant or suspects she is pregnant during the 
study, including the protocol-defined post-treatment follow-up period, must report the 
information to the investigator. Instructions for reporting pregnancy, partner pregnancy, and 
pregnancy outcome are outlined in Section 7.7.2.1.


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 127
04 February 2022
Appendix 5.
Pandemic Risk Assessment and Mitigation Plan
In the event of an ongoing pandemic (such as COVID-19), potential risks associated with 
participants being unable to attend study visits have been identified for this study. 
These risks can be summarized as follows:

Study drug supplies to participants and sites:
Oral GS-6207 (600 mg and 300 mg doses) and SC GS-6207 study drug administration 
must occur at the study site. Dispensation of other oral study drug(s) must occur at the 
study site. Participants may be unable to return to the site for a number of visits to get the 
study drug, or the site may be unable to accept any participant visits. Without study 
drugs, the participant would not be able to stay on the study drug as planned per protocol.
Mitigation plan: Oral study drug supplies may be provided to the participant from the site 
without a clinic visit, once it is confirmed that the participant may safely continue on 
study drug as determined by the principal investigator (PI). A virtual visit must be 
performed prior to remote study drug resupply. At the earliest opportunity, the site will 
schedule in-person participant visits and return to the protocol’s regular schedule of 
assessments. A qualified courier may be utilized to ship the study drug from sites to study 
participants if permitted by local ethic committee (EC)/institutional review boards 
(IRBs)/Regulatory Authority as applicable and with sponsor's approval. If a participant is 
attending a visit in-clinic and there is a risk that the next visit may not occur in-clinic, the 
site may dispense an additional bottle(s) of oral study drug(s) to the participant in 
anticipation of the missed visit. In such cases, a virtual visit will be performed if the 
participant is not able to come for in-person visit at the clinic. At the earliest opportunity, 
the site will schedule in-person participant visits and return to the protocol’s regular 
schedule of assessments.
Study drug shortage at site level.
Mitigation plan: The sites' study drug inventory should be closely monitored. Site staff 
should notify the sponsor or delegate if they foresee shortage in study drug inventory or if 
there is any interruption in local shipping service. The sponsor will continue to monitor 
inventory at the study drug depot and study sites. Manual shipments will be triggered as 
necessary.

Participant safety monitoring and follow-up:
Participants cannot come to the study site for their scheduled study visits as required per 
protocol.


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 128
04 February 2022
Mitigation plan: For participants who cannot come to the study site for their scheduled 
study visits as required per protocol, the PI or qualified delegate will conduct a virtual 
study visit, via phone or video conferencing, to assess the participant within target visit 
window date whenever possible. During the virtual study visit, the following information 
at minimum will be reviewed: 
■
Confirm if participant has experienced any adverse events (AEs)/serious adverse 
events (SAEs) and follow-up on any unresolved AE/SAEs. 
■
Review current list of concomitant medications and document any new concomitant 
medications.
■
Review any changes in medical history.
■
Confirm participant’s oral study drug supply is sufficient to last until the next planned 
visit date. If study drug resupply is needed it will be provided as described above. 
GS-6207 SC dose can only be given at site. If participant is not able to come for 
in-person visit to receive GS-6207 SC dose at their scheduled visit, Sponsor should be 
notified receive guidance on next steps.
■
Remind participant to maintain current oral dosing and to keep all dispensed study 
drug kits for return at the next on-site visit.
Safety blood draws & central laboratory analysis cannot be done.
Mitigation plan: Local labs may be utilized as appropriate to monitor participant safety 
until the participant can return to the site for their regular follow-up per protocol per PI 
discretion. Any laboratory assessments conducted at a local lab due to the pandemic will 
be documented accordingly. 
Participants are unable to attend the study visit to sign an updated informed consent form 
(ICF) version.
Mitigation plan: The site staff will follow their approved consent process and remain in 
compliance with local EC/IRB and national laws and regulations. Remote consent will be 
allowed if approved by the local EC/IRB. The consent process will be documented and 
confirmed by normal consent procedure at the earliest opportunity.

Protocol and monitoring compliance:
Protocol deviations in case scheduled visits cannot occur as planned per protocol.


GS-6207
Protocol GS-US-200-4334
Final
Gilead Sciences, Inc.
Amendment 4
CONFIDENTIAL
Page 129
04 February 2022
Mitigation plan: If it is not possible to complete a required procedure at scheduled visit, 
the visit should be conducted as soon as possible when conditions allow. The situation 
should be recorded and explained as a protocol deviation (PD). Any missed participant 
visits or deviation to the protocol due to the pandemic must be reported in the e-case 
report form (CRF) and described in the clinical study report. Any virtual study visits that 
are conducted in lieu of clinic visits due to the pandemic will be documented as a PD 
related to the pandemic.
On-site monitoring visit is not feasible. 
Monitors may be unable to carry out source data review (SDR) or source data verification 
(SDV), study drug accountability, or protocol and GCP compliance. This may lead to 
delays in SDV, an increase in protocol deviations, or under reporting of AEs.
Mitigation plan: The study monitor is to remain in close communication with the site to 
ensure data entry and query resolution (remote SDV not allowed). The study monitor is 
to reference the Study Monitoring Plan for guidance on how to conduct a remote 
monitoring visit. The study staff is to save and document all relevant communication in 
the study files. The status of sites that cannot accept monitoring visits and/or participants 
on site, must be tracked centrally and updated on a regular basis.

Missing data and data integrity:
Increased number of missing data due to participants missing visits/assessments. This 
could have an impact on the analysis and the interpretation of clinical trial data. 
Mitigation plan: Implications of a pandemic on methodological aspects for the study will 
be thoroughly assessed and documented, and relevant actions will be taken as appropriate 
(ie, modification of the statistical analysis plan) and in compliance with Regulatory 
Authorities’ guidance. Overall, the clinical study report will describe the impact of the 
pandemic on the interpretability of study data.
Virtual visits should be documented in the participant’s source documents. For any completed 
virtual visits, associated data will be entered in EDC and a general comment will be added noting 
that the visit was completed virtually due to pandemic.
Risks will be assessed continuously, and temporary measures will be implemented to mitigate 
these risks as part of a mitigation plan, as described above. These measures will be 
communicated to the relevant stakeholders as appropriate and are intended to provide alternate 
methods that will ensure the evaluation and assessment of the safety of participants who are 
enrolled in this study. 
Since these potential risks would be considered mitigated with the implementation of these 
measures, the expected benefit risk assessment of study drug(s) in study participants remains 
unchanged.

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2 Randomized, Open Label, Active Controlled Study 
Evaluating the Safety and Efficacy of Long-acting Capsid 
Inhibitor GS-6207 in Combination with Other Antiretroviral 
Agents in People Living with HIV
Name of Test Drug:
Lenacapavir (LEN; GS-6207)
Study Number:
GS-US-200-4334
Protocol Version (Date):
Amendment 3 (01 September 2020)
Analysis Type:
Week 28 Interim Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
13 April 2021
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
GILEAU 


Lenacapavir 
GS-US-200-4334 
Statistical Analysis Plan - Week 28 Interim Analysis 
TABLE OF CONTENTS 
Version 1.0 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ .4 
LIST OF ABBREVIATIONS ......................................................................................................................................... 5 
PHARMACOKINETICABBREVIATIONS ................................................................................................................. 6 
1. 
INTRODUCTION .................................................................................................................................................. 7 
1. 1. 
Study Objectives ........................................................................................................................................ 7 
1.2. 
Study Design ............................................................................................................................................. 7 
1.3. 
Sample Size and Power ........................................................................................................................... 10 
2. 
TYPE OF PLANNED ANALYSIS ...................................................................................................................... 11 
2.1. 
Interi1n Analyses ...................................................................................................................................... 11 
2.1. 1. 
Data Monitoring Committee Analysis ................................................................................... 11 
2.1.2. 
Week 28 Interitn Analysis ..................................................................................................... 11 
2.1.3. 
Other Interim Analyses .......................................................................................................... 11 
2.2. 
Final Analysis .......................................................................................................................................... 11 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................. 12 
3.1. 
Analysis Sets ........................................................................................................................................... 12 
3 .1. 1. 
All Randomized Analysis Set ................................................................................................ 12 
3.1.2. 
Full Analysis Set. ................................................................................................................... 12 
3.1.3. 
Safety Analysis Set ................................................................................................................ 12 
3.1.4. 
Pharmacokinetic Anal sis Set ............................................................................................... 13 
3.2. 
Subject Grouping ..................................................................................................................................... 13 
3.3. 
Strata and Covariates ............................................................................................................................... 14 
3.4. 
Examination of Subject Subgroups ......................................................................................................... 14 
3.4.1. 
Subject Subgroups for Efficacy Analyses ............................................................................. 14 
3.4.2. 
Subject Subgroups for Safety Analyses ................................................................................ 14 
3.5. 
Multiple Co1nparisons ............................................................................................................................. 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 Transfo1mations .................................................................................. 15 
3.8. 
Analysis Visit Windows .......................................................................................................................... 16 
3.8.1. 
Definition of Key Dates and 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 ................................................................................................................................. 19 
4. 
SUBJECT DISPOSITION ................................................................................................................................... 20 
4.1. 
Subject Enrollment and Disposition ........................................................................................................ 20 
4.2. 
Extent of Study Thug Exposme and Adherence ...................................................................................... 21 
4.2.1. 
Duration of Exposw·e to Study Thug ..................................................................................... 21 
4.2.2. 
Adherence to Study D1ug ...................................................................................................... 21 
4.3. 
Protocol Deviations ................................................................................................................................. 23 
5. 
BASELINE CHARACTERISTICS ..................................................................................................................... 24 
CONFIDENTIAL 
Page2 
13 April 2021 


