A Phase 2a Study to Evaluate the Safety and Tolerability of a Regimen of Dual Anti-HIV Envelope Antibodies, VRC07-523LS and CAP256V2LS, in a Sequential Regimen With a TLR7 Agonist, Vesatolimod, in Early Antiretroviral-Treated HIV-1 Clade C-Infected Women
Phase: PHASE2
Conditions: HIV-1-infection
Sponsor: Gilead Sciences

CLINICAL STUDY PROTOCOL
Study Title:
A Phase 2a Study to Evaluate the Safety and Tolerability of a 
Regimen of Dual Anti-HIV Envelope Antibodies, VRC07-523LS 
and CAP256V2LS, in a Sequential Regimen with a TLR7 
Agonist, Vesatolimod, in Early Antiretroviral-Treated HIV-1 
Clade C-Infected Women 
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
This is a non-IND study
Not Applicable
Not Available
Indication:
HIV-1 Infection
Protocol ID:
GS-US-382-5445
Contact Information:
The Medical Monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol Version/Date:
Original:
18 December 2020
Amendment 1:
17 June 2021
Amendment 2:
26 August 2022
Amendment 3:
07 October 2022
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The information contained in this document, particularly unpublished data, is the property or 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.
NCT05281510
GILEAU 

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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF APPENDICES.................................................................................................................................................5
LIST OF IN-TEXT TABLES .........................................................................................................................................5
LIST OF IN-TEXT FIGURES........................................................................................................................................5
PROTOCOL SYNOPSIS................................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................................26
1.
INTRODUCTION................................................................................................................................................30
1.1.
Background..............................................................................................................................................30
1.2.
Investigational Medicinal Products .........................................................................................................32
1.2.1.
Nonclinical Studies of Vesatolimod......................................................................................32
1.2.2.
Nonclinical Studies of CAP256V2LS...................................................................................33
1.2.3.
Nonclinical Studies of VRC07-523LS ..................................................................................33
1.2.4.
Clinical Studies of Vesatolimod............................................................................................34
1.2.5.
Clinical Studies of CAP256V2LS.........................................................................................43
1.2.6.
Clinical Studies of VRC07-523LS ........................................................................................45
1.3.
Rationale for This Study..........................................................................................................................47
1.4.
Rationale for Dose Selection...................................................................................................................48
1.4.1.
Rationale for Dose Selection of Vesatolimod .......................................................................48
1.4.2.
Rationale for Dose Selection of CAP256V2LS ....................................................................48
1.4.3.
Rationale for Dose Selection of VRC07-523LS ...................................................................49
1.5.
Risk/Benefit Assessment for the Study ...................................................................................................49
1.6.
Compliance..............................................................................................................................................52
2.
OBJECTIVES.......................................................................................................................................................53
3.
STUDY DESIGN.................................................................................................................................................54
3.1.
Endpoints.................................................................................................................................................54
3.2.
Study Design ...........................................................................................................................................55
3.3.
Study Treatments.....................................................................................................................................58
3.4.
Duration of Treatment .............................................................................................................................58
3.5.
Protocol-specific Discontinuation Criteria..............................................................................................58
3.6.
End of Study............................................................................................................................................58
3.7.
Poststudy Care.........................................................................................................................................59
3.8.
Source Data .............................................................................................................................................59
3.9.
Biomarker Testing...................................................................................................................................59
3.9.1.
Biomarker Samples to Address the Study Objectives...........................................................59
3.9.2.
Biomarker Samples for Optional Future Research................................................................60
3.9.3.
Biomarker Samples for Optional Pharmacogenomic Research ............................................60
4.
PARTICIPANT POPULATION..........................................................................................................................61
4.1.
Number of Participants and Participant Selection...................................................................................61
4.1.1.
Participant Replacement........................................................................................................61
4.2.
Inclusion Criteria.....................................................................................................................................61
4.3.
Exclusion Criteria....................................................................................................................................62
5.
INVESTIGATIONAL MEDICINAL PRODUCTS.............................................................................................64
5.1.
Treatment Assignment.............................................................................................................................64
5.2.
Description and Handling........................................................................................................................64

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5.2.1.
Formulation ...........................................................................................................................64
5.2.2.
Packaging and Labeling ........................................................................................................64
5.2.3.
Storage and Handling ............................................................................................................65
5.3.
Dosage and Administration .....................................................................................................................65
5.4.
Prior and Concomitant Medications........................................................................................................66
5.5.
Accountability for Investigational Medicinal Product ............................................................................68
5.5.1.
Investigational Medicinal Product Return or Disposal .........................................................68
6.
STUDY PROCEDURES......................................................................................................................................69
6.1.
Participant Enrollment and Treatment Assignment ................................................................................69
6.2.
Pretreatment Assessments .......................................................................................................................69
6.2.1.
Screening Visit ......................................................................................................................69
6.2.2.
Prebaseline/Day −13 Assessments ........................................................................................71
6.2.3.
Treatment Assignment...........................................................................................................72
6.3.
Treatment Assessments–Period 1............................................................................................................72
6.3.1.
Treatment Assessments–Baseline/Day 0...............................................................................73
6.3.2.
Treatment Assessments–Days 1 to 28...................................................................................75
6.3.3.
ATI Eligibility Criteria..........................................................................................................77
6.4.
Treatment Assessments–Period 2............................................................................................................77
6.4.1.
Treatment Assessments–Days 29 to 133...............................................................................78
6.5.
Posttreatment Assessments–Period 3 ......................................................................................................80
6.5.1.
Treatment Assessments–Days 134 to 336.............................................................................81
6.5.2.
End of Period 3 Visit .............................................................................................................82
6.6.
Posttreatment Assessments–Period 4 ......................................................................................................83
6.6.1.
Treatment Assessments–Days 337 to 413.............................................................................86
6.7.
Posttreatment Assessments–Early Study Drug Discontinuation Visit ....................................................87
6.8.
End-of-Study Visit...................................................................................................................................88
6.9.
Assessments for Early Discontinuation from Study................................................................................90
6.9.1.
Criteria for Discontinuation of Study Drug...........................................................................90
6.9.2.
Follow Up and Procedures After Early Discontinuation of Study Drug...............................91
6.9.3.
Follow Up and Procedures After Treatment Completion......................................................92
6.9.4.
End-of-Follow-Up Visit ........................................................................................................93
6.10.
Management of Virologic Failure ...........................................................................................................94
6.10.1.
Virologic Rebound ................................................................................................................94
6.10.2.
Viremia at Last Visit .............................................................................................................94
6.11.
End of Study............................................................................................................................................94
6.12.
Poststudy Care.........................................................................................................................................94
6.13.
Sample Storage........................................................................................................................................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.........................................................................................................95
7.1.3.
Study Drugs and Gilead Concomitant Therapy Special Situations Reports .........................96
7.2.
Assessment of Adverse Events and Serious Adverse Events..................................................................97
7.2.1.
Assessment of Causality for Study Drugs and Procedures ...................................................97
7.2.2.
Assessment of Severity..........................................................................................................97
7.3.
Investigator Reporting Requirements and Instructions ...........................................................................98
7.3.1.
Requirements for Collection Prior to Study Drug Initiation .................................................98
7.3.2.
Adverse Events......................................................................................................................98
7.3.3.
Serious Adverse Events.........................................................................................................98
7.3.4.
Study Drug Special Situations Reports .................................................................................98
7.3.5.
Concomitant Therapy Reports...............................................................................................99
7.4.
Reporting Process for Serious Adverse Events and Special Situation Reports.......................................99

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7.4.1.
Serious Adverse Event Reporting Process ............................................................................99
7.4.2.
Special Situations Reporting Process ..................................................................................100
7.5.
Gilead Reporting Requirements ............................................................................................................102
7.6.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events.........................................................................................................................102
7.7.
Toxicity Management............................................................................................................................103
7.7.1.
Safety Monitoring Plan for CRS .........................................................................................103
7.7.2.
Management of Other Toxicities.........................................................................................105
8.
STATISTICAL CONSIDERATIONS...............................................................................................................106
8.1.
Analysis Objectives and Endpoints.......................................................................................................106
8.1.1.
Analysis Objectives.............................................................................................................106
8.1.2.
Primary Endpoints...............................................................................................................107
8.1.3.
Secondary Endpoints...........................................................................................................107
8.2.
Planned Analyses...................................................................................................................................108
8.2.1.
Interim Analysis ..................................................................................................................108
8.2.2.
Final Analysis......................................................................................................................109
8.3.
Analysis Conventions............................................................................................................................109
8.3.1.
Analysis Sets .......................................................................................................................109
8.3.2.
Data Handling Conventions ................................................................................................110
8.4.
Demographic and Baseline Characteristics Analysis............................................................................110
8.5.
Efficacy Analysis...................................................................................................................................110
8.5.1.
Virology Analysis................................................................................................................110
8.5.2.
Other Efficacy Analysis ......................................................................................................110
8.6.
Safety Analysis......................................................................................................................................110
8.6.1.
Extent of Exposure ..............................................................................................................111
8.6.2.
Adverse Events....................................................................................................................111
8.6.3.
Laboratory Evaluations .......................................................................................................111
8.7.
Pharmacokinetic Analysis .....................................................................................................................112
8.9.
Pharmacodynamic/Immunology Analysis.............................................................................................112
8.10.
Immunogenicity Analysis......................................................................................................................113
8.11.
Sample Size ...........................................................................................................................................113
8.12.
Data Monitoring Committee..................................................................................................................113
9.
RESPONSIBILITIES.........................................................................................................................................114
9.1.
Investigator Responsibilities .................................................................................................................114
9.1.1.
Good Clinical Practice.........................................................................................................114
9.1.2.
Financial Disclosure ............................................................................................................114
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval..............................................................................................................................114
9.1.4.
Informed Consent ................................................................................................................114
9.1.5.
Confidentiality.....................................................................................................................115
9.1.6.
Study Files and Retention of Records .................................................................................115
9.1.7.
Case Report Forms ..............................................................................................................117
9.1.8.
Investigator Inspections.......................................................................................................117
9.1.9.
Protocol Compliance ...........................................................................................................117
9.2.
Sponsor Responsibilities .......................................................................................................................117
9.2.1.
Protocol Modifications ........................................................................................................117
9.2.2.
Study Report and Publications ............................................................................................118
9.3.
Joint Investigator/Sponsor Responsibilities ..........................................................................................118
9.3.1.
Payment Reporting ..............................................................................................................118
9.3.2.
Access to Information for Monitoring.................................................................................118
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9.3.3.
Access to Information for Auditing or Inspections .............................................................118
9.3.4.
Study Discontinuation .........................................................................................................118
10.
REFERENCES...................................................................................................................................................119
11.
APPENDICES....................................................................................................................................................123
LIST OF APPENDICES
Appendix 1.
Investigator Signature Page...................................................................................................124
Appendix 2a.
Study Procedures Table.........................................................................................................125
Appendix 2b.
Follow-up Period: Study Procedures Table...........................................................................131
Appendix 3.
Management of Adverse Events and Laboratory Abnormalities ..........................................133
Appendix 4.
Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.........134
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements..................................................................................................155
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (Centers for Disease Control 
and Prevention [CDC] Guidelines)........................................................................................158
Appendix 7.
Pandemic Risk Assessment and Mitigation Plan ..................................................................159
LIST OF IN-TEXT TABLES
Table 1.
Serum PK Parameters Following Single Dose IV Administration of 1, 5, 20, or 40 
mg/kg VRC07-523LS..............................................................................................................47
Table 2.
Medications Prohibited............................................................................................................67
Table 3.
Period 1 Study Visits and Study Drug Administration............................................................73
Table 4.
Period 2 Study Visits and Study Drug Administration............................................................78
Table 5.
Period 3 Study Visits and Study Drug Administration............................................................80
Table 6.
Periods 4A and 4B Study Visits and Study Drug Administration...........................................84
Table 7.
The Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 
Grading Scale for Infusion-related Reaction and Cytokine Release Syndrome....................104
LIST OF IN-TEXT FIGURES
Figure 1.
Serum PK Following Single Dose IV Administration of 1, 5, 20, or 40 mg/kg 
VRC07-523LS.........................................................................................................................46
Figure 2.
Study Schema ..........................................................................................................................56

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 2a Study to Evaluate the Safety and 
Tolerability of a Regimen of Dual Anti-HIV Envelope 
Antibodies, VRC07-523LS and CAP256V2LS, in a 
Sequential Regimen with a TLR7 Agonist, 
Vesatolimod, in Early Antiretroviral-Treated HIV-1 
Clade C-Infected Women
IND Number:
EudraCT Number:
Clinical Trials.gov Identifier:
This is a non-IND study
Not Applicable
Not Available
Study Centers Planned:
Single center in South Africa
Objectives:
The primary objective of this study is as follows:

To evaluate the safety and tolerability of dual 
anti-HIV envelope monoclonal antibodies (mAbs), 
VRC07-523LS and CAP256V2LS, in a sequential 
regimen with a toll-like receptor (TLR)7 agonist, 
vesatolimod (VES), when administered in 
virologically suppressed HIV-1 Clade C-infected 
women on antiretroviral therapy (ART) and during 
analytical treatment interruption (ATI)
The secondary objectives of this study are as follows:

To evaluate the pharmacokinetics (PK) of 
VRC07-523LS, CAP256V2LS, and VES

To evaluate whether VRC07-523LS and 
CAP256V2LS induce anti-VRC07-523LS and/or 
anti-CAP256V2LS antibodies

To evaluate the effect of VRC07-523LS and 
CAP256V2LS in a sequential regimen with VES 
on viral control or the need for resumption of ART 
following an ATI

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s:
s 
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Study Design:
Number of Participants Planned:
Approximately 25 participants in total
Target Population:
Nonpregnant, nonlactating female adults recruited 
from the Females Rising through Education, Support, 
and Health (FRESH) acute HIV infection cohort, who 
have HIV-1 and have been virologically suppressed 
(HIV-1 RNA < 50 copies/mL) on ART for at least 12 
consecutive months prior to screening. Two or less 
unconfirmed virologic elevations of ≤ 1000 copies/mL 
at nonconsecutive visits within 12 months are 
acceptable.
Duration of Treatment:
Participants will receive administration of study drugs 
for a maximum of 18 weeks.
Diagnosis and Main Eligibility 
Criteria:
Participants with HIV-1 Clade C who meet the 
following criteria:

Females recruited from the FRESH acute HIV 
infection cohort

Age ≥ 18 years

Plasma HIV-1 RNA levels < 50 copies/mL at the 
screening visit

Documented plasma HIV-1 RNA viral load must 
be < 50 copies/mL for 12 consecutive months prior 
to screening:
o
≤ 2 detectable (≤ 1000 copies/mL) HIV-1 RNA 
measurements are acceptable
o
Determinations below the level of quantitation 
will be considered as detectable at the assay’s 
threshold level

Documented history of viral sensitivity to 
VRC07-523LS or CAP256V2LS at the screening 
visit

ART selection and allowances:
o
On ART regimen for ≥ 12 consecutive months 
prior to screening. The following agents are 
allowed as part of the current ART regimen: 
nucleoside reverse-transcriptase inhibitors, 
raltegravir, bictegravir, dolutegravir, and 
rilpivirine.

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o
A change in ART regimen ≤ 45 days prior to 
the prebaseline/Day −13 visit for reasons other 
than virologic failure (eg, tolerability, 
simplification, drug-drug interaction profile) is 
allowed. If the participant’s ART regimen is 
changed, a plasma HIV-1 RNA level 
< 50 copies/mL at the prebaseline/Day −13 
visit will be required to confirm eligibility.
o
Availability of a fully active alternative ART 
regimen, in the opinion of the investigator, in 
the event of discontinuation of the current ART 
regimen with development of resistance.

Hemoglobin ≥ 10.0 g/dL

White blood cells ≥ 2500 cells/μL

Platelets ≥ 125,000/mL

Absolute neutrophil counts ≥ 1000 cells/μL

CD4+ T cell count ≥ 500 cells/μL

Alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), and bilirubin ≤ 2 × upper 
limit of normal

Creatinine clearance ≥ 60 mL/min

In women of childbearing potential:
o
Agreement to follow study contraceptive 
requirements

Participants with coinfection and/or 
immunosuppression as described below will be 
excluded:
o
Autoimmune disease requiring ongoing 
immunosuppression (except in the case of mild 
autoimmune disease that only requires topical 
treatments)
o
Evidence of chronic hepatitis B virus (HBV) 
infection (defined as positive hepatitis B 
surface antigen OR positive hepatitis B core 
antibody and negative hepatitis B surface 
antibody)

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
Evidence of current hepatitis C virus (HCV) 
infection (defined as positive hepatitis C antibody 
and HCV RNA > lower limit of quantitation)
■
positive anti-HCV antibody and negative 
HCV polymerase chain reaction results are 
acceptable
o
Documented history of pre-ART CD4+ T cell 
count nadir < 200 cells/μL (unknown pre-ART 
CD4+ T cell count nadir is acceptable)
o
History of opportunistic illness indicative of 
Stage 3 HIV
o
Acute febrile illness within 4 weeks prior to the 
first dose
Study Procedures/
Frequency:
Screening
Participants will be evaluated for eligibility. The 
screening visit assessments will include the following:

Obtain written informed consent

PBMC sample for testing of viral sensitivity to the 
VRC07-523LS and CAP256V2LS mAbs, if not 
previously conducted

Blood and urine tests (hematology, serum 
chemistry, metabolic assessment, HIV-1 RNA, 
serum pregnancy, creatinine clearance, 
CD4+/CD8+ T cell counts, and urinalysis). 
Additional tests will include HBV and HCV 
serology

12-lead electrocardiogram (ECG)

Complete physical examination, vital signs, height, 
body weight, and medical (including HIV) history

Serum follicle-stimulating hormone test (for 
females < 54 years old who have ceased 
menstruating for ≥ 12 months, but are not 
permanently sterile or do not have documentation 
of ovarian hormonal failure)

Documentation of participant agreement to follow 
study contraceptive requirements

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
Documentation of HIV staging at detection using 
standard markers (eg, HIV-1 RNA, p24 antigen, 
fourth generation combination antigen/antibody 
enzyme-linked immunosorbent assay, HIV-1 
Western blot), duration of viremia during acute HIV 
infection and peak HIV RNA
Eligible participants should return to the study center 
for prebaseline/Day −13 assessments within 5 weeks of 
the screening visit.
Prebaseline/Day −13 Assessments
The prebaseline/Day −13 visit is to be completed 
within 35 days of the screening visit. The 
prebaseline/Day −13 visit will include the following 
assessments:

Review of inclusion/exclusion criteria to confirm 
participant eligibility

Review of adverse events (AEs) and changes in 
concomitant medications

Review medical history

Symptom-directed physical examination as needed, 
and body weight

Birth control will be checked and replaced, 
if required

Urine pregnancy test

Plasma HIV-1 RNA

Blood and urine tests (hematology, serum 
chemistry, creatinine clearance, and urinalysis). 
Additional blood tests will also be taken for 
virology and biomarker analyses
Treatment Assignment
Obtain participant number and assign treatment to the 
participant in the interactive web response system. The 
participant number assignment and treatment 
assignment will be performed in clinic at the 
baseline/Day 0 visit, provided that all screening 
procedures have been completed and participant 
eligibility has been confirmed. If a participant’s ART 
regimen is changed ≤ 45 days prior to 

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prebaseline/Day −13, plasma HIV-1 RNA 
< 50 copies/mL at prebaseline/Day −13 visit is 
required to confirm eligibility.
Period 1 (Days 0 to 28)
Participants will have up to 10 visits over 4 weeks.
Sentinel Dosing: Five participants will be enrolled 
first, to conduct visits and assessments up to Day 21. 
Upon review of the safety data and confirmation from 
an external data monitoring committee, up to a further 
20 participants will be enrolled into Period 1.
The following assessments are to be completed:

Dosing of VRC07-523LS and CAP256V2LS in a 
sequential regimen with VES:
Doses 1 to 3 of VES will be administered orally 
on baseline/Day 0, Day 14, and Day 28. One 
dose of VRC07-523LS and 1 dose of 
CAP256V2LS will be administered 
sequentially by intravenous (IV) infusions on 
Day 7.
Participants will continue to take their ART 
during this period (Days 0 to 28).
Fasted status and food consumption will be 
checked prior to dosing.
Participants will remain at the site for 24 hours 
after Dose 1 of VES, for at least 8 hours after 
Dose 2 of VES, and for at least 4 hours after 
Dose 3 of VES for monitoring. If participants 
experience significant influenza-like AEs (eg, 
moderate or severe pyrexia, chills, headache, 
myalgia, fatigue, malaise, joint pain) after the 
first 2 VES doses, or if dose is escalated to 
8 mg, monitoring may be extended to > 4 hours 
for subsequent doses.
Participants will remain at the site for 8 hours 
after the infusions of VRC07-523LS and 
CAP256V2LS for monitoring.
If participants experience new or worsening symptoms, 
postdose safety monitoring should be extended.

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
Vital signs (blood pressure, pulse, respiration rate, 
oxygen saturation, and temperature) at predose and 
frequent intervals following each scheduled dose of 
VES, VRC07-523LS, and CAP256V2LS:
Dose 1 of VES: Prior to administration and 
then at 1, 2, 4, 8, 12, 18, and 24 hours after 
administration. If the participant experiences 
new or worsening symptoms, evaluate for signs 
and symptoms of cytokine release syndrome 
(CRS), including vital signs.
Dose 2 of VES: Prior to administration and 
then at 1, 2, 4, and 8 hours after administration. 
If the participant experiences new or worsening 
symptoms, evaluate for signs and symptoms of 
CRS, including vital signs.
Dose 3 of VES: Prior to administration and 
then at 1, 2, and 4 hours after administration. If 
the participant experiences new or worsening 
symptoms, evaluate for signs and symptoms of 
CRS, including vital signs.
VRC07-523LS and CAP256V2LS: Prior to 
administration and at 1, 2, 4, and 8 hours after 
administration. If the participant experiences 
new or worsening symptoms, evaluate for signs 
and symptoms of CRS, including vital signs.

Plasma HIV-1 RNA and Plasma HIV-1 resistance 
testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART will be 
performed at each weekly visit.

Blood and urine safety monitoring (hematology, 
serum chemistry, creatinine clearance, and 
urinalysis) will be performed at all visits except 
Days 8 and 9. Additional blood samples will also 
be taken for PK, virology, and biomarker analyses 
at specified visits.

CD4+ and CD8+ T cell absolute count, percentage, 
and CD4/CD8 ratio will be evaluated at a visit 
every 2 weeks.

Body weight

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
Urine pregnancy test at the baseline/Day 0 and 
Day 28 visits

Birth control will be checked at every visit and 
replaced, if required.

Symptom-directed physical examination will be 
performed at every visit.

Adverse events and concomitant medications will 
be assessed at each visit. Participants will be 
reminded to report all symptoms, including flu-like 
symptoms (eg, fatigue, pyrexia, chills, myalgia, 
joint pain, or headache) or other unexpected 
symptoms.
Analytical treatment interruption eligibility will be 
assessed at Day 28, to determine whether the 
participant can proceed to Period 2.
Period 2 (Days 29 to 133)
Participants will have up to 18 visits over 15 weeks. 
The following assessments are to be completed:

Dosing of VES:
Doses 4 to 10 of VES will be administered 
orally at Days 42, 56, 70, 84, 98, 112, and 126
Participants will remain at the site for at least 
4 hours after dosing for monitoring. If 
participants experience significant 
influenza-like AEs (eg, moderate or severe 
pyrexia, chills, headache, myalgia, fatigue, 
malaise, joint pain) after the first 2 VES doses, 
monitoring may be extended to > 4 hours for 
subsequent doses.
No ART will be administered and ATI will 
start from Day 35.
Fasted status and food consumption will be 
checked prior to dosing

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
Vital signs (blood pressure, pulse, respiration rate, 
oxygen saturation, and temperature) at predose and 
at frequent intervals following each scheduled 
dose:
Doses 4 to 10 of VES: Prior to administration 
and at 1, 2 and 4 hours after administration. If 
the participant experiences abnormal vital 
signs, new or worsening symptoms, evaluate 
for signs and symptoms of CRS, including vital 
signs.

Plasma HIV-1 RNA and Plasma HIV-1 resistance 
testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART will be 
performed at Day 42 and at each visit every 
2 weeks thereafter.

Blood and urine safety monitoring (hematology, 
serum chemistry, creatinine clearance, and 
urinalysis) will be performed at Day 42 and at each 
visit every 2 weeks. Additional blood samples will 
also be taken for PK, virology, and biomarker 
analyses at required visits.

CD4+ and CD8+ T cell absolute count, percentage, 
and CD4/CD8 ratio will be evaluated at Day 42 
and each visit every 2 weeks.

Body weight at Day 42 and at each visit every 
2 weeks

Urine pregnancy test at Day 42 and at each visit 
every 4 weeks

Birth control will be checked at every visit and 
replaced, if required.

Known HIV-1 seronegative sexual partners of 
enrolled study participants may be referred for HIV 
preexposure prophylaxis (PrEP) to decrease the 
risk of HIV transmission during ATI.

Symptom-directed physical examination will be 
performed at every visit

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
Adverse events and concomitant medications will 
be assessed at each visit. Participants will be 
reminded to report all symptoms, including flu-like 
symptoms (eg, fatigue, pyrexia, chills, myalgia, 
joint pain, or headache) or other unexpected 
symptoms
Period 3 (Days 134 to 336)
Participants will have up to 14 study visits every 
2 weeks for a total of 29 weeks. At the end of Period 3, 
all participants will be required to complete an 
end-of-Period 3 visit prior to moving into Period 4.
No study drug (VES, VRC07-523LS, CAP256V2LS) 
or ART will be administered in this period.
The following assessments are to be completed:

Vital signs (blood pressure, pulse, respiration rate, 
oxygen saturation, and temperature) at Day 147 
and at each visit every 4 weeks

Plasma HIV-1 RNA and plasma HIV-1 resistance 
testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART will be 
performed at a visit every 2 weeks

CD4+ and CD8+ T cell absolute count, percentage, 
and CD4/CD8 ratio will be evaluated at Day 147 
and at each visit every 4 weeks

Blood and urine safety monitoring (hematology, 
serum chemistry, creatinine clearance, and 
urinalysis) will be performed at Day 147 and at 
each visit every 4 weeks. Additional blood samples 
will also be taken for PK, virology, and biomarker 
analyses at required visits.

Body weight at Day 147 and at each visit every 
4 weeks

Urine pregnancy test at Day 147 and at each visit 
every 4 weeks

Birth control will be checked at every visit and 
replaced, if required.

Known HIV-1 seronegative sexual partners of 
enrolled study participants may be referred for HIV 
PrEP to decrease the risk of HIV transmission 
during ATI.

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
Symptom-directed physical examination at 
Day 147 and at each visit every 4 weeks.

Adverse events and concomitant medications will 
be assessed at each visit. Participants will be 
reminded to report all symptoms, including flu-like 
symptoms (eg, fatigue, pyrexia, chills, myalgia, 
joint pain, or headache) or other unexpected 
symptoms.
End-of-Period 3 Visit
This visit will be completed at the end of Period 3 or if 
ART restart criteria are met prior to starting Period 4A. 
The assessments will include AEs and concomitant 
medication review, blood tests, vital signs, 
symptom-directed physical examination, body weight, 
and a 12-lead ECG.
Period 4 (Days 337 to 413)
Participants who have remained virologically 
suppressed (plasma HIV-1 RNA < 50 copies/mL) or 
have not met the ART restart criteria by the end of 
Period 3 will continue in either Period 4A and restart 
ART for 12 weeks, or Period 4B and remain off ART 
for a 12-week ATI extension. The choice of Period 4A 
or 4B will be at the discretion of the participant and 
investigator.
Participants who meet the ART restart criteria prior to 
the end of Period 3 may also take part in Period 4A.
Participants will complete 6 study visits scheduled 
every 2 weeks over a 12-week period and will 
conclude with a separate end-of-study visit.
The following assessments are to be completed:

Plasma HIV-1 RNA and plasma HIV-1 resistance 
testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART will be 
performed at a visit every 2 weeks during ART 
restart (Period 4A) and ATI extension (Period 4B)

Blood safety monitoring (hematology, serum 
chemistry, creatinine clearance, and urinalysis) will 
be performed at Day 343 and at each visit every 
4 weeks (Periods 4A and 4B). Additional blood 
samples will also be taken for PK, virology, and 
biomarker analyses at required visits

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
CD4+ and CD8+ T cell absolute count, percentage, 
and CD4/CD8 ratio will be evaluated at Day 343 
and at each visit every 4 weeks (Periods 4A and 
4B)

Urine pregnancy test at the first ART restart visit 
and every 4 weeks thereafter (Period 4A) and every 
4 weeks during the ATI extension (Period 4B)

Body weight at Day 343 and at each visit every 
4 weeks (Periods 4A and 4B)

Birth control will be checked at every visit and 
replaced, if required (Periods 4A and 4B).

Symptom-directed physical examination at 
Day 343 and at each visit every 4 weeks 
(Periods 4A and 4B)

Vital signs (blood pressure, pulse, respiration rate, 
oxygen saturation, and temperature) will be 
measured at Day 343 and at each visit every 
4 weeks (Periods 4A and 4B)

Known HIV-1 seronegative sexual partners of 
enrolled study participants may be referred for HIV 
PrEP to decrease the risk of HIV transmission 
during ATI (Period 4B only).

Adverse events and concomitant medications will 
be assessed at each visit. Participants will be 
reminded to report all symptoms, including flu-like 
symptoms (eg, fatigue, pyrexia, chills, myalgia, 
joint pain, or headache) or other unexpected 
symptoms (Periods 4A and 4B).
Early Discontinuation from Study Drug and 
Follow-up Procedures
If a participant should discontinue study dosing as 
described in Section 6.9.1, they will be required to 
complete an early study drug discontinuation (ESDD) 
visit and every attempt should be made to keep the 
participant in the study and continue to perform study 
procedures. If the participant is unable to complete all 
scheduled procedures, for criteria other than those 
described for study discontinuation in Section 3.5., the 
participant should be followed by telephone for a 
further duration of time as described in Section 6.9.2. 

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If a participant has completed all study drug dosing but 
is unable to complete all subsequent visits at the 
study site, as scheduled in Periods 3 and 4, for criteria 
other than those described for study discontinuation in 
Section 3.5. for study discontinuation, the participant 
they should be followed by telephone for up for 
250 days after mAb infusion. During follow up with 
telephone check-ups, participants should be followed 
every 4 weeks to monitor for AEs and retrieve urine 
pregnancy results (kits to be provided at the last study 
site visit and a positive urine pregnancy result will 
require confirmation with a serum pregnancy test at the 
study site). At the end of all follow-up monitoring, 
participants will undergo the end-of-follow-up visit at 
the study site.
End-of-Study Visit
The end-of-study visit will be completed for 
participants who have completed Period 4A or 4B. The 
assessments will include AEs and concomitant 
medication review, vital signs, symptom-directed 
physical examination, body weight, 12-lead ECG, 
creatinine clearance, hematology, serum chemistry, 
urine pregnancy test, urinalysis, and ATI remission 
tests.
ART Restart Criteria
Participants will receive ART in Periods 1 and 4A 
only. In Periods 2, 3, and 4B, participants will be in 
ATI and will restart ART if they have plasma HIV-1 
RNA measurements of ≥ 1,000 copies/mL for 8 
consecutive weeks and no drop of 0.3 log10 from 
previous week, or confirmed plasma HIV-1 RNA 
> 100,000 copies/mL, or a confirmed CD4+ T cell 
count < 350 cells/μL, or if a participant becomes 
pregnant, or per participant request, or at the discretion 
of the investigator or sponsor due to other clinical 
criteria. Once the first confirmed HIV-1 RNA value of 
≥ 50 copies/mL is detected, this will trigger weekly 
testing to monitor the HIV-1 RNA measurements.

