Safety and Therapeutic Efficacy of the Broadly Neutralizing HIV-1 Specific Monoclonal Antibody VRC01 During Analytic Treatment Interruption in Patients Who Initiated Antiretroviral Therapy During Early Acute HIV Infection
Phase: PHASE2
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

RV 397/WRAIR #2180/ SEARCH 024 
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PROTOCOL RV 397 
 
Safety and Therapeutic Efficacy of the Broadly Neutralizing HIV-1 Specific 
Monoclonal Antibody VRC01 during Analytic Treatment Interruption in 
Patients who Initiated Antiretroviral Therapy During Early Acute HIV 
Infection 
 
Study Agent Provided by  
Vaccine Research Center/NIAID/NIH, Bethesda, MD 
Study Conducted By  
U.S. Military HIV Research Program, Silver Spring, MD 
The Thai Red Cross AIDS Research Center, Bangkok, Thailand 
 
In Collaboration with 
Vaccine Research Center, NIAID, NIH 
Study Sponsored By 
National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS (DAIDS), 
National Institutes of Health (NIH) 
Bethesda, Maryland 
 
IND Number: 126,001 
 
DAIDS-ES ID: 12001 
 
 
 
 
Protocol Chair: 
 
 
 
 
Jintanat Ananworanich, MD, PhD 
Local Principal Investigator: 
 
 
Nittaya Phanuphak, MD, PhD 
Project Leader (USA): 
 
 
 
Trevor A. Crowell, MD 
Project Leader (Thailand):   
 
 
Donn J. Colby, MD, MPH 
DoD Research Monitor: 
 
 
 
Krisada Jongsakul, MD 
DAIDS Medical Officer:  
 
 
 
Randall Tressler, MD 
 

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TABLE OF CONTENTS 
SCHEMA 
5 
LIST OF ABBREVIATIONS 
7 
1.0 
INTRODUCTION 
10 
1.1 
Background 
10 
2.0 
STUDY AGENT 
11 
2.1 
Background 
11 
2.2 
Description of Study Agent VRC-HIVMAB060-00-AB (VRC01) 
11 
2.3 
Rationale for VRC01 as a Study Agent 
11 
2.4 
Preclinical GLP Toxicology Study 
12 
2.5 
Tissue Cross-Reactivity GLP Study of VRC01 with Human Tissues In Vitro 
13 
2.6 
Nonhuman Primate (NHP) Studies of VRC01 
14 
2.7 
Phase 1 Clinical Trials of VRC01 
14 
2.8 
Summary Statement on Safety of Study Agent 
16 
3.0 
STUDY OBJECTIVES, ENDPOINTS AND RATIONALE 
17 
3.1 
Study Objectives 
17 
3.2 
Study Endpoints 
17 
3.3 
Hypotheses 
19 
3.4 
Rationale for Study Timing 
19 
3.5 
Rationale for Inclusion of Placebo Arm 
20 
4.0 
STUDY DESIGN AND POPULATION 
21 
4.1 
General Design 
21 
4.2 
Participants 
21 
4.3 
Protease Inhibitor Substitution 
21 
4.4 
Intervention 
22 
4.5 
Analytic Treatment Interruption (ATI) 
22 
4.6 
Criteria for Resumption of ART 
23 
4.7 
Management of subjects after completion of protocol 
24 
4.8 
Management of Subjects after Resumption of ART 
24 
4.9 
Management of Subjects With Sustained Virologic Control at End of Study 
25 
4.10 
Management of Subjects Who Become Pregnant 
25 
5.0 
STUDY PROCEDURES 
27 
5.1 
Eligibility 
27 
5.2 
Rationale for Eligibility Criteria 
28 
5.3 
Schedule of Evaluations 
29 
5.4 
Management of Individual Research Results 
30 
5.5 
Neuropsychological Testing 
31 
5.6 
Control and Attention Testing 
31 
5.7 
Therapeutic Drug Monitoring 
31 
5.8 
Optional Procedures 
32 
5.9 
Concomitant Medications 
34 
5.10 
Solicited Adverse Events 
35 
5.11 
Study Discontinuation 
35 
6.0 
STUDY TREATMENT 
37 
6.1 
Study Treatment Regimens, Administration, and Duration 
37 
6.2 
Study Product Formulation and Preparation 
37 

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6.3 
Pharmacy: Product Supply, Distribution, and Accountability 
40 
6.4 
Disposition 
40 
7.0 
PHARMACOVIGILENCE, SAFETY, AND ADVERSE EXPERIENCE 
REPORTING 
41 
7.1 
Definitions 
41 
7.2 
Adverse Event Grading and Recording 
41 
7.3 
Protocol Safety Review Team (PSRT) and PSRT Reviews 
42 
7.4 
Safety Monitoring Committee (SMC) Reviews 
43 
7.5 
Criteria for Study Pause or Termination 
43 
7.6 
Expedited Reporting to IND Sponsor (DAIDS) 
45 
7.7 
Reporting Serious and Unexpected Adverse Events to the DoD In Addition To 
DAIDS 
46 
7.8 
Reporting Requirements to the Local IRB 
47 
7.9 
Reporting Requirements to the Thai FDA 
48 
7.10 
Unblinding 
48 
8.0 
STATISTICAL CONSIDERATIONS 
50 
8.1 
Power and Sample Size for Safety Objective 
50 
8.2 
Power and Sample Size for Efficacy Objective 
50 
8.3 
Analysis 
51 
9.0 
DATA COLLECTION 
54 
10.0 
ETHICAL CONSIDERATIONS 
55 
10.1 
Participation of Children 
55 
10.2 
Risks 
55 
10.3 
Risks Related to Optional Procedures 
58 
10.4 
Benefits 
60 
10.5 
Informed Consent 
60 
10.6 
Language 
61 
10.7 
Compensation 
61 
10.8 
DoD Research Monitor 
61 
10.9 
Participant Confidentiality 
62 
10.10 
Institutional Review Board 
62 
10.11 
Future Use and Storage of Blood Samples 
62 
10.12 
Study Documentation And Storage 
63 
11.0 
ADMINISTRATIVE AND LEGAL PROCEDURES 
64 
11.1 
Protocol Deviation Reporting 
64 
11.2 
Protocol Modifications 
64 
11.3 
Continuing Reviews/Closeout Report 
65 
11.4 
Volunteer Registry Database 
66 
11.5 
Policy Regarding Research-Related Injuries 
66 
11.6 
Use Of Information And Publication 
66 
12.0 
CONDUCT OF THE RESEARCH STUDY 
68 
12.1 
Regulatory Audits 
68 
12.2 
DAIDS Study Monitoring 
68 
13.0 
RELEVANCE 
69 
13.1 
Military Relevance 
69 
13.2 
Thai Relevance 
69 
14.0 
PRINCIPAL INVESTIGATOR AGREEMENT: 
71 

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15.0 
REFERENCES 
73 
APPENDIX I: CASE DEFINITION FOR ACUTE RETROVIRAL SYNDROME (ARS) 
79 
APPENDIX II:  SCHEDULE OF EVALUATIONS 
80 
ATTACHMENT I: STUDY TEAM ROSTER 
84 
ATTACHMENT II: ROLES AND RESPONSIBILITIES 
88 
ATTACHMENT III: DAIDS AE GRADING TABLE 
89 
ATTACHMENT IV: TEST OF UNDERSTANDING 
90 

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SCHEMA 
 
Title 
Safety and Therapeutic Efficacy of the Broadly Neutralizing HIV-1 Specific Monoclonal 
Antibody VRC01 during Analytic Treatment Interruption in Patients who Initiated Antiretroviral 
Therapy during Early Acute HIV Infection 
Clinical Phase 
Phase II 
Study Duration 
Study duration is up to 54 weeks. 
Study Design 
This is a placebo-controlled clinical trial of VRC01 administration and analytic treatment 
interruption (ATI) in adults who began antiretroviral therapy (ART) during early acute HIV 
infection (Fiebig stage I to III). Eligible volunteers will be randomized in a 3:1 ratio to either 
VRC01 or placebo, with randomization stratified by Fiebig stage. Volunteers who are receiving 
ART with a non-nucleoside reverse transcriptase inhibitor (NNRTI) will undergo 4 weeks of 
protease inhibitor (PI) substitution for their NNRTI prior to randomization. ATI will begin the 
day of the first dose of either VRC01 or placebo. Participants will be monitored closely for HIV 
viremia and other pre-defined criteria for ART resumption (see section 4.6). Administration of 
the study agent (VRC01) every three weeks will be discontinued after 24 weeks or if ART is 
resumed, whichever occurs first. Volunteers who are virally suppressed without laboratory or 
clinical indication for ART resumption at 24 weeks will continue intensive monitoring for ART 
resumption criteria for an additional 24 weeks, during which time no VRC01 or placebo will be 
administered. 
Sample Size 
Sample size is 24 participants 
Participants 
This study will recruit 24 adults aged 20-50 years in Bangkok, Thailand who were diagnosed 
during acute HIV infection (Fiebig stage I to III) and initiated on ART. 
Intervention 
The investigational agent, VRC-HIVMAB060-00-AB (VRC01), is a broadly neutralizing human 
mAb targeted against the HIV-1 CD4 binding site. It was developed by the Vaccine Research 
Center (VRC), National Institutes of Allergy and Infectious Diseases (NIAID), National 
Institutes of Health (NIH) and manufactured for the VRC by the Vaccine Pilot Plant operated by 
Leidos Biomedical Research, Inc, formerly SAIC-Frederick, Inc., Frederick, MD.  Vials are 
provided at 100 ± 10 mg/mL.   
 

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The placebo agent that will be used is normal saline (Sodium Chloride for Injection USP, 0.9%). 
Volunteers will receive either VRC01 or placebo administered intravenously every three weeks 
for a total duration of 24 weeks or until ART resumption criteria are met, whichever comes first. 
Study Objectives 
Primary 
1. To evaluate the safety of VRC01 when administered during an ATI. 
2. To evaluate the ability of VRC01 monotherapy to maintain virologic suppression at 24 
weeks.  
Secondary 
1. To assess the impact of VRC01 on viral dynamics following ATI, including time to viral 
rebound and level of rebound viremia. 
2. To assess the impact of VRC01 on CD4 count following ATI. 
3. To assess the impact of VRC01 on HIV reservoir replenishment and expression 
following ATI.  
4. To assess the impact of VRC01 on clinical characteristics of HIV infection following 
ATI. 
Exploratory 
1. To describe HIV-1 isolate neutralization sensitivity and genetic sequence, including sieve 
effect of VRC01. 
2. To characterize the effect of VRC01 on host cellular and innate immune responses, 
including broad and HIV-specific immune responses. 
3. To identify predictors of sustained virologic control, such as host genetic alleles, immune 
responses, and viral genetics. 
4. To identify the presence or absence of anti-VRC01 antibodies after ATI and 
administration of VRC01. 
5. To describe the impact of VRC01 on viral dynamics in multiple body compartments.  
6. To assess the distribution of VRC01 into various body compartments. 
 

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LIST OF ABBREVIATIONS 
TERM 
DEFINITION 
Ab 
Antibody 
ADCC 
Antibody-dependent cell-mediated cytotoxicity 
AE 
Adverse experience 
AFRIMS 
Armed Forces Research Institute of Medical Sciences 
AHI 
Acute HIV infection 
AI 
Associate Investigator 
AIDS 
Acquired immunodeficiency syndrome 
ALP 
Alkaline phosphatase 
ALT/AST 
Alanine aminotranferase and aspartate aminotransferase liver enzymes 
ART 
Antiretroviral therapy 
ATI 
Analytic treatment interruption 
BMA 
Bangkok Metropolitan Authority 
BRA 
Behavioral risk assessment 
CBC 
Complete blood count 
CBER 
Center for Biologics Evaluation and Research (FDA) 
CD4+ 
A functional subclass of T cells, helper T lymphocytes (Th) that are 
necessary for augmentation and coordination of innate and adaptive 
effector responses, humoral and cellular 
CD8+ 
Cytotoxic T-Cells that destroy host cells, which have become infected 
by viruses or other intracellular pathogens 
CFR 
Code of Federal Regulations 
cGMP 
Current Good Manufacturing Practices 
CHMP 
Committee for Medicinal Products for Human Use 
CHO 
Chinese Hamster Ovary 
CIOMS 
Council of International Organization of Medical Sciences 
CNS 
Central nervous system 
CRF 
Case report form 
CSF 
Cerebrospinal fluid 
CSRC 
Clinical Science Review Committee 
CXR 
Chest x-ray 
DAERS 
DAIDS Adverse Experience Reporting System 
DAIDS 
U.S. Division of AIDS, NIAID, NIH 
DCAC 
Data Coordinating and Analysis Center 
DNA 
Deoxyribonucleic acid 
DoD 
United States Department of Defense 
DTI 
Diffusion tensor imaging 
EAE 
Expedited Adverse Events 
EIA 
Enzyme immunoassay 
ELISA 
Enzyme linked immunosorbent assay 

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ELISPOT 
Enzyme-Linked Immunospot 
EKG 
Electocardiogram 
ERC 
Ethical Review Committee 
FDA 
U.S. Food and Drug Administration 
GALT 
Gut-associated lymphoid tissue 
GCP 
Good Clinical Practices 
GCLP 
Good Clinical and Laboratory Practices 
GFR 
Glomerular filtration rate 
GLP 
Good Laboratory Practices 
HBV 
Hepatitis B virus 
HCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 
HIV and HIV-1 
Human immunodeficiency virus, type 1 
HLA 
Human leukocyte antigen 
HRPO 
Human Research Protection Office, Office of Research Protection, 
USAMRMC 
HSPB 
Human Subjects Protection Branch, WRAIR 
IB  
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
ICS 
Intracellular cytokine staining 
IgG 
Immunoglobulin G 
IND 
Investigational New Drug  
IRB 
Institutional Review Board 
IV 
Intravenous(ly) 
LDL 
Low-density lipoprotein 
mAb 
Monoclonal antibody 
Mg 
Milligram 
MHA 
Multi-region hybridization assay 
MHRP 
U.S. Military HIV Research Program 
mL 
Milliliter  
Mm 
Millimeter 
MO 
Medical Officer 
MOP 
Manual of Operations 
MOPH 
Ministry of Public Health, Royal Thai Government 
MRI 
Magnetic resonance imaging 
MRS 
Magnetic resonance spectroscopy 
MSM 
Men who have sex with men 
NAAT 
Nucleic acid amplification tests 
Nab 
Neutralizing antibody 
NHP 
Non-human primate 

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NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NOAEL 
“no observed adverse effect level”  
NOEL 
“no observed effect level”  
OHRP 
Office for Human Research Protection 
ORP 
Office of Research Protections, USAMRMC 
ORTA 
WRAIR Office of Research Technology and Applications 
PBMC 
Peripheral blood mononuclear cells 
PCR 
Polymerase chain reaction 
PI 
Principal investigator 
PIR 
post-injection reactogenicity 
PK 
Pharmacokinetics 
PSRT 
Protocol Safety Review Team 
QA 
Quality assurance 
QVOA 
Qualitative viral outgrowth assay 
RAB 
DAIDS Regulatory Affairs Branch 
RBC 
Red blood cell count 
RSC 
DAIDS Regulatory Support Center 
SAE 
Serious adverse experience 
SBV 
Small blood volume 
SC 
Subcutaneous injection 
SEARCH 
South East Asia Research Collaboration with Hawaii 
SHIV 
Simian-human immunodeficiency virus 
SIV 
Simian immunodeficiency virus 
SOE 
Schedule of Evaluations 
TILDA 
Tat/Rev induced limiting dilution assay 
TRCAC 
Thai Red Cross Anonymous Clinic 
TRCARC 
Thai Red Cross AIDS Research Centre 
TULDA 
Tat/Rev uninduced limiting dilution assay 
U.S. 
United States 
UNAIDS 
The Joint United Nations Programme on HIV/AIDS 
UPIRTSOs 
Unanticipated problems related to the study and involving risk to 
subjects or others 
USAMRMC 
U.S. Army Medical Research and Materiel Command 
VCT 
Voluntary counseling and testing 
VRC01 
VRC-HIVMAB060-00-AB, a broadly neutralizing human monoclonal 
antibody targeted against the HIV-1 CD4 binding site 
WBC 
White blood cell count 
WRAIR 
Walter Reed Army Institute of Research 
 

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1.0 
INTRODUCTION 
1.1 
BACKGROUND 
Antiretroviral therapy (ART) is currently the cornerstone of HIV management. ART in the setting 
of chronic HIV reduces both morbidity and mortality [1-5]. There is a growing body of evidence 
that ART is also beneficial in the management of acute infection, wherein it may preserve immune 
function [6, 7], decrease viral evolution [8], and limit the viral reservoir [9-11]. Still, CDC 
estimates suggest that only 36% of persons living with HIV (PLWH) in the U.S. are currently 
prescribed ART and only 28% have achieved HIV suppression [12]. Barriers to the universal use 
of ART include the need for high-level and lifelong adherence, development of drug resistance, 
toxicities, and cost [13-16]. These barriers are intensified in resource-limited settings [17-19]. 
Treatment strategies that can confer durable virologic control and delay disease progression while 
minimizing ART exposure are highly desirable. Strategic interruption of ART has therefore been 
the focus of several large studies. In these studies involving patients chronically infected with HIV, 
interruption of ART was associated with worse clinical outcomes than continuous prescription of 
ART [20, 21]. Furthermore, peripheral blood HIV-1 RNA was seen to rapidly return to pre-ART 
levels upon discontinuation of therapy [21-23]. Inaccessible reservoirs of latently-infected resting 
memory CD4+ T cells, particularly in the gut-associated lymphoid tissue (GALT), are 
hypothesized to be the major source responsible for rebound viremia after discontinuation of ART 
[24-28]. 
In contrast to patients begun on ART late in the course of chronic HIV infection, some patients 
who begin ART at the time of acute infection demonstrate blunted or delayed rebound viremia 
after treatment interruption and 5-16% show sustained virologic control [9, 29-32]. Factors 
associated with successful virologic control include shorter duration from HIV onset to ART 
initiation, longer duration on ART and low peripheral blood mononuclear cell-associated HIV 
DNA. In the RV 254/SEARCH010 study in Thailand, early initiation of ART significantly 
restricted integration of HIV DNA in peripheral blood mononuclear cells, including central 
memory CD4+ T cells [33-35]. In this study, total HIV declines were also seen on serial sigmoid 
biopsies in several patients. Total blood HIV DNA at initiation of therapy predicted reservoir size 
after 24 weeks of aggressive ART, underscoring the importance of early initiation of ART. Prior 
evidence has shown that reservoir distribution in shorter-lived cells is associated with elite control 
status [36-38]. Patients in RV 254/SEARCH 010 demonstrated this favorable pattern of reservoir 
distribution. For multiple reasons, patients who have received ART early in acute HIV infection 
are ideal candidates for the evaluation of novel therapies that seek to achieve a functional cure of 
HIV. 
VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing human monoclonal antibody 
targeted against the HIV-1 CD4 binding site. VRC01 has shown promise in animal studies as a 
safe and potent therapy to both reduce HIV viremia in infected animals and prevent HIV 
acquisition in uninfected animals given a variety of challenges. Phase I studies have demonstrated 
safety in humans and elucidated pharmacokinetic parameters (see section 2.7). 
This is a randomized clinical trial to explore the impact of VRC01 on both virus and host-specific 
parameters in adults who began ART during acute HIV infection. 

