A Phase 1 Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC-HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB (VRC01LS) in the Serum and Mucosa of Healthy, HIV-Uninfected Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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PROTOCOL 
HVTN 116 
A phase 1 clinical trial to evaluate the safety, 
pharmacokinetics, and anti-viral activity of VRC-
HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB 
(VRC01LS) in the serum and mucosa of healthy, HIV-
uninfected adult participants 
DAIDS DOCUMENT ID 20733 
IND 125,494 HELD BY DAIDS 
CLINICAL TRIAL SPONSORED BY 
Division of AIDS (DAIDS) 
National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
Department of Health and Human Services (DHHS) 
Bethesda, Maryland, USA 
STUDY PRODUCTS PROVIDED BY 
Dale and Betty Bumpers Vaccine Research Center (VRC), NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
August 3, 2018 
FINAL 
HVTN 116, Version 2.0 

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Contents 
1 Ethical considerations ....................................................................................................5 
2 IRB/EC review considerations .......................................................................................7 
2.1 
Minimized risks to participants ......................................................................7 
2.2 
Reasonable risk/benefit balance .....................................................................8 
2.3 
Equitable participant selection .......................................................................8 
2.4 
Appropriate informed consent ........................................................................8 
2.5 
Adequate safety monitoring ...........................................................................9 
2.6 
Protect privacy/confidentiality .......................................................................9 
3 Overview ......................................................................................................................10 
3.1 
Protocol Team ..............................................................................................13 
4 Background ..................................................................................................................14 
4.1 
Rationale for trial concept ............................................................................14 
4.2 
VRC01: VRC-HIVMAB060-00-AB ............................................................16 
4.3 
VRC01LS: VRC-HIVMAB080-00-AB .......................................................19 
4.4 
Trial design rationale ....................................................................................20 
4.5 
Preclinical safety studies ..............................................................................23 
4.6 
Nonhuman primate studies ...........................................................................25 
4.7 
Clinical studies .............................................................................................28 
4.8 
Potential risks of study products and administration ...................................36 
5 Objectives and endpoints .............................................................................................40 
5.1 
Primary objectives and endpoints ................................................................40 
5.2 
Secondary objectives and endpoints ............................................................40 
5.3 
Exploratory objectives ..................................................................................40 
6 Statistical considerations ..............................................................................................42 
6.1 
Accrual and sample size calculations ...........................................................42 
6.2 
Randomization .............................................................................................46 
6.3 
Blinding ........................................................................................................46 
6.4 
Statistical analysis ........................................................................................46 
7 Selection and withdrawal of participants .....................................................................50 
7.1 
Inclusion criteria ...........................................................................................50 
7.2 
Exclusion criteria ..........................................................................................54 
7.3 
Participant departure from infusion schedule or withdrawal .......................57 
8 Study product preparation and administration .............................................................61 
8.1 
Infusion regimen ..........................................................................................61 
8.2 
Study product formulation ...........................................................................62 
8.3 
Preparation of study products .......................................................................62 
8.4 
Administration ..............................................................................................66 
8.5 
Acquisition of study products ......................................................................67 
8.6 
Pharmacy records .........................................................................................67 
8.7 
Final disposition of study products ..............................................................67 
9 Clinical procedures ......................................................................................................68 
9.1 
Informed consent ..........................................................................................68 

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9.2 
Pre-enrollment procedures ...........................................................................70 
9.3 
Enrollment visits ..........................................................................................72 
9.4 
Infusion visits ...............................................................................................73 
9.5 
Follow-up visits ............................................................................................74 
9.6 
Mucosal sampling ........................................................................................76 
9.7 
HIV counseling and testing ..........................................................................79 
9.8 
Contraception status .....................................................................................80 
9.9 
Urinalysis .....................................................................................................81 
9.10 Assessments of reactogenicity .....................................................................81 
9.11 Visit windows and missed visits ..................................................................82 
9.12 Early termination visit ..................................................................................83 
9.13 Pregnancy .....................................................................................................83 
9.14 HIV infection during the study .....................................................................83 
10 Laboratory ....................................................................................................................84 
10.1 HVTN CRS laboratory procedures ..............................................................84 
10.2 Total blood volume ......................................................................................84 
10.3 Drug detection and quantitation ...................................................................84 
10.4 Drug functionality ........................................................................................85 
10.5 Genotyping ...................................................................................................86 
10.6 Exploratory studies .......................................................................................87 
10.7 Other use of stored specimens ......................................................................87 
10.8 Biohazard containment .................................................................................87 
11 Safety monitoring and safety review ...........................................................................89 
11.1 Safety monitoring and oversight ..................................................................89 
11.2 Safety reporting ............................................................................................90 
11.3 Safety pause and prompt PSRT AE review..................................................92 
11.4 Review of cumulative safety data ................................................................94 
11.5 Study termination .........................................................................................94 
12 Protocol conduct ..........................................................................................................95 
12.1 Social impacts ..............................................................................................96 
12.2 Emergency communication with study participants ....................................96 
13 Version history .............................................................................................................97 
14 Document references (other than literature citations) ................................................100 
15 Acronyms and abbreviations......................................................................................102 
16 Literature cited ...........................................................................................................104 
Appendix A Sample informed consent form for Groups 1-3 .........................................110 
Appendix B Sample informed consent form for  Groups 4-5 ........................................132 
Appendix C Approved birth control methods (for sample informed consent form) for US 
sites .............................................................................................................153 
Appendix D Approved birth control methods (for sample informed consent form) for 
South African sites .....................................................................................154 
Appendix E Sample consent form for use of samples and information in other studies 155 

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Appendix F Table of procedures (for sample informed consent form, Groups 1-3)......160 
Appendix G Table of procedures (for sample informed consent form, Groups 4-5)......162 
Appendix H Laboratory procedures for Group 1 and Group 2 .......................................164 
Appendix I Laboratory procedures for Group 3 ............................................................166 
Appendix J Laboratory procedures for Group 4 ............................................................168 
Appendix K Laboratory procedures for Group 5 ............................................................170 
Appendix L Procedures at HVTN CRS for Group 1 and Group 2 .................................172 
Appendix M Procedures at HVTN CRS for Group 3 ......................................................176 
Appendix N Procedures at HVTN CRS for Group 4 ......................................................180 
Appendix O Procedures at HVTN CRS for Group 5 ......................................................184 
Appendix P Protocol Signature Page .............................................................................188 
 

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1 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of HIV prevention clinical trials. The HIV Vaccine Trials 
Network (HVTN) has addressed ethical concerns in the following ways: 
 HVTN trials are designed and conducted to enhance the knowledge base 
necessary to find new methods for preventing HIV, using methods that are 
scientifically rigorous and valid, and in accordance with Good Clinical 
Practice (GCP) guidelines. 
 HVTN scientists and operational staff incorporate the philosophies underlying 
major codes (1-3), declarations, and other guidance documents relevant to 
human subjects research into the design and conduct of HIV prevention 
clinical trials. 
 HVTN scientists and operational staff are committed to substantive 
community input—into the planning, conduct, and follow-up of its research—
to help ensure that locally appropriate cultural and linguistic needs of study 
populations are met. Community Advisory Boards (CAB) are required by 
DAIDS and supported at all HVTN research sites to ensure community input, 
in accordance with Good Participatory Practices (GPP) and all local and 
national guidelines.”  
 HVTN clinical trial staff counsel study participants routinely on how to 
reduce HIV risk. Participants who become HIV infected during the trial are 
provided counseling on notifying their partners and about HIV infection 
according to local guidelines. Staff members will also counsel them about 
reducing their risk of transmitting HIV to others. 
 The HVTN requires that all international HVTN sites lacking national plans 
for providing antiretroviral therapy (ART) develop plans for the care and 
treatment of participants who acquire HIV infection during a trial. Each plan 
is developed in consultation with representatives of host countries, 
communities from which potential trial participants will be drawn, sponsors, 
and the HVTN. If a program for ART provision is not available at a site and 
ART is needed, a privately established fund will be used to pay for access to 
treatment to the fullest extent possible. 
 The HVTN provides training so that all participating sites similarly ensure fair 
participant selection, protect the privacy of research participants, and obtain 
meaningful informed consent. During the study, participants will have their 
wellbeing monitored, and to the fullest extent possible, their privacy 
protected. Participants may withdraw from the study at any time. 
 Prior to implementation, HVTN trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration.  

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 HVTN trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
 The HVTN designs its research to minimize risk and maximize benefit to both 
study participants and their local communities. For example, HVTN protocols 
provide enhancement of participants’ knowledge of HIV and HIV prevention, 
as well as counseling, guidance, and assistance with any social impacts that 
may result from research participation. HVTN protocols also include careful 
medical review of each research participant’s health conditions and reactions 
to study products while in the study.  
 HVTN research aims to benefit local communities by directly addressing the 
health and HIV prevention needs of those communities and by strengthening 
the capacity of the communities through training, support, shared knowledge, 
and equipment. Researchers involved in HVTN trials are able to conduct other 
critical research in their local research settings. 
 The HVTN values the role of in-country Institutional Review Boards (IRBs), 
Ethics Committees (ECs), and other Regulatory Entities (REs) as custodians 
responsible for ensuring the ethical conduct of research in each setting. 

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2 
IRB/EC review considerations 
US Food and Drug Administration (FDA) and other US federal regulations 
require IRBs/ECs/REs to ensure that certain requirements are satisfied on initial 
and continuing review of research (Title 45, Code of Federal Regulations (CFR), 
Part 46.111(a) 1-7; 21 CFR 56.111(a) 1-7). The following section highlights how 
this protocol addresses each of these research requirements. Each HVTN 
Investigator welcomes IRB/EC/RE questions or concerns regarding these research 
requirements.  
This trial is being conducted in Africa and the US, with funding from the US 
NIH. Due to this, the trial is subject to both US and local regulations and 
guidelines on the protection of human research subjects and ethical research 
conduct. Where there is a conflict in regulations or guidelines, the regulation or 
guideline providing the maximum protection of human research subjects will be 
followed. 
In compliance with international and local (as appropriate) GCP, each research 
location has a locally based Principal Investigator (PI) who is qualified to conduct 
(and supervise the conduct of) the research; and the research addresses an 
important local health need for an HIV prevention method. In addition, the 
investigators take responsibility for the conduct of the study and the control of the 
study products, including obtaining all appropriate regulatory and ethical reviews 
of the research. Each participating site has a standard operating procedure for 
ensuring that participants have the necessary information to make a decision 
whether or not to consent to the research. 
The sections below address each of the review concerns by IRBs/ECs and any 
applicable REs regarding how the research will be conducted.  
2.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are 
minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly 
informing participants about risks so that they can join in partnership with the 
researcher in recognizing and reporting harms; (b) respecting local/national blood 
draw limits; (c) performing direct observation of participants postinfusion and 
collecting information regarding side effects for several days postinfusion; (d) 
having staff properly trained in administering study procedures that may cause 
physical harm or psychological distress, such as blood draws, infusions, HIV 
testing and counseling and HIV risk reduction counseling; (e) providing HIV risk 
reduction counseling and checking on contraception use (for women); and (f) 
providing safety monitoring. 

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2.2 
Reasonable risk/benefit balance 
45 CFR 46.111(a) 2 and 21 CFR 56.111(a) 2: Risks to subjects are 
reasonable in relation to anticipated benefits, if any, to subjects, and 
the importance of the knowledge that may reasonably be expected to 
result. 
In all public health research, the risk-benefit ratio may be difficult to assess 
because the benefits to a healthy participant are not as apparent as they would be 
in treatment protocols, where a study participant may be ill and may have 
exhausted all conventional treatment options. However, this protocol is designed 
to minimize the risks to participants while maximizing the potential value of the 
knowledge it is designed to generate.  
2.3 
Equitable participant selection  
45 CFR 46.111 (a) 3 and 21 CFR 56.111 (a) 3: Subject selection is 
equitable 
This protocol has specific inclusion and exclusion criteria for investigators to 
follow in admitting participants into the protocol. Participants are selected 
because of these criteria and not because of positions of vulnerability or privilege. 
Investigators are required to maintain screening and enrollment logs to document 
volunteers who screened into and out of the protocol and for what reasons. 
2.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 & 5 and 21 CFR 56.111 (a) 4 & 5: Informed 
consent is sought from each prospective subject or the subject’s 
legally authorized representative as required by 45 CFR 46.116 and 
21 CFR Part 50; informed consent is appropriately documented as 
required by 45 CFR 46.117 and 21 CFR 50.27 
The protocol specifies that informed consent must be obtained before any study 
procedures are initiated and assessed throughout the trial (see Section 9.1). Each 
site is provided training in informed consent by the HVTN as part of its entering 
the HVTN. The HVTN requires a signed consent document for documentation, in 
addition to chart notes or a consent checklist. 

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2.5 
Adequate safety monitoring 
45 CFR 46.111 (a) 6 and 21 CFR 56.111 (a) 6: There is adequate 
provision for monitoring the data collected to ensure the safety of 
subjects. 
This protocol has extensive safety monitoring in place (Section 11.1). Safety is 
monitored daily by HVTN Core and routinely by the HVTN 116 Protocol Safety 
Review Team (PSRT). In addition, the HVTN Safety Monitoring Board (SMB) 
periodically reviews study data. 
2.6 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate 
provisions to protect the privacy of subjects and maintain the 
confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or 
unreasonable intrusion into his/her private life and the right to control access to 
individually identifiable information about him/her. The term “privacy” concerns 
research participants or potential research participants as individuals whereas the 
term “confidentiality” is used to refer to the treatment of information about those 
individuals. This protocol respects the privacy of participants by informing them 
about who will have access to their personal information and study data (see 
Appendix A and Appendix B). The privacy of participants is protected by 
assigning unique identifiers in place of the participant’s name on study data and 
specimens. In the United States, a Certificate of Confidentiality from the US NIH, 
which can prevent disclosure of study participation even when that information is 
requested by subpoena, protects research participants in HVTN protocols. 
Participants are told of the use and limits of the certificate in the study consent 
form. In addition, each staff member at each study site in this protocol signs an 
Agreement on Confidentiality and Use of Data and Specimens with the HVTN 
and each study site participating in the protocol is required to have a standard 
operating procedure on how the staff members will protect the confidentiality of 
study participants. 

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3 
Overview 
Title  
A phase 1 clinical trial to evaluate the safety, pharmacokinetics, and anti-viral 
activity of VRC-HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB 
(VRC01LS) in the serum and mucosa of healthy, HIV-uninfected adult 
participants 
Primary objectives and endpoints 
Primary objective 1 
 To evaluate the safety and tolerability of VRC01/VRC01LS mAb 
administered through IV infusion 
Primary endpoint 1 
 Local and systemic reactogenicity, laboratory measures of safety, AEs, SAEs, 
and rates of discontinuation 
Primary objective 2 
 For each sex at birth, to evaluate the pharmacokinetics of VRC01 in serum 
versus mucosa in each mucosal compartment 
Primary endpoints 2 (Groups 1 & 2 & 4) 
 Serum concentration of VRC01 out to Month 6 after the last infusion  
 Levels of VRC01 in genital and rectal secretions, as well as cervical, vaginal, 
and rectal tissues at the collection timepoints 
Study products and routes of administration 
 VRC01: human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB in 
formulation buffer at pH 5.8 in sufficient normal saline (Sodium Chloride for 
Injection 0.9%, USP) to be administered intravenously (IV) 
 VRC01LS: human monoclonal antibody (mAb) VRC-HIVMAB080-00-AB 
in formulation buffer at pH 5.8 in sufficient normal saline (Sodium Chloride 
for Injection 0.9%, USP) to be administered IV 

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Table 3-1 Schema 
Group 
Treatment 
Infusion schedule (Months) 
N 
M0 
M2 
M3 
M4 
M6 
Group 
1 
VRC01  
10 mg/kg  
23 
IV 
Infusion 
IV 
Infusion 
 
IV 
Infusion 
IV 
Infusion 
Group 
2 
VRC01  
30 mg/kg  
23 
IV 
Infusion 
IV 
Infusion 
 
IV 
Infusion 
IV 
Infusion 
Group 
3 
VRC01LS  
30 mg/kg 
~6* 
IV 
Infusion 
 
IV 
Infusion 
 
IV 
Infusion 
Group 
4 
VRC01  
30 mg/kg  
16 
IV 
Infusion 
 
 
 
 
Group 
5 
VRC01LS  
30 mg/kg 
~6* 
IV 
Infusion 
 
 
 
 
*Enrollment will stop in Groups 3 and 5 when ≥12 volunteers have been enrolled across both groups 
(see Section 6.1). 
Participants 
About 74 healthy, HIV-uninfected adult volunteers aged 18 to 50 years, 
regardless of sex or gender 
Design 
Multicenter, randomized, open-label trial 
Duration per participant 
As VRC01LS is designed to have a longer half-life than VRC01, participants who 
receive VRC01 will be followed for 6 months after the last product administration 
and participants who receive VRC01LS will be followed for 12 months after the 
last product administration. Specifically, 
Groups 1, 2, and 5: 12 months of scheduled clinic visits 
Group 3: 18 months of scheduled clinic visits 
Group 4: 6 months of scheduled clinic visits 
Estimated total study duration 
40 months (includes enrollment and follow-up) 
Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 

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Study products provider 
Dale and Betty Bumpers Vaccine Research Center (VRC), NIAID, NIH, DHHS 
(Bethesda, Maryland, USA) 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Research Center (FHCRC) (Seattle, Washington, USA) 
Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), FHCRC 
(Seattle, Washington, USA) 
DF/Net Research (Seattle, Washington, USA) 
HVTN Laboratory Center (LC) 
 HIV diagnostic laboratories 
 University of Washington Virology Specialty Laboratory (UW-VSL) 
(Seattle, Washington, USA) 
 HIV Sero-Molecular Laboratory, National Institute for Communicable 
Diseases (HSML-NICD) (Johannesburg, South Africa) 
 Endpoint assay laboratories 
 Duke University Medical Center (Durham, North Carolina, USA) 
 FHCRC/University of Washington (Seattle, Washington, USA) 
 Cape Town HVTN Immunology Laboratory (CHIL) (Cape Town, South 
Africa)  
 NIAID Vaccine Immune T-Cell Antibody Laboratory (NVITAL) 
(Gaithersburg, Maryland, USA) 
 Vaccine Research Center (VRC) (Bethesda, Maryland, USA) 
Study sites 
HVTN Clinical Research Sites (HVTN CRSs) in the US and South Africa to be 
specified in the Site Announcement Memo 
Safety monitoring 
HVTN 116 PSRT; HVTN Safety Monitoring Board (SMB) 

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3.1 
Protocol Team 
Protocol leadership 
Chair 
Julie McElrath 
Seattle Vaccine Trials Unit 
206-667-6704 
jmcelrat@fredhutch.org 
Biostatistician 
Yunda Huang 
SCHARP, FHCRC 
206-667-5780 
yunda@scharp.org 
Cochair 
Linda-Gail Bekker 
Desmond Tutu HIV Centre 
+27 21 6506966 
Linda-Gail.Bekker@hiv-
research.org.za 
Medical officer 
Julia Hutter 
DAIDS, NIAID 
240-627-3039 
julia.hutter@nih.gov 
Protocol Team 
leader and Core 
medical monitor 
Philipp Mann 
HVTN Core, FHCRC 
206-667-1651 
pmann@fredhutch.org 
Laboratory lead 
John Hural 
HVTN Laboratory 
Program 
206-667-1683 
jhural@fredhutch.org 
Other contributors to the original protocol 
Vaccine developer 
representatives 
Julie Ledgerwood 
VRC 
Clinical safety specialist 
Megan Jones 
HVTN Core, FHCRC 
 
Barney Graham 
VRC 
Clinical trials managers 
Carissa Karg 
HVTN Core, FHCRC 
Laboratory Program 
representatives 
On Ho 
HVTN Laboratory 
Program, FHCRC 
 
Charlie Gregor 
HVTN Core, FHCRC 
 
Rena Astronomo 
HVTN Laboratory 
Program, FHCRC 
SDMC Project manager 
Evangelyn Nkwopara 
SCHARP, FHCRC 
 
Maria Lemos 
HVTN Laboratory 
Program, FHCRC 
Clinic coordinators 
Julie Czartoski 
Seattle CRS 
 
Mary Gross 
HVTN Laboratory 
Program, FHCRC 
 
Maureen Rattley 
Cape Town Groote 
Schuur CRS 
 
 
 
 
Regulatory affairs 
Meg Brandon 
HVTN Core, FHCRC 
HVTN SDMC program 
manager 
Gina Escamilla 
SCHARP, FHCRC 
 
 
 
 
Community Advisory 
Board (CAB) members 
Richard Laboy 
Philadelphia CAB 
Protocol development 
manager 
Ryan Jensen 
HVTN Core, FHCRC 
 
Dana Atkins 
Seattle CAB 
Community engagement 
unit representative 
Gail Broder  
HVTN Core, FHCRC 
DAIDS protocol 
pharmacist 
Lynette Purdue 
DAIDS, NIAID   240-
627-3061 
Community 
educator/recruiter 
Brian Kanyemba 
Cape Town Groote 
Schuur CRS 
Statistical research 
associate 
Abby Isaacs 
SCHARP, FHCRC 
Technical editor 
Erik Schwab 
HVTN Core, FHCRC 

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4 
Background 
4.1 
Rationale for trial concept 
Effective biomedical interventions are needed to reduce the acquisition of HIV. 
The global HIV-1 epidemic continues and while many countries have made 
progress toward leveling HIV prevalence over the last few years, micro-epidemics 
of infection continue to occur in nearly all regions, even in countries with access 
to the full toolkit of proven prevention approaches (4-6).  
Most HIV transmissions occur sexually and therefore involve the transmission of 
HIV across the epithelium of the vagina/cervix, rectum/distal colon, or penis. The 
colon and cervix are lined by a columnar epithelium, which protects a large pool 
of HIV target cells, such as activated CD4+ T cells, dendritic cells and 
macrophages. In contrast, the vagina and penis have stratified epithelium, 
protecting a less dense concentration of HIV target cells. Thus, whereas receptive 
anal sex has the highest probability of HIV-1 transmission (0.4-3.38%), receptive 
vaginal sex is associated with intermediate transmission probability (0.018-
0.150%), and transmission probability is lowest for insertive penile exposure 
(0.003-0.009%) (7-9). 
The central role of mucosal sites in HIV-1 transmission and early infection 
underscores the need for prevention approaches that protect mucosal sites from 
infection. Humoral and cellular responses in mucosal compartments have been 
analyzed by the HVTN in earlier HIV vaccine trials. Participants of HVTN 069 (a 
phase 1 HIV vaccine trial evaluating DNA and Ad5 containing regimens) at the 
Seattle site were offered enrollment into a companion mucosal study, and HVTN 
076 was specifically designed to evaluate mucosal responses to the vaccine 
regimen of a large scale efficacy study, HVTN 505, that was ongoing in parallel. 
As it is challenging to perform in-depth mucosal evaluations within the 
framework and study participant risk profile of a large scale efficacy trial, a 
scientifically and operationally sound approach is the strategy taken with HVTN 
076 and proposed here: a smaller scale study looking at the congruent intervention 
in a stringently designed phase 1 study that allows the consistent evaluation of 
mucosal samples.  
An alternative approach from active vaccination to the prevention and/or 
treatment of infectious diseases is passive administration of antibodies, a strategy 
that has been employed for more than 100 years against diverse disease targets 
and that is still used for hepatitis A and B prophylaxis (10, 11) and for 
postexposure prophylaxis (PEP) for rabies, measles, varicella zoster, and other 
infectious diseases (12). Most notably, palivizumab has been used for respiratory 
syncytial virus (RSV) infection prophylaxis in pre-term and other high-risk 
infants for nearly two decades. In 1998, a multinational, randomized controlled 
trial showed that palivizumab administered during the RSV infection season can 
reduce RSV-associated hospitalizations by 39–78% in premature infants and in 
children with bronchopulmonary dysplasia (13). Subsequent studies have 

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confirmed palivizumab’s safety, efficacy, and clinical benefit for infants at high 
risk for RSV infection (14, 15). Hence, palivizumab serves as a contemporary 
model for the use of mAbs to block a mucosally-acquired infection.  
Over the past several years, there has been a concerted and successful effort to 
isolate broadly neutralizing antibodies (bNAbs) to HIV-1 from chronically 
infected donors (16-28). Notably, many of these bNAbs are substantially more 
potent and have broader coverage of circulating HIV-1 strains than the first 
generation of bNAbs discovered in the 1990s. Subsequent research has provided 
considerable insight into the sites these antibodies target on the HIV-1 envelope 
glycoprotein and their functionality (ie, the mechanisms by which they neutralize 
the virus) (19, 20, 29, 30). This research has informed efforts to design 
recombinant protein immunogens that can elicit such antibodies (31-34), 
prompting optimism that vaccines that elicit bNAbs against HIV-1 can be 
developed (32, 35). In addition, the availability of safe and potent bNAbs against 
HIV opens the exciting possibility of antibody-mediated prevention (AMP) of 
HIV infection. 
The Vaccine Research Center (VRC), NIAID, NIH has developed VRC01, a 
broadly neutralizing human monoclonal antibody (mAb), which is targeted 
against the HIV-1 envelope (Env) CD4-binding site (18). This mAb was 
originally discovered in a person with chronic HIV-1 infection who maintained 
HIV-1 control without use of ARV therapy (36). By applying a novel method of 
isolating B cells that produce a specific antibody and recombinant DNA 
technology, the heavy and light chains encoding VRC01 were cloned and 
sequenced, allowing the synthetic production of codon-optimized genes encoding 
the Env variable regions that were inserted into proprietary immunoglobulin G1 
(IgG1) backbone sequences (18). Since the isolation of the VRC01 antibody, 
subsequent work evaluating longitudinal serum collected from HIV-1–infected 
individuals has demonstrated that although antibodies capable of binding to 
VRC01-like epitopes may be induced during HIV-1 infection, they occur in only 
a minority of HIV-infected individuals and may take years to develop (37). 
VRC01 will be evaluated for safety and HIV-1 prevention in the HVTN 
703/HPTN 081 and HVTN 704/HPTN 085 efficacy trials (see section 4.4). 
Recently, the VRC has developed a VRC01 variant, designated VRC01LS, which 
was designed to have a longer half-life by exploiting the functions of the neonatal 
Fc receptor (FcRn). The FcRn regulates the half-life of IgG antibodies through 
pH-dependent binding to IgG Fc regions, which favors binding at low pH (eg, 
lysosomal compartments and vaginal lumen) and release at neutral pH (eg, 
peripheral blood) (38). The FcRn is expressed in endothelial cells of the 
vasculature and some myeloid cells, where it can rescue IgG from lysosomal 
degradation by binding these molecules within this low pH compartment, then 
releasing them back into circulation (39-41). In the intestinal epithelium, the FcRn 
transports IgG bi-directionally: it transports IgG into the intestinal lumen and it 
recycles complexed antibody back to the tissue to support the induction of 
immunity, tolerance and/or susceptibility (42-44). In the genital tract, FcRn is 
expressed on columnar epithelial cells lining the human penile urethra (45) and 

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the endocervix, as well as on reserve epithelial cells lining the vagina. Thus, the 
tissue distribution of FcRn enables the delivery of IgG to relevant mucosal 
compartments and may thereby contribute to protection or susceptibility; the latter 
possibility has been suggested in the case of non-neutralizing Abs which may 
mediate the transmission of bound, infectious particles via FcRn transport 
pathways (46-48). 
The LS mutation (M428L / N434S) to the constant region of the VRC01 antibody 
enhances its binding affinity for FcRn at low pH, yet does not affect its release at 
pH 7.4 (49). Thus, the LS modification was found to alter antibody turnover in 
nonhuman primate (NHP) models, with increased persistence in serum and slower 
decay in rectal and cervicovaginal tissue. Intravenous administration of VRC01LS 
also afforded increased protection against intra-rectal challenge with simian-
human immunodeficiency virus (SHIV). Consequently, the increased persistence 
of anti-HIV neutralizing antibodies in mucosal tissue could have significant 
operational benefits, as increased maintenance at the portals of entry will allow 
for consistent protective levels with less frequent administrations and/or reduced 
dosing. 
4.2 
VRC01: VRC-HIVMAB060-00-AB 
VRC01 is a human mAb, developed by VRC/NIAID/NIH, directed against the 
CD4-binding site of HIV-1. The bulk lot of the drug substance was manufactured 
under current Good Manufacturing Practice (cGMP) conditions in a Chinese 
Hamster Ovary (CHO) cell line and the drug product vials were filled and labeled 
at the VRC Vaccine Pilot Plant (Frederick, Maryland, USA) operated by Leidos 
Biomedical Research, Inc. (formerly SAIC-Frederick), Frederick, Maryland 
(USA). Product is vialed at a concentration of 100 mg/mL VRC01 in formulation 
buffer containing 25 mM sodium citrate, 50 mM sodium chloride, and 150 mM L-
arginine hydrochloride at pH 5.8. VRC01 was produced using recombinant DNA 
technology. VRC01 is an IgG1 antibody and is highly somatically mutated from 
the germ-line precursor.  
The VRC01 antibody has been well characterized preclinically and exhibits 
favorable potency and half-life characteristics, which are important for the 
feasibility of a passive immunization approach (19). Figure 4-1 shows graphically 
the impressive breadth of VRC01, with 90% of 190 HIV-1 isolates across all 
clades tested showing sensitivity to neutralization by VRC01. As shown in Figure 
4-2 and Table 4-1, VRC01 has a 50% inhibitory concentration (IC50) of < 50 
mcg/mL against 91% of primary HIV-1 isolates and IC50 < 1 mcg/mL against 
72% of HIV-1 isolates. Notably, the IC50 for the vast majority of HIV-1 isolates 
tested is < 1 mcg/mL; the geometric mean IC50 for HIV-1 strains from all clades 
tested is 0.33 mcg/mL. In addition, VRC01 has demonstrated significant 
protection against both intravaginal and intrarectal SHIV challenge in NHP 
models (see Section 4.6.1).  

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While virus neutralization potency measured in vitro is not absolutely predictive 
of protection in vivo, several NHP challenge studies with a number of bNAbs 
have shown that plasma neutralization titers correlate well with in vivo protection. 
In a recent study, Shingai et al. calculated that a modest plasma neutralizing IC50 
titer of ~1:100 could protect 50% of NHP from a high dose IR SHIV challenge 
(50). This value is based upon the combined results from 60 macaques recipients 
of 5 different bNAbs, including VRC01, and challenged with either of two R5-
tropic SHIVs. The value may thus serve as a rough guide for predicting protection 
based on plasma neutralizing Ab titers. However, it should be noted that other 
studies have reported both higher (eg ~1:200-1:495 neutralization IC50 titer for 
PGT121) and lower plasma requirements (eg ~ 35 times neutralization IC50 for 
VRC01) to achieve protection against mucosal challenge (51, 52). Discrepancies 
may, in part, reflect imperfect correlations between Ab levels found in circulation 
and in mucosal tissues. Furthermore, the challenge doses used in these studies are 
orders of magnitude higher than what is considered physiologically relevant for 
HIV-1 mucosal transmission. Nonetheless, according to the 1:100 plasma 
neutralization titer estimate, modest plasma concentrations of VRC01 (~30-50 
mcg/mL) may provide protection against the majority of virus isolates tested.  

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Figure 4-1 Percentage of viruses neutralized at different serum concentrations. 
(A) < 50 mcg/mL; (B) < 10 mcg/mL; (C) < 1 mcg/mL.  
 
B 
C 
A

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Figure 4-2 CD4 binding site antibody: VRC01 with binding site on Env, in situ structure, and 
cross clade IC50 (18, 19)  
Table 4-1 Distribution of IC50 values across clades 
Virus clade 
Number of viruses 
IC50 < 50 mcg/mL 
IC50 < 10 mcg/mL 
IC50 < 1 mcg/mL 
A 
22 
100% 
100% 
95% 
B 
49 
96% 
94% 
80% 
C 
38 
87% 
84% 
66% 
D 
8 
88% 
88% 
50% 
CrRF01_AE 
18 
89% 
83% 
61% 
CRF02_AG 
16 
81% 
75% 
56% 
G 
10 
90% 
90% 
90% 
CRF07_BC 
11 
100% 
91% 
45% 
Other 
18 
83% 
83% 
78% 
Total 
190 
91% 
88% 
72% 
Details on VRC01 composition and manufacturing can be found in the 
investigator’s brochure (IB). 
4.3 
VRC01LS: VRC-HIVMAB080-00-AB  
VRC01LS is a broadly neutralizing human MAb targeted against the HIV-1 CD4 
binding site. It was developed by VRC/NIAID/NIH.  
VRC01 was modified by site-directed mutagenesis to increase its binding affinity 
for the neonatal Fc receptor (FcRn); the resulting antibody is designated 
VRC01LS. The LS designation specifies methionine to leucine (L) and asparagine 
to serine (S) (M428L/N434S, referred to as LS) changes within the C-terminus of 
the heavy chain constant region far outside of the antigen-combining site (53). 
The VRC01LS is an IgG1, and the glycosylation pattern is derived from its 
production in a Chinese Hamster Ovary (CHO) mammalian cell line.  