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Additional Procedures
Additional blood sampling or procedures will be 
completed in all participants, unless otherwise 
specified as optional:
Pharmacokinetics
Plasma VES PK collections will be obtained relative to 
Dose 1 of VES at: predose (≤ 5 minutes prior to 
dosing), 1, 2, 4, 8, 12, 24 (Day 1), and 48 hours 
(Day 2) after dosing.
Serum VRC07-523LS PK collections will be obtained 
relative to VRC07-523LS infusion at: 0 hours 
(predose), end of infusion, 1, 2, 4, and 8 hours after 
end of infusion, and then at Days 8, 9, 14, 21, 28, 56, 
84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 
371, and 413.
Serum CAP256V2LS PK collections will be obtained 
relative to CAP256V2LS infusion at: 0 hours 
(predose), end of infusion, 1, 2, 4, and 8 hours after 
end of infusion, and then at Days 8, 9, 14, 21, 28, 56, 
84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 
371, and 413.
Plasma dolutegravir PK collections will be obtained at: 
Days 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 
329, and for participants in Period 4B only Days 343, 
371, and 413.
Immunogenicity (Anti-VRC07-523LS and 
Anti-CAP256V2LS assessments)
Blood samples for detection of serum anti-
VRC07-523LS and anti-CAP256V2LS antibodies will 
be collected at the following timepoints: 
prebaseline/Day −13, Days 28, 56, 84, 112, 133, 161, 
189, 217, 245, 273, 301, 329, 343, 371, and 413.
Pharmacodynamics and Immunology
Whole blood messenger RNA (mRNA) expression 
(including ISGs) at: prebaseline/Day −13, within 
1 hour before Doses 1, 5, and 10 of VES and 1 day 
after Doses 1, 5, and 10 of VES, end-of-Period 3 visit, 
and if completing Period 4B only, the end-of-study 
visit.

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Change in HIV-specific antibody profiling using 
plasma samples at: prebaseline/Day −13, within 1 hour 
before Doses 1 and 10 of VES, 7 days after Doses 1 
and 10 of VES, end-of-Period 3 visit, and the 
end-of-study visit.
Prebaseline soluble proteins in TruCulture® Whole 
Blood Culture System (Day –13).
Changes in the levels of soluble proteins (cytokines, 
chemokines, and inflammatory markers) at: 
prebaseline/Day −13, within 1 hour before Doses 1, 5, 
and 10 of VES, 1 day and 7 days after Doses 1, 5, and 
10 of VES, end-of-Period 3 visit, and the end-of-study 
visit.
PBMC immune cell frequency, activation and 
phenotyping at: prebaseline/Day −13, within 1 hour 
before Doses 1, 5, and 10 of VES, 1 day and 7 days 
after Doses 1, 5, and 10 of VES, end-of-Period 3 visit, 
and the end-of-study visit.
HIV-specific T cell responses from PBMC by 
intracellular cytokine staining at: prebaseline/Day −13, 
7 days after Doses 1, 5, and 10 of VES, end-of-Period 
3 visit, and the end-of-study visit.
Participants who sign an additional consent will have 
the following optional samples taken:
Human leucocyte antigen genotype, TLR7, and Fc 
gamma receptors (FcgR) single nucleotide 
polymorphism (SNP) at: prebaseline/Day −13.
Lymph node and/or GALT biopsies at 
prebaseline/Day −13, Week 21 (beginning of 
Period 3), end-of-Period 3 visit, and the end-of-study 
visit will be used for some or all of the following tests: 
immune cell frequency, activation, and phenotype, 
gene expression, and HIV-specific T cell response 
evaluation.
Virology
Plasma viremia will be assessed throughout the study 
Periods 1, 2, 3, and 4.
Whole blood derived PBMC samples will be used to 
assess changes in latent HIV-1 reservoir at 
prebaseline/Day −13, Week 21 (beginning Period 3), 
end-of-Period 3 visit, and end-of-study visit.

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Whole blood derived plasma and PBMC samples will 
be used to assess changes in active HIV-1 reservoir at 
prebaseline/Day −13, Days 0, 2, 56, 57, 126, 127, 128, 
end-of-Period 3 visit, and end-of-study visit.
Whole blood derived PBMC samples will be used to 
assess for viral sensitivity to VRC07-523LS and 
CAP256V2LS mAbs at screening, Week 21 (beginning 
Period 3), end-of-Period 3 visit, and end-of-study visit.
In case of viral rebound at any time point during the 
study, plasma virus will be tested for resistance to 
VRC07-523LS, CAP256V2LS, and baseline ART.
Participants who sign an additional consent will have 
the following optional samples taken:
Immune cell isolates from lymph node and/or GALT 
biopsies will be assessed for changes in active and 
latent HIV-1 reservoir at prebaseline/Day −13, 
Week 21 (beginning of Period 3), end-of-Period 3 
visit, and the end-of-study visit
Procedure Definitions and Specifications
HIV-1 RNA will be performed by a validated assay 
with a lower limit of quantitation of at least 
50 copies/mL.
Hematology panel includes: complete blood count with 
differential and platelets, CD4+ and CD8+ T cell 
absolute count, percentage, and CD4/CD8 ratio.
Serum chemistry panel includes: alkaline phosphatase, 
AST, ALT, total bilirubin, direct and indirect bilirubin, 
total protein, albumin, creatine kinase, bicarbonate, 
blood urea nitrogen, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, 
and uric acid.
Urinalysis includes dipstick.
Serum and urine pregnancy tests are performed only 
on female participants of childbearing potential. A 
positive urine result will be confirmed with a serum 
pregnancy test.
Known HIV-seronegative male partners to the female 
study participants may be referred for HIV PrEP to 
decrease the risk of HIV transmission during ATI.

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Test Product, Dose, and Mode of 
Administration:

VRC07-523LS, 20 mg/kg, IV infusion over 
30 minutes

CAP256V2LS, 20 mg/kg, IV infusion over 
30 minutes

Vesatolimod, 6 mg (3 × 2 mg tablets) or 8 mg (4  
2 mg tablets), administered orally under fasted 
conditions
Reference Therapy, Dose, and 
Mode of Administration:

Not applicable
Criteria for Evaluation:
Safety:
Adverse events and clinical laboratory tests
Efficacy:
Time to viral rebound (confirmed ≥ 50 copies/mL and 
≥ 200 copies/mL) following ATI
Plasma viral load set-point following ATI
Viral load at the end of ATI
Time to ART resumption following ATI
Immunogenicity:
Proportion of participants with positive anti-
VRC07-523LS or anti-CAP256V2LS antibodies
Pharmacokinetics:
PK parameters for VES in plasma will include Cmax, 
Tmax, Clast, Tlast, AUCinf, AUClast, AUCexp, t1/2, CL/F, 
and Vz/F. PK parameters for VRC07-523LS and 
CAP256V2LS in serum will include Cmax, Tmax, Clast, 
Tlast, AUCinf, AUClast, AUCexp, t1/2, CL, Vss, and Vz. 
Plasma concentrations of dolutegravir may be analyzed
Pharmacodynamics and 
Immunology:
Induction of cytokines, chemokines, inflammatory 
markers, mRNA transcript (including ISGs), immune 
activation in response to VES, VRC07-523LS, and 
CAP256V2LS may be analyzed. TLR7 genotype may 
be analyzed
Statistical Methods:
Safety:

The incidences of treatment-emergent AEs and 
treatment-emergent laboratory abnormalities will 
be summarized.

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Sample Size: 
Final 
Amendment3 
The sample size in this study is detennined based on 
practical considerations and empirical experience with 
similar types of studies. No sample size and power 
calculation was perfo1med. Up to 25 paiticipants will 
provide a prelimina1y assessment of descriptive safety, 
efficacy and PK. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice 
including archiving of essential documents. 
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
z
terminal elimination rate constant, estimated by linear regression of the terminal 
elimination phase of the log concentration of drug versus time curve of the drug
ACTG
AIDS Clinical Trials Group
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ART
antiretroviral therapy
AST
aspartate aminotransferase
ATI
analytical treatment interruption
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated 
as AUClast + (Clast/z)
AV
atrioventricular
BCRP
breast cancer resistance protein
BLQ
below the limit of quantitation
BMD
bone mineral density
BUN
blood urea nitrogen
C28d
concentration 28 days postdose
C84d
concentration 84 days postdose
CAPRISA
Centre for the AIDS Programme of Research in South Africa
CBC
complete blood count
CD
cluster of differentiation
CDC
Centers for Disease Control and Prevention
CHB
chronic hepatitis B
CHF
congestive heart failure
CL
Clearance following intravenous administration
CL/F
Clearance following extravascular administration
Clast
last observed quantifiable concentration of the drug
Cmax
maximum observed concentration of drug
CK
creatine kinase
CRF
case report form
CRS
cytokine release syndrome
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450 enzyme
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DSMB
Data Safety Monitoring Board

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EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
ER
emergency room
ESDD
early study drug discontinuation
EVM
elipovimab
FAS
Full Analysis Set
FcgR
Fc gamma receptors
FcRn
neonatal Fc receptor
FDA
Food and Drug Administration
FEV1
forced expiratory volume in the first second of expiration
FRESH
Females Rising through Education, Support, and Health
GALT
gut-associated lymphoid tissue
GCP
Good Clinical Practice
GGT
gamma-glutamyltransferase
Gilead
Gilead Sciences
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HIV-1
human immunodeficiency virus type 1
HLA
human leucocyte antigen
IB
investigator’s brochure
IC50
50% inhibitory concentration
IC80
80% inhibitory concentration
ICH
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
IEC
independent ethics committee
IFN
interferon
IL
interleukin
IM
intramuscular
IND
investigational new drug
IRB
institutional review board
ISG
interferon-stimulated gene
ITAC
inducible T cell alpha chemoattractant
IUD
intrauterine device
IV
intravenous(ly)
IWRS
interactive web response system
L
leucine

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LLN
lower limit of normal
LLOQ
lower limit of quantitation
mAb
monoclonal antibody
MAD
multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
mRNA
messenger RNA
NA
not applicable
NK
natural killer
PBMC
peripheral blood mononuclear cell
PD
pharmacodynamic(s)
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PrEP
preexposure prophylaxis
PWH
people with HIV-1
GLPS
Global Patient Safety
Q1
first quartile
Q3
third quartile
QTc
QT interval corrected for heart rate
RBC
red blood cell
RBC/HPF
red blood cells per high power field
RNA
ribonucleic acid
S
serine
SAD
single ascending dose
SAE
serious adverse event
SAHPRA
South African Health Products Regulatory Authority
SC
subcutaneous(ly)
SD
standard deviation
SDV
source data verification
SGOT
serum glutamic oxaloacetic transaminase
SGPT
serum glutamic pyruvic transaminase
SHIV
simian-human immunodeficiency virus
SNP
single nucleotide polymorphism
SOP
standard operating procedure
SSRs
special situation reports
SUSAR
suspected unexpected serious adverse reaction
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
TLR
toll-like receptor

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ULN
upper limit of normal
UNAIDS
United Nations Programme on HIV/AIDS
US
United States
VES
vesatolimod
VR
virologic rebound
Vz
volume of distribution of the drug after intravenous administration

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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus type-1 (HIV-1) infection is a life-threatening and serious 
disease that is of major public health interest around the world. A 2021 report by the Joint United 
Nations Programme on HIV/AIDS (UNAIDS) estimates that 79.3 million people have been 
infected with HIV since the start of the epidemic, contributing to 36.3 million deaths from 
AIDS-related illnesses {Joint United Nations Programme on HIV/AIDS (UNAIDS) 2021}. 
Despite extensive prevention and treatment efforts, South Africa remains an epicenter of the HIV 
pandemic where young women carry a high burden of disease with persistent high HIV 
incidence and prevalence. Untreated infection leads to deterioration in immune function and 
death. Although antiretroviral therapy (ART) has been associated with a dramatic decrease in 
AIDS-related morbidity and mortality {Palella 1998}, {Mocroft 1998}, {Sterne 2005}, there is 
still an urgent medical need to develop new therapies and approaches to eradicate HIV. Current 
therapy is associated with challenges with tolerability, long-term adherence and safety, 
drug-drug interactions, and expense. Persistent HIV infection may also be associated with 
psychosocial stigma. Despite the availability of chronic treatment, morbidity and mortality due to 
HIV infection remain high due to the latent HIV reservoir, which may contribute to ongoing 
inflammation-driven disease. Persistent viral reservoirs fuel rebound viremia when treatment 
ceases. Thus, the discovery and development of therapeutic interventions that can eradicate or 
control HIV reservoirs, leading to long-term ART-free remission or HIV cure, is a major 
priority.
Following entry into the target cell, HIV-1 stably integrates into the host genome, thus 
establishing the basis for latent infection and the main barrier to HIV cure. Neither the host 
immune system nor ART can eliminate transcriptionally inactive virus. Therefore, adjunctive 
therapies that efficiently reactivate (“activate”) virus out of this latent reservoir to enable its 
destruction (“eliminate”) may be required for viral eradication. This activation strategy has been 
tested in clinical studies of latency reversal agents such as histone deacetylase inhibitors and 
toll-like receptor (TLR) 9 agonists {Sogaard 2015, Vibholm 2017}.
One challenge of HIV curative efforts is the lack of a fully validated biomarker for the detection 
of the latent HIV-1 reservoir. This can be overcome by measuring the time to viral rebound 
and/or new viral load set-points following analytical treatment interruption (ATI). While the 
AIDS Clinical Trials Group (ACTG) has reported that certain measures of the HIV reservoir may 
be correlated with time to viral rebound {Li 2016}, ATI remains the most accurate endpoint to 
evaluate the efficacy of “activate and eliminate” interventions and can be conducted safely in 
participants {Bar 2016}.

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Cohorts of acutely treated people with HIV provide an ideal opportunity to evaluate novel HIV 
cure interventions with ATI, maximizing the chances of effectively achieving durable control 
without ART {Dihel 2001}. In fact, initiation of ART during acute HIV infection can reduce the 
size and dissemination of the viral reservoir {Chun 2007}, thereby potentially facilitating 
viremic control after ATI. Additionally, early ART initiation results in decrease in viral 
diversification and preservation of immune function and in some individuals, leads to long-term 
viral remission after withdrawal of treatment {Saez-Cirion 2013}.
It is postulated that a combination of therapies exerting viral activation and engagement of the 
host immune system will be necessary to have a demonstrable effect on reducing the HIV-1 
reservoir. Combining multiple agents, such as immunomodulators and monoclonal antibodies 
(mAbs) could therefore provide a multipronged approach to viral control. Given the enormous 
genetic diversity of HIV-1, the use of multiple mAbs may be required to ensure adequate 
coverage of circulating strains. Recently, in vitro studies have demonstrated that a combined use 
of mAbs, simultaneously targeting different epitopes of the virus, results in an improved 
neutralization breadth and potency. In addition, a combination of mAbs reduces the selective 
immune pressure created by the virus and thus prevent viral escape mutants.
VRC07-523LS, is a highly potent and broadly neutralizing HIV-1 human mAb targeted against 
the HIV-1 cluster of differentiation 4 (CD4) binding site, engineered from an antibody isolated 
from a participant whose immune system controlled the virus without ART. This antibody is 
characterized by high neutralization potency in vitro and prolonged half-life, which correlates 
with improved protection against simian-human immunodeficiency virus (SHIV) infection in 
vivo in animal studies, making it an ideal candidate for clinical application against HIV-1 
infection in humans in therapeutic settings. Clinical studies are ongoing.
CAP256V2LS is an engineered variant of CAP256-VRC26.25, a highly potent broadly 
neutralizing mAb isolated from a South African participant with HIV-1 Clade C enrolled in the 
Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 acute HIV 
infection study. The neutralization breadth of CAP256-VRC26.25 makes it particularly well 
suited as a complementary mAb with antibodies targeting a different epitope. Furthermore, this 
mAb provided 100% protection against SHIV challenges in macaque experiments {McLellan 
1996}. Clinical studies are ongoing.
Vesatolimod (VES) is a TLR7 agonist currently in clinical development for the treatment and 
remission of HIV-1 infection. Vesatolimod has been shown to induce interferon-stimulated gene 
(ISG) messenger RNA (mRNA) expression and production of cytokines and chemokines, and to 
induce activation of CD4+ and cluster of differentiation 8 (CD8)+ T lymphocytes in people with 
HIV-1 (PWH) virologically suppressed on ART. The ability of VES to increase the cytotoxic 
activity of HIV-specific T lymphocytes and activate phagocytic cells, improving 
antibody-dependent cell-mediated cytotoxicity in vitro, suggests that its immunomodulatory 
effect could enhance the antiviral activity of mAbs. In fact, in rhesus macaque studies, sequential 
regimens including TLR7 agonists and either therapeutic vaccination or mAbs have led to SHIV 
ART-free viral control {Borducchi 2016, Borducchi 2018b}.

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This study will evaluate the safety, tolerability, pharmacokinetics (PK), and effect of dual 
anti-HIV envelope mAbs, VRC07-523LS and CAP256V2LS, in a sequential regimen with a 
TLR7 agonist, VES, in virologically suppressed women with HIV-1 Clade C on ART and during 
ATI.
1.2.
Investigational Medicinal Products
1.2.1.
Nonclinical Studies of Vesatolimod
1.2.1.1.
General Information on Vesatolimod
Vesatolimod is an orally administered TLR7 agonist in development for the treatment of HIV 
infection. Data in vitro have shown that VES is a potent and selective TLR7 receptor agonist 
with > 30-fold selectivity for TLR7 (32-fold based on half-maximal effective concentration and 
81-fold based on minimum effective concentration) over TLR8, with no detectable stimulation of 
other human TLRs at concentrations up to 100 μM.
1.2.1.2.
Nonclinical Pharmacology of Vesatolimod
Nonclinical data in mice and in chimpanzees chronically infected with hepatitis B virus (HBV) 
demonstrated that oral administration of VES induce a type I interferon (IFN)-dependent innate 
response in the liver, as measured by induction of ISGs, in the absence of concomitant serum 
detectable levels of IFN-α (ie, a presystemic response) {Fosdick 2013}, {Lanford 2013}.
In a rhesus macaque model of chronic SHIV infection, treatment with VES demonstrated the 
ability to enhance the benefits of treatment with a broadly neutralizing antibody, PGT121 
{Borducchi 2018a}. Treatment of ART-suppressed SHIV-infected rhesus macaques with VES 
induced transient increases in cytokine levels and activation of CD4+ T cells, CD8+ T cells, and 
natural killer (NK) cells. Viral DNA in lymph node biopsies was reduced in the VES and 
PGT121 combination-treated monkeys, but not in animals receiving VES alone. Following ART 
discontinuation, the combination treatment group showed the greatest increase in days to viral 
rebound and number of animals that did not rebound (5 of 11 in combination versus 2 of 11 with 
PGT121 alone). In animals with sustained ART-free control, depletion of CD8/NK cells did not 
lead to rebound. Collectively, these results demonstrate that the replication competent viral 
reservoir was reduced to extremely low levels or eliminated. This study demonstrates that 
therapeutic administration of VES in combination with a neutralizing anti-HIV envelope 
antibody can lead to viral remission in a subset of SHIV-infected rhesus macaques in the absence 
of ART.
For further information on VES, refer to the investigator’s brochure (IB) for VES, including 
information on the following:

Nonclinical PK and in vitro metabolism

Nonclinical pharmacology and toxicology

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1.2.2.
Nonclinical Studies of CAP256V2LS
1.2.2.1.
General Information on CAP256V2LS
CAP256V2LS is an engineered variant of CAP256-VRC26.25, a highly potent broadly 
neutralizing mAb isolated from a South African participant with HIV-1 Clade C enrolled in the 
CAPRISA 002 acute HIV infection study {Doria-Rose 2016}. CAP256V2LS differs from its 
parent by 3 amino acids found in 2 locations: a mutation of lysine to alanine, which prevents 
proteolytic cleavage by cellular proteases during Chinese hamster ovary cell culture in the 
CDRH3 region (CAP256V2LS IB Edition 1); and the methionine to leucine (L) and asparagine 
to serine (S) mutations (referred to as the LS mutation) in the C-terminus of the heavy chain 
Fc region, which increase the antibody binding affinity for the neonatal Fc receptor (FcRn) 
resulting in an extended half-life of human antibodies in vivo {Ko 2014},{Gaudinski 2018}.
1.2.2.2.
Nonclinical Pharmacology and Pharmacokinetics of CAP256V2LS
CAP256V2LS neutralized 63% of the multiclade 208-pseudovirus panel with high potency, a 
median 50% inhibitory concentration (IC50) of 0.001 μg/mL and 80% inhibitory concentration 
(IC80) of 0.004 μg/mL.
In human FcRn transgenic mice and rhesus macaques, CAP256V2LS displays a PK profile 
similar to other anti-HIV-1 antibodies. In mice, the average serum half-life for CAP256V2LS 
was calculated to be 7.7 days with a range of 6.2 to 8.5 days. In rhesus macaques, the average 
half-life was calculated to be 14.3 days for the intravenous (IV) route and 9.9 days for the 
subcutaneous (SC) route.
For further information on CAP256V2LS, refer to the IB for CAP256V2LS, including 
information on the following:

Nonclinical PK and in vitro metabolism

Nonclinical pharmacology and toxicology
1.2.3.
Nonclinical Studies of VRC07-523LS
1.2.3.1.
General Information on VRC07-523LS
VRC07-523LS, is a highly potent and broadly neutralizing HIV-1 human mAb targeted against 
the HIV-1 CD4 binding site. The predecessor, VRC01 mAb, was originally discovered in a 
participant with HIV-1 for more than 15 years and whose immune system controlled the virus 
without ART {Wu 2012}.
The VRC07 (wild-type) heavy chain was identified by deep sequencing based on its similarity to 
the VRC01 mAb and paired with the VRC01 (wild-type) light chain {Rudicell 2014}, {Kwon 
2012}. The LS mutations increase the binding affinity for the FcRn, resulting in increased 
recirculation of functional immunoglobulin G and therefore increasing plasma half-life {Ko 
2014}, {Zalevsky 2010}

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1.2.3.2.
Nonclinical Pharmacology and Pharmacokinetics of VRC07-523LS
VRC07-523LS was found to be 5- to 8-fold more potent than VRC01, with a median IC50 of 
0.046 μg/mL (breadth 96%, 50 μg/mL cutoff) and an IC80 of 0.229 μg/mL (breadth 95%, 
50 μg/mL cutoff) of HIV-1 pseudoviruses representing the major circulating HIV-1 clades.
In cynomolgus macaques administered 10 mg/kg of VRC07-523LS, the half-life of 
VRC07-523LS was determined to be approximately 10 to 12 days for the IV route and 
approximately 14 days for the SC route.
For further information on VRC07-523LS, refer to the IB for VRC07-523LS, including 
information on the following:

Nonclinical PK and in vitro metabolism

Nonclinical pharmacology and toxicology
1.2.4.
Clinical Studies of Vesatolimod
1.2.4.1.
Studies in Participants with HIV-1 Infection
As of March 2022, 63 virologically suppressed adults with HIV-1 were dosed with VES in the 
following Phase 1b Gilead clinical studies:

GS-US-382-1450: A Phase 1b, Randomized, Blinded, Placebo-Controlled Dose-Escalation 
Study of the Safety and Biological Activity of VES in HIV-1-Infected, Virologically 
Suppressed Adults

GS-US-382-3961: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety and Efficacy of VES in Antiretroviral-Treated HIV-1-Infected 
Controllers

GS-US-420-3902: A Phase 1b, Randomized, Blinded, Placebo-Controlled, Staggered, Single 
and Multiple Ascending Dose Study Evaluating the Safety, Tolerability, and 
Pharmacokinetics of GS-9722, Administered Alone or in Combination with Vesatolimod, in 
Virologically Suppressed HIV-1 Infected Subjects on ART
Details on the primary objectives, study design, study and control drug regimens, number of 
participants by treatment, study status, and key findings for these clinical studies are provided 
below. Vesatolimod is also being dosed in an external study (AELIX-003 [National Clinical 
Trial number NCT04364035]) either alone or in combination with other investigational agents. 
Additionally, VES is planned to be dosed in the following studies.
Study GS-US-382-1587: A Phase 1, Open-label, Multicohort Study to Evaluate the Impact of 
Inhibitors and Inducers of Cytochrome P450 Enzyme (CYP)3A and/or P-glycoprotein (P-gp) on 
the Pharmacokinetics (PK) of Vesatolimod (VES) in Virologically Suppressed Adults With HIV-
1 on Antiretroviral Therapy (ART)

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1.2.4.1.1.
Study GS-US-382-1450
Study Design
This Phase 1b, randomized, double-blind, placebo-controlled, dose-escalation study was 
conducted to evaluate the safety and biological activity of VES with the following dose cohorts: 
Cohort 1 (1 mg), Cohort 2 (2 mg), Cohort 3 (4 mg), Cohort 4 (6 mg), Cohort 5 (8 mg), 
Cohort 6 (3 doses of 10 mg followed by 7 doses of 12 mg). Three optional cohorts (Cohorts 7, 8, 
and 9) were not conducted.
For each cohort, 8 participants were randomized in a 6:2 ratio to receive VES or placebo.
Participants received a total of either 6 doses in Cohorts 1 to 3 or 10 doses in Cohorts 4 to 6, 
administered once every other week. Vesatolimod was administered with a meal in Cohorts 1 to 
4, and under fasted conditions in Cohorts 5 and 6. Participants continued with their existing ART 
regimen throughout the whole study. After all participants in a cohort received at least 3 doses 
(Cohorts 1 to 3) or 5 doses (Cohorts 4 to 6), a Safety Evaluation Committee reviewed safety data 
from that cohort, including adverse events (AEs) and clinical laboratory results before approving 
the opening of enrollment in the next cohort.
The study is now complete.
Participant Disposition and Baseline Characteristics
Overall, 48 participants were enrolled. Eight participants were dosed in each of 6 cohorts with 
doses up to 12 mg (based on the assigned cohort). Participants had a median age of 47 years and 
89.6% were male. All participants had HIV-1 RNA levels < 50 copies/mL at baseline.
Administration of VES at doses of 1, 2, 4, 6, 8, 10, or 12 mg did not lead to consistent increases 
in viremia from baseline.
Virology Results
The following participants had plasma HIV-1 RNA ≥ 50 copies/mL in the VES or placebo 
groups:

1 participant in the placebo group had an HIV-1 RNA level peak at 1040 copies/mL 7 days 
after Dose 3 and returned to < 50 copies/mL 17 days after Dose 3

1 participant in the placebo group had an HIV-1 RNA level of 81 copies/mL 2 days after 
Dose 5 and returned to < 50 copies/mL 4 days after Dose 5

1 participant in the VES 4 mg group had HIV-1 RNA levels of 60 copies/mL 4 days after 
Dose 4 and returned to < 50 copies/mL 7 days after Dose 4, and 69 copies/mL 7 days after 
Dose 5 and returned to < 50 copies/mL 14 days after Dose 5

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
1 participant in the placebo group had HIV-1 RNA levels peak at 2430 copies/mL 7 days 
after Dose 6 and returned to < 50 copies/mL 14 days after Dose 6, another peak at 
112 copies/mL 2 days after Dose 7 and returned to < 50 copies/mL 14 days after Dose 7, 
another peak at 78 copies/mL 7 days after Dose 8 and returned to < 50 copies/mL 16 days 
after Dose 8, and a range of 64 to 98 copies/mL from 7 to 76 days after Dose 10
Administration of VES at doses of 1, 2, 4, 6, 8, 10, or 12 mg did not lead to consistent increases 
from baseline median plasma viremia.
There were no statistically significant differences between any VES dose groups and placebo 
group in the number of participants with HIV-1 RNA ≥ 50 copies/mL at any time after each dose 
(Dose 1 to Dose 10)
There were no statistically significant differences in median maximum change from baseline in 
plasma HIV-1 RNA for all doses compared to placebo with the exception of VES 8 mg 
(P = 0.0289). There were no statistically significant differences in change from baseline between 
any VES dose groups and placebo group for active or latent HIV-1 reservoir {Riddler 2020}.
Pharmacokinetics and Pharmacodynamics
Across all cohorts, VES was administered for up to 10 doses, every other week.
Vesatolimod PK in PWH was similar to VES PK in healthy volunteers and participants.
Increases in AUClast, AUCinf, and Cmax were generally dose proportional following single-dose 
administration of VES across the doses of 1 to 12 mg in PWH. The median Tmax ranged from 
1 to 3 hours postdose, and median t1/2 ranged from 9 to 19 hours across the dose levels evaluated. 
As no accumulation of VES is anticipated based on the observed half-life, the PK parameters 
observed after the first dose are representative of chronic exposure following every other week 
dosing.
The evaluated pharmacodynamic (PD) markers (cytokine, ISG markers, and lymphocyte 
activation) were induced following dosing with VES in PWH. The cytokine markers with the 
greatest fold increases in serum following dosing with VES were interleukin (IL)-1ra and IFN-α, 
which showed maximal 3.67-fold and 8.81-fold increases from baseline, respectively, in the VES 
12 mg group. Overall, absolute levels of IFN-α production were low. All ISGs assessed in this 
study were induced in a generally dose-dependent fashion following administration of VES 4 mg 
or more, with the greatest inductions in the 8 mg group at 21.18-fold, 8.42-fold, and 10.50-fold 
increases for ISG-15, 2'-5'-oligoadenylate synthetase 1, and MX Dynamin Like GTPase 1, 
respectively. The VES dose required to elicit an ISG response (VES ≥ 4 mg) was lower than that 
required for any substantial detection of serum IFN-α. Activation of the subpopulation of 
CD4+ CD38+ human leucocyte antigen (HLA) DR+ T cells and CD8+ CD38+ HLA-DR+ 
T cells was generally in a dose-dependent fashion in participants who received VES at doses of 
at least 6 mg. Activation of NK cells (CD69+) was achieved at VES doses of 8 and 12 mg.

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Safety Results
Overall, 32 of 48 participants (66.7%) reported at least 1 AE during the study. No Grade 4 AEs 
were reported in the study. No deaths were reported and there were no discontinuations from 
study drug due to AEs. The most frequently reported (≥ 25% of participants in any VES group) 
treatment-emergent AEs included: fatigue, nausea, myalgia, nasal congestion, and upper 
respiratory tract infection. These flu-like symptoms are not unexpected given the mechanism of 
action of VES. One participant (16.7%) in the VES 2 mg group experienced a Grade 3 AE of 
abdominal pain lower (unrelated to study drug). The same participant experienced a serious 
adverse event (SAE) during the study (diverticulitis); the SAE was not considered by the 
investigator to be related to study drug. Eleven participants experienced AEs (eg, headache, 
fatigue, myalgia) that were considered by the investigator to be related to study drug. Refer to the 
IB for details.
Three participants experienced Grade 3 or 4 laboratory abnormalities: 1 participant in the 8 mg 
group (Grade 4 creatine kinase increase associated with strenuous exercise and Grade 3 aspartate 
aminotransferase [AST] increase) and 2 participants in the 10/12 mg group (1 participant had 
Grade 4 creatine kinase increase and 1 participant had Grade 3 creatine kinase increase, both 
were associated with strenuous exercise).
Conclusion
This study demonstrated the following:

Multiple VES doses from 1 to 12 mg were well tolerated.

Immune stimulation was evident at VES doses ≥ 4 mg.

There were no consistent elevations in plasma HIV-1 RNA to ≥ 50 copies/mL compared with 
placebo.