Lenacapavir 
GS-US-200-4334 
Statistical Analysis Plan - Week 28 Interim Analysis 
Version 1.0 
5.1. 
Demographics and Baseline Characteristics ........................................................................................... 24 
5.2. 
Other Baseline Characteristics ................................................................................................................ 24 
5.3. 
Medical Histo1y ....................................................................................................................................... 24 
6. 
EFFICACY ANALYSES ..................................................................................................................................... 25 
6.1. 
Pri1nruy Efficacy Endpoint ...................................................................................................................... 25 
6.2. 
Secondruy Efficacy Endpoints ................................................................................................................ 25 
6.2.1. 
US FDA-defined Snapshot Algorithm .................................................................................. 25 
6.2.2. 
Anal sis of the Seconda1 Efficac End oints ..................................................................... 26 
6.4. 
Subgroup Analysis ................................................................................................................................... 28 
6.5. 
Changes from Protocol-Specified Efficacy Analyses ............................................................................. 28 
7. 
SAFETY ANALYSES ......................................................................................................................................... 29 
7.1. 
Adverse Events and Deaths ..................................................................................................................... 29 
7.1.1. 
Adverse Event Dictiona1y ..................................................................................................... 29 
7.1.2. 
Adverse Event Severity ......................................................................................................... 29 
7.1.3. 
Relationship of Adverse Events to Study Dmg ..................................................................... 29 
7.1.4. 
Serious Adverse Events ......................................................................................................... 29 
7.1.5. 
Treatinent-Emergent Adverse Events .................................................................................... 29 
7.1.6. 
SUllllllaries of Adverse Events and Deaths ............................................................................ 30 
7.1.7. 
Additional Analysis of Adverse Events ................................................................................ 32 
7.2. 
Laborato1y Evaluations ........................................................................................................................... 32 
7.2.1. 
SUllllllaries of Numeric Laborat01y Results .......................................................................... 33 
7.2.2. 
Graded Laborato1y Values .................................................................................................... 34 
7.3. 
Body Weight and Vital Signs .................................................................................................................. 35 
7.4. 
Prior and Concoinitant Medications ........................................................................................................ 35 
7.4.1. 
Nonstudy Dmg Antireti·oviral Medications ........................................................................... 35 
7.4.2. 
Conco1nitant Non-ARV Medications .................................................................................... 35 
7.5. 
Electrocru·diogra1n Results ....................................................................................................................... 36 
7 .5 .1. 
Investigator Electi·ocardiogram Assessment ......................................................................... 36 
7.6. 
Other Safety Measures ............................................................................................................................ 36 
7.7. 
Subject Subgroup for Safety Endpoints .................................................................................................. 36 
7.8. 
Changes from Protocol-Specified Safety Analyses ................................................................................. 36 
8. 
PHARMACOKINETIC (PK) ANALYSES ......................................................................................................... 37 
8.1. 
PK Sample Collection ............................................................................................................................. 37 
8.2. 
PK Analyses Related to PK Sampling ..................................................................................................... 38 
8.2.1. 
Estimation of PK Parruneters ................................................................................................. 38 
8.2.2. 
PK Parameters ....................................................................................................................... 38 
8.2.3. 
Statistical Analysis Methods ................................................................................................. 39 
8.2.4. 
Sensitivity Analyses ............................................................................................................. .40 
8.2.5. 
Changes from Protocol-Specified Phrumacokinetic Analysis .............................................. .40 
9. 
REFERENCES .................................................................................................................................................... .41 
10. SOFTWARE ........................................................................................................................................................ .42 
11. SAP REVISION .................................................................................................................................................. .43 
12. APPENDICES ...................................................................................................................................................... 44 
Appendix 1. 
Schedule of Assessments ........................................................................................................ .45 
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Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm(for Naïve Trial) ....................................49
Appendix 3.
Programming Specification .....................................................................................................50
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, Hematology, 
Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, Urine Pregnancy Laboratory 
Tests, Vital Signs, and Weight for the LEN-containing Regimen Groups 
(Treatment Groups 1-3)...........................................................................................................18
Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, Hematology, 
Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, Urine Pregnancy Laboratory 
Tests, Vital Signs, and Weight for the B/F/TAF Group (Treatment Group 4)........................18
Table 8-1.
Study Treatment Groups and Associated Analytes .................................................................38
Table 8-2.
PK Parameters for Each Analyte.............................................................................................39


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LIST OF ABBREVIATIONS
AE
adverse event
B/F/TAF
Bictegravir/Emtricitabine/Tenofovir Alafenamide
BIC
Bictegravir
BLQ
below the limit of quantitation
BMI
body mass index
CI
confidence interval
CK
creatine kinase
CRF
case report form
CSR
clinical study report
DMC
data monitoring committee
ECG
Electrocardiogram
eGFRCG
estimated glomerular filtration rate using Cockcroft-Gault formula
FAS
Full Analysis Set
Hb
Hemoglobin
HLT
high-level term
ITT
intent to treat
LOQ
limit of quantitation
LPLV
last patient last visit
MedDRA
Medical Dictionary for Regulatory Activities
PBMC 
peripheral blood mononuclear cell
PWH
people with HIV
PT
preferred term
Q1, Q3
first quartile, third quartile
SAP
statistical analysis plan
SC
subcutaneous 
SD
standard deviation
SE
standard error
SOC
system organ class
TAF
tenofovir alafenamide
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
TFV
tenofovir
TFV-DP
tenofovir diphosphate
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCtau
area under the concentration versus time curve over the dosing interval
Clast
last observed quantifiable concentration of the drug 
Cmax
maximum observed concentration of drug 
Ctau
observed drug concentration at the end of the dosing interval
CLss/F
apparent oral clearance after administration of the drug:
at steady state: CLss/F = Dose/AUCtau , where “Dose” is the dose of the drug
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 
2 by the terminal elimination rate constant (z)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination 
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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) of Week 28 interim analysis for 
Study GS-US-200-4334. A formal interim analysis will be performed when all subjects have 
completed Week 28 assessment or prematurely discontinued from study drug. The purpose of 
this interim analysis is to support the lenacapavir (LEN; GS-6207) regulatory filing for the 
indication in the heavily treatment experienced people with HIV (PWH).
This SAP is based on the study protocol amendment 3 dated 01 September 2020 and the 
electronic case report form (eCRF). The SAP will be finalized prior to data finalization for the 
Week 28 analysis. Any changes made after the finalization of the SAP will be documented in the 
clinical study report (CSR).
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate the efficacy of LEN containing regimens in PWH as determined by the 
proportion of subjects with HIV-1 RNA  50 copies/mL at Week 54
The secondary objectives of this study are as follows:

To evaluate the efficacy of LEN containing regimens in PWH as determined by the 
proportion of subjects with HIV-1 RNA  50 copies/mL at Weeks 28, 38, and 80

To evaluate the change from baseline in log10 HIV-1 RNA and in CD4+ cell count at 
Weeks 28, 38, 54, and 80

To evaluate the safety and tolerability of the LEN containing regimens through 28, 38, 54, 
and 80 weeks of treatment

To evaluate the pharmacokinetics (PK) of LEN, bictegravir (BIC), and tenofovir alafenamide 
(TAF)
1.2.
Study Design
Design Configuration and Subject Population
This is a Phase 2, randomized, open label, active controlled, multicenter study.
Approximately 175 treatment-naive PWH who meet all eligibility criteria will be randomized in 
a 2:2:2:1 ratio to 1 of the following 4 treatment groups. Randomization will be stratified by 
HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.


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Treatment Groups
Treatment Group 1 (n = 50)
Induction: Subjects will receive oral LEN 600 mg, 600 mg, and 300 mg, without regard to food, 
at Days 1, 2, and 8 respectively. Subjects will also begin oral daily emtricitabine (F)/TAF 
(200/25 mg), without regard to food from Day 1 onwards for a total of 28 weeks. On Day 15 
subjects will receive subcutaneous (SC) LEN 927 mg, without regard to food.
Maintenance: Subjects will receive SC LEN 927 mg at Week 28 and every 26 weeks thereafter. 
Subjects will discontinue oral daily F/TAF (200/25 mg) at Week 28 and begin taking oral daily 
TAF (25 mg), without regard to food.
Treatment Group 2 (n = 50)
Induction: Subjects will receive oral LEN 600 mg, 600 mg, and 300 mg, without regard to food 
at Days 1, 2, and 8 respectively. Subjects will also begin oral daily F/TAF (200/25 mg), without 
regard to food from Day 1 onward for a total of 28 weeks. On Day 15 subjects will receive SC 
LEN 927 mg, without regard to food.
Maintenance: Subjects will receive SC LEN 927 mg at Week 28 and every 26 weeks thereafter. 
Subjects will discontinue oral daily F/TAF (200/25 mg) at Week 28 and begin oral daily BIC 
(75 mg) without regard to food.
Treatment Group 3 (n = 50)
Subjects will receive oral LEN 600 mg and 600 mg without regard to food at Days 1 and 2, 
respectively. On Day 3, subjects will begin oral daily LEN 50 mg, without regards to food. 
Subjects will begin oral daily F/TAF (200/25 mg), without regard to food from Day 1 onwards.
Treatment Group 4 (n = 25)
Subjects will receive oral daily bictegravir/emtricitabine/TAF (B/F/TAF, 50/200/25 mg), without 
regard to food at Day 1 and throughout their participation in the study.
Key Eligibility Criteria
Treatment naive PWH who meet the following criteria:

Age ≥ 18 years of age at Screening

Plasma HIV-1 RNA  200 copies/mL at Screening

CD4+ cell count  200 cells/L at Screening

Antiretroviral (ARV) naive with no use of any ARV medications within one month of 
Screening. Use of pre-exposure prophylaxis (PrEP) (any duration), post-exposure 
prophylaxis (PEP) (any duration), or HIV-1 treatment (< 10 days therapy total) > 1 month 
prior to Screening is permitted.


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Schedule of Assessments
At screening, laboratory analyses (hematology, chemistry, and urinalysis, and serum pregnancy 
test [for women]), HIV-1 RNA, CD4+ cell count, vital signs, electrocardiogram (ECG), 
complete physical examination and estimated glomerular filtration rate (eGFR) will be 
performed, and hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies will be analyzed. 
Analysis of the subject’s HIV-1 resistance to support eligibility will be completed.
After screening procedures, eligible subjects will be randomized into 1 of the 4 treatment groups 
in a 2:2:2:1 ratio.
Subjects in Treatment Groups 1, 2, and 3 only, will have visits on Day 1, Day 2, 
 