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While the LS mutation confers enhanced FcRn binding capability to the bNAb 
and allows its efficient transport to and accumulation in mucosal compartments, 
VRC01LS displays normal binding to other FcRs, such as FcγRIIIa, thus not 
impeding ADCC activity. The VRC01LS variant also retains comparable 
neutralization breadth and potency to wild-type (WT) VRC01. In Indian rhesus 
macaques, the LS mutant exhibited a 2.5-fold longer half-life (VRC01, 4.65 days; 
VRC01-LS, 11.80 days) and a 2.5-fold slower clearance rate than the wild type 
mAb (VRC01, 16.52 ml day-1 kg-1; VRC01-LS, 6.47 ml day-1 kg-1). The LS 
variant also persisted in rectal mucosal tissues for more than 70 days whereas the 
VRC01 (WT) antibody was undetectable at day 28 (49). 
The bulk lot of the drug substance was manufactured under cGMP using a stably 
transfected CHO cell line, purified, and the drug product vials were filled and 
labeled at the VRC, Vaccine Clinical Material Program operated by Leidos 
Biomedical Research, Inc., Frederick, MD. Each product vial contains 6.25 mL 
volume at a concentration of 100 mg/mL VRC01LS in formulation buffer 
containing 25 mM Sodium Citrate, 50 mM Sodium Chloride, and 150 mM L-
Arginine Hydrochloride at pH 5.8.  
Details on VRC01LS composition and manufacturing can be found in the IB. 
4.4 
Trial design rationale 
Two large scale phase 2b efficacy studies of VRC01 opened in parallel in 2016. 
HVTN 703/HPTN 081 enrolled the first participant on May 17, 2016, and will 
enroll 1900 participants at risk of contracting HIV-1 infection in Sub Saharan 
Africa; whereas HVTN 704/HPTN 085 will enroll 2700 participants at risk of 
contracting HIV-1 infection in the Americas and Switzerland. HVTN 704/HPTN 
085 opened for accrual on March 31st 2016, and the first participant was enrolled 
on April 6th 2016. Both studies will evaluate the ability of two different IV doses 
(10 mg/kg and 30 mg/kg, administered every 8 weeks) of VRC01 to prevent HIV-
1 infection. Since the target populations for HVTN 703/HPTN 081 and HVTN 
704/HPTN 085 predominantly acquire HIV-1 infection through sexual exposure, 
the concentration and function of Abs in the rectal and genital mucosae following 
systemic administration are potentially key to the effectiveness of the passive 
immunoprophylaxis approach. While phase 1-2a studies have collected limited 
samples to measure Ab levels in human mucosal secretions, there is very little 
data (recently generated in a Mucosal Sub-study to HVTN 104) on the Ab levels 
or distribution in human mucosal tissues, which serve as critical portal of entry for 
HIV-1 infection. Mucosal biopsies cannot be performed in the context of an 
efficacy trial enrolling high risk individuals because of potential alterations in risk 
of infection; however, HVTN 116 presents a crucial opportunity to examine the 
pharmacokinetic behavior and functionality of VRC01 and VRC01LS in mucosal 
tissues. 
In parallel with HVTN 703/HPTN 081 and HVTN 704/HPTN 085, it is desirable 
to gather in-depth data on the distribution and persistence, as well as the 

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functionality of VRC01 in mucosal secretions and tissues at the dosages planned 
in the phase 2b trial. HVTN 116 will investigate concentrations and tissue 
distributions of the VRC01 antibody in mucosal tissues that are common sites of 
HIV exposure, and compare these to paired serum levels. HVTN 703/HPTN 081 
and HVTN 704/HPTN 085 will establish serum antibody levels and correlate 
those with protection. However, a correlation between HIV prevention, the serum 
antibody levels, and the mucosal antibody levels of the VRC01 antibody cannot 
be established in these efficacy trials alone. HVTN 116, which includes arms that 
mirror the infusion schedule of HVTN 703/HPTN081 and HVTN 704/HPTN 085, 
can bridge the gap from serum to mucosal levels and therefore help us in 
understanding the underlying biological tenets of Antibody Mediated Protection 
(AMP), particularly with respect to mucosal challenge. Furthermore, HVTN 116 
will give us the opportunity to investigate a novel variant, designated VRC01LS, 
with enhanced FcRn binding capability. HVTN 116 will therefore compare serum 
and mucosal pharmacokinetics and functionality of this LS variant of the antibody 
to the wild-type VRC01 antibody, in single- and repeated-dose regimens of 
30mg/kg. 
Generally, the minimum number of biopsies needed in order to conduct 
measurements of levels is 1 per tissue, for immunohistochemistry it is also 1 per 
tissue, and for the infectivity assays the numbers we propose are 3 for colon, 3 for 
vagina, and 2 for cervix. Due to the uneven distribution of vasculature, FcRs and 
immune aggregates in tissue, we expect mucosal biopsies to display increased 
variability in infectivity challenge assays. Therefore, replicates are essential. The 
necessity of replicates was illustrated by the rectal explant infections we 
conducted on 7 male participants after VRC01 infusions in HVTN104. Upon 
challenge with a VRC01 sensitive virus, 4 participants demonstrated resistance to 
infection in 3/3 biopsies, 2 participants showed resistance in 2/3 biopsies, and 1 
showed resistance in 1/3 biopsies. Consequently, the infectivity assay will need a 
minimum of 2 biopsies in order to evidence any partial protection. 
Congruently, two ectocervical and three vaginal biopsies are requested to lend 
power to our ability to measure true Ab-mediated inhibition of HIV-1 infection ex 
vivo. In pilot experiments utilizing vaginal biopsies from participants who had not 
received an Ab infusion, we found that 16 of 20 vaginal biopsies collected from 5 
participants were infected (one participant was sampled twice; 1 participant had 
0/3 biopsies infected by the challenge virus and 1 participant had 4/5 biopsies 
infected). Due to the immunological heterogeneity of the mucosal tissue and the 
small size of the biopsies, triplicate biopsies (vaginal) are needed, whenever 
possible, particularly when a small number of participants is recruited for each 
group. Multiple collection timepoints are required to answer the following 
questions: what concentration of VRC01 or VRC01LS reaches mucosal sites and 
how quickly do these levels decay? Do functional levels reach the mucosal tissues 
and if so, how long are they maintained? 
In summary, HVTN 116 will provide additional supportive data for planned and 
postulated uses of VRC01 for the prevention of HIV acquisition. The primary 
goals are to further validate the safety of two doses and to interrogate the 

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distribution, persistence, and functionality of the antibody in relevant mucosal 
compartments. Additionally, HVTN 116 will provide safety data for the novel 
variant, VRC01LS, and will establish the distribution, persistence, and 
functionality of this Ab in mucosal tissues. 
Collections will include cervicovaginal secretions as well as cervical and vaginal 
biopsies (as well as rectal secretions and biopsies at the Seattle site) in those born 
female and the collection of rectal secretions and semen as well as rectal biopsies 
in those born male. The proposed timepoints will provide the opportunity to 
establish the mucosal levels of the respective antibodies over time, as well as the 
functional capabilities at peak levels and low levels.  
4.4.1 
Dose and schedule 
The proposed VRC01 doses for this mucosal study are based on doses that are 
being administered in the phase 2b efficacy trials, HVTN 703/HPTN 081 and 
HVTN 704/HPTN 085. As these doses (10 mg/kg and 30 mg/kg) are being 
evaluated on a large scale, interrogating the levels and functions of the antibody 
when administered at these same doses in serum, mucosal secretions, and mucosal 
tissues will be most informative and valuable for the field. 
VRC01LS should have a longer half-life, therefore the dosing interval proposed is 
three months compared to a two-month interval with the VRC01 wild-type 
antibody. This interval is considered most likely to be utilized in a prevention 
effort and is also applied in the VRC 606 phase 1 study (Section 4.7.2). The 30 
mg/kg VRC01LS dose also allows a direct comparison with the 30 mg/kg group 
of VRC01. 
Groups 4 and 5, with a single infusion at 30 mg/kg will provide the opportunity to 
compare the PK profiles of the two antibodies in a more detailed manner. 
VRC01 and VRC01LS are both formulated in vials at 100mg/ml (+/- 10mg/ml). 
Due to the concentration of the VRC01 antibody, large volumes are required for 
adult dosing and therefore IV administration will be used in this study. 

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4.5 
Preclinical safety studies 
4.5.1 
Preclinical toxicology and PK study of VRC01  
Table 4-2 Summary of preclinical studies 
Study 
number 
Product 
Type of 
study 
Animal 
N 
Dose 
groups 
Route 
Schedule 
SRI No 
M896-11 
VRC-
HIVMAB060-
00-AB 
Repeat dose 
toxicity 
Sprague-
Dawley rats 
10m, 10f 
each 
50m, 50f 
total 
Vehicle* 
4mg/kg IV 
40 mg/kg 
IV 
400 mg/kg 
IV 
40 mg/kg 
SC 
IV & 
SC 
D1, D8 
SRI No 
M896-11 
VRC-
HIVMAB060-
00-AB 
Single-dose 
PK 
Sprague-
Dawley rats 
9m, 9f 
each 
27m, 27f 
total 
4 mg/kg IV 
40 mg/kg 
IV 
40 mg/kg 
SC 
IV & 
SC 
D1 
* Vehicle consists of VRC01 formulation buffer. 
A repeat dose toxicity study of IV and SC administration and a single dose PK 
study was performed by SRI International (Menlo Park, CA) with VRC01 in male 
and female Sprague-Dawley rats in accordance with US FDA “Good Laboratory 
Practice (GLP) for Nonclinical Laboratory Studies” (Table 4-2). This study was 
conducted with a pre-GMP pilot lot of VRC01 manufactured at smaller scale 
using a similar purification process to that of the GMP clinical grade drug 
product. 
For the safety assessment, various doses of VRC01 (4 mg/kg, 40 mg/kg, or 400 
mg/kg) or a comparable control vehicle were administered by tail vein infusion on 
Days 1 and 8 to Groups 1 through 4, respectively. 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 comprised 10 male and 10 female rats. Five animals of 
each sex were sacrificed on Day 9, one day after the second VRC01 
administration; the remaining animals were sacrificed on Day 30, 22 days after 
the second VRC01 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 clinical observation, body weight, food consumption, body 
temperature, infusion site irritation, hematology, coagulation, or organ weight 
evaluations that are attributed to administration of VRC01. 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 

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administration. There were no histopathology findings that were considered 
related to IV administration of VRC01.  
The pre-specified IV dose studied in rats was 400 mg/kg and SC was 40 mg/kg, 
which will greatly exceed the dose levels in the adult clinical studies. 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 for VRC01 by the IV route of administration in rats was 400 mg/kg, 
the highest dose used in this study.  
For the PK analysis, 3 groups of rats (9 males and 9 females in each group) 
received VRC01 on Day 1 at 4 mg/kg IV, 40 mg/kg IV, and 40 mg/kg SC 
respectively. VRC01 levels in serum were determined using an enzyme-linked 
immunosorbent assay (ELISA) with samples collected predose from each animal 
and from an additional 3 males and 3 females to provide untreated control serum. 
Blood was collected from 3 rats/sex/PK group for a total of 4–5 collections per 
PK animal at each of the following postdose timepoints: 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 was about 10 days, with clearance of 
approximately 20 mL/day/kg and volume of distribution about 0.28 L/kg, 
indicating that the drug was distributed primarily in the serum and eliminated 
slowly. The development of anti-drug antibodies that contribute to an increased 
rate of clearance is often observed in preclinical safety studies of protein-based 
test articles when they are not tested in the species of origin. Although 
immunogenicity was not examined in this study, the presence of such antibodies 
might have contributed to the increased rate of clearance of VRC01 after SC 
administration that was observed in this study (54, 55). 
4.5.2 
Tissue cross reactivity of VRC01 and VRC01LS with human tissues 
in vitro  
The in vitro preclinical safety studies performed to assess potential off target 
binding by VRC01 and VRC01LS are summarized in Table 4-3 and Table 4-4. 
VRC01LS and VRC01 were assessed in GLP tissue cross reactivity (TCR) studies 
using research-grade materials and tissues from a single adult human donor. 
VRC01LS and VRC01 showed nearly identical minimal tissue binding. There 
was no unexpected off -target binding. 

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Table 4-3 In vitro preclinical safety studies with VRC01  
Study Purpose 
Study Outcome 
Assessment of anti-phospholipid reactivity 
VRC01 does not react to phospholipids 
Assessment of anti-nuclear antigen reactivity 
VRC01 does not react with nuclear antigens 
Assessment of anti-phospholipid characteristics 
by impact on activated partial thromboplastin 
time (aPTT) 
VRC01 does not impact aPTT by binding 
phospholipids 
Assessment of binding to a human cell line by 
Immunohistochemistry  
Fluorescently labeled VRC01 does not bind 
HEp-2 cells 
Normal adult and neonate human tissue 
cross-reactivity study  
 
No evidence of tissue cross reactivity in 
the panel of normal adults and neonatal 
tissues tested  
 
Table 4-4 In vitro preclinical safety studies with VRC01LS 
Study Purpose 
Study Outcome 
Assessment of anti-phospholipid reactivity 
VRC01LS does not react to phospholipids  
Assessment of anti-nuclear antigen reactivity 
VRC01LS does not react with nuclear antigens 
Assessment of binding to a human epithelial cell 
line (HEp-2) by Immunohistochemistry  
VRC01LS does not bind to HEp-2 cells 
Assessment of potential “off target” 
binding to protein arrays microchips 
precoated with 9400 full-length human 
proteins 
No clinically significant binding identified 
Assessment of potential “off target” binding in a 
human Tissue Cross-Reactivity study with 
VRC01LS and VRC01 
VRC01LS and VRC01 variably stained 
cytoplasm and cytoplasmic granules in epithelial 
and/or decidual cells in several human tissues. 
The findings were judged of no toxicologic 
significance for Mab as the cytoplasmic 
compartment is not available to Mab in vivo. 
4.6 
Nonhuman primate studies 
4.6.1 
NHP studies of VRC01  
Several non-GLP studies of VRC01 have been completed in NHP to assess for 
plasma and secretion concentrations and for preclinical data to support potential 
efficacy for prevention of HIV infection. Table 4-5 summarizes the studies 
performed and supports the plan to evaluate up to 40 mg/kg administered IV as a 
dose range of potential interest for a preventive indication. The current assay 
being used to detect VRC01 in serum has a lower limit of quantitation (LOQ) of 
1.1mcg/mL. Detectable concentrations of VRC01 were measured in vaginal, 
rectal, nasal and saliva samples after IV administration of 20 mg/kg of VRC01. 
Concentrations of VRC01 were lower in mucosal samples after IV administration 
of 5 mg/kg of VRC01. Please refer to the VRC01 IB for more details.  

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Table 4-5 Preclinical proof-of-concept studies performed with VRC01 mAb in NHP models 
Study Purpose 
Study Outcome 
Demonstration of plasma and secretion 
concentrations of VRC01 given 
intravenously at two dose levels in male 
rhesus macaques 
Kinetics of decay of VRC01 administered IV at 5 mg/kg 
and 20 mg/kg in plasma, nasal and rectal secretions, and 
saliva established 
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 
rhesus male macaques 
100% protection from challenge demonstrated at 20 
mg/kg dose administered IV 
4.6.2 
NHP studies of VRC01LS  
Several non-GLP studies have been conducted in NHP models to evaluate 
potential efficacy of VRC01LS for prevention of HIV infection. 
Table 4-6 summarizes the studies performed to date, which support plans to 
evaluate up to 40 mg/kg dose administered IV as a dose range of potential interest 
for a preventive or therapeutic indication.  
One investigation in NHP assessed the concentrations of VRC01, VRC01LS, and 
VRC01IHH (a mutation with an FcRn binding knockout) in serum and rectal 
tissue in female rhesus macaques. Three groups of NHP were administered a 
single IV dose of 10 mg/kg of either VRC01 (n=4), VRC01LS (n=4) or VRC01-
IHH (n=2). Introduction of the LS mutation increased half-life 2.5-fold (VRC01: 
4.65 days, VRC01LS: 11.80 days) and reduced clearance approximately 3-fold 
compared to the WT (VRC01: 16.52 mL/day/kg, VRC01LS: 6.47 mL/day/kg). In 
contrast, VRC01IHH displayed markedly reduced persistence (see Figure 4-3a). 
The levels of VRC01 (WT), VRC01LS (LS) and VRC01-IHH (IHH) were 
measured in the rectal tissues. The amount of each mAb was normalized relative 
to total tissue protein. As shown Figure 4-3b, VRC01LS remained detectable in 
rectal tissue for more than 70 days and persisted at significantly higher levels 
(p<0.001, t-test), while the VRC01 (WT) could not be measured after 28 days. 
VRC01-IHH could not be detected in rectal tissues after 14 days. 

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Table 4-6 Pre-clinical proof-of-concept studies performed with VRC01LS in NHP models 
Study Purpose 
Study Outcome 
Determine whether VRC01LS could 
protect male Rhesus Macaques against 
SHIV infection more effectively than 
VRC01 after IV administration of low 
sub-optimal protective dose (0.3 mg/kg) of 
MAb  
10/12 and 5/12 NHP were infected after receiving VRC01 and 
VRC01LS respectively. VRC01LS conferred superior protection 
against SHIV infection compared to VRC01. Levels of VRC01LS 
in rectal tissues were higher compared to levels of VRC01.  
Determine serum and rectal tissue 
concentrations in Indian rhesus macaques 
administered 10 mg/kg of VRC01 or 
VRC01LS IV  
Introduction of the LS mutation increased the serum half-life of 
VRC01LS 2.5-fold and reduced clearance 3-fold compared to 
VRC01. VRC01LS remained detectable in rectal tissue for more 
than 70 days and persisted at significantly higher levels, while the 
VRC01 (WT) was not detectable after 28 days (49).  
Determine serum and mucosal sample 
concentrations in female cynomolgus 
macaques administered 10 mg/kg of 
VRC01 or VRC01LS IV  
When administered IV at a single dose of 10 mg/mL in 
cynomolgus macaques, the half-life of VRC01LS was about 30 
days, a 3-fold increase compared to VRC01. Increased levels of 
VRC01LS were noted in rectal tissue, rectal secretions and vaginal 
tissue at 28 days post antibody infusion compared to VRC01 (49).  
Determine serum and mucosal secretion 
concentrations in male and female rhesus 
macaques administered 10 mg/kg of 
VRC01LS SC  
When administered SC at a single dose of 10 mg/kg to rhesus 
macaques, the half-life of VRC01LS was about 28 days and 
VRC01LS was found in rectal, vaginal and nasal secretions up to 
day 49 post administration (last day of testing).  
Demonstrate SHIV challenge protection in 
rhesus macaques administered 20 mg/kg 
of VRC01LS IV  
Complete protection from a rectal SHIV SF162P3 challenge was 
demonstrated in 5/6 animals after administration of VRC01LS at a 
dose of 20 mg/kg dose administered IV. The remaining animal had 
a single timepoint with viremia after challenge. 
 
Figure 4-3 VRC01LS (LS), VRC01 (WT) and VRC01-IHH (IHH) Levels in (a) Serum and (b) 
Rectal Tissues in Rhesus Macaques 
Another study was performed in male (n=2) and female (n=2) cynomolgus 
macaques. Each animal received a single 10 mg/kg dose of either VRC01 (WT) or 
VRC01LS, and blood samples as well as rectal secretion samples were collected 
through day 28 post infusion. Mucosal tissue samples (rectal or vaginal pinch 
biopsies) were collected at days 2, 13 and 28 post administration. The VRC01 and 
VRC01LS serum and mucosal concentrations are shown in Figure 4-4 and Figure 
4-5. Similar to the results in rhesus macaques (described above), VRC01LS 
circulated 3-fold longer than VRC01 (Figure 4-4a) in serum of cynomolgus 

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macaques. Compared to VRC01, increased levels of VRC01LS were noted in 
rectal tissue (Figure 4-4b), rectal secretions (Figure 4-4c) and vaginal tissue 
(Figure 4-5) at 28 days post antibody infusion, though the rectal tissue sampling 
showed more consistency.  
 
Figure 4-4 Levels of VRC01 (WT) and VRC01LS (LS) in Serum, Rectal Tissues and Rectal 
Secretions in Cynomolgus Macaques. The values from each monkey and the mean values 
for the groups are shown as dotted lines and heavier solid lines, respectively. 
 
 
Figure 4-5 Levels of VRC01 (WT) and VRC01LS (LS) in Vaginal Tissue in Cynomolgus 
Macaques. The values from each monkey and the mean values for the groups are shown as 
dotted lines and heavier solid lines, respectively. 
More information on these studies can be found in the VRC01LS IB. 
4.7 
Clinical studies 
4.7.1 
Clinical studies of VRC01 
As of March 2016, VRC01 has been tested in HIV-infected adults in the VRC 601 
(56) in healthy adults in the VRC 602 (57) and HVTN 104 studies, and in infants 
born from HIV-1–infected mothers in P1112 (IND 113611). Under IND 126001 
in 2015, studies of VRC01 were initiated in HIV-1–infected adults to evaluate the 
safety and virological effect of VRC01 administration during acute HIV infection 
(RV398), during a brief analytical treatment interruption (ATI) (A5340) and the 
effect on the HIV reservoir (A5342). Under IND 126664, a phase 1 study to 

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evaluate the safety, tolerability, and effect of VRC01 on markers of HIV 
persistence in ART-treated HIV-infected adults undergoing ATI was initiated. As 
of February 22, 2018, VRC01 has been administered to over 2600 HIV-
uninfected and about 88 HIV-infected adults and about 40 HIV-exposed infants. 
As of May 10, 2018, no SAEs related to VRC01 have been reported across all 
studies (communication from DAIDS). 
4.7.1.1 
VRC 601 
VRC 601 (NCT01950325) titled, “A Phase 1, Open-Label, Dose-Escalation Study 
of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-
HIVMAB060-00-AB (VRC01), with Broad HIV-1 Neutralizing Activity, 
Administered Intravenously or Subcutaneously to HIV-Infected Adults.” 
VRC 601 (Table 4-7) was the first study of the VRC01 mAb in HIV-infected 
participants. It was a dose-escalation study to examine safety, tolerability, dose, 
PK, and anti-antibody immune responses. VRC 601 opened in September 2013 as 
a single site study at the NIH Clinical Center, Bethesda, Maryland and in total, 23 
HIV-infected participants, including 15 aviremic ARV-treated participants and 8 
viremic non-ARV treated participants, were infused with one or two doses of 
VRC01 at doses up to 40 mg/kg IV. 
Table 4-7 VRC 601 study schema 
VRC 601 Dose Groups 
VRC01 Administration Schedule 
Group 
No. of 
evaluable 
participants* 
Day 0 
Week 4 
1 
3-5 
1 mg/kg IV 
1 mg/kg IV 
2 
3-5 
5 mg/kg IV 
5 mg/kg IV 
3 
3-5 
5 mg/kg SC 
5 mg/kg SC 
4 
3-5 
20 mg/kg IV 
20 mg/kg IV 
5 
3-5 
40 mg/kg IV 
40 mg/kg IV 
Total 
15-25 
IV doses administered in 100 mL of normal saline over 30-60 
minutes. 
SC doses administered in the minimum volume at 15 mL/hr. 
*Only participants who begin infusion are evaluable. Only 3 
evaluable participants per group will be enrolled into the dose 
group until the safety review is completed. Additional slots are 
available, if needed, to have sufficient data for the safety review or 
to include at least one eligible subject with a detectable viral load 
later after the dose escalation is complete. 
The first infusion at 1 mg/kg IV was administered in the VRC 601 study on 
September 30, 2013. Beginning on March 28, 2014, the dose escalation proceeded 
according to the schema. The first 40 mg/kg IV administration in this study 
occurred May 12, 2014 and the last infusion in VRC 601 occurred on April 6, 
2015. All IV and SC infusions have been well-tolerated with no serious adverse 
events (SAEs) or dose limiting toxicity. 

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VRC 601 demonstrated evidence of VRC01-mediated antiviral effect. An interim 
analysis of the VRC 601 viral load data obtained from 8 viremic adults through 
April 30, 2015 shows that VRC01 has a statistically significant in vivo virological 
effect on HIV viral load when administered as a single 40 mg/kg IV dose. None 
of these adults were taking antiretroviral therapy (ART) when enrolled into the 
study and had not started ART during the time period when the viral load data 
were collected. Six of the eight adult participants had ≥ 1 log10 copies/mL 
decrease in viral load and the remaining two participants had a viral load drop of 
0.26 and 0.18 log10 copies/mL respectively. These interim data indicate the 
following for a single dose of VRC01 at 40 mg/kg IV:  
 A statistically significant change from baseline viral load postinfusion days 5 
to 16; 
 The median time to reach ≥ 0.5 log10 decrease in viral load is 5 days; and, 
 The median time to greatest decrease in viral load is 7 days. 
A 0.5 log10 copies/mL or greater decrease in viral load is considered to be a 
positive response to ART. To have clinical benefit, such a change would need to 
be sustained. In VRC 601, participants were administered only one dose of 
VRC01 at 40 mg/kg and, thus, a sustained effect on viral load was not expected. 
However, the data demonstrate a VRC01 mediated anti-viral effect. 
4.7.1.2 
VRC 602 
VRC 602 (NCT01993706) is titled, “A Phase 1 Dose-Escalation Study of the 
Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-
HIVMAB060-00-AB (VRC01), Administered Intravenously or Subcutaneously to 
Healthy Adults.” 
VRC 602 was the first study of the VRC01 mAb in HIV-uninfected adults. It was 
a dose-escalation study to examine safety, tolerability, dose, and PK of VRC01. 
VRC 602 opened in December 2013 as a single site study at the NIH Clinical 
Center, Bethesda, Maryland and the final infusion was administered in August 
2014. 
As shown in Table 4-8, there were 3 open-label, dose escalation groups (Groups 
1, 2, and 3) for IV administration and 1 double-blinded, placebo-controlled group 
(Group 4) for SC administration.  

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Table 4-8 VRC 602 study schema 
VRC 602 Groups 
VRC01 Administration Schedule 
Group 
Initial 
Enrollments  
Additional 
Enrollments 
Day 0 
Week 4 
1 
3 
2 
5 mg/kg IV 
5 mg/kg IV 
2 
3 
2 
20 mg/kg IV 
20 mg/kg IV 
3 
3 
2 
40 mg/kg IV 
40 mg/kg IV 
4 
SC administration 
4A 
3 
2 
5 mg/kg SC 
5 mg/kg SC 
4B 
3 
2 
Placebo SC 
Placebo SC 
Total 
25 
20 participants treated with VRC01 at 
different dosage levels and 5 
participants treated with placebo 
administered SC 
IV doses administered in 100 mL of normal saline over 1 hr. 
First SC dose administered at about 15 mL/hr via SC infusion pump; subject option for 
second dose administration (Week 4) by direct SC injection with needle and syringe. 
All IV and/or SC infusions were well-tolerated with no SAEs or dose limiting 
toxicity.  
PK analysis from VRC 602 revealed a VRC01 terminal half-life of 15 days across 
all IV infused dose groups. Trough levels are shown in Table 4-9 below. 
Table 4-9: Trough levels 28 days post first and second infusion 
Time 
Dose 
20 mg/kg 
40 mg/kg 
28 days post infusion #1 
35 mcg/ml 
57 mcg/ml 
28 days post infusion #2 
57 mcg/ml 
89 mcg/ml 
4.7.1.3 
HVTN 104 
HVTN 104, titled A phase 1 clinical trial to evaluate the safety and drug levels of 
a human monoclonal antibody, VRC-HIVMAB060-00-AB (VRC01) administered 
in multiple doses intravenously and subcutaneously in different dosing schedules 
to healthy, HIV-uninfected adults, is examining safety profiles and serum levels of 
5 different regimens for the IV and SC administration of VRC01 (Table 4-10). IV 
administration is being evaluated at doses of 10, 20, 30, and 40 mg/kg; SC 
administration is being tested at 5 mg/kg. 

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Table 4-10 HVTN 104 study schema 
Dose 
Groups 
Study product administration schedule in months (days) 
Group N 
0 
0.5 
(14) 
1 (28) 
1.5 
(42) 
2 (56) 
2.5 
(70) 
3 (84) 
3.5 
(98) 
4 (112) 
4.5 
(126) 
5 (140) 
5.5 
(154) 
1 
20 
VRC01 
40mg/kg 
IV 
 
VRC01 
20mg/kg 
IV 
 
VRC01 
20mg/kg 
IV 
 
VRC01 
20mg/kg 
IV 
 
VRC01 
20mg/kg 
IV 
 
VRC01 
20mg/kg 
IV 
 
2 
20 
VRC01 
40mg/kg 
IV 
 
 
 
VRC01 
40mg/kg 
IV 
 
 
 
VRC01 
40mg/kg 
IV 
 
 
 
3 
20 
VRC01 
40mg/kg 
IV 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
VRC01 
5mg/kg 
SC 
4 
IV 
placebo 
for 
VRC01  
SC 
placebo 
for 
VRC01  
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
SC 
placebo 
for 
VRC01 
4 
12 
VRC01 
10mg/kg 
IV 
 
 
 
VRC01 
10mg/kg 
IV 
 
 
 
VRC01 
10mg/kg 
IV 
 
 
 
5 
12 
VRC01 
30mg/kg 
IV 
 
 
 
VRC01 
30mg/kg 
IV 
 
 
 
VRC01 
30mg/kg 
IV 
 
 
 
Total 
88 Intravenous (IV) doses administered in 100 mL of normal saline over 1 hr 
Subcutaneous (SC) doses administered by needle and syringe injection 
HVTN 104 is a phase 1 clinical trial designed to evaluate the safety and drug 
levels of VRC01 administered in multiple intravenous or subcutaneous doses and 
different dosing schedules to 88 healthy, HIV-uninfected adults. The first 
participant enrolled in HVTN 104 on September 9, 2014. Enrollment was 
completed by July 15, 2015 and infusions were completed November 30, 2015. 
The study has 5 groups: Group 1 is evaluating the IV administration of a 40 
mg/kg loading dose, with 2 subsequent 20 mg/kg doses given at 8 week intervals. 
Groups 2, 4, and 5 are evaluating 3 infusions of 40 mg/kg, 10 mg/kg, or 30 mg/kg 
respectively given 8 weeks apart. Group 3 is evaluating 5 mg/kg given every 2 
weeks subcutaneously for 24 weeks (which will inform the design of perinatal 
prophylaxis studies). Secondary aims of HVTN 104 are: (1) to evaluate the serum 
kinetics of in vitro neutralization of a single VRC01 sensitive virus isolate 
(TZM.bl assay); (2) to determine whether anti-idiotypic antibody (AIA) can be 
detected and whether there is a correlation between VRC01 levels and AIA levels 
in serum; (3) to determine whether measurable levels of VRC01 can be detected 
in genital, rectal, and oral secretions; (4) to evaluate the kinetics in mucosal 
secretions of in vitro neutralization of a single VRC01-sensitive virus isolate; (5) 
to assess binding of VRC01 to multiple Env proteins; and (6) to further assess the 
serum levels of VRC01. 
VRC01 infusions and injections have been well tolerated in HVTN 104. Most 
participants have had no local reaction or mild local reactogenicity from a 
particular infusion or injection. Most participants had no systemic reactogenicity 
symptoms after injections or infusions. When present, most symptoms were mild, 
with malaise/fatigue, myalgias, and headaches being most common. Of 230 AE’s 

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reported as of February 19, 2016, only 12 (5%), all of them mild, were considered 
product-related. No SAE/EAEs were reported.  
Initial analyses were generated including VRC01 serum levels up to the day 168 
visit. The trough level in Group 1 reached an average of 75.6 (64.6, 88.5) ug/ml 
before the second infusion (day 28), then decreased to trough levels of 50.7 (43, 
59.8), 43.4 (36.8, 51.2), 37.3 (26.7, 52.1), and 31.7 (19.9, 50.3), prior to the 3rd 
(day 56), 4th (day 84), 5th (day 112), and 6th (day 140) infusions, respectively. 
The last measured level, 28 days after the 6th infusion, was 39.7 (28, 56.3) ug/ml. 
In Group 2, the trough levels, measured before the second (day 56) and third (day 
112) infusions, averaged 20.1 (16.4, 24.6) ug/ml and 21.4 (15.7, 29.2) ug/ml, 
respectively. The last trough level observation, 28 days after the 3rd infusion, 
measured 15.1 (6.5, 35.3) ug/ml. In Group 3 (including placebo recipients), the 
trough levels, measured right before each subsequent 2-weekly SC injection, 
decreased steadily from 27.7 (8.8, 87.7) ug/ml at day 28 to 8.2 (2.6, 26.3) ug/ml at 
day 154. The last trough measurement at 14 days after the SC injection was 6 
(1.9, 19.3) ug/ml. In Group 4, the trough levels, measured before the second (day 
56) and third (day 112) infusions, averaged 4.1 (3.1, 5.3) ug/ml and 2.5 (0.8, 7.9) 
ug/ml, respectively. The last trough level observation, 28 days after the 3rd 
infusion, measured 4.2 (1.6, 11.4) ug/ml. In Group 5, the trough levels, measured 
before the second (day 56) and third (day 112) infusions, averaged 10.4 (6.8, 
16.1) ug/ml and 11.5 (7.5, 17.5) ug/ml, respectively. The last trough level 
observation, 28 days after the 3rd infusion, measured 11.9 (3.8, 38) ug/ml. 
VRC01 serum levels for Group 4 and Group 5, which use the same doses as 
HVTN 116, ie VRC01 10mg/kg and 30mg/kg at two month intervals respectively, 
are shown in Figure 4-6 and Figure 4-7. 
 
Figure 4-6 VRC01 serum levels in the HVTN 104 per-protocol analysis for Group 4.  

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Figure 4-7 VRC01 serum levels in the HVTN 104 per-protocol analysis for Group 5. 
4.7.1.4 
Safety summary of VRC01  
The VRC01 SC administrations were sometimes associated with mild local 
reactions during the administration 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 erythema or swelling events 
that were observed during infusions ranged up to about 9 cm. One subject in VRC 
602 receiving placebo SC reported mild flushing during administration and one 
subject in VRC 601 (5 mg/kg SC) reported mild nausea during VRC01 SC 
administration. 
The solicited local and systemic signs and symptoms following administration of 
VRC01 are generally none to mild. In higher dose groups, 25% of subjects or 
fewer have reported any moderate or greater solicited reactions after product 
administration.  
There have been no serious adverse events attributed to VRC01 administration. 
AEs attributed to study product administration on the basis of temporal 
relationship that did not result in study product discontinuation have included 
AST, ALT and creatinine elevation, decreased neutrophil count, diarrhea, herpes 
zoster, and pruritus at the administration site.  
In the blinded HVTN 104 trial, there have been three product discontinuations, 
two in participants receiving subcutaneous administration of VRC01 or placebo 
and one in the 20mg/kg IV group (Group 1). One discontinuation was for a 20-
minute episode of chest tightness occurring approximately 25 minutes after SC 

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injection of VRC01 or placebo in a participant who is a chronic smoker on 
nicotine replacement while smoking. One discontinuation was in a participant 
who reported a generalized rash that began three days after SC injection of 
VRC01 or placebo, and resolved after a few hours. The discontinuation of the 
group 1 participant was for an episode of syncope 6 hours after receipt of the third 
infusion. This incident was deemed not related to study product administration but 
out of an abundance of caution, the decision was made to withhold the 
participant’s final study drug administration, while continuing safety monitoring 
visits. In addition, one person in HVTN 104 had study product discontinued due 
to pregnancy occurring during the trial. 
Overall, VRC01 administration in the dose range from 1 to 40 mg/kg IV and at 5 
mg/kg SC has been assessed as well-tolerated and safe for further evaluation.  
4.7.2 
Clinical studies of VRC01LS 
VRC01LS is initially being evaluated in the VRC 606 study: “A Phase 1, Dose-
Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal 
Antibody, VRC-HIVMAB080-00-AB (VRC01LS), and VRC-HIVMAB060-00-AB 
(VRC-01), Administered Intravenously or Subcutaneously to Healthy Adults”. 
VRC 606 is the first study of the VRC-HIVMAB080-00-AB (VRC01LS) 
monoclonal antibody (mAb) in healthy adults. It is a dose-escalation study to 
examine safety, tolerability, dose, and pharmacokinetics of VRC01LS. There are 
4 open-label, dose escalation groups (Groups 1-4) to assess VRC01LS 
administered IV and SC once per subject and 2 open-label groups (Groups 5 and 
6) to assess VRC01LS at 5 mg/kg SC or at 20 mg/kg IV administered every 12 
weeks for a total of 3 administrations per subject. Two additional open-label 
groups (Groups 7 and 8) assess VRC01 at 5 mg/kg SC or at 20 mg/kg IV 
administered every 4 weeks for a total of 2 administrations per subject. The study 
schema is depicted in Table 4-11.  
Table 4-11: VRC 606 Study Schema 
Group 
Subjects 
Product 
Administration Schedule 
Day 0 
Week 4 
Week 12 
Week 24 
1 
3 
VRC01LS 
5 mg/kg IV 
 
 
 
2 
3 
VRC01LS 
5 mg/kg SC 
 
 
 
3 
3 
VRC01LS 
20 mg/kg IV 
 
 
 
4 
5 
VRC01LS 
40 mg/kg IV 
 
 
 
5 
15 
VRC01LS 
5 mg/kg SC 
 
5 mg/kg SC 
5 mg/kg SC 
6 
10 
VRC01LS 
20 mg/kg IV 
 
20 mg/kg IV 
20 mg/kg IV 
7 
5 
VRC01 
5 mg/kg SC 
5 mg/kg SC 
 
 
8 
5 
VRC01 
20 mg/kg IV 
20 mg/kg IV 
 
 
Total* 
49 
 
 
 
 
 
*Enrollment up to a total of 60 subjects is permitted in case there are subjects who do not complete the 
schedule, if additional PK evaluations are needed, or if an enrollment of additional subjects is necessary 
for safety evaluations (Section 4.3). 
 