Increases in plasma exposure (as measured by AUCinf, AUClast, and Cmax) were generally 
dose proportional following single-dose administration of VES at doses of 1 to 12 mg.
1.2.4.1.2.
Study GS-US-382-3961
This Phase 1b randomized, double-blind, placebo-controlled study with a single cohort of HIV-1 
controllers on ART with a history of pre-ART plasma HIV-1 RNA between 50 and 
≤ 5000 copies/mL was conducted to evaluate the safety and efficacy of VES. The study was 
conducted in 3 periods. In Period 1, 25 participants were randomized 2:1 to receive VES 
(17 participants) or placebo-to-match (8 participants), while continuing ART. Randomization 
was stratified by pre-ART viral load (≥ 50 to < 2000 copies/mL or ≥ 2000 to ≤ 5000 copies/mL) 
at screening. In addition, 3 participants from the 8 mg cohort in Study GS-US-382-1450 rolled 
over to Study GS-US-382-3961 after completing VES dosing. All participants received up to 
10 doses of their assigned study treatment administered orally once every 14 days. In Period 2, 
all participants discontinued both ART and VES during an ATI and were monitored for rebound 
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restarted ART during Period 2 due to virologic rebound completed ART reinitiation visits, and 
then post-ART resuppression visits monthly for 6 additional months. Participants who completed 
24 weeks of ATI without restarting ART moved onto Period 3. In Period 3, participants could 
either restart ART (along with post-ART resuppression visits for 6 additional months) or remain 
off ART for an additional 24 weeks after the first 24 weeks of ATI were completed, if low viral 
loads were maintained.
Study GS-US-382-3961 opened for screening on 09 March 2017. All participants completed 
dosing of VES (4 to 8 mg intraparticipant dose escalation) or placebo (Period 1), and underwent 
ATI (Period 2), or restarted ART per protocol (Periods 2 or 3).
Participant Disposition and Baseline Characteristics
The Full Analysis Set (FAS) for Study GS-US-382-3961 consisted of 25 participants. The 
median age was 45 years and 84.0% of participants were male. Median baseline HIV-1 RNA 
level was 1.28 log10 copies/mL and 24 of 25 participants had HIV-1 RNA < 50 copies/mL. 
Median CD4 T lymphocyte count was 755/μL and 92.0% of participants had a CD4 cell count 
≥ 500/μL.
Virology Results
The effect of VES on change from baseline in HIV-1 RNA was assessed at multiple postdose 
timepoints throughout the study. There was no consistent induction of plasma viremia during 
VES or placebo dosing pre-ATI. During the ATI period, increases in plasma HIV-1 RNA were 
generally lower in participants receiving VES compared with those receiving placebo. 
Vesatolimod was associated with a longer period of viral suppression following ATI compared 
with placebo. The median (first quartile [Q1], third quartile [Q3]) time to viral rebound 
(≥ 50 copies/mL) was 4.3 (3.1, 6.1) weeks for the VES group compared with 4.0 (3.0, 4.2) weeks 
for the placebo group (P = 0.035). For rebound to ≥ 200 copies/mL, the median (Q1, Q3) time to 
viral rebound was 5.1 (4.1, 6.3) weeks for the VES group compared with 4.1 (3.8, 4.6) weeks for 
the placebo group (P = 0.024). Five participants in the VES group had no virologic rebound 
(≥ 50 copies/mL) for 6 or more weeks. One of these participants (VES 6 mg) did not rebound to 
≥ 50 copies/mL until 15 weeks after ATI. This participant did not rebound to ≥ 200 copies/mL 
until 28 weeks after ATI. All participants in the placebo group had virologic rebound within 
5 weeks of stopping ART.
For VES, median pre-ART viral set-point was 3.23 log10 copies/mL and median viral set-point 
following ATI was 2.78 log10 copies/mL. The median plasma viral set-point change was 
-0.37 log10 copies/mL (P = 0.022 compared with the pre-ART viral set-point). For placebo, 
median pre-ART viral set-point was 3.05 log10 copies/mL and median viral set-point following 
ATI was 2.85 log10 copies/mL. The median plasma viral set-point change was -0.28 log10 
copies/mL (P = 0.38 compared with the pre-ART viral set-point). Median peak viral load during 
ATI was 4.21 log10 copies/mL and 3.97 log10 copies/mL for VES and placebo, respectively 
(P = 0.67). Peak viral load was reached faster in the placebo group (largest median change at 
ATI Visit 6) compared with the VES group (largest median change at ATI Visit 9). The active 
HIV-1 reservoir was evaluated by measuring change in plasma HIV-1 RNA via Single Copy 
Assay during the dosing period and no consistent changes were observed after VES or placebo 

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dosing. The latent HIV-1 reservoir was evaluated by Intact Proviral DNA Assay (IPDA) and 
Inducible Virus Production Assay (IVPA). No consistent change was observed following VES or 
placebo dosing by IVPA or total HIV DNA measured by IPDA. However, a significant decrease 
in the estimated frequency of cells harboring intact HIV DNA measured by IPDA was observed 
in the VES group (P = 0.046) but not in the placebo group. The delayed viral rebound was 
associated with lower intact proviral DNA at the end of VES treatment {Riddler 2021, SenGupta 
2021}.
Pharmacokinetics/Pharmacodynamics Results
Vesatolimod PK following administration of 4 mg or 6 mg was similar to that observed 
previously (Studies GS-US-243-0101 and GS-US-382-1450). Mean exposure (AUC and Cmax) 
following administration of VES 8 mg was numerically higher than previously observed 
following administration of VES 8 mg or 12 mg (Studies GS-US-243-0101 and 
GS-US-382-1450); this may be due to the small number of participants in this group (N = 3).
The evaluated PD markers (cytokine, ISG markers, and lymphocyte activation) were induced 
following dosing with VES in PWH. The cytokine markers with the greatest fold increases in 
serum following dosing with VES were IP-10 and IFN-α. Overall, absolute levels of IFN-α 
production were low and comparable to previous studies of VES. There was a 4.11-fold maximal 
mean increase from baseline in IL-1RA observed 1 day after the 10th VES dose. There was a 
6.02-fold maximal mean increase from baseline in IP-10 observed 1 day after the 10th VES dose. 
There was a 3.45-fold maximal mean increase from baseline in inducible T cell alpha 
chemoattractant (ITAC) observed 1 day after the 10th dose of VES. There was a 62.57-fold 
maximal mean increase from baseline in IFN-α observed 1 day after the fourth dose of VES.
All ISGs assessed in this study were induced with the greatest mean inductions of 19.71-fold, 
7.44-fold, and 10.29-fold increases for ISG-15, OAS-1, and MX1, respectively. IL-1RA, IP10, 
and ITAC decreased to baseline levels 7 days after each dosing cycle, while IFN-α decreased to 
baseline levels by Day 1 of the next VES dose. An increase in the activation of T cells, DCs 
(CD54+pDC), monocytes (CD14+CD16+), T cells (CD4+HLA-DR+CD38+ and 
CD8+HLA-DR+CD38+) and NK cells (CD69+CD56+CD16+, CD69+CD56dimCD16- and 
CD69+CD56brCD16dim) was observed 1 and 3 days following dosing with VES, which 
returned to baseline 13 days after each dose.
Safety Results
Adverse events were reported in 22 of 25 participants (88.0%) as follows: VES 4 mg, 2 of 
2 participants (100.0%); VES 4/6 mg, 3 of 4 participants (75.0%); VES 6 mg, 5 of 5 participants 
(100.0%); VES 6/8 mg, 3 of 3 participants (100.0%); VES 8 mg, 3 of 3 participants (100.0%); 
and placebo, 6 of 8 participants (75.0%). No deaths, study drug-related SAEs, pregnancies, or 
AEs leading to discontinuation of study drug were reported. The most common AEs in the VES 
group (occurring in > 2 participants) were headache and nausea (5 participants each), chills 
(4 participants), and sinusitis, arthralgia, fatigue, lymphadenopathy, and pyrexia (3 participants 
each). The most common AEs in the placebo group (occurring in > 1 participant) were headache 
(3 participants) and sinusitis (2 participants). Nine participants (53%) who received VES and 
1 participant (13%) who received placebo experienced study drug-related AEs. The majority of 

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the VES-related AEs were mild, transient influenza-like symptoms: 2 participants with fatigue, 
3 participants with chills, 2 participants with pyrexia, 3 participants with headache, and 
3 participants with lymphadenopathy. One participant who received VES had Grade 3 AEs of 
gout, arthralgia, and sciatica exacerbation occurring on Days 102, 109, and 113, respectively 
(between Doses 8 and 9), that were considered study drug-related, as well as an unrelated 
Grade 3 AE of viral gastroenteritis. One participant who received VES had a Grade 2 SAE of 
chronic gastritis that was not considered related to study drug. There were no Grade 3 or 4 AEs 
or SAEs reported in the placebo group.
Overall 19 of 25 participants (76.0%) had any graded laboratory abnormality as follows: VES 
4 mg, 2 of 2 participants; (100.0%); VES 4/6 mg, 4 of 4 participants (100.0%); VES 6 mg, 4 of 
5 participants (80.0%); VES 6/8 mg, 1 of 3 participants (33.3%); VES 8 mg, 2 of 2 participants 
(100.0%); and placebo, 6 of 8 participants (75.0%). The majority of laboratory abnormalities 
were Grade 1 or 2 in severity. One participant with a history of diabetes who received VES had 
transient Grade 3 nonfasting hyperglycemia, and Grade 3 glycosuria. No Grade 4 laboratory 
abnormalities were observed. There were no treatment-emergent graded abnormalities in 
platelets or lymphocytes.
Conclusions
This study demonstrated that:

Multiple doses of VES (up to 8 mg) were well tolerated.

Time to viral rebound after ATI was modestly increased with VES compared with placebo, 
and viral set-point was decreased from pre-ART levels with VES.

Compared with VES exposures observed in previous studies at the same doses, VES 
exposures at 4 mg and 6 mg were similar, while VES exposure at 8 mg was numerically 
higher in this study.
The induced ISG expression, induced cytokine release, and activated immune cells observed in 
this study were potentially due to an augmented antiviral immune response.
1.2.4.1.3.
Study GS-US-420-3902
This Phase 1b randomized, double-blinded, placebo-controlled, staggered single ascending dose 
(SAD) and multiple ascending dose (MAD) study was conducted to evaluate the safety, 
tolerability, and PK of EVM, an HIV-1 broadly neutralizing antibody (bNAb), administered 
alone or in combination with VES in virologically suppressed PWH. This study was designed to 
evaluate EVM as a single agent (Cohorts 1 to 4), and in combination with VES (Cohorts 5 to 8). 
Following completion of screening and Day −1 procedures, eligible participants were 
randomized in a 3:1 ratio per cohort to receive either EVM or placebo (either alone or in 
combination with VES). Following completion of enrollment and dosing in Cohort 5, Gilead 
decided to terminate Study GS-US-420-3902; accordingly, no participants were enrolled in 
Cohorts 6 to 8. Cessation of this clinical study was not the result of any safety concerns related to 
EVM or VES. Gilead completed follow-up visits for participants in Cohort 5 prior to closing the 
study.

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In Cohorts 1 to 4, participants received either EVM or placebo. In the SAD Cohorts 1 and 2, a 
single IV dose of 150 mg or 500 mg, respectively, was administered. In the MAD Cohorts 3 and 
4, five IV doses of 150 mg or 500 mg, respectively, were administered, a single dose every other 
week. In Cohort 5, participants received 6 mg VES orally administered alone for the first dose 
(Day 1) followed by 150 mg of EVM coadministered intravenously with 6 mg of VES orally 
once every other week for 4 doses. Final results from Cohort 5, in which participants received 
EVM in combination with VES, are presented below.
The study is now complete.
Participant Disposition and Baseline Characteristics
Overall, 42 participants were randomized (8 participants in each of the Cohorts 1 to 4 and 
10 participants in Cohort 5). Of these, 39 participants completed study drug treatment and 39 
participants completed the study. In Cohort 5, 10 participants were randomized, and 7 
participants completed study drug treatment. The age range in Cohort 5 was 28 to 64 years, 
inclusive, and all the participants were male. All participants had HIV-1 RNA < 50 copies/mL. 
The median (Q1, Q3) baseline HIV-1 RNA value was 1.28 (1.28, 1.28) log10 copies/mL.
Virology Results
Overall, no median changes from baseline in plasma HIV-1 RNA were observed across 
treatment groups during the study, with the exception of a transient median (Q1, Q3) increase 
from baseline at Day 28 in participants in Cohort 5 who received VES 6 mg + placebo (0.11 
[0.00, 0.23] log10 copies/mL [n = 2]). This median increase was attributable to 1 participant who 
had a quantifiable plasma HIV-1 RNA level < 50 copies/mL on Day 28 and was not clinically 
significant. No clinically relevant changes from baseline in CD4 and CD8 cell counts or CD4 
percentage were observed across treatment groups, and no participant met the criteria for 
confirmed virologic rebound or resistance testing during the study.
Pharmacokinetics/Pharmacodynamics Results
Co-administration of EVM and VES did not appear to impact the PK of either study drug.
Safety Results
Co-administration of EVM and VES was generally safe and well tolerated in virologically 
suppressed people with HIV-1 on ART. In Cohort 5, most AEs were Grade 1 or 2 in severity. 
One participant who received VES 6 mg + EVM 150 mg had a Grade 1 AE of SARS CoV 2 test 
positive, which was considered not related to study drug and led to premature discontinuation of 
study drug. No Grade 4 AEs, Stage 3 HIV-related opportunistic illnesses, deaths, or pregnancies 
were reported during the study.
One participant in Cohort 5 who received VES 6 mg + EVM 150 mg had Grade 2 increased 
creatine kinase (1992 U/L) on Day 14 and Grade 4 increased creatine kinase (7391 U/L) on 
Day 17, which were attributed to exercise by the investigator and resolved by Day 22.
There were no clinically relevant findings in vital signs, oxygen saturation, or electrocardiogram 
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External Clinical Studies With Vesatolimod
Based on preliminary data communicated to Gilead from the ongoing externally sponsored 
clinical study investigating the safety of VES with HIV-1 vaccines in participants who started 
ART in early stages of HIV-1 infection (AELIX-003; National Clinical Trial number 
NCT04364035), no new safety signals have been identified with administration of VES to date.
1.2.4.2.
Studies in Healthy Participants and Participants with Chronic Hepatitis B 
and C Virus
Five Phase 1 clinical studies (GS-US-420-5372, GS-US-243-0101, GS-US-243-0102, 
GS-US-283-0102, and GS-US-283-0106), 2 Phase 2 clinical studies (GS-US-283-1059, 
GS-US-283-1062), and 1 registry study (GS-US-283-0110) have been completed in which 
59 healthy participants, 42 participants with hepatitis C virus (HCV), 162 viremic participants 
with chronic hepatitis B (CHB), and 230 participants with HBV (189 virologically suppressed 
and 41 treatment-naive participants) were dosed with VES. Vesatolimod was initially developed 
to provide participants with CHB infection with a finite duration, curative treatment option. 
However, no significant declines in HBV DNA, hepatitis B surface antigen (HBsAg) levels, or 
HBsAg loss were detected through the program. Therefore, due to the lack of efficacy, VES is no 
longer being investigated in the CHB therapeutic area. Safety data from the program are included 
in the IB to provide additional context for AEs.
1.2.4.2.1.
Study GS-US-420-5372
Study GS-US-420-5372 was a Phase 1, randomized, blinded, placebo-controlled, single-center, 
multiple-dose study of EVM in combination with VES with staggered dose escalations and 
adaptive VES dose selection.
A total of 5 cohorts were planned for evaluation in this study, of which 2 cohorts were optional. 
Only a single dose of study treatment (EVM 250 mg with VES 8 mg or EVM 250 mg with 
placebo for VES) was received by 4 participants in Cohort 1 of the study. Cohorts 2 through 
5 were not initiated and the study was terminated after completion of study assessments in the 
4 participants in Cohort 1, as an SAE considered related to study treatment by the investigator 
was reported in 1 participant.
Overall, AEs were reported in 3 of the 4 participants, of which all except one were Grade 1 in 
severity. No deaths were reported during the study. A Grade 3 SAE of cytokine release 
syndrome (CRS) was reported on Day 1 in 1 participant who received EVM with VES; this 
Grade 3 SAE was considered related to the study treatment and led to discontinuation of study 
treatment for this participant and termination of study treatment for the other 3 participants. This 
participant had myalgias, back pain, tachycardia, fever, chills, nausea, and vomiting 6 hours after 
receiving study treatment. The participant was also hypotensive; therefore, IV fluid and 
solumedrol were administered to stabilize the blood pressure. Approximately 2 hours after the 
onset of symptoms, the participant had another episode of hypotension and was treated with IV 
solumedrol prior to being transported to the hospital. At the hospital, the participant was 
normotensive, tachycardic, febrile, and hypoxic. Physical examination showed no rash, normal 
conjunctiva, moist oral mucosa, normal breath sounds, and no swelling. The participant received 
acetaminophen for fever and supplemental oxygen by nasal canula for hypoxia with resolution. 

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Venous lactic acid was elevated above the laboratory reference range and the participant was 
admitted to the hospital for observation. The SAE of CRS resolved, and laboratory values for the 
participant returned to baseline without additional intervention; the participant was discharged 
from the hospital on Day 3. The SAE was considered related to study treatment by the 
investigator and study treatment was withdrawn.
Although this SAE was reported as Grade 3 by the investigator, according to the NCI CRS 
grading this SAE was consistent with Grade 2 as the associated hypotension responded to fluids 
{Shimabukuro-Vornhagen 2018}. The participant did not require vasopressors and was 
discharged from the hospital 2 days after the SAE occurred. No other SAEs or AEs leading to 
premature discontinuation of study treatment were reported, and no other AEs were considered 
related to study treatment.
Preliminary assessment of cytokines including those associated with CRS (eg, IL-1, IL-6, 
granulocyte-macrophage colony-stimulating factor [GM-CSF], MCP-1, macrophage 
inflammatory protein-1 [MIP-1], IP-10 and IFN-γ) did not show elevated baseline or 
on-treatment levels for the study participant with CRS relative to the other participants. Analysis 
of serum taken at baseline from the participant with the SAE of CRS showed a unique biomarker 
profile with higher E-selectin (a marker of vascular inflammation) and lower Factor VII than the 
other participants at baseline (though within normal ranges), as well as higher acute elevation of 
IFN-α and ISGs after treatment with EVM and VES. The participant with the SAE of CRS tested 
positive for cocaine use at an outpatient visit on Day 57. It is unclear whether chronic cocaine 
use contributed to higher baseline vascular inflammation or greater risk for CRS. No other SAEs 
or AEs leading to premature discontinuation of study treatment were reported, and no other AEs 
were considered related to study treatment. The only AE reported in > 1 participant was 
constipation (1 participant in each treatment group).
1.2.5.
Clinical Studies of CAP256V2LS
First-in-human studies (VRC 611 in healthy participants and CAPRISA 012B in both healthy 
participants and participants with HIV) are ongoing. As of 04 January 2021, 37 HIV-negative 
participants have been enrolled into the CAPRISA 012B study and no participants have been 
enrolled in the VRC 611 study. Emerging data from these 2 studies will inform on dose selection 
for this study.
1.2.5.1.
VRC 611
The VRC 611 Phase 1 study, entitled “A Phase I Safety and Pharmacokinetics Study to Evaluate 
a Human Monoclonal Antibody (mAb) VRC-HIVMAB0102-00-AB (CAP256V2LS) 
Administered Via Subcutaneous and Intravenous Injection in Healthy Adults” is being conducted 
at the VRC Vaccine Evaluation Clinic in the National Institutes of Health Clinical Center in the 
United States (US). This study will include 2 dosing regimens with CAP256V2LS administered 
as a single dose at 5 mg/kg SC or 5 mg/kg IV (N = 5 per cohort). Safety, PK, and formation of 
antidrug antibodies will be evaluated throughout the study.

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1.2.5.2.
CAPRISA 012B
The South African Phase 1 study, CAPRISA 012B, entitled “A Phase I Dose-Escalation Study of 
the Safety, Tolerability and Pharmacokinetics of a Human Monoclonal Antibody, CAP256V2LS 
(VRC-HIVMAB0102-00-AB) Administered Intravenously to HIV-Negative and HIV-Positive 
Women or Subcutaneously Alone and in Combination with VRC07-523LS and/or PGT121 to 
HIV-Negative Women in South Africa,” is being conducted, in parallel to VRC 611, under the 
South African Health Products Regulatory Authority (SAHPRA).
A total of 66 women, aged 18 to 45 years, will enroll into the study at the CAPRISA eThekwini 
Clinical Research Site in Durban, South Africa. Groups 1a, 1b, 2, 3, and 4 will consist of 
HIV-negative women (N = 52), while Group 1c and 1d will enroll HIV-positive women (N = 14) 
who have not yet started ART. Safety and PK will be evaluated throughout the study. No SAEs 
have been reported in this study thus far.
This Phase 1 double-blinded, randomized placebo-controlled trial in South African women is 
currently ongoing with only blinded interim safety data available. As of 23 August 2021, 
42 HIV-negative participants have been enrolled into the CAPRISA 012B study.
Overall, reported reactogenicity events ranged from mild to severe and all reactogenicity events 
resolved within the 3-day reactogenicity assessment period. Solicited local reactions were 
reported by 14 out of 42 participants (33%) with 10 (24%) experiencing mild tenderness, 9 
(21%) experiencing pain (8 mild in severity, 1 moderate), 5 (12%) experiencing 
swelling/induration (1 mild in severity, 2 moderate, 1 severe), and 2 (5%) experiencing moderate 
redness/erythema. In the combination group 3a, 2 participants experienced solicited local 
reactions that occurred at the injection site attributed to the VRC07-523LS/placebo injection. In 
the combination group 3b, 4 participants experienced solicited local reactions that occurred at the 
injection site and were attributed to the VRC07-523LS/placebo injection.
Solicited systemic reactions were reported by 40 out of 42 participants (95%) including 
90 participants (86%) experiencing headache, 28 participants (67%) experiencing chills, 
17 participants (40%) experiencing nausea, 20 participants (48%) experiencing malaise and/or 
fatigue, 14 participants (33%) experiencing arthralgia, 10 participants (24%) experiencing raised 
temperature, 7 participants (17%) experiencing vomiting, and 11 participants (26%) experiencing 
myalgia. The majority of systemic symptoms were mild to moderate in severity. Three events 
were reported as severe: 1 (2%) participant with severe headache and 2 (5%) participants with 
severe chills and 1 (2%) participant reported severe malaise and/or fatigue.
There have been no infusion reactions during study drug administration. There were 
76 unsolicited AEs reported in 37 out of 42 (88%) participants, of which 50 events were 
attributed as related to study drug. All events attributed to study injection have resolved to date.
Common events attributed to study drug included:
There were 8 lymphocytopenia events observed in 8 participants, of which 2 were mild (Grade 1 
range, 600 to < 650 cells/mm3), 2 were moderate (Grade 2 range, 500 to < 600 cells/mm3), 
2 events were severe (Grade 3 range, 350 to < 500 cells/mm3), and 2 were graded potentially life 
threatening (Grade 4 range, < 350 cells/mm3). There were 10 proteinuria events observed in 
9 participants, of which 7 were mild and 3 were moderate in severity. There were 8 events of 

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increased AST observed in 8 participants, all of which were mild in severity. There were 
6 events of increased alanine aminotransferase (ALT) observed in 7 participants, of which 6 
were mild and 1 was moderate in severity.
The 2 related Grade 3 AEs of transient decline in lymphocyte counts were observed in 1 
participant who received CAP256V2LS at 5 mg/kg SC without hyaluronidase and 1 participant 
who received CAP256V2LS at 20 mg/kg SC with hyaluronidase. The 2 related Grade 4 AEs of 
transient decline in lymphocyte counts were both observed in participants who received either a 
combination of CAP256V2LS 10 mg/kg and VRC07-523LS 10 mg/kg, or a placebo, with 
hyaluronidase. These events occurred at Day 1 post study drug administration and resolved by 
Day 3 to Day 7. Lymphocytopenia in these participants was accompanied by transient 
nongradable total white blood cell increases due to neutrophilia and transient nongradable 
decreases in eosinophils and monocytes in these participants occurring Day 1 post study drug 
administration that also rapidly resolved by Day 3. One participant with severe lymphocytopenia 
also had Grade 1 transient thrombocytopenia (122,000 cells/mm3) on Day 3 that resolved the 
same day. There were no other hematologic abnormalities and no clinical signs or symptoms in 
any of these participants. Gradable lymphocytopenia events were not associated with route of 
administration, dosage, or hyaluronidase.
The transient decline in lymphocyte counts observed during conduct of the trial prompted a 
protocol-specified study pause by the principal investigators and a Data Safety Monitoring Board 
(DSMB) meeting was convened. After review of the data and consultation with expert 
hematologists, the DSMB concluded that the transient laboratory abnormality did not seem to be 
a safety concern, as occurrences of transient declines in lymphocyte count have been observed in 
animal studies and human studies following the administration of monoclonal antibodies 
{Brinkman 2011, Buysmann 1996, Dettmar 2012, Hansel 2010, Schulz 2007, Soler 2009} and 
all participants were clinically stable and remain well to date. The DSMB also agreed with the 
CAPRISA team recommendation to inform participants about this observation, and to further 
investigate the transient lymphocytopenia in future participants. The DSMB advised that the trial 
resume with recommendations in place.
There were no SAEs and AEs did not result in study drug discontinuation in any participant. 
There have been no suspected unexpected serious adverse reactions (SUSARs) reported to the 
SAHPRA.
For updated clinical information on CAP256V2LS, please refer to the IB for CAP256V2LS.
1.2.6.
Clinical Studies of VRC07-523LS
The clinical experience with VRC07-523LS is derived from 15 clinical studies (3 completed and 
12 ongoing with preliminary data) conducted in the US, the Republic of South Africa, and/or 
Switzerland. Cumulatively (as of October 2020 based on the data presented in the VRC07-523LS 
IB), VRC07-523LS has been administered by IV, SC, or intramuscular (IM) infusion/injection, 
either individually or in combination with other HIV mAbs of different HIV-1 envelope epitope 
specificity, to approximately 230 HIV-uninfected adults and 28 adults with HIV, and 
22 HIV-1-exposed infants. Overall, single-dose regimens of VRC07-523LS ranging from 1 to 
40 mg/kg IV or 5 to 10 mg/kg SC; or repeat-dose regimens ranging from 2.5 to 30 mg/kg IV, 

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2.5 to 10 mg/kg SC, or 2.5 mg/kg IM; have generally been well tolerated in all adult populations 
examined. The limited data in the 22 HIV-1-exposed infants administered VRC07-523LS 
(maximum 100 mg per dose) by SC injection has shown it was well tolerated. No SAEs related 
to VRC07-523LS have been reported in any studies as of 14 October 2020.
Preliminary data obtained from 9 viremic adults with HIV-1 enrolled in Study VRC 607/A5378, 
have shown a majority of participants (8 of 9) administered a single IV dose of VRC07-523LS at 
40 mg/kg achieved a 1.2log10 or greater decrease in viral load 7 days postinfusion {Kippax 
2019}.
Safety summaries for clinical studies of VRC07-523LS are presented in the VRC07-523LS IB.
Pharmacokinetic data from Study VRC605, in which VRC07-523LS was administered IV as a 
single dose of 1, 5, 20, or 40 mg/kg in healthy participants are presented in Figure 1 (blue, red, 
gray, and green lines, respectively) and Table 1 {Gaudinski 2018}. VRC07-523LS Cmax and 
CDay84 increased in a dose-proportional manner across the dose range of 1 to 40 mg/kg. Tmax 
occurred within 0.04 to 0.7 days (1 to 16 hours), and the mean (SD) t1/2 following IV 
administration was approximately 38 (12) days (Figure 1, Table 1). The PK of VRC07-523LS in 
aviremic HIV-positive participants is similar to that observed in healthy volunteers (data not 
shown).
Figure 1.
Serum PK Following Single Dose IV Administration of 1, 5, 20, or 
40 mg/kg VRC07-523LS
IV = intravenous; PK = pharmacokinetics(s)
1000 
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20 
30 
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Time after administration (weeks) 

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Table 1.
Serum PK Parameters Following Single Dose IV Administration of 1, 
5, 20, or 40 mg/kg VRC07-523LS
Dose 
(mg/kg)
Cmax
(μg/mL)
Tmax
(days)
AUCinf
(μg•day/mL)
C28d
(μg/mL)
C84d
(μg/mL)
t1/2 (days)
1
47 (16)
0.7 (0.5)
1381 (325)
14 (7.5)
3.8 (0.7)
48 (26)
5
240 (35)
0.04 (0.02)
4551 (904)
57 (11)
12 (1.8)
32 (1.1)
20
869 (190)
0.3 (0.4)
13,748 (1853)
148 (28)
44 (14)
45 (5.2)
40
1630 (644)
0.04 (0.02)
25,517 (5097)
272 (52)
85 (30)
42 (5.1)
IV = intravenous; PK = pharmacokinetics
Data are presented as mean (standard deviation).
Source: {Gaudinski 2019}
1.3.
Rationale for This Study
Despite the extensive advances made in the treatment of chronic HIV-1 infection, control and/or 
eradication of the latent HIV-1 reservoir is still needed to achieve sustained viral remission or a 
functional cure that abrogates the requirement for lifelong ART. To this end, strategies to target 
latent virus have been tested in a number of clinical studies, but none have resulted in 
long-lasting virologic remission. The immune modulator VES and mAb constitute a promising 
candidate regimen given the preclinical evidence that it can lead to enhanced SHIV control in the 
absence of ART, both in terms of time to rebound and number of animals demonstrating 
sustained control. CD8 depletion in animals with sustained viral control did not lead to 
immediate rebound, indicating the latent SHIV reservoir was reduced to extremely low levels or 
eliminated. In the subsequent studies, the combination of VES with the mAb PGT121 led to 
sustained viral control after ART cessation in 33% to 50% of animals, whereas all control 
animals rebounded {Barouch 2020}. Additionally, VES resulted in a modest, but significant 
delay in time to viral rebound and decrease in viral load set-point in a clinical study of VES in 
HIV viremic controllers (PWH whose pre-ART plasma HIV-1 RNA was between 50 to 
≤ 5000 copies/ml).
These results suggest a promising path toward reduction of HIV reservoirs and ultimately finite 
therapies for HIV-1 infection via a combination of TLR agonists and mAbs on ART. To test this 
concept, clinical trials combining immune modulators (eg, TLR9 agonist, lefitolimod) with 
anti-HIV mAbs (eg, 3BNC117 and 10-1074) in PWH are ongoing without any safety signals to 
date (NCT03837756).
Clinically, 6 mg and 8 mg VES appears to be safe in healthy volunteers and participants with 
HIV infection on ART. The next goal is to measure the efficacy of VES in a sequential regimen 
with mAbs in reducing and/or controlling the HIV-1 reservoir. Measurement of the time to viral 
rebound and/or new viral set-point following ATI is the most definitive method for evaluating 
HIV-1 cure interventions. The ACTG and other groups have demonstrated the safety of ATI in 
chronically-infected PWH, despite the risk associated with viral rebound to high levels. 
Additionally, the safety of ATI has been demonstrated in cohorts from acutely treated 
participants in Spain and Thailand {Julg 2019}, {Li 2016}, {Bar 2016}. Therefore, studying 
“activate and eliminate” interventions in the setting of an ATI in these participants could 
potentially provide useful information and maximize the chances of sustained viral load rebound 
in the absence of ART.