Day 8, and Day 15. All subjects will have a Week 4 visit and will continue to attend 
study visits every 6 weeks until Week 28.
Subjects in Treatment Groups 1 and 2 will need to have HIV-1 RNA results < 50 copies/mL at 
Weeks 16 and 22 to initiate treatment with a two agent regimen at Week 28; those with values 
≥ 50 copies/mL will discontinue the study drug at or prior to Week 28.
After Week 28, subjects will attend study visits on Week 38, Week 54, Week 64, and Week 80. 
After Week 80, subjects in Treatment Group 4 will complete the study and subjects in Treatment 
Groups 1, 2, and 3 will be given the option to receive further treatment and continue to attend 
visits alternating between every 10 weeks and every 16 weeks visits.
At each visit, adverse events (AEs), concomitant medications, laboratory tests, physical 
examinations, PK, and patient reported outcomes (PROs) will be performed in accordance with 
the Study Procedures Table.
More details for study procedures could be found in Section 12 (Appendix 1). 
Study Duration
Duration of treatment is at least 80 weeks. Subjects in Treatment Group 4 will complete the 
study at Week 80.
Following successful completion of Week 80 visit, subjects receiving LEN will be given the 
option to receive further treatment and continue to attend visits on Week 90, Week 106, 
Week 116, Week 132, Week 142, and will continue to alternate between every 10 weeks and 
every 16 weeks visits. Subjects willing to continue the study beyond Week 80 in Treatment 
Groups 1 and 2 will continue to receive SC LEN 927 mg every 6 months (26 weeks) from 
Week 80 onwards and subjects in Treatment Group 3 will receive oral LEN 50 mg daily from 
Week 80 until the product becomes accessible to subjects through an access program, or until 
Gilead elects to discontinue the study in the country. Subjects in Treatment Groups 1, 2, and 3 
will also receive TAF, F/TAF, or BIC as applicable.
Subjects who discontinue study drugs prior to Week 80 visit or prior to study completion may be 
required to complete 30-Day, 90-Day and/or 180-Day Follow Up visits after Early Termination 
Visit.
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1.3.
Sample Size and Power
A sample size of 50 subjects in Treatment Groups 1 to 3, respectively, was chosen to estimate 
the response rate of HIV-1 RNA < 50 copies/mL at Week 54. A total sample size of 75 subjects 
for each pair of comparisons (ie, between each of the LEN-containing regimen groups 
[Treatment Groups 1 to 3, n = 50] and the B/F/TAF [Treatment group 4, n = 25]) will provide 
39% power to evaluate non-inferiority with respect to the response rate of HIV-1 RNA 
 50 copies/mL at Week 54. In this sample size and power calculation, it is assumed a response 
rate is 90.9% (based on pooled data from Studies GS-US-380-1489 and GS-US-380-1490) for 
each treatment group and a non-inferiority margin is 0.12.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Data Monitoring Committee Analysis 
One external multidisciplinary Data Monitoring Committee (DMC) analysis will be conducted 
after all subjects have completed their Week 16 visit or prematurely discontinued from study 
drug, all outstanding data queries have been resolved or adjudicated as unresolvable, and the data 
have been cleaned and finalized for the analysis. No formal stopping rules will be used by the 
DMC for safety outcomes. Rather, a clinical assessment will be made to determine if the nature, 
frequency, and severity of AEs associated with a study treatment warrant the early termination of 
the study in the best interest of the subjects. No alpha penalty will be applied for the primary 
analysis of the primary efficacy endpoint given that the study is not adequately powered for a 
formal efficacy evaluation. The DMC’s role and responsibilities and the scope of analysis to be 
provided to the DMC are provided in a mutually agreed upon charter, which defines the DMC 
membership, meeting logistics, and meeting frequency. More details are documented in the 
DMC charter. 
2.1.2.
Week 28 Interim Analysis
The Week 28 interim analysis is a planned secondary analysis and will be conducted after all 
subjects have completed the Week 28 visit or have prematurely discontinued the study drug, 
outstanding data queries have been resolved or adjudicated as unresolvable, and the data have 
been cleaned and finalized for the analysis. The data from this analysis will be used to support 
the LEN regulatory filing for the indication in the heavily treatment experienced PWH.
This SAP describes the analysis plan for the Week 28 interim analysis.
2.1.3.
Other Interim Analyses
Three planned interim analyses are prespecified in the protocol: Week 38, Week 54 (primary 
analysis), and Week 80 analyses. Each analysis will be conducted after all subjects have 
completed the visit of interest or have prematurely discontinued from study drug prior to the visit 
of interest.
2.2.
Final Analysis
Final analysis will be conducted after all subjects have completed the study, outstanding data 
queries have been resolved or adjudicated as unresolvable, and the data have been cleaned and 
finalized, the final analysis of the data will be performed.


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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.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set and 
sorted by subject identification (ID) number, visit date, and time (if applicable). Data collected 
on log forms, such as AEs, will be presented in chronological order within the subject. The 
treatment group to which subjects were randomized will be used in the listings. Age, sex at birth, 
race, and ethnicity will be included in the listings, as space permits.
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. The analysis set will be identified and included as a subtitle of each 
table, figure, and listing.
For each analysis set, the number and percentage of subjects eligible for inclusion will be 
summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set includes all subjects who were randomized into the study. 
This is the primary analysis set for by-subject listings.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all subjects who were randomized and received at least 
1 dose of study drug. This is the primary analysis set for efficacy analyses.
3.1.3.
Safety Analysis Set
The Safety Analysis Set includes all subjects who were randomized and received at least 1 dose 
of study drug. This is the primary analysis set for safety analyses.


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3.1.4. 
Pharmacokinetic Analysis Set 
Version 1.0 
The PK Analysis Set will include all subjects who (1) are randomized into the study, (2) have 
received at least 1 dose of active study diug, and (3) have at least 1 nonmissing PK concentrntion 
value for any analyte of interest repo1ted by the PK lab. The PK analysis set will be used for 
general PK analyses. 
-
-
3.2. 
Subject Grouping 
For analyses based on the All Randomized Analysis Set or the FAS, subjects will be grouped 
according to the treatment group to which they were randomized. For all other analyses, subjects 
will be grouped according to the actual treatment received. The actual treatment received will 
differ from the randomized treatment only when their actual treatment differs from randomized 
treatment for the entire treatment duration. 
Subjects will be grouped as follows for table summaiy: 
• 
Treatment Group 1: SC LEN + (FIT AF 
T AF) 
• 
Treatment Group 2: SC LEN+ (F/TAF 
BIC) 
• 
Treatment Group 3: Oral LEN + F/TAF 
• 
Treatment Group 4: B/F/TAF 
• 
Treatment Groups 1 and 2: SC LEN (for all tables unless specified othe1wise) 
• 
Treatment Groups 1, 2 and 3: LEN (for all tables unless specified othe1wise) 
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3.3.
Strata and Covariates
Randomization was stratified by HIV-1 RNA level (≤ 100,000 copies/mL or 
> 100,000 copies/mL) at screening. 
Efficacy analyses will include HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) at 
baseline as a stratification factor. The HIV-1 RNA stratum will be reclassified using baseline 
HIV-1 RNA level for analysis purposes. 
3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Efficacy Analyses
The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 28 as determined by the 
United States (US) Food and Drug Administration (FDA)-defined snapshot algorithm 
{U. S. Department of Health and Human Services 2015} will be analyzed for the following 
subject subgroups based on FAS:

Age (years): (a) < 50 and (b) ≥ 50

Sex: (a) male and (b) female

Race: (a) black and (b) nonblack

Baseline HIV-1 RNA (copies/mL): (a) ≤ 100,000 and (b) > 100,000

Baseline CD4 Cell Count (/uL): (a) < 200 and (b)  ≥ 200
3.4.2.
Subject Subgroups for Safety Analyses
Incidence of all treatment-emergent AEs (TEAEs) will be analyzed for the following subject 
subgroups: 

Age (years): (a) < 50 and (b) ≥ 50 

Sex: (a) male and (b) female 

Race: (a) black and (b) nonblack 
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be made in this Phase 2, non-confirmatory trial.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
For missing last dose date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for 
prior and concomitant medications in Section 7.4.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
Only year of birth is collected in this study. The following conventions will be used for the 
imputation of full date of birth: 

If year of birth is collected, “01 July” will be imputed as the day and month of birth

If year of birth is missing, date of birth will not be imputed
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, age derived based on date of birth and the Day 1 visit 
date will be used instead. If a randomized subject was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (eg, estimates of creatinine clearance) will 
be based on age derived from date of birth and the date of the measurement or event, unless 
otherwise specified.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “ x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate 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 to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).


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Logarithmic (base 10) transformations will be applied to HIV-1 RNA data for efficacy analysis. 
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “<20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purposes. 
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 subjects 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 subjects 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 subjects 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 subjects 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 Key Dates and Study Day
Study Day 1 is defined as the day when the first dose of study drug was taken, as recorded on 
the Study Drug Administration eCRF. For subjects in Treatment Groups 1-3, the earliest of the 
first dose dates of any component (ie, LEN or F/TAF) is considered as the first dose date of the 
study drug.
Last Dose Date is defined as follows for subjects who prematurely discontinued study drug 
according to Study Drug Completion eCRF. 

For subjects who receive SC injection, the last dose date is defined as the latest nonmissing 
end date of the study drug used with LEN.

For subjects who do not receive SC injection, the last dose date is defined as the earliest of 
the last dose date of any study drug.

If the date of last dose is incomplete or missing (eg, due to lost to follow-up), the latest 
nonmissing study drug start dates and end dates, the clinic visit dates, and the laboratory visit 
dates excluding the dates of any follow-up visits will be used to impute the last dose date.


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Study Days are calculated relative to Study Day 1 of study drug and derived as follows:

For postdose study days: Assessment Date – First Dose Date + 1

For days prior to the first dose: Assessment Date – First Dose Date
Baseline Value is defined as the last value obtained on or prior to the first dose of study drug.
Last Study Date is the latest clinic visit dates, and/or the laboratory visit dates, and/or latest AE 
onset date and end date, whichever is latest, including the any follow-up visit dates, for subjects 
who prematurely discontinued study according to the Study Completion eCRF.
Last Exposure Date is defined as follows for subjects who prematurely discontinued study drug 
according to Study Drug Completion eCRF. This date is defined considering the prolonged 
exposure of LEN after the last dose date of LEN.

Treatment Groups 1 and 2:
For subjects who receive SC injection, last exposure date is defined as last study date.  
For subjects who do not receive SC injection, last exposure date is defined as the 
minimum of the last dose date plus 60 days and the last study date.

Treatment Group 3: last exposure date is defined as the minimum of the last dose date plus 
60 days and the last study date.

Treatment Group 4: last exposure date is defined as the minimum of the last dose date plus 
30 days and the last study date. 
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 %, Hematology, Chemistry, Lipid 
Panel, Urinalysis, Urine Chemistry, Urine Pregnancy Laboratory Tests, Vital Signs, and Weight 
are provided in Table 3-1 and Table 3-2 for the LEN-containing regimen groups 
(Treatment Groups 1-3) and the B/F/TAF group (Treatment Group 4), respectively.