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The first product administration occurred on November 18, 2015 and the study is 
ongoing. As of July 17, 2017, 39 people have received VRC01LS in three dose 
groups: 5mg/kg IV and SQ, 20mg/kg IV, and 40mg/kg IV, and 25 participants 
have completed study participation. No dose limiting toxicities have occurred. 
There have been no severe adverse events. One participant who received 
subcutaneous product administration experienced moderate local reactogenicity 
(pain/tenderness at the injection site). 29 of 39 (74.4%) participants have had one 
or more unsolicited AEs, with maximum severity of Grade 1 for 18 participants 
and Grade 2 for 11 participants. Six AEs were assessed as related to study 
product: two instances of Grade 1 diarrhea, one instance of Grade 1 dizziness, one 
Grade 1 injection site reaction, and two instances of Grade 1 AST elevation. 
VRC01LS administrations have been generally well tolerated. 
4.8 
Potential risks of study products and administration 
In a preclinical study performed in rats, there was a small dose-dependent, but 
transient, increase in AST and ALP, but not in ALT following IV administration. 
In rats, there were no histopathology findings following IV administration.  
Thus far in VRC 601, VRC 602, and HVTN 104 there have been no safety 
concerns, including no SAEs deemed related to study product. Administration of 
any mAb may have a risk of immune reactions such as acute anaphylaxis, serum 
sickness, and the generation of auto-reactive antibodies; however, these reactions 
are rare and more often associated with mAbs targeted to human proteins or with 
the use of murine mAbs, which would have a risk of generating human anti-
mouse antibodies (58). In this regard, as VRC01 is targeted to a viral antigen and 
is a human mAb, it is expected to have a low risk of such side effects.  
Typically, the side effects of mAbs are mild but may include fever, flushing, 
chills, rigors, nausea, vomiting, pain, headache, dizziness, shortness of breath, 
bronchospasm, hypotension, hypertension, pruritus, rash, urticaria, angioedema, 
diarrhea, tachycardia, chest pain, or reactions at injection site (pain, redness, 
bruising, swelling). Clinical use of mAbs that are targeted to cytokines or antigens 
associated with human cells may be associated with an increased risk of infections 
(58); however, this is not expected to be a risk for a mAb targeted to a viral 
antigen. 
It is known from published experience with human mAbs directed against the cell 
surface targets on lymphocytes that infusion of a mAb may be associated with 
cytokine release, causing a reaction known as “cytokine release syndrome” (59). 
“Cytokine release syndrome” and other immune reactions such as tumor lysis 
syndrome have been observed with administration of chimeric and humanized 
mAbs (58). Most infusion-related events occur within the first 24 hours after 
beginning administration. Specifically, with regard to cytokine release syndrome 
reactions, these most commonly occur within the first few hours of beginning the 
infusion and are more common with the first mAb infusion received. This is 

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because the cytokine release is associated with lysis of the cells targeted by the 
mAb and the burden of target cells is greatest at the time of the first mAb 
treatment. With licensed therapeutic mAbs, cytokine release syndrome is 
managed by temporarily stopping the infusion, administering histamine blockers, 
and restarting the infusion at a slower rate (60). Severe reactions such as 
anaphylaxis, angioedema, bronchospasm, hypotension, and hypoxia are 
infrequent and more often associated with mAbs targeted to human proteins or 
with a non-human mAb, such as a murine mAb (58). Most infusion-related events 
occur within the first 24 hours after beginning administration. 
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 exposure to 
the mAb and are noted to be more common with chimeric types of mAb (58). 
Serum sickness has not been described with administration of licensed, fully 
human mAbs. 
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.  
Other side effects of licensed mAbs include infections, thrombocytopenia, 
autoimmune diseases, cancer, dermatitis, and cardiotoxicity (58). 
The HVTN laboratory tested plasma from HIV-uninfected individuals that was 
spiked with VRC01 in a range of concentrations that encompasses those likely to 
be observed in this clinical trial. VRC01 did not cause a reactive test result using 
several standard antibody-based HIV-1/2 diagnostic tests However, since VRC01 
is an antibody to an HIV protein, so, it may be theoretically possible for a 
standard antibody-based HIV diagnostic test to detect VRC01 for a short time 
period postinfusion or postinjection. However, in practice this has not been 
observed in clinical studies with VRC01 to date.  
Risks of 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. Problems from use of an IV for 
blood drawing are generally mild and may include pain, bruising, minor swelling 
or bleeding at the IV site and, rarely, infection, vein inflammation (phlebitis), or 
blood clot.  
Risks of IV Infusion: The placement of an IV catheter can allow for the 
development of bacteremia because of the contact between the catheter and 
unsterile skin during insertion. Risk of infection from IV infusion will be 
minimized through careful decontamination of skin prior to catheter placement 
and through the use of infection control practices during infusion. The risk of 
product contamination will be minimized through the use of aseptic techniques 
during product preparation and administration. 

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Risk of biopsy collections: Possible complications of biopsies are bleeding and 
infection. These complications are rare and risks of these complications will be 
minimized by careful hemostasis by the clinicians and detailed education of the 
participants to report bleeding and/or fever after the procedures. As biopsies 
create breaches in mucosal integrity, the risk of HIV infection - if exposed - is 
potentially increased during wound healing. Therefore (and to allow for 
undisturbed wound healing) an abstinence period is required of the participants 
(see Section 7.1, Criterion 26 and Section 9.6) after each biopsy. Healing of the 
superficial wounds in mucous membranes caused by these shallow, small (~2-
4mm) biopsies is rapid; by 5-14 days, healing is expected to be complete (61). In 
the proposed schedule, a minimum of 28 days between biopsy collections will be 
adhered to, and repetitious biopsies are not assumed to increase the risk as 
compared to a single biopsy. More than 150 clinic visits involving multiple 
biopsy collections have been performed at the Seattle HIV Vaccine Trials Unit in 
the past two years and thus far not a single complication has occurred. In the Cape 
Town Area Control (CTAC) study, seven female participants were enrolled for 
the collection of cervical and vaginal samples. Up to five biopsies (cervical, 
vaginal or a combination of both) were collected at a single visit. Twelve (male 
and female) participants were enrolled for rectal biopsy collections. To date, two 
participants underwent first, an anoscopy (with collection of five rectal biopsies), 
and then a second collection via flexible sigmoidoscopy 10 weeks later (with 
collection of 5 rectal biopsies and 19 colonic biopsies). Nine participants have 
undergone one biopsy collection via rigid sigmoidoscopy (with collection of 5 
rectal biopsies and 19 colonic biopsies). One participant has undergone two rigid 
sigmoidoscopies 10 weeks apart (with collection of 5 rectal biopsies and 19 
colonic biopsies). All participants were HIV negative at enrollment and have 
remained HIV negative 1 year post-biopsy collection visit. 
In MTN 007, 7 rectal biopsies have been collected three times within one month, 
respectively, in 65 volunteers. One participant (1.5%) reported grade 1 
hematochezia, two participants (3.1%) reported grade 1 painful defecation, and 
three participants (4.6%) reported grade 1 anal pruritus (62). In a recent phase 1 
study of a long-acting antiretroviral, multiple cervical, vaginal, and/or colonic 
biopsies were collected at baseline and every month for 6 months in 24 female 
and 12 male participants (ie, 7 collections within a 6-month time frame) with only 
one significant clinical event related to vaginal biopsies [prolonged bleeding 
following initial hemostasis that required medical attention but not hospitalization 
(personal communication Ian McGowan)]. 
Dr. Susan Cu-Uvin (Brown University), an internationally-recognized expert on 
gynecological sampling and global health, is currently conducting two different 
longitudinal biopsy studies that include up to 4 biopsy collection visits (3 cervical 
and 3 vaginal biopsies at each visit) within a 5-month (healthy women cohort) to 
12-month (HIV-infected women cohort) study period. With an overall completion 
to date of more than 160 cervicovaginal biopsy visits, no biopsy-related 
complications have been observed. 

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A review of 34 studies in which 8,330 cervical and vaginal biopsies were taken 
concluded that there are emerging data that cervical and vaginal biopsies taken 
among special populations, including women living in high HIV prevalence areas 
are also safe and well tolerated (63). 
 

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5 
Objectives and endpoints 
5.1 
Primary objectives and endpoints 
Primary objective 1 
 To evaluate the safety and tolerability of VRC01/VRC01LS mAb 
administered through IV infusion 
Primary endpoint 1 
 Local and systemic reactogenicity, laboratory measures of safety, AEs, SAEs, 
and rates of discontinuation 
Primary objective 2 
 For each sex at birth, to evaluate the pharmacokinetics of VRC01 in serum 
versus mucosa in each mucosal compartment 
Primary endpoints 2 (Groups 1 & 2 & 4) 
 Serum concentration of VRC01 out to Month 6 after the last infusion  
 Levels of VRC01 in genital and rectal secretions, as well as cervical, vaginal, 
and rectal tissues at the collection timepoints 
5.2 
Secondary objectives and endpoints 
Secondary objective 1 
 To evaluate the ability of the in vivo–infused VRC01/VRC01LS antibodies to 
inhibit HIV-1 infection in tissue explants 
Secondary endpoint 1 
 Ex vivo inhibition of HIV-1 infectivity in tissue biopsies in Groups 1 - 3 
5.3 
Exploratory objectives 
Exploratory objective 1: 
For each sex at birth, to evaluate the pharmacokinetics of VRC01LS in serum 
versus mucosa in each mucosal compartment 
Exploratory objective 2: 

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To evaluate the levels of VRC01LS in serum, mucosal secretions, and mucosal 
tissues and those of VRC01 at the 30 mg/kg dose level. 
Exploratory objective 3: 
To evaluate the tissue distribution of VRC01/VRC01LS in mucosal biopsies. 
Exploratory objective 4: 
To compare the levels and functionality of VRC01/VRC01LS in mucosal 
secretions and tissues between the cervical, vaginal, and rectal compartments 
from the same participant. 
Exploratory objective 5: 
To assess the relationship between inflammation in mucosal biopsies and levels of 
antibody in these tissues and related secretions. 
Exploratory objective 6: 
To assess the acceptability and tolerability of repeat mucosal sampling, including 
secretions and biopsies, for application in future studies. 
Exploratory objective 7: 
To assess the relationship between Fc receptor genotypes and VRC01/VRC01LS 
pharmacokinetics and/or ex vivo infectivity of biopsies. 
Exploratory objective 8: 
To further evaluate the retention of functional characteristics of in vivo–infused 
VRC01/VRC01LS in each group, additional assays may be performed, including 
on samples from other timepoints. 
Exploratory objective 9: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, antibody mediated prevention, and clinical trial conduct. 

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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling approximately 74 healthy, HIV-uninfected adult 
participants into five groups receiving IV administration of either VRC01 or 
VRC01LS at different schedules and/or dose levels. Groups 1 and 2 participants 
receive 4 infusions of VRC01 every 2 months at the 10 mg/Kg and 30 mg/Kg 
dose levels, respectively; Group 3 participants receive 3 infusions of VRC01LS 
every 3 months at the 30 mg/Kg dose level; Groups 4 and 5 participants receive a 
single infusion of VRC01 or VRC01LS, respectively, at the 30mg/Kg dose level. 
Because Groups 1-3 will be enrolled at different sites from Groups 4 and 5, 
Groups 1-3 were originally randomized with a ratio of 1:1:1, stratified by sex at 
birth and, separately, Groups 4 and 5 were also originally randomized with a ratio 
of 1:1 stratified by sex at birth. Groups 3 and 5 will stop enrolling once a minimal 
number of 12 participants, regardless of sex at birth, are enrolled. At that point, 
Groups 1 and 2 will be randomized together with a ratio of 1:1, stratified by sex at 
birth. Groups 1 and 2 will still be enrolled at different sites from Group 4. Groups 
1 and 2 (n=23/group) will now be randomized with a ratio of 1:1, stratified by sex 
at birth. A total of 10 male and 13 female participants will still be enrolled in each 
of Groups 1 and 2. In Groups 1-3, enrollment is concurrent with the first biopsy 
procedure(s). In Groups 4-5, enrollment is concurrent with the first infusion. For 
all groups, randomization occurs prior to the first infusion, ideally within 4 days. 
All participants receiving the first complete or partial infusion will provide some 
safety data. However, for PK analyses of drug levels in serum and mucosa, it is 
possible that data may be missing for various reasons, such as participants 
terminating from the study early, or problems in obtaining or shipping specimens. 
For this reason, the sample size calculations in Section 6.1.2 account for 15% 
enrolled participants having missing data for the primary lab data endpoint. 
6.1.1 
Sample size calculations for safety 
The goal of the safety evaluation in this study is to identify safety concerns 
associated with product administration. The ability of the study to detect SAEs 
can be expressed by the true event rate above which at least 1 SAE would likely 
be observed and the true event rate below which no events would likely be 
observed. Specifically, for a group size of n=16, there is a 90% chance of 
observing at least 1 event if the true rate of such an event is 13.39% or more; and 
there is a 90% chance of observing no events if the true rate is 0.64% or less. For 
a group size of n=23 , there is a 90% chance of observing at least 1 event if the 
true rate of such an event is 9.52% or more; and there is a 90% chance of 
observing no events if the true rate is 0.45% or less. For all three VRC01 groups 
combined (n=62), there is a 90% chance of observing at least 1 event if the true 
rate of such an event is 3.50% or more; and there is a 90% chance of observing no 
events if the true rate is 0.16% or less. For both VRC01 groups at the 30 mg/Kg 
dose level combined (n=39), there is a 90% chance of observing at least 1 event if 

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the true rate of such an event is 5.72 % or more; and there is a 90% chance of 
observing no events if the true rate is 0.26 % or less. As a reference, in HVTN 
vaccine trials from December 2000 through December 2012, about 4% of 
participants who received placebos experienced an SAE.  
Probabilities of observing 0, 1 or more, and 2 or more events among single arms 
or combined arms of sizes 5, 7, 12, 16, 23, 39, and 62 are presented in Table 6-1 
for a range of possible true AE or SAE rates. These calculations provide a more 
complete picture of the sensitivity of this study design to identify potential safety 
problems with either VRC01 or VRC01LS (based on the minimal sample sizes). 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
arms of size 5, 7, 12, 16, 23, 39, and 62, for a range of true event rates 
True event rate (%) 
Group Size 
0 Events 
1+ Events 
2+ Events 
1 
5 
0.95 
0.05 
<0.01 
7 
0.93 
0.07 
<0.01 
12 
0.89 
0.11 
<0.01 
16 
0.85 
0.15 
0.01 
 
23 
0.79 
0.21 
0.02 
 
39 
0.68 
0.32 
0.06 
 
62 
0.54 
0.46 
0.13 
 
 
 
 
 
4 
5 
0.82 
0.18 
0.01 
7 
0.75 
0.25 
0.03 
12 
0.61 
0.39 
0.08 
16 
0.52 
0.48 
0.13 
 
23 
0.39 
0.61 
0.23 
 
39 
0.20 
0.80 
0.47 
 
62 
0.08 
0.92 
0.71 
 
 
 
 
 
10 
5 
0.59 
0.41 
0.08 
7 
0.48 
0.52 
0.15 
12 
0.28 
0.72 
0.34 
16 
0.19 
0.81 
0.49 
 
23 
0.09 
0.91 
0.68 
 
39 
0.02 
0.98 
0.91 
 
62 
<0.01 
>0.99 
0.99 
 
 
 
 
 
20 
5 
0.33 
0.67 
0.26 
7 
0.21 
0.79 
0.42 
12 
0.07 
0.93 
0.73 
16 
0.03 
0.97 
0.86 
 
23 
<0.01 
>0.99 
0.96 
 
39 
<0.01 
>0.99 
>0.99 
 
62 
<0.01 
>0.99 
>0.99 
 
 
 
 
 
30 
5 
0.17 
0.83 
0.47 
7 
0.08 
0.92 
0.67 

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12 
0.01 
0.99 
0.91 
16 
<0.01 
>0.99 
0.97 
 
23 
<0.01 
>0.99 
>0.99 
 
39 
<0.01 
>0.99 
>0.99 
 
62 
<0.01 
>0.99 
>0.99 
An alternative way of describing the statistical properties of the study design is in 
terms of the 95% confidence interval for the true rate of an adverse event based 
on the observed data. Table 6-2 shows the 2-sided 95% confidence intervals for 
the probability of an event based on a particular observed rate. Calculations are 
done using the score test method (64). If none of 16 participants in either of the 
single infusion groups experiences a safety event, the 95% 2-sided upper 
confidence bound for the true rate of such events in the population is 19.36%. If 
none of 23 participants in Groups 1, 2, or 3 experiences a safety event, the 95% 2-
sided upper confidence bound for the true rate of such events is 14.31%. If none 
of the 39 participants in the Groups 2+4 experiences a safety event, the 95% 2-
sided upper confidence bound for the true rate of such events is 8.97%. For the 
total 62 participants in the VRC01 groups, the 95% 2-sided upper confidence 
bound for this rate is 5.83%. 
Table 6-2 Two-sided 95% confidence intervals based on observing a particular rate of safety 
endpoints for single or combined arms of size 5, 7, 12, 16, 23, 39, and 62 
Observed event rate 
Confidence interval (%) 
0/5 
(0.00, 0.43) 
1/5 
(0.04, 0.62) 
2/5 
(0.12, 0.77) 
 
 
0/7 
(0.00, 0.35) 
1/7 
(0.03, 0.51) 
2/7 
(0.08, 0.64) 
 
 
0/12 
(0.00, 0.24) 
1/12 
(0.01, 0.35) 
2/12 
(0.05, 0.45) 
 
 
0/16 
(0.00, 19.36) 
1/16 
(1.11, 28.33) 
2/16 
(3.50, 36.02) 
 
 
0/23 
(0.00, 14.31) 
1/23 
(0.77, 20.99) 
2/23 
(2.42, 26.80) 
 
 
0/39 
(0.00, 8.97) 
1/39 
(0.45, 13.18) 
2/39 
(1.42, 16.89) 
 
 

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0/62 
(0.00, 5.83) 
1/62 
 (0.29, 8.59)  
2/62 
(0.89, 11.02) 
6.1.2 
Sample size calculations for drug levels 
The main goal of this study regarding drug levels involves a preliminary 
assessment of the correlation between serum and mucosa drug level 
measurements or corresponding PK parameters estimated after the administration 
of VRC01 or VRC01LS. The statistical power to detect different levels of 
correlation (ρ) can be calculated using the Z-transformation (ie, Z'=arctanh(ρ)+ ρ 
/(2*(n-1)) followed by normal approximation. As shown in Table 6-3, there is 
limited power (≤ 77%) to detect a correlation of 0.9 or lower in a group size of 
n=6 or lower. However, for Groups 2+4 (VRC01 30mg/Kg) with n=15 in the 
assessment of male mucosal compartment, there is approximately 87% power to 
detect a correlation of 0.7 or higher, and with n = 17 in the assessment of female 
mucosal compartment, there is approximately 91% power to detect a correlation 
of 0.7 or higher. For Groups 1+2+4 (VRC01 10mg/Kg or 30 mg/Kg) in the 
assessment of each mucosal compartment with n=23 in male or n=25 in female, 
there is >88% or >94% power, respectively, to detect a correlation of 0.6 or 
higher.  
Based on earlier data in non-human primate studies with a total of 12 animals, the 
observed correlation between log-transformed peak serum and peak mucosa drug 
levels after a single infusion of VRC01 is in the range of 0.6 to 0.9 (personal 
communications with VRC colleagues). Therefore, this study is expected to 
provide reasonable power to achieve the primary objectives regarding drug levels 
for the combined VRC01 groups if the true correlation between serum and 
mucosa drug levels is similar to what was observed in the animal studies. There 
may be a reasonable power (> 77%) to detect correlations between serum and 
mucosal drug levels in the VRC01LS groups if such data are available from at 
least 6 participants and the true correlation is at least 0.9. 
Table 6-3 Statistical power (%) to detect different levels of correlation between log-
transformed serum and mucosal drug levels in group sizes of 6-28 assuming 15% missing 
data, respectively, in Group 4, Group 1 or 2, Groups 2+4, and Groups 1+2+4 for each 

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mucosal compartment among males or females (assuming 10 males and 13 females in 
groups 1 and 2, and 8 males and 8 females in group 4).  
True correlation 
coefficient 
Sample size for each mucosal compartment 
6 
8 
11 
15 
17 
23 
28 
0.3 
9 
11 
15 
20 
22 
29 
35 
0.4 
13 
17 
24 
33 
37 
49 
58 
0.5 
18 
25 
37 
50 
56 
71 
80 
0.6 
26 
37 
53 
69 
76 
88 
94 
0.7 
37 
53 
72 
87 
91 
98 
99 
0.8 
53 
73 
89 
97 
99 
100 
100 
0.9 
77 
93 
99 
100 
100 
100 
100 
6.2 
Randomization  
The randomization sequence will be obtained by computer-generated random 
numbers and provided to each HVTN CRS through the SDMC via a Web-based 
randomization system. Participants will be randomized to either one of Groups 1-
3 or one of Groups 4-5, depending on site. The randomization will be stratified by 
sex at birth and done in blocks to ensure balance. All participants will be 
randomized prior to the first infusion, ideally within 4 days. Once enrollment has 
stopped in Groups 3 and 5, participants will then be randomized to either one of 
Groups 1 and 2 or be enrolled in Group 4, depending on site. At each institution, 
the pharmacist with primary responsibility for dispensing study products is 
charged with maintaining consistency of the treatment assignments. 
6.3 
Blinding 
The study will be open label.  
6.4 
Statistical analysis 
This section describes the final study analysis. Of note, Groups 1-3 participants 
are enrolled 1 month before the first infusion. Groups 4 and 5 participants are 
enrolled at the first infusion. All analyses pertaining to the safety and drug level 
objectives of this study are intent-to-treat analyses that include all randomized 
individuals per their randomization allocation. In addition, analyses will also be 
performed as treated accounting for the actual infusions and dose levels each 
participant received. 
Analyses will be performed using SAS and R. Other software may be used to 
perform additional exploratory pharmacokinetics analyses. 
No formal multiple comparison adjustments will be employed for multiple safety 
endpoints. 

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6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, and 
laboratory measurements for primary- and secondary-objective analyses. 
6.4.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using 
descriptive statistics. 
6.4.3 
Safety/tolerability analysis 
All participants who received at least 1 partial or complete infusion will provide 
some safety data. 
6.4.3.1 
Reactogenicity 
The number and percentage of participants experiencing each type of 
reactogenicity sign or symptom will be tabulated by severity and treatment arm 
and the percentages displayed graphically by arm. For a given sign or symptom, 
each participant’s reactogenicity will be counted once under the maximum 
severity for all infusion visits. In addition, to the individual types of events, the 
maximum severity of local pain or tenderness, induration or erythema, and of 
systemic symptoms will be calculated. 
6.4.3.2 
AEs and SAEs 
AEs will be summarized using MedDRA System Organ Class and preferred 
terms. Tables will show by treatment arm the number and percentage of 
participants experiencing an AE within a System Organ Class or within preferred 
term category by severity or by relationship to study product. For the calculations 
in these tables, a participant with multiple AEs within a category will be counted 
once under the maximum severity or the strongest recorded causal relationship to 
study product. Formal statistical testing comparing arms is not planned since 
interpretation of differences must rely heavily upon clinical judgment. 
A listing of SAEs reported to the DAIDS Regulatory Support Center (RSC) 
Safety Office will provide details of the events including severity, relationship to 
study product, time between onset and last infusion, and number of infusions 
received.  
6.4.3.3 
Local laboratory values  
Boxplots of local laboratory values will be generated for baseline values and for 
values measured during the course of the study by treatment arm and visit. Each 
boxplot will show the first quartile, the median, and the third quartile. Outliers 
(values outside the boxplot) will also be plotted. If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted. 

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For each local laboratory measure, summary statistics will be presented by 
treatment arm and timepoint, as well as changes from baseline for postenrollment 
values. In addition, the number (percentage) of participants with local laboratory 
values recorded as meeting Grade 1 AE criteria or above as specified in the 
DAIDS AE Grading Table (see Section 11.2) will be tabulated by treatment arm 
for each postinfusion timepoint. Reportable clinical laboratory abnormalities 
without an associated clinical diagnosis will be included in the tabulation of AEs 
described above. 
6.4.3.4 
Reasons for discontinuation of study product administration and early 
study termination 
The number and percentage of participants who discontinue study product 
administration and who terminate the study early will be tabulated by reason and 
treatment arm. 
6.4.4 
Analysis of drug-level endpoints 
6.4.4.1 
General approach 
For the statistical analysis of endpoints, data from enrolled participants will be 
used according to the initial randomization assignment regardless of how many 
infusions they received. Additional analyses may be performed, limited to 
participants who received all scheduled infusions per protocol. Assay results that 
are unreliable, from specimens collected outside of the visit window, or from 
HIV-infected participants postinfection will be excluded. Since the exact date of 
HIV infection is unknown, any assay data from blood draws 4 weeks prior to an 
infected participant’s last seronegative sample and thereafter may be excluded. If 
an HIV-infected participant does not have a seronegative sample postenrollment, 
then all data from that participant may be excluded from the analysis.  
For continuous assay data (eg, serum concentration of VRC01), graphical and 
tabular summaries of the distributions by treatment arm and timepoint will be 
made. Scatterplot matrix with correlation coefficient information between each 
pair of serum and mucosa drug levels at different timepoints will be provided. An 
appropriate data transformation (eg, log transformation) may be applied prior to 
testing to better satisfy analysis assumptions. Inference from these analyses would 
be limited by the small sample sizes of the groups. 
For qualitative assay variables (eg, positive or negative), the analyses will be 
performed by tabulating the frequency of positive responses for each assay by 
group at each timepoint at which an assessment is performed. Crude response 
rates will be presented with their corresponding 95% confidence interval 
estimates calculated using the score test method (64).  
More sophisticated analyses of drug-level data and other assay data collected over 
time employing repeated measures methodology that is valid under the missing at 
random (MAR) assumption (for example, nonlinear mixed effects models) may 

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be utilized to incorporate outcome responses over several timepoints and to 
account for subject heterogeneity. MAR assumes that the probability of an 
observation being missing may depend upon the observed responses and upon 
observed covariates, but not upon any unobserved factors. Generalized nonlinear 
models for response rates will use a binomial error distribution and for 
quantitative endpoints, a normal error distribution. All models will include as 
covariates all available baseline predictors of the missing outcomes.  
In addition, non-compartment PK analysis will be performed to estimate PK 
parameters from individual time-concentration curves. The correlation between 
individual-level PK parameters estimated for different specimen types (serum vs. 
mucosa) may also be assessed. All statistical tests will be 2-sided and will be 
considered statistically significant if p  0.05.  
For the analysis of correlation between two continuous assay variables over time, 
graphical summary and tabular summary of the sample correlation at each given 
timepoint will be made. Cross-correlation of the 2 variables with different time 
lags may also be calculated and visually displayed if there are at least 10 
participants with no missing data over time from both variables. Nonlinear or 
linear mixed effects models may also be used to predict mucosal drug levels 
based on serum drug levels collected at the same or previous timepoints. More 
details of the statistical analysis approaches will be described in a separate 
Statistical Analysis Plan document. 
6.4.5 
Analyses prior to end of scheduled follow-up visits 
Any analyses conducted prior to the end of the scheduled follow-up visits should 
not compromise the integrity of the trial in terms of participant retention or safety, 
drug level or functional endpoint assessments.  
6.4.5.1 
Safety 
During the course of the trial, analyses of safety data will be prepared 
approximately every 4 months, as defined in Section 3, for review by the SMB. 
Ad hoc safety reports may also be prepared for SMB review at the request of the 
PSRT. The HVTN leadership must approve any other requests for safety data 
prior to the end of the scheduled follow-up visits. 
6.4.5.2 
Anti-VRC01, anti-VRC01LS and other Laboratory Assessments  
Generally, analysis of a primary laboratory endpoint may be performed when all 
participants have completed the corresponding visit and data are available for 
analysis from at least 80% of these participants. The Laboratory Program will 
review the analysis report prior to distribution to the protocol chairs, DAIDS, 
vaccine developer, and other key HVTN members and investigators. Distribution 
of reports will be limited to those with a need to know for the purpose of 
informing future trial-related decisions.  

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7 
Selection and withdrawal of participants 
Participants will be healthy, HIV-uninfected (seronegative) adults who 
comprehend the purpose of the study and have provided written informed consent. 
Volunteers will be recruited and screened; those determined to be eligible, based 
on the inclusion and exclusion criteria, will be enrolled in the study. Final 
eligibility determination will depend on results of laboratory tests, medical 
history, physical examinations, and answers to self-administered and/or interview 
questions.  
Investigators should always use good clinical judgment in considering a 
volunteer’s overall fitness for trial participation. Some volunteers may not be 
appropriate for enrollment even if they meet all inclusion/exclusion criteria. 
Medical, psychiatric, occupational, or other conditions may make evaluation of 
safety and/or pharmacokinetics difficult, and some volunteers may be poor 
candidates for retention. 
Determination of eligibility, taking into account all inclusion and exclusion 
criteria, must be made within 56 days prior to enrollment unless otherwise noted 
in Sections 7.1 and 7.2. 
7.1 
Inclusion criteria 
General and Demographic Criteria 
1. Age of 18 to 50 years 
2. Weight ≤ 115 kg 
3. Access to a participating HVTN CRS and willingness to be followed for the 
planned duration of the study 
4. Ability and willingness to provide informed consent 
5. Assessment of understanding: volunteer demonstrates understanding of this 
study; completes a questionnaire prior to enrollment with verbal demonstration of 
understanding of all questionnaire items answered incorrectly 
6. Agrees not to enroll in another study of an investigational research agent until 
completion of the last study visit 
7. Good general health as shown by medical history, physical exam, and screening 
laboratory tests 
HIV-Related Criteria: 
8. Willingness to receive HIV test results 

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9. Willingness to discuss HIV infection risks and amenable to HIV risk reduction 
counseling.  
10. Assessed by the clinic staff as being at “low risk” for HIV infection [low risk 
guidelines are found on the protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn116)] and committed to maintaining 
behavior consistent with low risk of HIV exposure through the last required 
protocol clinic visit. 
Laboratory Inclusion Values 
Hemogram/CBC 
11. Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for 
volunteers who were born male 
12. White blood cell count = 2,500 to 12,000 cells/mm3 
13. Total lymphocyte count ≥ 800 cells/mm3 
14. Remaining differential either within institutional normal range or with site 
physician approval 
15. Platelets = 125,000 to 550,000/mm3 
Chemistry 
16. Chemistry panel: ALT, AST, and alkaline phosphatase < 1.25 times the 
institutional upper limit of normal; creatinine ≤ institutional upper limit of normal. 
Virology 
17. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-
approved enzyme immunoassay (EIA). Non-US sites may use locally available 
assays that have been approved by HVTN Laboratory Operations. 
18. Negative Hepatitis B surface antigen (HBsAg)  
19. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV 
polymerase chain reaction (PCR) if the anti-HCV is positive 
Urine 
20. Normal urine: 
 Negative urine glucose, and 
 Negative or trace urine protein, and 

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 Negative or trace urine hemoglobin (if trace hemoglobin is present on 
dipstick, a microscopic urinalysis with red blood cells levels within 
institutional normal range). 
Reproductive Status 
21. Volunteers who were born female: negative serum or urine beta human 
chorionic gonadotropin (β-HCG) pregnancy test performed prior to initial biopsy 
for groups 1-3 and prior to initial infusion for groups 4-5 on the day of 
enrollment. Persons who are NOT of reproductive potential due to having 
undergone bilateral oophorectomy (verified by medical records), are not required 
to undergo pregnancy testing. 
22. Reproductive status:  
United States 
A volunteer who was born female must: 
 Agree to consistently use effective contraception (see Appendix C) for sexual 
activity that could lead to pregnancy from at least 21 days prior to enrollment 
through the last required protocol clinic visit. Effective contraception is 
defined as using the following methods: 
 Condoms (male or female) with or without a spermicide, 
 Diaphragm or cervical cap with spermicide, 
 Intrauterine device (IUD), 
 Hormonal contraception, or 
 Any other contraceptive method approved by the HVTN 116 PSRT 
 Successful vasectomy in the male partner (considered successful if a 
volunteer reports that a male partner has [1] documentation of 
azoospermia by microscopy, or [2] a vasectomy more than 2 years ago 
with no resultant pregnancy despite sexual activity postvasectomy); 
 Or not be of reproductive potential, such as having had a bilateral 
oophorectomy, or tubal ligation; 
 Or be sexually abstinent. 
South Africa 
A volunteer who was born female must: 
 Agree to consistently use effective contraception (see Appendix D) for sexual 
activity that could lead to pregnancy from at least 21 days prior to enrollment 

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through the last required protocol clinic visit. Effective contraception for 
participants in South Africa is defined as using 2 methods of birth control.  
ONE barrier contraceptive method: 
 Condoms (male or female) 
 Diaphragm or cervical cap 
PLUS ONE of the following methods: 
 Intrauterine device (IUD), 
 Hormonal contraception, or 
 Successful vasectomy in the male partner (considered successful if a 
volunteer reports that a male partner has [1] documentation of 
azoospermia by microscopy, or [2] a vasectomy more than 2 years ago 
with no resultant pregnancy despite sexual activity postvasectomy), or 
 Any other contraceptive method approved by the HVTN 116 PSRT 
 Or not be of reproductive potential, such as having had a bilateral 
oophorectomy, or tubal ligation; 
 Or be sexually abstinent. 
23. Volunteers who were born female must also agree not to seek pregnancy 
through alternative methods, such as artificial insemination or in vitro 
fertilization until after the last required protocol clinic visit 
Mucosal Specimen Collection 
24. Volunteers 21 years of age and older who were born female: Pap smear 
(verified by medical records) is required within: 
 the 3 years prior to enrollment with the latest result reported as normal or 
ASCUS (atypical squamous cells of undetermined significance), OR  
 the 5 years prior to enrollment, with the latest result reported as normal, or 
ASCUS with no evidence of high risk HPV. 
If no Pap smear was done within the last 3 years (or within the last 5 years, if high 
risk HPV testing was performed), the volunteer must be willing to undergo a Pap 
smear with the result reported (verified by medical records) as normal or ASCUS 
prior to sample collection. 
25. Willing to have mucosal secretions and tissue biopsies collected 
26. Willing to abstain from sexual intercourse for the required period after each 
biopsy collection 

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7.2 
Exclusion criteria 
General 
1. Blood products received within 120 days before first infusion, unless eligibility 
for earlier enrollment is determined by the HVTN 116 PSRT 
2. Investigational research agents received within 30 days before first infusion 
3. Intent to participate in another study of an investigational research agent or 
any other study that requires non-HVTN HIV antibody testing during the planned 
duration of the HVTN 116 study  
4. Pregnant or breastfeeding 
5. Active duty US military personnel with the potential of being deployed during 
the study 
Vaccines and other Injections 
6. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have 
received control/placebo in an HIV vaccine trial, the HVTN 116 PSRT will 
determine eligibility on a case-by-case basis. 
7. Non-HIV experimental vaccine(s) received within the last 6 months in a prior 
vaccine trial. Exceptions may be made for some vaccines and vaccine trials. For 
volunteers who have received an experimental vaccine(s) less than 6 months ago, 
eligibility for enrollment will be determined by the HVTN 116 PSRT on a case-
by-case basis. 
8. Live attenuated vaccines other than influenza vaccine received within 10 days 
before first Infusion or scheduled within 10 days after first infusion (eg, measles, 
mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever) 
9. Previous receipt of humanized or human mAbs whether licensed or 
investigational. 
Immune System  
10. Immunosuppressive medications received within 30 days before first infusion. 
(Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; or 
[3] topical corticosteroids for mild, uncomplicated dermatitis) 
11. Serious adverse reactions to VRC01 and VRC01LS formulation components 
such as sodium citrate, sodium chloride, and L-arginine hydrochloride, 
including history of anaphylaxis and related symptoms such as hives, respiratory 
difficulty, angioedema, and/or abdominal pain. 