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The prirmuy objective of this study is to evaluate the safety and tolerability of dual anti-HIV 
envelope mAbs, VRC07-523LS and CAP256V2LS, in a sequential regimen with a TLR7 
agonist, VES, when administered in virologically-suppressed women with HIV-1 Clade Con 
ART and dming ATI. The secondaiy objectives of this study are to evaluate the PK of 
VRC07-523LS, CAP256V2LS, and VES, to assess the induction of anti-VRC07-523LS and/or 
anti-CAP256V2LS antibodies, and to assess potential vir·al contrnl or the need for resumption of 
ART following an ATI. This pair of antibodies (VRC07-523LS and CAP256V2LS) was chosen 
due to the predicted complementai tar etin of HIV-1 Clade-C envelo e re ions CD4 bindin 
site and V2 loo 
res ectivel . 
1.4. 
Rationale for Dose Selection 
1.4.1. 
Rationale for Dose Selection of Vesatolimod 
Dose selection for VES is suppo1ted by the available PK, safety, and PD data from the completed 
Study GS-US-382-1450 and Study GS-US-382-3961 in ART-suppressed PWH, as well as the 
completed Study GS-US-243-0101 in healthy volunteers (for fmt her infonnation, please refer to 
the VES IB). The results from these studies indicate that VES is generally well tolerated up to 
12 mg administered as a single dose or multiple doses, given eve1y 2 weeks. As a TLR7 agonist, 
VES is expected to activate its receptor on plasmacytoid dendritic cells or B cells and stimulate 
the production of cytokines. Therefore, AEs related to influenza-like symptoms may be 
expected. When administered alone in ART-suppressed PWH and in healthy volunteers, VES up 
to 8 mg is well tolerated, with mild and infrequent influenza-like AEs (eg, fatigue, headache), 
whereas individuals receiving VES at the 10 mg dose or higher more frequently experienced 
influenza-like AEs. The VES staiting dose selected for this study is 6 mg, with the option for 
intrapaiticipant dose escalation to 8 mg at the thir·d VES administration (Day 28), pending safety 
and tolerability of the 6 mg dose in each paiticipant, with close safety monitoring. Paiticipants 
who escalate to 8 mg VES may remain on 8 mg VES, or de-escalate to 6 mg VES, pending 
safety and tolerability of the 8 mg VES dose in that paiticipant. Paiticipants who de-escalate to 
6 mg VES would remain on 6 mg VES for the remainder of the study. The proposed dose range 
of 6 mg to 8 mg VES is expected to provide exposmes associated with activity, as evidenced by 
induction ofISGs and cellulai· activation observed at VES doses of 4 to 12 mg. 
1.4.2. 
Rationale for Dose Selection of CAP256V2LS 
The dose of 20 mg/kg for CAP256V2LS was selected based on the PK and safety of the ongoing 
Study CAPRISA 012B. Following the 20 mg/kg IV dose, antibody levels in Periods 1 and 2 ai·e 
anticipated to provide antiviral activity, while in Period 3, antibody levels are anticipated to 
decline below therapeutic concentrations (as defined as approximately 100-fold higher than in 
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vitro IC50), allowing the assessment of viral control potentially resulting from HIV reservoir 
reduction and/or immunologic control.
1.4.3.
Rationale for Dose Selection of VRC07-523LS
Dose selection for VRC07-523LS is supported by PK and safety data from the completed 
Study VRC605 and the ongoing Study VRC607. In these studies, IV administration of 
VRC07-523LS single dose up to 40 mg/kg has been shown to be safe and well tolerated. The 
proposed dose of 20 mg/kg IV administered on Day 7 is predicted to provide concentrations of 
VRC07-523LS > 20 μg/mL through the end of Period 2 (Week 19); 20 μg/mL VRC07-523LS is 
approximately 100-fold higher than the in vitro IC80, corresponding to a predicted > 80% 
neutralization coverage of sensitive HIV viruses {Gaudinski 2019}. In Period 3, VRC07-523LS 
concentrations are predicted to be subtherapeutic (< 20 μg/mL), allowing the assessment of viral 
control potentially resulting from HIV reservoir reduction and/or immunologic control.
1.5.
Risk/Benefit Assessment for the Study
Based on the current available clinical data, potential risks associated with VES include transient 
influenza-like symptoms, such as chills, pyrexia, aches, and headache and CRS. In completed 
and ongoing studies of VES, the majority of the influenza-like symptoms have been mild and 
transient. One healthy volunteer who received 1 dose of VES 8 mg coadministered with EVM 
250 mg experienced a Grade 3 SAE of CRS that was considered related to VES, leading to 
treatment and observation in the hospital followed by full recovery (Section 1.2.1). The other 
3 participants receiving this regimen did not experience SAEs. Co-administration of EVM and 
VES 6 mg was generally safe and well tolerated in virologically-suppressed people with HIV-1 
on ART. In this study, VES will not be coadministered on the same day as VRC07-523LS and 
CAP256V2LS, but rather separated by at least 7 days. Furthermore, these antibodies are not 
known to have off-target binding and have not been engineered with the same Fc-enhancement 
mutations as EVM, further lowering the risk of toxicity. There is no known or expected 
overlapping safety risk with VES, VRC07-523LS, and CAP256V2LS. However, it is possible 
that administration of VES in the presence of detectable plasma concentrations of VRC07-523LS 
and CAP256V2LS may transiently increase the risk of inflammatory events (see below). 
Additionally, as VES-related AEs are more common following Doses 1 and 2, enhanced 
monitoring after the first 2 doses of VES is proposed with adaptive monitoring thereafter. 
Participants will be monitored on site following study drug administration, and an external data 
monitoring committee (DMC) will evaluate safety data after the first 5 participants have reached 
Day 21. Nonclinical studies have reported findings of thrombocytopenia, hematologic effects, 
and hepatic injury. Hematologic effects or hepatic injury have not been observed in clinical 
studies. At the 12 mg dose level of VES in healthy volunteers (Study GS-US-243-0101), 
nongraded nonclinically significant decreases in platelet counts were observed in some 
participants, which resolved within 2 days without intervention. Treatment-emergent platelet 
decreases have not been observed at doses up to 12 mg in PWH in Study GS-US-382-1450 or in 
Study GS-US-382-3961. Safety laboratory values, including complete blood count and chemistry 
panels, will be regularly monitored throughout the study.

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Intravenous administrations of VRC07-523LS to approximately 161 adults have been well 
tolerated. Observed local reactogenicity events have been of low frequency, and have included 
mild pain/tenderness, bruising, swelling, localized erythema, and mild paresthesia at the site of 
infusion that resolved within a few minutes to a few hours after the study drug administration. 
Most participants reported no systemic reactogenicity symptoms with VRC07-523LS IV 
administration; when observed, systemic symptoms were mostly mild, less frequently of 
moderate severity, started 1 to 3 days after study drug administration, and lasted 1 to 2 days. The 
most commonly reported symptoms following IV administration have been malaise, myalgia, 
headache, nausea, and joint pain. All other drug-related AEs have been of low frequency and 
mild or moderate in severity, and have resolved with no residual effects.
Among the approximately 161 participants who have received VRC07-523LS IV, 12 participants 
have experienced 16 infusion reaction episodes, including 1 participant who experienced an 
infusion reaction with all 3 administrations. Observed infusion reactions developed within 1 hour 
of infusion and were Grade 1 or 2 in severity, with symptoms typical of those observed with 
administration of other mAbs: fever, rigors, back pain, abdominal pain, nausea, flushing, 
pruritus, and changes in heart rate and blood pressure {Gaudinski 2018, Patel 2012}. No 
participants required treatment with epinephrine or steroids and were treated symptomatically. 
Three participants discontinued drug administrations due to an infusion reaction. For the 
remaining participants who experienced infusion-related reactions, VRC07-523LS dosing 
continued at a reduced infusion rate per protocol with no increase in severity of symptoms 
observed with subsequent infusions.
Clinical studies of CAP256V2LS are ongoing. As of 23 August 2021, 40 HIV-negative 
participants received CAP256V2LS in the CAPRISA012B study. There were no SAEs and AEs 
did not result in study drug-drug discontinuation in any participant. There have been no SUSARs 
reported to SAHPRA.
There were 8 transient lymphocytopenia events observed in 8 participants, ranging from Grade 1 
to 4 in severity. These events occurred at Day 1 post study drug administration and resolved by 
Day 3 to Day 7. There were no clinical signs or symptoms and no other clinically relevant 
hematologic abnormalities in these participants. There have been no infusion reactions during 
study drug administration.
To date, the transient laboratory abnormalities do not represent a safety concern, as occurrences 
of transient declines in lymphocyte count have been observed in animal studies and human 
studies following the administration of many monoclonal antibodies.
Participants will be monitored on site following study drug administration, and safety laboratory 
values, including complete blood count and chemistry panels, will be regularly monitored 
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Typically, the side effects of mAbs are mild to moderate and may include local reactions at the 
injection site (including pain, redness, bruising, swelling) and systemic reactions such as fever, 
chills, rigors, nausea, vomiting, pain, headache, dizziness, shortness of breath, bronchospasm, 
hypotension, hypertension, pruritus, rash, urticaria, angioedema, diarrhea, tachycardia, or chest 
pain. When infused IV, infusion-related events most commonly occur within hours of initiation 
of mAb administration. Infusion-related reactions are common with licensed therapeutic mAbs, 
and typical symptoms include mild fevers, rigors, backpain, abdominal pain, nausea, vomiting, 
diarrhea, dyspnea, flushing, pruritus, or changes in pulse rate and blood pressure {Patel 2012}. 
Infusion-related reactions are managed by temporarily stopping the infusion, administering 
histamine blockers and restarting the infusion at a slower rate {Vogel 2010}.
Clinical use of mAbs that are targeted to cytokines or antigens associated with human cells may 
be associated with an increased risk of infections {Hansel 2010}; however, this is not expected 
to be a risk for a mAb targeted to a viral antigen.
Less commonly, administration of mAbs may cause severe immune reactions such as acute 
anaphylaxis, CRS, serum sickness, and the generation of antidrug antibodies. These reactions are 
rare and more often associated with mAbs targeted to human proteins or with the use of mouse 
or chimeric mAbs that would have a risk of human antimouse antibodies {Hansel 2010}. In this 
regard, CAP256V2LS and VRC07-523LS are expected to have a low risk of such side effects 
since they are directed against a viral antigen and are of human in origin.
Published experience with other human mAbs directed against cell surface targets on 
lymphocytes shows that infusion of a mAb may be associated with cytokine release, causing a 
reaction known as CRS {Bugelski 2012}.In contrast to the mild infusion reactions described 
above, CRS is rare and mechanistically associated with indiscriminate activation of immune cells 
leading to a cytokine storm characterized by severe headaches, low back pain, nausea, vomiting, 
diarrhea, fever, disseminated intravascular coagulation, and other symptoms of critical illness 
including respiratory and renal failure requiring intensive care treatment.
Delayed allergic reactions to other mAbs that include a serum sickness type of reaction 
characterized by urticaria, fever, lymph node enlargement, and joint pains, typically occur 
several days after mAb exposure and are more commonly associated with chimeric types of 
mAbs {Hansel 2010}.
To mitigate the risk of infusion-related reactions, anaphylaxis, CRS, and serum sickness, 
intensive clinical monitoring will occur during the course of the study. Anaphylactoid and 
infusion-related reactions, including fevers, chills, rigors, changes in blood pressure, 
bronchospasm, and other AEs, will be closely monitored. Furthermore, sentinel dosing will 
occur, thereby limiting the numbers of participants exposed and the number of additional 
participants who may enroll and initiate study drug therapy.
Potential risks of ATI include rebound of plasma HIV-1 viremia to > 50 copies/mL, which may 
result in the development of HIV-1 resistance mutations, decrease in CD4+ T cell count, 
symptoms of retroviral syndrome, and transmission of virus to other individuals.

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To mitigate these risks, plasma viral load and CD4+ T cell count will be measured frequently 
during ATI, and ART will be promptly reinitiated according to the protocol-defined algorithm. 
Participants will also be monitored for AEs, and ART will be reinitiated if these are judged 
(by the investigator and/or sponsor) to be related to the ATI. The initial selection of participants 
who have a documented detection during acute HIV infection and timing of ART initiation, 
durable viral suppression for at least 12 consecutive months prior to the screening visit, and the 
availability of a fully active alternative ART regimen, in the event of discontinuation of the 
current ART regimen with development of resistance, will further minimize the risks of ATI.
Potential benefits include reduction of the latent HIV-1 viral reservoir, enhanced immune control 
of virus producing cells, and finally the combination of these effects on HIV-1 viral control 
(measured as plasma virus rebound and viral load set-point) in the absence of ART. There are no 
direct benefits to participants participating in this study.
During a pandemic, additional potential risks to the conduct of the study may include adequate 
study drug availability, interruptions to the study visit schedule, and adherence to 
protocol-specified treatment regimen, safety monitoring or laboratory assessments. Refer to 
Appendix 7 for further details on the risks and risk mitigation strategy.
Considering the above, the benefit-risk balance for this study is considered positive.
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.

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2_ 
OBJECTIVES 
The prima1y objective of this study is as follows: 
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• 
To evaluate the safety and tolerability of dual anti-HIV envelope mAbs, VRC07-523LS and 
CAP256V2LS, in a sequential regimen with a TLR7 agonist, VES, when administered in 
virologically suppressed HIV-1 Clade C-infected women on ART and during ATI 
The secondaiy objectives of this study are as follows: 
• 
To evaluate the PK ofVRC07-523LS, CAP256V2LS, and VES 
• 
To evaluate whether VRC07-523LS and CAP256V2LS induce anti-VRC07-523LS and/or 
anti-CAP256V2LS antibodies 
• 
To evaluate the effect ofVRC07-523LS and CAP256V2LS in a sequential regimen with 
VES on viral control or the need for resumption of ART following an ATI. 
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STUDY DESIGN 
3.1. 
Endpoints 
The prirmuy endpoints of this study are as follows: 
• 
The proportion of participants with ti·eatment-emergent AEs 
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• 
The propo1tion of pa1ticipants with ti·eatment-emergent graded laborato1y abnonnalities 
The secondaiy endpoints of this study ai·e as follows: 
Virology/Efficacy 
• 
Time to viral rebound (confinned 50 copies/mL and~ 200 copies/mL) following ATI 
• 
The change in plasma viral load set-point following ATI 
• 
Viral load at the end of ATI 
• 
Time to ART resumption following ATI 
Phaimacokinetics 
• 
PK pai·aineters for VES in plasma will include Cmax, Tmax, Clast, Tlast, AUCinf, AUClast, 
AUCexp, tl/2, CL/F, and Vz/F. 
• 
PK paraineters for VRC07-523LS and CAP256V2LS in senun will include Cmax, Tmax, 
Clast, Tlast, AUCinf, AUClast, AUCexp, tl/2, CL, Vss, and Vz. 
Immunogenicity 
• 
The proportion of paiticipants with positive anti-VRC07-523LS or anti-CAP256V2LS 
antibodies 
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3.2. 
Study Design 
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This is an open-label, single-center, single-aim study to evaluate a sequential regimen of dual 
mAbs, VRC07-523LS and CAP256V2LS with a TLR7 agonist, VES, in paiiicipants from the 
Females Rising through Education, Suppo1i, and Health (FRESH) coho1i . 
The FRESH coho1i consists of women with HIV-1 Clade C in Durban, South Africa, who were 
initiated on ART immediately after detection ofHIV-1 RNA and are virologically suppressed on 
ART. 
Paiiicipants will attend study visits and undergo assessments over 4 periods for a maximum of 
60 weeks. During Periods 1 and 2, paiticipants will be evaluated weekly at a minimum and 
during Periods 3 and 4, eve1y 2 weeks at a minimum. Vesatolimod will be dosed orally, eve1y 
2 weeks, for a total of 10 doses during Periods 1 and 2. Paiiicipants will receive a first dose of 
VES alone in Period 1 prior to single, sequential infusions ofVRC07-523LS and CAP256V2LS 
administration 1 week later. 
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Figure 2.
Study Schema
Screeninga
Prebaseline
Period 1b
Period 2c
Period 
3d
End-of-
Period 3 
Visite
Period 4f
ESDD and 
Follow-Up 
Procedureg
End-
of-
Study 
Visith
 
 
Continue 
ART 
ATI from 
Day 35
ATI 
 
4A–(ART 
restarti) or 
4B (ATI 
Extensionj)
 
 
≤ 35 days 
Day −13 
Days 0-28 
Days 29-
133 
Days 
134-
336 
 
Days 337-
413
 
 
 
 
VES Doses
1-3k
VES 
Doses
4-10k
No 
Dosing
 
No
Dosing 
 
 
 
 
VRC07-
523LS and 
CAP256V2LS
Dosesl
 
 
 
 
 
 
ART = antiretroviral therapy; ATI = analytical treatment interruption; VES = vesatolimod
a
Screening must occur 35 days prior to prebaseline/Day −13 visit.
b
During Period 1, participants will have a study visit every week at a minimum over 4 weeks. Participants will continue to 
take their ART during this period.
c
During Period 2, participants will have a study visit every week at a minimum over 15 weeks. No VRC07-523LS and 
CAP256V2LS dose to occur in this period. No ART will be administered and ATI will start from Day 35. If the ART restart 
criteria are met, the participant may stop Period 2, complete the end-of-Period 3 visit, and restart ART in Period 4A.
d
During Period 3, participants will have a study visit every 2 weeks over 28 weeks. No study drug (VES, VRC07-523LS, or 
CAP256V2LS) will be administered in this period. No ART will be administered, and ATI will continue. If the ART restart 
criteria are met, the participant may stop Period 3, complete the end-of-Period 3 visit, and restart ART in Period 4A.
e
The visit will be completed at the end of Period 3 or if ART restart criteria are met prior to starting Period 4A.
f
Participants who have remained virologically suppressed (plasma HIV-1 RNA < 50 copies/mL) or have not met the ART 
restart criteria by the end of Period 3 will continue into Period 4. The option will be available for either Period 4A, restart of 
ART for 12 weeks, or Period 4B, to remain off ART for a 12-week ATI extension. The choice of Period 4A or 4B will be at 
the discretion of the participant and investigator. Participants who meet the ART restart criteria prior to the end of Period 3 
may also take part in Period 4A. No study drug (VES, VRC07-523LS, and CAP256V2LS) will be administered in this 
period.
g
If a participant should discontinue study dosing as described in Section 6.9.1, they will be required to complete an early 
study drug discontinuation (ESDD) visit and every attempt should be made to keep the participant in the study and continue 
to perform study procedures. If the participant is unable to complete all scheduled procedures, for criteria other than those 
described for study discontinuation in Section 3.5., the participant should be followed by telephone for a further duration of 
time as described in Section 6.9.2. If a participant has completed all study drug dosing but is unable to complete all 
subsequent visits at the study site, as scheduled in Periods 3 and 4, for criteria other than those described for study 
discontinuation in Section 3.5. for study discontinuation, the participant they should be followed by telephone for up for 250 
days after mAb infusion. During follow up with telephone check-ups, participants should be followed every 4 weeks to 
monitor for AEs and retrieve urine pregnancy results (kits to be provided at the last study site visit and a positive urine 
pregnancy result will require confirmation with a serum pregnancy test at the study site). At the end of all follow-up 
monitoring, participants will undergo the end-of-follow-up visit at the study site.
i
Participants who restart ART in Period 4A will complete 6 study visits scheduled every 2 weeks over a 12-week period.
j
Participants who opt to remain off ART and complete the ATI extension will complete 6 study visits scheduled every 
2 weeks over a 12-week period.
k
VES dose administration to occur at baseline/Day 0 and then every 2 weeks up to Dose 10.
l
VRC07-523LS and CAP256V2LS sequential dose administration to occur only once at Day 7.

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During Period 1, VRC07-523LS, CAP256V2LS, and VES will be administered together with 
ART.
Sentinel Dosing: Participants will be enrolled and dosed in a staggered fashion, with a sentinel 
group consisting of 5 participants conducting Period 1 visits and assessments up to Day 21 first. 
The safety data of the first 5 participants will be reviewed by an external DMC, and upon 
confirmation, up to a further 20 participants will be enrolled into Period 1.
During Period 2, the participants will be administered VES and discontinue ART to start ATI 
with weekly plasma virus monitoring at each study visit.
In Period 3, no treatment (VES, VRC07-523LS, CAP256V2LS, or ART) will be administered, 
participants will continue ATI and plasma virus levels will be monitored.
At the end of Period 3 or if ART restart criteria are met prior to starting Period 4A, participants 
will be required to complete an end-of-Period 3 visit.
In Period 4, participants who have remained virologically suppressed (plasma HIV-1 RNA 
< 50 copies/mL) or have not met the ART restart criteria by the end of Period 3 will continue in 
either Period 4A and restart ART for 12 weeks, or in Period 4B and remain off ART for a 
12-week ATI extension. The choice of Period 4A or 4B will be at the discretion of the participant 
and investigator.
If the ART restart criteria are met prior to the end of Period 3, participants may also receive ART 
for 12 weeks in Period 4A.
At the end of Period 4, all participants will complete an end-of-study visit.
If a participant should discontinue study dosing as described in Section 6.9.1, they will be 
required to complete an early study drug discontinuation (ESDD) visit and every attempt should 
be made to keep the participant in the study and continue to perform study procedures. If the 
participant is unable to complete all scheduled procedures, for criteria other than those described 
for study discontinuation in Section 3.5, the participant should be followed by as described in 
Section 6.9.2.
If a participant has completed all study drug dosing but is unable to complete all subsequent 
visits at the study site, as scheduled in Periods 3 and 4, for criteria other than those described for 
study discontinuation in Section 3.5, the participant should be followed by telephone for up for 
250 days after mAb infusion.
During follow up with telephone check-ups, participants should be followed every 4 weeks to 
monitor for AEs and retrieve urine pregnancy results (kits to be provided at the last study site 
visit and a positive urine pregnancy result will require confirmation with a serum pregnancy test 
at the study site).
At the end of all follow-up monitoring, participants will undergo the end-of-follow-up visit at the 
study site..

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ART Restart Criteria: Participants will receive ART in Periods 1 and 4A only. In Periods 2, 3, 
and 4B, participants will be in ATI and will restart ART if they have plasma HIV-1 RNA 
measurements of ≥ 1,000 copies/mL for 8 consecutive weeks and no drop of 0.3 log10 from the 
previous week, or confirmed plasma HIV-1 RNA > 100,000 copies/mL, or a confirmed CD4+ 
T cell count < 350 cells/μL, or if a participant becomes pregnant, or per participant request, or at 
the discretion of the investigator or sponsor due to other clinical criteria. Once the first confirmed 
HIV-1 RNA value of ≥ 50 copies/mL is detected, this will trigger weekly testing to monitor the 
HIV-1 RNA measurements.
Known HIV-seronegative male partners to the female study participants may be referred for HIV 
preexposure prophylaxis (PrEP) to decrease the risk of HIV transmission during ATI.
3.3.
Study Treatments
Participants will receive a single, sequential infusion of VRC07-523LS and CAP256V2LS in 
combination with a total of 10 VES doses received every 2 weeks during Periods 1 and 2. 
Participants will receive the first dose of VES alone and VRC07-523LS and CAP256V2LS will 
be administered 1 week later. Participants will continue their prescribed ART regimen during 
Period 1, and may restart ART in Period 4A, upon conclusion of Period 3 or if the ART restart 
criteria are met during Periods 2, 3, and 4B.
3.4.
Duration of Treatment
Participants will receive study drugs, VRC07-523LS, CAP256V2LS, and VES, for a maximum 
of 18 weeks during Periods 1 and 2. Participants who have remained virologically suppressed 
(plasma HIV-1 RNA < 50 copies/mL) or have not met the ART restart criteria by the end of 
Period 3 (maximum 43 weeks ATI [Periods 2 and 3]) will continue in either Period 4A and 
restart ART for 12 weeks, or Period 4B and remain off ART for a 12-week ATI extension.
3.5.
 Protocol-specific Discontinuation Criteria

Intercurrent illness, unacceptable toxicity, or toxicity that would, in the judgment of the 
investigator, affect assessments of clinical status to a significant degree and/or compromises 
the participant’s ability to continue in the study or is considered to not be in the participant’s 
best interest

Participant request to discontinue for any reason

Participant noncompliance

Discontinuation of the study at the request of Gilead Sciences (Gilead), a regulatory agency, 
or an institutional review board (IRB) or independent ethics committee (IEC)
3.6.
End of Study
The end of study will be the last participant’s last observation (or visit).

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3.7.
Poststudy Care
After a participant has completed/terminated their participation in the study, long-term care for 
the participants will remain the responsibility of their primary treating physician.
3.8.
Source Data
The source data for this study will be obtained from participants clinical/hospital records, 
interactive web response system (IWRS), central laboratory, local laboratory, and specialty 
laboratory.
3.9.
Biomarker Testing
3.9.1.
Biomarker Samples to Address the Study Objectives
The following biological specimens will be collected from all participants who have provided 
consent to participate in this study and may be used to evaluate the association of systemic 
and/or tissue-based biomarkers with study drug response (including efficacy and/or AEs) and 
dosage selection, and to better understand the biological pathways, biology of HIV or related 
diseases, and/or the validation of a companion diagnostic for HIV cure. Because biomarker 
science is a rapidly evolving area of investigation, and AEs in particular are difficult to predict, it 
may not be possible to specify prospectively all tests that may be done on the specimens 
provided. The specific analyses will include but may not be limited to the biomarkers and assays 
listed below. The testing outlined below is based upon the current state of scientific knowledge. 
It may be modified during or after the end of study to remove tests no longer indicated and/or to 
add new tests based upon new state of the art knowledge.
Samples will be collected to measure biomarkers that may include but will not be limited to:
Blood specimens will be collected (> 1 time) at prebaseline/Day −13, baseline, 1-day and 7-day 
after VES, at various time points during the study (please see Appendix 2, Study Procedures 
Table), end-of-Period 3 visit, and at the end-of-study visit for the isolation of PBMCs and 
plasma/serum for analyzing immune cell activation/phenotype, HIV-specific T cell responses, 
soluble protein (cytokines, chemokines, and inflammatory markers), CD4+ and CD8+ T cell 
absolute count, percentage, and CD4/CD8 ratio, and HIV-specific antibody profiling. Blood 
samples will be collected at prebaseline/Day −13 to evaluate soluble proteins in the TruCulture® 
Whole Blood Culture System.
From participants who provide additional consent, lymph node and GALT biopsies will be taken 
for some or all of the following tests: immunophenotyping, viral reservoir measurements, gene 
expression analysis and glycosylation profile analysis (depending on viable cells isolated).
Samples collected for biomarker assessments will be destroyed no later than 15 years after the 
end of study or per country requirements.

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4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection
Approximately 25 participants will be enrolled in the study.
4.1.1.
Participant Replacement
Participants who discontinue before 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) Females recruited from the FRESH acute HIV infection cohort
2) Age ≥ 18 years
3) Plasma HIV-1 RNA levels < 50 copies/mL at the screening visit
4) On ART regimen for ≥ 12 consecutive months prior to the screening visit
a.
The following agents are allowed as part of the current ART regimen: nucleoside 
reverse-transcriptase inhibitors, raltegravir, bictegravir, dolutegravir, and rilpivirine.
b. A change in ART regimen ≤ 45 days prior to the prebaseline/Day −13 visit for reasons 
other than virologic failure (eg, tolerability, simplification, drug-drug interaction profile) 
is allowed. If the participant’s ART regimen is changed, a plasma HIV-1 RNA level 
< 50 copies/mL at the prebaseline/Day −13 visit will be required to confirm eligibility.
c.
Availability of a fully active alternative ART regimen, in the opinion of the investigator, 
in the event of discontinuation of the current ART regimen with development of 
resistance
5) Have all the following laboratory values at the screening visit:
a.
Hemoglobin ≥ 10.0 g/dL
b. White blood cells ≥ 2500 cells/μL
c.
Platelets ≥ 125,000/mL
d. Absolute neutrophil counts ≥ 1000 cells/μL
e.
CD4+ T cell count ≥ 500 cells/μL
f.
ALT, AST, and bilirubin ≤ 2 × upper limit of normal (ULN)
g. Creatinine clearance ≥ 60 mL/min using Cockcroft-Gault formula {Cockcroft 1976}
1) Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in 
kg)]/[72 × (serum creatinine in mg/dL)] × 0.85
6) Women of childbearing potential to have documentation of agreement to follow study 
contraceptive requirements as outlined in Appendix 5

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7) Documented plasma HIV-1 RNA viral load must be < 50 copies/mL for 12 consecutive 
months prior to screening:
a.
≤ 2 detectable HIV-1 RNA measurements that must be ≤ 1000 copies/mL at 
nonconsecutive visits within 12 months are acceptable
b. Determinations below the level of quantitation will be considered as detectable at the 
assay’s threshold level
8) In the judgment of the investigator, be in good general health, based on review of the results 
from a screening visit (to include physical examination, measurement of vital signs, resting 
12-lead electrocardiogram [ECG] and routine clinical laboratory testing), performed no more 
than 28 days prior to study drug administration
9) Must be willing and able to comply with all study requirements and available to complete the 
study schedule of assessments
10) Documented history of viral sensitivity to VRC07-523LS or CAP256V2LS at the screening 
visit
4.3.
Exclusion Criteria
Participants who meet any of the following exclusion criteria are not eligible to be enrolled in 
this study:
1) Positive serum pregnancy test
2) Nursing females
3) Participants with coinfection and/or immunosuppression as described below:
a.
Autoimmune disease requiring ongoing immunosuppression (except in the case of mild 
autoimmune disease that only requires topical treatments)
b. Evidence of chronic HBV infection (defined as positive HBsAg OR positive hepatitis B 
core antibody and negative hepatitis B surface antibody)
c.
Evidence of current HCV infection (defined as positive hepatitis C antibody and HCV 
RNA > lower limit of quantitation [LLOQ])

positive anti-HCV antibody and negative HCV polymerase chain reaction results are 
acceptable
d. Documented history of pre-ART CD4+ T cell count nadir < 200 cells/μL (unknown 
pre-ART CD4+ T cell count nadir is acceptable)
e.
History of opportunistic illness indicative of Stage 3 HIV as referenced in Appendix 6
f.
Acute febrile illness within 4 weeks prior to the first dose
4) Have current alcohol or substance abuse judged by the investigator to potentially interfere 
with participant’s compliance or participant’s safety
5) Have poor venous access that limits phlebotomy

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6) Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic 
agents within 3 months prior to screening or are expected to receive these agents during the 
study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
7) Have previous or current receipt of humanized or human mAbs, or polyclonal 
immunoglobulin
8) Have previous history of an antidrug antibodies response to a therapeutic agent
9) Have previous receipt of an HIV vaccine
10) Received any vaccine or immunomodulatory medication within 4 weeks prior to screening. 
Elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study 
will require prior approval from the sponsor
a.
COVID-19 vaccinations are allowed, with the requirement that they should not be 
administered within 5 days of receiving IMP
11) Have a history of any of the following:
a.
Significant serious skin disease, such as but not limited to rash, food allergy, eczema, 
psoriasis, or urticaria
b. Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity). Any 
history of anaphylaxis and related symptoms such as hives, respiratory difficulty, or 
angioedema
c.
Known hypersensitivity to the study drugs, metabolites, or formulation excipients
d. Previous or current history of bleeding disorder, platelet disorder including unexplained 
acute or chronic thrombocytopenia
e.
Autoimmune diseases including type 1 diabetes mellitus
12) Have current Class C AIDS-defining condition
13) Have any serious or active medical or psychiatric illness (including depression) that, in the 
opinion of the investigator, would interfere with participants treatment, assessment, or 
compliance with the protocol. This would include renal, cardiac, hematological, hepatic, 
pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, 
gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), 
immunodeficiency disorders other than HIV-1 infection, active infection, or malignancy that 
are clinically significant or requiring treatment
14) Participation in any other clinical study (including observation studies) without prior 
approval from the sponsor is prohibited while participating in this study

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Treatment Assignment
It is the responsibility of the investigator to ensure that the participants are eligible for the study 
prior to enrollment. Participants will be assigned a screening number at the time of consent.
Treatment assignment in the interactive voice/web response system will be performed in clinic at 
the baseline/Day 0 visit, provided that all other screening procedures have been completed and 
participant eligibility has been confirmed. If a participant’s ART regimen is changed ≤ 45 days 
prior to prebaseline/Day −13, plasma HIV-1 RNA < 50 copies/mL at prebaseline/Day −13 visit 
is required to confirm eligibility. Once a participant number has been assigned, it will not be 
reassigned to any other participant.
5.2.
Description and Handling
5.2.1.
Formulation
Vesatolimod, 2 mg tablets, are round, biconvex, plain-faced, and film-coated white. Vesatolimod 
tablets contain the following inactive ingredients: lactose anhydrous, microcrystalline cellulose, 
croscarmellose sodium, magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc, and 
titanium dioxide.
VRC07-523LS is a sterile, aqueous buffered solution filled into 10 mL single-dose glass vials. 
Each vial contains a volume of 6.25 ± 0.1 mL or 2.25 ± 0.1 mL at a concentration of 
100 ± 10 mg/mL in formulation buffer composed of 50 mM histidine, 50 mM sodium chloride, 
5% sucrose, and 2.5% sorbitol at pH 6.8.
CAP256V2LS is a sterile aqueous buffered solution filled into 10 mL single-dose glass vials. 
Each vial contains 6.25 ± 0.1 mL at a concentration of 100 ± 10 mg/mL in formulation buffer 
composed of 20 mM sodium phosphate, 100 mM sodium chloride, 75 mM L-arginine HCl, 
3% (w/w) sucrose, and 0.01% (w/v) polysorbate 80 at pH 7.0.
5.2.2.
Packaging and Labeling
Vesatolimod tablets are packaged in white, high-density polyethylene bottles. Each bottle 
contains 3 tablets or 4 tablets, silica gel desiccant, and polyester packing material. Each bottle is 
capped with a child-resistant polypropylene screw cap fitted with an induction-sealed, 
aluminum-faced liner.
VRC07-523LS drug product is aseptically filled into 10 mL single-dose glass vials, stoppered, 
and sealed.
CAP256V2LS drug product is aseptically filled into 10 mL single-dose glass vials, stoppered, 
and sealed.
Study drug(s) to be distributed to centers in South Africa shall be labeled to meet applicable 
requirements of the SAHPRA and/or other local regulations

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5.2.3.
Storage and Handling
Vesatolimod 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. Keep the bottles tightly closed.
VRC07-523LS vials should be stored at −35°C to −15°C as indicated on the product label until 
use. VRC07-523LS vials stored at clinical sites should be in a qualified, continuously monitored, 
temperature-controlled freezer with temperature excursions between −45°C to −10°C is 
acceptable.
CAP256V2LS vials should be stored at −35°C to −15°C as indicated on the product label until 
use. CAP256V2LS vials stored at clinical sites should be in a qualified, continuously monitored, 
temperature-controlled freezer. Each vial is intended strictly for single use; refreeze and reuse 
after thaw should be avoided.
Until dispensed to the participants, the study drug should be stored in a securely locked area, 
accessible only to authorized site personnel. To ensure proper product identification, the drug 
products should be stored in the containers in which they are 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 the study drug.
5.3.
Dosage and Administration
On dosing days, VES (6 mg [3  2 mg tablets] for Doses 1 and 2; 6 mg [3  2 mg tablets] or 
8 mg [4  2 mg tablets] for Doses 3-10 per discussion with and approval from the Gilead medical 
monitor based on safety and tolerability of prior doses) should be administered orally by a 
participant with approximately 240 mL of water on an empty stomach (ie, no food or liquids 
except water for at least 2 hours prior to dosing; overnight fasting is preferable). Participants will 
not be allowed to consume water 1 hour before and 2 hours after dosing, except for the 240 mL 
administered with VES. Participants should remain fasted without food until 2 hours after 
dosing. Participants will be asked to provide information on food consumption and total fasting 
time prior to dosing.
There are no fasting requirements on VRC07-523LS and CAP256V2LS dosing days:

VRC07-523LS, 20 mg/kg, IV infusion over 30 minutes

CAP256V2LS, 20 mg/kg, IV infusion over 30 minutes
Supportive medications, including but not limited to antihistamines (such as diphenhydramine), 
acetaminophen (paracetamol), and steroids, will be available in the clinic settings during the IV 
infusions.