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2.0 
STUDY AGENT 
2.1 
BACKGROUND 
The study agent, VRC-HIVMAB060-00-AB, was manufactured for the VRC by the Vaccine Pilot 
Plant operated by Leidos Biomedical Research, Inc, formerly SAIC-Fredrick, Inc, Fredrick, MD. 
Specific manufacturing information is included on the product vial labels and Certificates of 
Analysis and can be found in the Investigator’s Brochure (IB).  Quality Assurance (QA) lot release 
testing by the manufacturer and ongoing stability programs verify conformance to product 
specifications prior to use in clinical trials. 
2.2 
DESCRIPTION OF STUDY AGENT VRC-HIVMAB060-00-AB (VRC01) 
VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing human mAb targeted against the 
HIV-1 CD4 binding site. It was developed by the VRC/NIAID/NIH. VRC01 is of the IgG1 subtype 
and is highly somatically mutated from its germ-line precursor. The heavy chain CDR3 region is 
14 amino acids long, which is an average length relative to natural antibodies, and the 
glycosylation pattern is derived from its production in a Chinese Hamster Ovary (CHO) 
mammalian cell line. 
The study agent was produced using recombinant DNA technology. The mammalian Glutamine 
Synthetase Gene Expression System in the CHO cell line developed by Lonza Biologics (Slough, 
UK) was used to produce the VRC01 mAb. The methods by which VRC01 was isolated and 
produced have been described previously in detail. Briefly, PBMCs from HIV-1 infected adults 
stained with specific antigenic probes and passed through a flourescence activated cell sorter 
(FACS) through which single B lymphoctyes were isolated. Heavy and light chain variable regions 
of single B cell receptors were amplified by polymerase chain reaction (PCR) and sequenced. 
Heavy and light chains were initially expressed in an HEK 293 suspension cell culture.  
The bulk lot of the mAb, however, was manufactured under cGMP using a stably transfected CHO 
cell line. The product was then purified and labeled at the VRC Vaccine Pilot Plant (Frederick, 
MD), operated by Leidos Biomedical Research, Inc., Frederick, MD.  
More details on the VRC-HIVMAB060-00-AB composition and manufacturing can be found in 
the IB [39]. 
2.3 
RATIONALE FOR VRC01 AS A STUDY AGENT 
Administration of broadly neutralizing mAb has the potential to treat HIV infection by preventing 
viral spread (as with ART), and also by facilitating clearance of virus particles and mediating 
destruction of virus-producing cells, decreasing the viral reservoir and limiting immune activation. 
Several studies have demonstrated in non-human primate and humanized mouse models that 
therapy with broadly neutralizing monoclonal antibodies (mAbs) can control HIV viremia and 
reduce the HIV-1 reservoir in infected animals in the absence of ART [40-42].   
The VRC, NIAID, NIH developed the VRC01 study agent. This mAb was originally discovered 
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[43]. Using novel methods to isolate and screen memory B lymphocytes from the peripheral blood 
mononuclear cells (PBMCs) of HIV infected donors, investigators at the VRC were able to clone 
out this antibody that neutralized more than 90% of genetically diverse heterologous strains of 
HIV-1[44]. Since the initial isolation and characterization of the VRC01 mAb, subsequent 
investigations on longitudinal serum samples from HIV-1 infected individuals have shown that 
VRC01-like epitopes are induced during HIV-1 infection in a subset of HIV-infected individuals, 
but may take years to develop [45].  
In vitro, VRC01 demonstrates potent and broad neutralization capabilities, with a half-maximal 
inhibitory concentration (IC50) of <50 mcg/mL against 91% of primary isolates of various HIV-1 
clades and <1 mcg/mL against 72% of these HIV-1 clades [44]. Several proof-of concept studies 
have been conducted to determine whether the in vitro neutralization capabilities of VRC01 
translate into protecting NHPs from challenge with virulent chimeric simian-human 
immunodeficiency virus (SHIV), which contains the HIV envelope in a simian immunodeficiency 
virus (SIV) background. Rhesus macaques that received a single dose of IV VRC01 at 20mg/kg 
were fully protected against single high-dose rectal and vaginal challenges of SHIV-SF162P3 (a 
CCR5 tropic strain of HIV).  VRC01 at the same dose also protected infant macaques from oral 
SHIV challenge [39].  
Additional NHP work with VRC01 is exploring the impact of the mAb on viremia and the latent 
reservoir in acute SHIV infection.  Rhesus macaques were challenged intravenously with 
SHIVSF162P3 and subsequently administered a single dose of VRC01 40 mg/kg or started on a 
daily antiretroviral drug regimen, ten days following challenge. A control group was left untreated.  
Both VRC01 and ARV groups demonstrated a substantial antiviral effect compared to the control 
group, with reduced peak viremia [39].   
2.4 
PRECLINICAL GLP TOXICOLOGY STUDY 
A single-dose pharmacokinetics (PK) study and repeat-dose toxicity study of IV and subcutaneous 
(SC) administration of VRC-HIVMAB060-00-AB (VRC01) was performed by SRI International 
(Menlo Park, CA) in male and female Sprague-Dawley rats according to U.S. Food and Drug 
Administration (FDA) “Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies.”  
This study was conducted with a pre-GMP pilot lot of VRC01 manufactured at a smaller scale 
using a purification process similar to that of the GMP clinical-grade drug product. 
For the safety assessment, vehicle control, 4 mg/kg VRC01, 40 mg/kg VRC01, and 400 mg/kg of 
VRC01 were administered by tail vein injection on Days 1 and 8 to Groups 1 through 4, 
respectively.  The vehicle consisted of the VRC01 formulation buffer containing 25mM sodium 
citrate, 50mM sodium chloride and 150mM L-arginine-HCl at pH 5.8. An additional group (Group 
5) received 40 mg/kg VRC01 via SC administration to the dorsal scapular region on Days 1 and 
8.  Each group contained 10 male and 10 female rats. Five of each sex were sacrificed on Day 9, 
one day after the second administration; the remaining animals were sacrificed on Day 30, 22 days 
after the second administration. 
Results obtained showed that both routes of administration were well tolerated in the rats.  All 
animals survived until their scheduled necropsy.  No findings or changes were seen in general 
clinical condition, body weight, food consumption, body temperature, injection site irritation, 
organ weight or in hematologic or coagulation factor measurements that could be attributed to 

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VRC01. However, VRC01 administration resulted in small, transient, dose-dependent increases in 
aspartate aminotransferase (AST) and alkaline phosphatase (ALP) on Day 9. By Day 30, AST 
values had returned to normal, and ALP values were returning to normal.     
Other than red discoloration of the administration site in one male in the SC group on Day 9, there 
were no other gross necropsy observations attributable to VRC01 administration.  There were no 
histopathology findings that were considered related to IV administration of VRC01.  However, 
histopathology evaluation revealed subacute inflammation at the SC injection site on Day 9, one 
day after injection, in all 10 SC administered rats; dermal inflammation was usually minimal or 
mild while SC inflammation was usually mild, moderate, or marked.  By Day 30, this inflammation 
had completely resolved, and the SC dose site was normal in all rats.   
A “no observed effect level” (NOEL) was not determined in this study because transient elevations 
of AST and ALP were observed on Day 9 after IV administration and transient inflammation at 
the dose site was observed on Day 9 after SC administration. Because the elevated AST and ALP 
levels were transient and minor and did not correlate with histopathology findings, the “no 
observed adverse effect level” (NOAEL) for VRC01 by the IV route of administration in rats was 
400 mg/kg, the highest dose used in this study. The systemic NOAEL for the SC route of 
administration of VRC01 in rats was 40 mg/kg, the only SC dose level examined in this study. 
For the PK analysis, a separate cohort of rats received VRC01 on Day 1 at 4 mg/kg and 40 mg/kg 
by the IV route of administration and at 40 mg/kg by the SC route of administration.  VRC01 
levels in serum were determined by enzyme-linked immunosorbent assay (ELISA) on pre-dose 
samples collected from each animal. Untreated control samples were collected from and tested on 
an additional 3 males and 3 females. Blood was collected from 3 rats/sex/PK group for a total of 
4–5 collections per PK animal at each of the following post-dose time points:  1, 4, 8, 24, 48, and 
72 hours and 7, 14, 21, and 29 days.   
VRC01 administration by the IV route resulted in dose-proportional exposure.  The terminal 
elimination phase half-life (t1/2) was about 10 days, with clearance (Cl) of approximately 
20 ml/day/kg and volume of distribution (Vd) that was about 0.28 l/kg, indicating that the drug 
was distributed primarily in the serum and eliminated slowly. 
2.5 
TISSUE CROSS-REACTIVITY GLP STUDY OF VRC01 WITH HUMAN TISSUES IN VITRO 
A tissue cross-reactivity study of VRC-HIVMAB060-00-AB (VRC01) using normal adult and 
neonatal human tissues in vitro (Testing Facility Study No. A255-12) was performed by Charles 
River Laboratories (Reno, NV) in accordance with U.S. FDA “Good Laboratory Practice (GLP) 
for Nonclinical Laboratory Studies.”  The tissue panels used as the test system for this in vitro 
cross-reactivity study included all of the tissues on the “Suggested list of human tissues to be used 
for immunohistochemical or cytochemical investigations of cross reactivity of monoclonal 
antibodies” in Annex I of the “European Medicines Agency Guideline on Development, 
Production, Characterisation and Specifications for Monoclonal Antibodies and Related Product, 
Adopted by the Committee for Medicinal Products for Human Use (CHMP) on December 18, 
2008” and all of the tissues recommended in the FDA/Center for Biologics Evaluation and 
Research (CBER) “Points to Consider in the Manufacture and Testing of Monoclonal Antibody 
Products for Human Use (February 28, 1997).”  

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To determine the cross-reactivity of VRC01 binding, VRC01 was applied to cryosections from a 
full panel of tissues from normal human adults and a limited panel of human neonatal tissues, 
immunohistochemically detected using a biotinylated rabbit anti-human immunoglobulin G (IgG) 
secondary antibody and binding visualized with a streptavidin-horseradish peroxidase complex 
and a diaminobenzidine chromogen substrate. VRC01 binding was evaluated at concentrations of 
5 and 50 mcg/mL. 
Specific VRC01 staining was not observed in any normal adult human or neonatal human tissues 
evaluated. Therefore, in vitro evaluation of cross-reactivity in tissue specimens did not identify 
potential tissue sites or organ systems to more thoroughly evaluate in subsequent preclinical 
studies, thus supporting the use of VRC01 in humans. 
2.6 
NONHUMAN PRIMATE (NHP) STUDIES OF VRC01 
Several non-GLP preclinical studies of VRC01 have been completed in nonhuman primates 
(NHP), suggesting potential in vivo efficacy of this agent in the prevention of HIV infection.  Table 
1 is a brief summary of the studies performed [39]. 
 
Table 1: Pre-Clinical Non-Human Primate Studies of VRC01 
Study Purpose 
Study Outcome 
Demonstration of plasma and secretion 
concentrations of VRC01 given by IV or SC 
routes in female rhesus macaques 
Kinetics of decay of 40 mg/kg of VRC01 given 
IV or SC in plasma, rectal, vaginal and nasal 
secretions established 
Demonstration of challenge-protection against 
intrarectal high-dose SHIV SF162P3 in male 
rhesus macaques 
100% protection from challenge demonstrated 
at 20 mg/kg dose administered IV 
Demonstration of challenge-protection against 
intravaginal high-dose SHIV SF162P3 in 
female rhesus macaques 
100% protection from challenge demonstrated 
at 20 mg/kg dose administered IV  
Demonstration of challenge-protection against 
intrarectal high-dose SHIV-BaL in male rhesus 
macaques 
100% protection from challenge demonstrated 
at 20, 5 and 1.25 mg/kg dose administered IV 
Demonstration of effect of VRC01 during the 
acute and chronic phases of SHIV infection in 
rhesus macaques 
The administration of VRC01 (40 mg/kg IV) 
during the acute phase of infection led to a 
reduction of peak viremia and control of 
viremia during the chronic phase of infection. 
 
2.7 
PHASE 1 CLINICAL TRIALS OF VRC01 
Evaluation of VRC01 as an investigational drug began in humans with the initiation of the VRC 
601 study in September 2013. Initial development of VRC01 was based on an intended indication 
for the prevention of HIV-1 infection in infants at risk for HIV-1 infection through maternal 

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transmission at birth or during breastfeeding. Further evaluation of VRC01 in adults will continue 
towards possible therapeutic and preventive indications.   
 
This summary represents experience in human clinical trials with VRC01 mAb from September 
30, 2013 to May 22, 2014.  VRC 601 and VRC 602 are Phase 1, dose-escalation studies to examine 
safety, tolerability, dose, and pharmacokinetics (PK) of VRC-HIVMAB060-00-AB (VRC01) 
when it is administered to HIV-infected and healthy adults, respectively.  Both the intravenous 
(IV) or subcutaneous (SC) routes of administration are being evaluated.  The dose groups in these 
studies are as shown in Table 2. 
Table 2:   Dose Groups in Human Clinical Trials of VRC01 
Group 
VRC 601 
VRC 602 
1 
1 mg/kg IV 
5 mg/kg IV 
2 
5 mg/kg IV 
20 mg/kg IV 
3 
5 mg/kg SC 
40 mg/kg IV 
4 
20 mg/kg IV 
5 mg/kg or placebo SC 
5 
40 mg/kg IV  
  
 
Both studies followed their respective dose escalation plans and reached the 40 mg/kg IV 
administration dose level without the occurrence of any safety pauses or serious adverse events.   
As of May 22, 2014, cumulatively, 35 subjects had begun product administration: 30 had 
completed a second dose; 2 had withdrawn prior to second dose and 3 remained on the schedule 
for a second dose.  There have been no discontinuations due to an adverse event.   
The 65 product administrations to date were distributed among the dose schedules as follows: 
• 6 administrations at 1 mg/kg IV 
• 14 administrations at 5 mg/kg IV 
• 13 administrations at 20 mg/kg IV 
• 10 administrations at 40 mg/kg IV 
• 22 administrations at 5 mg/kg (or placebo) SC; of these, the estimate is 8 administrations 
in VRC 602 are placebo.  The method of SC administration has been by SC infusion 
pump into a single site in the abdomen for 15 SC administrations and by direct needle 
and syringe injection divided into two sites in abdomen or thigh for 7 SC administrations. 
The elimination half-life was similar in healthy and HIV-infected adults with an overall mean 
value of 14.6  4.8 days following 20 mg/kg or 40 mg/kg [39]. 
2.7.1 Adverse Events 
There have been no serious adverse events, safety pauses or unsolicited adverse events greater than 
grade 2 in severity.  No systemic or local reactions have been reported during the IV infusions 
administered to date.  No systemic reactions have been reported during SC product administration 
to date. The SC product administrations are sometimes associated with mild local reactions during 

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the infusions that may include some pruritus (itchiness), redness and swelling, which resolves 
within a few minutes to a few hours after the administration is completed. The largest diameter for 
those erythema or swelling events that were observed during infusions ranged from about 2 to 5 
cm. During the period of solicited adverse events for 3 to 7 days following product administration, 
reported local and systemic reactions have been no more than mild in severity.  All product 
administrations to date have been well tolerated. 
2.8 
SUMMARY STATEMENT ON SAFETY OF STUDY AGENT 
VRC01 displays several unusual structural features. It is highly affinity-matured, has a disulfide 
link between complementarity-determining regions (CDR) H1 and H3 and has a glycan in the 
variable (V) region of the light chain [46]. Unlike some HIV-1 neutralizing antibodies, VRC01 
does not have an unusually long CDR-H3 region, it is not self- or poly-reactive, and it lacks anti-
phospholipid antibody activity [47]. These features suggest that VRC01 is safe for human 
administration. 
 
Toxicology studies in rat models have demonstrated a “no observed adverse effect level” 
(NOAEL) for VRC01 by the intravenous route of administration of 400 mg/kg, the highest dose 
used in the study, and by the subcutaneous route of administration of 40 mg/kg, the only SC dose 
examined. VRC01 administration by the IV route resulted in dose-proportional exposure. The 
terminal elimination phase half-life (t1/2) was about 10 days, with clearance (Cl) of approximately 
20 mL/day/kg and volume of distribution (Vd) of about 0.28 L/kg, indicating that the drug was 
distributed primarily in the serum and eliminated slowly. 
 
Tissue cross-reactivity studies using normal adult and neonatal human tissues did not identify any 
potential tissue sites or organ systems that required further evaluation in preclinical studies, again 
suggesting that VRC01 is safe for human administration. 
 
Phase I clinical trials are currently underway in both HIV-infected and uninfected adults. Accrual 
into VRC 601 was initiated in September 2013 with the first infusion at 1 mg/kg IV administered 
on September 30, 2013. Accrual into VRC 602 was initiated in December 2013 with the first 
infusion at 5 mg/kg IV administered on December 9, 2013. Both studies followed their respective 
dose escalation plans and reached the 40 mg/kg IV administration dose level without the 
occurrence of any safety pauses or serious adverse events. All IV and SC infusions have been well-
tolerated with no SAEs or dose limiting toxicity. 

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3.0 
STUDY OBJECTIVES, ENDPOINTS AND RATIONALE 
3.1 
STUDY OBJECTIVES 
3.1.1 Primary 
1. To evaluate the safety of VRC01 when administered during an ATI. 
2. To evaluate the ability of VRC01 monotherapy to maintain virologic suppression at 24 
weeks.  
3.1.2 Secondary 
1. To assess the impact of VRC01 on viral dynamics following ATI, including time to viral 
rebound and level of rebound viremia. 
2. To assess the impact of VRC01 on CD4 count following ATI. 
3. To assess the impact of VRC01 on HIV reservoir replenishment and expression 
following ATI.  
4. To assess the impact of VRC01 on clinical characteristics of HIV infection following 
ATI. 
3.1.3 Exploratory 
1. To describe HIV-1 isolate neutralization sensitivity and genetic sequence, including sieve 
effect of VRC01. 
2. To characterize the effect of VRC01 on host cellular and innate immune responses, 
including broad and HIV-specific immune responses. 
3. To identify predictors of sustained virologic control, such as host genetic alleles, immune 
responses, and viral genetics. 
4. To identify the presence or absence of anti-VRC01 antibodies after ATI and 
administration of VRC01. 
5. To describe the impact of VRC01 on viral dynamics in multiple body compartments.  
6. To assess the distribution of VRC01 into various body compartments. 
3.2 
STUDY ENDPOINTS 
3.2.1 Primary 
1. Serious adverse event at any time up to 10 weeks after the last infusion of VRC01 or 
placebo.  
2. Sustained virologic suppression, without indication for ART resumption, at 24 weeks. 

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3.2.2 Secondary 
1. Time to viral rebound and level of rebound viremia after cessation of ART. 
2. Time to ART resumption for any reason after cessation of ART. 
3. Detectable HIV RNA via single copy assay at various timepoints, such as weeks 24 and 
48, as compared to baseline at week 0. 
4. CD4+ T cell count various timepoints, such as weeks 24 and 48, as compared to baseline 
at week 0. 
5. Cell-associated HIV RNA and DNA in the peripheral compartment various timepoints, 
such as weeks 24 and 48, as compared to baseline at week 0. 
6. Neuropsychological battery performance at weeks 24 and 48, as compared to baseline at 
week 0. 
7. Control and attention testing performance at various timepoints, such as weeks 24 and 
48, as compared to baseline at week 0. 
8. Frequency of hospitalization and incidence of non-AIDS related conditions. 
3.2.3 Exploratory 
1. Viral sequence evolution and the development of VRC01 escape mutations.  
2. Neutralization sensitivity of virus isolates, including sensitivity to VRC01. 
3. Measures of cellular immune responses, such as percentage of peptide specific T cell 
responses as measured by enzyme-linked immunospot (ELISPOT), breadth and 
magnitude of epitope-specific T cell responses, and polyfunctionality of cellular 
responses. 
4. Measures of innate immune response such as natural killer cell activity. 
5. HIV RNA quantification in the CSF and mucosal compartments, including single copy 
assays, in volunteers consenting to the necessary optional procedures.   
6. Cell-associated HIV RNA and DNA in the CSF, mucosal and tissue compartments, in 
volunteers consenting to the necessary optional procedures. 
7. Correlation of HIV RNA and DNA measurements across biologic compartments that 
include the peripheral blood, CSF, mucosal, and tissue compartments, in volunteers 
consenting to the necessary optional procedures. 
8. HIV RNA and DNA in sorted memory CD4+ T cell subsets, in volunteers with 
sufficient PBMC collections. 
9. Viral outgrowth in total CD4+ T cells and sorted memory CD4+ T cell subsets, in 
volunteers with sufficient PBMC collections. 

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10. Host genetic determinants of virologic suppression. 
11. Presence of anti-VRC01 antibody. 
12. Binding and neutralizing activities of elicited antibodies. 
13. Biomarkers of immune activation, such as soluble markers, cellular markers, and gene 
expression. 
14. Non-neutralizing antibody functional assays including antibody-dependent cell-mediated 
cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), 
antibody-dependent cell-mediated viral inhibition (ADCVI), and viral capture.  
15. VRC01 levels across biologic compartments that include the CSF and mucosal 
secretions, in volunteers consenting to the necessary optional procedures.   
3.3 
HYPOTHESES 
We hypothesize that patients receiving VRC01 will have a significantly higher rate of HIV viral 
suppression at 24 weeks following ATI as compared to patients receiving placebo. 
3.4 
RATIONALE FOR STUDY TIMING 
This substudy of RV 254 will begin enrolling participants after the initiation of another substudy 
of RV 254 that also includes an analytic treatment interruption, “RV 411: Viral Suppression after 
Analytic Treatment Interruption in Thai Patients who Initiated Highly Active Antiretroviral 
Therapy during Acute HIV Infection.” RV 411 may or may not be completed by the time that the 
currently proposed investigation begins, but early results from that study will be made available 
for review by the Data Safety and Monitoring Board for this study in case any new data has 
emerged that might impact participant safety. 
 
The currently proposed study differs from RV 411 in that this study will recruit participants who 
initiated therapy during Fiebig stages I through III, whereas the previously described study only 
enrolls patients started on therapy during Fiebig stage I. It is not known how Fiebig stage may 
impact rebound viremia during ATI in these patients. Patients who start therapy during Fiebig 
stage I or II demonstrate lower total HIV DNA and more robust gut CD4 reconstitution than 
patients started on therapy later in infection [33]. However, patients who start therapy during 
Fiebig stage III have mounted HIV-specific immune responses that are not detectable in patients 
started at earlier stages of infection [48, 49].  
 
RV 411 is designed with 85% power to detect a rate of sustained virologic control of 30%, so there 
is a 15% chance of missing a true rate of 30%. There is an even greater chance of missing a true 
rate that is greater than 0 but less than 30%. Whatever success rate is observed in RV 411 cannot 
be assumed to apply across Fiebig stages. The results of the currently proposed study will remain 
relevant regardless of the outcome of RV 411, although amendments to this protocol may be 
considered based on early results from that study. 

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3.5 
RATIONALE FOR INCLUSION OF PLACEBO ARM 
Since little is known about the clinical course of HIV during ATI in patients who were started on 
antiretroviral therapy during early acute infection, it is essential that a placebo arm be included as 
an appropriate comparator group in order to characterize the impact of VRC01 administration. 
No existing cohort of patients could serve this purpose.  
Subjects enrolled in this study have received ART during acute HIV infection and have achieved 
an undetectable integrated HIV DNA. Therefore, these participants have a likelihood of achieving 
virologic control during treatment interruption even without any specific intervention [32]. 
Inclusion of the placebo control group is essential to assess whether any observed sustained 
virologic control might be due to VRC01. Since differences in HIV-specific immune responses 
among patients started on ART during different Fiebig stages may influence the endpoint of 
sustained virologic control, it is important that the comparator group in this study include the same 
spectrum of Fiebig stages (I-III) that is represented in the VRC01 arm [48, 49]. RV 411 may not 
run contemporaneously with this study and enrolls only participants started on ART during Fiebig 
stage I. Therefore, participants in RV 411 cannot serve as a control group for this study. 
Participants in this study, including those randomly assigned to the placebo arm, will be monitored 
closely for clinical and laboratory indications to resume ART. These criteria are designed to protect 
the subjects from any possible clinical, immunological, or virological adverse effects of study 
participation while maintaining the scientific validity of study.   
 