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12. Autoimmune disease (Not exclusionary: mild, well-controlled psoriasis) 
13. Immunodeficiency 
Clinically significant medical conditions  
14. Untreated or incompletely treated syphilis infection 
15. Clinically significant medical condition, physical examination findings, 
clinically significant abnormal laboratory results, or past medical history with 
clinically significant implications for current health. A clinically significant 
condition or process includes but is not limited to: 
 A process that would affect the immune response, 
 A process that would require medication that affects the immune response, 
 Any contraindication to repeated infusions or blood draws, including 
perceived inability to establish venous access 
 A condition that requires regular use of any anticoagulant medications (not 
including aspirin or NSAIDs), 
 A condition that requires active medical intervention or monitoring to avert 
grave danger to the volunteer’s health or well-being during the study period, 
 A condition or process for which signs or symptoms could be confused with 
reactions to study product, or 
 Any condition specifically listed among the exclusion criteria below. 
16. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication 
to, protocol adherence, assessment of safety or reactogenicity, or a volunteer’s 
ability to give informed consent 
17. Psychiatric condition that precludes compliance with the protocol. 
Specifically excluded are persons with psychoses within the past 3 years, ongoing 
risk for suicide, or history of suicide attempt or gesture within the past 3 years. 
18. Current anti-tuberculosis (TB) prophylaxis or therapy 
19. Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity 
as defined in the most recent National Asthma Education and Prevention Program 
(NAEPP) Expert Panel report).  
 
Exclude a volunteer who: 

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 Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or 
 Uses moderate/high dose inhaled corticosteroids, or 
 In the past year has either of the following: 
 Greater than 1 exacerbation of symptoms treated with oral/parenteral 
corticosteroids; 
  Needed emergency care, urgent care, hospitalization, or intubation for 
asthma. 
20. Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. 
(Not excluded: history of isolated gestational diabetes.) 
21. Thyroidectomy, or thyroid disease unless well controlled (normal T3/T4/TSH) 
with medication. 
22. Hypertension: 
 If a person has been found to have elevated blood pressure or hypertension 
during screening or previously, exclude for blood pressure that is not well 
controlled. Well-controlled blood pressure is defined as consistently ≤ 140 
mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with 
only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg 
systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must 
be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment. 
 If a person has NOT been found to have elevated blood pressure or 
hypertension during screening or previously, exclude for systolic blood 
pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg 
at enrollment. 
23. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or 
platelet disorder requiring special precautions) 
24. Malignancy (Not excluded from participation: Volunteer who has had 
malignancy excised surgically and who, in the investigator’s estimation, has a 
reasonable assurance of sustained cure, or who is unlikely to experience 
recurrence of malignancy during the period of the study) 
25. Seizure disorder: History of seizure(s) within past three years. Also exclude if 
volunteer has used medications in order to prevent or treat seizure(s) at any time 
within the past 3 years. 
26. Asplenia: any condition resulting in the absence of a functional spleen 
27. History of hereditary angioedema, acquired angioedema, or idiopathic 
angioedema 

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28. For those undergoing rectal biopsies, a rectal condition, such as an active 
infection or inflammation of the colorectal area (eg, an HSV-2 outbreak or 
inflamed hemorrhoids or colitis/diarrhea), internal hemorrhoids, or any other 
condition noted during screening rectal exam via anoscope or in medical history 
that in the opinion of the clinician represents a contraindication to mucosal 
sampling.  
29. For those undergoing vaginal and cervical biopsies, any condition noted 
during pelvic exam via speculum or in medical history that in the opinion of the 
clinician represents a contraindication to mucosal sampling.  
30. An active genital tract condition, such as an active infection or inflammation of 
the genital tract (eg, genital sores or ulcers, penile or abnormal vaginal discharge, 
genital warts that are symptomatic or requiring treatment) or any other condition 
that in the opinion of the clinician represents a contraindication to mucosal 
sampling. 
31. Hysterectomy 
32. Menopause 
7.3 
Participant departure from infusion schedule or withdrawal 
This section concerns an individual participant’s departure from the infusion 
schedule. Pause rules for the trial as a whole are described in Section 11.3. 
7.3.1 
Delaying infusions for a participant 
Under certain circumstances, a participant’s scheduled infusion will be delayed. 
The factors to be considered in such a decision include but are not limited to the 
following: 
 Within 10 days prior to any infusion 
 Receipt of live attenuated vaccines other than influenza vaccine. The delay 
may be reduced if residual inflammation from receiving the vaccine has 
resolved sooner  
 Within 14 days prior to any infusion 
 Intercurrent illness that is not expected to resolve prior to the next 
scheduled infusion which is assessed by the site principal investigator (or 
designee) to require delay or withdrawal from the infusion schedule. The 
investigator may consult the HVTN 116 PSRT. 
 Pre-infusion abnormal vital signs or clinical symptoms that may mask 
assessment of study product reaction. 

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 Pregnancy: for participants who become pregnant, no study product 
administrations will be given, except for participants who may have been 
pregnant during the study but are no longer pregnant as shown by 2 negative 
urine pregnancy tests taken from 2 different urine samples that may be 
collected on the same day. In this circumstance, the HVTN 116 PSRT should 
be consulted to determine if the participant may resume study product 
administrations. 
Study product should not be administered outside the visit window period 
specified in the HVTN 116 Study Specific Procedures. 
In order to avoid infusion delays and missed infusions, participants who plan to 
receive live attenuated licensed vaccines other than influenza vaccine should be 
counseled to schedule receipt of these substances, when possible, outside the 
intervals indicated above. The effects of these substances on safety and laboratory 
assessments and their interactions with study products are unknown.  
7.3.2 
Participant departure from infusion schedule 
Every effort should be made to follow the infusion schedule per the protocol. If a 
participant misses an infusion and the visit window period for the infusion has 
passed, that infusion cannot be given. The participant should resume the infusion 
schedule with the next infusion unless there are circumstances that require further 
delay or permanent discontinuation of study product administrations (Sections 
7.3.1 and 7.3.3). 
7.3.3 
Discontinuing study product administrations for a participant 
Under certain circumstances, an individual participant’s infusions will be 
permanently or temporarily discontinued. Specific events that will result in 
stopping a participant’s infusion schedule include: 
 Co-enrollment in a study with an investigational research agent (rare 
exceptions allowing for the continuation of infusions may be granted with the 
unanimous consent of the HVTN 116 PSRT). 
 Clinically significant condition (ie, a condition that affects the immune system 
or for which continued infusions and/or blood draws may pose additional 
risk), including but not limited to the following: 
 Pregnancy (infusions will be stopped while a participant is pregnant. If the 
participant is no longer pregnant and can be infused within an appropriate 
visit window, infusions may resume, see Section 7.3.1); 
 HIV infection; 
 Any grade 4 local or systemic reactogenicity symptom, lab abnormality, or 
AE that is subsequently considered to be related to study product 
administration; 

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 Any grade 3 lab abnormality or other clinical AE (exception: fever or 
vomiting and subjective local and systemic symptoms) that is 
subsequently considered to be related to study product administration; or 
 Clinically significant type 1 hypersensitivity reaction associated with 
study product administration. Consultation with the HVTN 116 PSRT is 
required prior to subsequent infusions following any type 1 
hypersensitivity reaction associated with study product administration; or 
 Investigator determination in consultation with Protocol Team leadership (eg, 
for repeated nonadherence to study staff instructions). 
Participants discontinuing study product for reasons other than HIV infection 
should be counseled on the importance of continuing with the study and strongly 
encouraged to participate in follow-up visits and protocol-related procedures per 
the protocol for the remainder of the trial, unless medically contraindicated. 
Participants diagnosed with HIV infection during the study should be encouraged 
to participate in follow-up visits as indicated in Section 9.14. 
7.3.4 
Delaying biopsy collections for a participant 
An individual participant’s biopsy collections may be delayed in certain 
circumstances as described in section 9.6. Apart from medical reasons (eg, 
menstruation or infection), personal reasons may also trigger such delays. If 
biopsy collection is delayed, it should be performed as soon as possible, within 
the visit window. Biopsies should not be performed outside the visit windows 
specified in the HVTN 116 Study Specific Procedure. The participant should 
resume the biopsy collection schedule with the next biopsy collection unless there 
are circumstances that require further delay or permanent discontinuation of 
biopsy collections (see section 7.3.5).  
Pregnancy: for participants who become pregnant, no biopsies will be collected, 
except for participants who may have been pregnant during the study but are no 
longer pregnant as shown by 2 negative urine pregnancy tests taken from 2 
different urine samples that may be collected on the same day. In this 
circumstance, the HVTN 116 PSRT should be consulted to determine if the 
participant may resume biopsy collection. 
7.3.5 
Discontinuing biopsy collections for a participant 
An individual participant’s biopsy collections will be permanently discontinued 
under certain circumstances, including: 
 Increase in risk of HIV infection, as indicated by: 
 New diagnosis of chlamydia, gonorrhea, syphilis, or any other disease 
that, in the clinician’s opinion may indicate an increased risk of HIV 
infection 

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 Change in HIV risk behavior 
 HIV infection 
 Any medical condition that presents a contraindication for biopsies (eg, a 
condition requiring anticoagulants), in consultation with the PSRT 
 Investigator determination in consultation with the PSRT and/or Protocol 
Team leadership (this may include, but is not limited to, situations in which no 
tissue Ab levels were detected at a previous visit) 
 The participant is no longer willing to provide biopsies 
7.3.6 
Participant termination from the study 
Under certain circumstances, an individual participant may be terminated from 
participation in this study. Specific events that will result in early termination 
include: 
 Participant refuses further participation, 
 Participant relocates and remote follow-up or transfer to another HVTN CRS 
is not possible, 
 HVTN CRS determines that the participant is lost to follow-up, or 
 Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff). 
 Any condition where termination from the study is required by applicable 
regulations. 
 Participant declines further mucosal biopsies between the baseline biopsies 
and the first infusion (Groups 1-3). 
If study product is not detectable in any of the samples (including biopsies) at two 
consecutive follow-up visits, participants may be excluded from further sample 
collections at the discretion of the HVTN 116 PSRT. If such a decision is reached, 
the participant will be terminated after a final study visit. 

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8 
Study product preparation and administration 
CRS pharmacists should consult the Pharmacy Guidelines and Instructions for 
DAIDS Clinical Trials Networks for standard pharmacy operations. The protocol 
schema is shown in Table 3-1. 
See the Investigator’s Brochures for further information about study products. 
8.1 
Infusion regimen 
The schedule of infusions is shown in Section 3 and additional information is 
given below. The study is open label. 
Group 1  
Treatment 1 (T1): VRC01 (VRC-HIVMAB060-00-AB) 10 mg/kg to be 
administered IV in 100 mL of Sodium Chloride for Injection USP, 0.9% at Month 
0, Month 2, Month 4, and Month 6.  
Group 2  
Treatment 2 (T2): VRC01 (VRC-HIVMAB060-00-AB) 30 mg/kg to be 
administered IV in 100 mL of Sodium Chloride for Injection USP, 0.9% at Month 
0, Month 2, Month 4, and Month 6 
Group 3 
Treatment 3 (T3): VRC01LS (VRC-HIVMAB080-00-AB ) 30 mg/kg to be 
administered IV in 100 mL of Sodium Chloride for Injection USP, 0.9% at Month 
0, Month 3, and Month 6 
Group 4  
Treatment 4 (T4): VRC01 (VRC-HIVMAB060-00-AB) 30 mg/kg to be 
administered IV in 100 mL of Sodium Chloride for Injection USP, 0.9% at Month 
0. 
Group 5  
Treatment 5 (T5): VRC01LS (VRC-HIVMAB080-00-AB )30 mg/kg to be 
administered IV in 100 mL of Sodium Chloride for Injection USP, 0.9% at Month 
0. 

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8.2 
Study product formulation  
VRC01 (Labeled as VRC01 HIV MAb Drug Product VRC-HIVMAB060-
00-AB) 
VRC01 will be 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 ± 
0.1 mL fill volume and 3 mL glass vials with a 2.25 ± 0.1 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. The vials are intended for single use only 
and thus do not contain a preservative.  
VRC01 product label designates the long-term storage as -35°C to -15°C (-31°F 
to 5°F). Clinical site storage in a continuously monitored, temperature-controlled 
freezer with temperature excursions between -45°C to -10°C (-49°F to 14°F) is 
acceptable. 
VRC01LS (Labeled as VRC01LS HIV MAb Drug Product VRC-
HIVMAB080-00-AB) 
VRC01LS will be supplied in 10 mL glass vials with a 6.25 ± 0.1 mL fill volume 
at a concentration of 100 ± 10 mg/mL and 3 mL glass vials with a 2.25 + 0.1 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 thus do not contain a preservative. 
VRC01LS product label designates the long-term storage as -35°C to -15°C (-
31F to 5F). Clinical site storage in a continuously monitored, temperature-
controlled freezer with temperature excursions between -45°C to -10°C (-49F to 
14F) is acceptable. 
8.3 
Preparation of study products 
8.3.1 
VRC01 (T1, T2, T4) 
Thawing instructions 
Thaw vials of VRC01 at controlled room temperature (maximum 27oC) for a 
minimum of 1 hour. Thawed vials should contain fluid that is a clear, colorless to 
yellow liquid essentially free of visible particles. VRC01 vials must either be used 
to prepare an infusion or placed in a refrigerator at 2°C to 8°C (36°F to 46°F) 

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before reaching the maximum storage of 24 hours at room temperature; VCR01 
may be stored up to 4 weeks at 2°C to 8°C (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, opaque-
to-translucent particles after thawing. Vial(s) of VRC01 containing particles 
should be placed in the refrigerator as particles may continue to dissipate at 2-
8°C. Vials of VRC01 that previously contained particles but subsequently become 
clear of particles may be used. Vials that continue to have visible particles after a 
maximum of 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 destroyed 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. 
IV infusion preparation instructions 
The pharmacist must receive a prescription that states the participant’s weight 
obtained at the most recent visit where weight was measured. Participants’ 
screening weight, entry weight, or last obtained weight may be used for 
estimating the dose to thaw vials. After removal from 2-8°C, vials of VRC01 
must be equilibrated to controlled room temperature (maximum 27°C) 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 
(maximum 27°C) prior to product preparation is 8 hours after removal from the 
refrigerator.  
Prior to preparation for administration, vials should be swirled for 30 seconds with 
sufficient force to resuspend any visible particles, yet avoiding foaming. DO NOT 
SHAKE THE VIALS. If particles are observed, return the vials to 2°C to 8°C storage. 
If particles continue to be observed, do not use the vialed product for IV 
administration. If the particles redissolve within the maximum storage times of up to 
4 weeks at 2°C to 8°C, the vials may be used for product preparation. 
1. Calculate the total milligrams of VRC01 required based on the participants 
weight and the randomized treatment group of either 10 mg/kg or 30 
mg/kg and the 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. 
2. Gently swirl thawed vials for 30 seconds, yet avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright at all times until ready to 
withdraw the contents. Do not invert the vial during inspection. 
3. Observe vials for particles. If particles are observed refer to the thawing 
instructions for further information. 

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4. Add the required volume for the calculated total milligrams needed to 
0.9% Sodium Chloride for Injection, USP 100 mL IV bag or IV glass 
bottle using aseptic technique to maintain sterility in a clean room with 
limited access using either an isolator, laminar flow hood, or biological 
safety cabinet following the country’s requirements for medium risk 
sterile compounding. The 0.9% Sodium Chloride for 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. Alternatively, the pharmacist can 
obtain a different volume of 0.9% Sodium Chloride for Injection, USP (50 
ml, 150 mg, 200 mg, 250 ml, 500 ml, etc.) for use to prepare the study IV 
infusion in 100 mls of 0.9% Sodium Chloride for Injection, USP. 
5. Label the IV bag with patient identifier, the randomized dose of VRC01 of 
either 10mg/kg or 30 mg/kg, and the total amount (mg) of VRC01 added 
to the 0.9% Sodium Chloride Injection, USP, 100 mL, the final volume of 
the bag, lot number, storage instructions, Investigational Use Statement 
(“Limited by Federal Law to Investigational Use”), and manufacturer 
information.  
After product preparation in IV bags, the prepared VRC01 may be stored at 2°C to 
8°C up to 96 hours or at room temperature (maximum 27°C) for a maximum of 6 
hours total including the infusion. 
The IV bag will also be labeled with a DO NOT INFUSE after date and time as 
follows: 
o 96 hours if stored at 2°C to 8°C 
o 6 hours, including completion of infusion, if at room temperature (maximum 
27°C). 
Any unused portion of a VRC01 vial will not be used for another participant. Any 
empty vials, unused portion of entered vials, or unused IV solution which contains 
study product should be discarded in a biohazard containment bag and incinerated 
or destroyed in accordance with institutional or pharmacy policy.  
8.3.2 
VRC01LS (T3, T5) 
Thawing instructions 
Thaw vials of VRC01LS at controlled room temperature (maximum 27°C) for a 
minimum of 1 hour after removing from freezer. Thawed vials should contain 
fluid that is a clear, colorless to yellow liquid and no particles are observed. 
VRC01LS vials must either be used to prepare an infusion or placed in a 
refrigerator at 2°C to 8°C (36°F to 46°F) before reaching the maximum storage of 

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24 hours at controlled room temperature (maximum 27°C); VCR01LS may be 
stored up to 4 weeks at 2°C to 8°C (36°F to 46°F). 
If stored at 2°C to 8°C (36°F to 46°F), vials must be equilibrated to controlled 
room temperature (maximum 27°C) for a minimum of 30 minutes and may be 
held at controlled room temperature (maximum 27°C) for up to 8 hours prior to 
product preparation.  
VRC01LS may not be stored in direct sunlight at anytime. 
VRC01LS is a highly concentrated protein solution and may develop white, 
opaque-to-translucent particles after thawing. Vial(s) of VRC01LS containing 
particles should be placed in the refrigerator as particles may continue to dissipate 
at 2-8°C. Vials of VRC01LS that previously contained particles but subsequently 
become clear of particles may be used.  
Vials that continue to have visible particles after a maximum of 4 weeks at 2°C to 
8°C (36°F to 46°F) are not to be used and will be quarantined and continued to be 
stored at 2°C to 8°C (36°F to 46°F.) Contact the protocol pharmacist for further 
instructions regarding handling of vials of VRC01LS with particles. 
IV infusion preparation instructions 
The pharmacist must receive a prescription that states the participant’s weight 
obtained at the most recent visit where weight was measured. Participants’ 
screening weight, entry weight, or last obtained weight may be used for 
estimating the dose to thaw vials. After removal from 2-8°C, vials of VRC01LS 
must be equilibrated to controlled room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to preparing IV infusions.  
1. Calculate the total milligrams of VRC01LS required based on the 
participants weight, 30 mg/kg and the total number of vials required based 
on a 6 mL withdrawal volume containing 600 mg of VRC01LS or 2 ml 
withdrawal volume containing 200 mg of VRC01LS. 
2. Gently swirl thawed vials for 30 seconds, yet avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright at all times until ready to 
withdraw the contents. Do not invert the vial during inspection. 
3. Observe vials for particles. If particles are observed refer to the thawing 
instructions for further information. 
4. Add the required volume for the calculated total milligrams needed to 
0.9% Sodium Chloride for Injection, USP 100 mL IV bag or glass bottle 
using aseptic technique to maintain sterility in a clean room with limited 
access using either an isolator, laminar flow hood, or biological safety 
cabinet following the country’s requirements for medium risk sterile 
compounding. The 0.9% Sodium Chloride for Injection, USP, 100 mL bag 

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will accommodate the additional volume required for the dose of 
VRC01LS to be used in this study. Do not withdraw fluid from the 0.9% 
Sodium Chloride for Injection, USP, 100 mL bag to make room for the 
volume of study product to be added. Alternatively, the pharmacist can 
obtain a different volume of 0.9% Sodium Chloride for Injection, USP (50 
ml, 150 mg, 200 mg, 250 ml, 500 ml, etc.) for use to prepare the study IV 
infusion in 100 mls of 0.9% Sodium Chloride for Injection, USP. 
5. Label the IV bag with patient identifier, dose of VRC01LS 30 mg/kg, and 
the total amount (mg) of VRC01LS added to the 0.9% Sodium Chloride 
Injection, USP, 100 mL, the final volume of the bag, lot number, storage 
instructions, Investigational Use Statement (“Limited by Federal Law to 
Investigational Use”), and manufacturer information. 
After product preparation in IV bags, the prepared VRC01LS may be stored at 
2°C to 8°C (36°F to 46°F) up to 24 hours or at room temperature (maximum 
30°C) for a maximum of 8 hours total including infusion time. 
The IV bag will also be labeled with a DO NOT INFUSE after date and time as 
follows: 
o 24 hours if stored at 2°C to 8°C 
o 8 hours, including completion of infusion, if at room temperature (maximum 
30°C). 
Any unused portion of a VRC01LS vial will not be used for another participant. 
Any empty vials, unused portion of entered vials, or unused IV solution which 
contains study product should be discarded in a biohazard containment bag and 
incinerated or destroyed in accordance with institutional or pharmacy policy.  
8.4 
Administration 
VRC01 and VRC01LS (intravenously) 
An in-line filter infusion set must be used for IV administration (see the HVTN 
116 SSP for specifications and additional details). In-line filters must comply with 
the following specifications: 1.2 micron PES (polyethersulfone) filter membrane, 
DEHP-free, latex-free (equivalent to Braun #473994 filter extension set). When 
the in-line filter is added to the tubing, prime the administration set. Flush the 
administration set with about 30 mL or appropriate volume of normal saline at the 
end of product administration. 
For Groups T1, T2, T3, T4, and T5: The IV bag prepared by the pharmacy will 
include the total amount (mg) of VRC01 or VRC01LS added to the 100 mL 
normal saline bag and the final volume of the bag. The clinician responsible for 
administration and another clinician will each check the bag label and confirm 

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that the identifier is correct and that the correct total milligrams to be 
administered is shown based on subject weight and dosage level before beginning 
the IV administration. The investigational study product solution will typically be 
administered IV over about 15 to 60 minutes using a volumetric pump. The rate 
of infusion (mL/hr) will vary based on the total volume needed to administer the 
full dose. The total time needed to administer the dose may be longer based on 
factors such as subject tolerance. 
8.5 
Acquisition of study products 
VRC01 (VRC-HIVMAB060-00-AB) and VRC01LS (VRC-HIVMAB080-00-
AB) are provided by the VRC/DAIDS/NIAID. 
Once an HVTN CRS is protocol registered, the pharmacist can obtain study 
products from the NIAID Clinical Research Products Management Center 
(CRPMC) by following the ordering procedures given in Pharmacy Guidelines 
and Instructions for DAIDS Clinical Trials Networks. 
8.6 
Pharmacy records 
The HVTN CRS pharmacist is required to maintain complete records of all study 
products. The pharmacist of record is responsible for maintaining randomization 
codes and randomization confirmation notices for each participant in a secure 
manner. 
8.7 
Final disposition of study products 
All unused study products must be returned to the CRPMC after the study is 
completed or terminated unless otherwise instructed by the CRPMC. The 
procedures and relevant form are included in the Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks.  

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9 
Clinical procedures 
The schedules of clinical procedures are shown in Appendix L, Appendix M, 
Appendix N, and Appendix O. 
9.1 
Informed consent 
Informed consent is the process of working with participants so that they fully 
understand what will and may happen to them while participating in a research 
study. The HVTN informed consent form documents that a participant (1) has 
been informed about the potential risks, benefits, and alternatives to participation, 
and (2) is willing to participate in an HVTN study. Informed consent 
encompasses all written or verbal study information HVTN CRS staff provide to 
the participant, before and during the trial. HVTN CRS staff will obtain informed 
consent of participants according to HVTN policies and procedures. 
The informed consent process continues throughout the study. Key study concepts 
should be reviewed periodically with the participant and the review should be 
documented. At each study visit, HVTN CRS staff should consider reviewing the 
procedures and requirements for that visit and for the remaining visits. 
Additionally, if any new information is learned that might affect the participants’ 
decisions to stay in the trial, this information will be shared with trial participants. 
If necessary, participants will be asked to sign revised informed consent forms. 
An HVTN CRS may employ recruitment efforts prior to the participant 
consenting. For example, some HVTN CRSs use a telephone script to prescreen 
people before they come to the clinic for a full screening visit. Participants must 
sign a screening or protocol-specific consent before any procedures are performed 
to determine eligibility. HVTN CRSs must submit recruitment and prescreening 
materials to IRB/EC and any applicable Regulatory Entity (RE) for human 
subjects protection review and approval. 
Note: As defined in the DAIDS Protocol Registration Manual, an RE is “Any 
group other than the local IRB/EC responsible for reviewing and/or approving a 
clinical research protocol and site-specific ICFs [informed consent forms] prior to 
implementation at a site.” CRSs are responsible for knowing the requirements of 
their applicable REs. 
9.1.1 
Screening consent form 
Without a general screening consent, screening for a specific study cannot take 
place until the site receives protocol registration from the DAIDS RSC Protocol 
Registration Office. 
Some HVTN CRSs have approval from their IRB/EC and any applicable RE to 
use a general screening consent form that allows screening for an unspecified HIV 
vaccine or other prevention trial. In this way, HVTN CRS staff can continually 

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screen potential participants and, when needed, proceed quickly to obtain 
protocol-specific enrollment consent. Sites conducting general screening or 
prescreening approved by their IRB/EC and any applicable RE may use the 
results from this screening to determine eligibility for this protocol, provided the 
tests are conducted within the time periods specified in the eligibility criteria.  
9.1.2 
Protocol-specific consent forms 
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. 
A sample protocol-specific consent form for the study is located in Appendix A 
for Groups 1-3 and Appendix B for Groups 4-5. A separate sample consent form 
for other uses of specimens is located in Appendix E for all groups. 
Each HVTN CRS is responsible for developing a protocol-specific consent 
form(s) for local use, based on the sample protocol-specific consent forms in 
Appendix A for Groups 1-3 and Appendix B for Groups 4-5. The consent form(s) 
must be developed in accordance with requirements of the following: 
 CRS’s IRB/EC, 
 CRS’s institution and any applicable REs, and 
 Elements of informed consent as described in Title 45, CFR Part 46 and 
Title 21 CFR, Part 50, and in the International Conference on 
Harmonisation (ICH) E6, Good Clinical Practice: Consolidated Guidance 
4.8.  
Study sites are strongly encouraged to have their local CABs review their site-
specific consent forms. This review should include, but should not be limited to, 
issues of cultural competence, local language considerations, and the level of 
understandability. 
The sample informed consent form includes instructions throughout the document 
for developing specific content. 
Sites should follow the instructions in the Protocol-specific Official Memo 
distributed along with this protocol regarding when they may begin using their 
site-specific protocol consent forms. 
Regarding protocol registration, sites should follow procedures outlined in the 
current version of the DAIDS Protocol Registration Manual. 
9.1.3 
Assessment of Understanding 
Study staff are responsible for ensuring that participants fully understand the 
study before enrolling them. This process involves reviewing the informed 

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consent form with the participant, allowing time for the participant to reflect on 
the procedures and issues presented, and answering all questions completely.  
An Assessment of Understanding is used to document the participant’s 
understanding of key concepts in this trial. The participant must complete the 
Assessment of Understanding before enrollment. Staff may provide assistance in 
reading and understanding the questions and responses, if necessary. Participants 
must verbalize understanding of all questions answered incorrectly. This process 
and the participant’s understanding of the key concepts should be recorded in 
source documentation at the site. 
IRB/EC and any applicable RE may require that a participant has signed either a 
screening or protocol-specific consent document prior to administering the 
Assessment of Understanding. The consent process (including the use of the 
Assessment of Understanding) should be explained thoroughly to the IRB/EC and 
any applicable RE, whose recommendations should be followed. 
9.2 
Pre-enrollment procedures 
Screening may occur over the course of several contacts/visits, up to and 
including before baseline biopsy collection on day -14 (Groups 1-3), or infusion 
on day 0 (Groups 4 and 5). All inclusion and exclusion criteria must be assessed 
within 56 days before enrollment, unless otherwise specified in the eligibility 
criteria (or below in this section). 
After the appropriate informed consent has been obtained and before enrollment, 
the following procedures are performed: 
 Medical history, documented in the case history record; 
 Assessment of whether the volunteer is at low risk for HIV infection; 
 Complete physical examination, including height, weight, vital signs, and 
clinical assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; 
heart; chest; abdomen; extremities; neurological function; skin; and pelvic 
and/or rectal exam; 
 Assessment of concomitant medications the volunteer is taking, including 
prescription and nonprescription drugs, vitamins, topical products, 
alternative/complementary medicines (eg, herbal and health food 
supplements), recreational drugs, vaccinations, and allergy shots (record the 
complete generic name for all medications); 
 Pap smear (only for volunteers 21 years or older who were born female and 
who did not have a Pap smear performed within the last 3-5 years; for specific 
requirements see Section 7.1, Criterion 24) 

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 Specimen collection (including mucosal sampling as described in Section 9.6, 
for groups 4 and 5) 
 Laboratory tests, including: 
 Complete Blood Count including differential and platelets 
 ALT, AST, AP, and Creatinine 
 Urine or serum pregnancy test (for participants who were born female). 
Persons who are NOT of reproductive potential due to having undergone 
bilateral oophorectomy (verified by medical records), are not required to 
undergo pregnancy testing; 
 Urine dipstick (Urinalysis if indicated) 
 Screening HIV testing 
 Hepatitis B and C 
 Syphilis  
 Gonorrhea and chlamydia  
 Trichomonas vaginalis (for participants providing cervicovaginal 
samples), 
 Bacterial vaginosis (for participants providing cervicovaginal samples), 
 Yeast (for participants providing cervical samples, if clinically indicated),  
 Administration of behavioral risk assessment questionnaire; 
 Obtaining volunteer demographics in compliance with the NIH Policy on 
Reporting Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 
2001 (available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-
053.html); 
 Counseling on HIV testing and risk reduction, performed in compliance with 
the US Centers for Disease Control and Prevention (CDC)’s current 
guidelines or other local guidelines for HIV counseling, testing, and referral as 
described in Section 9.7; and 
 Discussion of pregnancy prevention. A pregnant or breastfeeding person may 
not be enrolled in this trial. Specific criteria and assessment of contraception 
and pregnancy status are described in study inclusion criteria. Discussion of 
pregnancy prevention includes advising a participant who was born female 
and who reports no current sexual activity that could lead to that participant 
becoming pregnant to have a plan to begin adequate birth control. This plan 
would be put to use if, during the study, the participant becomes sexually 
active in a way that could lead to that participant becoming pregnant.  

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9.2.1 
Use of screening results from another HVTN study 
If a participant screens for an HVTN study at the same HVTN CRS but then does 
not join that study, screening results from that effort may be applied to the 
screening for this protocol, as long as the screening was done under participant 
consent, the participant has signed a consent form to begin screening for this 
study, and the tests were conducted within the time periods specified in the 
eligibility criteria (Sections 7.1 and 7.2). 
9.3 
Enrollment visits 
Enrollment in Groups 1, 2, and 3 is simultaneous with baseline biopsy collections 
on day -14. Enrollment in Groups 4 and 5 is simultaneous with the infusion on 
day 0. The time interval between randomization and first infusion should not 
exceed 4 working days. The CRS requests the randomization assignment from the 
Web-based randomization system. Randomization will be performed prior to first 
infusion for all groups.  
At the baseline biopsy collection visit (Groups 1-3; day -14), cervical, vaginal, 
and/or rectal biopsies will be collected. These samples will serve as baseline 
controls and will help to assess the acceptability of the biopsy procedures to 
participants and the fitness of participants to continue in these groups with 
extensive mucosal biopsy collections. Participants with conditions not amenable 
to repeated biopsy sampling or participants not willing to continue in the trial 
after these baseline biopsies have been performed may be replaced. 
At the baseline biopsy collection visit (Groups 1-3; day -14), the following 
procedures are performed: 
 Abbreviated physical examination, including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints 
 Assessment of concomitant medications (Section 9.2) 
 Assessment of any new or unresolved AEs/intercurrent illnesses 
 Urine or serum pregnancy test (for participants who were born female). 
Persons who are NOT of reproductive potential due to having undergone 
bilateral oophorectomy (verified by medical records), are not required to 
undergo pregnancy testing 
 Risk reduction counseling (Section 9.7) 
 Pregnancy prevention assessment (Section 9.2 and 9.8) 

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 Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation) 
 Specimen collection (including mucosal sampling as described in Section 
9.6); 
 HSV 1/2 testing  
 Blood hormone levels (estradiol and progesterone) (persons born female only) 
 Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate. 
For the enrollment infusion visit (Groups 4 and 5; day 0) procedures are described 
in Section 9.4. 
9.4 
Infusion visits 
At all infusion visits, the following procedures are performed before infusion: 
 Abbreviated physical examination, including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
 Assessment of baseline reactogenicity parameters; 
 Assessment of concomitant medications (Section 9.2); 
 Assessment of any new or unresolved AEs/intercurrent illnesses; and 
 Urine or serum pregnancy test (for participants who were born female). 
Persons who are NOT of reproductive potential due to having undergone 
bilateral oophorectomy (verified by medical records), are not required to 
undergo pregnancy testing; 
 Blood collection for serum trough levels and storage (not applicable at the 
first infusion visit in Groups 1-3, as baseline samples will be collected at 
enrollment). 
Following completion of all procedures in the preceding list, and if results 
indicate that infusion may proceed, infusion is administered (Sections 8.3 and 
8.4). 
Immediately following infusion, the participant remains in the clinic for 
observation. An initial reactogenicity assessment is made at a target of 30 minutes 
after all IV infusions, with an acceptable range of 25-60 minutes. Before leaving 

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the clinic, the participant is given the postinfusion memory tool and is instructed 
on how to complete it. The site will make arrangements to obtain daily reports of 
reactogenicity events from the participant during the reactogenicity period 
(Section 9.10). 
The following procedures will be performed at infusion visits as specified in 
Appendix L, Appendix M, Appendix N, and Appendix O. These procedures may 
be performed prior to, during, or following infusion:  
 Risk reduction counseling (Section 9.7);  
 Pregnancy prevention assessment (Section 9.2 and 9.8); and 
 Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation). 
 Administration of the social impact assessment questionnaire (types of 
impacts assessed involve personal relationships, health insurance, life 
insurance, educational or employment opportunities, housing, immigration, or 
travel); 
 Administration of behavioral risk assessment questionnaire; 
 Biopsy acceptability questionnaire; 
 HSV 1/2 testing 
 Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate. 
9.5 
Follow-up visits 
The following procedures are performed at all scheduled follow-up visits: 
 Risk reduction counseling (Section 9.7);  
 Pregnancy prevention assessment (Section 9.2 and 9.8); and 
 Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation); 
 Assessment of new or continuing concomitant medications (Section 9.2); and 
 Assessment of new or unresolved AEs/intercurrent illnesses. 