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Study drug infusion may be slowed and/or discontinued if an infusion-related adverse reaction 
occurs. Symptom severity will be evaluated, and supportive medications will be provided as 
clinically indicated. Study drug infusion may be resumed upon symptom resolution. If the 
symptoms, in the judgment of the investigator and the medical monitor, compromise the ability 
to continue study-specific procedures or are considered to not be in the participant’s best 
interests, the infusion will be permanently discontinued.
5.4.
Prior and Concomitant Medications
Due to potential for interference with VRC07-523LS or CAP256V2LS mAb binding or activity, 
CCR5 inhibitors (maraviroc), fusion inhibitors, and mAb HIV entry inhibitors (Trogarzo) are 
prohibited from use during this study.
No clinical drug-drug interaction studies have been conducted with VES. Based on nonclinical 
data, VES is predominantly metabolized by cytochrome P450 enzyme (CYP)3A with minor 
contribution of CYP2C8 and CYP2D6 and was shown to be a substrate of P-glycoprotein (P-gp) 
and breast cancer resistance protein (BCRP). Vesatolimod plasma exposure may increase or 
decrease on co-administration with CYP3A/P-gp/BCRP inhibitors or inducers.
ART agents known to inhibit or induce CYP3A/P-gp/BCRP are excluded from use in this study. 
Due to the potential for a PK-mediated drug-drug interaction, the following agents are NOT 
allowed as part of the current ART regimen: HIV protease inhibitors (including low-dose 
ritonavir), cobicistat-containing regimens, elvitegravir, efavirenz, etravirine, and nevirapine.
Concomitant use of herbal/natural supplements with VES may result in PK interactions resulting 
in alterations in exposure of VES. Administration of VES with grapefruit juice or Seville orange 
juice may result in higher exposures to VES. Participants will refrain from consumption of 
grapefruit juice, grapefruits, and Seville orange juice from enrollment to the end of Period 2.
Medications that are prohibited or to be used with caution are listed in Table 2; this table is not 
exhaustive. Administration of any of the disallowed medications listed in Table 2 must be 
discontinued at least 14 days prior to the prebaseline/Day −13 and through completion of 
Period 2 or the ESDD visit.
Any medications not on the list must be reviewed with the sponsor prior to enrollment and 
during the study treatment period.
Vitamins and/or acetaminophen (paracetamol) and/or ibuprofen and/or hormonal contraceptive 
medications are exceptions and are allowed during the study period. No immunomodulatory 
concomitant medications are allowed within 4 weeks prior to screening.
At clinically achieved plasma concentrations, VES is not expected to be a perpetrator of systemic 
drug-drug interactions.

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Table 2.
Medications Prohibited
Drug Class
Agents Disallowed
Acetyl-coenzyme A acetyltransferase inhibitor
Avasimibe
Angiotensin-converting enzyme inhibitors
Captopril
Analeptic
Modafinil, lomitapide
Angiotensin II inhibitors
Telmisartan
Anti-anginals
Ranolazine
Anti-arrhythmics
Amiodarone, dronedarone, quinidine
Antibiotics
Azithromycin, clarithromycin, erythromycin, nafcillin, 
telithromycin
Anticonvulsants
Carbamazepine, phenytoin, phenobarbital, 
oxcarbazepine, cenobamate
Antidepressants
Fluvoxamine, nefazodone, venlafaxine, ziprasidone, 
paroxetine
Antidiabetics
Pioglitazone
Antiepileptics
Divalproex
Antiemetics
Aprepitant, casopitant
Antifungals
Caspofungin, ketoconazole, itraconazole, voriconazole, 
posaconazole, fluconazole, clotrimazole
Antimigraine
Rimegepant
Antimycobacterials
Rifampin, rifapentine 
Beta-blockers
Carvedilol, talinolol
Calcium channel blockers
Amlodipine, diltiazem, felodipine mibefradil, 
nicardipine, nifedipine, nitrendipine, verapamil
Diuretics
Conivaptan
Endothelin receptor antagonists
Bosentan
Gonadotropin-releasing hormone receptor antagonist
Elagolix
Herbal/natural supplements
St John’s wort, echinacea, gingko, milk thistle, Chinese 
herb sho-saiko-to (or Xiao-Shai-Hu-Tang)
Histamine-2 receptor antagonists
Cimetidine, ranitidine
3-hydroxy-3-methylglutaryl-coenzyme A reductase 
inhibitors 
Atorvastatin
Immunosuppressants
Cyclosporine, rapamycin, sirolimus, tacrolimus
Systemic corticosteroids
All agents, including dexamethasone
Systemic chemotherapeutic (antineoplastic) agents
All agents
a
Use of complementary or alternative medicines is prohibited at least 14 days prior to baseline/Day 0 through the end of the 
follow up.

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Should participants have a need to initiate treatment with any concomitant medication, the 
Gilead medical monitor must be consulted prior to initiation of the new medication. In instances 
where a medication is initiated prior to discussion with the sponsor, the investigator must notify 
Gilead as soon as he/she is aware of the use of the medication.
5.5.
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

The date, participant number, and the amount of study drug dispensed

The date, quantity of used and unused study drug returned, along with the initials of the 
person recording the information
5.5.1.
Investigational Medicinal Product Return or Disposal
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 trial master file. If study drug is destroyed at the 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.
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.

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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 2a and Appendix 2b 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.
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 
time.
Rescreening may be allowed. Investigators must consult with the Gilead medical monitor and 
receive approval prior to re-screening a participant.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Participants will be screened within 35 days prior to prebaseline/Day −13 to determine eligibility 
for participation in the study. The following will be performed and documented at the screening 
visit:

Obtain written informed consent

Obtain medical history including route and estimated duration of HIV-1 infection, history of 
HIV-1 disease-related events, ART history for at least 12 consecutive months prior to 
screening, and prior concomitant medications within 35 days of the screening visit

Obtain HIV staging at detection using standard markers (eg, HIV-1 RNA, p24 antigen, 
fourth generation combination antigen/antibody enzyme-linked immunosorbent assay, 
HIV-1 Western blot), duration of viremia during acute HIV infection and peak HIV RNA

Complete physical examination, including vital signs (blood pressure, pulse, respiration rate, 
oxygen saturation, and temperature)

Body weight and height

Obtain urine for urinalysis

Obtain blood samples for:
o
Plasma HIV-1 RNA
o
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
participants will not be enrolled

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o
Serum follicle-stimulating hormone test (for females < 54 years old who have ceased 
menstruating for ≥ 12 months, but are not permanently sterile or do not have 
documentation of ovarian hormonal failure)
o
Chemistry profile: alkaline phosphatase (ALP), AST, ALT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, creatine kinase (CK), bicarbonate, blood urea 
nitrogen (BUN), calcium, chloride, creatinine, glucose, phosphorus, magnesium, 
potassium, sodium, uric acid
o
Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, high-density lipoprotein, 
direct low-density lipoprotein, and triglycerides). If the participant has not fasted prior to 
the visit, the visit may proceed, but the participant must return within 72 hours in a fasted 
state to draw blood for the metabolic assessments
o
Hematology profile: complete blood count (CBC) with differential and platelet count
o
Creatinine clearance according to the Cockcroft-Gault formula:
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)] /
[72 × (serum creatinine in mg/dL)] × 0.85
o
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio
o
HBV serology
o
HCV serology
o
PBMC sample for testing of viral sensitivity to the VRC07-523LS and CAP256V2LS 
mAbs, if not previously conducted

12-lead ECG

Documentation of participant agreement to follow study contraceptive requirements as 
outlined in Appendix 5
Participants who meet all of the inclusion criteria and none of the exclusion criteria will return to 
the clinic within 5 weeks of the screening visit for the prebaseline/Day −13 assessments.
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.

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6.2.2.
Prebaseline/Day −13 Assessments
The prebaseline/Day −13 visit is to be completed within 35 days of the screening visit. The 
following evaluations are to be completed at the prebaseline/Day −13 visit:

Review of inclusion/exclusion criteria to confirm participant eligibility

Review of AEs and changes in concomitant medications

Review of medical history

Symptom-directed physical examination as needed

Body weight

Obtain blood samples for:
o
Plasma HIV-1 RNA
o
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid
o
Hematology profile: CBC with differential and platelet count
o
Creatinine clearance according to the Cockcroft-Gault formula:
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)] /
[72 × (serum creatinine in mg/dL)] × 0.85
o
Whole blood ISG mRNA panel
o
Anti-VRC07-523LS and anti-CAP256V2LS antibody profiling from serum
o
HIV-specific antibody profiling using plasma
o
Soluble proteins (cytokines, chemokines, and inflammatory markers)
o
Prebaseline soluble proteins in the TruCulture® Whole Blood Culture System
o
PBMC sample for immune cell frequency, activation, and phenotyping
o
PBMC sample for HIV-specific T cell responses
o
PBMC sample for latent HIV-1 reservoir
o
Plasma sample for active HIV-1 reservoir
o
PBMC sample for active HIV-1 reservoir

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
From participants who provide additional consent, HLA genotype, TLR7, and FcgR SNP 
samples will be collected for pharmacogenetic research.

From participants who provide additional consent, lymph node and/or GALT (GALT 
obtained by rectosigmoid biopsy) tissue collection (within window of ± 5 days) for some or 
all the following tests:
o
Immune cell frequency, activation, and phenotype, gene expression, and HIV-specific 
T cell response evaluation (PD and immunology)
o
HIV-1 reservoir measurements (virology)

Obtain urine collection for:
o
Urinalysis
o
Urine pregnancy test (females of childbearing potential only). A positive result will be 
confirmed with a serum pregnancy test. If the serum pregnancy test is positive, the 
participant will not be able to participate.

Birth control will be checked and replaced, if required
6.2.3.
Treatment Assignment
Obtain participant number and assign treatment to the participant in the IWRS. The participant 
number assignment and treatment assignment will be performed in clinic at the baseline/Day 0 
visit, provided that all screening procedures have been completed and participant eligibility has 
been confirmed.
If a participant’s ART regimen is changed ≤ 45 days prior to prebaseline/Day −13, plasma HIV-1 
RNA < 50 copies/mL at prebaseline/Day −13 visit is required to confirm eligibility. Once a 
participant number has been assigned, it will not be reassigned to any other participant.
6.3.
Treatment Assessments–Period 1
Participants will have up to 9 visits over 4 weeks. Dosing of VRC07-523LS and CAP256V2LS 
will occur in a sequential regimen with VES.
Doses 1 to 3 of VES will be administered orally on baseline/Day 0, Day 14, and Day 28. For 
Dose 3 only, 6 mg [3x2 mg tablets] or 8 mg [4x2 mg tablets]) will be administered per 
discussion with and approval from the Gilead medical monitor based on safety and tolerability of 
prior doses.
One dose of VRC07-523LS and 1 dose of CAP256V2LS will be administered sequentially by IV 
infusions on Day 7.

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Participants will remain at the site for monitoring for 24 hours after Dose 1 of VES, for at least 
8 hours after Dose 2 of VES, and for at least 4 hours after Dose 3 of VES. If participants 
experience significant influenza-like AEs (eg, moderate or severe pyrexia, chills, headache, 
myalgia, fatigue, malaise, joint pain) after the first 2 VES doses, or if dose is escalated to 8 mg, 
monitoring may be extended to > 4 hours for subsequent doses. For VRC07-523LS and 
CAP256V2LS, participants will remain on site for at least 8 hours after infusion on Day 7 for 
monitoring. If participants experience new or worsening flu-like symptoms, postdose safety 
monitoring should be extended.
Fasted status and food consumption will be checked prior to dosing.
Participants will continue to take their ART during this period (Days 0 to 28).
Sentinel Dosing:
Five participants will be enrolled first, to conduct visits and assessments up to Day 21. Upon 
review of the safety data and confirmation from an external DMC, up to a further 20 participants 
will be enrolled into Period 1.
Table 3.
Period 1 Study Visits and Study Drug Administration
Period 1 
Week
 -
 -
- 
1
-
-
2
3
4
Day
Baseline/0
1
2
7
8
9
14
21
28
VES Dose
1
 
 
 
2
 
3
VRC07-523LS 
and 
CAP256V2LS 
Dose
 
 
 
1
 
 
 
ART (Days 0 to 28)
ART = antiretroviral therapy
6.3.1.
Treatment Assessments–Baseline/Day 0
The following assessments are to be completed at the baseline/Day 0 visit. The investigator must 
confirm eligibility before proceeding with the baseline/Day 0 visit.
Participants must complete all study procedures before being administered study drug.

Symptom-directed physical examination

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature) at 
predose and then at 1, 2, 4, 8, 12, and 18 hours after VES administration

Body weight

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
Obtain blood samples for:
o Plasma HIV-1 RNA
o Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART
o Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid
o Hematology profile: CBC with differential and platelet count
o Creatinine clearance according to the Cockcroft-Gault formula:
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)]/[72 × 
(serum creatinine in mg/dL)] × 0.85
o Plasma sample for active HIV-1 reservoir
o PBMC sample for active HIV-1 reservoir
o Whole blood ISG mRNA panel
o Soluble proteins (cytokines, chemokines, and inflammatory markers)
o HIV-specific antibody profiling using plasma
o CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio
o PBMC sample for immune cell frequency, activation, and phenotyping
o Plasma VES PK collection: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, and 12 hours 
after Dose 1 of VES

Obtain urine collection for:
o
Urinalysis
o
Urine pregnancy test (females of childbearing potential only). If the urine pregnancy test 
is positive at baseline/Day 0, study drug will not be dispensed. A positive result will be 
confirmed with a serum pregnancy test. If the serum pregnancy test is positive, the 
participant will not be able to participate.

Birth control will be checked and replaced, if required.

Adverse events and changes in concomitant medications will be assessed and recorded. 
Participants will be reminded to report all symptoms, including flu-like symptoms 
(eg, fatigue, pyrexia, chills, myalgia, joint pain, or headache) or other unexpected symptoms.

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6.3.2.
Treatment Assessments–Days 1 to 28
All study visits are to be completed within ± 3 days of the protocol-specified visit date (based on 
the Day 0 visit) except for the Day 7 visit, and study procedures are to be completed within ± 2 
hours of the protocol-specified time point.
At the Day 28 visit and prior to moving into Period 2, each participant will be assessed to 
determine whether the criteria to start ATI has been met as described in Section 6.3.3.
The following assessments are to be completed at every visit, unless otherwise specified.

Symptom-directed physical examination

Body weight

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature) at:
o
Dose 1 of VES 24 hours after administration (Day 1)
o
VRC07-523LS and CAP256V2LS infusions prior to administration and at 1, 2, 4, and 
8 hours after administration (Day 7)
o
Dose 2 of VES prior to administration and at 1, 2, 4 and 8 hours after administration 
(Day 14)
o
Dose 3 of VES prior to administration and at 1, 2 and 4 hours after administration 
(Day 28)
o
If the participant experiences new or worsening symptoms, evaluate for signs and 
symptoms of CRS, including vital signs

Obtain blood samples for:
o
Plasma HIV-1 RNA (Day 7 and each weekly visit thereafter)
o
Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART (Day 7 and each weekly visit thereafter)
o
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid (all visits except Days 8 and 9)
o
Hematology profile: CBC with differential and platelet count (all visit days except 
Days 8 and 9)
o
Creatinine clearance according to the Cockcroft-Gault formula (all visits except Days 8 
and 9):

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Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)]/[72 × 
(serum creatinine in mg/dL)] × 0.85
o
Anti-VRC07-523LS and anti-CAP256V2LS antibody profiling from serum (Day 28)
o
HIV-specific antibody profiling using plasma (Day 8)
o
Whole blood ISG mRNA panel (Day 1)
o
Soluble proteins (cytokines, chemokines, and inflammatory markers) (Days 1 and 8)
o
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio (Days 14 and 
28)
o
PBMC sample for immune cell frequency, activation, and phenotyping (Days 1 and 8)
o
PBMC sample for HIV-specific T cell responses (Day 8)
o
Plasma sample for active HIV-1 reservoir (Days 1 and 2)
o
PBMC sample for active HIV-1 reservoir (Days 1 and 2)
o
Plasma VES PK collections (Day 1 and 2 [24 and 48 hours after VES Dose 1 at 
baseline/Day 0])
o
Serum VRC07-523LS PK collections (0 hours [predose], end of infusion, 1, 2, 4, and 
8 hours after end of infusion on Day 7 and then at Days 8, 9, 14, 21, and 28)
o
Serum CAP256V2LS PK collections (0 hours [predose], end of infusion, 1, 2, 4, and 
8 hours after end of infusion on Day 7, and then at Days 8, 9, 14, 21, and 28)

Obtain urine collection for:
o
Urinalysis (all visits except Days 8 and 9)
o
Urine pregnancy testing; a positive result will be confirmed with a serum pregnancy test. 
If the serum pregnancy test is positive, the participant will discontinue from study drug 
(Day 28)

Birth control will be checked and replaced, if required.

Ongoing eligibility assessment prior to the participant being administered study drug on site 
(Days 7, 14, and 28)

Adverse events and changes in concomitant medications will be assessed and recorded. 
Participants will be reminded to report all symptoms, including flu-like symptoms 
(eg, fatigue, pyrexia, chills, myalgia, joint pain, or headache) or other unexpected symptoms.

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6.3.3.
ATI Eligibility Criteria
At the Day 28 visit and prior to the Period 2 Day 35 visit, participants will be assessed to 
determine whether the criteria necessary to begin ATI are met. All of the following criteria must 
be met for a participant to begin ATI (Period 2):

Viral load < 50 copies/mL

CD4+ T cell count > 400 cells/μL

Negative urine pregnancy test

Participant has received VRC07-523LS, CAP256V2LS, and at least 3 of the 10 scheduled 
doses of VES.

Participant confirms agreement to request their partners to use condoms throughout the ATI 
period.
The initiation of ATI (Period 2) may be postponed for up to 4 weeks after the last VES dose for 
participants to meet the above requirements. If a participant develops any other acute event 
during this time that may require treatment before the participant starts the ATI (Period 2), the 
investigator should consult with the medical monitor. The investigator may delay the initiation of 
the ATI (Period 2), after consultation with the medical monitor, for up to a further 4 weeks if it is 
determined that the participant may proceed to ATI (Period 2) once the acute event has been 
treated successfully. The investigator should consult with the medical monitor to determine if 
repeat assessments should be performed to re-confirm the participant’s eligibility for the ATI 
(Period 2).
Participants who do not meet the requirements for ATI (Period 2) will complete an ESDD visit 
within 3 days of informing the investigator/site and may undergo early discontinuation of study 
follow up and procedures as described in Section 6.9.2.
6.4.
Treatment Assessments–Period 2
Participants will have up to 18 visits over 15 weeks. Doses 4 to 10 of VES will be administered 
orally on Day 42, Day 56, Day 70, Day 84, Day 98, Day 112, and Day 126.
For Doses 4 to 10, 6 mg [3x2 mg tablets] or 8 mg [4x2 mg tablets]) will be administered per 
discussion with and approval from the Gilead medical monitor based on safety and tolerability of 
prior doses.
Participants will remain at the site for monitoring for at least 4 hours after VES dosing. If 
participants experience significant influenza-like AEs (eg, moderate or severe pyrexia, chills, 
headache, myalgia, fatigue, malaise, joint pain) after the first 2 VES doses, monitoring may be 
extended to > 4 hours for subsequent doses. Fasted status and food consumption will be checked 
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No ART will be administered and ATI will start from Day 35.
If the ART restart criteria are met, the end-of-Period 3 visit (Section 6.5.2) will be completed and 
the participant may begin Period 4A.
Table 4.
Period 2 Study Visits and Study Drug Administration
Period 2 
Week
5
6
7
8
-
9
10
11
12
13
14
15
16
17
18
-
-
19
Day
35
42
49
56
57
63
70
77
84
91
98
105
112
119
126
127
128
133
VES Dose
 
4
 
5
 
 
6
 
7
 
8
 
9
 
10
 
 
 
VRC07-
523LS and 
CAP256V2LS 
Dose
No dosing
ATI (Days 35 to 133)
ATI = analytical treatment interruption; VES = vesatolimod
Every Period 2 study visit is based on the Day 0 visit + the number of postponement days required to confirm ATI eligibility in 
Period 1, if applicable
6.4.1.
Treatment Assessments–Days 29 to 133
The following assessments are to be completed at every visit, unless otherwise specified. All 
study visits are to be completed within ± 3 days of the protocol-specified visit date (based on the 
Day 0 visit + the number of postponement days required to confirm ATI eligibility in Period 1, 
if applicable), and study procedures are to be completed within ± 2 hours of the 
protocol-specified time point. Symptom-directed physical examination

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature) at:
Doses 4 to 10 of VES prior to administration and at 1, 2, and 4 hours after administration 
(Day 42 and at each visit every 2 weeks thereafter)
If the participant experiences new or worsening symptoms, evaluate for signs and 
symptoms of CRS, including vital signs

Body weight (Day 42 and at each visit every 2 weeks thereafter)

Obtain blood samples for:
Plasma HIV-1 RNA (Day 42 and at each visit every 2 weeks thereafter)
■
If a confirmed rebound of ≥ 50 copies/mL occurs, the test should be completed 
weekly

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Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART (Day 42 and at each visit every 2 weeks thereafter)
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid (Day 42 and at each visit every 
2 weeks thereafter)
Hematology profile: CBC with differential and platelet count (Day 42 and at each visit 
every 2 weeks thereafter)
Creatinine clearance according to the Cockcroft-Gault formula (Day 42 and at each visit 
every 2 weeks thereafter):
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)]/[72 × 
(serum creatinine in mg/dL)] × 0.85
Anti-VRC07-523LS and anti-CAP256V2LS antibody profiling from serum (Days 56, 84, 
112, and 133)
HIV-specific antibody profiling using plasma (Days 126 and 133)
Whole blood ISG mRNA panel (Days 56, 57, 126, and 127)
Soluble proteins (cytokines, chemokines, and inflammatory markers) (Days 56, 57, 63, 
126, 127, and 133)
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio (Days 42, 56, 70, 
84, 98, 112, 126, and 133)
PBMC sample for immune cell frequency, activation, and phenotyping (Days 56, 57, 63, 
126, 127, and 133)
PBMC sample for HIV-specific T cell responses (Days 63 and 133)
Serum VRC07-523LS PK collection (Days 56, 84, 112, and 133)
Serum CAP256V2LS PK collection (Days 56, 84, 112, and 133)
Plasma dolutegravir PK collection (Days 56, 84, 112, and 133)
Plasma sample for active HIV-1 reservoir (Days 56, 57, 126, 127, and 128)
PBMC sample for active HIV-1 reservoir (Days 56, 57, 126, 127, and 128)

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
Obtain urine collection for:
Urinalysis (Day 42 and at each visit every 2 weeks thereafter)
Urine pregnancy testing; a positive result will be confirmed with a serum pregnancy test. 
If the serum pregnancy test is positive, the participant will discontinue from study drug 
(Day 42 and at each visit every 4 weeks thereafter)

Birth control will be checked and replaced, if required.

Ongoing eligibility assessment prior to the participant being administered study drug on site 
(Days 42, 56, 70, 84, 98, 112, and 126)
Known HIV-1 seronegative sexual partners of enrolled study participants may be referred 
for HIV PrEP to decrease risk of HIV transmission during ATI.

Adverse events and changes in concomitant medications will be assessed and recorded. 
Participants will be reminded to report all symptoms, including flu-like symptoms 
(eg, fatigue, pyrexia, chills, myalgia, joint pain, or headache) or other unexpected symptoms
6.5.
Posttreatment Assessments–Period 3
Participants will have up to 14 study visits every 2 weeks for a total of 29 weeks.
No study drug (VES, VRC07-523LS, or CAP256V2LS) will be administered during this period.
No ART will be administered during this period and ATI will continue. If the ART restart 
criteria are met, the participant will stop Period 3, complete the end-of-Period 3 visit 
(Section 6.5.2), and may restart ART in Period 4A.
Upon completion of Period 3, all participants will be required to complete an 
end-of-Period 3 visit prior to moving into Period 4.
Table 5.
Period 3 Study Visits and Study Drug Administration
Period 3
Week
21
23
25
27
29
31
33
35
37
39
41
43
45
47
Day
147
161
175
189
203
217
231
245
259
273
287
301
315
329
VES Dose
No dosing
VRC07-523LS 
and 
CAP256V2LS 
Dose
No dosing
ATI (Days 134 to 336)

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Every Period 3 study visit is based on the Day 0 visit + the number of postponement days required to confirm ATI eligibility in 
Period 1, if applicable
6.5.1.
Treatment Assessments–Days 134 to 336
The following assessments are to be completed at every visit, unless otherwise specified. All 
study visits are to be completed within ± 3 days of the protocol-specified visit date (based on the 
Day 0 visit + the number of postponement days required to confirm ATI eligibility in Period 1, 
if applicable), and study procedures are to be completed within ± 2 hours of the 
protocol-specified time point.

Symptom-directed physical examination (Day 147 and at each visit every 4 weeks thereafter)

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature) 
(Day 147 and at each visit every 4 weeks thereafter)

Body weight (Day 147 and at each visit every 4 weeks thereafter)

Obtain blood samples for:
Plasma HIV-1 RNA
■
If a confirmed rebound of ≥ 50 copies/mL occurs, the test should be completed 
weekly
Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid (Day 147 and at each visit every 
4 weeks thereafter)
Hematology profile: CBC with differential and platelet count (Day 147 and at each visit 
every 4 weeks thereafter)
Creatinine clearance according to the Cockcroft-Gault formula (Day 147 and at each 
visit every 4 weeks thereafter):
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)] /
[72 × (serum creatinine in mg/dL)] × 0.85
Anti-VRC07-523LS and anti-CAP256V2LS antibody profiling from serum (Days 161, 
189, 217, 245, 273, 301, and 329)
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio (Day 147 and at 
each visit every 4 weeks thereafter)

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PBMC sample for latent HIV-1 reservoir (Day 147)
PBMC sample for testing of viral sensitivity to the VRC07-523LS and CAP256V2LS 
mAbs (Day 147)
Serum VRC07-523LS PK collection (Days 161, 189, 217, 245, 273, 301, and 329)
Serum CAP256V2LS PK collection (Days 161, 189, 217, 245, 273, 301, and 329)
Plasma dolutegravir PK collection (Days 161, 189, 217, 245, 273, 301, and 329)

From participants who provide additional consent, lymph node and/or GALT (GALT 
obtained by rectosigmoid biopsy) tissue collection (within window of ± 5 days) will be taken 
at Day 134 for some or all of the following tests:
Immune cell frequency, activation, and phenotype, gene expression and HIV-specific 
T cell response evaluation (PD and immunology)
HIV-1 reservoir measurements (virology)

Obtain urine collection for:
Urinalysis (Day 147 and at each visit every 4 weeks thereafter)
Urine pregnancy testing; a positive result will be confirmed with a serum pregnancy test. 
(Day 147 and at each visit every 4 weeks thereafter)

Birth control will be checked and replaced, if required.

Known HIV-1 seronegative sexual partners of enrolled study participants may be referred for 
HIV PrEP to decrease risk of HIV transmission during ATI.