 
 
 

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4.0 
STUDY DESIGN AND POPULATION 
4.1 
GENERAL DESIGN 
This is a placebo-controlled clinical trial of VRC01 administration and ATI in adults who began 
ART during early acute HIV infection (Fiebig stage I to III). Eligible volunteers will be 
randomized in a 3:1 ratio to either VRC01 or placebo. Participants will undergo randomization 
stratified by Fiebig stage. Volunteers who are receiving ART with an NNRTI will undergo 4 weeks 
of PI substitution prior to randomization. ATI will begin the day of the first dose of either VRC01 
or placebo. Participants will be monitored closely for HIV viremia and other pre-defined criteria 
for ART resumption (see section 4.6). Administration of the study agent (VRC01) every 3 weeks 
will be discontinued after 24 weeks or at the time ART resumed, whichever occurs first. Volunteers 
who are virally suppressed without laboratory or clinical indication for ART resumption at 24 
weeks will continue intensive monitoring for ART resumption criteria for an additional 24 weeks, 
during which time no VRC01 or placebo will be administered. Clinical study visits will take place 
at the Thai Red Cross AIDS Research Centre, and the optional procedures may occur at the King 
Chulalongkorn Memorial Hospital. 
4.2 
PARTICIPANTS 
This study will recruit 24 adults aged 20-50 years who were diagnosed during acute HIV infection 
(Fiebig stage I to III) and initiated on ART in Bangkok, Thailand. Participants will be recruited 
from protocol RV 254 (SEARCH 010, WRAIR 1494). This ongoing parent study cohort enrolls 
participants with documented acute HIV infection at the Thai Red Cross AIDS Research Center 
in Bangkok, Thailand. All participants in RV 254 are offered ART at the time of enrollment 
through a separately funded protocol. 
4.3 
PROTEASE INHIBITOR SUBSTITUTION 
Subjects prescribed an ART regimen that contains a non-nucleoside reverse transcriptase inhibitor 
(NNRTI) at study enrollment will be switched to a regimen that replaces the NNRTI with a 
protease inhibitor (PI) such as lopinavir/ritonavir, atazanavir/ritonavir, or darunavir/ritonavir for 
four weeks prior to ATI. This will minimize the risk of developing NNRTI resistance mutations. 
Post-hoc analysis of the SMART trial suggests that this strategy is associated with the lowest risk 
for the development of drug resistance mutations as compared to staggered interruption or 
simultaneous discontinuation of all antiretroviral agents. None of the 13 volunteers in the SMART 
study who replaced efavirenz with a protease inhibitor prior to treatment interruption developed 
NNRTI resistance mutations [50]. Subjects on other ART regimens that do not contain an NNRTI 
will continue their usual regimen until ATI.  
Data from Thai children enrolled in the PENTA 11 trial showed that the majority of children had 
no efavirenz level detected by day 14 after cessation and none developed NNRTI resistance 
mutations [51]. Since a small minority did demonstrate detectable NNRTI plasma levels at the 14-
day mark, this study will conservatively extend the period off NNRTIs to 28 days prior to ATI and 
administration of VRC01 or placebo. Since pharmacokinetic parameters of NNRTIs in this 
population in the setting of PI co-administration are not clearly defined, plasma NNRTI level will 
be monitored at the time of NNRTI discontinuation, and 2 and 4 weeks following discontinuation. 

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Results of this testing will be available within 2-3 weeks and will be evaluated in aggregate as they 
become available. The study protocol may be modified based on these results if needed for patient 
safety. If rebound viremia occurs in any patient, the investigators will perform resistance testing 
at the time of ART resumption. The results will be available in 7 days, and results will be made 
available to the treating physician for treatment modification considerations.  
4.4 
INTERVENTION 
4.4.1 Study Agent 
VRC-HIVMAB01060-00-AB (VRC01) is a monoclonal antibody directed towards the site of 
CD4 attachment on the HIV-1 gp120 envelope (Env) glycoprotein. Vials contain an isotonic, 
sterile solution that is a colorless to yellow liquid, essentially free of visible particles; some 
opaque or translucent particles may be present. The formulation buffer is composed of 25 mM 
sodium citrate, 50 mM sodium chloride, and 150 mM L-arginine hydrochloride at pH 5.8. Vials 
are intended for single use only and do not contain a preservative. Vials with visible particles at 
the end of the thaw procedure should not be used for infusion. 
VRC01 will be administered at a dose of 40 mg/kg intravenously every three weeks to 
participants assigned to the intervention arm of the trial for a total duration of 24 weeks or until 
ART resumption criteria are met, whichever comes first.  
The first dose of VRC01 will be administered on the same day that ART is interrupted. In the 
simian model, VRC01 administered intravenously achieved peak serum levels within one hour of 
infusion and was slowly metabolized with an average half-life of 7.61 days. All animals had 
detectable VRC01 levels 28 days after infusion. Preliminary human data suggest a mean half-life 
of 13.6 days (range 6.76-21.3 days). These pharmacokinetic parameters suggest that serum levels 
will remain above the target level of >50 micrograms/mL throughout the dosing interval. 
Furthermore, the evidence suggests that the mAb will be well-distributed by the expected time of 
highest risk for rebound viremia at 2-6 weeks after treatment interruption [31, 52]. The second 
infusion of VRC01 will occur at the midpoint of this highest risk period. 
4.4.2 Placebo 
Normal saline (Sodium Chloride for Injection USP, 0.9%) will be administered intravenously 
every three weeks to participants assigned to the placebo arm of the trial for a total duration of 24 
weeks or until ART resumption criteria are met, whichever comes first. 
4.5 
ANALYTIC TREATMENT INTERRUPTION (ATI) 
Analytic treatment interruption will begin on the day of administration of the first dose of either 
VRC01 or placebo. During the ATI, participants will be monitored closely for clinical and 
laboratory indications to resume ART (see Section 4.6). These criteria are designed to protect the 
subjects from clinical, immunological, or virological adverse effects during the ATI.  
Because several vaccinations have been associated with induction of HIV-1 replication in the 
absence of ART [53-59], participants will be counseled to avoid non-essential vaccination during 

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the period of ATI and any essential vaccinations, such as seasonal influenza, will be administered 
outside of weeks 2-6 and 26-30, when the risk of rebound viremia is considered to be highest (2-6 
weeks after stopping ART and 2-6 weeks after plasma VRC01 is expected to drop below 
therapeutic levels). Volunteers are generally expected to have received routine vaccinations 
against viral hepatitis through their prior participation in the RV 254 cohort. 
Prior data from RV 254 demonstrated that Fiebig I patients in the cohort had a median (range) 
HIV-1 RNA of 4.8 (2.8-5.7) log10copies/mL, at a median (range) of 12 (4-40) days after exposure 
to HIV, prior to initiation of antiretroviral therapy (ART) and have therefore already been exposed 
to high levels of plasma virus during acute infection [60]. Despite this previous exposure, our data 
to this point indicate that these patients have very small or no HIV viral reservoirs, as assessed by 
integrated HIV DNA levels in PBMCs, CD4+ T cells, and CD8+ T cells. In the proposed protocol, 
participants will have very frequent monitoring for viral rebound; detection of HIV viremia via 
qualitative or quantitative assessments will prompt repeat testing via PCR every three days until 
either (1) the PCR reverts to undetectable or (2) criteria for resumption of ART are met. ART may 
be resumed for multiple reasons, including a swift rise in HIV-1 RNA of ≥ 0.5 log10copies/ml per 
day provided that the last HIV-1 RNA is above 1000 copies/mL or a sustained HIV-1 RNA above 
1,000 copies/mL for a period of 3 days or more (see Section 4.6 for a full list of criteria for 
resumption of ART). This level of viremia is lower than that already experienced by virtually all 
subjects in the cohort. Therefore, we believe that the protocol poses little additional risk for 
establishment or increase of an HIV reservoir in these subjects. The HIV reservoir will be 
measured both before treatment interruption (in this protocol) and after ART resumption (in RV 
412).  
Prior investigation of subjects undergoing ATI has shown that some may develop similar transient 
viremias <1,000 copies/mL and that these reversible viremias do not always indicate viral rebound 
[32]. In the setting of acute HIV infection, this low-level viremia is associated with Fiebig stage I, 
which appears to have little or no impact on the HIV reservoir. We have previously demonstrated 
that even patients started on therapy at Fiebig stage III, with much higher viral loads (median 5.9, 
IQR 5.6-6.9 log10copies/ml), have comparable virologic and reservoir outcomes as patients started 
at lower viral loads associated with Fiebig stage I after 48 weeks of ART. 
The viral load threshold selected as an indication for ART resumption in this protocol is an 
evidence-based threshold chosen to maximize study subject safety while also providing subjects 
an opportunity to demonstrate subsequent virologic control. Additional virologic, CD4 and clinical 
criteria for ART resumption are included to further enhance participants’ safety. 
4.6 
CRITERIA FOR RESUMPTION OF ART 
ART will be resumed in study participants demonstrating any one of the following criteria during 
ATI:  
• HIV-1 RNA above 1,000 copies/mL on 2 consecutive determinations at least 3 
days apart.  
• HIV-1 RNA rise of ≥ 0.5 log10copies/ml per day provided that the last HIV-1 
RNA is above 1000 copies/mL. 

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• A single HIV-1 RNA above 10,000 copies/mL. 
• CD4+ T-cell counts below 350 cells/mm3 on 2 consecutive determinations at least 
2 weeks apart. 
• CD4+ T-cell count decline of > 50% from baseline prior to ATI. 
• Clinical progression to CDC Category B or C disease. 
• Diagnosis of acute retroviral syndrome (ARS) (Appendix I). 
• Pregnancy. 
• Participant request for re-initiation of ART. 
If new information becomes available during the course of the study suggesting that additional 
ART resumption criteria should be employed or that earlier resumption of ART may be 
beneficial to volunteers, the protocol and guidance for study participants will be modified to 
reflect this. 
HIV-1 RNA will be measured frequently throughout the study period, including twice weekly 
assessments during weeks 2-6 and 26-30. HIV-1 RNA will be measured either quantitatively 
using a venous blood sample (3mL) or qualitatively using a small blood volume collection 
(0.6mL). The latter may be performed either via finger stick or venous sampling. 
4.7 
MANAGEMENT OF SUBJECTS AFTER COMPLETION OF PROTOCOL 
Due to the exploratory nature and unknown risks of ATI, an individualized treatment plan will be 
developed on exit from the study for all subjects, regardless of the reason or reasons for exiting 
the study.  The treatment plan will be developed by the study physician in consultation with the 
subject and any other physicians involved in the subject’s medical care. Treatment plans will 
take account of the subject’s specific medical needs, as well as their status at the end of study 
participation. 
 
4.8 
MANAGEMENT OF SUBJECTS AFTER RESUMPTION OF ART 
If the decision is made to reinitiate ART for any reason, then procedures scheduled for study end 
at week 48 will instead be conducted at the study visit before ART resumption. If this occurs within 
10 weeks of a volunteer’s last infusion of VRC01, that volunteer will continue to be followed for 
safety evaluations only under this protocol until 10 weeks after the last infusion of VRC01 and 
will be offered co-enrollment in RV 412: Safety and Virologic Outcomes after Analytic Treatment 
Interruption in Thai Patients who Initiated Antiretroviral Therapy During Early Acute HIV 
Infection. Evaluations that are listed under both protocols will not be duplicated in volunteers who 
are co-enrolled. Volunteers who have met criteria for resumption of ART more than 10 weeks after 
their last infusion of VRC01 will no longer be considered enrolled in this protocol and will be 
offered enrollment in RV 412. Volunteers who have met the criteria for resumption of ART under 

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this protocol will resume ART at the time of enrollment or co-enrollment in RV 412 and will be 
monitored closely for viral suppression. If ART is reinitiated due to rebound viremia with 
peripheral HIV-1 RNA sufficient to allow amplification, then HIV genotype testing will be 
performed at the time of ART resumption. The results of genotype testing will be available in 
seven days and may be used to guide ART selection. The final regimen will be determined by 
discussion between the subject and the study physician. ART is available through the Thai national 
treatment program or through co-enrolled research protocols. 
In RV 412, volunteers will undergo quantitative HIV-1 RNA testing every two weeks for the first 
four weeks and then every four weeks for up to 48 weeks. Safety monitoring to include CD4/CD8 
counts, complete blood counts, renal function testing, liver function testing, lipid profile, and urine 
pregnancy testing will also be performed routinely. Participation in RV 412 will end when 
volunteers demonstrate two consecutive HIV-1 RNA measurements <50 copies/mL or when 48 
weeks of follow-up has been completed, after which time volunteers will return to routine follow-
up in the parent RV 254 cohort every 12 weeks and as needed.  
4.9 
MANAGEMENT OF SUBJECTS WITH SUSTAINED VIROLOGIC CONTROL AT END OF 
STUDY 
Volunteers who demonstrate sustained virologic control at the end of this study will be offered 
enrollment in RV 412 for continued observation. This continued monitoring will help to ensure 
the safety of study participants and will also allow further assessment of host and virus parameters 
that can improve our understanding of HIV pathogenesis and inform future efforts to achieve a 
functional cure of HIV. For volunteers not on ART, the RV 412 protocol includes HIV-1 RNA 
testing every two weeks for 12 weeks, every 4 weeks for the subsequent 28 weeks, and every 8 
weeks for the remaining 56 weeks for a total of 96 weeks of aggressive monitoring off of ART. 
Volunteers who meet criteria for resumption of ART (which are the same in RV 412 as in RV 397) 
at any time will be offered therapy using either the subject’s last known ART regimen or another 
empiric regimen as determined by discussion with the subject’s medical provider. Patient 
preference will always be considered an indication to resume ART. If peripheral HIV-1 RNA is 
sufficient to allow amplification at the time of ART resumption, an HIV genotype will be checked. 
Results of genotype testing will be available in seven days and will inform any potential adjustment 
to the ART regimen. Volunteers who complete 96 weeks of observation without an indication for 
ART will return to routine follow-up every 12 weeks in the parent RV 254 cohort. 
   
4.10 
MANAGEMENT OF SUBJECTS WHO BECOME PREGNANT 
Volunteers who become pregnant during the study period will complete all procedures scheduled 
for study end at the time the pregnancy is diagnosed. If the volunteer was scheduled to receive 
infusions of VRC01 or placebo, these will not be administered after pregnancy has been diagnosed. 
Procedures scheduled for study end at week 48 will instead be conducted at the visit at which 
pregnancy is diagnosed or immediately following the diagnosis (if diagnosed outside the study). 
If pregnancy occurs within 10 weeks of a volunteer’s last infusion of VRC01, that volunteer will 
continue to be followed for safety evaluations only under this protocol until 10 weeks after the last 
infusion of VRC01. All pregnant volunteers will be offered enrollment or co-enrollment in RV 
412 for continued observation and initiation of ART. Evaluations that are listed under both 

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protocols will not be duplicated in volunteers who are co-enrolled. Participation in RV 412 will 
require separate informed consent. If the volunteer completes participation in RV 412 before the 
pregnancy is completed, she will subsequently return to the RV 254 parent study. Pregnant 
volunteers 
will 
also 
be 
enrolled 
in 
the 
antiretroviral 
pregnancy 
registry 
(http://www.apregistry.com/who.htm). 
The site PI or designated associate investigator will be responsible for reporting any pregnancy to 
the PSRT.  This information will be reviewed by the PSRT weekly in aggregate with other safety 
data.  The PSRT will forward notification as necessary to IRBs, study sponsors, and regulatory 
agencies. 
Pregnancy outcomes will be recorded via a standardized case report form. Information documented 
on this form will include date of last menstrual period, date pregnancy confirmed, history of 
complications during prior pregnancies (such as congenital abnormalities or spontaneous 
abortions), and the outcome of the pregnancy including date of termination or delivery, any 
complications of pregnancy, and the status of the child. A separate case report form will be 
completed for the delivered child to document date of delivery, gender, weight, presence of any 
congenital abnormalities, APGAR score, HIV status, and any other complication of delivery. 

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5.0 
STUDY PROCEDURES 
5.1 
ELIGIBILITY 
5.1.1 Inclusion Criteria 
1. Able and willing to provide written informed consent or, in the case of illiteracy, 
witnessed verbal informed consent with documentation of a thumbprint in lieu of a 
signature. 
2. Passes Test of Understanding 
3. Man or woman aged 20-50 years. 
4. Initiated on ART during acute HIV infection (Fiebig Stage I to III at RV 254 enrollment).  
5. Prescribed ART for at least 24 months prior to enrollment. 
6. HIV-1 RNA < 50 copies/mL on at least three consecutive measurements within the past 
12 months. 
7. Integrated HIV DNA in PBMCs below the level of detection (1 copy/105 PBMCs) within 
6 months prior to enrollment. 
8. Last documented peripheral blood CD4 >400 cells/mm3 within 3 months prior to 
enrollment. 
 
9. No HIV-related or AIDS-defining illness within 6 months prior to enrollment. 
10. In general, good health  
11. Able to participate in study visits. 
Female-specific Criteria: 
12. Agrees not to become pregnant from the time of study enrollment until the last study 
visit. If a woman is sexually active and has no history of hysterectomy or tubal ligation or 
menopause, she must agree to use a prescription birth control method or a barrier birth 
control method. 
13. Negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day 
of enrollment for any women unless she is post-menopause for 24 consecutive months or 
has undergone a surgical procedure that precludes pregnancy 
5.1.2 Exclusion Criteria 
1. Previous receipt of humanized or human monoclonal antibody whether licensed or 
investigational. 
2. Ongoing AIDS-related opportunistic infection (including oral thrush). 
3. Active injection drug use within previous 12 months. 
4. History of a severe allergic reaction with generalized urticaria, angioedema or 
anaphylaxis in the 2 years prior to enrollment. 

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5. History of chronic urticaria requiring daily treatment. 
6. Physical finding on examination considered indicative of significant disease such as 
murmur (other than functional), hepatosplenomegaly, or focal neurologic deficit. 
7. Hypertension that is not well controlled by medication. 
8. Hepatitis B surface antigen positive at any time in the past. 
9. Hepatitis C antibody positive at any time in the past. 
10. Untreated syphilis 
11. Estimated GFR < 50 ml/min within the past 90 days. 
12. Pregnant or breast-feeding. 
13. Receipt of licensed vaccine or other investigational study agent within 28 days prior to 
enrollment or past participation in an investigational HIV vaccine study with receipt of 
active product. 
14. Current or planned participation in another interventional clinical trial during the study 
period. 
15. Chronic or recurrent use of medications that modify host immune response, e.g., oral or 
parenteral steroids, cancer chemotherapy. 
16. Any other chronic or clinically significant medical condition that in the opinion of 
investigator would jeopardize the safety or rights of the volunteer.  Including, but not 
limited to:  diabetes mellitus type I, chronic hepatitis, renal failure; OR clinically 
significant forms of: drug or alcohol abuse, mental illness, severe asthma, autoimmune 
disease, psychiatric disorders, heart disease, or cancer. 
17. Study site employee. 
5.2 
RATIONALE FOR ELIGIBILITY CRITERIA 
Eligibility criteria for this study largely reflect criteria already being used for enrollment in the 
ongoing prospective cohort study of Thai patients with acute HIV infection, RV 254, also being 
conducted at the Thai Red Cross AIDS Research Center in Bangkok, Thailand.   
 
These criteria were selected to ensure that participants enrolled in the study satisfy the 
demographic characteristics of the study’s target population, demonstrate laboratory 
characteristics suggesting a high likelihood of achieving the study endpoint of sustained HIV 
suppression at 24 weeks after ATI, and lack clinical or laboratory indicators that might suggest a 
heightened risk of adverse outcome as a result of study participation. 
 
These eligibility criteria ensure that participants in this study have demonstrated sustained HIV 
suppression below the limit of detection by conventional clinical assays for HIV RNA via PCR 
(<50 copies/mL) and are immunologically intact according to both CD4 and clinical criteria. 
Furthermore, participants must demonstrate undetectable HIV DNA in peripheral blood 
mononuclear cells (PBMCs) within 6 months of enrollment. Integrated HIV DNA in PBMCs is 
thought to be the most relevant measure of the size of the latent and inducible HIV reservoir, since 
non-integrated HIV DNA molecules are unlikely to produce viral particles upon stimulation [61, 

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62]. Importantly, the measurement of integrated HIV DNA in PBMCs is the only assay that 
correlates with the Quantitative Viral Outgrowth Assay (QVOA) [63]. Quantifications of 
integrated DNA in PBMCs from RV 254 subjects treated during Fiebig I to III indicate that almost 
all subjects display undetectable levels of integrated HIV DNA by week 24 of ART. As a marker 
of little or no inducible HIV reservoir, an undetectable HIV DNA suggests that a volunteer may 
be a good candidate for achieving the primary study endpoint. If sustained HIV suppression is not 
achieved and rebound viremia does occur, the proposed research includes processes for intensive 
monitoring and resumption of ART via a companion study (RV 412). These processes are designed 
to prevent full evolution of acute viremia. Even at Fiebig stage III, we have previously shown that 
reservoir status can be restored to that seen at Fiebig stage I with 48 weeks of ART. 
 
Participants are excluded from this study for reasons that would interfere with the safety or 
feasibility of adhering to the study protocol. Pregnancy is considered an exclusion criterion for 
multiple reasons, including lack of data on the safety and pharmacokinetics of VRC01. 
Furthermore, pregnancy is considered an indication for ART in HIV-positive women. Women of 
child-bearing potential who enroll in this study will be required to use contraception during the 
entirety of the study, including the 24 weeks during which VRC01 or placebo is administered and 
the subsequent 24 weeks of observation off all therapy for HIV. The mean half-life of intravenous 
VRC01 in human studies is 13.6 days with a range of 6.76 to 21.3 days. The requirement for 
contraceptive use minimizes the risk for potential harm to study participants or the fetus due to 
either VRC01 administration or transient HIV viremia.  
5.3 
SCHEDULE OF EVALUATIONS 
5.3.1 Week -6 
All screening, enrollment, and consent procedures will be completed, including screening 
laboratory and clinical evaluations. 
5.3.2 Week -4 
Subjects prescribed an ART regimen that contains an NNRTI drug will be switched to a regimen 
that substitutes a boosted PI for the NNRTI. Subjects on other ART regimens that do not contain 
an NNRTI will continue their usual ART medications until ATI at week 0. 
5.3.3 Week 0 
Subjects will be randomized in a 3:1 ratio to receive an intravenous infusion of either VRC01 or 
placebo, with randomization stratified by Fiebig stage. All women of child-bearing potential will 
need to have a negative pregnancy test prior to the infusion. All antiretroviral medications will be 
stopped. Baseline laboratory studies (fasted blood collection) for safety parameters will be 
performed. 