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Additional procedures will be performed at scheduled follow-up visits as 
specified in in Appendix L, Appendix M, Appendix N, and Appendix O:  
 Administration of the social impact assessment questionnaire (types of 
impacts assessed involve personal relationships, health insurance, life 
insurance, educational or employment opportunities, housing, immigration, or 
travel);  
 Administration of behavioral risk assessment questionnaire; 
 Biopsy acceptability questionnaire; 
 HIV infection assessment including pre-test counseling. A subsequent follow-
up contact is conducted to provide post-test counseling and to report results to 
participant; 
 Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate; 
 Abbreviated physical examination including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
 Complete physical examination, including weight, vital signs, and clinical 
assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; heart; 
chest; abdomen; extremities; neurological function; and skin; 
 Specimen collection (including mucosal sampling as described in Section 
9.6); 
 Clinical laboratory tests including: 
 CBC with differential and platelets, 
 Chemistry panel (Section 9.2),  
 Blood hormone levels (estradiol and progesterone) (persons born female 
only), 
 Urine dipstick (urinalysis if appropriate; Section 9.9),  
 Gonorrhea and chlamydia, 
 Trichomonas vaginalis, 
 Bacterial vaginosis, 
 Yeast (if clinically indicated). 
 Urine or serum pregnancy test (for participants who were born female). 
Persons who are NOT of reproductive potential due to having undergone 

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bilateral oophorectomy (verified by medical records), are not required to 
undergo pregnancy testing. 
9.6 
Mucosal sampling 
Mucosal secretion and biopsy samples will be collected at the timepoints 
indicated in Appendix L, Appendix M, Appendix N, and Appendix O. All 
participants in this trial will have consented to mucosal specimen collections. 
Participants born male will provide semen, rectal fluids, and rectal biopsies. 
Participants born female will provide cervicovaginal fluids, as well as cervical 
and vaginal biopsies. At the Seattle CRS, female participants will also provide 
rectal fluids and rectal biopsies, if they agree to do so. Small (~2-4 mm) tissue 
biopsies are obtained from the vagina and cervix using a speculum and from the 
rectum by anoscopy by experienced clinicians. The number of biopsies per 
mucosal compartment and visit is described in detail in Table 9-1 and Table 9-2, 
and also outlined in Appendix H, Appendix I, Appendix J, and Appendix K, 
however fewer samples may be taken based on the judgment of the performing 
clinician. If a female participant is no longer willing to provide cervicovaginal 
specimens, a switch to the rectal compartment is possible. During the trial, a 
participant may decline all or some of the mucosal biopsies or secretion 
collections, but they should be encouraged to continue with any collections that 
they deem acceptable until the end of the trial. 
Table 9-1 Mucosal biopsy collection schedule for Groups 1-3 
Tissue 
Function 
Visit 2 
(Baseline) 
Visit 14 
(Month 6) 
Visit 15 
(Month 7) 
Visit 16 
(Month 9) 
Visit 17 
(Month 
12) 
Visit 18** 
(Month 
15) 
Visit 19** 
(Month 
18) 
Rectal 
# of Bx and 
Use 
Ab levels 
1 
1 
1 
1 
1 
1 
1 
IHC 
1 
1 
1 
1 
1 
1 
1 
Infectivity 
3 
3 
3 
3 
3 
3 
3 
Total = 
35*/25 
5 
5 
5 
5 
5 
5 
5 
Ectocervical 
# of Bx and 
Use 
Ab levels 
1 
1 
1 
1 
1 
1 
(1)*** 
IHC 
1 
1 
1 
1 
1 
1 
(1)*** 
Infectivity 
2 
2 
- 
- 
- 
- 
- 
Total = 
16*/14 
4 
4 
2 
2 
2 
2 
(2)*** 
Vaginal 
# of Bx and 
Use 
Ab levels 
1 
1 
1 
1 
1 
1 
(1)*** 
IHC 
1 
1 
1 
1 
1 
1 
(1)*** 
Infectivity 
3 
3 
3 
3 
(3)*** 
(2-3)*** 
(2-3)*** 
Total = 
24*/22 
5 
5 
5 
5 
2 [(5)***] 
2 [(4-
5)***] 
(2-5)*** 
* Number of samples refers to Group 3 
** Visits only apply to group 3 
*** These samples will only be collected if the participant has missed prior collection visit(s), in order to maintain 
the total number of biopsies indicated in the “Function” column.  

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Table 9-2 Mucosal biopsy collection schedule for Groups 4-5 
Tissue 
Function 
Visit 4 
(0 mo) 
Visit  5 
(1 mo) 
Visit 9 
(3 mo) 
Visit  12 
(4.5 mo) 
Visit 14 
(6 mo) 
Visit  16** 
(9 mo) 
Visit  17** 
(12 mo) 
Rectal 
# of Bx and 
Use 
Ab levels 
1 
1 
2 
2 
1 
2 
1 
IHC 
1 
1 
- 
- 
1 
- 
1 
Infectivity 
- 
- 
- 
- 
- 
- 
- 
Total = 
14*/10 
2 
2 
2 
2 
2 
2 
2 
Ectocervical 
# of Bx and 
Use 
Ab levels 
1 
1 
2 
2 
1 
2 
1 
IHC 
1 
1 
- 
- 
1 
- 
1 
Infectivity 
- 
- 
- 
- 
- 
- 
- 
Total = 
14*/10 
2 
2 
2 
2 
2 
2 
2 
Vaginal 
# of Bx and 
Use 
Ab levels 
1 
1 
2 
2 
1 
2 
1 
IHC 
1 
1 
- 
- 
1 
- 
1 
Infectivity 
- 
- 
- 
- 
- 
- 
- 
Total = 
14*/10 
2 
2 
2 
2 
2 
2 
2 
* Number of samples refers to Group 5 
** Visits only apply to group 5 
 At each biopsy visit, prior to biopsy, participants must be confirmed to be 
low-risk for HIV infection. 
 Participants will regularly be tested for gonorrhea and chlamydia. 
Additionally, participants who were born female will be tested for 
trichomoniasis and bacterial vaginosis and may be tested for hyphae/budding 
yeast (if clinically indicated) as outlined in Appendix L, Appendix M, 
Appendix N, and Appendix O. In addition to the pre-defined testing 
timepoints, such tests may be performed at any time according to the 
clinicians’ discretion. Test results will be provided to participants and all 
participants who test positive for 1 or more of these infections will receive 
counseling, as well as treatment or referral for treatment as appropriate. 
Sample collection will not be performed or may be deferred to a later date 
within the visit window if a contraindication to sampling (eg, active GTI) is 
present (as indicated below). 
 Rectal fluid and/or biopsy sampling. For participants born female and capable 
of becoming pregnant, a pregnancy test must be performed and be negative 
prior to any rectal mucosal sampling. Participants should abstain from 
receptive anal sex, insertion of any foreign object or substance into the anus 
(including but not limited to cleaning products [creams, gels, lotions, pads, 
etc.], lubricant, enemas, and douching even with water), and using perianal or 
intra-anal steroid or other anti-inflammatory cream in or around the anus for 
48 hours prior to sample collection. Rectal secretion sampling may be 
deferred if a participant is menstruating, but should be performed as soon as 
possible, within the visit window. In addition, rectal sampling will not be 

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performed (or may be deferred to a later date within the visit window) if there 
is a contraindication to rectal secretion sampling, such as an active infection 
or inflammation of the colorectal area (such as an HSV-2 outbreak or 
inflamed hemorrhoids or colitis/diarrhea).  
 Additional biopsy-specific criteria: 
 Biopsies will be collected a minimum of 28 days from previous 
biopsies.  
 Participants should not have taken antithrombotic medication (except 
ASA and NSAIDs) for 5 days prior to the procedure. If a participant is 
taking these medications for medical reasons, biopsies should not be 
collected and these medications should not be interrupted. 
 Participants should not have rectal sex and/or insert any foreign object 
or substance into the rectum for 5 days after biopsy samples have 
been collected; 
 Participants should contact the clinic if they experience a large amount 
of bleeding, have a temperature of more than 38.1°C (100.5°F), 
experience chills, or have pain that is not improving. 
 Cervicovaginal secretion and/or biopsy sampling. Participants who are age 21 
or older must report having had a Pap smear within the 5 years prior to 
enrollment, with the latest result reported as normal, or ASCUS (atypical 
squamous cells of undetermined significance) with no evidence of high-risk 
HPV; if high-risk HPV testing was not conducted, the participant must report 
having had a Pap smear within the 3 years prior to enrollment, with the latest 
result reported as normal or ASCUS. Pap smear results must be verified by 
medical records. For participants capable of becoming pregnant, a pregnancy 
test must be performed and must be negative prior to any cervicovaginal 
mucosal sampling with a sponge. For sampling with menstrual cup, the 
pregnancy test can be performed after collection has taken place, but should 
be performed on the same day as the collection. Cervicovaginal mucosal 
sampling should be deferred if a participant is menstruating, but should be 
performed as soon as possible, within the visit window. If this is not possible, 
cervicovaginal biopsies may be collected within the visit window during 
menses at the clinician’s discretion. In addition, cervicovaginal sampling will 
not be performed (or may be deferred to a later date within the visit window) 
if a participant has an active ulcerative genital lesion or is known to have an 
active GTI at the scheduled timepoint. Participants providing cervicovaginal 
samples should be advised as follows:  
 Do not use anything with spermicide, lubricants, or topical/intravaginal 
medications (eg, topical yeast infection treatments) for 48 hours before the 
samples are collected;  
 Do not douche for 48 hours before the samples are collected;  

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 Do not have vaginal sex and/or insert any foreign object or substance into 
the vagina for 48 hours before the samples are collected;  
 Additional biopsy-specific criteria: 
 Biopsies will be collected a minimum of 28 days from previous 
biopsies.  
 Participants should not have taken antithrombotic medication (except 
ASA and NSAIDs) for 5 days prior to the procedure. If a participant is 
taking these medications for medical reasons, biopsies should not be 
collected and these medications should not be interrupted. 
 Participants should not have vaginal sex and/or insert any foreign 
object or substance into the vagina for 7 days after biopsy samples 
have been collected; 
 Participants should contact the clinic if they experience a large amount 
of bleeding, have a temperature of more than 38.1°C (100.5°F), 
experience chills, or have pain that is not improving.  
 Semen sampling. Participants providing semen samples are asked to refrain 
from ejaculation, using anything with lubricants, putting saliva on the penis, 
or having receptive oral sex for at least 48 hours prior to specimen collection. 
In addition, semen sampling will not be performed (or may be deferred to a 
later date within the visit window) if a participant is known to have an active 
GTI at the scheduled timepoint. 
9.7 
HIV counseling and testing 
HIV counseling will be performed in compliance with the CDC’s guidelines or 
other local guidelines for HIV counseling and referral. HIV testing will be 
performed in accordance with the current HVTN HIV testing algorithm following 
enrollment. 
Participants will be counseled routinely during the trial on the avoidance of HIV 
infection.  
Potential participants identified as being HIV infected during screening are not 
enrolled. Potential and enrolled participants identified as being HIV-infected will 
be referred for medical treatment, counseling, and management of the HIV 
infection. Participants who are found to be HIV-infected after enrollment will not 
receive any additional study product but will continue to be followed in the study 
for safety assessments. These individuals may also be referred to appropriate 
ongoing clinical trials or observational studies. 

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It is theoretically possible that anti-HIV mAb administration may cause common 
antibody tests to show that someone is HIV-negative, even if they are actually 
infected. An anti-HIV mAb is not likely to directly reduce or inhibit the assays 
used to detect HIV-1 infection. 
9.7.1 
Study product–related seroreactivity 
Human sera containing purified VRC01 at concentrations up to 200 mcg/mL have 
been tested using a variety of commercially available HIV test kits without any 
indication of reactivity. For this reason, we do not anticipate that receipt of 
VRC01/VRC01LS will cause a reactive result on currently available HIV test kits, 
but this remains a theoretical possibility.  
Because this possibility cannot be categorically eliminated, study staff will advise 
study participants to confine their HIV testing while in the study to that provided 
through the CRS. Staff will also inform study participants of the likelihood of 
routine HIV testing being offered or performed outside the study CRS at 
emergency rooms, clinics, and medical offices, and will inform participants of 
their right to opt out of HIV testing outside the study site. CRS staff should 
inform study participants if local and/or state/regional policies and regulations 
permit medical providers to perform HIV testing without first informing patients. 
If this is the case, then CRS staff should advise study participants that they may 
decline testing preemptively. CRS staff should also inform participants if positive 
results must be reported to local public health authorities. CRS staff should 
provide participants with CRS contact information and should encourage 
participants to ask medical providers to contact the CRS. The CRS can verify that 
the participant is in an HIV mAb clinical trial and should only be tested at the 
study CRS. 
Study staff should also stress that the study product is completely cleared from the 
body within a few months, so even the theoretical risk of VRC01/VRC01LS 
causing a misleading HIV test result will disappear before their final scheduled 
clinic visit. 
9.8 
Contraception status 
Contraception status is assessed and documented at every scheduled clinic visit 
for a participant who was born female and who is sexually active in a way that 
could cause that participant to become pregnant. Prior to enrollment and 
throughout the study, staff will ask participants to verbally confirm their use of 
adequate contraceptive methods. A participant who was born female and is 
sexually active in a way that could cause that participant to become pregnant 
should be reminded at all scheduled clinic visits of the importance of using 
contraception and should be referred to specific counseling, information, and 
advice as needed. (Specific contraception requirements are listed in Section 7.1). 
This reminder should be documented in the participant’s study record. 

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Self-reported infertility—including having undergone bilateral oophorectomy or 
tubal ligation—must be documented in the participant’s study record. 
9.9 
Urinalysis 
Dipstick testing may be performed in the clinic or the lab, as long as the required 
elements (glucose, protein, and hemoglobin) are tested. The examination is 
performed on urine obtained by clean catch. 
If the screening dipstick is transiently abnormal due to non-urinary bleeding, eg, 
uterine or vaginal bleeding or spotting or infection, document this issue in the 
participant’s source documentation. For infection, provide appropriate treatment 
and/or referral. Following resolution, repeat the dipstick and, if within the 
eligibility limits specified in the protocol, the participant may be enrolled. 
Follow-up urinalysis should be deferred if a participant is experiencing non-
urinary bleeding (eg, menstruating), but should be performed as soon as possible. 
If a follow-up dipstick is abnormal due to a participant’s menstrual period, 
document in the comment section of the case report form (CRF) and repeat the 
dipstick once the participant is no longer menstruating. A micro-urinalysis is not 
required. 
9.10 
Assessments of reactogenicity 
For all participants, baseline assessments are performed before and reactogenicity 
assessments are performed after infusions per SSP. All reactogenicity symptoms 
are graded according to the Division of AIDS Table for Grading the Severity of 
Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, except as 
noted in Section 11.2.2. 
The reactogenicity assessment period is 3 full days following each infusion per 
the assessment schedule shown in Table 9-3. Participants are instructed to record 
symptoms using a postinfusion memory tool. Contacts between the participant 
and the site staff should take place daily during the assessment period. Clinic staff 
will follow new or unresolved reactogenicity symptoms present at day 3 to 
resolution. Participants are instructed to contact the clinic for events that arise 
during the period between infusions and the next scheduled visit. In general, a 
participant who self-reports any postinfusion reaction greater than mild is seen by 
a clinician within 48 hours after onset, unless the reaction is improving and/or has 
completely resolved.  
Reactogenicity events are reported using CRFs that correspond to the time of 
assessment in Table 9-3. Reactogenicity assessments include assessments of 
systemic and local symptoms and infusion-related lesions. Events not listed on a 
CRF, or with an onset after the reactogenicity assessment period (day of infusion 

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and 3 full days after), or those meeting SAE/adverse events requiring expedited 
reporting to DAIDS criteria, are recorded on an adverse event log form.  
Table 9-3 Schedule of reactogenicity assessments 
Day 
Time 
Performed by 
0a 
Baseline: before study product 
administration 
HVTN CRS staff 
 
Early: 25-60 minutes after all infusions  
HVTN CRS staff 
 
Between early assessment and 11:59pm 
day 0 
HVTN CRS staff or 
participant 
1 
Between 12:00am and 11:59pm day 1 
HVTN CRS staff or 
participant 
2 
Between 12:00am and 11:59pm day 2 
HVTN CRS staff or 
participant 
3b 
Between 12:00am and 11:59pm day 3 
HVTN CRS staff or 
participant 
a Day of study product administration 
b New or unresolved reactogenicity symptoms present on day 3 are followed until resolution 
9.10.1 
Assessment of systemic and local symptoms 
Systemic symptoms include increased body temperature, malaise and/or fatigue, 
myalgia, headache, chills, arthralgia, nausea, pruritus, diarrhea, and vomiting. 
Local symptoms include pain and/or tenderness proximal to the infusion site. The 
daily maximum severity reached for each symptom during the assessment period 
is reported.  
Body temperature is measured by oral or infrared thermometry and reported in 
degrees Celsius. If temperature is measured in Fahrenheit, the conversion to 
Celsius should be documented in the participant’s chart note. A measurement is 
taken once daily during the assessment period and should be repeated if 
participant is feeling feverish. 
9.10.2 
Assessment of infusion site 
Infusion site reactions may include redness or erythema and induration or 
swelling. The maximum horizontal and maximum vertical measurements for all 
infusion site reactions are recorded. 
All infusion site reactions are monitored until resolution. Areas greater than 25 
cm2 are followed daily; otherwise, the frequency of follow-up is based on 
clinician judgment. 
9.11 
Visit windows and missed visits 
Visit windows are defined in HVTN 116 Study Specific Procedures. For a visit 
not performed within the window period, a Missed Visit form is completed. If the 
missed visit is one that required safety assessments or local safety labs, HVTN 

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CRS staff should attempt to bring the participant in for an interim visit as soon as 
possible. 
Procedures performed at an interim visit are usually toxicity/safety assessments 
(including local safety labs) and HIV testing. With the exception of HIV testing, 
these procedures are performed only if they were required at the missed visit or if 
clinically indicated. HIV testing may be performed as deemed appropriate by the 
study staff. If a participant missed an infusion visit or if infusions must be 
permanently discontinued, see Section 7.3.2 and Section 7.3.3 for resolution. 
9.12 
Early termination visit 
In the event of early participant termination, site staff should consider if the 
following assessments are appropriate: a final physical examination, clinical 
laboratory tests (including urine dipstick, CBC with differential, and chemistry 
panel), pregnancy testing, social impact assessment, biopsy acceptability 
questionnaire, and HIV test. For participants who have a confirmed diagnosis of 
HIV infection, see Section 9.14. 
9.13 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more 
infusions of study product will be given and no more mucosal biopsies will be 
collected during the pregnancy, but remaining visits and other study procedures 
should be completed unless medically contraindicated. For participants who are 
no longer pregnant, see Section 7.3.1. If the participant terminates from the study 
prior to the pregnancy outcome, the site should make every effort to keep in touch 
with the participant in order to ascertain the pregnancy outcome. 
9.14 
HIV infection during the study 
If a participant becomes HIV-infected during the course of the study, no 
additional study product will be administered. Participants will be encouraged to 
continue scheduled study visits for up to 16 weeks following their last study 
product administration. Follow-up duration for participants diagnosed with HIV 
infection may be adjusted in consultation with the CRS investigator and the 
HVTN 116 PSRT (eg, to avoid interference with participant initiation of HIV 
treatment). At post-infection follow-up visits, only specimens required for 
protocol-specified safety laboratory tests will be collected; in addition, some 
clinic procedures may be modified or discontinued (see Appendix H, Appendix I, 
Appendix J, Appendix K, Appendix L, Appendix M, Appendix N, and Appendix 
O). 

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10 
Laboratory 
10.1 
HVTN CRS laboratory procedures 
The HVTN 116 Site Lab Instructions provide further guidelines for operational 
issues concerning the clinical and processing laboratories. This document includes 
guidelines for general specimen collection, special considerations for phlebotomy, 
specimen labeling, whole blood processing, HIV screening/diagnostic testing, and 
general screening and safety testing. 
Tube types for blood collection are specified in Appendix H, Appendix I, 
Appendix J, and Appendix K. For tests performed locally, the local lab may 
assign appropriate tube types. 
In specific situations, the blood collection tubes may be redirected to another 
laboratory or may require study-specific processing techniques. In these cases, 
laboratory special instructions will be posted on the protocol-specific section of 
the HVTN website. 
10.2 
Total blood volume 
Required blood volumes per visit are shown in Appendix H, Appendix I, 
Appendix J, and Appendix K. Not shown is any additional blood volume that 
would be required if a safety lab needs to be repeated, or if a serum pregnancy test 
needs to be performed, in which case, additional blood volume would likely be 
minimal. The total blood volume drawn for each participant will not exceed 500 
mL in any 56-day (8-week) period (includes estimated maximal blood loss 
associated with the biopsy procedures). 
10.3 
Drug detection and quantitation 
10.3.1 
VRC01/VRC01LS mAb levels in serum, mucosal tissue lysates and 
mucosal secretions 
VRC01/VRC01LS levels will be measured in serum, semen, cervicovaginal 
secretions, rectal secretions, and mucosal tissue lysates prepared from cervical, 
vaginal and rectal biopsies collected at the designated timepoints. A quantitative 
assay (such as an ELISA), binding multiplex antibody assay (BAMA), or 
Singulex assay may be used to determine the concentration of VRC01/VRC01LS 
in the aforementioned samples and/or to assess their binding to various Env 
proteins, such as Consensus gp120, Consensus gp140 and CD4 binding site 
proteins. ELISA assays employing two different antigens may be used for 
VRC01/VRC01LS quantitation. One assay employs the resurfaced core 3 antigen 
(RSC3), designed for selective detection of CD4 binding site bNAbs, such as 
VRC01/VRC01LS (46). The other assay employs the VRC01 Fab-specific 5C9 

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mAb, which is an anti-idiotype antibody cloned from a single B cell that was 
sorted by flow cytometry using a VRC01 scFv probe. The operational sensitivity 
of the BAMA and ELISAs with respect to the various sample specimens will be 
determined for the clinical grade VRC01/VRC01LS mAbs used for this study. 
However, ongoing studies currently indicate that the interim lower LOD for 
VRC01 mAb is ≤ 129 +/- 30 ng/ml, 125 +/- 22 ng/ml, and 93 +/- 14 ng/ml in 
serum, semen, and saliva, respectively, using RSC3 protein on the BAMA 
platform (with validated plasma LOD of 2.3 -8.0 ng/ml). The LOQ of the 
validated ELISA using the VRC01 Fab-specific 5C9 mAb is currently 1.1 
mcg/mL in serum. The Singulex assay combines a proprietary digital Single 
Molecule Counting (SMC) technology with a robust microparticle-based 
immunoassay utilizing the mAb 5C9 to provide higher sensitivity (lower limit of 
quantification = 50 pg/mL) and broad dynamic range. As the technology for all of 
these assays continues to develop, an updated assay(s) may be utilized. Any assay 
that may be used for this study will first be qualified, at a minimum, for linearity, 
precision, and accuracy. 
10.3.2 
Immunohistochemistry 
The presence of VRC01/VRC01LS and its distribution in cervical, vaginal and 
rectal tissue will be assessed using immunohistochemical (IHC) methods 
employing biotinylated versions of mAb 5C9 or RSC3, on optimum cutting 
temperature (OCT) medium or paraffin embedded biopsies collected at the 
designated timepoints. The distribution of VRC01/VRC01LS will be described 
qualitatively or semi-quantitatively relative to the mucosal epithelium, stroma 
and/or lamina propria. The assay has been used to assess the distribution 
VRC01/VRC01LS in mucosal tissues from NHP infused with these mAbs and is 
being adapted for use with human mucosal tissues. As the technology for this 
assay continues to develop, updated versions may be utilized. 
To assess the immunological and inflammatory milieu within which the infused 
mAbs are found (or not) in the cervical, vaginal and/or rectal compartments, 
additional IHC assays may be utilized. These assays may include the detection of 
various Fc receptors, including FcRn, effector cell/inflammatory cell infiltrates 
and other markers of local inflammation. 
10.4 
Drug functionality  
10.4.1 
Infectivity assay 
Cervical, vaginal and rectal biopsies will be used to assess the protection provided 
by VRC01 and VRC01LS at different timepoints post infection. The assay uses 
immediate challenge of the biopsy tissue ex vivo. Currently, the assay measures 
luminescence from nanoluciferase as a readout of viral replication kinetics in the 
tissue explant.  

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We may use several challenge viruses with differential susceptibility to VRC01 
neutralization, and may conduct the infection assay in the presence of the 
participant’s serum to explore if serum antibody levels can be protective. 
10.4.2 
Anti-VRC01/VRC01LS antibody assay 
Assessment for development of anti-VRC01/VRC01LS antibodies in subjects will 
be performed using the Meso Scale Discovery (MSD) platform based on 
electrochemiluminescence. Serial dilutions of sera/plasma samples are incubated 
with optimized concentrations of biotinylated VRC01 and SULFO-TAG labeled 
VRC01 at 2-8°C overnight. Samples are transferred to a Biotin-coated MSD plate 
and incubated for 1 hour at room temperature. Samples are read with the MSD-
2400 with end point dilutions defined as the greatest sample dilution with a 
response above the positivity threshold for the assay. This assay is independent of 
the anti-VRC01 antibody isotype, and permits the detection of both high and low 
affinity antibodies. 
The same assay format will be utilized for anti-VRC01LS, with reagents specific 
for that protein. 
10.4.3 
Neutralizing antibody assay 
Depending upon the concentrations measured in collected specimens, the 
functional capacity of infused VRC01/VRC01LS (in serum and mucosal 
secretions) to neutralize HIV may be evaluated by an in vitro cell-based virus 
neutralization assay (65-67) using pseudotyped viruses.  
One or more viruses, including those matching the Envs encoded by ex vivo 
challenge viruses that range from highly to moderately sensitive to VRC01 (eg, 
MN.3, BaL26 and DU151.2), will be assayed. The IC50 of VRC01 against MN.3, 
BaL26 and DU151.2 are in the range of 0.04 mcg/mL (MN.3 and BaL26) and 
~4.0 mcg/mL (DU151.2). The IC80 values of VRC01 against these viruses are 
around 0.07, 0.15 and 45.3 mcg/mL, respectively. The TZM-bl assay is validated 
for this range of sensitivities. It has been shown that the neutralization potency 
and breadth are similar between VRC01 and VRC01LS (49). 
10.5 
Genotyping 
Fc-receptor, CCR5 delta-32 and human leukocyte antigen (HLA) molecular 
genotyping may be performed on enrolled participants using cryopreserved 
PBMC collected at baseline. Other markers, such as genes associated with 
immune functions or HIV-1 disease progression, may also be assessed.  

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10.6 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV, immunology, vaccines, antibody mediated prevention, and 
clinical trial conduct. In addition, cryopreserved samples may be used to perform 
additional assays to support standardization and validation of existing or newly 
developed methods.  
10.7 
Other use of stored specimens 
The HVTN stores specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if required by IRB/EC, or RE. 
Other use of specimens is defined as studies not described in the protocol. 
This research may relate to HIV, vaccines, the immune system, and other 
diseases. This could include limited genetic testing and, potentially, genome-wide 
studies. This research is done only to the extent authorized in each study site’s 
informed consent form, or as otherwise authorized under applicable law. Other 
testing on specimens will occur only after review and approval by the HVTN, the 
IRB/EC of the researcher requesting the specimens, and the CRS’s IRBs/ECs if 
required. 
The protocol sample informed consent form is written so that the participant 
either explicitly allows or does not allow their samples to be used in other 
research when they sign the form. Participants who initially agree to other use of 
their samples may rescind their approval once they enter the study; such 
participants will remain in this study and their samples will only be used for the 
studies described in this protocol. If a participant decides against allowing other 
research using his or her samples, or at any time rescinds prior approval for such 
other use, the study site investigator or designee must notify HVTN Regulatory 
Affairs in writing. In either case, HVTN Regulatory Affairs directs the HVTN 
Lab Program not to use samples from these participants for such other uses.  
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on other use of 
specimens. 
10.8 
Biohazard containment 
As the transmission of HIV and other blood-borne pathogens can occur through 
contact with contaminated needles, blood, and blood products, appropriate 
precautions will be employed by all personnel in the drawing of blood, collecting 
of tissue, and shipping and handling of all specimens for this study, as currently 
recommended by the CDC and the NIH or other applicable agencies. 

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All dangerous goods materials, including Biological Substances, Category A or 
Category B, must be transported according to instructions detailed in the 
International Air Transport Association Dangerous Goods Regulations. 

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11 
Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
11.1.1 
HVTN 116 PSRT 
The HVTN 116 PSRT is composed of the following members: 
 DAIDS medical officer representative, 
 Protocol chair and cochair, 
 Protocol Team leader, 
 Core medical monitor,  
 Clinical safety specialist, and 
 Regional Medical Liaison (RML). 
The clinician members of HVTN 116 PSRT are responsible for decisions related 
to participant safety. 
The Protocol Team clinic coordinator, project manager, product developer 
representative, clinical trial manager, and others may also be included in HVTN 
116 PSRT meetings. 
11.1.2 
HVTN SMB 
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, 
and experts in HIV prevention research that, collectively, has experience in the 
conduct and monitoring of HIV prevention trials. Members of the SMB are not 
directly affiliated with the protocols under review.  
The SMB reviews safety data, unblinded as to treatment arm, approximately 
every 4 months. The reviews consist of evaluation of cumulative reactogenicity 
events, AE, laboratory safety data, and individual reports of adverse events 
requiring expedited reporting to DAIDS. To increase the sensitivity for detecting 
potential safety problems, the SMB will review safety data aggregated across 
multiple protocols that use the same or similar prevention approaches. The SMB 
conducts additional special reviews at the request of the HVTN 116 PSRT.  
Study sites will receive SMB summary minutes and are responsible for 
forwarding them to their IRB/EC and any applicable RE. 

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11.1.3 
SDMC roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring 
include: 
 Maintaining a central database management system for HVTN clinical data; 
 Providing reports of clinical data to appropriate groups such as the HVTN 116 
PSRT and HVTN SMB (Section 11.1.2); 
11.1.4 
HVTN Core roles and responsibilities in safety monitoring 
The roles and responsibilities of HVTN Core in relation to safety monitoring 
include: 
 Daily monitoring of clinical data for events that meet the safety pause and 
HVTN 116 PSRT AE review criteria (Section 11.3); 
 Notifying HVTN CRSs and other groups when safety pauses are instituted 
and lifted (Section 11.3); 
 Querying HVTN CRSs for additional information regarding reported clinical 
data; and 
 Providing support to the HVTN 116 PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
Sites must submit all safety forms (eg, reactogenicity, adverse experience, 
urinalysis, local lab results, and concomitant medications) before the end of the 
next business day after receiving the information. The forms should not be held in 
anticipation of additional information at a later date. If additional information is 
received at a later date, the forms should be updated and resubmitted before the 
end of the next business day after receiving the new information. 
11.2.2 
AE reporting 
An AE is any untoward medical occurrence in a clinical investigation participant 
administered a study product/procedure(s) and which does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of an investigational study 
product/procedure(s), whether or not related to the investigational study 
product/procedure(s). All AEs are graded according to the Division of AIDS 
Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected 

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Version 2.1, July 2017, available on the RSC website at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting/daids-grading-tables, except: 
 Unintentional weight loss is required to be reported as an AE only if it is 
considered to be potentially deleterious to the participant’s health (see HVTN 
116 Study Specific Procedures); 
 Infusion Site Erythema or Redness and Infusion Site Induration or Swelling 
will not consider interference with usual social and functional activities such 
that: 
 Grade 1 is: 2.5 to < 5 cm in diameter OR 6.25 to < 25 cm2 surface area; 
 Grade 2 is: ≥ 5 to < 10 cm in diameter OR ≥ 25 to < 100 cm2 surface area; 
 Grade 3 is: ≥ 10 cm in diameter OR ≥ 100 cm2 surface area OR Ulceration 
OR Secondary infection OR Phlebitis OR Sterile abscess OR Drainage; 
 Grade 4 is: Potentially life-threatening consequences (eg, abscess, 
exfoliative dermatitis, necrosis involving dermis or deeper tissue); 
 Infusion reactions 
All AEs are reported to the SDMC on the appropriate CRF. Clinic staff should 
evaluate every AE to determine if (1) the AE meets the requirements for 
expedited reporting to DAIDS (Section 11.2.3) and (2) if the AE meets the criteria 
for a safety pause/prompt AE review (Section 11.3). 
Sites are expected to notify the CSS or RML of any serious safety concern 
requiring their attention (Table 11-1). Telephone numbers and email addresses are 
found on the protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn116). Concerns requiring immediate 
attention should be communicated by calling the clinical safety phone. 
In the case of email notification, the CSS or RML will reply during working hours 
(ie, US Pacific Time, South African Standard Time) to confirm that the email has 
been received and reviewed. If email service is not available, the HVTN CRS 
should notify the CSS or RML of the event by telephone, then submit CRFs. 
In addition, site investigators are required to submit AE information in accordance 
with IRB/EC and any applicable RE requirements. 
11.2.3 
Expedited reporting of adverse events to DAIDS 
Requirements, definitions and methods for expedited reporting of AEs are 
outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of 
Adverse Events to DAIDS (DAIDS EAE Manual), which is available on the RSC 
website at http://rsc.tech-res.com/clinical-research-sites/safety-reporting/manual. 
The SAE Reporting Category will be used for this study.  

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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 AE reports may be 
submitted via the DAIDS EAE Form. This form is available on the DAIDS RSC 
website at http://rsc.tech-res.com/clinical-research-sites/safety-
reporting/daids/paper-eae-reporting. For questions about DAERS, please contact 
NIAID CRMS Support at CRMSsupport@niaid.nih.gov. Please note that site 
queries may also be sent from within the DAERS application itself.  
For questions about expedited AE reporting, please contact the DAIDS RSC 
Safety Office at (DAIDSRSCSafetyOffice@tech-res.com).  
The study products for which expedited reporting is required are:  
 VRC01 (VRC-HIVMAB060-00-AB) 
 VRC01LS (VRC_HIVMAB080-00-AB) 
While the participant is in the study reporting period (from the first study product 
administration until the last scheduled clinic visit), the SAE Reporting Category 
will be used.  
After the protocol-defined AE reporting period for the study, unless otherwise 
noted, only Suspected, Unexpected Serious Adverse Reactions as defined in 
Version 2.0 of the DAIDS EAE Manual must be reported to DAIDS, if the study 
staff become aware of the events.  
The NIAID/DAIDS will report all unexpected SAEs related to the study products 
observed in this clinical trial to the FDA in accordance with 21 CFR 312.32 (IND 
Safety Reports). 
11.3 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all infusions with the product related to the 
event that triggered the pause will be held until further notice. The AEs that will 
lead to a safety pause or prompt HVTN 116 PSRT AE review are summarized in 
Table 11-1. Infusions may be suspended for safety concerns other than those 
described in the table, or before pause rules are met, if, in the judgment of the 
HVTN 116 PSRT, participant safety may be threatened. Criteria for an individual 
participant’s departure from the infusion schedule are listed in Section 7.3. 