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Table 3-1.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, 
Hematology, Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, 
Urine Pregnancy Laboratory Tests, Vital Signs, and Weight for the 
LEN-containing Regimen Groups (Treatment Groups 1-3)
Visit ID
Nominal Day
Lower Limit
Upper Limit
Day 1
1
≤ 1
1
Day 2
2
2
5
Day 8
8
6
11
Day 15
15
12
21
Week 4
28
22
49
Week 10
70
50
91
Week 16 
112
92
133
Week 22
154
134
175
Week 28
196
176
231
Week 38
266
232
322
Week 54
378
323
413
Week 64
448
414
504
Week 80
560
505
595
Table 3-2.
Analysis Windows for HIV-1 RNA, CD4+ cell count, CD4 %, 
Hematology, Chemistry, Lipid Panel, Urinalysis, Urine Chemistry, 
Urine Pregnancy Laboratory Tests, Vital Signs, and Weight for the 
B/F/TAF Group (Treatment Group 4)
Visit ID
Nominal Day
Lower Limit
Upper Limit
Day 1
1
≤ 1
14
Week 4
28
15
49
Week 10
70
50
91
Week 16 
112
92
133
Week 22
154
134
175
Week 28
196
176
231
Week 38
266
232
322
Week 54
378
323
413
Week 64
448
414
504
Week 80
560
505
595


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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 may be 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 1 value per analysis window.
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dose date of study drug will be 
selected, unless specified differently. If there are multiple records with the same time or no 
time recorded on the same day, the baseline value will be the average of the measurements 
for continuous data (except for HIV-1 RNA, see below), or the measurement with the lowest 
severity (eg, normal will be selected over abnormal for safety ECG findings) for categorical 
data.

For postbaseline values:
The record closest to the nominal day for that visit will be selected with the exception of 
CD4 cell counts and CD4% in which the latest record will be selected and HIV-1 RNA 
level (see below).
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken for 
continuous data (except for HIV-1 RNA, see below) and the worse severity will be taken 
for categorical data, unless otherwise specified.

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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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
Key study dates on the first subject screened, first subject randomized, last subject randomized, 
and last subject last visit for the CSR will be provided.
A summary of subject enrollment will be provided by treatment group for each country, 
investigator within a country, and overall. For each column, the denominator for the percentage 
calculation will be the total number of subjects analyzed for that column. 
A similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of subjects in the stratum will be the total number of randomized subjects. If there are 
discrepancies in the value used for stratification assignment between the interactive web 
response system (IWRS) and the clinical database, the value collected in the clinical database 
will be used for the summary. A listing of subjects with discrepancies in the value used for 
stratification assignment between the IWRS and the clinical database at the time of data 
finalization will be provided. If there are differences between randomization stratum using 
screening HIV-1 RNA value and baseline HIV-1 RNA value, a listing of the differences will also 
be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group and total based on all 
screened subjects. This summary will present the number of subjects screened, the number of 
subjects who met all eligibility criteria but were not randomized with reasons subjects not 
randomized, the number of subjects randomized but never dosed (if applicable), number of 
subjects in the Safety Analysis Set and the number of subjects in each of the following 
categories: 

Continuing study drug 

Completed study drug

Did not complete study drug with reasons for premature discontinuation of study drug

Continuing study 

Completed study

Did not complete the study with reasons for premature discontinuation of study
For the status of study drug and study completion and reasons for premature discontinuation, the 
number and percentage of subjects in each category will be provided. The denominator for the 
percentage calculation will be the total number of subjects in the Safety Analysis Set 
corresponding to that column. In addition, a flowchart will be provided to depict the disposition.


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The following by-subject listings will be provided by subject ID number in ascending order to 
support the above summary tables:

Reasons for premature study drug or study discontinuation

Reasons for screen failure (will be provided by screening ID number in ascending order)
4.2.
Extent of Study Drug Exposure and Adherence
Study drug administration and study drug dispensing information will be collected in the Study 
Drug Administration and Study Drug Accountability eCRFs. All data including lot number and 
kit ID (if applicable) will be listed. 
4.2.1.
Duration of Exposure to Study Drug
Due to long acting feature of LEN, duration of follow-up to study drug will consider the 
prolonged exposure of LEN after the last dose date of LEN. Duration of exposure to study drug 
will be defined as (the last exposure date – the first dose date + 1), and will be expressed in 
weeks using up to 1 decimal place (eg, 4.5 weeks). Last exposure date is defined in Section 3.8.1 
for subjects who prematurely discontinued study drug. For subjects who are still on study drug at 
the time of the data cut date of the Week 28 analysis, the data cut date will be used to impute the 
last exposure date.  
Duration of exposure will be summarized using descriptive statistics (n, mean, SD, median, Q1, 
Q3, minimum, and maximum) and as the number and percentage of subjects exposed and 
remained through the following time periods: 1 day, 2 days, 8 days, 15 days, 4 weeks (28 days), 
10 weeks (70 days), 16 weeks (112 days), 22 weeks (154 days), 28 weeks (196 days), etc. 
Summaries will be provided based on the Safety Analysis Set. No inferential statistics will be 
provided.
4.2.2.
Adherence to Study Drug
4.2.2.1.
Adherence to SC LEN
The adherence to SC LEN will be assessed by adherence to the projected injection interval, 
which is 26 weeks (182 days) between 2 adjacent injection visits. The number of days from the 
projected injection visit date will be calculated for each injection visit (excluding the 1st injection 
visit) as the injection visit date – the previous injection visit date plus 1 day minus 182 days. The 
number of days from the projected injection visit date will be classified into the following 
categories: 

< - 14 days

-14 to -8 days

 -7 to -3 days


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
± 2 days

3 to 7 days

8 to 14 days

> 14 days
The number and percentage of subjects in each category will be summarized for subjects in 
Treatment Groups 1 and 2 who receive SC injections for the injection visit of interest. 
4.2.2.2.
Adherence to Once Daily Study Drug(s)
The adherence to once daily (QD) study drug(s) will be calculated based on 1 study drug for 
Treatment Groups 1, 2, and 4 (ie, F/TAF up to Week 28 and TAF or BIC from Week 28 onwards 
for Treatment Groups 1 and 2, and B/F/TAF for Treatment Group 4), and 2 study drugs for 
Treatment Group 3 (ie, oral QD LEN and F/TAF), excluding long acting LEN used for oral 
lead-in.
Adherence (%) of QD study drug(s) will be calculated as follows:
Adherence (%) =  100 ×
𝑇𝑜𝑡𝑎𝑙 No. of pills taken
Total No. of pills prescribed
=  100 ×
∑∑No. of pills taken at each dispensing period  for each study drug[1]
∑∑No. of pills prescribed at each dispensing period for each study drug[2]
[1]
Number of pills taken at a distinct dispensing period for QD study drug(s) will be calculated as the minimum of (a) the daily 
number of pills prescribed multiplied by the duration of treatment of QD study drug(s) at the dispensing period of the same 
dispensing date, and (b) the number of pills taken (number of pills dispensed minus the number of pills returned). Total 
number of pills taken is determined by summing the number of pills taken from all evaluable dispensing periods for all QD 
study drug(s).
[2]
Number of pills prescribed at a distinct dispensing period for QD study drug(s) will be calculated as the daily number of 
pills prescribed multiplied by the duration of treatment of QD study drug(s) at the dispensing period of the same dispensing 
date. Total number of pills prescribed is determined by summing the number of pills prescribed from all evaluable 
dispensing periods for all QD study drug(s).
The duration of treatment of QD study drug(s) at a dispensing period for the study drug is 
calculated as the minimum of (a) the last returned date of the study drug at a dispensing period, 
(b) date of premature discontinuation of the study drug, and (c) next pill dispensing date of the 
study drug, minus dispensing date of the study drug.
The next pill dispensing date is the following dispensing date of the study drug regardless of the 
bottle return date. 


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For a record where the number of pills returned was missing (with “Yes” answered for “Was 
Bottle returned?” question), it is assumed the number of pills returned was zero. If the number of 
pills dispensed was missing or any study drug bottle was not returned or the bottle return status 
was unknown, all records in that dispensing period for that study drug will be excluded from 
both denominator and numerator calculation.
Adherence will be calculated for each subject for the entire dosing period up to the date of 
permanent discontinuation of the study drug for subjects who prematurely discontinued study 
drug or using all available data for subjects ongoing on study drug by the data cut date. 
Descriptive statistics for adherence (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
along with the number and percentage of subjects belonging to adherence categories (eg, < 80%, 
≥ 80% to < 90%, ≥ 90% to < 95%, ≥ 95%) will be provided for subjects who return at least 
1 bottle of randomized QD study drug, and who have calculable adherence in the Safety Analysis 
Set. No inferential statistics will be provided.
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized. The summary will present the number and percentage of subjects who did not meet 
at least 1 eligibility criterion and the number of subjects who did not meet specific criteria based 
on the Safety Analysis Set. A by-subject listing will be provided for those subjects who did not 
meet at least 1 eligibility (inclusion or exclusion) criterion.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations and 
number of important protocol deviations by deviation category (eg, eligibility criteria, informed 
consent) will be summarized by treatment group for the Safety Analysis Set. A by-subject listing 
will be provided for those subjects with important protocol deviation.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic variables (ie, age, sex at birth, gender identity, sexual orientation, race, and 
ethnicity) and baseline characteristics (body weight [in kg], height [in cm], body mass index 
[BMI; in kg/m2]) will be summarized by treatment group and overall using descriptive statistics 
for continuous variables and using number and percentage of subjects for categorical variables. 
The summary of demographic data will be provided for the Safety Analysis Set.
Statistical comparison across treatment groups will be performed. For categorical data, the 
Cochran-Mantel-Haenszel (CMH) test will be used to compare across treatment groups except 
for gender identity and sexual orientation. For continuous data, the 2-sided Kruskal-Wallis test 
will be used to compare across treatment groups. 
A by-subject demographic and baseline characteristic listing, including the informed consent 
date, will be provided by subject ID number in ascending order.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics for subjects in the Safety Analysis Set: 

HIV-1 RNA (log10 copies/mL)

HIV-1 RNA categories (copies/mL): (a) ≤ 100,000, (b) > 100,000

CD4 cell counts (/uL)

CD4 cell counts categories (/uL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥ 200 to < 350, (d) ≥ 350 to 
< 500, and (e) ≥ 500

CD4 percentage (%)
Statistical comparison across treatment groups will be conducted similarly as described for the 
demographic and baseline characteristics. 
A by-subject listing of other baseline characteristics will be provided by subject ID number in 
ascending order.
5.3.
Medical History
Medical history will be collected at screening including HIV-1 disease-related events. Medical 
history data will be coded and listed.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA  50 copies/mL at 
Week 54 as determined by the United States (US) Food and Drug Administration (FDA)-defined 
snapshot algorithm {U. S. Department of Health and Human Services 2015}. The primary 
efficacy endpoint will not be performed in this analysis given the majority of subjects will not 
have reached Week 54. 
6.2.
Secondary Efficacy Endpoints
The secondary efficacy endpoints of this study are:

The proportion of subjects with HIV-1 RNA  50 copies/mL at Weeks 28, 38, and 80 as 
determined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and in CD4+ cell count at Weeks 28, 38, 54, 
and 80
The proportion of subjects with HIV-1 RNA < 50 copies/mL as determined by the US 
FDA-defined snapshot algorithm at Weeks 38 and 80 will not be summarized for the Week 28 
interim analysis as the majority of subjects will not have reached the timepoints of interest. 
6.2.1.
US FDA-defined Snapshot Algorithm
The analysis window at Week 28 is defined as from Study Day 176 to Study Day 231, inclusive. 
All HIV-1 RNA data collected on-treatment (ie, data collected up to 1 day after the last dose 
date) will be used in the US FDA-defined snapshot algorithm. Virologic outcome will be defined 
as the following categories:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available on-treatment 
HIV-1 RNA < 50 copies/mL in the Week 28 analysis window

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 28 
analysis window, or
Who do not have on-treatment HIV-1 RNA data in the Week 28 analysis window and
■
Who discontinue study drug prior to or in the Week 28 analysis window due to lack 
of efficacy, or
■
Who discontinue study drug prior to or in the Week 28 analysis window due to 
reasons other than AE, death, or lack of efficacy and have the last available 
on-treatment HIV-1 RNA ≥ 50 copies/mL


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
No Virologic Data in the Week 28 analysis window: this includes subjects who do not have 
on-treatment HIV-1 RNA data in the Week 28 analysis window because of the following:
Discontinuation of study drug prior to or in the Week 28 analysis window due to AE or 
death (regardless of whether the last available on-treatment HIV-1 RNA < 50 copies/mL 
or not) or,
Discontinuation of study drug prior to or in the Week 28 analysis window due to reasons 
other than AE, death, or lack of efficacy and the last available on-treatment HIV-1 RNA 
< 50 copies/mL or,
Missing data during the window but on study drug.
The flowchart of the US FDA-defined snapshot algorithm is provided in Section 12 
(Appendix 2). 
6.2.2.
Analysis of the Secondary Efficacy Endpoints 
The proportion of subjects with HIV-1 RNA < 50 copies/mL as determined by the US 
FDA-defined snapshot algorithm at Week 28 will be based on the FAS. Point estimates (P1 – P2)  
and its 95% confidence interval (CI) for the difference in the response rates between each of the 
LEN-containing regimen groups (Treatment Groups 1 to 3) and the B/F/TAF group 
(Treatment Group 4) will be constructed using stratum-adjusted Mantel-Haenszel (MH) 
proportion as described as follows {Koch 1989}, stratified by baseline HIV-1 RNA level 
(≤ 100,000 copies/mL or > 100,000 copies/mL):
where 

(P1 – P2) = 
, is the stratum-adjusted MH proportion difference, 
where 
 = 
is the difference in the response rate between of the LEN-containing 
regimen groups (Treatment Groups 1 to 3) and the B/F/TAF group (Treatment Group 4) in 
stratum h (h=1 to 4).  

=
, is the weight based on the harmonic mean of sample size per treatment group 
for each stratum where 
and 
are the sample sizes of the LEN-containing regimen 
groups (Treatment Groups 1 to 3) and the B/F/TAF group (Treatment Group 4) in stratum h.  


h
h
h
w
d
w
h
d
h
h
p
p
2
1 
h
w
h
h
h
h
n
n
n
n
2
1
2
1

h
n1
h
n2
P1 - P2 ± Zo-a12 )* SE(P1 - P2), 


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
SE(P1 – P2) = 
, where 
and 
. 
 and 
are the number of subjects with HIV-1 RNA < 50 copies/mL 
in the LEN-containing regimen groups (Treatment Groups 1 to 3) and the B/F/TAF group 
(Treatment Group 4) in stratum h.  

α = 0.05 for this study 

Z(1-α/2 ) = Z0.9750 = 1.96 is the 97.50th percentile of the normal distribution
Note that if the computed lower confidence bound is less than –1, the lower bound is defined as 
–1. If the computed upper confidence bound is greater than 1, the upper bound is defined as 1.
The number and percentage of subjects with HIV-1 RNA < 50 copies/mL at Week 28 will be 
summarized. The associated p-values will be estimated based on the CMH test stratified by 
baseline HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL).
The change from baseline in log10 HIV-1 RNA and in CD4+ cell counts will be based on the 
FAS and summarized up to the visits with available data using descriptive statistics. The 
differences in changes from baseline in log10 HIV-1 RNA and CD4+ cell count between each of 
the LEN-containing treatment groups (Treatment Groups 1-3) and the B/F/TAF group 
(Treatment Group 4) and the associated p-values and 95% CIs will be constructed using analysis 
of variance (ANOVA) models adjusting for the baseline HIV-1 RNA level (≤ 100,000 copies/mL 
or > 100,000 copies/mL).
Mean ± 95% CI and median (Q1, Q3) of the change from baseline in log10 HIV-1 RNA and 
CD4+ cell counts will be plotted by visit.  
6.3.
Other Efficacy Endpoints
6.3.1.
Proportion of Subjects with HIV-1 RNA < 50 copies/mL by Missing = Failure 
and Missing = Excluded Analyses
Number and percentage of subjects with HIV-1 RNA < 50 copies/mL by visit will be analyzed 
using the following 2 analyses:  

Missing = Failure (M = F): 
In this approach, missing data will be treated as virologic failure and summarized into the 
“missing” category (see list of HIV-RNA categories below). Results will be summarized by 
treatment group for all visits up to Week 28. 
2
2
*
2
*
2
1
*
1
*
1
2
)
(
1
)
1(
1
)
1(













h
h
h
h
h
h
h
h
w
n
p
p
n
p
p
w
1
5.0
1
1
*
1



h
h
h
n
m
p
1
5.0
2
2
*
2



h
h
h
n
m
p
h
m1
h
m2


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
Missing = Excluded (M = E): 
In this approach, missing data will be excluded in the computation of the percentages 
(ie, missing data points will be excluded from both the numerator and denominator in the 
computation). The denominator for percentages at a visit is the number of subjects in the 
FAS with nonmissing HIV-1 RNA value at that visit. Results will be summarized by 
treatment group for all visits up to Week 28.
For both M = F and M = E analyses, the number and percentage of subjects with HIV-1 RNA in 
the following categories will be summarized based on the FAS:

< 50 copies/mL 
< 20 copies/mL
■
< 20 copies/mL Not Detectable
■
< 20 copies/mL Detectable
20 to < 50 copies/mL 

50 to < 200 copies/mL 

200 to < 400 copies/mL 

400 to < 1000 copies/mL

≥ 1000 copies/mL 

Missing (only applicable to M = F analysis)
Statistical comparison between each of the LEN-containing treatment groups (Treatment Groups 
1-3) and the B/F/TAF group (Treatment Group 4) will be performed. Point estimates and its 95% 
CIs will be estimated using stratum-adjusted MH proportion as described in Section 6.2.2. The 
associated p-values will be estimated based on the CMH test stratified by baseline HIV-1 RNA 
level (≤ 100,000 copies/mL or > 100,000 copies/mL).
6.4.
Subgroup Analysis
Subgroups defined in Section 3.4.1 will be performed for the proportion of subjects with HIV-1 
RNA < 50 copies/mL at Week 28 as determined by the US FDA-defined snapshot algorithm. 
Subgroup analysis will be performed on subjects who have reached Week 28 at the time for the 
Week 28 analysis in the FAS. Results will be descriptive and the associated 95% CIs will be 
constructed using Exact method.
6.5.
Changes from Protocol-Specified Efficacy Analyses
No change from protocol-specified efficacy analysis is planned. 


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7.
SAFETY ANALYSES
Safety data will be summarized for subjects in the Safety Analysis Set. All safety data collected 
up to the last exposure date for subjects who prematurely discontinued study drug or all available 
data for subjects who were still on study drug will be included in the table summary, unless 
specified otherwise. All collected data will be included in data listings. 
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of 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 provided in the 
AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to toxicity 
criteria specified in the protocol. The severity grade of events for which the investigator did not 
record severity will be categorized as “missing” for tabular summaries and data listings. The 
missing category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s 
choice, not that of the medical monitor. 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 the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs 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 AEs are defined as follows:

Any AEs leading to premature discontinuation of study drug, or

Any AEs with an onset date on or after the study drug start date and no later than the last 
exposure date after permanent discontinuation of the 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 dose 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 as follows:

Subjects who receive SC injection: the AE onset date is the same as or after the month and 
year (or year) of the first dose date of study drug

Subjects who do not receive SC injection: 
The AE onset is the same as or after the month and year (or year) of the first dose date of 
study drug, and
The AE onset date is the same as or before the month and year (or year) of the last 
exposure date
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dose 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 dose date of study drug will 
be considered treatment emergent.
When calculating the duration of event or time to onset, the following imputation rule will be 
used:
Missing start month/day: Jan 1/first day of the month will be used unless this is before the start 
date of study drug; in this case the study drug start date will be used;
Missing stop month/day: Dec 31/last day of the month will be used, unless this is after the last 
study date; in this case the last study date will be used.
Completely missing start or end dates will remain missing, with no imputation applied.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE incidence in Combined Severity Grade Subsets 
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.


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The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC and PT and by PT only for the following AE categories: 

TEAEs

TEAEs with Grade 3 or higher 

TEAEs with Grade 2 or higher 

TE treatment-related AEs

TE treatment-related AEs with Grade 3 or higher 

TE treatment-related AEs with Grade 2 or higher 

TE SAEs

TE treatment-related SAEs 

TEAEs leading to death (by SOC and PT only)

TEAEs leading to premature discontinuation of study drug

TEAEs leading to premature discontinuation of study 
Multiple events will be counted only once per subject in each summary. For summaries by SOC 
and PT, AEs will be summarized and listed first in alphabetical order of SOC and then by PT in 
descending order of total frequency within each SOC. For summarizes by PT only, AEs will be 
summarized and listed by PT in descending order of total frequency. For summaries by severity 
grade, the most severe grade will be used for those AEs that occurred more than once in an 
individual subject during the study. 
In addition, data listings will be provided for the following:

All AEs

All SAEs

All Deaths

All AEs with severity of Grade 3 or higher 

All AEs leading to discontinuation of study drug

All AEs leading to discontinuation of study
For each listing, whether the event is treatment emergent will be indicated.