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5.3.4 Weeks 1-24 
Subjects will continue to receive intravenous infusions of either VRC01 or placebo every three 
weeks until week 24 or until criteria for resumption of ART are met. Women of child-bearing 
potential will have a negative pregnancy test result prior to each infusion of study drug.  Subjects 
will be observed for 1 hours after receiving intravenous infusions. Clinical and laboratory 
monitoring will follow the schedule in Appendix II, which includes qualitative or quantitative 
assessments for HIV-1 RNA weekly until week 2, then twice weekly until week 6, and then HIV-
1 RNA testing via quantitative or qualitative assessments weekly until resumption of ART or the 
end of this study period. Willing participants may continue twice weekly assessments for HIV-1 
RNA during this period, though this will not be required. Any positive qualitative assessment for 
HIV-1 RNA will be immediately followed by quantitative HIV-1 RNA testing via PCR. Any 
positive HIV-1 RNA PCR will prompt repeat testing via PCR every three days until either (1) the 
PCR reverts to undetectable or (2) criteria for resumption of ART are met, as described in Section 
4.6. In subjects who meet criteria for resumption of ART, the study visit prior to resumption of 
ART will be considered the final study visit and will follow the data and specimen collection 
schedule for end of study. ART blood levels may be checked during this period at investigator 
discretion in order to monitor for surreptitious ART use. 
5.3.5 Weeks 25-47 
Subjects will no longer receive intravenous infusions of VRC01 or placebo. Subjects who are 
virally suppressed and without clinical or laboratory indication for resumption of ART will 
continue laboratory monitoring every week until week 26, then twice weekly until week 30, then 
weekly until week 32, then every 2 weeks until end of study, as described in the SOE. Willing 
participants may continue twice weekly assessments for HIV-1 RNA during this period, though 
this will not be required. To reduce participants’ discomfort due to frequent assessments, 
qualitative HIV-1 RNA (Aptima) may be performed using small blood volume collection via 
finger stick or venous sampling, which has a lower bound 95% confidence interval that exceeds 
95% detection at 30 copies/mL. ART blood levels may be checked during this period at 
investigator discretion in order to monitor for surreptitious ART use. 
5.3.6 Week 48/End of Study 
Subjects will undergo final clinical and laboratory evaluation as described in the SOE (Appendix 
II). The procedures for week 48 will be performed earlier in the event that study participation ends 
early due to resumption of ART. After completing this study, the participants will be offered 
enrollment into the RV412 substudy of RV254 for close monitoring during either resumption of 
ART or continued treatment interruption. Participants will also continue to be enrolled in RV254, 
where a maximum follow-up time of eight years is anticipated. 
5.4 
MANAGEMENT OF INDIVIDUAL RESEARCH RESULTS  
Results of clinical testing (CD4, HIV RNA, safety tests) will be placed in the patient medical 
record and will be available to both the treating physicians and to study participants. For other 
incidental findings of known clinical significance but not related to participation in the study, 
research physicians will refer the subject to the appropriate facility for treatment and will ensure 

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that the subject receives appropriate care. National health insurance programs cover all Thai people 
and include treatment for any HIV-related events. No human leukocyte antigen (HLA) testing will 
be performed as part of this study.   
 
Research testing results for which clinical significance is unknown will not be shared with study 
participants. In this study, such tests include but are not limited to, integrated HIV DNA, total HIV 
DNA, 2LTR circles, qualitative viral outgrowth assay (QVOA), Tat/Rev Induced Limiting 
Dilution Assay (TILDA), and TULDA. 
5.5 
NEUROPSYCHOLOGICAL TESTING 
Visits at week 0, 24, and 48/End of Study, testing conducted at TRCARC will include 
neuropsychological (NP) testing consisting of a set of memory and thinking tests, questions about 
mood, and questions about ability to function in day-to-day activities. Volunteers will be asked to 
remember things, do easy tasks as fast as possible (such as put pegs in holes), and draw objects. 
Mood and anxiety measures are necessary for the accurate interpretation of the neuropsychological 
measures and will be captured as covariates, as will information about recentsleep patterns and use 
of intoxicants. We will also capture a brief assessment of quality of life and stress as it may be 
impacted by treatment. 
A trained psychometrist completes this cognitive testing using a modification of published 
international neuropsychological battery [64]. For this study a brief NP battery will be used,  Non-
Dominant Hand Grooved Pegboard Test, Trails A Test, and Color Trails 1 and 2.  To assess stress 
and depression the following tools will be used: the Hospital Anxiety and Depression Scale 
(HADS), the Patient Health Questionnaire-9 (PHQ-9), the World Health Organization-Quality of 
Life (WHO-QOL), and the Distress Thermometer. 
5.6 
CONTROL AND ATTENTION TESTING 
The Control and Attention task (i.e., Flanker Task) is a computerized test of cognition developed 
and managed by the National Institutes of Health.  The test requires the participant to focus on a 
stimulus presented on a computer screen while inhibiting attention to arrows adjacent to the 
stimulus (the flankers).  On some trials the middle stimulus points in the same direction as the 
flanker and on other trials the middle stimulus points in the opposite direction.  The test is scored 
based on a combination of accuracy and reaction time.  The test requires approximately 3 minutes 
to complete.  It is a valid and reliable measure of attention and mental control across a broad age 
range. This will be performed upon enrollment and repeated at weeks 0, 1, 4, 12, 24, and 48/EOS. 
5.7 
THERAPEUTIC DRUG MONITORING 
For patients on NNRTI prior to ATI, substitution of the NNRTI with a PI drug will be done at 
week -4 in order to minimize the possibility of developing resistance to the NNRTI during ATI. 
Plasma drug levels of the NNRTI will be tested at weeks -4, - 2, and 0 to assess the 
pharmacodynamics effects of this schedule. 

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Plasma drug levels of NNRTI and/or other antiretroviral medications will be checked on all 
subjects who are virologically suppressed at week 24 in order to monitor for possible ART use. 
ART blood levels may be performed at other time points at investigator discretion. 
5.8 
OPTIONAL PROCEDURES 
Volunteers will have the option of participating in separately consented collections and procedures 
to characterize the impact of VRC01 in addition to early ART on the HIV-1 reservoir and 
pathogenesis. These will be offered to volunteers at the discretion of investigators at specific 
timepoints as described in the SOE (Appendix II).  
Little is known about the distribution of VRC01 in body tissues. Among other things, these 
optional procedures will include assessments of penetration into some body compartments, such 
as the cerebrospinal fluid. The observation that peak serum levels of VRC01 are followed by a 
decline over several hours suggests that equilibrium across body compartments occurs quickly. It 
is possible, however, that VRC01 will not distribute uniformly into all body compartments and 
potential HIV reservoir sites. Similarly, various antiretroviral drugs have differing penetration into 
body sites, such as the gut associated lymphoid tissue, lymph nodes, and central nervous system 
[65-68]. The clinical relevance of distribution into these sites is uncertain, but may theoretically 
contribute to HIV persistence despite ART, rebound after ART, and even selection of resistance 
[69].  
5.8.1 Genital Secretion Collection 
Genital secretion collection will be performed on a subset of consenting individuals. Consenting 
women will be instructed on how to use a Softcup device to collect cervical and vaginal secretions. 
The cup will remain in place for 4 -12 hours. Pregnant women and those with a history of toxic 
shock syndrome will be excluded. Collection will not take place if the woman is menstruating or 
has symptoms of active inflammation or infection of the vagina or cervix. Date of last menstrual 
period will be recorded at each collection visit and blood samples for hormone levels will be 
drawn. If, during the course of the study, a woman becomes pregnant, she will be excluded from 
further genital secretion collections. 
Consenting men will be asked to ejaculate into a sterile container. Additionally, rectal sponge 
secretions will be collected from volunteers who are men who have sex with men.  Semen and 
rectal sponge collections will be deferred from men if there are signs or symptoms of urethral or 
perianal inflammation, respectively. The anal rectal sponge used for this procedure is the 
Medtronic Merocel sponge, which is approved for use in nasal and ear packing and as an ear wick.  
According to the package insert, the product is “non-toxic and is considered safe to pass once it is 
completely in the alimentary tract.” There is no maximum time for product insertion.  In this study, 
the Merocel sponge is used only as a specimen collection tool for rectal secretions, will be inserted 
and removed by trained medical staff, and will be placed in the rectum for a maximum of 5 
minutes.  For all genital secretion specimen collections, volunteers are requested to refrain from 
sexual intercourse or insertion of foreign objects into the vagina or rectum for 3 days and, for 
semen collection, to refrain from ejaculation for 48 hours prior to specimen collection.  
Examination and specimen collections take up to 30 minutes to complete. 

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Genital secretion samples will be assayed for HIV RNA PCR using the Roche Amplicor® 2.0 kit 
or other nucleic acid amplification method. Left over samples will be stored at –80˚C and will be 
used to isolate and sequence HIV, to assay cytokines and inflammatory markers, and to detect 
sexually transmitted infections. Other HIV-specific immune responses may also be evaluated.   
5.8.2 Colon Biopsy 
Colon biopsy will also be performed on a subset of consenting individuals. Sigmoidoscopy will be 
performed by a gastroenterologist at King Chulalongkorn Memorial Hospital following standard 
procedures. The procedure lasts about 90 minutes, including preparation just prior to the 
procedure. In addition, observation and recovery from the procedure take approximately 3 hours. 
Biopsy specimens will be cryo-preserved for reservoir and transcriptional analysis and 
immunohistochemistry and collected in RPMI medium 1640 (Invitrogen) for flow cytometric 
analysis.  
As HIV preferentially infects the gut, the infection density in the gut is usually higher than in the 
peripheral blood and this tissue infection may be responsible for viral rebound when ART is 
interrupted [26, 27]. In addition, the majority of CD4+ T cells resides in the gut and may play a 
critical role in anti-HIV defense following ATI. Therefore, it is critical to characterize the HIV-
specific immune responses and reservoir in the gut before and after ATI, as well as to characterize 
the influence of VRC01 on these parameters. 
5.8.3 Inguinal Lymph Node Biopsy 
Inguinal lymph node biopsy will be performed at King Chulalongkorn Memorial Hospital by a 
qualified surgeon. The procedure itself will be performed under local anesthesia and last 
approximately 30-40 minutes, however, subjects will also be asked to rest under observation for 
approximately another 4 hours. An inguinal lymph node will be removed via a surgical incision 
and divided to be sent for immuno-fluorescence confocal microscopy, flow cytometry, gene 
expression/whole transcriptome analysis and, if sufficient, cytokine production assays. Other HIV-
specific immune responses may also be evaluated. Subjects agreeing to inguinal lymph node 
biopsy may be asked to undergo photography of the biopsy wound immediately after the procedure 
and again six months later in order to provide an objective reference for assessment of wound 
healing and for possible use as volunteers’ educational material. Subjects are free to refuse 
photography of their wound at any point should they not be amenable for any reason.   
Similar to the gut, HIV preferentially infects cells in the lymph nodes in acute HIV infection and 
destroys lymph node architecture leading to fibrosis and CD4+ T cell loss [70, 71]. The function 
of T follicular helper cells is negatively affected by HIV and results in dysfunctional humoral 
immune responses against HIV [72]. In treated chronic HIV infection, the lymph nodes continue 
to harbor latently infected cells despite prolong periods of viral suppression, and contribute to the 
rapid return of viremia if ART is interrupted [73]. It will therefore be critical to understand the 
reservoir characteristics and the HIV-specific immune responses before and after ATI, as well as 
to characterize the influence of VRC01 on these parameters. Such investigations may allow for the 
identification of correlates to viremic control post ATI. 

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5.8.4 Leukapheresis 
Leukapheresis also requires separate consent.  At specific study visits identified in the SOE, 
volunteers will have the option of undergoing apheresis in lieu of peripheral blood phlebotomy to 
collect PBMC and plasma. Each occurrence of this procedure is associated with a maximum blood 
loss of 50 mL.   
Leukapheresis will be performed in the Blood Bank Unit at King Chulalongkorn Memorial 
Hospital, and procedures will be scheduled by study staff according to the SOE. Leukocytes and 
plasma for in vitro investigation will be obtained using automated apheresis techniques conducted 
by a qualified apheresis nurse/technician.  During apheresis, whole blood is withdrawn through a 
catheter placed in an antecubital vein and channeled into a cell separator where cellular and plasma 
fractions are separated by centrifugation.  The component to be harvested, e.g. leukocytes, is 
directed into a collection bag and the red cells, platelets, and plasma are returned to the donor.  The 
return is accomplished through a second needle placed at another site, usually in the other 
antecubital vein. The cells collected will allow for detailed examination of the HIV reservoir 
including QVOA and HIV-specific immune responses. 
5.8.5 Lumbar Puncture 
Lumbar puncture for CSF collection (20ml) will be done at the TRCARC by the study investigator 
or other trained personnel in volunteers who give consent for this procedure regardless of 
neurological symptoms, provided that the procedure is deemed safe by the study investigator or 
other qualified study physician. Procedures will be performed according to the SOE. CSF will be 
assayed for HIV RNA PCR using the Roche Amplicor® 2.0 kit or another nucleic acid 
amplification method. CSF cell count, glucose and protein quantification will be performed. Left 
over CSF will be spun and stored at –80˚C and will be used to isolate and sequence HIV, and for 
cytokine/chemokine and biomarker assays (such as MCP-1, neopterin, IL6, T-tau, P-tau, Abeta42, 
sAPPalpha, sAPPbeta, neurofilament light and other biomarkers relevant to immune response to 
HIV) (at the Retrovirology laboratory at WRAIR and/or laboratory at Yale, and/or University of 
Gothenburg). To facilitate interpretation of CSF data, blood glucose, protein and HIV RNA will 
also be measured at the time of lumbar puncture. 
5.8.6 Brain MRI/MRS/DTI 
Brain MRI may be performed at King Chulalongkorn Memorial Hospital (which is 100 meters 
from the TRCARC in Bangkok) or at the Pattaya Memorial Hospital-affiliated radiology facility, 
according to patient convenience and availability. The procedure lasts approximately 60 minutes. 
Brain MRS and DTI will be performed at King Chulalongkorn Memorial Hospital only.  No 
preparations or precautions are needed. MRI/MRS/DTI is a standard medical procedure and 
MRI/MRS for this study follows the standard hospital protocol. 
5.9 
CONCOMITANT MEDICATIONS 
Concomitant medications will be recorded for the time period beginning 45 days prior to study 
enrollment and at every study visit. This will include documentation of prescription and over-

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the-counter drugs as well as vitamin and mineral supplements. Study participants can receive 
medications such as acetaminophen, NSAIDs, or antihistamines as required; although they must 
be documented. No medications will be prohibited during study participation. Participants will 
be counseled to avoid non-essential vaccination during the period of ATI and any essential 
vaccinations, such as seasonal influenza, will be administered outside of weeks 2-6 and weeks 
26-30, when the risk of rebound viremia is considered to be highest. 
5.10 
SOLICITED ADVERSE EVENTS 
Temperature and solicited systemic symptoms will be recorded in the clinic prior to each infusion 
of either VRC01 or placebo, at a minimum of 60 minutes after the infusion, and then daily by the 
participant for 7 days after infusion. All participants will be given a thermometer, trained in its 
use, and provided a diary card for the purpose of recording these data after each infusion. The diary 
card may be used as a source document. 
For this study, solicited adverse events occurring during the 7 days after receipt of study agent will 
include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, rash and joint 
pain. Subjects will also record daily measured temperature. The diary cards are reviewed for 
completeness at follow-up visits and are recorded without an attribution assessment (unless they 
are Grade 3 or higher in severity in order to assess whether the event is relevant to the study pause 
criteria). Severity will be graded by the study team at the time of diary card review. Clinicians will 
collect resolution information for any systemic symptoms that are not resolved after 3 days. 
Clinician assessment of the local IV administration site will be conducted on day of study agent 
administration and during the scheduled follow-up timepoints on days 1, 3 and 7 after 
administration. 
At every visit, all participants will be asked about other adverse experiences, which will be 
recorded and entered the same day into the study database. The PI will assess the relationship of 
the study products to the events.  
5.11 
STUDY DISCONTINUATION 
5.11.1 Early Discontinuation or Withdrawal of Study Participants 
A participant may be removed from the study entirely for any of the following reasons: 
1. Repeated failure to comply with protocol requirements. 
2. Decision by DAIDS, the PI, Walter Reed Army Institute of Research Institutional Review 
Board (IRB), U.S. FDA, and the Office for Human Research Protection (OHRP), or local 
regulatory authorities and local IRB(s) to stop or cancel the study. 
3. Participant request. 
4. Pregnancy (with subsequent offer to enroll in RV 412) 
 
Each subject has the right to withdraw from the study at any time for any reason without affecting 
the right to treatment. The investigators will attempt to contact subjects who do not return for 
scheduled visits or follow-up. Although the subject is not obliged to give the reason(s) for 

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withdrawing prematurely, the investigators will make a reasonable effort to ascertain the reason(s) 
while fully respecting the subject’s rights. 
 
For those subjects who are unable to continue participation in the study, but who do not withdraw 
consent, an exit visit will be conducted (refer to SOE, Appendix II, for list of procedures to be 
conducted). Any subject who withdraws consent will not have any further data collected after 
consent has been withdrawn. Data that were collected prior to withdrawal of consent will remain 
a part of the research database and will be included in data analysis. Stored specimens will remain 
available for the conduct of IRB-approved non-human research.  
 
The investigator also has the right to withdraw a subject, e.g., because of worsening health status, 
intercurrent illness, or AEs. 
 
If a subject withdraws from the study before the first infusion of VRC01 or placebo, the next 
available participant will be placed in the vacated randomization slot. Replacements for 
participants who withdraw from the study before the first infusion will only be permitted while 
enrollment is open. Subjects will not be replaced if withdrawal from the study occurs after the first 
infusion of VRC01 or placebo. To minimize bias, only the study pharmacist will know whether 
the replacement has been assigned to placebo or VRC01 and the study staff and all volunteers will 
be blinded to assignment. 
5.11.2 Premature Termination of the Study 
Walter Reed Army Institute of Research IRB, DAIDS, the U.S. FDA, and OHRP reserve the right 
to terminate the study.  The investigator will notify reviewing IRBs in writing of the study’s 
completion or early termination. 
 

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6.0 
 STUDY TREATMENT 
Study treatment is defined as VRC-HIVMAB060-00-AB (VRC01) or placebo for VRC01.  
6.1 
STUDY TREATMENT REGIMENS, ADMINISTRATION, AND DURATION 
6.1.1 Regimens 
Twenty-four men and women aged 20-50 years who began ART during early acute HIV infection 
(Fiebig stage I to III) will be randomized in a 3:1 ratio to either VRC01 or placebo, with 
randomization stratified by Fiebig stage. 
 
VRC01 will be dosed at 40 mg/kg and administered intravenously in 100 ml of normal saline every 
three weeks for a total of up to 24 weeks.  
 
Placebo for VRC01 will be normal saline (0.9% sodium chloride for injection, USP) administered 
intravenously at a volume of 100 mL every three weeks for a total of up to 24 weeks. 
6.1.2 Administration 
VRC01 or placebo for VRC01 will be administered as an intravenous infusion about 30-60 minutes 
using a volumetric pump. The infusion rate may vary based on the total volume needed to 
administer the full dose The total time needed to administer the dose may be longer than 60 minutes 
based on factors such as participant tolerance. Infusion access should be maintained and the 
participant observed for a minimum of 1 hour following completion of the infusion. There is 
currently very little data concerning administering the study drug over 30 min. 
6.1.3 Duration 
Study agents will be administered for up to 24 weeks, or until criteria for ART resumption are 
met (see Section 4.6), whichever comes first. Participants will be followed for up to 48 weeks 
after the first dose of a study agent.  
6.2 
STUDY PRODUCT FORMULATION AND PREPARATION 
6.2.1 Formulation 
VRC01 (labeled as VRC01 HIV MAb Drug Product VRC-HIVMAB060-00-AB) is supplied  at a 
concentration of 100 ± 10 mg/mL in an isotonic, sterile solution. Two fill volumes are available: 
10 mL glass vials with a 6.25 ± 0.10 mL fill volume and 3 mL glass vials with a 2.25 ± 0.10 mL 
fill volume. The vials contain a clear, colorless to yellow liquid, essentially free of visible particles; 
some opaque or translucent particles may be present. The formulation buffer is composed of 25 
mM sodium citrate, 50 mM sodium chloride, and 150 mM L-arginine hydrochloride at pH 5.8. 
Vials are intended for single use only and do not contain a preservative. All dose calculations 
should be based on a concentration of VRC01 of 100 mg/mL.  
 

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Placebo for VRC01 will be sodium chloride for injection 0.9%, USP.  
6.2.2 Preparation for Intravenous Administration 
A new prescription must be sent to the pharmacy after the participant is weighed on the day of 
each visit during which study product will be administered.  Participants’ screening weight or entry 
weight or last obtained weight may be used for calculation of the dose to thaw vials, but actual 
weight on the day of dosing will be used for calculating the final dose of study product to be 
infused.  The prescription must contain the participants’ weight and dose prior to being sent to the 
pharmacy (verbal orders are not permitted). 
 
The pharmacist must verify the dose prior to preparing the study product. 
 
Thawing Instructions:  
Thaw vials of VRC01 at controlled room temperature 15°C to 25°C (59°F to 77°F) for a 
minimum of one hour up to a maximum of 24 hours. Continue to thaw the vials until the solution 
is clear, colorless to yellow with no visible particles.  Prior to 24 hours at room temperature, the 
vials of VRC01 must either be used to prepare an infusion or may be placed in a refrigerator and 
stored up to 4 weeks at 2-8⁰C (36°F to 46°F).  
VRC01 may not be stored in direct sunlight at anytime. 
VRC01 is a highly concentrated protein solution and may develop white-to-translucent particles 
after thawing. Particles have been observed in 1-3% of the vials and generally disappear over a 
few hours at room temperature and may continue to dissipate at 2-8⁰C.  
Vials of VRC01 containing particles should be placed in the refrigerator as particles may 
continue to dissipate at 2-8⁰C. Vials of VRC01 that previously contained particles but are now 
clear of particles may be used. Vials that continue to have visible particles after a maximum of 24 
hours at controlled room temperature and up to 4 weeks at 2°C to 8°C (36°F to 46°F) are not to 
be used and will be discarded in a biohazard containment bag and incinerated or autoclaved in 
accordance with institutional or pharmacy policy. Report to the protocol pharmacist the quantity 
and the reason why for the disposal of any unused vials. 
After removal from 2-8⁰C, vials of VRC01 should be equilibrated to controlled room 
temperature 15°C to 25°C (59°F to 77°F) for a minimum of 30 minutes prior to preparing 
IV infusions.  The maximum length of time that VRC01 in the vial may be held at 
controlled room temperature 15°C to 25°C (59°F to 77°F) prior to product preparation is 8  
hours after removal from the refrigerator. 
 