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Table 11-1 AE notification and safety pause/AE review rules 
Event and relationship 
to study products 
Severity 
HVTN CRS actiona 
HVTN Core action 
SAE, related 
Grade 5 or 
Grade 4 
Phone immediately, email and 
submit forms immediately 
Immediate pause 
SAE, not related 
Grade 5 
Phone immediately, email and 
submit forms immediately 
Immediate HVTN 116 PSRT 
notification 
SAE, related 
Grade 3 
Email and submit forms 
immediately 
Prompt HVTN 116 PSRT 
AE review to consider pause 
AEb, related 
Grade 4 or 3 
Email and submit forms 
immediately 
Prompt HVTN 116 PSRT 
AE review to consider pause 
a Phone numbers and email addresses are found on the Protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn116). 
b Does not include subjective reactogenicity symptoms (infusion site pain, tenderness, fatigue/malaise, 
myalgia, arthralgia, chills, headache, and nausea). Does include pruritus, which should be reviewed 
promptly. 
For all safety pauses, HVTN Core notifies the HVTN 116 PSRT, HVTN 
Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), DAIDS 
Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance Team 
(SPT), and participating HVTN CRSs. When an immediate safety pause is 
triggered, HVTN Core notifies the SMB.  
Once a trial is paused, the HVTN 116 PSRT reviews safety data and decides 
whether the pause can be lifted or permanent discontinuation of infusions is 
appropriate, consulting the SMB if necessary. HVTN Core notifies the 
participating HVTN CRSs, HVTN Regulatory Affairs, DAIDS PAB, DAIDS 
RAB, and DAIDS SPT of the decision regarding resumption or discontinuation of 
study infusions. Based on the HVTN 116 PSRT assessment, DAIDS RAB notifies 
the FDA as needed. 
If an immediate HVTN 116 PSRT notification or prompt HVTN 116 PSRT AE 
review is triggered, HVTN Core notifies the HVTN 116 PSRT as soon as possible 
during working hours (US Pacific Time)—or, if the information was received 
during off hours, by the morning of the next work day. If a prompt HVTN 116 
PSRT AE review cannot be completed within 72 hours of notification (excluding 
weekends and US federal holidays), an automatic safety pause occurs. 
The HVTN requires that each CRS submit to its IRB/EC and any applicable RE 
protocol-related safety information (such as IND safety reports, notification of 
infusion holds due to the pause rules, and notification of other unplanned safety 
pauses). CRSs must also follow all applicable RE reporting requirements. 
In addition, all other AEs are reviewed routinely by the HVTN 116 PSRT 
(Section 11.4.2). 

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11.4 
Review of cumulative safety data 
Routine safety review occurs at the start of enrollment and then throughout the 
study. 
Reviews proceed from a standardized set of protocol-specific safety data reports. 
These reports are produced by the SDMC and include queries to the HVTN CRSs. 
Events are tracked by internal reports until resolution.  
11.4.1 
Daily review 
Daily safety reviews are routinely conducted by HVTN Core for events requiring 
expedited reporting to DAIDS, and events that meet safety pause criteria or 
prompt HVTN 116 PSRT AE review criteria. 
11.4.2 
Weekly review 
During the infusion phase of the trial, the HVTN 116 PSRT reviews clinical 
safety reports on a weekly basis and conducts calls to review the data as 
appropriate. After the infusions and the following two-week safety visit are 
completed, less frequent reporting and safety reviews may be conducted at the 
discretion of the HVTN 116 PSRT. HVTN Core reviews reports of clinical and 
laboratory AEs. Events identified during the review that are considered 
questionable, inconsistent, or unexplained are referred to the HVTN CRS clinic 
coordinator for verification. 
11.5 
Study termination 
This study may be terminated early by the determination of the HVTN 116 PSRT, 
HVTN SMB, FDA, SAHPRA, NIH, Office for Human Research Protections 
(OHRP), or product developer. In addition, the conduct of this study at an 
individual HVTN CRS may be terminated by the determination of the IRB/EC 
and any applicable RE. 

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12 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICHe6), and according to DAIDS and 
HVTN policies and procedures as specified in the HVTN Manual of Operations, 
DAIDS Clinical Research Policies and Standard Procedures Documents including 
procedures for the following: 
 Protocol registration, activation, and implementation; 
 Informed consent, screening, and enrollment; 
 Study participant reimbursement; 
 Clinical and safety assessments; 
 Safety monitoring and reporting; 
 Data collection, documentation, transfer, and storage; 
 Participant confidentiality; 
 Study follow-up and close-out; 
 Quality control; 
 Protocol monitoring and compliance; 
 Advocacy and assistance to participants regarding negative social impacts 
associated with the clinical trial; 
 Risk reduction counseling;  
 Specimen collection, processing, and analysis;  
 Ancillary studies, and 
 Destruction of specimens. 
Any policies or procedures that vary from DAIDS and HVTN standards or require 
additional instructions (eg, instructions for randomization specific to this study) 
will be described in the HVTN 116 Study Specific Procedures.  

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12.1 
Social impacts 
Participants in this study risk experiencing discrimination or other personal 
problems, resulting from the study participation itself. The HVTN CRS is obliged 
to provide advocacy for and assistance to participants regarding these negative 
social impacts associated with the clinical trial. If HVTN CRS staff have 
questions regarding ways to assist a participant dealing with a social impact, a 
designated NIAID or HVTN Core representative can be contacted.  
Social harms are tabulated by the SDMC and are subjected to descriptive analysis. 
The goal is to reduce their incidence and enhance the ability of study staff to 
mitigate them when possible. 
Summary tables of social impact events will be generated weekly, and made 
available for review by the protocol chairs, protocol team leader, and the 
designated NIAID representative. 
12.2 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare.  
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site should contact the participant first, and then notify the 
IRB/EC and any applicable RE of the matter as soon as possible. 

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13 
Version history 
The Protocol Team may modify the original version of the protocol. 
Modifications are made to HVTN protocols via clarification memos, letters of 
amendment, or full protocol amendments.  
The version history of, and modifications to, Protocol HVTN 116 are described 
below. 
Protocol history and modifications 
Date: August 3, 2018 
Protocol version: Version 2.0 
Protocol modification: Full Protocol Amendment 1 
Item 1 
Added in Appendices A, B, and E: Broad regulatory agency access to 
participant study records 
Item 2 
Updated in Section 11.5, Section 15, and Appendices A, B, E: MCC 
changed to SAHPRA 
Item 3 
Added in Section 8.4, Administration, in-line filter language 
Item 4 
Clarified in Section 9.3: conditions upon when a participant may be 
replaced after enrollment 
Item 5 
Clarified in Section 9.6 and Appendices H and I: vaginal biopsies can still 
be collected at late visits if the total number of biopsies has not been 
reached 
Item 6 
Updated based on revisions made in Letter of Amendment 2 to Version 1.0 
(US sites), dated September 18, 2017 and Amendment to Version 1.1 (RSA 
site), dated October 5, 2017 
Item 7 
Updated based on revisions made in Letter of Amendment 1 (US sites) and 
Clarification Memo 3 (RSA site) to Version 1.0, dated March 24, 2017 
Item 8 
Updated based on revisions made in Clarification Memo 2 to Version 1.0, 
dated December 16, 2016 
Item 9 
Updated based on revisions made in Clarification Memo 1 to Version 1.0, 
dated June 17, 2016 
Item 10 Per live template changes on May 22, 2018, HIV infection moved from 
Section 7.3.6, Participant termination from the study, to Section 7.3.3, 
Discontinuing study product administrations for a participant, and other 
sections updated 
Date: September 18, 2017  

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Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 2 / Same changes made in Version 1.1, 
dated October 5, 2017 for South African sites 
Item 1 
Revised in Section 3, Overview; Section 5, Objectives and endpoints; 
Section 6, Statistical considerations; Appendices A and B, Sample 
informed consent forms: enrollment/sample sizes in Groups 3 and 5 
Item 2 
References to the DAIDS table for grading of adverse events updated to 
current version 2.1 and clarifications to the protocol to be consistent with 
new version of the grading table 
Item 3 
Clarified in Appendices L and M, Procedures at HVTN CRS: duration of 
screening period in footnote “a” 
Item 4 
Updated in Section 8, Study product preparation and administration: 
revisions regarding VRC01 and VRC01LS based on the updated IBs 
Date: March 24, 2017 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 1 / Clarification Memo 3 (same content) 
Item 1 
Clarified in Section 6.3, Blinding: lab staff will likely not be blinded to 
group assignment 
Item 2 
Clarified in Section 7.3.1 Delaying infusions for a participant, Section 
7.3.3 Discontinuing study product administrations for a participant, and 
Section 7.3.4 Delaying biopsy collections for a participant: details 
regarding participation in the study in the event of a pregnancy 
Item 3 
Updated in Section 8.2, Study product formulation: VRC01 and VRC01LS 
descriptions 
Item 4 
Revised in Section 8.3, Preparation of study products: IV infusion 
preparation instructions and holding times for study products after 
preparation 
Item 5 
Added the requirement for an in-line filter to be in place for all IV 
administrations in Section 8.4, Administration 
Item 6 
Updated in Section 8.4, Administration: Minimum infusion time period 
Item 7 
Clarified in Section 10.3.2, Immunohistochemistry: biopsy collection 
instructions 
Item 8 
Clarified in Section 11.3, Safety pause and prompt PSRT AE review, Table 
11-1: pruritus is a subjective reactogenicity symptom 
Item 9 
Clarified in Appendix M, Procedures at HVTN CRS for Group 3, Visit 19 
Colorectal biopsy collection 
Date: December 16, 2016 
Protocol version: Version 1.0 
Protocol modification: Clarification Memo 2 
Item 1 
Clarification in Section 9.3, Enrollment visits, Section 9.5, Follow-up visits, 
Appendices H-K, Laboratory procedures, and Appendices L-O, 

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Procedures at HVTN CRS: blood hormone levels will be assessed in 
persons born female only 
Date: June 17, 2016 
Protocol version: Version 1.0 
Protocol modification: Clarification Memo 1 
Item 1 
Deleted in Section 7.3.3, Discontinuing study product administrations for a 
participant: incorrect instruction for discontinuing infusions 
Item 2 
Clarified Section 9.6, Mucosal sampling: procedures for cervicovaginal 
secretion collections and pregnancy testing 
Item 3 
Corrected blood draw volumes in Appendices J & K: Laboratory procedures 
for Groups 4 and 5 
Date: April 22, 2016 
Protocol version: 1.0 
Protocol modification: Original protocol 
 

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14 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant 
to the conduct of this study, include: 
 Assessment of Understanding. Accessible through the HVTN protocol-
specific website. 
 Current CDC Guidelines. Revised Recommendations for HIV Testing of 
Adults, Adolescents, and Pregnant Women in Health-Care Settings. Available 
at http://www.cdc.gov/mmwr/PDF/rr/rr5514.pdf.  
 Division of AIDS (DAIDS) Clinical Research Policies and Standard 
Procedures Documents. Available at  
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-
procedures 
 Division of AIDS Protocol Registration Manual. Available at  
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf 
 Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events. Corrected Version 2.1, July 2017. Available at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting/daids-grading-tables 
 The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 
2.0, January 2010. Available at http://rsc.tech-res.com/clinical-research-
sites/safety-reporting/manual  
 HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
 HVTN 116 Special Instructions. Accessible through the HVTN protocol-
specific website. 
 HVTN 116 Study Specific Procedures. Accessible through the HVTN 
protocol-specific website. 
 HVTN Laboratory Manual of Operations. Accessible through the HVTN 
website. 
 HVTN Manual of Operations. Accessible through the HVTN website. 
 Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
http://www.iata.org/publications/dgr/Pages/index.aspx  
 Lab assay algorithm 

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 HVTN algorithm for diagnosis of HIV infections. Part of the HVTN 
Laboratory Manual of Operations (see above). 
 International Conference on Harmonisation (ICH) E6 (R1), Guideline for 
Good Clinical Practice: Section 4.8, Informed consent of trial subjects. 
Available at http://www.ich.org/products/guidelines/efficacy/article/efficacy-
guidelines.html 
 Participants’ Bill of Rights and Responsibilities. Accessible through the 
HVTN website. 
 NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic 
Acid Molecules. Available 
athttp://osp.od.nih.gov/biotechnology/biosafety/nih-guidelines. 
 NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical 
Research. Available at http://grants1.nih.gov/grants/guide/notice-files/NOT-
OD-01-053.html. 
 Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks, 
July 2008. 
 Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials. Available at 
https://www.niaid.nih.gov/sites/default/files/daids-sourcedocpolicy.pdf  
 Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFR
Part=50 
 Title 45, Code of Federal Regulations, Part 46. Available at 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html 
See Section 16 for literature cited in the background and statistics sections of this 
protocol. 

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15 
Acronyms and abbreviations 
Ab 
antibody 
Ad 
adenovirus 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase 
β-HCG 
beta human chorionic gonadotropin 
BMI 
body mass index 
bNAb 
broadly neutralizing antibody 
CAB 
Community Advisory Board 
CBC 
complete blood count 
CDC 
US Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CRF 
case report form 
CRPMC 
NIAID Clinical Research Products Management Center 
CRS* 
clinical research site 
CTL 
cytotoxic T lymphocyte 
DAERS 
DAIDS Adverse Experience Reporting System 
DAIDS 
Division of AIDS (US NIH) 
DHHS 
US Department of Health and Human Services 
EAE 
adverse events requiring expedited reporting to DAIDS 
EC 
Ethics Committee 
EIA 
enzyme immunoassay 
ELISA 
enzyme-linked immunosorbent assay 
FDA 
US Food and Drug Administration 
FHCRC 
Fred Hutchinson Cancer Research Center 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HCV 
hepatitis C virus 
HLA 
human leukocyte antigen 
HVTN 
HIV Vaccine Trials Network 
IB 
Investigator’s Brochure 
IBC 
Institutional Biosafety Committee 
ICH 
International Conference on Harmonisation 
IND 
Investigational New Drug 

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IRB 
Institutional Review Board 
IUD 
intrauterine device 
MAR 
missing at random 
MMR 
measles, mumps, and rubella 
mAb 
monoclonal antibody 
NHP 
nonhuman primate 
NIAID 
National Institute of Allergy and Infectious Diseases (US NIH) 
NICD 
National Institute for Communicable Diseases (Johannesburg, South 
Africa) 
NIH 
US National Institutes of Health 
NOEL 
no observed effect level 
OHRP 
US Office for Human Research Protections 
OPV 
oral polio vaccine 
PAB 
DAIDS Pharmaceutical Affairs Branch 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PI 
Principal Investigator 
PK 
pharmacokinetics 
PSRT 
Protocol Safety Review Team 
RAB 
DAIDS Regulatory Affairs Branch 
RE 
regulatory entity 
RSC 
DAIDS Regulatory Support Center 
SAE 
serious adverse event 
SAHPRA South African Health Products Regulatory Authority  
SC 
subcutaneous 
SCHARP Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
statistical and data management center 
SHIV 
simian-human immunodeficiency virus 
SMB 
Safety Monitoring Board 
SPT 
DAIDS Safety and Pharmacovigilance Team 
UW-VSL University of Washington Virology Specialty Laboratory 
VRC 
Vaccine Research Center (NIAID) 
WT 
wild type 
* CRSs were formerly referred to as HIV Vaccine Trial Units (HVTUs). 
Conversion to use of the term CRS is in process, and some HVTN documents 
may still refer to HVTUs. 

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16 
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al. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human 
monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015;182(3):289-301. 
58. 
Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side 
effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9(4):325-38. 
59. 
Bugelski PJ, Achuthanandam R, Capocasale RJ, Treacy G, Bouman-Thio E. 
Monoclonal antibody-induced cytokine-release syndrome. Expert Rev Clin Immunol. 
2009;5(5):499-521. 
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Vogel WH. Infusion reactions: diagnosis, assessment, and management. Clin J Oncol 
Nurs. 2010;14(2):E10-E21. 
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Hasselrot K, Cheruiyot J, Kimani J, Ball TB, Kaul R, Hirbod T. Feasibility and safety 
of cervical biopsy sampling for mucosal immune studies in female sex workers from Nairobi, 
Kenya. PLoS ONE. 2012;7(10):e47570. 
62. 
McGowan I, Hoesley C, Cranston RD, Andrew P, Janocko L, Dai JY, et al. A phase 1 
randomized, double blind, placebo controlled rectal safety and acceptability study of 
tenofovir 1% gel (MTN-007). PLoS ONE. 2013;8(4):e60147. 
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Thurman A. Safety of Cervical and Vaginal Biopsies in Microbicide and 
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Agresti A, Coull BA. Approximate is better than "exact" for interval estimation of 
binomial proportions. Am Stat. 1998;52(2):119-26. 
65. 
Montefiori DC. Measuring HIV neutralization in a luciferase reporter gene assay. 
Methods Mol Biol. 2009;485:395-405. 
66. 
Todd CA, Greene KM, Yu X, Ozaki DA, Gao H, Huang Y, et al. Development and 
implementation of an international proficiency testing program for a neutralizing antibody 
assay for HIV-1 in TZM-bl cells. J Immunol Methods. 2012;375(1-2):57-67. 
67. 
Ozaki DA, Gao H, Todd CA, Greene KM, Montefiori DC, Sarzotti-Kelsoe M. 
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Appendix A 
Sample informed consent form for 
Groups 1-3 
Title: A phase 1 clinical trial to evaluate the safety, pharmacokinetics, and anti-
viral activity of VRC-HIVMAB060-00-AB (VRC01) and 
VRC-HIVMAB080-00-AB (VRC01LS) in the serum and mucosa of healthy, 
HIV-uninfected adult participants 
HVTN protocol number: HVTN 116 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study.  
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. 
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name]  are doing a 
study to test 2 versions of an antibody against HIV called VRC01 and VRC01LS. 
HIV is the virus that causes AIDS. Antibodies are one of the ways the human 
body fights infection. Antibodies are natural proteins that the body can make to 
prevent infectious agents such as bacteria and viruses from making you sick. 
Researchers can also make antibodies in laboratories and give them to people 
intravenously (with an IV). We will tell you more about this procedure below. 
This has been done successfully to prevent or treat some other health problems, 
such as a virus that causes respiratory infections in infants. 
Originally, about 101 people were planned to take part in this study at multiple 
sites. The study has since been changed so that now only about 74 people will 
take part in it. The two groups (Groups 3 and 5) that are testing the VRC01LS 
antibody will stop enrolling because the researchers feel that a smaller number of 
participants is enough to provide the information needed regarding the VRC01LS 
antibody. Enrollment will stop once at least 12 people have enrolled in Group 3 
and Group 5 combined. Participants that have enrolled in these two groups will 
continue their study schedule as planned, and should complete all study visits, as 
the information collected will be important for the research. The researcher in 
charge of this study at this clinic is [Insert name of site PI]. The US National 
Institutes of Health (NIH) is paying for the study.  
1. We are doing this study to answer several questions. 
 Are the antibodies safe to give to people? 

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 Are people able to take the antibodies without becoming too uncomfortable? 
 Do the antibodies move around in the body?  
 Do the antibodies get to where they need to be in the body to protect people 
from HIV?  
 How much of the antibodies remain in your body as time passes? 
2. The antibodies cannot give you HIV. 
The antibodies are not made from actual HIV. It is impossible for the antibodies 
to give you HIV. Also, they cannot cause you to give HIV to someone else. 
However, we do not know if the antibody will decrease, increase, or not change 
your chance of becoming infected with HIV if you are exposed to the virus. 
3. These antibodies are experimental. 
The 2 versions of the antibody are called VRC-HIVMAB060-00-AB and 
VRC-HIVMAB080-00-AB. They are both antibodies against the HIV virus. From 
here on, we will call them VRC01 and VRC01LS or the antibodies.  
They are experimental. That means we do not know whether they will be safe to 
use in people, or whether they will work to prevent HIV infection. These 
antibodies are used only in research studies. 
The antibodies were developed by the Vaccine Research Center at the US 
National Institutes of Health (NIH). In laboratory and animal studies, the 
antibodies attached to and disabled many kinds of HIV viruses. We do not know 
if they will act the same way when given to people. It will take many studies to 
learn if they will be useful for prevention of HIV or treatment of HIV. This study 
alone will not answer these questions. 
VRC01 and VRC01LS are identical to each other except for a small structural 
change in VRC01LS. The purpose of this change is to make VRC01LS last longer 
in the body.  
Risks of the antibodies: 
There have been 6 studies using the VRC01 antibody in people in the United 
States at the NIH Clinical Center and at HVTN clinics. As of February 22, 2018, 
VRC01 has been given to over 2600 HIV-uninfected and about 88 HIV-infected 
adults and about 40 HIV-exposed infants. The VRC01 antibody has been tested in 
one study with HIV-positive people and in 2 studies with HIV-negative people. 
So far, it has not made them too uncomfortable or caused serious health problems. 
One participant had chest discomfort and one had a rash. These participants might 
have gotten the antibody or the placebo. The placebo is made from inactive 
ingredients made to look like the antibody. To be safe, no more antibody or 

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placebo was given to these participants. Some participants have had mild body 
discomfort, muscle, or joint pain after getting the VRC01 antibody.  
There is 1 ongoing study using the VRC01LS antibody for the first time in people 
in the US at the NIH Clinical Center. As of July 17, 2017, 39 people received the 
VRC01LS antibody. So far, it has not made them too uncomfortable or caused 
serious health problems. 
These antibodies may have other side effects that we do not know about yet. 
General risks of antibodies: 
Antibodies that are different from the antibodies in this study have been given to 
people for other illnesses. With those antibodies most side effects happen within 
the first 24 hours or, rarely, over a few days to weeks. Those antibodies have 
caused fever, chills, shaking, nausea, vomiting, pain, headache, dizziness, muscle 
and joint pains, diarrhea, chest discomfort, high or low blood pressure, racing 
heartbeat , or chest pain, and itchiness, rash, or hives where you got the infusion.  
Rarely, an antibody can cause an allergic reaction. If the reaction occurs, it 
usually occurs soon after getting an antibody. It can include hives, itchiness, or 
rash, and swelling in the mouth and face with difficulty in breathing. It can also 
include racing heartbeat, chest pain, and dizziness. With treatment this reaction 
usually will go away. 
Rarely, antibodies licensed for treatment of other diseases have been linked to a 
blood disorder that interferes with blood clotting, to cancer, to damage to the heart 
muscle, and to the body’s immune system attacking healthy cells. 
These rare side effects and reactions have not been seen in other studies with the 
VRC01 or VRC01LS antibody.  
When antibodies are given to a person by IV they do not last in the body more 
than a few months. Any antibody given to you in this study should be gone from 
your body several months after your last dose. 
Joining the study 
4. It is completely up to you whether or not to join the study.  
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention studies now or in the future. You cannot be in this study while you are 

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in another study where you get a study product. Also during the study, you should 
not donate blood or tissue. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 5 if you use a separate screening consent that covers these 
procedures. 
5. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
 Checking your weight, temperature and blood pressure 
 Looking in your mouth and throat 
 Listening to your heart and lungs 
 Feeling your abdomen (stomach and liver) 
 Checking your veins to assess how easy it might be to start an IV 
 Rectal and/ or pelvic exam 
We will also do blood and urine tests. These tests tell us about some aspects of 
your health, such as how healthy your kidneys, liver, and immune system are. We 
will also test you for syphilis, chlamydia, gonorrhea, trichomonas vaginalis, 
bacterial vaginosis, hepatitis B, and hepatitis C. We will ask you about 
medications you are taking. We will ask you about behaviors that might put you 
at risk for getting HIV.  
If you were born female, we will test you for pregnancy. If you have had your 
ovaries removed (an oophorectomy), verified by medical records, you are not 
required to have a pregnancy test. If you were born female and are 21 years or 
older you may need to have a Pap smear if you have not had one within the last 3-
5 years. 
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
(Sites: adapt the following section so it is applicable to the care available at your 
site) 

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6. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
7. If you were born female and are sexually active in a way that could lead you 
to get pregnant, you must agree to use effective birth control to join this 
study. 
Site: If you want to include Appendix C or Appendix D, Approved birth control 
methods (for sample informed consent form), in this consent form, paste it below and 
delete paragraph below. 
You should not become pregnant during the study because we do not know how 
the antibodies could affect the developing baby. You must agree to use effective 
birth control from 21 days before enrollment through the last scheduled clinic 
visit. We will talk to you about effective birth control methods. They are listed on 
a handout that we will give to you.  
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
8. You will come to the clinic for scheduled visits about 13-14 times over about 
1 to 1½ years. 
Site: Insert number of visits and range of visit lengths. (There is site-specific variation 
in screening protocols and in the number of possible follow-up visits between 
protocol-mandated visits.) 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the study ends (for example, to tell you about the study 
results). 
9. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for female participants 
who could become pregnant). 
US sites only: 

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Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
10. We will give you one of the antibodies by intravenous (IV) infusion.  
Everyone will receive one of the antibodies by IV infusion. To get an IV, a sterile 
needle is used to place a small plastic tube into a vein in your arm. The tube is 
connected to a small bag of fluid that contains the antibody. An IV pump controls 
how fast the fluid drips from the bag, through the tube, and into your vein.  
11. We will give you the IV infusions on a schedule. 
There are 5 groups in this study. You will be in either Group 1, 2 or 3. However, 
the two groups (Groups 3 and 5) that are testing the VRC01LS antibody may have 
stopped enrolling so you may only be in either Group 1 or 2. There will be 23 
people in Groups 1 and 2. Group 3 will stop enrolling once about 6 people have 
enrolled. Groups 4 and 5 will not be done at this clinic.  
Groups 1 and 2 will get VRC01. Group 1 will get a lower dose than Group 2. The 
high and low doses of the antibody will be adjusted for your body weight. We will 
weigh you to determine the amount you will get. Group 3 will get VRC01LS.  
Site: Modify the randomization metaphor in the next sentence as appropriate to your 
local culture. 
We have no say in whether you are in Group 1, 2 or 3. It will be random, like 
flipping a coin. You cannot change groups.  
Group 
Treatment 
IV Infusion Schedule 
First 
Infusion 
2 
months 
later 
3 
months 
later 
4 
months 
later 
6 
months 
later 
Group 
1 
VRC01  
10 mg/kg  
IV 
Infusion 
IV 
Infusion 
 
IV 
Infusion 
IV 
Infusion 
Group 
2 
VRC01  
30 mg/kg  
IV 
Infusion 
IV 
Infusion 
 
IV 
Infusion 
IV 
Infusion 
Group 
3 
VRC01LS  
30 mg/kg 
IV 
Infusion 
 
IV 
Infusion 
 
IV 
Infusion 
Each IV infusion will take about 15 to 60 minutes. You will have to wait in the 
clinic for about a half hour after each infusion to see if there are any problems. 
Then for that night and for three more days, you will need to keep track of how 
you are feeling and if you have any symptoms. Contact the clinic staff if you have 
any issues or concerns after getting an infusion. If you have a problem, we will 
continue to check on you until it goes away. 

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12. In addition to giving you one of the antibodies, we will:  
 Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV; 
 Do physical exams; 
 Do pregnancy tests if you were born female;  
 Ask questions about your health, including medications you may be taking; 
 Ask questions about any personal problems or benefits you may have from 
being in the study; 
 Take urine and blood samples. 
If you were born female, we will test you at some visits for gonorrhea, chlamydia, 
trichomonas vaginalis, bacterial vaginosis, herpes simplex virus, and yeast. If you 
were born male, we will test you at some visits for gonorrhea, herpes simplex 
virus, and chlamydia. 
We will give you your test results. If you need care, we will tell you about the 
care we can give you here. We will also tell you about care we can help you get 
elsewhere. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 9 mL and 160 mL (about 2 teaspoons to about 2/3 
of a cup). Your body will make new blood to replace the blood we take out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix F, Table of procedures (for informed consent form) in this 
section or distribute it as a separate sheet if it is helpful to your study participants. 
You are not required to do either. 
We will be looking for side effects. We will review the results of these procedures 
and tests with you at your next visit, or sooner if necessary. If any of the results 
are important to your health, we will tell you.  
13. We will also collect semen, rectal fluid and tissue, cervical fluid and cervical 
and vaginal tissue samples from you. 
We want to see if the antibodies get to the parts of the body where people may be 
exposed to HIV: their rectum, vagina, and penis. We will take samples from these 
areas.  

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We will ask you to avoid some activities before we collect these samples. This 
will help make sure your samples give accurate lab readings. There are also some 
activities we will ask you to avoid after collecting the samples that are described 
below. 
We will ask all participants born male to provide semen as well as rectal fluids 
and tissue. We will ask all participants born female to provide cervical fluids as 
well as cervical and vaginal tissues. For every site except Seattle use this 
sentence: If participants born female become uncomfortable providing cervical 
fluids as well as cervical and vaginal tissues at any time, we will ask you to 
provide rectal fluids and/or tissues instead.  
Seattle site: Insert the following sentences instead.  
In addition, we will ask participants born female to provide rectal fluids and 
tissues. You can decide not to give rectal fluids and tissues and still be in the 
study.  
Site: localize measurement units throughout the following sections as needed. 
Semen collections (for persons born male) 
You will provide semen at the clinic. We will ask you to ejaculate into a plastic 
cup, which we will give to you.  
For the 2 days before we collect your semen, we will ask you to follow these 
instructions: 
 Do not ejaculate,  
 Do not use anything with lubricants,  
 Do not put saliva (your own or someone else’s) on the penis,  
 Do not receive oral sex.  
Rectal fluid collections (for all participants) 
We will collect rectal fluid by first placing a plastic tube about 2 cm wide (a little 
less than an inch) into your rectum. The tube will go in about 6½ cm (about 2½ 
inches). We will then place in your rectum either a small, absorbent sponge for 5 
minutes or an absorbent balloon for less than a minute. The balloon will be 
inflated to the size of a chicken egg (2 x 1 inches, 5 x 3 cm) after it is inside your 
rectum, and deflated before it is removed.  
For the 2 days before we collect your rectal fluid, we will ask you to follow these 
instructions:  

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 Do not have receptive anal intercourse  
 Do not put anything into your anus, including cleaning products (creams, gels, 
lotions, pads, etc.), lubricant, enemas or douches (even with water) 
 Do not use any anti-inflammatory creams in or around your anus.  
 We will not collect rectal fluid if you are pregnant, or if we think you may 
have an anal or rectal infection. You should tell us if your rectal area is sore. 
Rectal tissue collections (for all participants) 
Cape Town site: include a description of where the biopsies will take place, if needed.  
We will collect small samples of tissue about the size of a grain of rice from the 
lining of your rectum. These are called rectal biopsies. We will collect 5 biopsies 
at up to 7 different visits. To take the samples, we will place a plastic tube about 2 
cm wide (a little less than an inch) into the anus to view the lower part of the 
rectum. You may feel some discomfort, but the biopsies are almost always 
painless. It will take about 15 minutes.  
You may see blood in your first few stools. This is normal after a biopsy. If you 
think the bleeding is excessive, contact your study clinician immediately. 
For the 2 days before we collect your rectal tissues, we will ask you to follow the 
same instructions as above. In addition, we will ask you to follow these 
instructions after the procedure:  
 Do not have rectal sex and/or insert any foreign object or substance into the 
rectum for 5 days after biopsy samples have been collected; 
 You should call the clinic if you have a lot of bleeding, have a temperature of 
more than 38.1°C (100.5°F), experience chills, or have pain that is not getting 
better. 
Cervical fluid collections (for persons born female) 
You must have had a Pap smear within the last 3 to 5 years with the most recent 
result being normal. If you have not had a Pap smear within the last 3 years and 
would like to get one, we will tell you where you can get one. 
We will collect cervical fluids by using either a soft sponge inserted into the 
opening of your cervix, or by using something call a menstrual cup inserted into 
your vagina. If we use a soft sponge to collect cervical fluids, we will insert a 
speculum (a device that holds your vagina open) into your vagina and place the 
sponge in the opening of the cervix. This is similar to getting a pap smear. If we 
use the menstrual cup, we will explain how to insert it into your vagina. You may 
insert it before you come to the clinic. You will wear it for up to 6 hours and 

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remove it at the clinic. You will insert a second menstrual cup at the clinic and 
wear it for 10-15 minutes. If you are uncomfortable doing any of this on your 
own, you may come to the clinic and we will help you.  
For the 2 days before we collect your cervical fluid, we will ask you to follow 
these instructions:  
 Do not use any spermicide, lubricants, douche (even with water), or 
medication in or around your vagina;  
 Do not have vaginal intercourse or insert anything into your vagina; 
 Using a vaginal ring for contraception is fine and can continue to be used. 
You will need to remove it for a few hours before the procedure. The clinic 
staff can explain this to you. 
We will not collect cervical fluid if you are menstruating or pregnant, or if we 
think you may have a cervical or vaginal infection. If you are menstruating, we 
may ask you to return to collect this sample at another time. 
Cervical and vaginal tissue collections (for persons born female) 
We will collect small samples of tissue about the size of a grain of rice. We will 
collect up to 4 cervical and up to 5 vaginal biopsies at up to 6 different visits. We 
will insert a speculum into your vagina. A speculum is a metal or plastic tool that 
looks like a bird’s beak. It is used to help open your vagina a few inches.  
After the speculum is put into your vagina, the cervix and vaginal wall will be 
cleaned with a clean cotton ball or swab.  
Biopsies will be taken with clean forceps. Forceps are a metal or plastic tool to 
help get the tissue from inside your vagina and cervix. You may feel cramping, 
pain or discomfort. We will check to make sure that there is no bleeding from 
where the biopsies are taken. If there is bleeding, we will use a medication to stop 
it. One type of medication, silver nitrate, has a gray color. You may see gray 
flecks in your vaginal discharge after the biopsy. This is normal. The procedure 
will take about 15 minutes. 
For the 2 days before we collect your cervical/vaginal tissue, we will ask you to 
follow the same instructions as above. In addition, we will ask you to follow these 
instructions after the procedure:  
 Do not have vaginal sex and/or insert any foreign object or substance, 
including tampons, into the vagina for 7 days after biopsy samples have been 
collected; 

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 Participants should contact the clinic if they experience a large amount of 
bleeding, have a temperature of more than 38.1°C (100.5°F), experience 
chills, or have pain that is not improving.  
 Using a vaginal ring for contraception is fine and can continue to be used.  
14. We will counsel you on avoiding HIV infection. 
We will ask you personal questions about your HIV risk factors such as sexual 
behavior, alcohol, and drug use. We will talk with you about ways to keep your 
risk of getting HIV low.  
15. We will test your samples for this study. 
We will send your samples (without your name) to labs approved by the HVTN 
for this study, which are located in the United States and South Africa. 
Researchers at these labs will test your samples to see how your immune system 
responds to the antibodies. In rare cases, some of your samples may be sent to 
labs approved by the HVTN in other countries for research related to this study. 
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. They affect how you look 
and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. These types of genetic tests 
involve some of your genes, not all of your genes (your genome). The researchers 
will study the genes related to the immune system and HIV and those that affect 
how people get HIV.  
If you become HIV infected, the researchers may look at all of the genes of the 
virus found in your samples. The researchers will use this information to learn 
more about HIV and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
Tests done on your samples are for research purposes only. The labs will not give 
the results to you or this clinic, and the results will not become part of your study 
record. 
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 

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16. When samples are no longer needed for this study, the HVTN wants to keep 
them for use in other studies by HVTN or other researchers. We will call 
these “extra samples.” 
This section gives you information so you can decide if you want your extra 
samples and information used in other studies. You will mark your decision at the 
end of the form. If you have any questions, please ask.  
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, we will destroy all extra samples that we 
have. Your decision will not affect your being in this study or have any negative 
consequences here.  
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. [Site: choose one of the following two sentences. African sites 
should choose the sentence referencing the repository in South Africa. All other 
sites should choose the sentence referencing the repository in the United States]. 
Your samples will be stored in the HVTN repository in South Africa. Your 
samples will be stored in the HVTN repository in the United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: insert limits if your regulatory authority imposes 
them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN sell my samples and information? No, but the HVTN may share 
your samples with other researchers. Once we share your samples and 
information, we will not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and/or information, their research plan must be 
approved by the HVTN. Also, the researcher’s institutional review board (IRB) or 
ethics committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the 
rights and well-being of people in research. If the research plan is approved, the 
HVTN will send your samples to the researcher’s location. 
What information is shared with other researchers? The samples and limited 
information will be labeled with a code number. Your name will not be part of the 

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information. However, some information that we share may be personal, such as 
your race, ethnicity, sex, health information from the study, and HIV status. We 
may share information about the study product you received and how your body 
responded to the study product.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, antibody mediated prevention, the 
immune system and other diseases.  
Researchers may also do genetic testing on your samples.  
If you become HIV infected, the researchers may look at all of the genes of the 
virus found in your samples. The researchers will use this information to learn 
more about HIV and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it. Usually, no one would be able to look at your genome and link it to 
you as a person. However, if another database exists that also has information on 
your genome and your name, someone might be able to compare the databases 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this is very small. 
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
 Researchers who use your stored samples and limited information for other 
research 
 Government agencies that fund or monitor the research using your samples or 
information 
 Any regulatory agency that reviews clinical trials  
 The researcher’s Institutional Review Board or Ethics Committee 
 The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples or information may be published. No 
publication will use your name or identify you personally. 