Adverse events and changes in concomitant medications will be assessed and recorded. 
Participants will be reminded to report all symptoms, including flu-like symptoms 
(eg, fatigue, pyrexia, chills, myalgia, joint pain, or headache) or other unexpected symptoms.
At the end of Period 3, all participants will be required to complete an end-of-Period 3 visit prior 
to moving into Period 4.
6.5.2.
End of Period 3 Visit
Participants who complete Period 3 or meet the ART restart criteria will be required to complete 
an end-of-Period 3 visit 1 week after their last visit (to be completed within ± 1 day of the 
protocol-specified visit date [based on the Day 0 visit + the number of postponement days 
required to confirm ATI eligibility in Period 1, if applicable]). All participants will complete the 
following procedures:

Symptom-directed physical examination

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature)

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
Body weight

Review of AEs and changes in concomitant medications

12-lead ECG

Obtain blood samples for:
Plasma HIV-1 RNA
Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART
HIV-specific antibody profiling using plasma
Whole blood ISG mRNA panel
Soluble proteins (cytokines, chemokines, and inflammatory markers)
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio
PBMC sample for testing of viral sensitivity to the VRC07-523LS and CAP256V2LS 
mAbs
PBMC sample for immune cell frequency, activation, and phenotyping
PBMC sample for HIV-specific T cell responses
PBMC sample for latent HIV-1 reservoir
PBMC sample for active HIV-1 reservoir
Plasma sample for active HIV-1 reservoir

From participants who provide additional consent, lymph node and/or GALT (GALT 
obtained by rectosigmoid biopsy) tissue collection (within window of ± 5 days) for some or 
all of the following tests:
Immune cell frequency, activation and phenotype, gene expression and HIV-specific 
T cell response evaluation (PD and immunology)
HIV-1 reservoir measurements (virology)
6.6.
Posttreatment Assessments–Period 4
Participants who have remained virologically suppressed (plasma HIV-1 RNA < 50 copies/mL) 
or have not met the ART restart criteria at the end of Period 3 will continue into Period 4. The 
option will be available for either Period 4A, restart of ART for 12 weeks, or Period 4B, to 
remain off ART for a 12-week ATI extension. The period will begin after end of Period 3 Visit 

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to the end-of-study visit. The choice of Period 4A or 4B will be at the discretion of the 
participant and investigator.
Participants who meet the ART restart criteria prior to the end of Period 3 may also take part in 
Period 4A. The first Period 4A visit will require a urine pregnancy test. The ART restart criteria 
are:

Plasma HIV-1 RNA measurements of ≥ 1,000 copies/mL for 8 consecutive weeks AND no 
drop of 0.3 log10 from the previous week
Once the first confirmed HIV-1 RNA value of ≥ 50 copies/mL is detected, this will 
trigger weekly testing to monitor the HIV-1 RNA measurements,
OR

Confirmed plasma HIV-1 RNA > 100,000 copies/mL
OR

If a confirmed CD4+ T cell count < 350 cells/μL
OR

If a participant becomes pregnant
OR

ART may also be reinitiated during ATI per participant request, or at the discretion of the 
investigator, or sponsor due to other clinical criteria
Participants who restart ART in Period 4A will complete 6 study visits scheduled every 2 weeks 
over a 12-week period.
Participants who opt to remain off ART in Period 4B for the ATI extension will complete 
6 study visits scheduled every 2 weeks over a 12-week period. If the participant’s HIV-1 RNA 
remains at < 50 copies/mL throughout Period 4B, additional procedures may be required at the 
end-of-study visit.
No study drug (VES, VRC07-523LS, or CAP256V2LS) will be administered in this period.
Table 6.
Periods 4A and 4B Study Visits and Study Drug Administration
Periods 4A & 4B
Week
49
51
53
55
57
59
Day
343
357
371
385
399
413
VES Dose
No dosing
VRC07-523LS 
and 
CAP256V2LS 
Dose
No dosing
4A: ART Restart
4B: ATI Extension
Days 337 to 413

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VES = Vesatolimod, Every Period 4 study visit is based on the Day 0 visit + the number of postponement days required to 
confirm ATI eligibility in Period 1, if applicable

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6.6.1.
Treatment Assessments–Days 337 to 413
The following assessments are to be completed at every visit for Periods 4A and 4B, unless 
otherwise specified. All study visits are to be completed within ± 3 days of the protocol-specified 
visit date (based on the Day 0 visit + the number of postponement days required to confirm ATI 
eligibility in Period 1, if applicable), and study procedures are to be completed within ± 2 hours 
of the protocol-specified time point.

Symptom-directed physical examination (Day 343 and at each visit every 4 weeks 
thereafter)

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature) 
(Day 343 and at each visit every 4 weeks thereafter)

Body weight (Day 343 and at each visit every 4 weeks thereafter)

Obtain blood samples for:
Plasma HIV-1 RNA
■
Period 4A: If a confirmed rebound of ≥ 50 copies/mL occurs, the test should be 
completed at each scheduled visit until the end-of-study visit
■
Period 4B: If a confirmed rebound of ≥ 50 copies/mL occurs, the test should be 
completed weekly until ART restart criteria are met or the end-of-study visit
Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid (Day 343 and at each visit every 
4 weeks thereafter)
Hematology profile: CBC with differential and platelet count (Day 343 and at each visit 
every 4 weeks thereafter)
Creatinine clearance according to the Cockcroft-Gault (Day 343 and at each visit every 
4 weeks thereafter):
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)]/[72 × 
(serum creatinine in mg/dL)] × 0.85
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio (Day 343 and at 
each visit every 4 weeks thereafter)

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Serum VRC07-523LS PK collection (Days 343, 371, and 413)
Serum CAP256V2LS PK collection (Days 343, 371, and 413)
Plasma dolutegravir PK collection (Days 343, 371, and 413) [Period 4B only]
Anti-VRC07-523LS and anti-CAP256V2LS antibody profiling from serum (Days 343, 
371, and 413)

Obtain urine collection for:
Urinalysis (Day 343 and at each visit every 4 weeks thereafter)
Urine pregnancy testing; a positive result will be confirmed with a serum pregnancy test 
(At the first ART visit/Day 343 and at each visit every 4 weeks thereafter)

Birth control will be checked and replaced, if required.

Known HIV-1 seronegative sexual partners of enrolled study participants may be referred for 
HIV PrEP to decrease risk of HIV transmission during ATI (Period 4B only).

Adverse events and changes in concomitant medications will be assessed and recorded. 
Participants will be reminded to report all symptoms, including flu-like symptoms 
(eg, fatigue, pyrexia, chills, myalgia, joint pain, or headache) or other unexpected symptom.
6.7.
Posttreatment Assessments–Early Study Drug Discontinuation Visit
Participants who prematurely discontinue study drug prior to completing the infusions of the 
VRC07-523LS and CAP256V2LS, or all 10 doses of VES, as described in Section 6.9.1, Criteria 
for Discontinuation of Study Drug, will complete an ESDD visit within 3 days of informing the 
investigator/site.
At the ESDD visit, any evaluations showing abnormal results indicating that there is a 
possible or probable causal relationship with the study drug should be repeated weekly 
(or as often as deemed prudent by the investigator) until the abnormality is resolved, 
returns to baseline, or is otherwise explained.
The following assessments will be performed at the ESDD visit:

Symptom-directed physical examination

Review of AEs and changes in concomitant medications

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature)

Body weight

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
Obtain blood samples for:
Plasma HIV-1 RNA
Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid
Hematology profile: CBC with differential and platelet count
Creatinine clearance according to the Cockcroft-Gault:
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)]/[72 × 
(serum creatinine in mg/dL)] × 0.85
Whole blood ISG mRNA panel
Soluble proteins (cytokines, chemokines, and inflammatory markers)
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio

Obtain urine collection for:
Urinalysis
Urine pregnancy testing; a positive result will be confirmed with a serum pregnancy test.
■
Urine pregnancy kits will be provided to participants who completed the 
VRC07-523LS and CAP256V2LS infusion for monitoring as described in 
Section 6.9.2
6.8.
End-of-Study Visit
The end-of-study visit will occur for participants who have completed Period 4A or 4B. The visit 
will occur 1 week after completion of the last Period 4 visit. For the purpose of scheduling the 
end-of-study visit, a ± 3 day window may be used based on the based on the Day 0 visit + the 
number of postponement days required to confirm ATI eligibility in Period 1, if applicable.
The ART reinitiation after the end-of-study visit will be up to the participant’s health care 
provider discretion.

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The following assessments will be performed at the end-of-study visit:

Symptom-directed physical examination

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature)

Body weight

Review of AEs and changes in concomitant medications

12-lead ECG

Obtain urine collection for:
Urinalysis
Urine pregnancy testing; a positive result will be confirmed with a serum pregnancy test

Obtain blood samples for:
Plasma HIV-1 RNA
Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid
Hematology profile: CBC with differential and platelet count
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio
Creatinine clearance according to the Cockcroft-Gault formula:
Female Estimated Creatinine Clearance = [(140 − age in years) × (weight in kg)]/72 × 
(serum creatinine in mg/dL)] × 0.85

The following additional ATI remission tests will be required:
HIV-specific antibody profiling using plasma
Whole blood ISG mRNA panel
Soluble proteins (cytokines, chemokines, and inflammatory markers)
PBMC sample for testing of viral sensitivity to the VRC07-523LS and CAP256V2LS 
mAbs
PBMC sample for immune cell frequency, activation, and phenotyping
PBMC sample for HIV-specific T cell responses

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PBMC sample for latent HIV-1 reservoir
PBMC sample for active HIV-1 reservoir
Plasma sample for active HIV-1 reservoir
From participants who provide additional consent, lymph node and/or GALT (GALT 
obtained by rectosigmoid biopsy) tissue collection (within window of ± 5 days) for some 
or all of the following tests:
■
Immune cell frequency, activation and phenotype, gene expression, and HIV-specific 
T cell response evaluation (PD and immunology)
■
HIV-1 reservoir measurements (virology)
6.9.
Assessments for Early Discontinuation from Study
If a participant should discontinue study dosing as described in Section 6.9.1, they will be 
required to complete an early study drug discontinuation (ESDD) visit and every attempt should 
be made to keep the participant in the study and continue to perform study procedures. If the 
participant is unable to complete all scheduled procedures, for criteria other than those described 
for study discontinuation in Section 3.5, the participant should be followed by telephone as 
described in Section 6.9.2.
If a participant has completed all study drug dosing but is unable to complete all subsequent 
visits at the study site, as scheduled in Periods 3 and 4,for criteria other than those described for 
study discontinuation in Section 3.5, the participant should be followed by telephone for 250 
days after mAb infusion.
At the end of all follow-up monitoring, participants will undergo the end-of-follow-up visit at the 
study site.
6.9.1.
Criteria for Discontinuation of Study Drug
Study drug 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

Participant request to discontinue for any reason

Participant noncompliance

Pregnancy during the study; refer to Appendix 5

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
Discontinuation of the study at the request of Gilead, a regulatory agency or an IRB or IEC

Participant receives study drug(s) and experiences 1 or more AE or laboratory abnormality as 
follows:
o
≥ Grade 3 treatment-emergent AE (including new finding of splenomegaly, mucosal 
petechiae or purpura on physical examination or CRS) judged by the investigator as at 
least possibly related to study drug, OR
o
≥ Grade 3 confirmed laboratory abnormality (including a confirmed significant drop in 
platelets to < 50,000/mm3 and/or confirmed drop of 50% from baseline), unless there is a 
clear and obvious physiologic explanation for the events (eg, blood in urine occurring in 
a menstruating female, CK elevation after strenuous exercise, or triglyceride elevation 
that is nonfasting) judged by the investigators as at least possibly related to study drug, 
OR
o
A persistent (≥ 72 hours) ≥ Grade 2 pyrexia considered related to study drug by the 
investigator, OR
o
Any SAE considered at least possibly related to study drug
6.9.2.
Follow Up and Procedures After Early Discontinuation of Study Drug
After early discontinuation of study drug, for criteria other than those described in Section 3.5 
every attempt should be made to keep the participant in the study and continue to perform planned 
study procedures. Antiretroviral therapy may be restarted at the discretion of the investigator. If 
participant is unable to complete all scheduled procedures, the participant should undergo the 
following follow-up procedures:

If a participant discontinues study drug after having received VES alone, the participant 
should be followed for 30 days after the last VES dose, to monitor for AEs.
o
The participant will complete the ESDD visit within 3 days of informing the 
investigator/site. Participants should then be followed with a telephone check-up at 14 
days after the last VES dose to monitor for AEs. The end of the monitoring period will be 
30 days after the last VES dose and participants will undergo the end-of-follow-up visit at 
the study site.

If a participant discontinues study drug after having received CAP256V2LS and 
VRC07-523LS, and before ATI is initiated, the participant should not start ATI and should 
be followed for 250 days after mAb infusion.
o
The participant will complete the ESDD visit within 3 days of informing the 
investigator/site. Participants should be followed with telephone check-ups after the 
ESDD visit every 4 weeks thereafter to monitor for AEs and retrieve urine pregnancy 
results. At the end of the monitoring period, participants will undergo the end-of-follow-
up visit at the study site.

A positive urine pregnancy result will require confirmation with a serum pregnancy 
test at the study site.

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
If a participant discontinues study drug after having received CAP256V2LS and 
VRC07-523LS, and after ATI is initiated, the participant should undergo the following 
procedures:
o
If ART is reinitiated, the participant should be followed for 250 days after mAb infusion. 
An ESDD visit will be completed within 3 days for the last study drug dose. Participants 
should continue the study visit schedule and undergo all other planned study-related 
procedures. If participants are not able to attend the visit, participants may then be 
followed with telephone check-ups every 4 weeks thereafter to monitor for AEs and 
retrieve urine pregnancy results. At the end of the monitoring period, participants will 
undergo the end-of-follow-up visit at the study site.

A positive urine pregnancy result will require confirmation with a serum pregnancy 
test at the study site.
o
If ART is not reinitiated (ATI is continued), an ESDD visit will be completed within 
3 days of informing the investigator/site and the participant should continue the study 
visit schedule and undergo all other planned study-related procedures.

If a participant experiences any AE or reports any unexpected symptoms during telephone 
check-ups, an unscheduled visit should be arranged to perform the following:
o
Symptom-directed physical examination
o
Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature)
o
Symptom-directed acquisition of blood and urine samples
Participants may be followed with weekly on-site visits until the AE has been treated 
successfully. Telephone check-ups every 4 weeks will resume thereafter, as applicable.
6.9.3.
Follow Up and Procedures After Treatment Completion
If a participant completes all doses of study drug but is unable to complete all of the subsequent 
visits at the study site, as scheduled in Periods 3 and 4, for criteria other than those described in 
Section 3.5, the participant should be offered follow up for 250 days after mAb infusion. During 
this period, participants should be followed with telephone check-ups every 4 weeks to monitor 
for AEs and retrieve urine pregnancy results (kits to be provided at the last study site visit and a 
positive urine pregnancy result will require confirmation with a serum pregnancy test at the study 
site). At the end of the monitoring period, participants will undergo the end-of-follow-up visit at 
the study site.

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If a participant experiences any AE or reports any unexpected symptoms during telephone 
check-ups, an unscheduled visit should be arranged to perform the following:

Symptom-directed physical examination

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature)

Symptom-directed acquisition of blood and urine samples
Participants may be followed with weekly on-site visits until the AE has been treated 
successfully. Telephone check-ups every 4 weeks will resume thereafter, as applicable.
6.9.4.
End-of-Follow-Up Visit
At the end of the monitoring period described in Sections 6.9.2 and 6.9.3, participants will 
complete a final visit at the study site. All participants will complete the following procedures:

Symptom-directed physical examination

Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature)

Body weight

Review of AEs and changes in concomitant medications

12-lead ECG

Obtain urine collection for:
Urinalysis
Urine pregnancy testing; a positive result will be confirmed with a serum pregnancy test.

Obtain blood samples for:
Plasma HIV-1 RNA
Plasma HIV-1 resistance testing (in case of viral rebound) to VRC07-523LS, 
CAP256V2LS, and baseline ART
Chemistry profile: ALP, AST, ALT, total bilirubin, direct and indirect bilirubin, total 
protein, albumin, CK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid
Hematology profile: CBC with differential and platelet count
CD4+ and CD8+ T cell absolute count, percentage, and CD4/CD8 ratio
Creatinine clearance according to the Cockcroft-Gault formula:
Female Estimated Creatinine Clearance = [(140 – age in years) × (weight in kg)] /
[72 × (serum creatinine in mg/dL)] × 0.85

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6.10.
Management of Virologic Failure
Participants who experience virologic rebound (VR) or are viremic at their last visit, as defined 
below, will be considered to have virologic failure for the purposes of resistance analysis.
6.10.1.
Virologic Rebound
Virologic rebound is defined as follows:

At any visit a rebound in HIV-1 RNA to ≥ 50 copies/mL, which is subsequently confirmed at 
the following scheduled or unscheduled visit
At any visit, if the HIV-1 RNA is ≥ 50 and < 200 copies/mL, a reflex HIV-1 RNA repeat test 
will be conducted on stored plasma samples, if available. If the repeat result is < 50 copies/mL, 
no further action is required. If the repeat result is ≥ 50 copies/mL, participants will be asked to 
return to the clinic for a scheduled or unscheduled blood draw (1 week after the date of the 
original test that resulted in HIV-1 RNA VR) for confirmation of VR.
A plasma sample from either the first instance or the VR confirmation visit will be tested for 
resistance to VRC07-523LS, CAP256V2LS, and baseline ART.
6.10.2.
Viremia at Last Visit
Participants with HIV-1 RNA ≥ 50 copies/mL at their last study visit (ie, participants will not be 
returning to study site to confirm the result) will be tested for resistance to VRC07-523LS, 
CAP256V2LS, and baseline ART.
6.11.
End of Study
The end of study will be the last participant’s last observation (or visit).
6.12.
Poststudy Care
After a participant has completed/terminated their participation in the study, long-term care for 
the participant will remain the responsibility of their primary treating physician.
6.13.
Sample Storage
The stored biological samples may be used by Gilead or its research partner for future testing to 
provide additional data to answer questions that relate to the main study. At the end of this study, 
these samples may be retained in storage by Gilead for a period up to 15 years or per country 
requirements.

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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 a study 
drug that does not necessarily have a causal relationship with the treatment. An AE can therefore 
be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the 
use of a study drug, whether or not the AE is considered related to the study drug. Adverse 
events may also include pretreatment or posttreatment complications that occur as a result of 
protocol-specified procedures or special situations (Section 7.1.3).
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 7.1.3)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the informed consent form is signed and not related to a protocol-associated procedure 
is not an AE but rather considered to be preexisting and should be documented as medical 
history
Preexisting events or conditions that increase in severity or change in nature after study drug 
initiation or as a consequence of participation in the clinical study will be considered AEs.
7.1.2.
Serious Adverse Events
An SAE is defined as an event that, at any dose, results in the following:

Death

A life-threatening situation (Note: The term “life-threatening” in the definition of “serious” 
refers to an event in which the participant was at risk of death at the time of the event; it does 
not refer to an event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: Such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participants 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.
7.1.2.1.
Protocol-Specific Serious Adverse Event Definitions
Protocol-specific SAEs: In this study, thrombocytopenia < 50,000 platelets will be considered 
medically important and therefore “serious.”
7.1.3.
Study Drugs and Gilead Concomitant Therapy Special Situations Reports
Special situation reports (SSRs) include all reports of medication error, abuse, misuse, overdose, 
occupational exposure, drug interactions, exposure via breastfeeding, unexpected benefit, 
transmission of infectious agents via the product, counterfeit of falsified medicine, and 
pregnancy regardless of an associated AE.
Medication error is any unintentional error in the prescribing, dispensing, preparation for 
administration, or administration of a study drug while the medication is in the control of a 
health care professional, participant, 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 a study drug by a 
participant.
Misuse is defined as any intentional and inappropriate use of a study drug that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a study 
drug given per administration or cumulatively that 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).

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Occupational exposure is defined as exposure to a study drug as a result of one’s professional or 
nonprofessional occupation.
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.
Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to 
be desirable and beneficial.
Transmission of infectious agents is defined as any suspected transmission of an infectious agent 
through a Gilead study drug.
Counterfeit or falsified medicine is defined as any study drug with a false representation of (a) its 
identity, (b) its source, or (c) its history.
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, concomitant medication).

Yes: There is reasonable possibility that the AE 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 Gilead Grading Scale for Severity of Adverse 
Events and Laboratory Abnormalities, Antiviral Toxicity Grading Scale, Version 01 April 2015 
(Appendix 4). For each episode, the highest grade attained should be reported as defined in the 
Antiviral Toxicity Grading Scale (Appendix 4). The CTCAE v5 grading scale will be used to 
grade AEs determined to be cytokine release syndrome and infusion-related reactions.

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7.3.
Investigator Reporting Requirements and Instructions
7.3.1.
Requirements for Collection Prior to Study Drug Initiation
After informed consent, but prior to initiation of study drug, the following types of events must 
be reported on the applicable eCRFs: all SAEs and AEs related to protocol-mandated procedures.
7.3.2.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until the end-of-study visit, after completion of Period 4, on the eCRFs as instructed. In case of 
early discontinuation or early transition from Periods 2 or 3 to Period 4, all AEs, regardless of 
cause or relationship, must be collected until 250 days after last dose of study drug.
All AEs should be followed 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.
7.3.3.
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 form) and throughout the duration of 
the study, including the posttreatment follow-up visit, must be reported on the applicable eCRFs 
and Gilead Global Patient Safety (GLPS) as instructed below in this section. This also includes 
any SAEs resulting from protocol-associated procedures performed after the informed consent 
form is signed.
Any SAEs and deaths that occur throughout the duration of the study including the 
protocol-defined follow-up period, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period; 
however, if the investigator learns of any SAEs that occur after the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study drug, the investigator 
should promptly document and report the event to Gilead GLPS.
Instructions for reporting SAEs are described in Section 7.4.1.
7.3.4.
Study Drug Special Situations Reports
All study drug SSRs that occur from study drug initiation and throughout the duration of the 
study, including the posttreatment follow-up visit, must be reported to Gilead GLPS 
(Section 7.4.1.2). Adverse events and SAEs resulting from SSRs must be reported in accordance 
with the AE and SAE reporting guidance (Section 7.3.2).

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7.3.5.
Concomitant Therapy Reports
7.3.5.1.
Gilead Concomitant Therapy Special Situations Report
Special situation involving a Gilead concomitant therapy (not considered study drug), that occurs 
after the participant first consents to participate in the study (ie, signing the informed consent) 
and throughout the duration of the study, including the posttreatment follow-up visit, must be 
reported to Gilead GLPS utilizing the paper SSR form (Section 7.4.2.2).
7.3.5.2.
Non-Gilead Concomitant Therapy Report
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the SSR form; however, for special situations that result in AEs due to a non-Gilead concomitant 
medication, the AE should be reported on the AE form.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
All clinical sequelae in relation to these SSRs 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.
7.4.
Reporting Process for Serious Adverse Events and Special Situation Reports
7.4.1.
Serious Adverse Event Reporting Process

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be transmitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal participant identification, 
maintaining the traceability of a document to the participant identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the participant’s eCRF and the SAE narrative section of the Safety 
Report Form eCRF.
7.4.1.1.
Electronic Serious Adverse Event Reporting Process

Site personnel will 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 from informed consent form signature throughout the duration of the study, including 
the protocol-required posttreatment follow-up period

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
If it is not possible to record and transmit the SAE information electronically, record the SAE 
on the paper SAE reporting form and transmit within 24 hours:
Gilead GLPS
Email: Safety_FC@gilead.com 
Or
Fax: 1-650-522-5477

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary. If the database is not locked, any SAE reported via paper must be 
transcribed as soon as possible on the applicable eCRFs and transmitted to Gilead GLPS.
7.4.1.2.
Reporting Process for Gilead Standard-of-Care Treatment

If participants receive commercially available standard-of-care treatment for HIV during 
Periods 1 and 4, all AEs, SAEs, and SSRs associated with a Gilead product administered as 
part of standard-of-care treatment for HIV during participation in this study must be recorded 
on the paper noninterventional AE/SAE/SSR form and sent within 24 hours to:
Gilead GLPS
Email: Safety_FC@gilead.com
Or
Fax: 1-650-522-5477

All AEs, SAEs, and SSRs associated with a non-Gilead product administered as part of 
standard-of-care treatment for HIV during participation in this study must be reported via 
available standard methods (eg, FDA MedWatch form) to the Marketing Authorization 
holder of the product.
7.4.2.
Special Situations Reporting Process
7.4.2.1.
Paper Special Situations Reporting Process for Study Drug

All special situations will be recorded on the SSR form and transmitted by emailing or faxing 
the report form within 24 hours of the investigator’s knowledge of the event to the attention 
of Gilead GLPS from study drug initiation throughout the duration of the study, including the 
protocol-required posttreatment follow-up period.
Gilead GLPS
Email: Safety_FC@gilead.com 
Or
Fax: 1-650-522-5477

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7.4.2.2.
Reporting Process for Gilead Concomitant Medications

Special situations that involve Gilead concomitant medications that are not considered study 
drug must be reported within 24 hours of the investigator’s knowledge of the event to Gilead 
GLPS utilizing the paper special situations report form to:
Gilead GLPS
Email: Safety_FC@gilead.com
Or
Fax: 1-650-522-5477

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.

Special situations involving non-Gilead concomitant medications do not need to be reported 
on the SSR form; however, special situations that result in AEs due to a non-Gilead 
concomitant medication must be reported as an AE.
7.4.2.3.
Pregnancy Reporting Process

Participants will be instructed to notify the investigator if they become pregnant at any time 
during the study, or if they become pregnant within 10 days after the last dose of VES or 
250 days after the last dose of VRC07-523LS and CAP256V2LS, whichever date is later.

The investigator should report pregnancies in female study participants that are identified 
after initiation of study drug and throughout the study, including the posttreatment follow-up 
period, to Gilead GLPS using the pregnancy report form within 24 hours of becoming aware 
of the pregnancy. Contact details for transmitting the pregnancy report form are as follows:
Gilead GLPS
Email: Safety_FC@gilead.com
Or
Fax: 1-650-522-5477

The pregnancy itself is not considered an AE, nor is an induced elective abortion to terminate 
a pregnancy without medical reasons.

All other premature terminations 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, as described in Section 7.4.1. The underlying medical reason for this 
procedure should be recorded as the AE term.

A spontaneous abortion is always considered to be an SAE and will be reported as described 
in Section 7.4.1. Furthermore, any SAE occurring as an adverse pregnancy outcome after 
study must be reported to the Gilead GLPS.

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
The participant should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome of the pregnancy should be reported to 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. Gilead GLPS contact 
information is as follows:
Gilead GLPS
Email: Safety_FC@gilead.com
Or
Fax: 1-650-522-5477

Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements.
7.5.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the European Union Clinical Trials Directive (2001/20/EC) and relevant 
updates, and other country-specific legislation or regulations, Gilead may be required to expedite 
to worldwide regulatory agencies reports of SAEs, which may be in the form of line listings, 
serious adverse drug reactions, or SUSARs. In accordance with the European Union Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.6.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not to be recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, 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).

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Severity should be recorded and graded according to the Gilead Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities, Antiviral Toxicity Grading Scale, Version 01, 
April 2015, and the CTCAE v5 grading scale. 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 agree with the grading of the laboratory abnormality.
7.7.
Toxicity Management
7.7.1.
Safety Monitoring Plan for CRS
As described in Section 1.4 and the VES IB, clinical signs and symptoms consistent with CRS 
have been reported in a minority of participants administered VES. Clinical manifestations 
include influenza-like symptoms such as fever, fatigue, chills, myalgias, and headache, which are 
generally transient and mild to moderate in severity. Infrequent but serious clinical 
manifestations that may be associated with CRS include hypoxia and hypotension and may 
require hospitalization and treatment. It is possible that administration of CAP256V2LS and 
VRC07-523LS in a sequential regimen with VES may increase the risk of CRS. The grading 
scale of CRS is shown in Table 7.
Participants should be closely monitored for signs and symptoms of CRS during and after VES 
administration. For at least 24 hours following the first dose of VES and at least 4-8 hours 
following subsequent doses of VES, appropriately trained medical personnel and emergency 
equipment for the management of CRS should be on site and immediately available.
Following administration of VES, the participants will be monitored at the study site, and 
monitoring should include evaluation for signs and symptoms of CRS and assessment of vital 
signs (ie, blood pressure, pulse, respiration rate, oxygen saturation, and temperature) as follows:
First dose of VES (Day 0): Prior to administration of VES and then at 1, 2, 4, 8, 12, 18, and 
24 hours after administration of VES, or if the participant experiences new or worsening 
symptoms, evaluate for signs and symptoms of CRS and vital signs.
Doses 2 of VES: Prior to administration and then at 1, 2, 4, and 8 hours after administration. If 
the participant experiences new or worsening symptoms, evaluate for signs and symptoms of 
CRS, including vital signs.
Dose 3 of VES: Prior to administration and then at 1, 2, and 4 hours after administration. If 
participants experience significant influenza-like AEs (eg, moderate or severe pyrexia, chills, 
headache, myalgia, fatigue, malaise, joint pain) after the first 2 VES doses, or if dose is escalated 
to 8 mg, monitoring may be extended to > 4 hours for subsequent doses. If the participant 
experiences new or worsening symptoms, evaluate for signs and symptoms of CRS, including 
vital signs.
Doses of VRC07-523LS and CAP256V2LS: Prior to administration and at 1, 2, 4, and 8 hours 
after administration. If the participant experiences new or worsening symptoms, evaluate for 
signs and symptoms of CRS, including vital signs.

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Doses 4 to 10 of VES: Prior to administration and at 1, 2, and 4, hours after administration. If the 
participant experiences abnormal vital signs, new or worsening symptoms, evaluate for signs and 
symptoms of CRS, including vital signs.
Following VES administration, treatment-related Grade 1 CRS with influenza-like symptoms 
such as fever, fatigue, chills, myalgia, or headache without more severe manifestations such as 
changes in blood pressure or oxygen saturation may be managed with supportive care at the 
clinical site (eg, acetaminophen [paracetamol] for myalgia or fever). Vesatolimod may be 
continued at the discretion of the investigator.
For ≥ Grade 2 treatment-related CRS, including hypotension and/or hypoxia, immediate transfer 
to a hospital or emergency department for management in a monitored setting is advised. 
Administration of steroids, IV fluid for hypotension, and supplemental oxygen for hypoxia 
should also be considered. Vesatolimod may be continued at the discretion of the investigator 
and in consultation with the Gilead medical monitor.
Vesatolimod may be discontinued for treatment-related ≥ Grade 3 CRS.
Table 7.
The Common Terminology Criteria for Adverse Events (CTCAE) 
Version 5.0 Grading Scale for Infusion-related Reaction and Cytokine 
Release Syndrome
General Disorders and Administration Site Conditions
CTCAE Term
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Infusion-related 
reaction
Mild transient 
reaction; infusion 
interruption not 
indicated; 
intervention not 
indicated
Therapy or infusion 
interruption indicated 
but responds promptly 
to symptomatic 
treatment (eg, 
antihistamines, 
NSAIDS, narcotics, IV 
fluids); prophylactic 
medications indicated 
for ≤ 24 hours
Prolonged (eg, not 
rapidly responsive 
to symptomatic 
medication and/or 
brief interruption 
of infusion); 
recurrence of 
symptoms 
following initial 
improvement; 
hospitalization 
indicated for 
clinical sequelae
Life-threatening 
consequences; 
urgent intervention 
indicated
Death
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological 
substances.
Cytokine release 
syndrome
Fever with or without 
constitutional 
symptoms
Hypotension responding 
to fluids; hypoxia 
responding to
< 40% O2
Hypotension 
managed with one 
pressor; hypoxia 
requiring ≥ 40% O2
Life-threatening 
consequences; 
urgent intervention 
indicated
Death
Definition: A disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia 
caused by the release of cytokines.
Navigational Note: Also consider reporting other organ dysfunctions including neurological toxicities such as: Psychiatric 
disorders: Hallucinations or Confusion; Nervous system disorders: Seizure, Dysphasia, Tremor, or Headache.
CTCAE = Common Terminology Criteria for Adverse Events; IV = intravenous, NSAID = non-steroidal anti-inflammatory 
drugs
Source: National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0

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7.7.2.
Management of Other Toxicities
Unless otherwise specified in Section 7.7.1, toxicities will be managed according to the 
guidelines below.

All clinically significant Grade 3 and 4 laboratory abnormalities should be repeated within 
3 calendar days to confirm toxicity grade. Confirmation of toxicity grade is required prior to 
the next dose of study drug for any Grade 3 and 4 laboratory abnormality that in the opinion 
of the investigator is clinically significant and may pose a risk to the participant’s safety.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(refer to Appendix 4).

Infusion-related reactions and cytokine release syndrome should be graded according to the 
CTCAE Version 5.0 grading scale (see Table 7).
Any questions regarding toxicity management should be directed to the Gilead medical monitor.
7.7.2.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the investigator.
7.7.2.2.
Grades 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, study drug may be 
continued if the event is considered to be unrelated to study drug.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to study drug, study drug should be withheld 
until the toxicity returns to ≤ Grade 2.