After thawing, the vials should be gently swirled for 30 seconds to avoid foaming. Vials must 
not be shaken. DO NOT SHAKE THE VIALS. Keep the vials upright at all times until ready to 
withdraw the contents. Do not invert the vial during inspection. Observe vials for particles. If 
particles are observed follow the instructions above. 

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divided Calculate the total milligrams of VRC01 required based on the participants weight and 
40mg/kg dose and total number of vials required based on a 6 mL withdrawal volume containing 
600 mg of VRC01 or 2 ml withdrawal volume containing 200 mg of VRC01.  
 
The calculated total milligrams needed of VRC01 should be added to a 100 mL bag of 0.9% 
sodium chloride for injection, USP, using aseptic technique to maintain sterility in a clean room 
with limited access using either an isolator, laminar flow hood, or biological safety cabinet. The 
0.9% Sodium Chloride Injection, USP, 100 mL bag will accommodate the additional volume 
required for the dose of VRC01 to be used in this study.   Do not withdraw fluid from the 0.9% 
Sodium Chloride Injection, USP, 100 mL bag to make room for the volume of study product to be 
added.  A total of up to 50 mL of VRC01 may be added to a 100 mL bag of sodium chloride.. 
Please note: The prepared infusion bag must include expiration time of 7 days from the time of 
preparation when stored at room temperature (maximum 32°C ) or 2°C to 8°C. When prepared IV 
bags are held at 2°C to 8°C the IV bags should be equilibrated to controlled room temperature 
(maximum 27°C) for a minimum of 30 minutes and may be additionally held at room temperature 
for up to 24 hours prior to and during product administration. The IV bag should then be labeled to 
maintain blinding 
 
 
Any unused portion of a VRC01 vial will not be used for another subject. 
 
Placebo for VRC01 will be 0.9% sodium chloride for injection, USP and should be added to a 100 
mL bag of 0.9% sodium chloride for injection, USP, using aseptic technique. The volume of 
placebo to be infused will be approximately 100 mL plus 0.4 mL/kg to be consistent with the 
volume infused in the active VRC01 arms. Do not withdraw fluid from the 0.9% Sodium Chloride 
Injection, USP, 100 mL bag to make room for the volume of placebo to be added. The IV bag 
should then be covered with an amber bag and labeled to maintain blinding. 
 
6.2.3 Storage 
VRC01 should be stored in a qualified, continuously monitored, temperature-controlled freezer 
at -35°C to -15°C (-31°F to 5°F). Freezer temperature from -45°C to -10°C (-49°F to 14°F) is 
acceptable.  
 
The site pharmacist must promptly report any storage temperature excursions outside of the 
normal allowance for the freezer to the NIAID Clinical Research Products Management Center 
(CRPMC). The product must be quarantined in a separate area. The NIAID CRPMC will notify 
the site pharmacist if continued clinical use of the product is acceptable. 
 
 
Placebo for VRC01 (0.9% sodium chloride for injection, USP) should be stored according to 
manufacturer recommendations. 
 

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6.3 
PHARMACY: PRODUCT SUPPLY, DISTRIBUTION, AND ACCOUNTABILITY 
6.3.1 Study Product Acquisition and Distribution 
VRC01 is manufactured by the VRC and will be available through the National Institute of Allergy 
and Infectious Diseases (NIAID) Clinical Research Products Management Center (CRPMC). The 
site pharmacist should obtain the VRC01 product(s) for this protocol by following the instructions 
in the manual Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks. 
 
The placebo for VRC01 (0.9% sodium chloride for injection, USP) will not be provided through 
the study and must be obtained locally.  
 
Sodium chloride for injection 0.9%, USP, 100 ml bags required to prepare the dose for VRC01 and 
placebo for VRC01, will not be provided through the study and must be obtained locally. 
6.3.2 Study Product Accountability 
The site pharmacist is required to maintain complete records of all study products received from 
the NIAID CRPMC and subsequently dispensed. All unused study products must be returned to 
the NIAID CRPMC or destroyed (as directed by the sponsor, DAIDS) after the study is completed 
or terminated. The procedures to be followed are in the manual Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks. 
6.4 
DISPOSITION 
The empty vials and the unused portion of a vial will be discarded in a biohazard containment bag 
and incinerated or autoclaved. Any unopened vials that remain will be returned to the production 
facility or discarded at the discretion of DAIDS in accordance with policies that apply to 
investigational agents. Partially used vials will not be administered to other subjects or used for in 
vitro experimental studies. They will be disposed of in accordance with institutional or pharmacy 
policy. 
 
Vials or IV infusion bags of VRC01 with particles should be quarantined and stored at 2-8⁰C. 
Contact the protocol pharmacist for further instructions regarding management of VRC01 vials 
or infusion bags VRC01 with particles. 
 

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7.0 
PHARMACOVIGILENCE, SAFETY, AND ADVERSE EXPERIENCE 
REPORTING 
7.1 
DEFINITIONS  
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and does not necessarily have a causal relationship 
with this product. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. (International Conference on Harmonization (ICH) E6) (Synonym: Adverse Experience).   
 
A serious adverse event (SAE):  An adverse event or suspected adverse reaction is considered 
"serious" if, in the view of either the investigator or sponsor, it results in any of the following 
outcomes: Death, a life-threatening adverse event, inpatient hospitalization or prolongation of 
existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events 
that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject 
and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse (21 CFR 312.32). 
 
“Life-threatening” refers to an adverse event that at occurrence represents an immediate risk of 
death to the subject. An event that may cause death if it occurs in a more severe form is not 
considered life-threatening. Similarly, a hospital admission for an elective procedure is not 
considered an SAE. 
7.2 
ADVERSE EVENT GRADING AND RECORDING 
Recording of all AEs will occur during the period from the first study agent administration 
through 175 days after the last study agent administration.  After this and through completion of 
study participation, only SAEs and new chronic medical conditions that require ongoing medical 
management will be recorded as AEs in the study database.   
 
All recorded AE and lab data will be coded for severity using the current version of the Division 
of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
(DAIDS AE Grading Table), included as Attachment III and found on the website http://rsc.tech-
res.com/safetyandpharmacovigilance/. 
 
For adverse events not identified in the grading table, the following guidelines in Table 3 will be 
applied:  

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Table 3.  Additional Categories for Grading of Adverse Events 
Category 
Grade 
Description 
Mild 
Grade 1 
Symptoms causing no or minimal interference with usual 
social & functional activities 
Moderate 
Grade 2 
Symptoms causing greater than minimal interference with 
usual social & functional activities 
Severe 
Grade 3 
Symptoms causing inability to perform usual social & 
functional activities 
Potentially 
Life-Threatening 
Grade 4 
Symptoms causing inability to perform basic self-care 
functions OR medical or operative intervention indicated to 
prevent permanent impairment, persistent disability or 
death 
Death 
Grade 5 
Symptoms resulting in fatal outcome 
 
The site clinical research team will ascertain accurate recording of AEs during the study. AE case 
report forms (CRFs) will be completed by the research staff on a daily basis as the data become 
available from the clinic or laboratory.  
 
The clinical investigators will monitor and analyze study data including all AE and lab data as they 
become available and will make determinations regarding the severity of the adverse experiences 
and their relation to study product. To insure that all AEs are captured in a timely manner, CRFs 
will be entered in real-time and also subjected to analysis to identify AEs that may invoke study 
pause rules. 
 
Although post injection reactogenicity (PIR)/Solicited AEs are documented separately from 
unsolicited AEs, they are reported to DAIDS if they meet SAE or study pause rule definitions as 
noted below.  Therefore, the PI or designee must review both PIR and AE CRFs to insure prompt 
and complete identification of all events that require expedited reporting as SAEs, study pause 
rules or other serious and unexpected events.  
 
Study related AEs will be followed by the clinical research team through resolution.  Non-study 
related AEs will be followed to resolution or study completion, whichever occurs first. 
7.3 
PROTOCOL SAFETY REVIEW TEAM (PSRT) AND PSRT REVIEWS 
The PSRT will review all AEs (including reportable AEs) on a regular and expedited basis as 
needed. In addition, the PSRT will review aggregate safety data reports from all sites on a weekly 
basis. This team includes the following: Study Chair, Site PI, a DoD research monitor, and the 
DAIDS medical officer or their designees. Additional participants could include associate 
investigators, and senior clinical research nursing staff. A quorum is established with the Protocol 
Chair, site PI and the DAIDS medical officer (MO) or their designee. 
 

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7.4 
SAFETY MONITORING COMMITTEE (SMC) REVIEWS 
The SMC for this study will be comprised of an independent group of experts established with 
consultation of DAIDS to review safety data during the clinical trial.  The Protocol Chair (or 
designee) will submit written recommendations and cumulative safety data, grouped according to 
treatment group, to the SMC Executive Secretary after the first enrollee has completed 90 days of 
the study.  Subsequently, the SMC will convene every six months to review the completeness of 
the study data collected, the adherence to the protocol, and the Protocol Chair’s review summaries.  
The SMC will also meet as needed to deliberate upon the initial interim safety data, the disposition 
of study pauses, and/or to provide other recommendations regarding the safe conduct of the study 
as requested by the Protocol Chair, Principal Investigator and/or DAIDS Medical Officer.  The 
SMC Executive Secretary will provide the Protocol Chair and DAIDS Medical Officer with SMC 
recommendations, and the Protocol Chair and site PI will inform IRBs and regulatory authorities 
as appropriate. 
7.5 
CRITERIA FOR STUDY PAUSE OR TERMINATION  
If the trial is placed on safety pause, all enrollment and infusions will be suspended until further 
notice. Study visits will continue. Enrollment and infusions will resume if and when safety is 
ensured. Study pauses should not delay the initiation of ART according to the study schedule. 
 
Table 4 summarizes the AEs, which when experienced by at least one participant will lead to a 
safety pause or prompt PSRT AE review. For any AE where the outcome is death, the severity of 
the AE is classified as Grade 5.  Related AEs refer to AEs deemed to be definitely, probably, or 
possibly related to the study; Not related AEs refer to AEs deemed to be unlikely related or not 
related to the study. 
 
Grade 5 or 4 events that are judged related to study product administration should be reported 
immediately (within hours of the site learning of the event). These events require immediate pause. 
 
Grade 3 events that are judged related to study product administration should be reported promptly 
i.e., within 24 hours.  These events require prompt review by the PSRT.  
 
All events that are related to study product administration and are similar grade 2 AEs in two or 
more participants will be routinely reviewed by the PSRT but will not necessarily prompt a pause. 
The PSRT may take that action after review.  
 
When the administration of study products has been paused, VRC01 administration and 
enrollments would resume only if review of the triggering AEs by the PSRT (and where applicable, 
the SMC), result in a recommendation to permit further study product administration and study 
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Table 4.  Adverse Event Notification and Study Pausing Guidelines 
Toxicity 
Post-Injection Reactogenicity (PIR) and Study 
Treatment Related Adverse Events (AEs) 
Action 1 
Grade 5/Grade 4 
Related2 
 
“Verified” 3 abnormal laboratory values, local or 
systemic reactogenicity, or related AEs  
(if fever, must persist for ≥ 48 hours) 
Automatic pause  
Immediate reporting 
 (Concurrent with observation or report) 
Grade 3 
Related2 
“Verified”3 abnormal laboratory values, fever for 
≥ 48 hours, vomiting, or other clinical study mAb 
infusion related AEs (Except for subjective 
symptoms) 
Consider pause 
Prompt reporting (within 24 hours of 
observation or report) 
1Follow-Up and Resolution: All promptly or immediately reportable AEs are followed until resolution or condition is medically 
stable. 
 2Related AEs refer to AEs deemed to be definitely, probably, or possibly related to the study; Not related AEs refer to AEs 
deemed to be unlikely related or not related to the study 
3If no evidence of disease is present other than the abnormal laboratory value, the test must be repeated at least one time in 
order to be considered “verified”. The verification period will be a maximum of 48 hours after initial awareness of the abnormal 
laboratory value.  When signs and symptoms are present, repeat test WILL NOT be needed 
 
For events in the table above, the Site PI notifies the PSRT, which includes the Study Chair and 
DAIDS MO, within a few hours after the site observes, or is notified of, the AE. The PSRT will 
convene within one business day to review these adverse events. The PSRT will review and 
determine disposition (including whether the SMC needs to review the event). Any Grade 4 or 
Grade 5 AE will automatically trigger SMC review.  
 
If a decision to resume study enrollment and study treatment administration is made, the PSRT 
and/or SMC will record its judgment in a memorandum to the study file and notify DAIDS, who 
will then forward the memorandum to the principal investigator and protocol chair. The protocol 
chair or designee will instruct the clinical site to resume activities upon receipt of written 
notification from DAIDS. As needed, the appropriate regulatory authorities will be informed in 
writing of the decision to resume or discontinue study activities. Site is responsible for notifying 
the Chulalongkorn IRB according to their standards and regulations, and the WRAIR IRB within 
48 hours for awareness. The sponsor (DAIDS) is responsible for notifying the FDA.  

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7.6 
EXPEDITED REPORTING TO IND SPONSOR (DAIDS) 
Requirements, definitions and methods for expedited reporting of Adverse Events (AEs) are 
outlined in the current version of the DAIDS Expedited Adverse Events (EAE) Manual, which is 
available on the RSC website at http://rsc.tech-res.com/safetyandpharmacovigilance/.  Reporting 
AEs to DAIDS will be conducted according to this Manual. 
 
The SAE Reporting Category, as defined in the current version of the DAIDS EAE Manual, will 
be used for this study. All SAEs will be reported by the site PI or designee to the DAIDS RSC 
Safety Office.  
 
The DAIDS Adverse Experience Reporting System (DAERS), an internet-based reporting system, 
must be used for expedited AE reporting to DAIDS. In the event of system outages or technical 
difficulties, expedited AEs may be submitted via the DAIDS EAE Form. This form is available on 
the RSC website: http://rsc.tech-res.com/safetyandpharmacovigilance/. For questions about 
DAERS, please contact DAIDS-ES at DAIDS-ESSupport@niaid.nih.gov.  Site queries may also 
be sent from within the DAERS application itself.  For questions about EAE reporting, please 
contact the RSC (DAIDSRSCSafetyOffice@tech-res.com).  
 
At the time of SAE submission, any supplemental forms as required by Chulalongkorn University 
and DoD IRBs must also be submitted to DAIDS RSC Outcomes of the SAE will need to be 
provided as updates through DAERS or on the EAE form until the adverse event is resolved, is 
stable, or chronicity has been established and documented.  
 
For questions or other communication with RSC on SAEs, please note the following:  
 Website:  
http://rsc.tech-res-intl.com  
 Office Phone*:  
1-800-537-9979 (U.S. only) or +1-301-897-1709  
 Office Fax*:  
1-800-275-7619 (U.S. only) or +1-301-897-1710  
Office Email:  
DAIDSRSCSafetyOffice@tech-res.com  
Office Hours:  
Monday through Friday, 8:30 AM to 5:00 PM (U.S. Eastern 
Time) 
Mailing Address:  
DAIDS Safety Office 6500 Rock Spring Drive Suite 650 
Bethesda, MD 20817 
*Office phone and fax are accessible 24 hours per day 
7.6.1 Study Agents for Expedited Reporting to DAIDS 
The study agents that must be considered in determining relationships of AEs requiring 
expedited reporting to DAIDS is the VRC01 MAb (VRC-HIVMAB060-00-AB) and placebo. In 
the event of an EAE, subject randomization will be unblinded as described in section 7.10 in 
order to meet reporting criteria. 
7.6.2 Study Recording Period for SAEs 
The protocol-defined expedited event reporting period for this protocol is 175 days after the last 
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participation for any reason.  After the end of the protocol-defined EAE Reporting Period stated 
above, the site must report serious, unexpected, suspected adverse drug reactions (SUSARS) if the 
study site becomes aware of the event on a passive basis (i.e, from publicly available information). 
7.6.3 Timeframe for Expedited Reporting of Individual Adverse Events  
The timeframe for expedited reporting of an individual AE begins when the site recognizes that an 
event fulfills reportable AE criteria. For SAEs sites must submit adverse events requiring 
expedited reporting to the DAIDS RSC Safety Office as soon as possible, but no later than 3 
reporting days (as defined in the DAIDS EAE Manual), after the site’s recognition that the event 
fulfills the criteria for SAE reporting.  The RSC will submit written IND Safety Reports to the 
FDA in accordance with 21 CFR 312.32 as soon as possible and, in no event, later than 7 or 15 
calendar days following receipt of reportable adverse event information. 
 
For IND Safety Reports submitted to the FDA and received from DAIDS, COG will complete the 
necessary reporting to the WRAIR IRB by contacting them by phone or email within 48 hours, 
and submitting a written report within 10 working days of the initial safety report.  The WRAIR 
HSPB will report IND Safety Reports to the USAMRMC ORP HRPO as per UWZ-C-636. 
 
The necessary AE reporting documents and any study pauses will also be submitted to the WRAIR 
IRB and the USAMRMC ORP.   
7.7 
REPORTING SERIOUS AND UNEXPECTED ADVERSE EVENTS TO THE DOD IN ADDITION 
TO DAIDS 
All related serious adverse events (SAEs) and deaths should be reported to the WRAIR IRB within 
48 hours by telephone, email or fax. A complete written report should follow the initial notification 
within 10 working days.  All SAEs occurring within the reporting period should also be 
summarized in the continuing review reports submitted to the WRAIR IRB. The contact 
information for the WRAIR IRB is as follows: 
 
Director, Human Subjects Protection Branch 
503 Robert Grant Avenue 
Silver Spring, MD 20910 
Telephone: 301-319-9940 
Fax: 301-319-9961 
Email: usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil 
 
The WRAIR HSPB will report SAEs to USAMRMC ORP HRPO as per SOP UWZ-C-636. 
7.7.1 Social Harms Reporting 
Unanticipated events and social harms may occur during the course of the study.  When such 
events are related to study participation, the study staff, informed of these events, will inform the 
PI or his/her designee. The PI or designee will then prepare a narrative summary of the event and 
report to the Chulalongkorn University IRB, WRAIR IRB and PSRT including DAIDS Medical 

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Officer.  The local medical monitor should also review the social harms and provide an 
independent assessment of these to the WRAIR IRB. The WRAIR HSPB will report these reports 
to the USAMRMC ORP HRPO as per UWZ-C-636. A summary of these reports should also be 
provided in the continuing review report. 
7.7.2 Unanticipated Problems Reporting to WRAIR 
Unanticipated problems involving risks to subjects or others (UPIRTSO) encompass a broader 
category of events than SAEs and may include issues such as problems with loss of control of 
subject data or the investigational product; adverse psychological reactions; or breach of 
confidentiality. Risks to others (e.g., program personnel) must also be reported. 
 
Unanticipated problems involving risks to subjects or others (UPIRTSO) are any incident, 
experience, or outcome that meets all of the following criteria: 
• Unexpected (in terms or nature, severity, or frequency) given (a) the procedures that are 
described in the protocol, investigators brochure or informed consent document; and (b) 
the characteristics of the subject population. 
• Related or possibly related to a subject’s participation in the study; and 
• Suggests that the study places subjects or others at a greater risk of harm than was 
previously known or recognized. 
 
 
All unanticipated problems related to the study and involving risk to subjects or others (UPIRTSO) 
should be promptly reported (48 hours) by telephone, email or fax to the WRAIR IRB.   A complete 
written report should follow the initial notification within 10 working days.  All unanticipated 
problems occurring within the reporting period should also be summarized in the continuing 
review reports submitted to the WRAIR IRB. The contact information for the WRAIR IRB is as 
follows: 
Director, Human Subjects Protection HSPB 
503 Robert Grant Ave. 
Silver Spring, MD 20910-7500 
Telephone: 301-319-9940 
Fax: 301-319-9961 
Email: usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil  
 
The local medical monitor will also be responsible for reviewing the unanticipated problems and 
providing an independent assessment for all potential UPIRTSOs to the WRAIR IRB. A summary 
of all unanticipated problems will be included in the continuing review reports. The WRAIR HSPB 
will report unanticipated problems to the USAMRMC ORP HRPO as per UWZ-C-636.  The report 
will be forwarded to the DAIDS. 
7.8 
REPORTING REQUIREMENTS TO THE LOCAL IRB 
The site PI will be responsible for providing all Safety Reports and reporting all SAEs, study 
pauses, social harms, UPIRTSOs, and major deviations to the local regulatory authority, such as 

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the Chulalongkorn University IRB and any country-specific regulatory agencies, in a timely 
manner according to the institution’s guidelines.   
7.9 
REPORTING REQUIREMENTS TO THE THAI FDA 
Study investigators will inform the Thai FDA of adverse events in accordance with Thai 
regulations. It is the responsibility of the PI or designee to fulfill the reporting requirements.  
A SUSAR resulting in death or which is life-threatening must be reported in an initial report within 
7 days of awareness, followed by a full report within the following 8 days. Additional periodical 
reporting will be required if additional data emerges.  
A SUSAR not leading to death and not life-threatening must be reported within 15 days of 
awareness. Any unexpected adverse reaction arising after the volunteer has left the research or 
after research is completed must also be reported within 15 days of awareness. A periodical report 
is also required if additional data emerge after the filing of the initial report.  
An Annual Safety Report will be submitted to the Thai FDA of all AEs and SAEs, regardless of 
whether they were related to study agents and regardless of intensity. The Thai FDA wishes to 
receive any safety reporting, including from animal studies, that may change the evaluation of risk 
of the study products under investigation, the method of study product administration, or the 
overall conduct of the study. 
Any reporting will use Thai FDA specific forms to be sent to the Health Product Vigilance Centre 
at http://thaihpvc.fda.moph.go.th. In case the system is not ready for use or develops technical 
problems, the report shall be sent to the Pre-Marketing Drug Supervision Group, Bureau of Drug 
Control, Thai Food and Drug Administration. 
Thai FDA 
Health Product Vigilance Centre 
Pre-Marketing Drug Supervision Group 
Bureau of Drug Control, 
Food and Drug Administration 
Ministry of Public Health 
Tiwanon Road, Nonthaburi 11000 
Tel: +66- 2590-7160, +66- 2590-7171  
Fax: +66-2591-8390, +66-2591-8489, +66-2590-7170  
e-mail:drug@fda.moph.go.th 
Electronic submission at: http://thaihpvc.fda.moph.go.th 
7.10 
UNBLINDING 
A request for unblinding, with its rationale, should be forwarded through the PI. The PI will 
evaluate the request and notify the DoD Research Monitor.  The DoD Research Monitor will 
evaluate the request and advise the Sponsor regarding the course of action.  The Sponsor will 
decide whether to approve the request for unblinding.  In the case of the former, the Sponsor will 
authorize the independent statistician to provide this information to the PI. It should be noted that 
there are very few circumstances in which unblinding will be essential to the medical management 

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of a VRC01 or placebo recipient. In case of VRC01-related death or life-threatening SAE, 
knowledge of whether a participant received VRC01 or placebo can be critical for the 
interpretation of the significance of clinical findings and thus impact decisions regarding 
continuation of study participation. In such cases, the assignment of a participant will be unblinded. 
Episodes of unblinding, whether accidental or intentional, will be reported by the site investigator 
with an explanation to the Protocol Chair who will inform participating IRBs, Sponsor and other 
necessary regulatory bodies. Follow-up of such participants will continue through the duration of 
the trial. 