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17. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
 The US National Institutes of Health and its study monitors, 
 The US Food and Drug Administration, 
 South African Health Products Regulatory Authority (SAHPRA), 
 [Insert name of local IRB/EC] , 
 Any regulatory agency that reviews clinical trials, 
 The HVTN and people who work for them,  
 The HVTN Safety Monitoring Board, and 
 The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. At this clinic, we have to report the 
following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.). 
 [Item 1] 
 [Item 2] 
 [Item 3] 
US sites: Include the following boxed text. You can remove the box. 

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We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
When the study is done, we may share the information from the study with others 
so they can see it and use it. We will not share any information that will let 
someone identify you. 
18. We may stop your infusions or take you out of the study at any time. We may 
do this even if you want to stay in the study and even if you were scheduled 
for more infusions.  
This may happen if: 
 you do not follow instructions, 
 we think that staying in the study might harm you, 
 you enroll in a different research study where you get another study product, 
or 
 the study is stopped for any reason. 
If we stop your infusions, we may ask you to stay in the study to complete other 
study procedures. 
19. We will stop your infusions and most sample collections if you become 
pregnant during the study. We will continue blood draws to check your 
health. 
We will encourage you to stay in the study if you choose. We will discuss your 
study options with you. 
If you leave the study while you are still pregnant, we will contact you after your 
due date to ask some questions about your pregnancy and delivery. 

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20. If you get infected with HIV during the study, we will stop your study 
product administration, take fewer samples, and help you get care and 
support. 
We will encourage you to stay in the study for up to 16 weeks if you choose. We 
will discuss your study options with you. We will counsel you about your HIV 
infection and about telling your partner(s). We will tell you where you can get 
support and medical care, and if there are other studies you may want to join. Site: 
Modify the following sentence as appropriate. We will not provide or pay for any 
of your HIV care directly.  
Other Risks 
21. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of taking blood:  
In this study, we will take your blood. This can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) or infection 
where the needle was inserted. Taking blood can cause a low blood cell count 
(anemia), making you feel tired. 
Risks of IV infusion procedures: 
Getting an IV may cause stinging, discomfort, pain, soreness, redness, bruising, 
itching, rash and swelling where the needle goes into the skin. Rarely, needle 
sticks can result in a blood clot or infection. 
Risks of taking rectal and genital fluids and tissues: 
We will ask you to stop some activities before and after we collect these samples. 
You may find this inconvenient. These sample collections may cause some 
anxiety, temporary discomfort, and embarrassment. We will try to make you as 
comfortable as possible. 
All biopsies may cause a small amount of bleeding, which usually stops on its 
own. In rare cases, excess bleeding or infection may occur from a biopsy. If you 
need care, we will tell you about the care we can give you here. We will also tell 
you about care we can help you get elsewhere. 
Until the areas where the biopsies were taken heal, you are at increased risk for 
HIV infection if you are exposed. Most people heal within 5 to 7 days, but some 
may take longer. 

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Personal problems/discrimination: 
Some people who join HVTN studies report personal problems or discrimination 
because of joining an HIV prevention study. Family or friends may worry, get 
upset or angry, or assume that you are infected with HIV or at high risk and treat 
you unfairly as a result. Rarely, a person has lost a job because the study took too 
much time away from work, or because their employer thought they had HIV.  
HIV testing 
HIV antibody tests are the usual way to test for HIV infections. We do not expect 
you to test positive on HIV antibody tests. We have used several common HIV 
antibody tests to test samples of blood containing the antibodies and none of them 
detected the antibody.  
To be absolutely safe we ask you to get HIV tests only at this clinic during the 
study. Our tests can always detect true HIV infection. They can also tell if 
someone is really not HIV infected. Since the antibodies do not last long in the 
body, we do not expect you to have any problems with HIV testing after the study 
ends. 
Although it has not been seen so far, getting VRC01 or VRC01LS may cause 
common HIV antibody tests to show that someone is HIV-negative, even if they 
are actually infected. 
Embarrassment/anxiety:  
You may feel embarrassed when we ask about your HIV risks, such as having sex 
and using drugs. Also, waiting for your HIV test results or other health test results 
could make you feel anxious. You could feel worried if your test results show that 
you are infected with HIV. If you feel embarrassed or anxious, please tell us and 
we will try to help you. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it.  
Risks of genetic testing: 
The genetic testing could show you may be at risk for certain diseases. If others 
found out, it could lead to discrimination or other problems. However, it is almost 
impossible for you or others to know your test results from the genetic testing. 
The results are not part of your study records and are not given to you.  

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U.S. Sites, include the following paragraph In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Unknown risks:  
We do not know if the antibodies will increase, decrease, or not change your risk 
of becoming infected with HIV if exposed. If you get infected with HIV, we do 
not know how the antibodies might affect your HIV infection or how long it takes 
to develop AIDS. 
We do not know how the antibodies will affect a pregnant participant or a 
developing baby.  
Benefits 
22. The study may not benefit you. 
We do not know whether getting the antibodies might benefit you in any way. 
However, being in the study might still help you in some ways. The counseling 
that you get as part of the study may help you avoid getting HIV. The lab tests 
and physical exams that you get while in this study might detect health problems 
you don’t yet know about.  
This study may help in the search for a vaccine to prevent HIV. However, if the 
antibodies later become approved and sold, there are no plans to share any money 
with you.  
Your rights and responsibilities 
23. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Participant’s Bill of Rights and Responsibilities. We will give you a 
copy of it. 
Leaving the study 
24. Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know.  

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We will ask you to come back to the clinic one last time for a physical exam, and 
we may ask to take some blood and urine samples. We will also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Do not make changes to the following section without obtaining approval from 
HVTN Regulatory Affairs at vtn.core.reg@hvtn.org. 
25. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere. 
If you become sick or injured in this study, there is a process to decide if it is 
related to the antibodies and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met.  
Next paragraph for Cape Town site only: 
In this study, our clinic has insurance to cover your medical treatment in the case 
of a study-related injury, following the Association of the British Pharmaceutical 
Industry guidelines for payment of study-related injury. We can give you a copy 
of these guidelines. In rare cases, the insurance funds may not be enough. If 
needed, the HVTN has limited funds to pay medical costs for study-related 
injuries that it determines are reasonable. (Sites: insert locale- appropriate 
medical insurance language in the following sentence) If the injury is not study 
related, then you and your health insurance will be responsible for treatment costs.  
Next paragraph for all other sites: 
The HVTN has limited funds to pay medical costs for study-related injuries that it 
determines are reasonable. (Sites: insert locale- appropriate medical insurance 
language in the following sentence) If the injury is not study related, then you and 
your health insurance will be responsible for treatment costs. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV prevention study. Or you might lose wages because you cannot 
go to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 

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You may disagree with the decision about whether your injury is study related. If 
you wish, the HVTN will ask independent experts to review the decision. You 
always have the right to use the court system if you are not satisfied. 
Questions  
26. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, or problems 
or concerns about how you are being treated in this study, contact 
[name/title/phone of person on IRB or other appropriate organization]. 
If you want to leave this study, contact 
[name and telephone number of the investigator or other study staff]. 
South African sites, include the following paragraph: 
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Health Products Regulatory Authority (SAHPRA) at: 
 
The Acting Chief Executive Officer 
South African Health Products Regulatory Authority 
Department of Health 
Private Bag X828 
PRETORIA 
0001 
Tel: (012) 395 8126 
Fax: (012) 395 9201 
e-mail: portia.nkambule@health.gov.za 
 Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
27. In Section 16 of this form, we told you about possible other uses of your extra 
samples and limited information, outside this study. Please choose only one of 
the options below and write your initials or make your mark in the box next 

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to it. Whatever you choose, the HVTN keeps track of your decision about 
how your samples and information can be used. 
 
 
I allow my extra samples combined with limited information to be used for other 
studies related to HIV, vaccines, antibody mediated prevention, the immune system, 
and other diseases. This may include genetic testing and keeping my cells growing over 
time.  
OR 
 
 
I agree to the option above and also to allow my extra samples combined with limited 
information to be used in genome wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes not 
allowing genetic testing, growing more of my cells, or genome wide studies.  
28. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
 You have read this consent form, or someone has read it to you. 
 You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
 You have had your questions answered and know that you can ask more. 
 You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 

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Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process. 
 
 

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Appendix B 
Sample informed consent form for  
Groups 4-5 
Title: A phase 1 clinical trial to evaluate the safety, pharmacokinetics, and anti-
viral activity of VRC-HIVMAB060-00-AB (VRC01) and 
VRC-HIVMAB080-00-AB (VRC01LS) in the serum and mucosa of healthy, 
HIV-uninfected adult participants 
HVTN protocol number: HVTN 116 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or 
ask someone to read it to you. If you decide to join the study, we will ask you to 
sign or make your mark on this form. We will offer you a copy to keep. We will 
ask you questions to see if we have explained everything clearly. You can also 
ask us questions about the study.  
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions. 
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name]  are doing a 
study to test 2 versions of an antibody against HIV called VRC01 and VRC01LS. 
HIV is the virus that causes AIDS. Antibodies are one of the ways the human 
body fights infection. Antibodies are natural proteins that the body can make to 
prevent infectious agents such as bacteria and viruses from making you sick. 
Researchers can also make antibodies in laboratories and give them to people 
intravenously (with an IV). We will tell you more about this procedure below. 
This has been done successfully to prevent or treat some other health problems, 
such as a virus that causes respiratory infections in infants. 
Originally, about 101 people were planned to take part in this study at multiple 
sites. The study has since been changed so that now only about 74 people will 
take part in it. The two groups (Groups 3 and 5) that are testing the VRC01LS 
antibody will stop enrolling because the researchers feel that a smaller number of 
participants is enough to provide the information needed regarding the VRC01LS 
antibody. Enrollment will stop once at least 12 people have enrolled in Group 3 
and Group 5 combined. Participants that have enrolled in these two groups will 
continue their study schedule as planned, and should complete all study visits, as 
the information collected will be important for the research. The researcher in 
charge of this study at this clinic is [Insert name of site PI]. The US National 
Institutes of Health (NIH) is paying for the study.  
1. We are doing this study to answer several questions. 
 Are the antibodies safe to give to people? 

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 Are people able to take the antibodies without becoming too uncomfortable? 
 Do the antibodies move around in the body?  
 Do the antibodies get to where they need to be in the body to protect people 
from HIV?  
 How much of the antibodies remain in your body as time passes? 
2. The antibodies cannot give you HIV. 
The antibodies are not made from actual HIV. It is impossible for the antibodies 
to give you HIV. Also, they cannot cause you to give HIV to someone else. 
However, we do not know if the antibody will decrease, increase, or not change 
your chance of becoming infected with HIV if you are exposed to the virus. 
3. These antibodies are experimental. 
The 2 versions of the antibody are called VRC-HIVMAB060-00-AB and 
VRC-HIVMAB080-00-AB. They are both antibodies against the HIV virus. From 
here on, we will call them VRC01 and VRC01LS or the antibodies.  
They are experimental. That means we do not know whether they will be safe to 
use in people, or whether they will work to prevent HIV infection. These 
antibodies are used only in research studies. 
The antibodies were developed by the Vaccine Research Center at the US 
National Institutes of Health (NIH). In laboratory and animal studies, the 
antibodies attached to and disabled many kinds of HIV viruses. We do not know 
if they will act the same way when given to people. It will take many studies to 
learn if they will be useful for prevention of HIV or treatment of HIV. This study 
alone will not answer these questions. 
VRC01 and VRC01LS are identical to each other except for a small structural 
change in VRC01LS. The purpose of this change is to make VRC01LS last longer 
in the body.  
Risks of the antibodies: 
There have been 6 studies using the VRC01 antibody in people in the United 
States at the NIH Clinical Center and at HVTN clinics. As of February 22, 2018, 
VRC01 has been given to over 2600 HIV-uninfected and about 88 HIV-infected 
adults and about 40 HIV-exposed infants. The VRC01 antibody has been tested in 
one study with HIV-positive people and in 2 studies with HIV-negative people. 
So far, it has not made them too uncomfortable or caused serious health problems. 
One participant had chest discomfort and one had a rash. These participants might 
have gotten the antibody or the placebo. The placebo is made from inactive 
ingredients made to look like the antibody. To be safe, no more antibody or 

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placebo was given to these participants. Some participants have had mild body 
discomfort, muscle, or joint pain after getting the VRC01 antibody.  
There is 1 ongoing study using the VRC01LS antibody for the first time in people 
in the US at the NIH Clinical Center. As of July 17, 2017, 39 people received the 
VRC01LS antibody. So far, it has not made them too uncomfortable or caused 
serious health problems. 
These antibodies may have other side effects that we do not know about yet. 
General risks of antibodies: 
Antibodies that are different from the antibodies in this study have been given to 
people for other illnesses. With those antibodies most side effects happen within 
the first 24 hours or, rarely, over a few days to weeks. Those antibodies have 
caused fever, chills, shaking, nausea, vomiting, pain, headache, dizziness, muscle 
and joint pains, diarrhea, chest discomfort, high or low blood pressure, racing 
heartbeat , or chest pain, and itchiness, rash, or hives where you got the infusion.  
Rarely, an antibody can cause an allergic reaction. If the reaction occurs, it 
usually occurs soon after getting an antibody. It can include hives, itchiness, or 
rash, and swelling in the mouth and face with difficulty in breathing. It can also 
include racing heartbeat, chest pain, and dizziness. With treatment this reaction 
usually will go away.  
Rarely, antibodies licensed for treatment of other diseases have been linked to a 
blood disorder that interferes with blood clotting, to cancer, to damage to the heart 
muscle, and to the body’s immune system attacking healthy cells. 
These rare side effects and reactions have not been seen in other studies with the 
VRC01 or VRC01LS antibody. 
When antibodies are given to a person by IV they do not last in the body more 
than a few months. Any antibody given to you in this study should be gone from 
your body several months after your last dose. 
Joining the study 
4. It is completely up to you whether or not to join the study.  
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention studies now or in the future. You cannot be in this study while you are 

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in another study where you get a study product. Also during the study, you should 
not donate blood or tissue. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 5 if you use a separate screening consent that covers these 
procedures. 
5. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
 Checking your weight, temperature and blood pressure 
 Looking in your mouth and throat 
 Listening to your heart and lungs 
 Feeling your abdomen (stomach and liver) 
 Checking your veins to assess how easy it might be to start an IV 
 Rectal and/ or pelvic exam 
We will also do blood and urine tests. These tests tell us about some aspects of 
your health, such as how healthy your kidneys, liver, and immune system are. We 
will also test you for syphilis, chlamydia, gonorrhea, trichomonas vaginalis, 
bacterial vaginosis, hepatitis B, and hepatitis C. We will ask you about 
medications you are taking. We will ask you about behaviors that might put you 
at risk for getting HIV.  
If you were born female, we will test you for pregnancy. If you have had your 
ovaries removed (an oophorectomy), verified by medical records, you are not 
required to have a pregnancy test. If you were born female and are 21 years or 
older you may need to have a Pap smear if you have not had one within the last 3-
5 years. 
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
(Sites: adapt the following section so it is applicable to the care available at your 
site) 

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6. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
7. If you were born female and are sexually active in a way that could lead you 
to get pregnant, you must agree to use effective birth control to join this 
study. 
Site: If you want to include Appendix C, Approved birth control methods (for sample 
informed consent form), in this consent form, paste it below and delete paragraph 
below. 
You should not become pregnant during the study because we do not know how 
the antibodies could affect the developing baby. You must agree to use effective 
birth control from 21 days before enrollment through the last scheduled clinic 
visit. We will talk to you about effective birth control methods. They are listed on 
a handout that we will give to you.  
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
8. You will come to the clinic for scheduled visits about 7-9 times over about 6 
months to 1 year. 
Site: Insert number of visits and range of visit lengths. (There is site-specific variation 
in screening protocols and in the number of possible follow-up visits between 
protocol-mandated visits.) 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the study ends (for example, to tell you about the study 
results). 
9. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for female participants 
who could become pregnant). 
US sites only: 

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Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
10. We will give you one of the antibodies by intravenous (IV) infusion.  
Everyone will receive one of the antibodies by IV infusion. To get an IV, a sterile 
needle is used to place a small plastic tube into a vein in your arm. The tube is 
connected to a small bag of fluid that contains the antibody. An IV pump controls 
how fast the fluid drips from the bag, through the tube, and into your vein. We 
will give you one IV infusion. 
11. We will give you the IV infusions on a schedule. 
There are 5 groups in this study. You will be in either Group 4 or 5. However, the 
two groups (Groups 3 and 5) that are testing the VRC01LS antibody may have 
stopped enrolling so you may only be Group 4. There will be 16 people in Group 
4. Group 5 will stop enrolling once about 6 people have enrolled. Groups 1-3 will 
not be done at this clinic.  
Group 4 will get VRC01 and Group 5 will get VRC01LS. Each group will get one 
IV infusion at their first visit.  
Site: Modify the randomization metaphor in the next sentence as appropriate to your 
local culture. 
We have no say in whether you are in Group 4 or 5. It will be random, like 
flipping a coin. You cannot change groups.  
The IV infusion will take about 15 to 60 minutes. You will have to wait in the 
clinic for about a half hour after the infusion to see if there are any problems. 
Then for that night and for three more days, you will need to keep track of how 
you are feeling and if you have any symptoms. Contact the clinic staff if you have 
any issues or concerns after getting an infusion. If you have a problem, we will 
continue to check on you until it goes away. 
12. In addition to giving you one of the antibodies, we will:  
 Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV; 
 Do physical exams; 
 Do pregnancy tests if you were born female;  
 Ask questions about your health, including medications you may be taking; 

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 Ask questions about any personal problems or benefits you may have from 
being in the study; 
 Take urine and blood samples. 
If you were born female, we will test you at some visits for gonorrhea, chlamydia, 
trichomonas vaginalis, bacterial vaginosis, herpes simplex virus, and yeast. If you 
were born male, we will test you at some visits for gonorrhea, herpes simplex 
virus, and chlamydia. 
We will give you your test results. If you need care, we will tell you about the 
care we can give you here. We will also tell you about care we can help you get 
elsewhere. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 30 mL and 150 mL (about 2 tablespoons to a little 
more than a ½ cup). Your body will make new blood to replace the blood we take 
out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix G, Table of procedures (for informed consent form) in this 
section or distribute it as a separate sheet if it is helpful to your study participants. 
You are not required to do either. 
We will be looking for side effects. We will review the results of these procedures 
and tests with you at your next visit, or sooner if necessary. If any of the results 
are important to your health, we will tell you.  
13. We will also collect semen, rectal fluid and tissue, cervical fluid and cervical 
and vaginal tissue samples from you. 
We want to see if the antibodies get to the parts of the body where people may be 
exposed to HIV: their rectum, vagina, and penis. We will take samples from these 
areas.  
We will ask you to avoid some activities before we collect these samples. This 
will help make sure your samples give accurate lab readings. There are also some 
activities we will ask you to avoid after collecting the samples that are described 
below. 
We will ask all participants born male to provide semen as well as rectal fluids 
and tissues. We will ask all participants born female to provide cervical fluids as 
well as cervical and vaginal tissues. If participants born female become 

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uncomfortable providing cervical fluids as well as cervical and vaginal tissues at 
any time we will ask you to provide rectal fluids and/or tissues instead.  
Site: localize measurement units throughout the following sections as needed. 
Semen collections (for persons born male) 
You will provide semen at the clinic. We will ask you to ejaculate into a plastic 
cup, which we will give to you.  
For the 2 days before we collect your semen, we will ask you to follow these 
instructions: 
 Do not ejaculate,  
 Do not use anything with lubricants,  
 Do not put saliva (your own or someone else’s) on the penis,  
 Do not receive oral sex.  
Rectal fluid collections (for all participants) 
We will collect rectal fluid by first placing a plastic tube about 2 cm wide (a little 
less than an inch) into your rectum. The tube will go in about 6½ cm (about 2½ 
inches). We will then place in your rectum either a small, absorbent sponge for 5 
minutes or an absorbent balloon for less than a minute. The balloon will be 
inflated to the size of a chicken egg (2 x 1 inches, 5 x 3 cm) after it is inside your 
rectum and deflated before it is removed.  
For the 2 days before we collect your rectal fluid, we will ask you to follow these 
instructions:  
 Do not have receptive anal intercourse  
 Do not put anything into your anus, including cleaning products (creams, gels, 
lotions, pads, etc.), lubricant, enemas or douches (even with water) 
 Do not use any anti-inflammatory creams in or around your anus.  
 We will not collect rectal fluid if you are pregnant, or if we think you may 
have an anal or rectal infection. You should tell us if your rectal area is sore. 
Rectal tissue collections (for all participants) 
We will collect small samples of tissue about the size of a grain of rice from the 
lining of your rectum. These are called rectal biopsies. We will collect 2 biopsies 
at 5-7 different visits. To take the samples, we will place a plastic tube about 2 cm 

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wide (a little less than an inch) into the anus to view the lower part of the rectum. 
You may feel some discomfort, but the biopsies are almost always painless. It will 
take about 15 minutes.  
You may see blood in your first few stools. This is normal after a biopsy. If you 
think the bleeding is excessive, contact your study clinician immediately. 
For the 2 days before we collect your rectal tissues, we will ask you to follow the 
same instructions as above. In addition, we will ask you to follow these 
instructions after the procedure:  
 Do not have rectal sex and/or insert any foreign object or substance into the 
rectum for 5 days after biopsy samples have been collected; 
 You should call the clinic if you have a lot of bleeding, have a temperature of 
more than 38.1°C (100.5°F), experience chills, or have pain that is not getting 
better. 
Cervical fluid collections (for persons born female) 
You must have had a Pap smear within the last 3 to 5 years with the most recent 
result being normal. If you have not had a Pap smear within the last 3 years and 
would like to get one, we will tell you where you can get one. 
We will collect cervical fluids by using either a soft sponge inserted into the 
opening of your cervix, or by using something call a menstrual cup inserted into 
your vagina. If we use a soft sponge to collect cervical fluids, we will insert a 
speculum (a device that holds your vagina open) into your vagina and place the 
sponge in the opening of the cervix. This is similar to getting a pap smear. If we 
use the menstrual cup, we will explain how to insert it into your vagina. You may 
insert it before you come to the clinic. You will wear it for up to 6 hours and 
remove it at the clinic. You will insert a second menstrual cup at the clinic and 
wear it for 10-15 minutes. If you are uncomfortable doing any of this on your 
own, you may come to the clinic and we will help you.  
For the 2 days before we collect your cervical fluid, we will ask you to follow 
these instructions:  
 Do not use any spermicide, lubricants, douche (even with water), or 
medication in or around your vagina;  
 Do not have vaginal intercourse or insert anything into your vagina; 
 Using a vaginal ring for contraception is fine and can continue to be used. 
You will need to remove it for a few hours. The clinic staff can explain this to 
you. 

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We will not collect cervical fluid if you are menstruating or pregnant, or if we 
think you may have a cervical or vaginal infection. If you are menstruating, we 
may ask you to return to collect this sample at another time. 
Cervical and vaginal tissue collections (for persons born female) 
We will collect small samples of tissue about the size of a grain of rice. We will 
collect 2 cervical and 2 vaginal biopsies at 5-7 different visits. We will insert a 
speculum into your vagina. A speculum is a metal or plastic tool that looks like a 
bird’s beak. It is used to help open your vagina a few inches.  
After the speculum is put into your vagina, the cervix and vaginal wall will be 
cleaned with a clean cotton ball or swab.  
Biopsies will be taken with clean forceps. Forceps are a metal or plastic tool to 
help get the tissue from inside your vagina and cervix. You may feel cramping, 
pain or discomfort. We will check to make sure that there is no bleeding from 
where the biopsies are taken. If there is bleeding, we will use a medication to stop 
it. One type of medication, silver nitrate, has a gray color. You may see gray 
flecks in your vaginal discharge after the biopsy. This is normal. The procedure 
will take about 15 minutes. 
For the 2 days before we collect your cervical/vaginal tissue, we will ask you to 
follow the same instructions as above. In addition, we will ask you to follow these 
instructions after the procedure:  
 Do not have vaginal sex and/or insert any foreign object or substance, 
including tampons, into the vagina for 7 days after biopsy samples have been 
collected; 
 Participants should contact the clinic if they experience a large amount of 
bleeding, have a temperature of more than 38.1°C (100.5°F), experience 
chills, or have pain that is not improving.  
 Using a vaginal ring for contraception is fine and can continue to be used.  
14. We will counsel you on avoiding HIV infection. 
We will ask you personal questions about your HIV risk factors such as sexual 
behavior, alcohol, and drug use. We will talk with you about ways to keep your 
risk of getting HIV low.  
15. We will test your samples for this study. 
We will send your samples (without your name) to labs approved by the HVTN 
for this study, which are located in the United States and South Africa. 
Researchers at these labs will test your samples to see how your immune system 

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responds to the antibodies. In rare cases, some of your samples may be sent to 
labs approved by the HVTN in other countries for research related to this study. 
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. They affect how you look 
and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. These types of genetic tests 
involve some of your genes, not all of your genes (your genome). The researchers 
will study the genes related to the immune system and HIV and those that affect 
how people get HIV.  
If you become HIV infected, the researchers may look at all of the genes of the 
virus found in your samples. The researchers will use this information to learn 
more about HIV and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
Tests done on your samples are for research purposes only. The labs will not give 
the results to you or this clinic, and the results will not become part of your study 
record. 
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 
16. When samples are no longer needed for this study, the HVTN wants to keep 
them for use in other studies by HVTN or other researchers. We will call 
these “extra samples.” 
This section gives you information so you can decide if you want your extra 
samples and information used in other studies. You will mark your decision at the 
end of the form. If you have any questions, please ask.  
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, we will destroy all extra samples that we 
have. Your decision will not affect your being in this study or have any negative 
consequences here.  
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. [Site: choose one of the following two sentences. African sites 
should choose the sentence referencing the repository in South Africa. All other 
sites should choose the sentence referencing the repository in the United States]. 
Your samples will be stored in the HVTN repository in South Africa. Your 
samples will be stored in the HVTN repository in the United States. 

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How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: insert limits if your regulatory authority imposes 
them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN sell my samples and information? No, but the HVTN may share 
your samples with other researchers. Once we share your samples and 
information, we will not be able to get them back. 
How do other researchers get my samples and information? When a researcher 
wants to use your samples and/or information, their research plan must be 
approved by the HVTN. Also, the researcher’s institutional review board (IRB) or 
ethics committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the 
rights and well-being of people in research. If the research plan is approved, the 
HVTN will send your samples to the researcher’s location. 
What information is shared with other researchers? The samples and limited 
information will be labeled with a code number. Your name will not be part of the 
information. However, some information that we share may be personal, such as 
your race, ethnicity, sex, health information from the study, and HIV status. We 
may share information about the study product you received and how your body 
responded to the study product.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, antibody mediated prevention, the 
immune system and other diseases.  
Researchers may also do genetic testing on your samples.  
If you become HIV infected, the researchers may look at all of the genes of the 
virus found in your samples. The researchers will use this information to learn 
more about HIV and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 

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compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it. Usually, no one would be able to look at your genome and link it to 
you as a person. However, if another database exists that also has information on 
your genome and your name, someone might be able to compare the databases 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this is very small. 
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
 Researchers who use your stored samples and limited information for other 
research 
 Government agencies that fund or monitor the research using your samples or 
information 
 Any regulatory agency that reviews clinical trials  
 The researcher’s Institutional Review Board or Ethics Committee 
 The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples or information may be published. No 
publication will use your name or identify you personally. 
17. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Clinic staff will have access to your study records. Your records may also be 
reviewed by groups who watch over this study to see that we are protecting your 
rights, keeping you safe, and following the study plan. These groups include: 
 The US National Institutes of Health and its study monitors, 
 The US Food and Drug Administration, 
 South African Health Products Regulatory Authority (SAHPRA), 

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 [Insert name of local IRB/EC] , 
 Any regulatory agency that reviews clinical trials, 
 The HVTN and people who work for them,  
 The HVTN Safety Monitoring Board, and 
 The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. At this clinic, we have to report the 
following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.). 
 [Item 1] 
 [Item 2] 
 [Item 3] 
US sites: Include the following boxed text. You can remove the box. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
When the study is done, we may share the information from the study with others 
so they can see it and use it. We will not share any information that will let 
someone identify you. 
18. We may take you out of the study at any time. We may do this even if you 
want to stay in the study.  
This may happen if: 

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 you do not follow instructions, 
 we think that staying in the study might harm you, 
 you enroll in a different research study where you get another study product, 
or 
 the study is stopped for any reason. 
19. We will stop most of your sample collections if you become pregnant during 
the study. We will continue blood draws to check your health. 
We will encourage you to stay in the study if you choose. We will discuss your 
study options with you. 
If you leave the study while you are still pregnant, we will contact you after your 
due date to ask some questions about your pregnancy and delivery. 
20. If you get infected with HIV during the study, we will stop your study 
product administration, take fewer samples, and help you get care and 
support. 
We will encourage you to stay in the study for up to 16 weeks if you choose. We 
will discuss your study options with you. We will counsel you about your HIV 
infection and about telling your partner(s). We will tell you where you can get 
support and medical care, and if there are other studies you may want to join. Site: 
Modify the following sentence as appropriate. We will not provide or pay for any 
of your HIV care directly.  
Other Risks 
21. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of taking blood:  
In this study, we will take your blood. This can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) or infection 
where the needle was inserted. Taking blood can cause a low blood cell count 
(anemia), making you feel tired. 
Risks of IV infusion procedure: 

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Getting an IV may cause stinging, discomfort, pain, soreness, redness, bruising, 
itching, rash and swelling where the needle goes into the skin. Rarely, needle 
sticks can result in a blood clot or infection. 
Risks of taking rectal and genital fluids and tissues: 
We will ask you to stop some activities before and after we collect these samples. 
You may find this inconvenient. These sample collections may cause some 
anxiety, temporary discomfort, and embarrassment. We will try to make you as 
comfortable as possible. 
All biopsies may cause a small amount of bleeding, which usually stops on its 
own. In rare cases, excess bleeding or infection may occur from a biopsy. If you 
need care, we will tell you about the care we can give you here. We will also tell 
you about care we can help you get elsewhere. 
Until the areas where the biopsies were taken heal, you are at increased risk for 
HIV infection if you are exposed. Most people heal within 5 to 7 days, but some 
may take longer. 
Personal problems/discrimination: 
Some people who join HVTN studies report personal problems or discrimination 
because of joining an HIV prevention study. Family or friends may worry, get 
upset or angry, or assume that you are infected with HIV or at high risk and treat 
you unfairly as a result. Rarely, a person has lost a job because the study took too 
much time away from work, or because their employer thought they had HIV.  
HIV testing 
HIV antibody tests are the usual way to test for HIV infections. We do not expect 
you to test positive on HIV antibody tests. We have used several common HIV 
antibody tests to test samples of blood containing the antibodies and none of them 
detected the antibody.  
To be absolutely safe we ask you to get HIV tests only at this clinic during the 
study. Our tests can always detect true HIV infection. They can also tell if 
someone is really not HIV infected. Since the antibodies do not last long in the 
body, we do not expect you to have any problems with HIV testing after the study 
ends. 
Although it has not been seen so far, getting VRC01 or VRC01LS may cause 
common HIV antibody tests to show that someone is HIV-negative, even if they 
are actually infected. 
Embarrassment/anxiety:  

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You may feel embarrassed when we ask about your HIV risks, such as having sex 
and using drugs. Also, waiting for your HIV test results or other health test results 
could make you feel anxious. You could feel worried if your test results show that 
you are infected with HIV. If you feel embarrassed or anxious, please tell us and 
we will try to help you. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it.  
Risks of genetic testing: 
The genetic testing could show you may be at risk for certain diseases. If others 
found out, it could lead to discrimination or other problems. However, it is almost 
impossible for you or others to know your test results from the genetic testing. 
The results are not part of your study records and are not given to you.  
U.S. Sites, include the following paragraph In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Unknown risks:  
We do not know if the antibodies will increase, decrease, or not change your risk 
of becoming infected with HIV if exposed. If you get infected with HIV, we do 
not know how the antibodies might affect your HIV infection or how long it takes 
to develop AIDS. 
We do not know how the antibodies will affect a pregnant participant or a 
developing baby.  
Benefits 
22. The study may not benefit you. 
We do not know whether getting the antibodies might benefit you in any way. 
However, being in the study might still help you in some ways. The counseling 
that you get as part of the study may help you avoid getting HIV. The lab tests 
and physical exams that you get while in this study might detect health problems 
you don’t yet know about.  

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This study may help in the search for a vaccine to prevent HIV. However, if the 
antibodies later become approved and sold, there are no plans to share any money 
with you.  
Your rights and responsibilities 
23. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Participant’s Bill of Rights and Responsibilities. We will give you a 
copy of it. 
Leaving the study 
24. Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know.  
We will ask you to come back to the clinic one last time for a physical exam, and 
we may ask to take some blood and urine samples. We will also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Do not make changes to the following section without obtaining approval from 
HVTN Regulatory Affairs at vtn.core.reg@hvtn.org. 
25. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere. 
If you become sick or injured in this study, there is a process to decide if it is 
related to the antibodies and/or procedures. If it is, we call it a study-related 
injury. There are funds to pay for treatment of study-related injuries if certain 
conditions are met.  
Next paragraph for Cape Town site only: 
In this study, our clinic has insurance to cover your medical treatment in the case 
of a study-related injury, following the Association of the British Pharmaceutical 
Industry guidelines for payment of study-related injury. We can give you a copy 

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of these guidelines. In rare cases, the insurance funds may not be enough. If 
needed, the HVTN has limited funds to pay medical costs for study-related 
injuries that it determines are reasonable. (Sites: insert locale- appropriate 
medical insurance language in the following sentence) If the injury is not study 
related, then you and your health insurance will be responsible for treatment costs.  
Next paragraph for all other sites: 
The HVTN has limited funds to pay medical costs for study-related injuries that it 
determines are reasonable. (Sites: insert locale- appropriate medical insurance 
language in the following sentence) If the injury is not study related, then you and 
your health insurance will be responsible for treatment costs. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV prevention study. Or you might lose wages because you cannot 
go to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, the HVTN will ask independent experts to review the decision. You 
always have the right to use the court system if you are not satisfied. 
Questions  
26. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, or problems or 
concerns about how you are being treated in this study, contact 
[name/title/phone of person on IRB or other appropriate organization]. 
If you want to leave this study, contact 
[name and telephone number of the investigator or other study staff]. 
South African sites, include the following paragraph: 
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Health Products Regulatory Authority (SAHPRA) at: 
 

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The Acting Chief Executive Officer 
South African Health Products Regulatory Authority 
Department of Health 
Private Bag X828 
PRETORIA 
0001 
Tel: (012) 395 8126 
Fax: (012) 395 9201 
e-mail: portia.nkambule@health.gov.za 
Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
27. In Section 16 of this form, we told you about possible other uses of your extra 
samples and limited information, outside this study. Please choose only one of 
the options below and write your initials or make your mark in the box next 
to it. Whatever you choose, the HVTN keeps track of your decision about 
how your samples and information can be used. 
 