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7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Study Drug Related Injection Site Reactions
Additional analysis of AEs will be performed for injection site reaction (ISR) related to study 
drug, which is defined as an AE related to study drug reported as any event within the MedDRA 
HLT of “Injection Site Reactions”. The following summaries will be provided for each SC 
injection visit (eg, Day 1, Week 28) and the overall for subjects in Treatment Groups 1 and 2.

Number of subjects received SC injection    

Number and percentage of subjects with study drug related ISRs   

Number and percentage of subjects with study drug related ISRs by grade 

Number and percentage of subjects with study drug related ISRs by PT 
The denominator for the percentage calculation for the by visit summary and the overall 
summary will be based on the total number of subjects who receive at least 1 SC injection at the 
visit of interest and the total number of subjects who receive at least 1 SC injection at any 
injection visit, respectively.
Duration of the ISR will also be calculated and summarized. Duration of a given ISR event is 
defined as the ISR stop date minus the ISR onset date plus 1 day. For ISR with ongoing stop 
date, stop date will be imputed as last study date or data cut date, whichever is the earliest. 
Duration of ISR events in days will be summarized using descriptive statistics. 
A by-subject listing for study drug-related ISRs and the corresponding duration will be provided.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include all available data at the time of the data cut date for the 
interim analysis. The analysis will be based on values reported in conventional units. When 
values are below the LOQ, they will be listed as such, and the closest imputed value will be used 
for the purpose of calculating summary statistics as specified in Section 3.7. Hemolyzed test 
results will not be included in the analysis, but they will be listed in by-subject laboratory 
listings.
Calcium Corrected for Albumin
Calcium corrected for albumin will be calculated and summarized for the study. The following 
formula will be used when both serum calcium and albumin results for a given blood drawn are 
available and serum albumin value is < 4.0 g/dL. 
Calcium corrected for albumin (mg/dL) = serum calcium (mg/dL) + 0.8 × (4.0 – albumin (g/dL))
Toxicity grading for calcium will be applied based on the corrected values.


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Estimated Glomerular Filtration Rate
The following formulae will be used to calculate the estimated glomerular filtration rate using 
Cockcroft-Gault formula (eGFRCG):
eGFRCG (mL/min) = [(140 – age (yrs)) × weight (kg) × (0.85 if female)] / (SCr (mg/dL) × 72),
where weight is total body mass in kilograms and SCr is serum creatinine.
Low-Density Lipoprotein
The following formulae will be used to calculate the low-density lipoprotein(LDL) using 
Friedewald formula when cholesterol, high-density lipoprotein(HDL), and triglyceride for a 
given blood drawn are available: 
LDL (mg/dL) = total cholesterol (mg/dL)– HDL (mg/dL) – triglyceride (mg/dL)/5; 
The fourth generation LDL is calculated from above Friedewald formula. The third generation 
LDL is a direct measurement from blood drawn. Both generation of LDL will be listed in the 
listing. Only fourth generation LDL calculated from the Friedewald formula will be used for 
analysis. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, (urine) chemistry, and urinalysis separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher based on 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events, Version 2.1 dated July 2017, will be flagged in the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for selected laboratory test as follows:

Baseline values 

Values at each postbaseline visit 

Change from baseline at each postbaseline visit 
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date of first dose of study drug. Change from baseline to a postbaseline visit will be defined as 
the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and maximum 
values will be displayed to the reported number of digits; SD values will be displayed to the 
reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.


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7.2.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 
dated July 2017, will be used to assign toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (ie, increased, decreased) will be presented separately.
For triglycerides, LDL (4th generation), and cholesterol, toxicity grading scale is for fasting test 
values, so nonfasting lipid results (or lipid results without a known fasting status) will not be 
graded or summarized by toxicity grades.
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline visit. If the relevant baseline laboratory value 
is missing, any abnormality of at least Grade 1 observed at any postbaseline visit will be 
considered treatment emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
subjects in the study with the given response at baseline and each scheduled postbaseline visit.
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Graded laboratory abnormalities 

Grade 3 or 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values. 
A by-subject listing of treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities, respectively, will be provided by subject ID number and 
visit in chronological order. This listing will include all test results that were collected 
throughout the study for the lab test of interest, with all applicable severity grades and abnormal 
flags displayed.


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7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI and vital signs 
as follows:

Baseline value

Values at each postbaseline visit 

Change from baseline at each postbaseline visit 
A baseline value will be defined as the last available value collected on or prior to the first dose 
date of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. Body weight, height, and BMI will be included in the vital signs listing, if 
space permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
7.4.1.
Nonstudy Drug Antiretroviral Medications
Any nonstudy drug ARV medications used prior to, during, or after the study (if collected) will 
be coded using the World Health Organization (WHO) Drug Dictionary for ARV medications. 
The WHO preferred name and drug code will be attached to the clinical database. All nonstudy 
drug ARV medications will be listed. No inferential statistics will be provided.
7.4.2.
Concomitant Non-ARV Medications
Concomitant non-ARV medications (ie, medications other than study drug that are taken while 
receiving study drug) will be coded using the WHO Drug Dictionary. The WHO preferred name 
and drug code will be attached to the clinical database. Use of concomitant medications from 
Study Day 1 up to the last exposure date will be summarized (number and percentage of 
subjects) by treatment group, WHO drug class and preferred name. Multiple drug use 
(by preferred name) will be counted only once per subject. The summary will be sorted 
alphabetically by drug class and then by decreasing total frequency within a class.
If the start or stop date of non-ARV medications is incomplete, the month and year (or year 
alone, if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARVs are concomitant or not. The medication is concomitant if the month and year of the 
start or stop (or year of the start or stop, if month is not recorded) of the medication does not 
meet either of the following criteria:

The month and year of start of the medication is after the last exposure date

The month and year of stop of the medication is before the first dose date of study drug


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If the start and stop date of non-ARV medications are complete, the start date is not after last 
exposure date and the stop date is not before first dose date, or the non-ARV medications are 
marked as ongoing and start date is on or before last exposure date, the non-ARV medications 
are concomitant.
Summaries of non-ARV concomitant medications will be based on the Safety Analysis Set. No 
formal statistical testing is planned. A by-subject listing for all non-ARV concomitant 
medications will be listed and sorted by subject ID number and administration date in 
chronological order.
7.5.
Electrocardiogram Results
7.5.1.
Investigator Electrocardiogram Assessment
The investigators’ assessment of ECG results (normal; abnormal, not clinically significant; 
abnormal, clinically significant) are collected at screening only. A by-subject listing for ECG 
assessment results will be provided by subject ID number.
7.6.
Other Safety Measures
A data listing will be provided for subjects experiencing pregnancy and subjects using/misusing 
any substances (eg, illicit drug) during the study, respectively. Physical examination was not 
collected in the eCRF. Therefore, it will not be included in the analysis.
7.7.
Subject Subgroup for Safety Endpoints 
Incidence of all treatment-emergent AEs will be repeated within each subgroup defined in 
Section 3.4.2 using the Safety Analysis set. No formal statistical testing is planned. 
7.8.
Changes from Protocol-Specified Safety Analyses
No change from protocol-specified safety analyses is planned. 


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PHARMACOKINETIC (PK) ANALYSES 
8.1. 
PK Sample Collection 
Version 1.0 
Blood samples will be collected to detennine PK (and metabolites, if applicable) in plasma at the 
following timepoints: 
For Treatment Groups 1 and 2: 
Plasma PK sampling will occm relative to dosing of LEN at the following time points for all 
subjects: 
• 
Days 1, 2, and 8: 
-
Predose (within 30 minutes of dosing) 
-
A single timed PK sample between 1 and 6 homs postdose 
I 
• 
At Day 15 and at all visits with SC LEN injections: A single predose PK sample will be 
collected 
• 
Staiiing at Week 4 visit, at all visits without SC LEN injections: A single anytime PK sample 
will be collected. 
I 
I 
I 
For Treatment Group 3: 
• 
Staiiing at Day 1 visit, a single anytime PK sample will be collected at all study visits 
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For Treatment Group 4:

Starting at Day 1 visit, a single anytime PK sample will be collected at all study visits.
Only plasma 
 samples collected through Week 16 last patient last visit (LPLV) 
date were analyzed and included in the Week 28 interim analysis. 
8.2.
PK Analyses Related to PK Sampling
8.2.1.
Estimation of PK Parameters
PK parameters will be estimated using Phoenix WinNonlin® software using standard 
noncompartmental methods. The linear/log trapezoidal rule will be used in conjunction with the 
appropriate noncompartmental model, with input values for dose level, dosing time, 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 0.
For area under the curve (AUC), samples BLQ of the bioanalytical assays occurring prior to the 
achievement of the first quantifiable concentration will be assigned a concentration value of 0 to 
prevent overestimation of the initial AUC. Samples that are BLQ at all other time points will be 
treated as missing data in WinNonlin. The nominal time point for a key event or dosing 
interval (τ) may be used to permit direct calculation of AUC over specific time intervals. The 
appropriateness of this approach will be assessed by the PK scientist on a profile-by-profile 
basis.
Pharmacokinetic parameters such as AUCtau, λz and t1/2 are dependent on an accurate estimation 
of the terminal elimination phase of drug. The appropriateness of calculating these parameters 
will be evaluated upon inspection of PK data on a profile-by-profile basis by the PK scientist.
8.2.2.
PK Parameters
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The analytes and parameters presented in Table 8-2 will be used to evaluate the PK objectives of 
the study. The PK parameters to be estimated in this study are listed and defined in the PK 
abbreviations section. 
Table 8-2. 
PK Parameters for Each Analyte 
Analyte 
Parameters 
TAF 
TFV 
BIC 
TFV-DP 
8.2.3. 
Statistical Analysis Methods 
Plasma concentrntion for LEN, TAF, TFV, and TFV-DP will be listedl!lll!
or all sub·ects and 
summarized b nominal time oint for subjects in the PK Analysis Set 
by treatment group and analyte. P asma concentration for 
BIC will not be summarized by sunnnaiy statistics but will be included in the data listing. 
PK ai·ameters estimated for T AF and TFV will be listed for all sub· ects. 
Summaiy statistics (n, mean, SD, coefficient of variation [%CV], median, min, max, Ql , and 
Q3) will be presented for both individual subject concentrntion data by time point and individual 
subject PK parameters by treatment group and analyte. Moreover, the geometi·ic mean, 95% CI, 
and the mean and SD of the natural log-ti·ansfo1med values will be presented for individual 
subject PK pai·ameter data. 
Individual concenb'ation data listings and sUilllnai·ies will include all subjects with concenti·ation 
data. The sample size for each time point will be based on the number of subjects with 
nonmissing concenb'ation data at that time point. The number of subjects with concenti·ation 
BLQ will be presented for each time point. For sUilllnaiy statistics, BLQ values will be b'eated as 
0 at predose and one-half of the lower LOQ for postdose time points. 
Individual PK parameter data listings and sUilllnai·ies will include all subjects for whom PK 
pai·ameter(s) can be derived. The sample size for each PK parameter will be based on the number 
of subjects with nonmissing data for that PK parameter. 
The following tables will be provided for each analyte by ti·eatment group and visit: 
• 
Individual subject concenb'ation data and summaiy statistics 
• 
Individual subject plasma PK parameters and sUilllnaiy statistics 
I 
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The following figures may be provided for each analyte by treatment group:

Mean (± SD) concentration data versus time (on linear and semilogarithmic scales)

Median (Q1, Q3) concentration data versus time (on linear and semilogarithmic scales)
Individual, mean, and median postdose concentration values that are ≤ LOQ will not be 
displayed in the figures and remaining points connected.
PK sampling details by subject, including procedures, differences in scheduled and actual draw 
times, and sample age will be provided in listings.
The molecular weight of TFV-DP (447.17 g/mol) and the density of 5000 million cells/mL will 
be used in the conversion of concentration from ng/million cells to µmol/L; where the value in 
ng/million cells * (5000/447.17) results in the value in µmol/L or µM.  
𝑛𝑔
𝑚𝑖𝑙𝑙𝑖𝑜𝑛 𝑐𝑒𝑙𝑙𝑠×
1 𝑛𝑚𝑜𝑙
447.17 𝑛𝑔×
1 µ𝒎𝒐𝒍
1000 𝑛𝑚𝑜𝑙× 5000 𝑚𝑖𝑙𝑙𝑖𝑜𝑛 𝑐𝑒𝑙𝑙𝑠
1 𝑚𝐿
× 1000 𝑚𝐿
𝑳
=  µ𝑚𝑜𝑙
𝐿
=  µ𝑀
8.2.4.
Sensitivity Analyses
Sensitivity analysis may be conducted for the key PK analyses if the PK scientist identifies PK 
data as questionable. The sensitivity analysis will exclude specific data from analyses, if 
appropriate. If a sensitivity analysis is deemed necessary, a listing of the PK parameter(s) data 
being excluded, with associated reason(s) provided by the PK scientist, will be generated.
8.2.5.
Changes from Protocol-Specified Pharmacokinetic Analysis
No change from the protocol-specified PK analyses is planned.


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9.
REFERENCES
Koch GG, Carr GJ, Amara IA, Stokes ME, Uryniak TJ. Categorical Data Analysis. Chapter 13 in 
Berry, D.A. (ed.).  Statistical Methodology in the Pharmaceutical Sciences. New 
York: Marcel Dekker, Inc., 1989:pp. 414-21. 
U. S. Department of Health and Human Services, Food and Drug Administration (FDA), Center 
for Drug Evaluation and Research (CDER). Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. 
Silver Spring, MD.  November, 2015.


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
nQuery Advisor(R) Version 7.0. Statistical Solutions, Cork, Ireland.
Phoenix WinNonlin® 7.0 Pharsigh Corporation, Princeton, NJ, 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
Appendix 2.
Flowchart of US FDA-defined Snapshot Algorithm(for Naïve Trial)
Appendix 3.
Programming Specification


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Appendix 1.
Schedule of Assessments
Screeninga
Day 
1b
Day 
2
Day 
8
Day 
15
Every 
6 weeks 
from 
Week 4 
to 
Week 28 
±2 Days
Week 38 
±2 Days
Week 54 
±2 Days
Week 64 
±2 Days
Week 80 
±2 Days
Post 
Week 80 
Visitsc 
±6 Days
30, 90, 
180 Day 
Follow-Upd
Early 
Terminatione
Written Informed 
Consent
X
Obtain demographic 
information
X
Medical History 
X
Complete Physical 
Examination
X
X
X
Xf
X
X
X
Symptom-Directed 
Physical 
Examination
X
X
Xg
X
X
X
X
Vital Signsh 
(including weight)
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG 
(supine)
X
Height
X
Hematologyi, 
Chemistryj, Lipid 
panelk, Urinalysis 
and Urine 
Chemistryl, CD4+ 
Cell Count
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Storage 
Sample
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy 
Testm
X
X
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Eveiy 
6weeks 
ti'Om 
Week4 
Post 
to 
Week8() 
30, 90, 
Day 
Day 
Week28 
Week38 
Week54 
Week64 
Week8() 
Visits' 
18()Day 
Early 
Scr'eel1ing" 
lb 
15 
±2 Days 
±2Days 
±2Days 
±2 Days 
±2 Days 
±6Days 
Follow-Upd 
Te11nination• 
91 
"U
I 
I
l
l 
SeiumFSH" 
X ·--1 --
Urine Pregnancy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Test"' 
HBV,HCVTesting 
X 
!I ••1 --
IDV-1 Genotyping 
X 
Phenotyping 
--1 --
PlasmaIDV-1 RNA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma Storage 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Sample 
--1 --
PKPlasma 
X 
X 
X 
X 
X 
X 
X 
X 
·. ~.: 
. . ' 
Dispensation• 
X 
X 
X 
X 
X 
X 
X 
Subcutaneous 
GS-0207 
X 
X 
X 
X 
X 
Administration' 
F/f AF Dispensationu 
X 
X 
X 
X 
X 
X 
X 
TAF Dispensationv 
X 
X 
X 
X 
X 
X 
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Screeninga
Day 
1b
Day 
2
Day 
8
Day 
15
Every 
6 weeks 
from 
Week 4 
to 
Week 28 
±2 Days
Week 38 
±2 Days
Week 54 
±2 Days
Week 64 
±2 Days
Week 80 
±2 Days
Post 
Week 80 
Visitsc 
±6 Days
30, 90, 
180 Day 
Follow-Upd
Early 
Terminatione
Bictegravir 
Dispensationw
X
X
X
X
X
X
B/F/TAF 
Dispensationx
X
X
X
X
X
Study Drug 
Accountability
X
X
X
X
X
X
X
X
X
X
QoL Administrationy
X
X
X
X
X
Injection Site 
Reaction Assessment 
Worksheetz
X
X
X
X
Adverse Events/ 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Screening evaluations must be completed within 30 days prior to Day 1
b
Day 1 tests and procedures must be completed prior to administration of the dose of study drug. Participants must begin dosing on the same day as Day 1
c
Assessments will be performed post Week 80 (Week 90, Week 106, Week 116, Week 132, Week 142) and will continue to alternate between every 10 weeks and every 
16 weeks with the visit window ±6 days.
d
Participants may be required to return to the clinic for a 30, 90 and 180-Day Follow-Up Visit after Early Termination visit. 
e
Within 72 hours of permanently discontinuing study. Counsel participant regarding the importance of continuing a complete ARV therapy in accordance to standard of care 
and refer participant to an appropriate HIV treatment facility.
f
Complete physical exam is only required at Week 28
g
Symptom directed physical to be completed at Weeks 4, 10, 16, and 22, as necessary
h
Vital signs – blood pressure, pulse, respiration rate, temperature, and weight
i
Hematology: CBC with differential and platelet count
j
Chemistries: Alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, lipase, magnesium, phosphorus, potassium, sodium, and uric acid. eGFR according to the Cockcroft-Gault formula
k
Fasting is not required for the lipid panel
l
Urinalysis and Urine Chemistry: including color & clarity, specific gravity, pH, glucose, ketones, bilirubin, urobilinogen, blood, nitrite, leukocyte esterase and microscopic 
(if microscopic elements are seen), urine protein, albumin, creatinine, phosphate, calcium, magnesium and uric acid
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m 
Women will have a serum test pe1fo1med at Screening. Urine pregnancy test will only be done for women of childbearing potential. In Treatment Groups 1 and 2, urine 
pregnancy tests should be confomed to be negative prior to subcutaneous GS-6207 administration. If any pregnancy test is positive, study dmg should be immediately 
intem1pted, and participant should come to the site for serum pregnancy test. 
n 
FSH test is required for women who are <54 years old and have stopped menstruating for :;:: 12 months but do not have documentation of ovarian honuonal failllle. 
o 
PK collection: For Treatment Groups 1 and 2, plasma PK sam lino will occlll relative to dosing of GS-6207 at Da s 1 2 and 8 redose (within 30 minutes of dosing) and a 
single timed PK sample between 1 and 6 hotu·s postdose. 
At Day 15 and all visits with SC 
GS-6207, a single predose PK sample will be collected. Startmg at Wee 4 an at a VISlts w, out SC GS-6207, a smg e anytime PK sample will be collected. PK sampling 
r 
I 
I 
will continue at visits past Week 80. 
For Treatment Grou s 3 and 4 a,tici ants, sta,ting at Da 1, a single an 
s 
reatment 
cup an 
·cup will receive oral GS-6207 lead in at Days 1 and 2 and will begin oral daily 
GS-6207 at Day 3. 
Treatment Group 1 and 2 Subcutaneous administration at Day 15 and every 26 weeks 
u 
Treatment Group 1, 2, and 3 F/TAF once daily for 28 weeks sta,ting at Day 1. Treatment Group 3 pa,t icipants will continue F/TAF until study completion. 
v 
Treatment Group 1 daily oral TAF to be initiated at Week 28 
w 
Treatment Group 2 daily oral BIC to be initiated at Week 28 
x 
Treatment Group 4 daily oral B/F/TAF 
y 
Prior to completion of other study procedm·es, pa,ticipants will complete HIVTSQ12, HIVDQoL, and EQ-ED-5L at Day 1 (except HIVTSQ12), Day 15 (HIVTSQ12 only), 
Week 4, Week 28, Week 54, Week 80. Injection Acceptability Scale and Ntuueric Pain Rating Scale to be completed at Day 15, Weeks 28, 54 and 80 (for Treatment Groups 1 
and 2 pa,ticipants only) after SC GS-6207 administration and completion of other study procedllles. 
z 
Provide Injection Site Reaction Assessment Worksheet and instruct the participants to measllle and report injection site reactions following the administration of the 
subcutaneous injections (for Treatment Group 1 and 2 pa,ticipants only) 
CONFIDENTIAL 
Page48 
13 April 2021 