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8.0 
STATISTICAL CONSIDERATIONS 
8.1 
POWER AND SAMPLE SIZE FOR SAFETY OBJECTIVE 
The goal of the safety evaluation for this study is to identify safety concerns associated with 
VRC01 administration. Sample size calculations for safety are expressed in terms of the ability to 
detect SAEs. 
Table 5 shows possible two-sided exact 95% confidence intervals for various proportions of 
VRC01 subjects experiencing an adverse event. If no subjects experience an SAE in the VRC01 
arm, then the upper limit of the two-sided exact 95% confidence interval will be 18.5%. 
Table 5. Exact Two-Sided 95% Confidence Intervals for Various Proportions of VRC01 
Subjects Experiencing a Serious Adverse Event 
Enrollment (N) 
 
Total  
Placebo  
VRC01  
Observed SAEs in 
VRC01 Arm 
SAE Rate  
(95% Confidence Interval) 
24 
6 
18 
0 
0 (0-18.5) 
24 
6 
18 
1 
5.6 (0.1-27.3) 
24 
6 
18 
2 
11.1 (1.4-34.7) 
24 
6 
18 
4 
22.2 (6.4-47.6) 
24 
6 
18 
6 
33.3 (13.3-59.0) 
24 
6 
18 
9 
50.0 (26.0-74.0) 
8.2 
POWER AND SAMPLE SIZE FOR EFFICACY OBJECTIVE 
The primary efficacy endpoint for success is sustained virologic control, as defined above, at 24 
weeks following ATI. Assuming a placebo success rate of 15% and using a type I error of 5% as 
the threshold for statistical significance, this study design has 84% power for a two-sided exact 
unconditional test to detect an 80% success rate in the VRC01 arm. Exact unconditional tests have 
been shown to have more power than Fisher’s Exact test and have been recommended for use in 2 
x 2 tables [74]. Other assumptions and power predictions are summarized in Table 6. 
 
Table 6. Power to Detect Differences in Success Rates Between VRC01 and Placebo with 3:1 
Randomization and Two-Sided Type I Error of 5% 
Enrollment (N) 
Success Rate Assumptions (%) 
 
Total  
Placebo  
VRC01  
Placebo  
VRC01  
Power 
24 
6 
18 
5 
50 
46% 
24 
6 
18 
5 
65 
82% 
24 
6 
18 
5 
70 
89% 
24 
6 
18 
15 
50 
27% 
24 
6 
18 
15 
70 
68% 
24 
6 
18 
15 
80 
84% 
 

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8.3 
ANALYSIS 
The primary analysis will consist of all subjects receiving at least one dose of the study product. 
A secondary per-protocol analysis will consist of subjects compliant with study treatment. 
Analysis will be performed for the entire study population and also stratified by Fiebig stage in 
order to explore the impact of Fiebig stage on study endpoints, recognizing that the study is not 
powered to detect outcomes across participants at any single Fiebig stage.  
Baseline characteristics including demographics and laboratory measurements will be summarized 
using descriptive statistics.   
The analysis of study data will be primarily descriptive, with emphasis on tabular and graphical 
displays. Summary statistics will be calculated, along with point and interval estimates of solicited 
and unsolicited adverse event and immune response rates. This study is exploratory, and any 
statistical inferences will be hypothesis generating, and not confirming.  
8.3.1 Primary Endpoints 
The primary efficacy endpoint is sustained virologic control (HIV RNA <50 copies/mL) at 24 
weeks after ATI. The rate of virologic control will be compared between treatment groups using a 
two-sided exact unconditional test with a significance level of 0.05. 
To assess safety, summaries of the number and percentage of subjects experiencing any SAE, AE, 
or reactogenicity will be tallied by treatment group and presented along with two-sided exact 95% 
confidence intervals for the proportion. 
For solicited AEs/reactogenicity, number and percentage of subjects experiencing each type of 
solicited sign or symptom will be tabulated by severity. For a given sign or symptom, each 
subject’s solicited AEs will be counted once under the maximum severity for all assessments.   
For unsolicited AEs, number and percentages of participants experiencing each specific adverse 
event will be tabulated by severity and relationship to treatment. For the calculations in these 
tables, each participant’s adverse experience will be counted once under the maximum severity or 
strongest recorded causal relationship to treatment. 
Further, frequency of solicited and unsolicited adverse events will be reported (together and 
seperately) by system organ class, preferred term, and treatment group overall and at various 
timepoints throughout the study. 
A complete listing of adverse experiences for each participant will provide details including 
severity, relationship to treatment type, onset, duration and outcome. 
8.3.2 Secondary Endpoints 
1. Time to viral rebound and level of rebound viremia after cessation of ART.  
Time to viral load rebound will be described using a Kaplan-Meier estimator to account for 

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possible censoring and compared between treatment groups using an exact log-rank test. 
Number of HIV RNA copies at the time of rebound viremia will be described using medians 
and interquartile ranges and compared between treatment groups using a Wilcoxon-Rank 
Sum test.  
2. Time to ART resumption for any reason after cessation of ART 
Time to ART resumption will be described using a Kaplan-Meier estimator to account for 
possible censoring and compared between treatment groups using an exact log-rank test. 
3. Detectable HIV RNA via single copy assay at various timepoints, such as weeks 24 and 
48, as compared to baseline at week 0. 
Number of HIV RNA copies will be described using medians and interquartile ranges at 
baseline, week 24, and week 48 for subjects with HIV RNA <50 copies/mL by standard 
PCR. Change from baseline at week 24 and week 48 will be compared between treatment 
groups using a Wilcoxon-Rank Sum test.  
4. CD4+ T cell count various timepoints, such as weeks 24 and 48, as compared to baseline 
at week 0. 
CD4+ T cell counts will be described using medians and interquartile ranges at baseline, 
week 24, and week 48. Change from baseline at week 24 and week 48 will be compared 
between treatment groups using a Wilcoxon-Rank Sum test.  
5. Cell-associated HIV RNA and DNA in the peripheral compartment various timepoints, 
such as weeks 24 and 48, as compared to baseline at week 0. 
Cell-associated HIV RNA and DNA in the peripheral compartment will be described using 
medians and interquartile ranges at baseline, week 24, and week 48. Change from baseline 
at week 24 and week 48 will be compared between treatment groups using a Wilcoxon-
Rank Sum test.  
6. Neuropsychological battery performance at weeks 24 and 48, as compared to baseline at 
week 0. 
Neropsychological data will be summarized using z-scores based on age-matched normative 
data when such data is available or as raw scores when not available. With either approach, 
individual performance can be compared longitudinally to determine the impact of the 
intervention on cognitive performance, the primary interest of the neuropsychological 
testing portion of this study.    
7. Frequency of hospitalization and incidence of non-AIDS related conditions. 
Frequency of hospitalizations will be summarized and described by treatment group, 
Number of hospitalizations can be compared between groups using a Wilcoxon-Rank Sum 
test and proportion of subjects experiencing a hospitalization will be compared using an 

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exact unconditional test. Incidence of non-AIDS related conditions will be compared in a 
similar fashion. 
Exploratory objectives will be analyzed in a similar fashion to primary and secondary objectives 
although if the rate of consent for invasive procedures is low then analyses may be primarily 
descriptive. Continuous variables will bedescribed at each timepoint using medians and 
interquartile ranges. Change from baseline will be compared between treatment groups at weeks  
24 and 48 using Wilcoxon-Rank Sum tests. If possible repeated measures models will be fit to 
account for within subject correlation and assess a treatment group effect. Binary endpoints will 
be compared between treatment groups using exact unconditional tests. Clinical characteristics 
will be summarized and described by treatment groups. Significance will be assessed using two-
sided testing at the 0.05 level. Given the size and exploratory nature of the trial, adjustments for 
multiple comparisons will not be made.  

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9.0 
DATA COLLECTION 
Data collection will be conducted using paper records or tablets or microcomputers with eventual 
secure transfer to a central database. Paper records will include CRFs without personally 
identifiable information. These files will be maintained in secured cabinets with access restricted 
to study personnel via key. Access to any software used for data collection is limited by individual 
username and password. Data is stored in encrypted fashion on the local computer. After the data 
is uploaded to the central database it is automatically deleted from the local tablet or 
microcomputer.  
Data obtained in the conduct of this study are housed in a secure database maintained by the 
DCAC, MHRP.  All research data are entered in a secure database with standardized quality 
assurance review procedures in accordance with Good Clinical Practices (GCP).  
The DCAC serves as the central data management facility for MHRP research protocols. Data 
managed by DCAC are entered into and maintained in a password-protected database. Data are 
accessible only to participating sites, DCAC, and Information Technology staff authorized to work 
on the protocol. The database is located at the Bethesda campus of MHRP and is protected by a 
firewall. Data from this protocol will be retained indefinitely. 
This data does not contain participant names or Social Security or other national identification 
number, but is referenced only by the study specific identification code.  
Every attempt must be made to follow the protocol and to obtain and record all data requested for 
each subject at the specified times. However, ethical considerations or other events may result in 
the failure to obtain and record certain data, or to record data at the times specified. If this occurs, 
the events and, the reasons for the event must be clearly documented on the case report form for 
deviations and reported as described above.  
Analysis files are created on a periodic basis and made available to the Protocol Chair, Principal 
Investigator (PI) and Associate Investigators (AI) at the direction of the PI and/or Protocol Chair.  
Other collaborators may be given access to these analysis files, or data gathered from them, at the 
direction of the PI.  Data may be made available as a listing, external file, or through a query 
program. 

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10.0 ETHICAL CONSIDERATIONS 
10.1 
PARTICIPATION OF CHILDREN  
Children are not eligible to participate in this clinical trial because it does not meet the guidelines 
for inclusion of children in research.  These guidelines (45 CFR 46, Subpart D, 401-409) state the 
Department of Health and Human Services protections for children who participate in research. 
Generally, healthy children can be studied when the research is considered as "not greater than 
minimal risk."  Children can be involved in research with greater than minimal risk only when it 
presents the prospect of direct benefit to the individual child or is likely to yield generalizable 
knowledge about the child's disorder or condition. 
10.2 
RISKS 
10.2.1 Risks Related to IV infusions 
General risks of IV infusion include stinging, discomfort, pain, soreness, redness, bruising, 
swelling or a tiny cut at the needle insertion site. 
10.2.2 Risks Related to VRC01 
Limited human experience with administration of VRC01 has thus far demonstrated IV infusion 
to be safe and well tolerated (described in Section 2.7 Phase 1 Clinical Trials of VRC01). In a 
preclinical study performed in rats, there was a small dose-dependent, but transient, increase in 
aspartate aminotransferase (AST) and alkaline phosphatase (ALP), but not in alanine 
aminotransferase (ALT) following IV administration.  In rats, there were no histopathology 
findings following IV administration.  
Administration of any mAb may carry a risk of immune reactions such as acute anaphylaxis, serum 
sickness and the generation of antibodies against the mAb; however, these reactions are rare and 
more often associated with mAb targeted to human proteins or with the use of murine monoclonal 
antibodies, which would have a risk of human anti-mouse antibodies.  In this regard, as VRC01 is 
targeted to a viral antigen and is a human monoclonal antibody (IgG1), it is expected to have a low 
risk of such side effects.  
Typically, the side effects of mAbs are mild but may include fever, chills, rigors, nausea, vomiting, 
pain, headache, dizziness, shortness of breath, bronchospasm, hypotension, hypertension, pruritus, 
rash, urticaria, angioedema, diarrhea, tachycardia or chest pain. Clinical use of monoclonal 
antibodies that are targeted to cytokines or antigens associated with human cells may be associated 
with an increased risk of infections and cytokine release syndrome (CRS) [75, 76]. Most infusion-
related events occur within the first 24 hours after beginning administration.  Severe  reactions, 
such as anaphylaxis, angioedema, bronchospasm, hypotension and hypoxia, are infrequent and 
more often associated with mAbs targeted to human proteins or when a nonhuman mAb, such as 
a murine mAb, is used.  The VRC01 mAb is a human mAb that is directed to a viral target rather 
than a host cell target.  Severe CRS has not been reported in such pathogen-directed human mAbs, 
and CRS has not been observed in the human experience with VRC01. With licensed therapeutic 

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mAbs, CRS is managed by temporarily stopping the infusion, administration of histamine blockers 
and restarting the infusion at a slower rate [77]. Delayed allergic reactions to a mAb may include 
a serum sickness type of reaction, which is characterized by urticaria, fever, lymph node 
enlargement, and joint pains.  These symptoms may not appear until several days after the exposure 
to the mAb and are noted to be more common with chimeric types of mAbs [75]. 
There are several FDA-licensed mAbs for which reactions related to the rate of infusion have been 
described.  Some symptoms may be treated by slowing or stopping the infusion. Supportive 
treatment may also be indicated for some signs and symptoms.   
A theoretical risk is that receiving VRC01 might affect the subject’s drug sensitivity profile for 
ARV medications that work through entry or fusion inhibition, or may limit eligibility for some 
future monoclonal antibody treatments. There is also the risk that not all viruses within a swarm 
may be neutralized by VRC01, which could lead to selection of viruses with resistance against this 
agent. The frequent monitoring and strict ART resumption criteria in this study are designed to 
catch breakthrough viremia early and investigators will evaluate for VRC01 resistance in 
volunteers experiencing breathrough during this therapy.  
10.2.3 Risks Related to Blood Drawing  
Blood drawing may cause pain and bruising and may, infrequently, cause a feeling of 
lightheadedness or fainting. Rarely, it may cause infection at the site where the blood is taken.  
10.2.4 Risks Related to Treatment Interruption 
Treatment interruption is not a therapeutic intervention and the possible effects of treatment 
interruption in the setting of volunteers who began ART during early acute HIV infection have not 
been characterized. This protocol includes multiple measures to minimize risk for study 
participants during the period of treatment interruption, including frequent monitoring for viral 
rebound and procedures to initiate ART before HIV viremia reaches levels that may cause 
symptoms or expansion of HIV reservoirs. It is possible, however, that volunteers experiencing 
viral rebound could experience symptoms of acute retroviral syndrome, which can include fever, 
rash, pharyngitis, fatigue, myalgias, arthralgias and lymphadenopathy. It is also possible that 
volunteers may establish or expand reservoirs of HIV infection or develop resistance to certain 
antiretroviral medications, including those used prior to ATI (Appendix I). Volunteers may 
experience an increase in immune activation during ATI.  
If subjects develop viremia, there is a risk of transmitting HIV to sexual partners. All subjects will 
be notified of this risk and advised to use condoms for any sexual contact during participation in 
the study. 
There is a risk that subjects could develop HIV resistant virus after ATI.  Changing all subjects to 
a PI-based ART regimen is designed to minimize this risk.  If HIV resistance develops it could 
potentially lead to a higher risk of treatment failure or death during future ART. To detect and 
address any possible HIV resistance, an HIV genotype test will be done on all patients with 
rebound viremia before restarting ART. 

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10.2.5 Risks Related to Pregnancy 
The possible effects of VRC01 on a fetus or nursing infant are unknown. Since VRC01 is a human 
monoclonal antibody and not a chemotherapeutic agent, traditional toxicology and animal 
reproduction studies are not possible. However, the antibody is directed against a viral protein and 
showed no cross-reactivity with fetal or adult human tissue in preliminary safety studies. 
Furthermore, anti-HIV antibodies are routinely transferred from the mother to the fetus during 
pregnancy without any known adverse affect on the mother or infant [78]. As with the majority of 
IgG antibodies, transfer of anti-HIV antibodies occurs from the mother to the fetus predominantly 
during the third trimester; since VRC01 (T1/2=13.6 days; range 6.76-21.3 days) infusions will be 
stopped if pregnancy is diagnosed, they are unlikely to be present at the time of IgG transfer to the 
fetus [78].  
This evidence suggests that adverse affects to the infant of a mother exposed to VRC01 are 
unlikely, but pregnant women are still conservatively excluded from participation in this phase II 
study of an investigational new agent. Women of reproductive potential must agree to not get 
pregnant during study participation and must use at least one method of effective birth control 
during study participation.  Effective birth control includes not having sex; male or female 
condoms; diaphragm or cervical cap with spermicide; intrauterine device; birth control pills, patch 
or injections; and other prescription methods; or a male partner who has previously undergone a 
vasectomy.   
Women must have a negative pregnancy test before each infusion of study drug and before 
collection of cervicovaginal secretion samples. Women becoming pregnant during the study will 
be referred for obstetric care, reported to the antiviral pregnancy registry and offered enrollment 
in RV 412. Via that protocol, a pregnant woman will be prescribed ART and monitored for 
sustained viral suppression. The outcome of the pregnancy will be documented.   
10.2.6 Risks Related to Possible Breach of Confidentiality 
Loss of confidentiality about HIV status could result in discrimination by family, employers, 
and in the community.  It is also acknwledged that involuntary disclosure of HIV status may result 
in depression and rarely suicide.  Breaching of confidentiality is greatest during enrollment and the 
interviewing stages of the study, and steps have been taken to mitigate that risk. All interviews and 
data collection procedures will take place in private rooms where subjects can neither be seen nor 
heard from the outside. Source documents such as medical records and laboratory reports will be 
coded with only subject ID numbers and will be stored in locked cabinets in the clinic, The clinic 
itself is not accessible to anyone other than study staff and is locked on nights and weekends. The 
electronic database will contain only coded data and is stored and maintained on a password-
protected computer system. 
 
In addition to procedures put in place to assure participant confidentiality, participants will 
not be identified in any reports on this study. Mitigating steps also include that, by design, 
no subject identifying information will be extracted from clinical records. Any copies of case 
report forms and data forms bearing any identifiers will be kept in locked, secured areas. 
Finally, data management security measures are in place at the local site to assure data safety and 
confidentiality. 

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10.2.7 Risks Related to Questionnaires and Neuropsychological Testing 
Subjects will be asked to provide information about their sexual behavior, mood, cognitive 
functioning, and overall mental health.  Some of the questions may make subjects feel 
uncomfortable or cause anxiety.  In order to mitigate risks, subjects reserve the right not to answer 
certain questions.  In addition, study staff are trained to administer questionnaires about sensitive 
topics, recognize signs of adverse psychological impact, and can provide referrals for counseling 
or mental health services if necessary. 
 