If a laboratory abnormality recurs to ≥ Grade 3 following rechallenge with study drug and is 
considered related to study drug, then study drug should be permanently discontinued, and 
the participant managed according to local practice. Recurrence of laboratory abnormalities 
considered unrelated to study drug may not require permanent discontinuation.
7.7.2.3.
Grade 4 Laboratory Abnormality or Clinical Event
For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality confirmed 
by repeat testing that is considered related to study drug, study drug should be permanently 
discontinued, and the participant managed according to local practice. The participant should be 
followed as clinically indicated until the laboratory abnormality returns to baseline or is 
otherwise explained, whichever occurs first. A clinically significant Grade 4 laboratory 
abnormality that is not confirmed by repeat testing should be managed according to the 
algorithm for the new toxicity grade.
Study drug may be continued without dose interruption for a clinically nonsignificant Grade 3 to 
4 laboratory abnormality (eg, CK elevation after strenuous exercise, or triglyceride elevation that 
is nonfasting or that can be medically managed) or a Grade 3 to 4 clinical event considered 
unrelated to study drug.

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STATISTICAL CONSIDERATIONS 
8.1. 
Analysis Objectives and Endpoints 
8.1.1. 
Analysis Objectives 
The prirmuy objective of this study is as follows: 
Final 
Amendment3 
• 
To evaluate the safety and tolerability of dual anti-HIV envelope mAbs, VRC07-523LS and 
CAP256V2LS, in a sequential regimen with a TLR7 agonist, VES, when administered in 
virologically suppressed HIV-1 Clade C-infected women on ART and during ATI 
The secondaiy objectives of this study are as follows: 
• 
To evaluate the PK ofVRC07-523LS, CAP256V2LS, and VES 
• 
To evaluate whether VRC07-523LS and CAP256V2LS induce anti-VRC07-523LS and/or 
anti-CAP256V2LS antibodies 
• 
To evaluate the effect ofVRC07-523LS and CAP256V2LS in a sequential regimen with 
VES on viral control or the need for resumption of ART following an ATI. 
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8.1.2. 
Primary Endpoints 
The prirmuy endpoints of this study are as follows: 
• 
The propo1tion of pa1ticipants with treatment-emergent AEs 
Final 
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• 
The propo1tion of pa1ticipants with treatment-emergent graded laborato1y abnonnalities 
8.1.3. 
Secondary Endpoints 
The secondaiy endpoints of this study ai·e as follows: 
Vir·ology/Efficacy 
• 
Time to viral rebound (confin ned 50 copies/mL and~ 200 copies/mL) following ATI 
• 
The change in plasma viral load set-point following ATI 
• 
Viral load at the end of ATI 
• 
Time to ART resumption following ATI 
Phaimacokinetics 
• 
PK pai·aineters for VES in plasma will include Cmax, Tmax, C1ast, T1ast, AUCinf, AUC1ast, 
AUCexp, t112, CL/F, and V ,jF. PK pai·ameters for VRC07-523LS and CAP256V2LS in sennn 
will include Cmax, Tmax, C1ast, T1ast, AUCinf, AUC1ast, AUCexp, t112, CL, Vss, and Vz 
Immunogenicity 
• 
The proportion of paiticipants with positive anti-VRC07-523LS or anti-CAP256V2LS 
antibodies 
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8.2.1. 
Planned Analyses 
Interim Analysis 
Final 
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Prior to the final analysis, interim analyses will be conducted. These analyses may be submitted 
to regulato1y agencies to seek guidance regarding the overall clinical development program. 
8.2.1.1. 
Data Monitoring Committee Analysis 
There will be 1 planned DMC analysis of safety. The committee will convene after the 
5 paiiicipants from the sentinel coho1i have completed their Day 21 visit or have prematurely 
discontinued the study. 
No fonnal stopping rnles will be used by the DMC for safety outcomes. Rather, a clinical 
assessment will be made to detennine if the nature, frequency, and severity of AEs associated 
with a study regimen wairnnt the eai·ly tennination of the study in the best interest of the 
paiiicipants. 
8.2.1.2. 
Planned Internal Analysis 
Two interim internal analyses will be conducted: 
• 
After all pa1iicipants have completed their Day 133 visit (last scheduled study visit of 
Period 2), sta1ied Period 4A (if the ART restaii criteria ai·e met), or prematurely discontinued 
from the study 
• 
After all paiticipants have completed the end-of-Period 3 visit, or prematurely discontinued 
from the study 
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8.2.2.
Final Analysis
The final analysis will be performed after all participants have completed the study or 
prematurely terminated from the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized.
8.3.
Analysis Conventions
8.3.1.
Analysis Sets
8.3.1.1.
All Enrolled
The Enrolled Analysis Set includes all participants who are enrolled into the study. This is the 
primary analysis set for by-participant listings.
8.3.1.2.
Efficacy
8.3.1.2.1.
Full Analysis Set
The FAS will include all participants who (1) are enrolled into the study and (2) have received at 
least 1 dose of study drug.
8.3.1.3.
Safety
The Safety Analysis Set will include all enrolled participants who received at least 1 dose of 
study drug. All safety data, including data collected after the last dose of study drug through the 
end of the protocol-defined follow-up period, will be included in the safety summaries.
8.3.1.4.
Pharmacokinetics
The VES PK Analysis Set will include all participants who are enrolled and have received at 
least 1 dose of VES and for whom PK concentrations of analyte VES are available.
The VRC07-523LS PK Analysis Set will include all participants who are enrolled and have 
received at least 1 dose of VRC07-523LS and for whom PK concentrations of analyte 
VRC07-523LS are available.
The CAP256V2LS PK Analysis Set will include all participants who are enrolled and have 
received at least 1 dose of CAP256V2LS and for whom PK concentrations of analyte 
CAP256V2LS are available.
8.3.1.5.
Immunogenicity
The VRC07-523LS Immunogenicity Analysis Set will include all enrolled participants who 
received at least 1 dose of VRC07-523LS and have had at least 1 nonmissing value for the 
immunogenicity evaluation of interest (ie, anti-VRC07-523LS antibody).

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The CAP256V2LS Immunogenicity Analysis Set will include all enrolled participants who 
received at least 1 dose of CAP256V2LS and have had at least 1 nonmissing value for the 
immunogenicity evaluation of interest (ie, anti-CAP256V2LS antibody).
8.3.2.
Data Handling Conventions
Natural logarithm transformation for key PK parameters, such as Cmax and AUCinf, will be 
applied for PK analysis, as appropriate.
For summary statistics, PK concentration values below the limit of quantitation (BLQ) will be 
imputed as zero at predose and one-half the LLOQ at postdose, where LLOQ is corrected for the 
dilution factor (ie, reported dilution/dilution factor). Individual values that are BLQ will be 
presented as “BLQ” in the concentration data listing and will be imputed as specified above for 
summary purpose.
8.4.
Demographic and Baseline Characteristics Analysis
Demographic and baseline measurements will be summarized using standard descriptive 
methods.
Demographic summaries will include sex, race/ethnicity, and age.
Baseline data including body weight, height, body mass index, and HIV-1 infection will be 
summarized.
8.5.
Efficacy Analysis
The efficacy analysis will be based on the FAS.
8.5.1.
Virology Analysis
Time to viral rebound (confirmed ≥ 50 copies/mL and ≥ 200 copies/mL) following ATI will be 
summarized.
The change in plasma viral load set-point between pre-ART value and prior to ART reinitiation 
following ATI will be summarized.
Viral load at the end of ATI will also be summarized.
8.5.2.
Other Efficacy Analysis
Time to ART resumption following ATI will be summarized.
8.6.
Safety Analysis
All safety analyses will be performed using the Safety Analysis Set.

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All safety data collected on or after the date that study drug was first taken up to the date of 
last dose of study drug through the end of the protocol-defined follow-up period will be 
summarized according to the study drug received. Data for the pretreatment period and after the 
first dose of the study drug will be included in data listings.
8.6.1.
Extent of Exposure
A participant’s extent of exposure to study drug will be generated from the study drug 
administration data. Exposure data will be summarized.
Duration of exposure to study drug will be expressed as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration and summarized.
Dosing information for individual participants will be listed.
8.6.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System organ class, high-level group term, high-level term, preferred 
term, and lower-level term will be attached to the clinical database.
Summaries (number and percentage of participants) of treatment-emergent AEs (by system 
organ class, high-level term [if applicable], and preferred term) will be provided. 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 will be summarized using only observed data. Absolute values and 
changes from baseline at all scheduled visits will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in 
Appendix 4.
Incidence of treatment-emergent laboratory abnormalities will be summarized. If baseline data 
are missing, any graded abnormality (ie, at least a Grade 1) will be considered treatment 
emergent. The maximum toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the participant has 
been discontinued from treatment through the end of the protocol-defined follow-up period will 
be included in a data listing.

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Pharmacokinetic Analysis 
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The concentrntion data of each analyte (VES, VRC07-523LS, CAP256V2LS) will be 
summarized by nominal sampling time using descriptive statistics. For each analyte, PK 
parameters will be listed and summarized using descriptive statistics ( eg, sample size, arithmetic 
mean, geometric mean (CV%), coefficient of variation[%], SD, median, minimum, and 
maximum). PK parameters for VES in plasma will include Cmax, Tma.x, C1ast, T1ast, AUCinf, 
AUCiast, AUCexp, t12, CL/F, and V/ F. PK parameters for VRC07-523LS and CAP256V2LS in 
sernm will include Cmax, Tmax, C1ast, T1ast, AUCinf, AUC1ast, AUCexp, t12, CL, Vss, and Vz. Plasma 
concentrations over time will be plotted in semilogarithmic and linear scales as mean± SD and 
median (Ql , Q3). The PK of dolutegravir may be explored. 
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Pharmacodynamic/lmmunology Analysis 
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8.10.
Immunogenicity Analysis
The proportion of participants with positive anti-VRC07-523LS or anti-CAP256V2LS antibodies 
will be summarized.
8.11.
Sample Size
The sample size in this study is determined based on practical considerations and empirical 
experience with similar types of studies. No sample size and power calculation was performed. 
Up to 25 participants will provide a preliminary assessment of descriptive safety, efficacy, and 
PK.
8.12.
Data Monitoring Committee
An external multidisciplinary DMC includes independent experts who do not have direct 
involvement in the conduct of the study. The DMC will review the progress of the study, 
perform an interim review of safety data of a sentinel cohort before opening enrollment of up to 
a further 20 participants, 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 whether 
the study should continue with modifications. The DMC’s specific activities will be defined by a 
mutually agreed charter that 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 study 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 participant.
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 informed consent form for documenting written 
informed consent. Each informed consent form (or assent as applicable) will be appropriately 
signed and dated by the participant or the participant’s legally authorized representative, the 
person conducting the consent discussion, and an impartial witness (if required by IRB or IEC or 
local requirements).

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The informed consent form will inform participant about planned sample retention. In addition to 
the study-specific informed consent form to be signed by each participant participating in the 
study, participants will be required to document agreement to provide additional samples or to 
allow the use of the remainder of their already-collected specimens for optional future research, 
in accordance with applicable regulations. In addition to the study-specific informed consent 
form to be signed by each participant participating in the study, participants will be required to 
document agreement to provide additional samples for optional pharmacogenomic research. The 
results of the tests done on the samples will not be given to the participant or the investigator.
9.1.5.
Confidentiality
The investigator must ensure that participants’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as year of birth) will be recorded on any form 
or biological sample submitted to Gilead, IEC, or the laboratory. Laboratory specimens must be 
labeled in such a way as to protect participant identity while allowing the results to be recorded 
to the proper participant. Refer to specific laboratory instructions. NOTE: The investigator must 
keep a screening log with details for all participants screened and enrolled in the study, in 
accordance with the site procedures and regulations. Participant data will be processed in 
accordance with all applicable regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
IB, this protocol, case report form (CRFs)/eCRFs, study drug information, and any other study 
information, remain the sole and exclusive property of Gilead during the conduct of the study 
and thereafter. This information is not to be disclosed to any third party (except employees or 
agents directly involved in the conduct of the study or as required by law) without prior written 
consent from Gilead. The investigator further agrees to take all reasonable precautions to prevent 
the disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.6.
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) participant clinical source documents.
The investigator’s study file will contain the protocol/amendments, participants’ eCRFs, and 
governmental approval with correspondence, the informed consent form(s), drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.

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The required source data should include sequential notes containing at least the following 
information for each participant:

Participant identification

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; causality and severity), 
and documentation that adequate medical care has been provided for any AE

Concomitant medication (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 for 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, for 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
An eCRF casebook will be completed by an authorized study personnel member whose training 
for this function is completed in the EDC system unless otherwise directed. The eCRF casebook 
will only capture the data required per the protocol schedule of events and procedures, unless 
collected by a nonelectronic data capture vendor system (eg, central laboratory). The 
Inclusion/Exclusion Criteria and Enrollment eCRFs should be completed only after all data 
related to eligibility are available. Data entry should be performed in accordance with the case 
report form Completion Guidelines provided by the sponsor. Subsequent to data entry, a study 
monitor may perform source data verification. System-generated or manual queries will be 
issued in the EDC system as data discrepancies are identified by the study monitor or Gilead 
personnel who routinely review the data for completeness, correctness, and consistency. The site 
investigator, site coordinator, or other designee is responsible for responding to the queries in a 
timely manner, within the system, either by confirming the data as correct or updating the 
original entry, and providing the reason for the update (eg, data entry error). Original entries as 
well as any changes to data fields will be stored in the audit trail of the system. Regular oversight 
by the principal investigator of the data entered into the EDC system is expected to occur on an 
ongoing basis throughout the study to ensure quality and completeness. At a minimum, before 
any interim, final, or other time points (as instructed by Gilead), the investigator will apply 
his/her electronic signature to confirm that the forms have been reviewed and that the entries 
accurately reflect the information in the source documents. At the conclusion of the study, Gilead 
will provide the site investigator with a read-only archive copy of the data entered. This archive 
must be stored in accordance with the records retention requirements outlined in Section 9.1.6.
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 Gilead 
in accordance with local requirements and receive documented approval before modifications 
can be implemented.

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9.2.2.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency when applicable 
and in accordance with local regulatory requirements. Gilead will ensure that the report meets 
the standards set out in the ICH Guideline for Structure and Content of Clinical Study Reports 
(ICH E3). Note that an abbreviated report may be prepared in certain cases. Investigators in this 
study may communicate, orally present, or publish in scientific journals or other scholarly media 
in accordance with the Gilead clinical trial agreement.
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.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or 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
Gilead reserves the right to terminate the study at any time, and the investigator has the right to 
terminate the study at his or her site. Should this be necessary, both parties will arrange 
discontinuation procedures and notify the participants, appropriate regulatory authority, IRBs, 
and IECs. In terminating the study, Gilead and the investigator will ensure that adequate 
consideration is given to the protection of the participants’ interests.

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10.
REFERENCES
Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, et al. Effect of HIV 
Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med 
2016;375 (21):2037-50.
Barouch D, Mercado N, Chandrashekar A, Borducchi E, Nkolola J, Pau M, et al. Combined 
Active and Passive Immunization in SHIV-Infected Rhesus Monkeys. Conference 
on Retroviruses and Opportunistic Infections; 2020 March 8-11 2020; Boston, 
MA.
Borducchi EN, Cabral C, Stephenson KE, Liu J, Abbink P, Ng'ang'a D, et al. Ad26/MVA 
Therapeutic Vaccination with TLR7 Stimulation in SIV-Infected Rhesus 
Monkeys. Nature 2016;540 (7632):284-7.
Borducchi EN, Liu J, Nkolola JP, Cadena AM, Yu WH, Fischinger S, et al. Antibody and TLR7 
Agonist Delay Viral Rebound in SHIV-Infected Monkeys [Abstract]. Nature 
2018a;563 (7731):360-4.
Borducchi EN, Liu J, Nkolola JP, Cadena AM, Yu WH, Fischinger S, et al. Antibody and TLR7 
Agonist Delay Viral Rebound in SHIV-Infected Monkeys [Author Manuscript]. 
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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2a.
Study Procedures Table
Appendix 2b.
Follow-up Period: Study Procedures Table
Appendix 3.
Management of Adverse Events and Laboratory Abnormalities
Appendix 4.
Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (Centers for Disease Control 
and Prevention [CDC] Guidelines)
Appendix 7.
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 2a Study to Evaluate the Safety and Tolerability of a Regimen of Dual Anti-HIV 
Envelope Antibodies, VRC07-523LS and CAP256V2LS, in a Sequential Regimen with a TLR7 
Agonist, Vesatolimod, in Early Antiretroviral-Treated HIV-1 Clade C-Infected Women
GS-US-382-5445, Original Version 1.0, dated 18 December 2020
Amendment 1, dated 17 June 2021, Amendment 2, dated 26 August 2022
Amendment 3, dated 07 October 2022
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval.
Medical Monitor
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
PPD

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Appendix 2a.
Study Procedures Table
P1
P2a
P3 
a,b
P4 
a,b
Visitc
Screeningd
Day –13/Prebaseline
VES Dose1-Day 0/Baseline
Day 1
Day 2
VRC & CAP Dose–Day 7
Day 8
Day 9
VES Dose 2-Day 14
Day 21
VES Dose 3-Day 28e
Day 35
VES Dose 4-Day 42
Day 49
VES Dose 5-Day 56
Day 57
Day 63
VES Dose 6-Day 70
Day 77
VES Dose 7-Day 84
Day 91
VES Dose 8-Day 98
Day 105
VES Dose 9-Day 112
Day 119
VES Dose 10-Day 126
Day 127
Day 128
Day 133
Day 134-336
End-of-Period 3 Visitf
Day 337-413
End-of-Study Visitg
ESDDh
Informed consent
X
Medical history 
Xi
X
AE and Con Med
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
Complete physical 
exam
X
Symptom-directed 
physical exam
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
Xj
X
Xk
X
X
12-Lead ECG
X
X
X
Vital signsl
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
X
Xk
X
X
Body weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
X
Xk
X
X
Height
X
Review of I/E 
criteria
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xk
X
X
Urine pregnancy 
testm
X
X
X
X
X
X
X
Xj
Xk
X
X
Chemistryn
X
X
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xk
X
X
Hematologyp
X
X
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xk
X
X
Metabolic 
assessmentq
X
Creatinine 
clearancer
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xj
Xk
X
X
Follicle-stimulating 
hormones
X

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Gilead Sciences, Inc. 
Amendment 3
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P1
P2a
P3 
a,b
P4 
a,b
Visitc
Screeningd
Day –13/Prebaseline
VES Dose1-Day 0/Baseline
Day 1
Day 2
VRC & CAP Dose–Day 7
Day 8
Day 9
VES Dose 2-Day 14
Day 21
VES Dose 3-Day 28e
Day 35
VES Dose 4-Day 42
Day 49
VES Dose 5-Day 56
Day 57
Day 63
VES Dose 6-Day 70
Day 77
VES Dose 7-Day 84
Day 91
VES Dose 8-Day 98
Day 105
VES Dose 9-Day 112
Day 119
VES Dose 10-Day 126
Day 127
Day 128
Day 133
Day 134-336
End-of-Period 3 Visitf
Day 337-413
End-of-Study Visitg
ESDDh
Whole blood ISG 
mRNA panel
X
Xo
X
X
X
X
X
X
X
X
HIV-specific 
antibody profiling 
using plasma 
X
Xo
X
X
X
X
X
HIV stagingff
X
Serum pregnancy 
testm
X
CD4+ and CD8+ T 
cell absolute count, 
percentage, and 
CD4/CD8 ratio
X
Xo
X
X
X
X
X
X
X
X
X
X
Xj
X
Xk
X
X
HBV/HCV 
serologyt
X
VES PKu
X
X
X
Serum VRC07-
523LS & 
CAP256V2LS PKv
X
X
X
X
X
X
X
X
X
X
X
X
Plasma dolutegravir 
PKw
X
X
X
X
X
X
Plasma HIV-1 
RNAx
X
X
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Plasma HIV-1 
resistance testing to 
VRC07-523LS, 
CAP256V2LS, and 
baseline ART
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Plasma for active 
HIV-1 reservoir
X
Xo
X
X
X
X
X
X
X
X
X
Soluble proteins in 
the TruCulture® 
Whole Blood 
Culture System
X

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Gilead Sciences, Inc. 
Amendment 3
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P1
P2a
P3 
a,b
P4 
a,b
Visitc
Screeningd
Day –13/Prebaseline
VES Dose1-Day 0/Baseline
Day 1
Day 2
VRC & CAP Dose–Day 7
Day 8
Day 9
VES Dose 2-Day 14
Day 21
VES Dose 3-Day 28e
Day 35
VES Dose 4-Day 42
Day 49
VES Dose 5-Day 56
Day 57
Day 63
VES Dose 6-Day 70
Day 77
VES Dose 7-Day 84
Day 91
VES Dose 8-Day 98
Day 105
VES Dose 9-Day 112
Day 119
VES Dose 10-Day 126
Day 127
Day 128
Day 133
Day 134-336
End-of-Period 3 Visitf
Day 337-413
End-of-Study Visitg
ESDDh
Soluble proteins 
(cytokines, 
chemokines, and 
inflammatory 
markers)
X
Xo
X
X
X
X
X
X
X
X
X
X
X
PBMC sample for 
testing of viral 
sensitivity to the 
VRC07-523LS and 
CAP256V2LS 
mAbs
Xy
Xz
X
X
PBMC HIV-
specific T cell 
responses
X
X
X
X
X
X
PBMC immune cell 
frequency, activation
and phenotyping 
X
Xo
X
X
X
X
X
X
X
X
X
X
PBMC latent HIV-
1 reservoir
X
Xz
X
X
PBMC active HIV-
1 reservoir
X
Xo
X
X
X
X
X
X
X
X
X

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Gilead Sciences, Inc. 
Amendment 3
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P1
P2a
P3 
a,b
P4 
a,b
Visitc
Screeningd
Day –13/Prebaseline
VES Dose1-Day 0/Baseline
Day 1
Day 2
VRC & CAP Dose–Day 7
Day 8
Day 9
VES Dose 2-Day 14
Day 21
VES Dose 3-Day 28e
Day 35
VES Dose 4-Day 42
Day 49
VES Dose 5-Day 56
Day 57
Day 63
VES Dose 6-Day 70
Day 77
VES Dose 7-Day 84
Day 91
VES Dose 8-Day 98
Day 105
VES Dose 9-Day 112
Day 119
VES Dose 10-Day 126
Day 127
Day 128
Day 133
Day 134-336
End-of-Period 3 Visitf
Day 337-413
End-of-Study Visitg
ESDDh
Anti-VRC07-
523LS and anti-
CAP256V2LS 
antibody profiling 
from serumaa
X
X
X
X
X
X
Xbb
Xc
c
Review of ongoing 
eligibility check 
prior to study 
dosing
X
X
X
X
X
X
X
X
X
X
X
Birth control check
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
Participant 
agreement to 
follow study 
contraceptive 
requirements
X
In-clinic dosing
X
X
X
Xgg
Xhh
Xhh
Xhh
Xhh
Xhh
Xhh
Xhh
VES dose
X
X
X
X
X
X
X
X
X
X
VRC07-523LS and 
CAP256V2LS dose
X
HLA genotype, 
TLR7, FcgR SNP
X
CCI
I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 

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Final
Gilead Sciences, Inc. 
Amendment 3
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P1
P2a
P3 
a,b
P4 
a,b
Visitc
Screeningd
Day –13/Prebaseline
VES Dose1-Day 0/Baseline
Day 1
Day 2
VRC & CAP Dose–Day 7
Day 8
Day 9
VES Dose 2-Day 14
Day 21
VES Dose 3-Day 28e
Day 35
VES Dose 4-Day 42
Day 49
VES Dose 5-Day 56
Day 57
Day 63
VES Dose 6-Day 70
Day 77
VES Dose 7-Day 84
Day 91
VES Dose 8-Day 98
Day 105
VES Dose 9-Day 112
Day 119
VES Dose 10-Day 126
Day 127
Day 128
Day 133
Day 134-336
End-of-Period 3 Visitf
Day 337-413
End-of-Study Visitg
ESDDh
HIV-1 reservoir 
measurement
X
Xee
X
X
Gene expression
X
Xee
X
X
HIV-specific T cell 
responses
X
Xee
X
X
Immune cell 
frequency, activation
and phenotyping 
X
Xee
X
X
ESDD = early study drug discontinuation; GALT = gut-associated lymphoid tissue; HBV = hepatitis B virus; HCV = hepatitis C virus; HLA = human leucocyte antigen; 
I/E = inclusion/exclusion; ISG = interferon-stimulated gene; mAb = monoclonal antibody; mRNA = messenger RNA; P1/2/3/4 = Period ½/3/4; PBMC = peripheral blood 
mononuclear cell; PK = pharmacokinetic(s); PrEP = preexposure prophylaxis; SNP = single nucleotide polymorphism; TLR = toll-like receptor; VES = vesatolimod; 
VRC = VRC07-523LS
a
Known HIV-1 seronegative sexual partners of enrolled study participants may be referred for HIV PrEP to decrease risk of HIV transmission during ATI in Periods 2, 3, and 
4B.
b
Periods 3 and 4 have study visit every 2 weeks.
c
All study visits are to be completed within ± 3 days of the protocol-specified visit date (except end-of-Period 3 visit, which is ± 1 day). This tolerance window does not apply 
to screening, pre-baseline, Day 0, and Day 7.
d
Evaluations to be completed within 35 days prior to prebaseline/Day −13.
e
At the Day 28 visit and prior to the Period 2 Day 35 visit, participants will be assessed to determine whether the criteria necessary to begin ATI are met. All of the following 
criteria must be met for a participant to begin ATI: Viral load < 50 copies/mL; CD4+ T cell count > 400 cells/μL; negative urine pregnancy test; participant has received 
VRC07-523LS, CAP256V2LS, and at least 3 of the 10 scheduled doses of VES. Participant confirms agreement to request their partners to use condoms throughout the ATI 
period. The initiation of ATI (Period 2) may be postponed for up to 4 weeks after the last VES dose for participants to meet these requirements.
f
Participants who complete Period 3 or meet the ART restart criteria will be required to complete an end-of-Period 3 visit 1 week after their last visit.
g
End-of-study visit will occur 7 days (± 3 days) after completion of the final Period 4 visit.
h
ESDD visit is required for participants who prematurely discontinue study drug prior to completing the infusions of the VRC07-523LS and CAP256V2LS, or all 10 doses of 
VES, as described in Section 6.9.1, will complete an ESDD visit within 3 days of informing the investigator/site.
i
Medical history including route and estimated duration of HIV-1 infection, history of HIV-1 disease-related events, ART history for at least 12 consecutive months prior to 
screening, and prior concomitant medications within 35 days of the screening visit.
j
Day 147 and at each visit every 4 weeks thereafter
CCI

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Amendment 3
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k
Day 343 and at each visit every 4 weeks thereafter
l
Vital signs (blood pressure, pulse, respiration rate, oxygen saturation, and temperature) will be monitored on dosing days at the following time points: (1) VES Dose 1 on 
baseline/Day 0, at predose, then at 1, 2, 4, 8, 12, 18, and 24 hours (Day 1) postdose (2) VRC07-523LS and CAP256V2LS infusion, and remaining VES Doses 2 to 10 at 
predose, then at 1, 2, 4, and 8 hours postdose.
m
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
n
Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct and indirect bilirubin, total protein, albumin, creatine kinase, bicarbonate, 
blood urea nitrogen, calcium, chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid.
o
Sample to be taken before VES dosing.
p
Complete blood count with differential and platelet count.
q
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, high-density lipoprotein, direct low-density 
lipoprotein, triglycerides). If the participant has not fasted prior to the visit, the visit may proceed, but the participant must return within 72 hours in a fasted state to draw 
blood for the metabolic assessments.
r
Creatinine clearance according to the Cockcroft-Gault formula: Female Estimated Creatinine Clearance = [(140–− age in years) × (weight in kg)]/[72 × (serum creatinine in 
mg/dL)] × 0.85.
s
Serum follicle-stimulating hormone test is required for female participants < 54 years old who have stopped menstruating for ≥ 12 months, but are not permanently sterile or 
do not have documentation of ovarian hormonal failure.
t
Hepatitis B virus blood panel will be performed at screening (hepatitis B virus surface antigen, hepatitis B virus surface antibody, and hepatitis B virus core antibody). 
Hepatitis C antibody will also be performed.
u
PK samples for VES will be collected at predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24 (Day 1), and 48 hours (Day 2) after the first dose.
v
Serum VRC07-523LS and CAP256V2LS PK collection on Day 7, at 0 hours (predose), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then at Days 8, 9, 14, 
21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413.
w
Plasma dolutegravir PK collections will be obtained at: Days 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, and for participants in Period 4B PK collections at 
Days 343, 371, and 413.
x
From Period 2, if a confirmed rebound of HIV-1 RNA viral load ≥ 50 copies/mL occurs, the test should be completed weekly.
y
Only if not previously conducted.
z
Only at Day 147 visit.
aa
Blood samples anti-VRC07-523LS and anti-CAP256V2LS antibody profiling from serum will be collected at the following timepoints: prebaseline/Day −13, Days 28, 56, 84, 
112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413.
bb
Days 161, 189, 217, 245, 273, 301, and 329 only.
cc
Days 343, 371 and 413 only.
dd
Lymph node and GALT biopsy will be collected from participants who provide additional consent at prebaseline/Day −13, Week 21 (beginning of Period 3), end-of-Period 3 
visit, and the end-of-study visit. The samples can be collected within a window of ± 5 days.
ee
Only at Day 134 visit.
ff
Obtain HIV staging at detection using standard markers (eg, HIV-1 RNA, p24 antigen, fourth generation combination antigen/antibody enzyme-linked immunosorbent assay, 
HIV-1 Western blot), duration of viremia during acute HIV infection and peak HIV RNA
gg
For Dose 3 only, 6 mg [3x2 mg tablets] or 8 mg [4x2 mg tablets]) will be administered per discussion with and approval from the Gilead medical monitor based on safety and 
tolerability of prior doses.
hh
For Doses 4 to 10, 6 mg [3x2 mg tablets] or 8 mg [4x2 mg tablets]) will be administered per discussion with and approval from the Gilead medical monitor based on safety 
and tolerability of prior doses.

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Appendix 2b.
Follow-up Period: Study Procedures Table
Follow-up period 
for participants 
who discontinued 
study drug after 
having received 
VES alonea,b
Follow-up period for 
participants who discontinued 
study drug after having 
received CAP256V2LS and 
VRC07-523LS, and before ATI 
is initiatedb,c
Follow-up period for participants 
who discontinued study drug after 
having received CAP256V2LS and 
VRC07-523LS, and after ATI is 
initiatedc,d,e
Follow-up period for 
participants who completed 
all doses of study drug but 
is unable to complete all of 
the subsequent visits at the 
study siteb,f
End-of-Follow-up visitb
Telephone check-
up 
X
X
X
X
Symptom-directed 
physical exam
Xg
Xg
Xg
Xg
X
Vital signs
Xg
Xg
Xg
Xg
X
Symptom-directed 
acquisition of 
blood and urine 
samples
Xg
Xg
Xg
Xg
Body weight
X
Review of AEs and 
changes in 
concomitant 
medications
X
X
X
X
X
12-Lead ECG
X
Urinalysis
X
Urine pregnancy 
test
Xh
Xh
Xh
X
Plasma HIV-1 
RNA
X
Plasma resistance 
testing to VRC07-
523LS, 
CAP256V2LS, and 
baseline ART
X

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Follow-up period 
for participants 
who discontinued 
study drug after 
having received 
VES alonea,b
Follow-up period for 
participants who discontinued 
study drug after having 
received CAP256V2LS and 
VRC07-523LS, and before ATI 
is initiatedb,c
Follow-up period for participants 
who discontinued study drug after 
having received CAP256V2LS and 
VRC07-523LS, and after ATI is 
initiatedc,d,e
Follow-up period for 
participants who completed 
all doses of study drug but 
is unable to complete all of 
the subsequent visits at the 
study siteb,f
End-of-Follow-up visitb
Chemistry
X
Hematology
X
CD4+ and CD8+ T 
cell absolute count, 
percentage, and 
CD4/CD8 ratio
X
Creatinine 
clearance
X
AE = adverse event; ART = antiretroviral therapy; ATI = analytical treatment interruption; ECG = electrocardiogram; ESDD = early study drug discontinuation; 
mAb = monoclonal antibody; VES = vesatolimod
a
Participants should be followed with a telephone check-up at 14 days after the last VES dose to monitor for AEs. The end of the monitoring period will be 30 days after the 
last VES dose and participants will undergo the end-of-follow-up visit at the study site.
b
All follow-up visits/calls are to be completed within ± 3 days of the protocol-specified visit date.
c
Participants should continue the study visit schedule and undergo all other planned study-related procedures. If participants are not able to attend the visit, participants may 
then be followed with telephone check-ups every 4 weeks thereafter to monitor for AEs and retrieve urine pregnancy results. At the end of the monitoring period, participants 
will undergo the end-of-follow-up visit at the study site.
d
If ART is reinitiated, the participant should be followed for 250 days after mAb infusion. An ESDD visit will be completed within 3 days for the last study drug dose. 
Participants should continue the study visit schedule and undergo all other planned study-related procedures. If participants are not able to attend the visit, participants may 
then be followed with telephone check-ups every 4 weeks thereafter to monitor for AEs and retrieve urine pregnancy results. At the end of the monitoring period, participants 
will undergo the end-of-follow-up visit at the study site.
e
If ART is not reinitiated (ATI is continued), an ESDD visit will be completed within 3 days of last study drug dose informing the investigator/site and the participant should 
continue the study visit schedule and undergo all other planned study-related procedures.
f
The participant should be offered follow up for 250 days after mAb infusion. During this period, participants should be followed with a telephone check-ups every 4 weeks to 
monitor for AEs and retrieve urine pregnancy results.
g
If participant experiences any AE or reports any unexpected symptoms during telephone check-ups, an unscheduled visit should be arranged to perform these assessments. 
Participants may be followed with weekly on-site visits until the AE has been treated successfully. Telephone check-up every 4 weeks will resume thereafter, as applicable.
h
A positive urine pregnancy result will require confirmation with a serum pregnancy test at the study site.