Lenacapavir 
GS-US-200-4334 
Statistical Analysis Plan - Week 28 Interim Analysis 
Version 1.0 
Appendix 2. 
Flowchart of US FDA-defined Snapshot Algorithm(for Nai've Trial) 
The following flowchaii for US FDA-defined snapshot algorithm is based on the US FDA 
Guidance on Human Immunodeficiency Virns-1 Infection: Developing Antiretroviral Drngs for 
Treatment {U. S. Depa1iment of Health and Human Services 2015} 
Yes 
Is there at least I on-
treatment• HIV-I RNA 
collected in the Snapshot 
window? 
Is the last available on-treatment• 
HIV-I RNA in the Snapshot 
window< 50 copies/mL? 
Yes 
HIV-1 RNA < 
50 copies/mL 
0 
Is study dmg premanu·ely 
discontinued on or prior to the 
upper limit of the Snapshot 
window? 
Yes 
Is discontinuation of the study 
dmg due to Lack of Efficacy? 
No 
Is discontinuation of the study 
dmg due to AE/Death? 
Is the last available on-
treatment• HIV-I RNA < 
50 copies/mL 
Yes 
Yes 
No Virologic Data: 
No 
No Virologic Data: 
HIV-lRNA ::::: 
50 copies/mL 
Discontinued Study Drug 
Due to Other Reasons and 
Last HIV-1 RNA < 50 
copies/mL 
No Virologic Data: 
Discontinued Study 
Drug Due to AE/Death 
Missing Data during 
Window but on Study 
Drug 
• On-treatment data include all data collected up to 1 day after permanent discontinuation of study 
drug or all available data for subjects who were still on study drug. 
CONFIDENTIAL 
Page49 
13 April 2021 


Lenacapavir 
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Statistical Analysis Plan – Week 28 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 50
13 April 2021
Appendix 3.
Programming Specification
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
a) AGE (years) is calculated from the number of days between the DOB and Study Day 1,
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
AGE = the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened subjects refer to all subjects who are screened (ie, with non-missing screening 
date) and have a screening number. For summaries the same subject is counted only once.
3) Screen failure subjects are the subjects who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the subject was consent to.
4) Subjects in the randomized analysis set are defined as subjects randomized into the study. 
IXRSRAND is the source to determine whether the subject is randomized (ie, subject with 
non-missing RGMNDTN in the IXRSRAND dataset), and confirmed by the eCRF ENROLL 
dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) is derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if subject 
took at least 1 dose of study drug and assigned as blank if the subject was never dosed.
6) In the disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.
7) Body mass index (BMI) 
BMI will be calculated only at baseline as follows:
BMI = (weight [kg]) / (height [meters]2)
Baseline height and weight will be used for this calculation if available.


Lenacapavir 
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Statistical Analysis Plan – Week 28 Interim Analysis
Version 1.0
CONFIDENTIAL
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13 April 2021
8) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
CMH test for nominal variable (Y), the p-value from the general association test should be 
used for nominal variables:
proc freq;
tables trt * Y /cmh; /*general association test*/
run;
CMH test for ordinal variable (Y), the p-value from the row mean score test should be used 
for ordinal variables:
proc freq;
tables trt * Y / cmh2 ; /*row mean score test*/
run;
Kruskal-Wallis test for continuous variable (Y):
proc npar1way wilcoxon;
class trt; 
var Y;
run;
9) For race and ethnicity, “Not Permitted”, “Missing”, or “Other” will be excluded from 
percentage calculation and also excluded for p-value generation for categorical data analysis 
(eg, CMH test or Kruskal-Wallis test).
10) Study Day 1, Last Dose Date and Last Exposure Date
a) All the key dates were defined in Section 3.8.1. 
11) Study Day 1 and Last Dose Date
a) All the key dates were defined in Section 3.8.1.
b) Study Day 1 is defined as the earliest of the dose start dates from any Study Drug 
Administration eCRF (ie, EX, EX_ARV or EX_IV). 
c) Last Dose Date is defined for subjects who prematurely discontinued study drug 
according to Study Drug Completion eCRF(ie, SDRGCOMP). 
i)
For subjects who receive SC injection(ie, A subject has data in EX_IV.), the last dose 
date is defined as the latest nonmissing end date of the study drug used with LEN 
(ie, the last dose date in EX_ARV).
ii) For subjects who do not receive SC injection(ie, A subject has no data in EX_IV.), 
the last dose date is defined as the earliest of the last dose date of any study drug 
(ie, the earliest of last dose date in EX or EX_ARV).


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Statistical Analysis Plan – Week 28 Interim Analysis
Version 1.0
CONFIDENTIAL
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13 April 2021
d) Study drug administration: Oral reload will be recorded as an “Unscheduled” visit in the 
Study Drug Administration eCRF. Subjects with oral reload prior to the 1st dose of SC 
have “Unscheduled” dosing visits occurred prior to Day 15 visit. Subjects who received a 
total of 5 tablets of LEN (300 mg) (ie, 2 x 300 mg LEN tablets each for the first 2 days 
and 1 x 300 mg LEN tablet on the 8th day) prior to “Unscheduled” dosing visits followed 
by Day 15 visit will be classified as oral reload due to missing scheduled SC dosing. 
Otherwise, subjects will be classified as oral reload due to missing scheduled oral dosing 
visit.
12) Adherence to QD Study Drug(s)
a) Adherence based on 1 study drug(Treatment Groups 1, 2, and 4):
Adherence (%) =  100 ×
𝑇𝑜𝑡𝑎𝑙 No. of pills taken
Total No. of pills prescribed
=  100 ×
∑No. of pills taken at each dispensing period  for each study drug[1]
∑No. of pills prescribed at each dispensing period for each study drug[2]
b) Adherence based on 2 study drugs(Treatment Group 3):
13) Efficacy Analysis
a) For categorical efficacy response (eg, Subjects with HIV-1 RNA < 50 copies/mL as 
determined by US FDA-defined snapshot algorithm, M=F, or M=E Analyses): the 
proportion difference between LEN-containing regimen groups (Treatment Groups 1 
to 3) and the B/F/TAF group (Treatment Group 4) and its 95% CIs are calculated based 
on the MH proportion adjusted by baseline HIV-1 RNA stratum ( 100,000 vs. 
 100,000 copies/mL) (see SAP Section 6.2 and 6.3 for details). The following SAS code 
will be used to compute p-value, where brnac is the baseline HIV-1 RNA stratum, trtgrp 
is the treatment, and response is the categorical efficacy response.
proc freq data=adeff;
tables brnac*trtgrp*response/cmh; /*p value from general 
association*/
run;






[2]
]1[
drug
each 
for 
period
dispensing
each 
at 
prescribed
pills
of
No.
drug
each 
for 
period
dispensing
each 
at 
 taken 
pills
of
No.
100
prescribed
pills
of
No.
Total
 taken
pills
of
No.
Total
100
(%)
Adherence


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Statistical Analysis Plan – Week 28 Interim Analysis
Version 1.0
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b) All the ANOVA model for continuous efficacy variable (eg, CD4+): The differences in 
changes from baseline in log10 HIV-1 RNA and CD4+ cell count between treatment 
groups and the associated 95% CI will be constructed using an ANOVA, including 
baseline HIV-1 RNA stratum brnac, region stratum region, and treatment trtgrp as fixed 
effects in the model.
proc glm data=adeff;
class brnac region trtgrp;
model CD4=brnac region trtgrp;
lsmeans trtgrp /alpha=0.05 cl pdiff;
run;
14) Listing for US FDA-defined snapshot outcome:
In addition flag the values of HIV-1 RNA < 50 or ≥ 50 copies/mL for virologic outcomes.
Flag the last available HIV-1 RNA value while on treatment for the following categories:
a) HIV-1 RNA ≥ 50 copies/mL - Discontinued Study Drug Due to Other Reasons and 
Last Available HIV-1 RNA ≥ 50 copies/mL
b) No virologic Data - Discontinued Study Drug Due to Other Reasons and Last 
Available HIV-1 RNA < 50 copies/mL
15) Injection site reaction (ISR)
a) To summarize ISRs by injection visit, each study drug related ISR will be associated with 
one injection visit (eg, Day 15 SC injection, Week 28 SC Injection, Week 54 SC 
injection) based on the start date of the ISR. If the start date of the ISR is on or after a 
given injection visit date and prior to the next injection visit date, if available, the ISR 
will be associated with that injection visit.
b) For ISR summarized by PT:
i)
For the overall summary (ie, subjects received at least one injection), multiple ISRs 
with the same PT will only be counted once per subject for each PT.
ii) For by visit summary (ie, subjects received injection for a given injection visit), 
multiple ISRs associated with the injection visit of interest with the same PT will only 
be counted once per subject for each PT.
c) For ISR summarized by grade:
i)
For the overall summary (ie, subjects received at least one injection), the most severe 
grade based on all ISRs will be used.
ii) For by visit summary (subjects received injection for a given injection visit), the most 
severe grade from all ISRs associated with the injection visit of interest will be used.


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Statistical Analysis Plan – Week 28 Interim Analysis
Version 1.0
CONFIDENTIAL
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13 April 2021
16) Concomitant nonstudy-drug ARV medications (ie, ARV medications other than study drug 
that are taken on or after first dose date) will be flagged in “Antiviral Medication” listings.
17) Graded Laboratory Abnormalities Summary 
The following labels will be used for treatment-emergent laboratory abnormalities and 
treatment-emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Hemoglobin (Hb)
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
Hematology
WBC
Decrease
WBC (Decreased)
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
GGT
Increase
GGT (Increased)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Fasting)
Decrease
Serum Glucose (Fasting, Hypoglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Decrease
Serum Glucose (Nonfasting, Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Urea Nitrogen (BUN)
Increase
Urea Nitrogen (Increased)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Chemistry
Uric Acid
Decrease
Uric Acid (Hypouricemia)
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine Protein
Increase
Urine Protein (Proteinuria)
Urinalysis
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative)


Lenacapavir 
GS-US-200-4334
Statistical Analysis Plan – Week 28 Interim Analysis
Version 1.0
CONFIDENTIAL
Page 55
13 April 2021
18) Clarification for “Pharmacokinetic Sampling Details and Concentrations” listings
“Sample age” will be added in this listing, defined as the duration in days between 
sample collection date and assay date, ie, sample age = assay date – sample collection 
date + 1. 
Scheduled PK sampling time for intensive PK samples at predose is 5 mins prior to 
dosing time. 
SAMTIME is calculated as the duration in hours between the dosing time before sample 
collected and sample collection time, except for intensive PK samples at predose. 
SAMTIME for intensive PK samples at predose is calculated as the duration in hours 
between the dose time on the same day (ie, right after the predose sample collection) and 
sample collection time.


GS-US-200-4334-Week28-SAP-v1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Pharmacology
eSigned
13-Apr-2021
23:13:04
Biostatistics eSigned
13-Apr-2021
23:24:08
Clinical Research eSigned
14-Apr-2021
02:47:45
PPD
PPD
PPD