10.3 
RISKS RELATED TO OPTIONAL PROCEDURES 
Mucosal Secretion Collection 
Mucosal secretion samples collected in the clinic (rectal sponges, semen, and cervicovaginal cups) 
will be obtained non-invasively.  Semen will be self-collected and for the collection of cervical-
vaginal secretions, women may elect to insert and remove cervical cups themselves, as well.  
Inserting an instrument or collection device into the anus or the vagina may cause discomfort and 
slight irritation. There is no evidence of rectal sponge or cervical cup sampling contributing to risk 
of HIV or other sexually transmitted infection.  For these non-invasive mucosal collections, men 
and women will be asked to refrain from receptive anal or vaginal, intercourse, douching, or 
inserting any product into the rectum or vagina for 3 days prior to the mucosal collection. Men 
will be asked not to masturbate nor ejaculate 3 days prior to semen collection. 
Use of the  for vaginal secretion collection carries the theoretic risk for toxic shock syndrome 
(TSS).  Female subjects who agree to genital secretion collection will be warned of this risk and 
will be advised to use the soft up for no more than 12 hours to decrease the risk.  In addition, they 
will be advised of the symptoms of TSS and to contact the study team immediately if any 
symptoms develop while using the soft cup. 
Colon Biopsy (via Sigmoidoscopy) 
Rectosigmoid biopsies will be performed through a flexible sigmoidoscopy. Brief cramping and 
gas pains may be flet as air iis inserted or as the scope advances. The passing of gas is necessary 
and should be expected after the procedures are terminated. Volunteers may choose to receive 
sedation during the procedure in order to ameliorate the discomfort and anxienty they may feel.  
There may be slight bleeding from the biopsy site, which generally stops spontaneously.  There is 
a remote possibility that a biopsy may result in significant bleeding or even perforation requiring 
emergency medical care. A gastroenterologist will perform this procedure in order to minimize 
these risks.  All volunteers will be counseled to avoid sexual rectal intercourse for 3 days prior to 
and 7 days following biopsy.  
. 
Lymph Node Biopsy 
Excisional inguinal lymph node biopsy will be performed under local anesthesia by a qualified 
surgeon. As with all surgical procedures, there is a risk of scarring, bruising or bleeding at the 

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surgical site; these risks are minimized by the small nature of the incision (approximately 1-2 
centimeters) and by prior clinical and laboratory evaluation to determine any bleeding risks. 
Subjects may experience some discomfort following the procedure despite use of local anesthesia; 
for subjects who complain of any subsequent discomfort, additional analgesia will be made 
available.  
There is a possibility of seroma formation at the biopsy site, which may require subsequent 
drainage or further management, or sensory nerve injury during the procedure which could result 
in temporary or permanent local reduction in feeling. Surgical site infection is a possible 
complication of any procedure involving an incision, however the risk is low.  There is a possibility 
of seroma formation at the biopsy site, which may require subsequent drainage or further 
management, or sensory nerve injury during the procedure which could result in temporary or 
permanent local reduction in feeling. There is a possibility of developing lymphedema, particularly 
with multiple lymph node biopsies. To minimize the risk of lymphedema, volunteers will be 
limited to a maximum of 4 inguinal lymph node biopsies over their lifetime in all studies, 
consistent with the report from Skarda et al in which a similar population of HIV-infected subjects 
underwent a mean of 3.1 biopsies each.[79] Surgical site infection is a possible complication of 
any procedure involving an incision; Skarda et al  reported a single infection out of 137 sterile 
asymptomatic inguinal lymph node biopsies, occurring in an individual whose wound dehisced 
following strenuous activity several days after biopsy and resulting in an overall infection rate of 
0.7%. They report an overall complication rate of 5%, The non-infectious complications were 
universally local and resolved completely with minimal medical management; they included two 
postoperative hematomas, a dorsal vein thrombosis with associated epididymitis (which may not 
have been related to the procedure) and a lymphocoele.  
Finally, there is the unlikely possibility that the procedure will be unsuccessful and no lymph node 
will be recovered. 
Leukapheresis 
Adverse reactions to leukapheresis procedure are rare and include vaso-vagal episodes related to 
needle insertions and transient volume shifts, peri-oral paresthesias, chills, nausea, and heartburn 
cause by the citrate anticoagulant used during the procedure.  Vaso-vagal reactions are handled by 
postural manipulation and fluid administration. Volunteers will be observed closely by an 
experienced technician during the procedure. Citrate reations are usually relieved by slowing the 
rate of the anticoagulant infusion and by administering oral calcium carbonate tablets. Seizures 
and allergic reactions are very rare possible reactions. 
Lumbar Puncture 
The risks of lumbar puncture include local soreness at the site of needle entry. There is a risk of 
headache or decreased blood pressure from removing the small amount of fluid or leaking of 
cerebral spinal fluid after the procedure.  About 1 in 10 people will experience a headache 
following lumbar puncture. There is a small risk of infection. There is also a very small risk of 
damage to nerves in the lumbar spinal roots after the procedure, which could cause pain, numbness, 
or loss of sensation to the legs. In order to reduce side effects of the lumbar puncture, the volunteers 
will be asked to remain lying flat for about an hour after the procedure and be given fluid to drink 
after the procedure. A band-aid will be placed on the skin where the needle went in and the 
volunteer will be asked to remove it the next day and tell the study doctor right away if any redness 

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or tenderness is present. The investigators will ask the volunteers about history of any allergies to 
anesthetics and will not perform lumbar puncture is any volunteer with such history. 
MRI/MRS/DTI 
Because MRI/MRS/DTI is a medical device which uses a magnet, any metal object placed in the 
strong magnetic field of the MRI/MRS/DTI scanner will be pulled to it and may cause injury. In 
order to avoid this, the volunteers will be asked to leave as many metal objects as possible at home, 
and they will be asked to remove all metallic objects including jewelry, dentures, glasses, watches, 
and artificial limbs before the MRI/MRS/DTI. Gadolinium will not be used for research purposes. 
The volunteers may feel claustrophobic (fear of being in a small, closed space) or anxious. If this 
is likely to happen, the investigators can give the volunteers a sedative such as lorazepam to take 
by mouth. 
10.4 
BENEFITS 
Volunteers should expect no direct benefit from participation in this study and VRC01 may not 
ultimately be developed for the treatment of HIV. This study explores the safety, 
pharmacokinetics, and antiviral effects of VRC01 given during ATI in patients who were treated 
with ART during early acute HIV infection. It is a proof of concept study that may help guide the 
development of VRC01 or other antibody-based therapies. This represents a novel paradigm for 
the treatment of HIV, the exploration of which has the potential to benefit society and shift research 
agendas related to achieving a functional cure of HIV.  
10.5 
INFORMED CONSENT 
The study informed consent describes the investigational product and placebo to be used and all 
aspects involved in protocol participation. A properly executed written site specific informed 
consent based on the template provided here, in compliance with the Declaration of Helsinki, 
guidelines of the Council of International Organization of Medical Sciences (CIOMS), the 
Belmont Report, the U.S. Code of Federal Regulations 21 CFR 50, must be obtained from each 
subject prior to entering the subject into trial or prior to performing any unusual or non routine 
procedure that involves risk to the subject. The signed informed consent form will be maintained 
in the subject’s record file, and a copy of the signed consent form will be given to the subject to 
keep.  Before a subject’s participation in the study, it is the investigator’s responsibility to obtain 
this written informed consent from the subject, after adequate explanation of the aims, methods, 
anticipated benefits, and potential hazards of the study and before any protocol-specific procedures 
or study medications are administered. 
For illiterate subjects, a thumbprint will be substituted for signature, and their informed 
consent will be witnessed by an adult who is not a member of the research study staff. 
Volunteers may take as much time as needed to decide if he/she wants to participate and may 
share the consent form with family members or friends prior to agreeing to participate. 

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10.5.1 Test of Understanding 
The procedures for informed consent include a test of understanding. The test of understanding 
will be a “one-on-one” review with the volunteer by a member of the study team. To pass, the 
volunteer must answer 90% or 9 out of 10 of the questions correctly. If the volunteer is unable to 
do so, he or she will be given 3 opportunities to repeat the test of understanding. If after 3 attempts 
to pass the test of understanding, the volunteer is unable to do so, the volunteer will become 
ineligible for study participation. 
Volunteers who pass the test of understanding and have given written informed consent will be 
enrolled in the study.  
10.6 
LANGUAGE 
The ICF and other study documents given to participants will be translated into Thai. 
10.7 
COMPENSATION 
Participants will be compensated for time and inconvenience in accordance with the standards and 
legal obligations for compensation.  Any applicable guidelines by IRBs/ECs for compensation of 
research subjects will be sought and followed. 
There may be compensation for lost time, travel expenses and inconvenience, for each scheduled 
visit.  Any applicable guidelines by IRBs/ECs for compensation will be sought and followed.   
10.8 
DOD RESEARCH MONITOR 
The DoD Research Monitor is required to review all unanticipated problems involving risks to 
participants or others, serious adverse event (SAE) reports, and all deaths. The DoD Research 
Monitor will provide an unbiased written report of all unanticipated problems involving risks to 
participants or others, and related SAEs and deaths, promptly within 10 working days to the 
WRAIR 
IRB 
by 
phone 
(301) 
319-9940, 
or 
by 
email 
(usarmy.detrick.medcom-
wrair.mbx.hspb@mail.mil ), by facsimile (301) 319-9961 or at the following address: Walter Reed 
Army Institute of Research, ATTN: Human Subjects Protection Branch, 503 Robert Grant Ave., 
Silver Spring, MD 20910.  All DoD Research Monitor’s reports for unrelated SAEs and deaths 
should be kept with the corresponding SAE reports at the study site. 
The WRAIR HSPB will submit copies of these reports to the USAMRMC ORP HRPO as per SOP 
UWZ-C-636. The DoD Research Monitor at a minimum must comment on the outcomes of the 
event or problem and in case of a serious adverse event or death, comment on the relationship to 
participation in the study. The DoD Research Monitor must also indicate  whether he/she concurs 
with the details of the report provided by the principal investigator. 
The DoD Research Monitor or their approved alternate should review all initial, follow up and 
final reports for SAEs, unanticipated problems involving risks to participants or others, and all 
participant deaths in a timely manner, and provide their own independent report. 

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The DoD research monitor will also: 
1. Discuss research progress with the PI, interview participants, consult on individual cases, 
or evaluate suspected adverse reaction reports on behalf of the IRB. 
2. Perform at the direction of the IRB, oversight functions (e.g., observe recruitment, 
enrollment procedures, and the consent process for individuals, groups or units; oversee 
study interventions and interactions; review monitoring plans and UPIRTSO reports; and 
oversee data matching, data collection and analysis) 
3. Promptly report discrepancies or problems to the IRB. 
4. Have the authority to stop a research study in progress, remove individual participants from 
a study, and take whatever steps are necessary to protect the safety and well-being of 
research participants until the  IRB can assess the research monitor’s report. 
10.9 
PARTICIPANT CONFIDENTIALITY 
The PI will maintain research records of participant’s participation at the site for this study.  All 
participants will receive study numbers that are known only to the investigators and clinic staff.  
Clinical tests will be identified by study number and the specimen bag will be identified by study 
number and bar code only.  Clinical and research records may be reviewed by the representative 
of the DAIDS, USAMRMC, WRAIR, representatives of the USAMRMC ORP HRPO, 
representatives of the FDA, OHRP, the product and device providers,  and other regulatory 
agencies as part of their responsibilities for insuring the protection of research participants.    
Every effort will be made to keep the records as confidential as possible within the limits of the 
law.  All data and medical information obtained about participants, as individuals will be 
considered privileged and held in confidence. Research and clinical information relating to 
participants will be shared with other investigators and the scientific community through 
presentation or publication; however, participants will NOT be identified by name or social 
security number. Electronic data will be stored at least as long as the IND remains open. 
10.10 INSTITUTIONAL REVIEW BOARD 
A copy of the protocol, proposed informed consent form, other written participant information, 
and any proposed advertising material will be submitted to the appropriate ethical and scientific 
review committees in each country for review and approval. In addition, the protocol will undergo 
review and approval by both the WRAIR IRB and the USAMRMC ORP at Medical Research and 
Materiel Command, U.S. Army (MRMC).  
10.11 FUTURE USE AND STORAGE OF BLOOD SAMPLES 
Each study participant will be asked to separately, and voluntarily consent to storage of their blood 
samples for other research studies that may be done after this study is completed. As stated above, 
the sample will be labeled with the bar code of the subject ID that can be linked to their study 
information. In case the volunteer is unwilling to have their blood samples stored for future use, 

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they can consent to participate in this study only, without having their blood samples stored for 
future testing. In this case, their blood samples will be destroyed after all the tests specified for this 
study have been concluded. 
Biological samples will be stored at the Thai Red Cross AIDS Research Centre in Bangkok, 
Thailand; the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand; and/or 
the U.S. Military HIV Research Program in Bethesda, MD, USA. 
All samples for which consent has been obtained and for which additional material is available 
after study specified testing is complete will be stored for future testing at the site. However, 
WRAIR IRB and Chulalongkorn University IRB approval will be sought before any such samples 
are used for analysis not specified in the protocol or a protocol amendment approved by the IRB. 
All samples belong to the site from which they were obtained and MHRP. 
10.12 STUDY DOCUMENTATION AND STORAGE  
Source documents are original documents, data, and records from which the subject’s data are 
obtained. These include but are not limited to hospital records, clinical and office charts, laboratory 
and pharmacy records, diaries, microfiches, radiographs, and correspondence.  
The investigator and staff are responsible for ensuring maintenance of a comprehensive and 
centralized filing system of all study-related (essential) documentation, suitable for inspection at 
any time by representatives from the WRAIR, MRMC, DAIDS, FDA, and/or applicable regulatory 
authorities. 

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11.0 ADMINISTRATIVE AND LEGAL PROCEDURES 
11.1 
PROTOCOL DEVIATION REPORTING 
All major protocol deviations that adversely affect the safety or rights of a subject or scientific 
integrity of the study, will be reported to the WRAIR IRB within 48 hours and written reports 
should be submitted within 10 working days.  The contact information for the WRAIR IRB is as 
follows: 
Director, Human Subjects Protection Branch 
503 Robert Grant Avenue 
Silver Spring, MD 20910 
Telephone: 301-319-9940 
Fax: 301-319-9961 
Email: usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil 
 
All protocol deviations occurring within the reporting period should be summarized in the 
continuing review reports that are submitted to the WRAIR IRB. Protocol deviations will be 
reported to the USAMRMC ORP HRPO by the HSPB as per UWZ-C-636. 
 
11.2 
PROTOCOL MODIFICATIONS 
Amendments to the protocol will be made only after consultation and agreement between DAIDS, 
the protocol chair, and the principal investigators. All protocol modifications (including but not 
limited to changes in the principal investigator, inclusion/exclusion criteria, number of participants 
to be enrolled study sites, or procedures) must be submitted as a written amendment to DAIDS,  
Chulalongkorn University IRB, and the WRAIR IRB for approval before implementation of the 
amendment. The WRAIR HSPB will submit protocol amendments and modifications to the 
USAMRMC ORP HRPO as per UWZ-C-636.   
Modifications or updates to the investigational brochures (IBs) will also be submitted as protocol 
amendments to the ERCs/IRBs for review and approval. 
The Informed Consent Form must be revised to concur with any significant amendment that 
directly affects volunteers, and must also be reviewed and approved with the amendment.  New 
volunteers enrolled in the study will be consented with the most recent approved consent form.  
Volunteers already enrolled in the study will be informed about the revision and, depending on the 
impact of the amendment, may be asked to re consent.  This may be accomplished by repeating 
the consent process with the revised consent form with attention given to the changes, or it may 
be done using an addendum consent that states the revision or new information.  The new 
document must be signed, placed in the study record, and a copy given to the volunteer. 
Prior to implementation of this protocol, and any subsequent full version amendments, the protocol 
and the protocol consent form(s) must be approved, as appropriate, by the Chulalongkorn 

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University institutional review board (IRB)/ethics committee (EC) and any other applicable 
regulatory entity (RE).  Upon receiving final approval, the site will submit all required protocol 
registration documents to the DAIDS Protocol Registration Office (DAIDS PRO) at the 
Regulatory Support Center (RSC).  The DAIDS PRO will review the submitted protocol 
registration packet to ensure that all of the required documents have been received. 
Informed consent forms (ICFs) WILL be reviewed and approved by the DAIDS PRO and the site 
will receive an Initial Registration Notification from the DAIDS PRO that indicates successful 
completion of the protocol registration process. A copy of the Initial Registration Notification 
should be retained in the site's regulatory files. 
Upon receiving final IRB/EC and any other applicable RE approval(s) for an amendment, the study 
site should implement the amendment immediately.  The site is required to submit an amendment 
registration packet to the DAIDS PRO at the RSC.   The DAIDS PRO will review the submitted 
protocol registration packet to ensure that all the required documents have been received.  ICF(s) 
WILL NOT be reviewed and approved by the DAIDS PRO and the site will receive an Amendment 
Registration Notification when the DAIDS PRO receives a complete registration packet. A copy 
of the Amendment Registration Notification should be retained in the site's regulatory files. 
For additional information on the protocol registration process and specific documents required 
for initial and amendment registrations, refer to the current version of the DAIDS Protocol 
Registration Manual. 
A list of proposed modifications or amendments to the protocol and an explanation of the need for 
these modifications will be submitted, along with a revised protocol incorporating the 
modifications.  The only exception occurs when the investigator considers that a study 
participants’s safety is compromised without immediate action.  In these circumstances, immediate 
approval of the chairman of the IRB must be sought, and the investigator should inform DAIDS 
and the IRB within five working days after the emergency occurred. As previously mentioned, all 
study amendments will be submitted as a written amendment to DAIDS for possible CSRC review 
and regulatory submission to the Chulalongkorn University IRB, and WRAIR.  In accordance with 
21 CFR 312.30 (b) any change in a Phase 1 protocol that significantly affects the safety of subjects 
will be submitted to the FDA. 
11.3 
CONTINUING REVIEWS/CLOSEOUT REPORT 
A continuing review report (CRR) will be submitted in the proper format to all ERCs/IRBs prior 
to the date determined by the IRBs. This report will also be submitted to the Thai FDA. If the 
continuing review is not approved by the Chulalongkorn University ERC/IRB and WRAIR IRB 
by the anniversary date, all protocol activities must stop at that site until such time as the approval 
is obtained.  A copy of the approved CRR and Chulalongkorn University IRB approval 
notifications will be submitted to the WRAIR HSPB as soon as these documents become available. 
After all study related activities, including data analysis, are completed a closeout report will be 
submitted as required to the IRBs and Thai FDA. A copy of the approved closeout report and 
Chulalongkorn University IRB approval notifications will be submitted to the WRAIR HSPB as 
soon as these documents become available.  

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11.4 
VOLUNTEER REGISTRY DATABASE 
It is the policy of the USAMRMC that Volunteer Registry Data Sheets are completed on all 
volunteers participating in greater than minimal risk research for entry into the Command’s 
Volunteer Registry Database. Ordinarily this information would include the individual’s unique 
identifier (e.g. SSN in the U.S.A.), study name and dates. But because many countries do not have 
a national identification system that would uniquely identify each person in the country, the 
Volunteer Registry Data Sheets will collect the following data on the volunteers:  
names (first and last name) 
date of birth, home district 
study name and study dates 
The intent of the database is two-fold: first, to readily answer questions concerning an individual’s 
participation in research sponsored by USAMRMC; and second, to ensure that the USAMRMC 
can exercise its obligation to ensure research volunteers are adequately warned (duty to warn) of 
risks and to provide new information as it becomes available.  The information will be stored at 
AFRIMS for a minimum of 75 years.  In countries other than the U.S., social security numbers do 
not exist and cannot be collected; all other data can.  If available, country-specific identity numbers 
may be used. This database will not be used for research. 
11.5 
POLICY REGARDING RESEARCH-RELATED INJURIES 
The US DoD and DAIDS/NIAID/NIH are funding this protocol. As stated in the consent form, 
participants who experience illness or injury arising from participation in the study will receive 
medical care for such illness or injury with costs for such care provided by a limited set-aside fund 
that is used for HJF/MHRP studies in Thailand and a clinical trials medical insurance policy that 
will be obtained by HJF/MHRP. While we anticipate the combination of the set-aside fund and the 
insurance policy is more than enough to pay for the research related injury medical care cost 
associated with this study, there is a limit to the amount of coverage available. Other than medical 
care, and other payments as stated in the consent form, there is no other compensation available 
from this research study. 
 
11.6 
USE OF INFORMATION AND PUBLICATION 
It is understood by the investigator that the information generated in this study may be used in 
connection with the development of the product and therefore may be disclosed to government 
agencies in various countries. To allow for the use of information derived from the study, it is 
understood that the investigator is obliged to provide DAIDS with complete test results, all study 
data, and access to all study records.  
WRAIR recognizes the importance of communicating medical study data and therefore encourages 
their publication in reputable scientific journals and at seminars or conferences.  Any results of 
medical investigations and or publication/lecture/manuscripts based thereon, shall be exchanged 
and discussed by the investigator, and the USAMRMC 60 days prior to submission for publication 
or presentation. 

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Results from investigations shall not be made available to any third party by the investigating team 
outside the publication procedure as outlined previously.  WRAIR will not quote from publications 
by investigators in its scientific information and/or promotional material without full 
acknowledgment of the source (i.e., author and reference).  All publications written by WRAIR 
investigators must be reviewed and approved by the WRAIR Office of Research Technology and 
Applications (ORTA). 

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12.0 CONDUCT OF THE RESEARCH STUDY 
This research study will be conducted in accordance with GCP, ICH guidelines, DOD Directive 
3216.2, the Declaration of Helsinki, the Belmont Report, the U.S. Code of Federal Regulations 21 
CFR 312, 812, 50 and 56, 32 CFR 219, 45 CFR 46, and all applicable local laws and regulations.  
12.1 
 REGULATORY AUDITS 
The knowledge of any pending compliance inspection/visit by the US FDA, OHRP, or other 
government agency concerning clinical investigation or research, the issuance of Inspection 
Reports, FDA Form 483, warning letters or actions taken by any regulatory agencies including 
legal or medical actions and any instances of serious or continuing noncompliance with the 
regulations or requirements will be reported immediately to DAIDS and the WRAIR HSPB.  The 
WRAIR HSPB will report knowledge of any pending inspections/audits by regulatory agencies to 
the USAMRMC ORP HRPO as per UWZ-C-636. 
12.2 
DAIDS STUDY MONITORING 
Site visits by study monitors will be made in accordance with DAIDS policy to monitor the 
following: study operations, the quality of data collected in the research records, the accuracy and 
timeliness of data entered in the database, and to determine that all process and regulatory 
requirements are met.  
Site investigators will allow the study monitors, DAIDS, the IRB/Ethical Review Committee 
(ERCs), MRMC, and the FDA to inspect study documents (e.g., consent forms, drug distribution 
forms, case report forms), and pertinent hospital or clinic records for confirmation of the study 
data.  
Study data will be closed and final after data cleaning activities are completed and resolutions 
have been documented. 

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13.0 
RELEVANCE 
 
13.1 
MILITARY RELEVANCE 
 
The HIV pandemic currently stands as one of the greatest threats to global public health. An 
estimated 35 million people are living with HIV/AIDS and 5700 new HIV infections are occurring 
in the world each day, the majority of which require life-saving ART. Recent advances in efforts 
to prevent and treat HIV disease are encouraging, but AIDS is still among the leading causes of 
death in the developing world; areas that are already burdened with lowered life expectancy and 
reduced economic growth. HIV/AIDS, therefore, exacerbates the disintegration of social and 
political cohesion in these affected areas. These conditions, in turn, affect the stability of nations 
and thus pose a risk to global security.  
The military relevance of HIV has, therefore, been recognized from the very beginning of the 
pandemic. In 1985, the U.S. military recognized the emerging HIV-1 epidemic as a new threat to 
U.S. and allied forces worldwide. Soon after, at the height of the HIV global pandemic, the United 
States Congress mandated the establishment of the U.S. Military HIV Research Program (MHRP) 
to develop effective prevention measures to combat the rise of HIV. Then, in 2001, the DoD Report 
on Biological Warfare Defense Vaccine Research and Development identified HIV as the 4th 
greatest infectious disease threat to DoD forces. Even as the global incidence of HIV has fallen in 
the past decade, the 2002, 2006 and 2010 President’s National Security Strategy plans have 
continued to highlight HIV as a persistent threat to national security as it continues to contribute 
to regional instability and, thus, affect military force readiness and deployment[80]. The US 
Department of Army Headquarters designated HIV vaccine development as an Army Technology 
Objective (ATO), a status reserved for the highest priority science and technology efforts.  
HIV also poses a direct health risk to military personnel through multiple modes of transmission. 
Bloodborne transmission is of particular concern given the potential contamination of the combat 
theater blood supply. The “walking blood bank,” which draws upon donated blood supplies from 
local populations, was used more than 21,000 times in the recent operations in Iraq and 
Afghanistan. In order to provide life-saving blood and plasma products in an expedient way for 
the battlefield, HIV screening cannot always be screened according to standard U.S. medical 
practice.  
In 2013, there were over 340 incident HIV infections in the U.S. military [81]. Currently, the 
cost to the US government for the treatment and care of its 1500 HIV-infected active service 
members ranges from 21 to 54 million dollars per year with an estimated lifetime accrued cost of 
$418 million [82, 83] . The total lifetime cost to the US government of the approximately 5000 
active and non-active infected service members identified since active force-wide screening was 
initiated is $8-$10 billion. Thus, in addition to identifying and implementing effective methods 
for HIV prevention, strategies to cure the disease will greatly benefit HIV-infected personnel, 
eliminate a potential source for HIV transmission and relieve an enormous health care burden 
necessitated by lifetime ART. 
 