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Amendment 3
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Appendix 3.
Management of Adverse Events and Laboratory Abnormalities
Grade 3 or 4 laboratory abnormalities include drop in platelets to < 50,000/mm3.
Continue study drug 
dosing at the discretion of 
the investigator 
Confirm toxicity grade of 
AE and/or repeat lab to 
confo:m toxic:ity grade of 
lab abno-rm.ality 
t 
If c.onficmed Grade 3 Lab or AE, and possibly or 
probably related to study drug(s): 
If confirmed and 
unrelated to study 
drug(s), dosing m.ay 
cont:inne at the 
discretion of the 
iinvestigator. 
I 
1. Withhold study drng(s) until :S Grade 2 I 
2. Restart all study drug(s) ait full dose upon 
discussion with Gilead Medical Monitor 
J-
T 
If Grade 3 or 4 recurrence is 
co-nfomed and possibly or 
prohalily related to study 
drug(s), disc.ontiinu.e aU study 
drug(s) permanently, and manage 
the subject according to local 
practice. 
If Grade 3 or 4 recon-eoc.e is 
confirmed and unrelated to stlidy 
drug(s), continue all 
investigational medicinal 
prnduct(s) at the same dose at the 
discretion of the investigator. 
r 
If c.onfinned Grade 4 lab or 
AE, and possibly or 
probably related to study 
drug(s), discontinue 
study(s) dosrog 
permanently, and manage 
subject according to local 
practice. Subject should be 
followed as clinically 
indicated UlIJtil th.e 
laboratory abnormality 
returns to baseliine, or is 
otherwise explain.ed. j 

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Appendix 4.
Gilead Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities
Antiviral Toxicity Grading Scale, Version 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric  
57 Days
8.5 to 10.0 g/dL
85 to 100 g/L
7.5 to  8.5 g/dL
75 to  85 g/L
6.5 to  7.5 g/dL
65 to  75 g/L
 6.5 g/dL
 65 g/L
HIV NEGATIVE
Adult and Pediatric  
57 days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from 
Baseline
2.5 to  3.5 g/dL
25 to  35 g/L
9.0 to  10.0 g/dL
90 to  100 g/L
OR
Any decrease from 
Baseline
3.5 to  4.5 g/dL
35 to  45 g/L
7.0 to  9.0 g/dL
70 to  90 g/L
OR
Any decrease from 
Baseline
 4.5 g/dL
 45 g/L
 7.0 g/dL
 70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR 
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to  8.5 g/dL
70 to  85 g/L
6.0 to  7.0 g/dL
60 to < 70 g/L
 6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR 
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to  9.5 g/dL
80 to  95 g/L
7.0 to  8.0 g/dL
70 to  80 g/L
 7.0 g/dL
 70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR 
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to  12.0 g/dL
100 to  120 g/L
9.0 to  10.0 g/dL
90 to  100 g/L
 9.0 g/dL
 90 g/L
1000 to 1300/mm3
750 to  1000/mm3
500 to  750/mm3
 500/mm3
Absolute Neutrophil 
Count
Adult and Pediatric,
≥ 7 Monthsa 
1.00 to 1.30 GI/L
0.75 to  1.00 GI/L
0.50 to  0.75 GI/L
 0.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE 
ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to  300/mm3
200 to  300/μL
100 to  200/mm3
100 to  200/μL
 100/mm3
 100/μL
Absolute Lymphocyte 
Count
HIV NEGATIVE 
ONLY
Adult and Pediatric 
 13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to  600/mm3
0.50 to  0.60 GI/L
350 to  500/mm3
0.35 to  0.50 GI/L
 350/mm3
 0.35 GI/L
Platelets
100,000 to 
< 125,000/mm3
100 to  125 GI/L
50,000 to 
 100,000/mm3
50 to  100 GI/L
25,000 to 
 50,000/mm3
25 to  50 GI/L
 25,000/mm3
 25 GI/L

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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
2000/mm3 to 
2500/mm3
1,500 to  2,000/mm3
1000 to  1,500/mm3
 1000/mm3
White Blood Cells 
2.00 GI/L to 2.50 GI/L
1.50 to  2.00 GI/L
1.00 to  1.50 GI/L
 1.00 GI/L
100 to 200 mg/dL
75 to  100 mg/dL
50 to  75 mg/dL
 50 mg/dL
Hypofibrinogenemia
1.00 to 2.00 g/L
0.75 to  1.00 g/L
0.50 to  0.75 g/L
 0.50 g/L
 ULN to 600 mg/dL
 600 mg/dL
—
—
Hyperfibrinogenemia
 ULN to 6.0 g/L
 6.0 g/L
—
—
20 to 40 μg/mL
 40 to 50 μg/mL
 50 to 60 μg/mL
 60 μg/mL
Fibrin Split Product 
20 to 40 mg/L
 40 to 50 mg/L
 50 to 60 mg/L
 60 mg/L
Prothrombin Time 
 1.00 to 1.25  ULN
 1.25 to 1.50  ULN
 1.50 to 3.00  ULN
 3.00  ULN
International 
Normalized Ratio of 
Prothrombin Time
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial 
Thromboplastin Time
 1.00 to 1.66  ULN
 1.66 to 2.33  ULN
 2.33 to 3.00  ULN
 3.00  ULN
Methemoglobin
5.0 to 10.0%
 10.0 to 15.0%
 15.0 to 20.0%
 20.0%
a
An overlap between the Grade 1 scale and the laboratory’s normal range for absolute neutrophils may result for pediatric 
participants. Please follow the Gilead convention of grading any result within the lower limit of normal and upper limit of 
normal (ULN) a 0.

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Amendment 3
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
130 to < LLN mEq/L
125 to  130 mEq/L
121 to  125 mEq/L
 121 mEq/L
Hyponatremia
130 to < LLN mmol/L
125 to  130 mmol/L
121 to  125 mmol/L
 121 mmol/L
>ULN to 150 mEq/L
 150 to 154 mEq/L
 154 to 159 mEq/L
 159 mEq/L
Hypernatremia
>ULN to 150 mmol/L
 150 to 154 mmol/L
 154 to 159 mmol/L
 159 mmol/L
3.0 to < LLN mEq/L
2.5 to  3.0 mEq/L
2.0 to  2.5 mEq/L
 2.0 mEq/L
Hypokalemia
Adult and Pediatric
 1 Year
3.0 to < LLN mmol/L
2.5 to  3.0 mmol/L
2.0 to  2.5 mmol/L
 2.0 mmol/L
Infant < 1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to  3.0 mEq/L
2.5 to < 3.0 mmol/L
2.0 to  2.5 mEq/L
2.0 to < 2.5 mmol/L
 2.0 mEq/L
< 2.0 mmol/L
Hyperkalemia
Adult and Pediatric
 1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
 6.0 to 6.5 mEq/L
 6.0 to 6.5 mmol/L
 6.5 to 7.0 mEq/L
 6.5 to 7.0 mmol/L
 7.0 mEq/L
 7.0 mmol/L
Infant < 1 Year
>ULN to 6.0 mEq/L
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
 6.5 to 7.0 mEq/L
 6.5 to 7.0 mmol/L
 7.0 mEq/L
 7.0 mmol/L
Hypoglycemia
Adult and Pediatric
 1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to  55 mg/dL
2.20 to  3.03 mmol/L
30 to  40 mg/dL
1.64 to  2.20 mmol/L
 30 mg/dL
 1.64 mmol/L
Infant  1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to  50 mg/dL
2.2 to  2.8 mmol/L
30 to  40 mg/dL
1.7 to  2.2 mmol/L
 30 mg/dL
 1.7 mmol/L
116 to 160 mg/dL
 160 to 250 mg/dL
 250 to 500 mg/dL
 500 mg/dL
Hyperglycemia 
(nonfasting)
6.42 to 8.91 mmol/L
 8.91 to 
13.90 mmol/L
 13.90 to 
27.79 mmol/L
 27.79 mmol/L
Hyperglycemia 
(fasting)
110 to 125 mg/dL
6.08 to 6.96 mmol/L
> 125 to 250 mg/dL
> 6.96 to 13.90 
mmol/L
> 250 to 500 mg/dL
> 13.90 to 27.79 
mmol/L
> 500 mg/dL
> 27.79 mmol/L
Hypocalcemia
(corrected for albumin 
if appropriatea)
Adult and Pediatric
≥ 2 Years
7.8 to < LLN mg/dL
1.94 to < LLN 
mmol/L
7.0 to  7.8 mg/dL
1.74 to  1.94 mmol/L
6.1 to  7.0 mg/dL
1.51 to  1.74 mmol/L
 6.1 mg/dL
 1.51 mmol/L
Pediatric ≥ 7 Days to 
2 Years
7.8 to 8.4 mg/dL
1.94 to 2.10 mmol/L
7.0 to < 7.8 mg/dL
1.74 to < 1.94 mmol/L
6.1 to < 7.0 mg/dL
1.51 to < 1.74 mmol/L
< 6.1 mg/dL
< 1.51 mmol/L
Infant  7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88 mmol/L
6.0 to  6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to  6.0 mg/dL
1.36 to < 1.49 mmol/L
 5.5 mg/dL
< 1.36 mmol/L

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Amendment 3
CONFIDENTIAL
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
>ULN to 11.5 mg/dL
 11.5 to 12.5 mg/dL
 12.5 to 13.5 mg/dL
 13.5 mg/dL
Hypercalcemia 
(corrected for albumin 
if appropriatea)
Adult and Pediatric  
7 Days
>ULN to 2.88 mmol/L
 2.88 to 3.13 mmol/L
 3.13 to 3.38 mmol/L
 3.38 mmol/L
Infant  7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10 mmol/L
 12.4 to 12.9 mg/dL
> 3.10 to 3.23 mmol/L
 12.9 to 13.5 mg/dL
> 3.23 to 3.38 mmol/L
 13.5 mg/dL
> 3.38 mmol/L
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to  2.5 mg/dL
 2.0 mg/dL
Hypocalcemia 
(ionized)
0.74 mmol/L to LLN
0.62 to  0.74 mmol/L
0.49 to  0.62 mmol/L
 0.49 mmol/L
ULN to 6.0 mg/dL
 6.0 to 6.5 mg/dL
 6.5 to 7.0 mg/dL
 7.0 mg/dL
Hypercalcemia 
(ionized)
ULN to 1.50 mmol/L
 1.50 to 1.63 mmol/L
 1.63 to 1.75 mmol/L
 1.75 mmol/L
1.40 to < LLN mg/dL
1.2 to < LLN mEq/L
1.04 to  1.40 mg/dL
0.9 to  1.2 mEq/L
0.67 to  1.04 mg/dL
0.6 to  0.9 mEq/L
 0.67 mg/dL
 0.6 mEq/L
Hypomagnesemia
0.58 to < LLN 
mmol/L
0.43 to  0.58 mmol/L
0.28 to  0.43 mmol/L
 0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
 14 Years
2.0 to < LLN mg/dL
0.63 to LLN mmol/L
1.5 to  2.0 mg/dL
0.47 to  0.63 mmol/L
1.0 to  1.5 mg/dL
0.31 to  0.47 mmol/L
 1.0 mg/dL
 0.31 mmol/L
Pediatric 1–14 Years 
3.0 to < LLN mg/dL
0.96 to < LLN 
mmol/L
2.5 to  3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to  2.5 mg/dL
0.47 to < 0.80 mmol/L
 1.5 mg/dL
< 0.47 mmol/L
Pediatric  1 Year
3.5 to < LLN mg/dL
1.12 to < LLN 
mmol/L
2.5 to  3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to  2.5 mg/dL
0.47 to < 0.80 mmol/L
 1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia
Adult and Pediatric 
> 14 Days
 1.0 to 1.5  ULN
 1.5 to 2.5  ULN
 2.5 to 5.0  ULN
 5.0  ULN
Infant  14 Days
(nonhemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
 25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
 30.0 mg/dL
> 513 μmol/L
Infant  14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
 25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50  ULN
 2.50 to 5.00  ULN
 5.00 to 10.00  ULN
 10.00  ULN

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Amendment 3
CONFIDENTIAL
Page 138
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CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
>ULN to 10.0 mg/dL
 10.0 to 12.0 mg/dL
 12.0 to 15.0 mg/dL
 15.0 mg/dL
Hyperuricemia
>ULN to 597 μmol/L
 597 to 716 μmol/L
 716 to 895 μmol/L
 895 μmol/L
1.5 mg/dL to LLN
87 μmol/L to LLN
to  1.5 mg/dL
57 to  87 μmol/L
0.5 to  1.0 mg/dL
27 to  57 μmol/L
 0.5 mg/dL
 27 μmol/L
Hypouricemia
Adult and Pediatric
≥ 1 Year
Infant < 1 Year
N/A
mg/dL to < LLN
57 μmol/L to < LLN
0.5 to  1.0 mg/dL
27 to  57 μmol/L
 0.5 mg/dL
 27 μmol/L
Creatinineb
 1.50 to 2.00 mg/dL
 133 to 177 μmol/L
 2.00 to 3.00 mg/dL
 177 to 265 μmol/L
 3.00 to 6.00 mg/dL
 265 to 530 μmol/L
 6.00 mg/dL
 530 μmol/L
16.0 mEq/L to  LLN
11.0 to  16.0 mEq/L
8.0 to  11.0 mEq/L
 8.0 mEq/L
Bicarbonate
Adult and Pediatric
≥ 4 Years
16.0 mmol/L to 
 LLN
11.0 to  16.0 mmol/L
8.0 to  11.0 mmol/L
 8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/L to < LLN
8.0 to  11.0 mEq/L
 8.0 mEq/L
11.0 mmol/L 
to < LLN
8.0 to  11.0 mmol/L
 8.0 mmol/L
Triglycerides
(fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
 750 to 1200 mg/dL
 8.47 to 13.55 
mmol/L
 1200 mg/dL
 13.55 mmol/L
130 to 160 mg/dL
> 160 to 190 mg/dL
> 190 mg/dL
NA
Low-Density 
Lipoprotein (fasting)
Adult
3.35 to 4.15 mmol/L
> 4.15 to 4.92 mmol/L
> 4.92 mmol/L
110 to 130 mg/dL
> 130 to 190 mg/dL
> 190 mg/dL
NA
Low-Density 
Lipoprotein (fasting)
Pediatric > 2 to < 18 
Years
2.84 to 3.37 mmol/L
> 3.37 to 4.92 mmol/L
> 4.92 mmol/L
200 to 239 mg/dL
 239 to 300 mg/dL
 300 mg/dL
NA
Hypercholesterolemia
(fasting)
5.16 to 6.19 mmol/L
 6.19 to 7.77 mmol/L
 7.77 mmol/L
Pediatric  18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
 199 to 300 mg/dL
 5.15 to 7.77 mmol/L
 300 mg/dL
 7.77 mmol/L
NA
Creatine Kinase
3.0 to  6.0  ULN
6.0 to  10.0  ULN
10.0 to  20.0  ULN
 20.0  ULN
a
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
b
An overlap between the Grade 1 scale and the laboratory’s normal range for creatinine may result for male participants > 70 
years. Please follow the Gilead convention of grading any result within the lower limit of normal (LLN) and upper limit of 
normal (ULN) a 0.

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ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50  ULN
 2.50 to 5.00  ULN
 5.00 to 10.00  ULN
 10.00  ULN
ALT (SGPT) 
1.25 to 2.50  ULN
 2.50 to 5.00  ULN
 5.00 to 10.00  ULN
 10.00  ULN
GGT
1.25 to 2.50  ULN
 2.50 to 5.00  ULN
 5.00 to 10.00  ULN
 10.00  ULN
Alkaline Phosphatase 
1.25 to 2.50  ULN
 2.50 to 5.00  ULN
 5.00 to 10.00  ULN
 10.00  ULN
Total Amylase
 1.0 to 1.5  ULN
 1.5 to 2.0  ULN
 2.0 to 5.0  ULN
 5.0  ULN
Pancreatic Amylase
 1.0 to 1.5  ULN
 1.5 to 2.0  ULN
 2.0 to 5.0  ULN
 5.0  ULN
Lipase 
 1.0 to 1.5  ULN
 1.5 to 3.0  ULN
 3.0 to 5.0  ULN
 5.0  ULN
-
2.0 g/dL to LLN
20 g/L to LLN
 2.0 g/dL
 20 g/L
NA
Albumin
Pediatric < 16 Years
Adult and Pediatric
≥ 16 Years
3.0 g/dL to LLN
30 g/L to LLN
2.0 to  3.0 g/dL
20 to  30 g/L
 2.0 g/dL
 20 g/L
NA
ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyltransferase; LLN = lower limit of 
normal; SGOT = serum glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic transaminase; ULN = upper limit of 
normal

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URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (dipstick)
1
2
3-4+
NA
Hematuria (quantitative)
See Note below
Females
>ULN to 
10 RBC/HPF
 10 to 75 RBC/HPF
> 75 RBC/HPF
NA
Males
6 to 10 RBC/HPF
 10 to 75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (dipstick)
1
2–3
4
NA
Proteinuria, 24-Hour 
Collection
Adult and Pediatric
 10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 
h
>1999 to 3500 
mg/24 h
 3500 mg/24 h
Pediatric  3 Months to 
< 10 Years
201 to 499 
mg/m2/24 h
>499 to 799 
mg/m2/24 h
>799 to 1000 
mg/m2/24 h
 1000 mg/m2/24 h
Glycosuria (dipstick)
1+
2-3
4
NA
RBC/HPF = red blood cells per high power field
Notes:

Toxicity grades for quantitative and dipstick hematuria will be assigned by Covance Laboratory; however, for other 
laboratories, toxicity grades will only be assigned to dipstick hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the lower limit of normal (LLN) 
and upper limit of normal (ULN) should be assigned Grade 0.

If the severity of a clinical adverse event (AE) could fall under either 1 of 2 grades (eg, the severity of an AE could be either 
Grade 2 or Grade 3), select the higher of the 2 grades for the AE.

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

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

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

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

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

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

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

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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Insomnia
NA
Difficulty sleeping 
causing greater than 
minimal interference 
with usual 
social/functional 
activities
Difficulty sleeping 
causing inability to 
perform usual social 
& functional 
activities
Disabling insomnia 
causing inability to 
perform basic self-care 
functions
Neuromuscular 
Weakness
(including myopathy & 
neuropathy)
Asymptomatic with 
decreased strength 
on exam OR 
Minimal muscle 
weakness causing no 
or minimal 
interference with 
usual social & 
functional activities
Muscle weakness 
causing greater than 
minimal interference 
with usual social & 
functional activities
Muscle weakness 
causing inability to 
perform usual social 
& functional 
activities
Disabling muscle 
weakness causing 
inability to perform basic 
self-care functions OR 
Respiratory muscle 
weakness impairing 
ventilation
Neurosensory Alteration 
(including paresthesia 
and painful neuropathy)
Asymptomatic with 
sensory alteration on 
exam or minimal 
paresthesia causing 
no or minimal 
interference with 
usual social & 
functional activities
Sensory alteration or 
paresthesia causing 
greater than minimal 
interference with 
usual social & 
functional activities
Sensory alteration or 
paresthesia causing 
inability to perform 
usual social & 
functional activities
Disabling sensory 
alteration or paresthesia 
causing inability to 
perform basic self-care 
functions
Seizure: (new onset)
NA
1 seizure
2–4 seizures
Seizures of any kind that 
are prolonged, repetitive 
(eg, status epilepticus), 
or difficult to control 
(eg, refractory epilepsy)
Seizure: (pre-existing)
For Worsening of 
Existing Epilepsy the 
Grades Should Be Based 
on an Increase from 
Previous Level of 
Control to Any of These 
Levels
NA
Increased frequency 
of pre-existing 
seizures 
(nonrepetitive) 
without change in 
seizure character OR 
infrequent 
breakthrough 
seizures while on 
stable meds in a 
previously 
controlled seizure 
disorder
Change in seizure 
character from 
baseline either in 
duration or quality 
(eg, severity or 
focality)
Seizures of any kind that 
are prolonged, repetitive 
(eg, status epilepticus), 
or difficult to control 
(eg, refractory epilepsy)
Seizure
–Pediatric  18 Years
Seizure, generalized 
onset with or 
without secondary 
generalization, 
lasting < 5 minutes 
with < 24 hours post 
ictal state
Seizure, generalized 
onset with or 
without secondary 
generalization, 
lasting
5 to 20 minutes with
< 24 hours post ictal 
state
Seizure, generalized 
onset with or 
without secondary 
generalization, 
lasting
> 20 minutes
Seizure, generalized 
onset with or without 
secondary 
generalization, requiring 
intubation and sedation

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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Syncope (not associated 
with a procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no 
or minimal 
interference with 
usual social & 
functional activities
Vertigo causing 
greater than minimal 
interference with 
usual social & 
functional activities
Vertigo causing 
inability to perform 
usual social & 
functional activities
Disabling vertigo 
causing inability to 
perform basic self-care 
functions
ER = emergency room

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

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

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

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

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

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Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a) Definition of Childbearing Potential
For the purposes of this study, a female-born participant is considered of childbearing potential 
following the initiation of puberty (Tanner Stage 2) until becoming postmenopausal, unless the 
participant is permanently sterile or has medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are ≥ 54 years of age with 
cessation of previously occurring menses for ≥ 12 months without an alternative cause. In 
addition, women < 54 years of any age with amenorrhea of ≥ 12 months are not permanently 
sterile may also be considered postmenopausal if their follicle-stimulating hormone level is in 
the postmenopausal range and they are not using hormonal contraception or hormonal 
replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female participant of any age.
2) Contraception Requirements for Female Participants
a) Study Drug Effects on Pregnancy and Hormonal Contraception
The overall potential for genetic toxicity of VES is considered to be low. In developmental 
toxicity studies in mice and rabbits, dose-developmental findings were observed in the rabbit 
only at doses that caused maternal toxicity (see VES IB edition 09, Sections 3.3.5. and 6.1.1.1.2). 
Such findings included increased incidence of early and late fetal resorptions, reduced fetal 
weights, and increased incidence of soft tissue/skeletal alterations (malformations and variations) 
at 15 and 30 mg/kg doses. Given these findings in nonclinical studies, VES has shown the 
potential for embryofetal developmental effects.
There are no clinical data regarding the use of VES in pregnant women. The effects of VES on 
an unborn child are unknown. A clinical PK study evaluating the drug interaction potential of 
VES has not been conducted; however, based on the nonoverlapping metabolic pathways for 
VES and oral contraceptives, no clinically relevant drug interactions are expected upon 
co-administration of these agents. Please refer to the latest version of the VES investigator’s 
brochure (IB) for additional information.
VRC07-523LS and CAP256V2LS are contraindicated in pregnancy as their 
teratogenicity/fetotoxicity profile is unknown. A reduction in the clinical efficacy of hormonal 
contraception is not expected as VRC07-523LS and CAP256V2LS are not cytokine modulators. 
As protein biologics, VRC07-523LS and CAP256V2LS are not expected to be genotoxic but 
genotoxicity has not been evaluated in these compounds. Please refer to the latest version of the 
IB for additional information.

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B) Contraception Requirements for Female Participants of Childbearing Potential
The inclusion of female participants of childbearing potential requires the use of highly effective 
contraceptive measures with a failure rate of < 1% per year. They must have a negative serum 
pregnancy test at screening and a negative urine pregnancy test at baseline/Day 0 visit prior to 
enrollment. Pregnancy tests will be performed at regular intervals thereafter until the end of 
contraception requirement.
Duration of required contraception for female participants in this clinical trial should start from 
screening visit until 10 days after the last dose of VES or until 250 days after the last dose of 
VRC07-523LS and CAP256V2LS, whichever date is later.
Female participants must agree to one of the following contraceptive methods:

Nonhormonal intrauterine device (IUD)

Hormonal IUD (must be used in conjunction with a barrier method)

Bilateral tubal occlusion (upon medical assessment of surgical success)
OR
Female participants who wish to use a hormonally based method must use it in conjunction with 
a barrier method, preferably a male condom. Hormonal methods are restricted to those associated 
with the inhibition of ovulation. Hormonally based contraceptives and barrier methods permitted 
for use in this protocol are as follows:
Hormonal methods (each method must be used with a barrier method, preferably male condom)

Oral contraceptives (either combined or progesterone only)

Injectable progesterone

Subdermal contraceptive implant

Transdermal contraceptive patch

Contraceptive vaginal ring
Barrier methods (each method must be used with a hormonal method)

Male condom (with or without spermicide)

Female condom (with or without spermicide)

Diaphragm with spermicide

Cervical cap with spermicide

Sponge with spermicide

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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 participants must also refrain from egg donation and in vitro fertilization during 
treatment and until the end of contraception requirement.
3) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. A female condom and a male condom should not be used 
together.
4) Procedures to be Followed in the Event of Pregnancy
Participants will be instructed to notify the investigator if they become pregnant at any time 
during the study, or if they become pregnant within 10 days after the last dose of VES or 
250 days after the last dose of VRC07-523LS and CAP256V2LS, whichever date is later. 
Participants who become pregnant or who suspect that they are pregnant must report the 
information to the investigator and discontinue study drug immediately. Instructions for 
reporting pregnancy and pregnancy outcome are outlined in Section 7.4.2.3.

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Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (Centers for 
Disease Control and Prevention [CDC] Guidelines)
1) Candidiasis of bronchi, trachea, or lungs
2) Candidiasis of esophagus
3) Cervical cancer, invasive
4) Coccidioidomycosis, disseminated or extrapulmonary
5) Cryptococcosis, extrapulmonary
6) Cryptosporidiosis, chronic intestinal (> 1-month duration)
7) Cytomegalovirus disease (other than liver, spleen, or nodes)
8) Cytomegalovirus retinitis (with loss of vision)
9) Encephalopathy, HIV-related
10) Herpes simplex: chronic ulcer(s) (> 1-month duration); or bronchitis, pneumonitis, or 
esophagitis
11) Histoplasmosis, disseminated or extrapulmonary
12) Isosporiasis, chronic intestinal (> 1-month duration)
13) Kaposi’s sarcoma
14) Lymphoma, Burkitt’s (or equivalent term)
15) Lymphoma, immunoblastic (or equivalent term)
16) Lymphoma, primary, of brain
17) Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
18) Mycobacterium tuberculosis, of any site, pulmonary, disseminated or extrapulmonary
19) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
20) Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia
21) Pneumonia, recurrent
22) Progressive multifocal leukoencephalopathy
23) Salmonella septicemia, recurrent
24) Toxoplasmosis of brain
25) Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 (57221)

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Appendix 7.
Pandemic Risk Assessment and Mitigation Plan
During an ongoing pandemic, potential risks associated with participants being unable to attend 
study visits have been identified for this study. For infectious disease pandemics, sites will utilize 
regional or local guidelines to manage the clinic and participants. Based on the nature of the 
local epidemic at the time of study initiation, participants may be screened prior to enrollment 
and administration of VES and may be subsequently tested for following any “flu-like AEs” after 
VES that may overlap with potential signs/symptoms of pandemic disease.
These risks can be summarized as follows:
1) Study drug supplies to participants and sites:
Due to the on-site study drug dosing requirements, there will be a pause in dosing during the 
pandemic. There will be no mitigation options available.
Shipments of study drug could be delayed because of transportation issues. Without study 
drug, the participant would not be able to continue receiving the study drug as planned per 
protocol.
Mitigation plan: The site’s 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 investigational sites. Manual shipments will be 
triggered as necessary.
2) Participant safety monitoring and follow up:
A. Participants may be unable or unwilling to come to the study site for their scheduled 
study visits as required per protocol.
Mitigation plan: For participants who may be unable or unwilling to visit the study site 
for their scheduled study visits as required per protocol, the principal investigator or 
qualified delegate will conduct a virtual study visit, via phone or video conferencing, to 
assess the participant within the target visit window date whenever possible. During the 
virtual study visit, the following information at minimum will be reviewed:
i.
Confirm if participant has experienced any adverse events (AEs)/serious adverse 
events (SAEs)/special situations (including pregnancy) and follow up on any 
unresolved AE/SAEs.
ii. Review current list of concomitant medications and document any new concomitant 
medications.
iii. If applicable, confirm electronic diary questionnaires and participant-reported 
outcomes have been completed and transmitted.

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iv. If applicable, confirm participant’s study drug supply is sufficient to last until the next 
planned visit date. If study drug resupply is needed it will be provided as described 
above in (1).
v. If applicable, remind participant to maintain current dosing and to keep all dispensed 
study drug kits for return at the next on-site visit.
B. Participants may be unable or unwilling to travel to the site for planned assessments 
(eg, safety blood draws); hence samples may not be sent for central laboratory analyses.
Mitigation plan: Local laboratories may be utilized as appropriate to monitor participant 
safety until the participant can return to the site for their regular follow up per protocol. 
Any laboratory assessments conducted at a local laboratory due to the pandemic will be 
documented accordingly. Pregnancy testing may be performed using a home urine 
pregnancy test if local laboratory pregnancy testing is not feasible.
C. Participants may be unable or unwilling to attend the study visit to sign an updated 
informed consent form version.
Mitigation plan: The site staff will follow their approved consent process and remain in 
compliance with local ethics committee (EC)/institutional review board (IRB) and 
national laws and regulations. Remote consent will be allowed if has been approved by 
the local EC/IRB. The consent process will be documented and confirmed by normal 
consent procedure at the earliest opportunity.
3) Protocol and monitoring compliance:
A. Protocol deviations may occur, in case scheduled visits cannot occur as planned per 
protocol.
Mitigation plan: If it is not possible to complete a required procedure, an unscheduled 
visit should be conducted as soon as possible when conditions allow. The situation should 
be recorded and explained as a protocol deviation. Any missed participant visits or 
deviation to the protocol due to the pandemic must be reported in the electronic case 
report form and described in the clinical study report. Any virtual study visits that are 
conducted in lieu of clinic visits due to the pandemic will be documented as a protocol 
deviation related to the pandemic.
B. Monitors may be unable to carry out source data review or source data verification 
(SDV), or study drug accountability or assess protocol and Good Clinical Practice 
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 may be arranged if 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.

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

Prot GS-US-382-5445 Amd 3
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Research eSigned
07-Oct-2022
21:37:17
PPD