13.2 
THAI RELEVANCE 
Thailand has the highest adult HIV prevalence in Asia, reported as 1.2% of the adult population 
living with HIV in 2012 [84]. In the early 1990s, Thailand was facing a generalized HIV epidemic 

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with HIV prevalence peaking at 4.0% among male military recruits and 2.6% among women 
attending antenatal clinics.  In 1991 alone, over 160,000 new HIV infections were estimated to 
have occurred [85] . In the past few years, it is estimated that the rate of new infections has fallen 
dramatically to approximately 8,000 per year [85]. Despite the great success in HIV prevention, 
Thailand faces an ongoing challenge in providing ART to the large number of Thai people living 
with HIV infection (PLHIV). Almost uniquely among developing countries, Thailand provides 
ART with entirely domestic funding and does not rely on international donors.  
In 2014 Thailand revised its national HIV treatment guidelines to recommend ART for all PLHIV 
[86]. Immediate ART along with increasing coverage of HIV testing among key populations are 
key strategies currently used by the country aiming to end its AIDS epidemic by 2030.  This change 
will increase the number of Thai citizens eligible for ART from 246,000 to 407,000 in 2015, an 
increase of 65% [87]. An increase in ART provision of this magnitude will challenge the Thai 
health system to provide the clinics and health care workers to manage the increased case load of 
ART patients as well as finding the financial resources to pay for the additional medications 
required. 
This study will contribute to the national HIV treatment program in Thailand by potentially 
demonstrating the therapeutic efficacy of VRC01 monoclonal antibody infusions in lieu of ART 
in selected patients who started ART during acute infection. If a subset of patients remains 
clinically and immunologically stable off ART and after completing a course of VRC01 infusions, 
this could result in substantial financial savings to public health systems. In addition, all of the 
patients who could be recruited for the study are Thai citizens who acquired HIV infection in 
Thailand, which provides direct relevance to the HIV epidemic in the country. 
 

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14.0 PRINCIPAL INVESTIGATOR AGREEMENT:  
1. I agree to follow this protocol version as approved by the IRBs/ERCs.  
2. I will conduct the study in accordance with applicable IRB/ERC requirements, Federal 
regulations, and state and local laws to maintain the protection of the rights and welfare 
of study participants.  
3. I certify that I, and the study staff, have received the requisite training to conduct this 
research protocol.  
4. I will not modify the protocol without first obtaining an IRB/ERC approved amendment 
and new protocol version unless it is necessary to protect the health and welfare of study 
participants.  
5. I have read and understand the information in the Investigators’ Brochure (or 
Manufacturer’s Brochure) regarding the risks and potential benefits. I agree to conduct 
the protocol in accordance with Good Clinical Practices (ICH-GCP), the applicable 
ethical principles, the Statement of Investigator (Form FDA 1572), and with local 
regulatory requirements. In accordance with the FDA Modernization Act, I will ensure 
the registration of the trial on the www.clinicaltrials.gov website.  
6. In accordance with Command Policy 2008-35, I will ensure that the Commanding 
General receives a pre-brief (or Executive Summary) and approves the study prior to 
execution.  
7. I will ensure that the data (and/or specimens) are maintained in accordance with the data 
(and/or specimen) disposition outlined in the protocol. Any modifications to this plan 
should first be reviewed and approved by the applicable IRBs/ERCs.   
8. I will promptly report changes to the research or unanticipated problems to the WRAIR 
IRB immediately via the WRAIR Human Subjects Protection Branch at (301) 319-9940 
(during duty hours) or to the usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil and 
submit a written report within 10 working days of knowledge of the event.  
9. I will prepare continuing review reports at an interval established by the IRB/ERC, and a 
study closure report when all research activities are completed.  
10. I will immediately report to the WRAIR Human Subjects Protection Branch knowledge 
of any pending compliance inspection by any outside governmental agency.  

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11. I agree to maintain adequate and accurate records in accordance with IRB policies, 
Federal, state and local laws and regulations.  
________________________________ 
 
____________________ 
RV 397 Protocol Chair 
 
 
 
Date (DD/MM/YYYY) 
________________________________ 
 
____________________ 
RV 397 PI 
 
 
 
 
 
Date (DD/MM/YYYY) 
 
 

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APPENDIX I: CASE DEFINITION FOR ACUTE 
RETROVIRAL SYNDROME (ARS) 
Case definition must include all of the following: 
·        Occurs within 30 days after documented rise in plasma HIV-1 RNA of > 1 log10 or 
to > 1,000 copies/mL 
·        Occurs within 60 days after discontinuation of ART 
·        Documented fever (temperature >38.5°C) 
·        At least two major criteria 
·        At least two minor criteria 
·        No other cause for signs and symptoms identified 
 
Major criteria (must be present for >7 days): 
·        Pharyngitis 
·        Fatigue 
·        Morbilliform rash 
·        Myalgia/arthralgia 
·        Lymphadenopathy 
·        Subjective fever as reported by subject (may be intermittent) 
 
Minor criteria (must be present for >7 days): 
·        Headache 
·        Nausea/vomiting 
·        Diarrhea 
·        Mucocutaneous ulceration (oral, genital, and/or anorectal) 
·        Meningismus/aseptic meningitis 
·        Night sweats 
·        Thrombocytopenia (platelets <150,000) 
·        Leukopenia (WBC <4,000) 
·        Malaise 
·        Abdominal pain 
·        Weight loss (loss of >5% of body weight) 
 

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APPENDIX II:  SCHEDULE OF EVALUATIONS 
 

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Procedure/Study Week1 
-6 
-4 
-2 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collection of Contact 
Information 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
PI Substition3 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC01/Placebo Infusion 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Interruption of ART 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
History 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Physical Exam 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Neuropsychological exam 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Control and attention testing 
X 
 
 
X 
X 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Plasma NNRTI level4 
 
4 
4 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Qualitative HIV RNA 
 
 
 
X 
X 
 
 
 
 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
Twice Weekly HIV RNA5 
 
 
 
* 
* 
X 
X 
X 
X 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
HIV RNA PCR  
6 
 
 
6 
 
3 
6 
 
 
6 
 
 
3 
 
 
6 
 
 
3 
 
 
6 
CD4/CD8 Count  
NB 
 
 
NB 
 
 
NB 
 
 
NB 
 
 
 
 
 
NB 
 
 
 
 
 
NB 
Complete Blood Count  
NB 
 
 
NB 
 
 
NB 
 
 
NB 
 
 
 
 
 
NB 
 
 
 
 
 
NB 
Liver Enzymes  
 
 
 
6 
 
 
4 
 
 
4 
 
 
 
 
 
4 
 
 
 
 
 
4 
Creatinine  
 
 
 
NB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lipids  
 
 
 
NB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Syphilis, HBV, HCV screen  
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine HCG6 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Urinalysis 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Integrated HIV DNA, Total HIV 
DNA, 2LTR Circles  
8.513 
 
 
8.5 
 
8.5 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
Single Copy HIV RNA7  
 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
QVOA7  
 
 
 
NB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TILDA7  
 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
TULDA8  
 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
 
 
8.5 
PBMC/Plasma Collection  
  
  
  
51 
17 
17 
25.5 
  
  
25.5 
  
  
25.5 
  
  
25.5 
  
  
25.5 
  
  
25.5 
Plasma collection (EDTA) 
 
 
 
3 
3 
3 
3 
 
 
3 
 
 
3 
 
 
3 
 
 
3 
 
 
3 
Serum collection  
 
 
 
4 
4 
4 
4 
 
 
4 
 
 
4 
 
 
4 
 
 
4 
 
 
4 
HIV Genotype9  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EKG 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Leukapheresis10* 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Mucosal Secretion 
Collection11* 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Colon Biopsy* 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Inguinal Lymph Node 
Biopsy* 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Lumbar Puncture12* 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Brain MRI/MRS/DTI* 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Daily Volume 
18.5 
4 
4 
108 
24 
35.5 
76.5 
0 
0 
76.5 
0 
0 
69.5 
0 
0 
76.5 
0 
0 
69.5 
0 
0 
76.5 
Cumulative Volume 
18.5 
22.5 
26.5 
134.5 
158.5 
194 
270.5 
270.5 
270.5 
347 
347 
347 
416.5 
416.5 
416.5 
493 
493 
493 
562.5 
562.5 
562.5 
639 
12week cumulative volume 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
358.5 
334.5 
299 
292 
292 
292 
292 

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390 
 
Procedure/Study Week1 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
34 
36 
38 
40 
42 
44 
46 
482 
Visit Number 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
36 
37 
38 
39 
40 
41 
42 
43 
44 
Screening 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collection of Contact 
Information 
 
 
X 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
PI Substition3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC01/Placebo Infusion 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Interruption of ART 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
History 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Physical Exam 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Neuropsychological exam 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Control and attention testing 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Plasma NNRTI level4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Qualitative HIV RNA5 
X 
X 
 
X 
X 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Twice Weekly HIV RNA5 
* 
* 
* 
* 
* 
* 
* 
X 
X 
X 
X 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
 
HIV RNA PCR  
 
 
3 
 
 
6 
 
3 
 
6 
 
3 
 
6 
 
6 
 
6 
 
6 
 
6 
CD4/CD8 Count  
 
 
 
 
 
NB 
 
 
 
NB 
 
 
 
NB 
 
NB 
 
NB 
 
NB 
 
NB 
Complete Blood Count  
 
 
 
 
 
NB 
 
 
 
 
 
 
 
 
 
NB 
 
 
 
 
 
NB 
Liver Enzymes  
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
6 
Creatinine  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NB 
Lipids  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NB 
Syphilis, HBV, HCV screen  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NB 
Urine HCG6 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
Urinalysis 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Integrated HIV DNA, Total HIV 
DNA, 2LTR Circles  
 
 
8.5 
 
 
8.5 
 
 
 
 
 
 
 
8.5 
 
 
 
8.5 
 
 
 
8.5 
Single Copy HIV RNA7  
 
 
8.5 
 
 
8.5 
 
 
 
8.5 
 
 
 
8.5 
 
8.5 
 
8.5 
 
8.5 
 
8.5 
QVOA7  
  
 
 
  
  
NB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NB 
TILDA7  
  
 
8.5 
  
  
8.5 
 
 
 
 
 
 
 
 
 
 
 
8.5 
 
 
 
8.5 
TULDA8  
  
 
8.5 
  
  
8.5 
 
 
 
 
 
 
 
 
 
 
 
8.5 
 
 
 
8.5 
PBMC/Plasma Collection  
  
  
25.5 
  
  
51 
  
25.5 
  
25.5 
  
25.5 
  
25.5 
  
25.5 
  
25.5 
  
25.5 
  
51 
HIV Genotype9  
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.5 
Chest X-ray 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasma collection (EDTA) 
 
 
3** 
 
 
3** 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Serum collection  
 
 
4** 
 
 
4** 
 
  
  
4 
  
4 
  
4 
  
4 
  
4 
  
4 
  
4 
EKG 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Leukapheresis10* 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional Mucosal Secretion 
Collection11* 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional Colon Biopsy* 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional Inguinal Lymph Node 
Biopsy* 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional Lumbar Puncture12* 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional Brain MRI/MRS/DTI* 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 

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Daily Volume 
0 
0 
69.5 
0 
0 
98 
0 
28.5 
0 
44 
0 
32.5 
0 
52.5 
0 
48 
0 
69.5 
0 
44 
0 
109.5 
Cumulative Volume 
639 
639 
708.5 
708.5 
708.5 
806.5 
806.5 
835 
835 
879 
879 
911.5 
911.5 
964 
964 
1012 
1012 
1081.5 
1081.5 
1125.5 
1125.5 
1235 
12 week cumulative volume 
292 
292 
292 
292 
292 
313.5 
313.5 
342 
272.5 
316.5 
316.5 
272.5 
272.5 
325 
255.5 
205.5 
177 
202.5 
170 
161.5 
161.5 
223 
 
This Schedule of Evaluations summarizes the required and optional evaluations to be performed at each scheduled study visit. Blood 
volumes (mL) associated with each evaluation are presented. Evaluations that require no blood collection are marked with an “X” at 
the study visits at which they are performed. Evaluations that will be performed using blood already drawn for other tests on the SOE 
for that visit are marked “NB” (no additional blood required). Daily, cumulative, and 12-week cumulative volumes of blood collection 
are shown. Blood collection volumes may be reduced for volunteers weighing <50 kg.  
 
1 Study procedures for each visit may be performed on different days depending on scheduling for mandatory and optional procedures, within pre-specified allowable time windows (± 3 days for 
mandatory procedures during study weeks 0-36 and ± 1 week for all other visits; ± 12 weeks for optional procedures).  
2 The duration of follow-up may vary among subjects depending on time to rebound viremia or other criteria for the resumption of ART. There is no minimum time in this study. For subjects whose 
study duration is less than 48 weeks, procedures listed for end of study under “Study Week 48” will be performed at the last study visit.  
3 PI substitution will be performed only for participants prescribed an NNRTI at the time of enrollment. 
4 Plasma NNRTI level will be scheduled only for participants prescribed an NNRTI at the time of enrollment and will occur at the time of NNRTI discontinuation, and 2 and 4 weeks following 
discontinuation. ART blood levels (NNRTI or other drugs) will be checked on all subjects who are virologically suppressed at week 24 in order to monitor for possible ART use. NNRTI and other 
ART levels may be checked at additional time points at the discretion of investigators. 
5 HIV-1 RNA VL will be performed twice per week from weeks 2 until week 6 and from week 26 until week 30 either quantitatively using a venous blood sample (3mL) or qualitatively using a small 
blood volume collection (0.6mL). Positive qualitative samples will be rechecked using the quantitative method. Participants with detectable viremia (>50 copies/mL) will be checked every 3 days. 
Once ART is resumed, HIV-1 RNA VL will be checked every 4 weeks until the result is undetectable (<50 copies/mL). Willing participants may optionally present for twice weekly HIV RNA testing 
at any time throughout the study. Small blood volume collection for this assay, performed via finger stick or venous sampling, contributes negligible additional volume to the reported daily total 
volumes. 
6 Urine HCG (pregnancy test) will be done only on females of childbearing age.   
7 Single copy HIV RNA, QVOA (quantitative viral outgrowth assay), and TILDA (tat/rev induced limiting dilution assay) will be performed only if plasma HIV RNA <50 copies/mL and adequate blood 
sample is available. 
8 TULDA (tat/rev uninduced limiting dilution assay) will be performed only if plasma HIV RNA >1000 copies/mL. 
9 HIV genotype will only be performed at time of reinitiating ART, either on plasma or pro-viral DNA, if levels are sufficient to allow amplification. 
10 Leukapheresis will be performed at select visits to collect PBMC and plasma in non-pregnant subjects who provide separate informed consent. Subjects who wish not to have leukapheresis performed 
will undergo phlebotomy for PBMC/plasma collection. The amount of blood drawn will be the same for either procedure.  
11 Mucosal secretion collection includes semen (male), cervico-vaginal secretion collection by Softcup (female), anal rectal sponge (men who have sex with men).  
12 Blood glucose, protein and HIV RNA will be performed at time of cerebrospinal fluid collection via lumbar puncture. The optional lumbar puncture scheduled for week 48/EOS may be performed 
earlier if impending viral rebound is suspected. 
13 Integrated HIV DNA, Total HIV DNA, and 2LTR Circles will be performed at week -6 only if volunteer does not have an available result within the preceding 12 weeks. 
* Optional studies 
 
 
 

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ATTACHMENT I: STUDY TEAM ROSTER 

85 
 
Protocol Chair: 
Jintanat Ananworanich, MD, PhD  
U.S. Military HIV Research Program 
6720-A Rockledge Drive, Suite 400 
Bethesda, MD 20817, USA 
Tel: +1 301 500 3949 
Fax: +1 301 762 7460 
Email: jananworanich@hivresearch.org 
 
Principal Investigator: 
Nittaya Phanuphak, MD, PhD  
The Thai Red Cross AIDS Research Centre 
104 Rajdamri Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 2 254 2566 
Fax: 662 254 7577 
Email: nittaya.p@searchthailand.org 
 
Project Leader (USA): 
Trevor A. Crowell, MD, PhD 
U.S. Military HIV Research Program 
6720-A Rockledge Drive, Suite 400 
Bethesda, MD 20817, USA 
Tel : +1 301 500 3990 
Fax: +1 301 500 3666 
Email: tcrowell@hivresearch.org 
 
Project Leader (Thailand): 
Donn J. Colby, MD, MPH 
The Thai Red Cross AIDS Research Centre 
104 Rajdamri Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 2 254 2566 
Fax: 66 2 254 7577 
Email: donn.c@searchthailand.org 
 
DoD Research Monitor: 
Krisada Jongsakul, MD 
Department of Retrovirology 
USAMC-AFRIMS 
315/6 Rajvithi Road 
Bangkok, Thailand 10400 
Tel: +662 696 2700 ext 4607 
Fax: +662 644 4784  
Email : krisadaj@afrims.org   
 
 
 
DAIDS Clinical Representative : 
Randall Tressler, MD 
Division of AIDS 
5601 Fishers Lane, Suite 9E47 
Rockville, MD 20852, USA 
Tel: +1 240 627 3072 
Email: randall.tressler@nih.gov 
 
Clinical Trials Specialist: 
Nitiya Chomchey, RN, MSc 
The Thai Red Cross AIDS Research Centre 
104 Rajdamri Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 2 254 2566 
Fax: 662 254 7577 
Email: nitiya.c@searchthailand.org 
 
Laboratory Coordinator: 
Leigh Ann Eller, MSc 
U.S. Military HIV Research Program 
6720-A Rockledge Drive, Suite 400 
Bethesda, MD 20817, USA 
Tel: +1 301 500 3600 
Fax: +1 301 762 7460 
leller@hivresearch.org 
 
Investigators 
U.S. Military HIV Research Program 
 
COL Nelson Michael, MD, PhD 
U.S. Military HIV Research Program 
6720-A Rockledge Drive, Suite 400 
Bethesda, MD 20817, USA 
Tel: +1 301 500 3601 
Email: nmichael@hivresearch.org 
 
Merlin Robb, MD 
U.S. Military HIV Research Program 
6720-A Rockledge Drive, Suite 400 
Bethesda, MD 20817, USA 
Tel: +1 301 500 3602 
Fax: +1 301 762 7460 
Email: mrobb@hivresearch.org 
 

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LTC Julie Ake, MD, MSc 
U.S. Military HIV Research Program 
6720-A Rockledge Drive, Suite 400 
Bethesda, MD 20817, USA 
Tel: +1 301 500 3621 
Fax: +1 301 762 7460 
Email: jake@hivresearch.org 
 
USAMC-AFRIMS 
 
COL Robert O'Connell, MD 
U.S. Military HIV Research Program 
USAMC-AFRIMS 
315/6 Rajvithi Road 
Bangkok, Thailand 10400 
Tel: 66 2 644 4888 ext. 3415  
Fax: 66 038 274911 
Email: Robert.OConnell@afrims.org 
 
Alexandra Schuetz, PhD 
U.S. Military HIV Research Program 
USAMC-AFRIMS 
315/6 Rajvithi Road 
Bangkok, Thailand 10400 
Tel: 66 2 644 4888 ext. 3415  
Fax: 66 038 274911 
Email: Alexandra.Schuetz@afrims.org 
 
The Thai Red Cross AIDS Research 
Centre 
 
Eugene Kroon, MD 
The Thai Red Cross AIDS Research Centre 
104 Rajdamri Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 2 254 2566 
Fax: 66 2 254 7577 
Email :  
Chulalongkorn University 
 
Prof. Praphan Phanuphak, MD, PhD 
Thai Red Cross AIDS Research Centre 
104 Rajdamri Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 2 253 0996 
Fax: 662 254 7577 
Email: Praphan.P@chula.ac.th 
 
Prof. Kiat Ruxrungtham, MD, MSc 
Division of Allergy and Clinical 
Immunology, Department of Medicine 
Chulalongkorn University 
1873 Rama 4 Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 86 335 4655 
Email: rkiatchula@gmail.com 
 
Rungsan Rerknimitr, MD 
Endoscopy unit 
Department of Internal Medicine 
Chulalongkorn University 
1873 Rama 4 Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 2 256 4265 
Email: ERCP@live.com 
 
Phandee Wattanaboonyongcharoen, MD 
Department of Laboratory Medicine 
Faculty of Medicine, Chulalongkorn 
University 
1873 Rama 4 Road, Pathumwan 
Bangkok, 10330, Thailand  
Tel: 66 2 256 4155 
Fax: 66 2 256 4155 
Email: phandee_w@yahoo.co.th 
 
Sopark Manasnayakorn, MD 
Department of Surgery 
Faculty of Medicine, Chulalongkorn 
University 
1873 Rama 4 Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 66 2 256 4117 
Fax: 66 2 256 4194 
Email: msopark@gmail.com 
 
Assoc. Prof. Sukalaya Lerdlum, MD 
Department of Radiology, Faculty of 
Medicine, Chulalongkorn University 
1873 Rama 4 Road, Pathumwan 
Bangkok, 10330, Thailand 
Tel: 02-2564412, 4418 

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Fax: 02-25644171873 
Email: lerdlum@hotmail.com 
 
Université de Montréal 
 
Nicolas Chomont, PhD 
Centre de Recherche du CHUM (CRCHUM) 
900, rue St Denis, Tour Viger 
Montréal, Québec, Canada 
H2X OA9 
Phone:+1-514-890-8000 
Email: nicolas.chomont@umontreal.ca 
 
Case Western University 
 
Rafick-Pierre Sékaly, Ph.D 
Division of Infectious Diseases and HIV 
Medicine, Case Western Reserve University, 
University Hospitals Case Medical Center 
11100 Euclid Ave. 
Cleveland, OH 44106 
Email: rafick.sekaly@case.edu 
 
 
The EMMES Corporation 
Peter Dawson 
401 N. Washington St., Suite 700 
Rockville, MD 20852 
Phone : 301 251 1161 
Email : pdawson@emmes.com  
 
 

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ATTACHMENT II: ROLES AND RESPONSIBILITIES 
 

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ATTACHMENT III: DAIDS AE GRADING TABLE 
 
 

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ATTACHMENT IV: TEST OF UNDERSTANDING