 
I allow my extra samples combined with limited information to be used for other 
studies related to HIV, vaccines, antibody mediated prevention, the immune system, 
and other diseases. This may include genetic testing and keeping my cells growing over 
time.  
OR 
 
 
I agree to the option above and also to allow my extra samples combined with limited 
information to be used in genome wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes not 
allowing genetic testing, growing more of my cells, or genome wide studies.  
28. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
 You have read this consent form, or someone has read it to you. 
 You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
 You have had your questions answered and know that you can ask more. 

HVTN 116, Version 2.0 / August 3, 2018 
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 You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process. 
 
 

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Appendix C 
Approved birth control methods (for sample 
informed consent form) for US sites 
You should not become pregnant during the study because we do not know how 
the antibodies could affect the developing baby. 
You must agree to use effective birth control from 21 days prior to enrollment 
through the last required protocol clinic visit.  
Effective birth control means using any of the following methods every time you 
have sex: 
 Birth control drugs that prevent pregnancy—given by pills, shots, patches, 
vaginal rings, or inserts under the skin; 
 Male or female condoms, with or without a cream or gel that kills sperm; 
 Diaphragm or cervical cap with a cream or gel that kills sperm; 
 Intrauterine device (IUD); or 
 Any other contraceptive method approved by the researchers. 
You do not have to use birth control if: 
 You are only having sex with a partner or partners who have had a vasectomy. 
(We will ask you some questions to confirm that the vasectomy was 
successful.); 
 You have had your ovaries removed; 
 You have a tubal ligation (your “tubes tied”) or confirmed successful 
placement of a product that blocks the fallopian tubes; 
 You are having sex only with a female partner or partners; 
 You only have oral sex; or, 
 You are sexually abstinent (no sex at all). 
Remember: If you are having sex, you need to use male or female condoms to 
protect yourself from HIV infection. 
If you join the study, we will test you for pregnancy at some visits, including 
before each study infusion. 

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Appendix D 
Approved birth control methods (for sample 
informed consent form) for South African sites 
You should not become pregnant during the study because we do not know how 
the antibodies could affect the developing baby.  
If you were born female and are sexually active in a way that could lead you to 
get pregnant, you must agree to use effective birth control, from 21 days before 
enrollment until your last study visit.  
Effective birth control is defined as using 2 methods of birth control. : 
ONE barrier contraceptive method:  
 Male or female condoms; or, 
 Diaphragm or cervical cap; 
PLUS ONE of the following methods: 
 Birth control drugs that prevent pregnancy—given by pills, injections, 
patches, vaginal rings, or inserts under the skin;  
 Intrauterine device (IUD); or 
 You are only having sex with a partner who has had a vasectomy. (We 
will ask you some questions to confirm that the vasectomy was 
successful.).  
You do not have to use birth control if: 
 You have had your ovaries removed; 
 You have a tubal ligation (your “tubes tied”) or confirmed successful 
placement of a product that blocks the fallopian tubes;  
 You are sexually abstinent (no sex at all) 
Sites may delete the bullets below, if desired. 
 You are having sex only with a female partner or partners; 
 You only have oral sex.  
Remember: If you are having sex, you need to use male or female condoms to protect 
yourself from HIV infection. 

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Appendix E 
Sample consent form for use of samples and 
information in other studies 
Title: A phase 1 clinical trial to evaluate the safety, pharmacokinetics, and anti-
viral activity of VRC-HIVMAB060-00-AB (VRC01) and 
VRC-HIVMAB080-00-AB (VRC01LS) in the serum and mucosa of healthy, 
HIV-uninfected adult participants 
HVTN protocol number: HVTN 116 
Site: [Insert site name] 
When samples are no longer needed for this study, the HVTN wants to keep them 
for use in other studies. We will call these “extra samples.” 
This form gives you information so you can decide if you want your extra 
samples and information used in other studies. You will mark your decision at the 
end of the form. If you have any questions, please ask.  
1. Do I have to agree?  
No. You are free to say yes or no, or to change your mind after you sign this form. 
At your request, we will destroy all extra samples that we have. Your decision 
will not affect your being in this study or have any negative consequences here.  
2. Where are the samples stored?  
Extra samples are stored in a secure central place called a repository. [Site: 
choose one of the following two sentences. African sites should choose the 
sentence referencing the repository in South Africa. All other sites should choose 
the sentence referencing the repository in the United States]. Your samples will 
be stored in the HVTN repository in South Africa. Your samples will be stored in 
the HVTN repository in the United States. 
3. How long will the samples be stored?  
There is no limit on how long your extra samples will be stored. [Site: insert 
limits if your regulatory authority imposes them.] 
4. Will I be paid for the use of my samples?  
No. Also, a researcher may make a new scientific discovery or product based on 
the use of your samples. If this happens, there is no plan to share any money with 
you. The researcher is not likely to ever know who you are. 

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5. Will I benefit from allowing my samples to be used in other studies?  
Probably not. Results from these other studies are not given to you, this clinic, or 
your doctor. They are not part of your medical record. The studies are only being 
done for research purposes. 
6. Will the HVTN sell my samples and information?  
No, but the HVTN may share your samples with other researchers. Once we share 
your samples and information, we will not be able to get them back. 
7. How do other researchers get my samples and information?  
When a researcher wants to use your samples and/or information, their research 
plan must be approved by the HVTN. Also, the researcher’s institutional review 
board (IRB) or ethics committee (EC) will review their plan. [Site: If review by 
your institution’s IRB/EC/RE is also required, insert a sentence stating this..] 
IRBs/ECs protect the rights and well-being of people in research. If the research 
plan is approved, the HVTN will send your samples to the researcher’s location. 
8. What information is shared with other researchers?  
The samples and limited information will be labeled with a code number. Your 
name will not be part of the information. However, some information that we 
share may be personal, such as your race, ethnicity, gender, health information 
from the study, and HIV status. We may share information about the study 
product you received and how your body responded to the study product.  
9. What kind of studies might be done with my extra samples and information?  
 The studies will be related to HIV, vaccines, antibody mediated prevention, 
the immune system and other diseases.  
Researchers may also do genetic testing on your samples.  
If you become HIV infected, the researchers may look at all of the genes of the 
virus found in your samples. The researchers will use this information to learn 
more about HIV and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study. 
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it. Usually, no one would be able to look at your genome and link it to 

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you as a person. However, if another database exists that also has information on 
your genome and your name, someone might be able to compare the databases 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this is very small. 
10. What are the risks of genetic testing?  
The genetic testing could show you may be at risk for certain diseases. If others 
found out, it could lead to discrimination or other problems. However, it is almost 
impossible for you or others to know your test results from the genetic testing. 
The results are not part of your study records and are not given to you.  
U.S. Sites, include the following paragraph  
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance.  
11. Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
 Researchers who use your stored samples and limited information for other 
research 
 Government agencies that fund or monitor the research using your samples or 
information 
 Any regulatory agency that reviews clinical trials  
 The researcher’s Institutional Review Board or Ethics Committee 
 The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples or information may be published. No 
publication will use your name or identify you personally. 

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Questions  
12. If you have questions or problems about allowing your samples and 
information to be used in other studies, use the following important contacts. 
If you have questions about the use of your samples or information or if you want 
to change your mind about their use, contact 
[name and telephone number of the investigator or other study staff]. 
If you think you may have been harmed because of studies using your samples or 
information, contact 
[name and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, contact 
[name/title/phone of person on IRB or other appropriate organization]. 
South African sites, include the following paragraph: 
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Health Products Regulatory Authority (SAHPRA) at: 
 
The Acting Chief Executive Officer 
South African Health Products Regulatory Authority 
Department of Health 
Private Bag X828 
PRETORIA 
0001 
Tel: (012) 395 8126 
Fax: (012) 395 9201 
e-mail: portia.nkambule@health.gov.za 
13. Please choose only one of the options below and write your initials or make 
your mark in the box next to it. Whatever you choose, the HVTN keeps track 
of your choice about how your samples and information can be used. 
 

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I allow my extra samples combined with limited information to be used for other 
studies related to HIV, vaccines, antibody mediated prevention, the immune system, 
and other diseases. This may include genetic testing and keeping my cells growing over 
time.  
OR 
 
 
I agree to the option above and also to allow my extra samples combined with limited 
information to be used in genome wide studies. 
 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes not 
allowing genetic testing, growing more of my cells, or genome wide studies.  
 
 
 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process.

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Appendix F 
Table of procedures (for sample informed consent form, Groups 1-3) 
Group 1 and Group 2 
Procedure 
Screening 
visit 
2 weeks 
before 
the first 
infusion 
visit 
First 
infusion 
visit 
Time after first infusion visit 
1-2 weeks 
5-6 weeks 
8 weeks (2 
months) 
9-10 weeks 
13-14 weeks 
16 weeks (4 
months) 
19-20 weeks 
24 weeks (6 
months) 
25-26 weeks 
29-30 weeks 
37-38 weeks 
51-52 weeks 
(1 year) 
IV Infusion 
 
 
√ 
 
 
√ 
 
 
√ 
 
√ 
 
 
 
 
Cervical fluid, rectal fluid, and 
semen samples  
 
√ 
 
√ 
√ 
 
√ 
√ 
 
√ 
 
√ 
√ 
√ 
√ 
Cervical, vaginal, and rectal 
tissue samples 
 
√ 
 
 
 
 
 
 
 
 
 
√ 
√ 
√ 
√ 
Genital and rectal infection testing 
√ 
 
 
 
 
 
 
√ 
 
 
 
√ 
 
 
√ 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
 
√ 
 
 
 
 
 
 
 
 
 
√ 
 
Blood drawn 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born 
female)a 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
HIV testing & pretest counseling 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
√ 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/ questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pap smear (if needed) 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
a Persons who had a both their ovaries removed (verified by medical records), are not required to have a pregnancy test. 
 
 
 

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Group 3 
Procedure 
Screening 
visit 
2 weeks 
before 
the first 
infusion 
visit 
First 
infusion 
visit 
Time after first infusion visit 
1-2 weeks 
5-6 weeks 
12 weeks  
(3 months) 
15-16 weeks 
24 weeks  
(6 months) 
25-26 weeks 
29-30 weeks 
37-38 weeks 
51-52 weeks  
(1 year) 
64-65 weeks 
76-77 weeks  
(1 1/2 years) 
IV Infusion 
 
 
√ 
 
 
√ 
 
√ 
 
 
 
 
 
 
Cervical fluid, rectal fluid, and 
semen samples  
 
√ 
 
√ 
√ 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
Cervical, vaginal, and rectal 
tissue samples 
 
√ 
 
 
 
 
 
 
√ 
√ 
√ 
√ 
√ 
(√)b 
Genital and rectal infection testing 
√ 
 
 
 
 
 
√ 
 
√ 
 
 
√ 
 
√ 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
 
√ 
 
 
 
 
 
 
 
 
√ 
 
Blood drawn 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born 
female)a 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
HIV testing & pretest counseling 
√ 
 
 
 
 
 
 
 
√ 
 
√ 
√ 
 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/ questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pap smear (if needed) 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
a Persons who had both their ovaries removed (verified by medical records), are not required to have a pregnancy test. 
b Cervical and vaginal biopsies will only be collected if the participant has missed prior collections. 
 
 
 

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Appendix G 
Table of procedures (for sample informed consent form, Groups 4-5) 
Group 4 
Procedure 
Screening 
visit 
Infusion 
visit 
Time after infusion visit 
1-2 weeks 
5-6 weeks 
9-10 weeks 
13-14 weeks 
19-20 weeks 
25-26 weeks 
IV Infusion 
 
√ 
 
 
 
 
 
 
Cervical fluid, rectal fluid, and 
semen samples  
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
Cervical, vaginal, and rectal 
tissue samples 
 
 
√ 
√ 
 
√ 
√ 
√ 
Genital and rectal infection testing 
√ 
 
 
 
 
√ 
 
√ 
Medical history 
√ 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
√ 
 
 
 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born 
female)a 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
HIV testing & pretest counseling 
√ 
 
 
 
 
√ 
 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/ questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pap smear (if needed) 
√ 
 
 
 
 
 
 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
a Persons who had both their ovaries removed (verified by medical records), are not required to have a pregnancy test. 
 
 
 

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Group 5 
Procedure 
Screening 
visit 
Infusion 
visit 
Time after infusion visit 
1-2 weeks 
5-6 weeks 
9-10 weeks 
13-14 weeks 
19-20 weeks 
25-26 weeks 
37-38 weeks 
51-52 weeks  
(1 year) 
IV Infusion 
 
√ 
 
 
 
 
 
 
 
 
Cervical fluid, rectal fluid, and 
semen samples  
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Cervical, vaginal, and rectal 
tissue samples 
 
 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
Genital and rectal infection testing 
√ 
 
 
 
 
√ 
 
√ 
 
√ 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
√ 
 
 
 
 
 
√ 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born 
female)a 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
HIV testing & pretest counseling 
√ 
 
 
 
 
√ 
 
√ 
√ 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/ questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pap smear (if needed) 
√ 
 
 
 
 
 
 
 
 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
a Persons who had both their ovaries removed (verified by medical records), are not required to have a pregnancy test. 
 
 
 

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Appendix H 
Laboratory procedures for Group 1 and Group 2 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Day:
D-14
D0
D1-15
D29-43
D56
D57-71
D84
D85-99
D99-113
D112
D127-141
D168
D169-
18315
D197-
21115
D253-
26715
D351-
36515
D442-456 D526-540
Week:
W-2
W0
W1-2
W5-6
W8
W9-10
W12
W13-14
W15-16
W16
W19-20
W24
W25-26
W29-30
W37-38
W51-52
W64-65
W76-77
Procedure
Ship to1, 2
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
Inf #1
Inf #2
Inf #3
Inf #4
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HSV-1/2
Local lab
Local lab
SST
5mL
—
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL/
HSML-NICD
UW-VSL/
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
—
—
—
—
—
—
10
—
10
20
—
—
40
Safety Labs21
CBC/ Diff / platelets
Local lab
Local lab
EDTA
5mL
5
—
—
5
—
—
5
—
—
—
—
5
—
5
—
5
—
—
—
30
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
5
—
—
5
—
—
—
—
5
—
5
—
5
—
—
—
30
Hormone Levels
Hormone panel18
Local lab
Local lab
SST
8.5mL
—
8.5
—
—
—
—
—
—
—
—
—
—
—
8.5
8.5
8.5
8.5
—
—
43
STI Serology
—
—
—
—
Syphilis10
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Drug Levels/Detection
VRC01 Ab levels
CSR
NVITAL/FHCRC
SST
8.5mL
—
y
—
y
y
y
y
—
y
—
y
y
y
y
y
y
y
—
—
0
Immunogenicity Assays
Host genetics 6
CSR
FHCRC
ACD
8.5mL
—
z
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
Anti-VRC01 Ab levels
CSR
VRC/NVITAL
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
—
—
y
—
—
y
—
—
0
Functional humoral 
assays9
CSR
Duke
SST
8.5mL
—
y
—
y
y
—
y
—
y
—
—
y
—
y
y
y
y
—
—
0
STORAGE
Serum storage
CSR
—
SST
8.5mL
—
76.5
—
51
51
8.5
51
—
51
—
8.5
51
8.5
51
51
51
51
—
—
561
PBMC storage
CSR
—
ACD
8.5mL
—
51W
—
—
—
—
34W
—
—
—
—
34W
—
—
—
—
34W
—
—
153
Visit total
25
151
0
61
51
9
95
0
51
0
9
95
9
90
70
90
124
0
0
927
56-Day total16
 
25
176
176
237
288
121
216
155
206
206
163
250
112
193
263
159
124
0
0
URINE COLLECTION
Urine dipstick17, 21
Local lab
Local lab
X
—
—
X
—
—
—
—
—
—
—
—
—
—
—
X
—
—
—
Pregnancy Test7, 21
Local lab
Local lab
X
X
X
X
X
X
X
—
X
—
X
X
X
X
X
X
X
—
—
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
Trichomonas vaginalis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
Bacterial vaginosis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
Yeast13
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
MUCOSAL BIOPSY COLLECTION14
Colorectal
Total Biopsies
VRC01 Ab levels
TBD
VRC/FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
—
—
IHC
TBD
FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
3
—
—
—
—
—
—
—
—
—
—
—
3
3
3
3
—
—
0
5
0
0
0
0
0
0
0
0
0
0
0
5
5
5
5
0
0
25
Cervical
VRC01 Ab levels
TBD
VRC/FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
—
—
IHC
TBD
FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
2
—
—
—
—
—
—
—
—
—
—
—
2
—
—
—
—
—
0
4
0
0
0
0
0
0
0
0
0
0
0
4
2
2
2
0
0
14
Vaginal
VRC01 Ab levels
TBD
VRC/FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
—
—
IHC
TBD
FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
3
—
—
—
—
—
—
—
—
—
—
—
3
3
3
(3)20
—
—
0
5
0
0
0
0
0
0
0
0
0
0
0
5
5
5
2 [(5)20]
0
0
22
MUCOSAL SECRETION COLLECTION14
Semen
CSR
VRC/Duke
—
X
—
X
X
—
X
—
X
—
—
X
—
X
X
X
X
—
—
Cervical Secretions
CSR
VRC/Duke
—
X
—
X
X
—
X
—
X
—
—
X
—
X
X
X
X
—
—
Rectal Secretions
CSR
VRC/Duke
—
X
—
X
X
—
X
—
X
—
—
X
—
X
X
X
X
—
—
Visit total vaginal biopsies19
Screening 
visit3
Total
Visit total colorectal biopsies19
Visit total cervical biopsies19
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 165 of 188 
 
Footnotes: 
Grayed out visits are not applicable to this group  
1 CSR = central specimen repository 
2 HVTN Laboratory Program includes laboratories at UW-VSL, FHCRC, Duke, NVITAL, VRC, CHIL, and HSML-NICD. UW-VSL = University of Washington Virology Specialty Laboratory 
(Seattle, Washington, USA); FHCRC = Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke = Duke University Medical Center (Durham, North Carolina, USA); NVITAL = 
NIAID Vaccine Immune T-Cell Antibody Laboratory(Gaithersburg, Maryland, USA); VRC = Vaccine Research Center (Bethesda, Maryland, USA); CHIL = Cape Town HVTN Immunology 
Laboratory (Cape Town, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory, National Institute for Communicable Diseases (Johannesburg, South Africa). 
3 Screening may occur over the course of several contacts/visits up to and including day -14 prior to biopsy collection. 
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment). 
6 Genotyping may be performed on enrolled participants using cryopreserved PBMC collected at baseline. 
7 Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical records), are not required 
to undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 17 above. If a 
participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Functional humoral assays may include nAb, ADCC, virion capture, and phagocytosis assays. 
10 Syphilis testing will be done by serology. 
11 Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and when clinically indicated. 
12 Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
13 Cervical/vaginal swabs will be collected from females for yeast only when clinically indicated. 
14 Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. 
15 Mucosal biopsy collections must be at least 28 days from the previous biopsy collection. 
16 The total 56-day blood collection includes 10mL maximum blood loss per biopsy collection visit. 
17 And microscopy if needed. 
18 Hormone panel (persons born female only) is defined in Sections 9.3 (enrollment visits) and 9.5 (follow-up visits). 
19 The visit total indicates the total number of colorectal, cervical, or vaginal biopsies collected per visit. 
20 These biopsies will only be collected if the participant has missed prior collection visit(s), in order to maintain the overall number of biopsies in the "Total Biopsies" column. 
21 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be collected. 
w = 5 x 1mL aliquots of ACD plasma will be harvested for storage during PBMC processing; no separate blood draw is needed. 
y = SST blood collected for serum storage will also cover specimen needs for the VRC01 drug level, anti-VRC01 Ab level, and functional humoral assays; no separate blood draw is needed. 
z = ACD blood collected for PBMC storage will also cover specimen needs for host genetics assay; no separate blood draw is needed. 
TBD = to be determined.  
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 166 of 188 
Appendix I 
Laboratory procedures for Group 3 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Day:
D-14
D0
D1-15
D29-43
D56
D57-71
D84
D85-99
D99-113
D112
D127-141
D168
D169-
18315
D197-
21115
D253-
26715
D351-
36515
D442-45615
D526-
54015
Week:
W–2
W0
W1-2
W5-6
W8
W9-10
W12
W13-14
W15-16
W16
W19-20
W24
W25-26
W29-30
W37-38
W51-52
W64-65
W76-77
Procedure
Ship to1, 2
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
Inf #1
Inf #2
Inf #3
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HSV-1/2
Local lab
Local lab
SST
5mL
—
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL/
HSML-NICD
UW-VSL/
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
—
—
—
—
—
—
10
—
10
10
—
20
50
Safety Labs21
CBC/ Diff / platelets
Local lab
Local lab
EDTA
5mL
5
—
—
5
—
—
—
—
—
5
—
—
—
5
—
—
—
5
—
25
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
5
—
—
—
—
—
5
—
—
—
5
—
—
—
5
—
25
Hormone Levels
Hormone panel18
Local lab
Local lab
SST
8.5mL
—
8.5
—
—
—
—
—
—
—
—
—
—
—
8.5
8.5
8.5
8.5
8.5
8.5
60
STI Serology
Syphilis10
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Drug Levels/Detection
VRC01 LS Ab levels
CSR
NVITAL/FHCRC
SST
8.5mL
—
y
—
y
y
—
—
y
—
y
—
—
y
y
y
y
y
y
y
0
Immunogenicity Assays
Host genetics 6
CSR
FHCRC
ACD
8.5mL
—
z
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
Anti-VRC01 LS Ab levels
CSR
VRC/NVITAL
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
—
—
—
y
—
—
—
—
y
0
Functional humoral 
assays9
CSR
Duke
SST
8.5mL
—
y
—
y
y
—
—
—
—
y
—
—
—
y
y
y
y
y
y
0
STORAGE
Serum storage
CSR
—
SST
8.5mL
—
76.5
—
51
51
—
—
8.5
—
51
—
—
8.5
51
51
51
51
51
51
553
PBMC storage
CSR
—
ACD
8.5mL
—
51W
—
—
—
—
—
—
—
34W
—
—
—
34W
—
—
—
—
34W
153
Visit total
25
151
0
61
51
0
0
9
0
95
0
0
9
124
70
80
80
80
124
955
56-Day total16
 
25
176
176
237
288
112
112
60
60
155
104
104
104
132
202
149
80
80
124
URINE COLLECTION
Urine dipstick17, 21
Local lab
Local lab
X
—
—
X
—
—
—
—
—
—
—
—
—
—
—
—
—
X
—
Pregnancy Test7, 21
Local lab
Local lab
X
X
X
X
X
—
—
X
—
X
—
—
X
X
X
X
X
X
X
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
—
X
—
—
—
X
—
—
X
—
X
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
—
X
—
—
—
X
—
—
X
—
X
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
—
X
—
—
—
X
—
—
X
—
X
Trichomonas vaginalis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
—
X
—
—
—
X
—
—
X
—
X
Bacterial vaginosis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
—
X
—
—
—
X
—
—
X
—
X
Yeast13
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
MUCOSAL BIOPSY COLLECTION14
Colorectal
Total Biopsies
VRC01 LS Ab levels
TBD
VRC/FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
1
1
IHC
TBD
FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
1
1
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
3
—
—
—
—
—
—
—
—
—
—
—
3
3
3
3
3
3
0
5
0
0
0
0
0
0
0
0
0
0
0
5
5
5
5
5
5
35
Cervical
VRC01LS Ab levels
TBD
VRC/FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
1
(1)20
IHC
TBD
FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
1
(1)20
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
2
—
—
—
—
—
—
—
—
—
—
—
2
—
—
—
—
—
0
4
0
0
0
0
0
0
0
0
0
0
0
4
2
2
2
2
(2)20
16
Vaginal
VRC01LS Ab levels
TBD
VRC/FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
1
(1)20
IHC
TBD
FHCRC
—
1
—
—
—
—
—
—
—
—
—
—
—
1
1
1
1
1
(1)20
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
3
—
—
—
—
—
—
—
—
—
—
—
3
3
3
(3)20
(2-3)20
(2-3)20
0
5
0
0
0
0
0
0
0
0
0
0
0
5
5
5
2 [(5)20]
2 [(4-5)20]
(2-5)20
24
MUCOSAL SECRETION COLLECTION14
Semen
CSR
VRC/Duke
—
X
—
X
X
—
—
—
—
X
—
—
—
X
X
X
X
X
X
Cervical Secretions
CSR
VRC/Duke
—
X
—
X
X
—
—
—
—
X
—
—
—
X
X
X
X
X
X
Rectal Secretions
CSR
VRC/Duke
—
X
—
X
X
—
—
—
—
X
—
—
—
X
X
X
X
X
X
Screening 
visit3
Total
Visit total cervical biopsies19
Visit total vaginal biopsies19
Visit total colorectal biopsies19
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 167 of 188 
 
Footnotes: 
Grayed out visits are not applicable to this group  
1 CSR = central specimen repository 
2 HVTN Laboratory Program includes laboratories at UW-VSL, FHCRC, Duke, NVITAL, VRC, CHIL, and HSML-NICD. UW-VSL = University of Washington Virology Specialty Laboratory 
(Seattle, Washington, USA); FHCRC = Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke = Duke University Medical Center (Durham, North Carolina, USA); NVITAL = 
NIAID Vaccine Immune T-Cell Antibody Laboratory(Gaithersburg, Maryland, USA); VRC = Vaccine Research Center (Bethesda, Maryland, USA); CHIL = Cape Town HVTN Immunology 
Laboratory (Cape Town, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory, National Institute for Communicable Diseases (Johannesburg, South Africa). 
3 Screening may occur over the course of several contacts/visits up to and including day -14 prior to biopsy collection. 
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment). 
6 Genotyping may be performed on enrolled participants using cryopreserved PBMC collected at baseline. 
7 Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical records), are not required 
to undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 19 above. If a 
participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Functional humoral assays may include nAb, ADCC, virion capture, and phagocytosis assays. 
10 Syphilis testing will be done by serology. 
11 Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and when clinically indicated. 
12 Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
13 Cervical/vaginal swabs will be collected from females for yeast only when clinically indicated. 
14 Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. 
15 Mucosal biopsy collections must be at least 28 days from the previous biopsy collection. 
16 The total 56-day blood collection includes 10mL maximum blood loss per biopsy collection visit. 
17 And microscopy if needed. 
18 Hormone panel (persons born female only) is defined in Sections 9.3 (enrollment visits) and 9.5 (follow-up visits). 
19 The visit total indicates the total number of colorectal, cervical, or vaginal biopsies collected per visit. 
20 These biopsies will only be collected if the participant has missed prior collection visit(s), in order to maintain the overall number of biopsies in the "Total Biopsies" column. 
21 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be collected. 
w = 5 x 1mL aliquots of ACD plasma will be harvested for storage during PBMC processing; no separate blood draw is needed. 
y = SST blood collected for serum storage will also cover specimen needs for the VRC01 drug level, anti-VRC01 Ab level, and functional humoral assays; no separate blood draw is needed. 
z = ACD blood collected for PBMC storage will also cover specimen needs for host genetics assay; no separate blood draw is needed. 
TBD = to be determined. 
 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 168 of 188 
Appendix J 
Laboratory procedures for Group 4 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Day:
D-14
D0
D1-15
D29-4315
D56
D57-71
D84
D85-9915
D99-113
D112
D127-
14115
D168
D169-
18315
D197-211 D253-267 D351-365 D442-456 D526-540
Week:
W–2
W0
W1-2
W5-6
W8
W9-10
W12
W13-14
W15-16
W16
W19-20
W24
W25-26
W29-30
W37-38
W51-52
W64-65
W76-77
Procedure
Ship to1, 2
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
Inf#1
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HSV-1/2
Local lab
Local lab
SST
5mL
—
—
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL/
HSML-NICD
UW-VSL/
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
—
10
—
—
—
—
20
—
—
—
—
—
30
Safety Labs21
CBC/ Diff / platelets
Local lab
Local lab
EDTA
5mL
5
—
—
5
—
—
—
—
—
—
—
5
—
—
—
—
—
—
—
15
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
5
—
—
—
—
—
—
—
5
—
—
—
—
—
—
—
15
Hormone Levels
Hormone panel19
Local lab
Local lab
SST
8.5mL
—
—
—
8.5
8.5
—
—
—
8.5
—
—
8.5
—
8.5
—
—
—
—
—
43
STI Serology
Syphilis10
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Drug Levels/Detection
VRC01 Ab levels
CSR
NVITAL/FHCRC
SST
8.5mL
—
—
y
y
y
—
y
—
y
—
—
y
—
y
—
—
—
—
—
0
Immunogenicity Assays
Host genetics 6
CSR
FHCRC
ACD
8.5mL
—
—
z
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
Anti-VRC01 Ab levels
CSR
VRC/NVITAL
SST
8.5mL
—
—
y
y
—
—
—
—
—
—
—
—
—
y
—
—
—
—
—
0
Functional humoral 
assays9
CSR
Duke
SST
8.5mL
—
—
y
y
y
—
y
—
y
—
—
y
—
y
—
—
—
—
—
0
STORAGE
Serum storage
CSR
—
SST
8.5mL
—
—
76.5
51
51
—
51
—
51
—
—
51
—
51
—
—
—
—
—
383
PBMC storage
CSR
—
ACD
8.5mL
—
—
51W
—
—
—
—
—
34W
—
—
—
—
34W
—
—
—
—
—
119
Visit total
25
0
133
75
65
0
51
0
109
0
0
75
0
119
0
0
0
0
0
649
56-Day total16
 
25
25
158
232
297
272
190
116
224
224
160
234
75
193
193
0
0
0
0
URINE COLLECTION
Urine dipstick17, 21
Local lab
Local lab
X
—
—
X
—
—
—
—
—
—
—
X
—
—
—
—
—
—
—
Pregnancy Test7, 21
Local lab
Local lab
X
—
X
X
X
—
X
—
X
—
—
X
—
X
—
—
—
—
—
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
—
—
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
—
—
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
—
—
—
Trichomonas vaginalis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
—
—
—
Bacterial vaginosis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
—
—
—
Yeast13
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
MUCOSAL BIOPSY COLLECTION14
Colorectal
Total Biopsies
VRC01 Ab levels
TBD
VRC/FHCRC
—
—
—
1
1
—
—
—
2
—
—
2
—
1
—
—
—
—
—
IHC
TBD
FHCRC
—
—
—
1
1
—
—
—
—
—
—
—
—
1
—
—
—
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
0
0
2
2
0
0
0
2
0
0
2
0
2
0
0
0
0
0
10
Cervical
VRC01 Ab levels
TBD
VRC/FHCRC
—
—
—
1
1
—
—
—
2
—
—
2
—
1
—
—
—
—
—
IHC
TBD
FHCRC
—
—
—
1
1
—
—
—
—
—
—
—
—
1
—
—
—
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
0
0
2
2
0
0
0
2
0
0
2
0
2
0
0
0
0
0
10
Vaginal
VRC01 Ab levels
TBD
VRC/FHCRC
—
—
—
1
1
—
—
—
2
—
—
2
—
1
—
—
—
—
—
IHC
TBD
FHCRC
—
—
—
1
1
—
—
—
—
—
—
—
—
1
—
—
—
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
0
0
2
2
0
0
0
2
0
0
2
0
2
0
0
0
0
0
10
MUCOSAL SECRETION COLLECTION14
Semen
CSR
VRC/Duke
X18
—
—
X
X
—
X
—
X
—
—
X
—
X
—
—
—
—
—
Cervical Secretions
CSR
VRC/Duke
X18
—
—
X
X
—
X
—
X
—
—
X
—
X
—
—
—
—
—
Rectal Secretions
CSR
VRC/Duke
X18
—
—
X
X
—
X
—
X
—
—
X
—
X
—
—
—
—
—
Screening 
visit3
Total
Visit total colorectal biopsies20
Visit total cervical biopsies20
Visit total vaginal biopsies20
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 169 of 188 
 
Footnotes: 
Grayed out visits are not applicable to this group  
1 CSR = central specimen repository 
2 HVTN Laboratory Program includes laboratories at UW-VSL, FHCRC, Duke, NVITAL, VRC, CHIL, and HSML-NICD. UW-VSL = University of Washington Virology Specialty Laboratory 
(Seattle, Washington, USA); FHCRC = Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke = Duke University Medical Center (Durham, North Carolina, USA); NVITAL = 
NIAID Vaccine Immune T-Cell Antibody Laboratory(Gaithersburg, Maryland, USA); VRC = Vaccine Research Center (Bethesda, Maryland, USA); CHIL = Cape Town HVTN Immunology 
Laboratory (Cape Town, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory, National Institute for Communicable Diseases (Johannesburg, South Africa). 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to infusion #1. 
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment). 
6 Genotyping may be performed on enrolled participants using cryopreserved PBMC collected at baseline. 
7 Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical records), are not required 
to undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 14 above. If a 
participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Functional humoral assays may include nAb, ADCC, virion capture, and phagocytosis assays. 
10 Syphilis testing will be done by serology. 
11 Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and when clinically indicated. 
12 Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
13 Cervical/vaginal swabs will be collected from females for yeast only when clinically indicated.. 
14 Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. 
15 Mucosal biopsy collections must be at least 28 days from the previous biopsy collection. 
16 The total 56-day blood collection includes 5mL maximum blood loss per biopsy collection visit. 
17 And microscopy if needed. 
18 Mucosal secretion specimens will be collected as part of screening. They may be collected up to the infusion at visit 3. 
19 Hormone panel (persons born female only) is defined in Sections 9.3 (enrollment visits) and 9.5 (follow-up visits). 
20 The visit total indicates the total number of colorectal, cervical, or vaginal biopsies collected per visit. 
21 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be collected.  
w = 5 x 1mL aliquots of ACD plasma will be harvested for storage during PBMC processing; no separate blood draw is needed. 
y = SST blood collected for serum storage will also cover specimen needs for the VRC01 drug level, anti-VRC01 Ab level, and functional humoral assays; no separate blood draw is needed. 
z = ACD blood collected for PBMC storage will also cover specimen needs for host genetics assay; no separate blood draw is needed. 
TBD = to be determined. 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 170 of 188 
Appendix K 
Laboratory procedures for Group 5 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Day:
D-14
D0
D1-15
D29-4315
D56
D57-71
D84
D85-9915
D99-113
D112
D127-
14115
D168
D169-
18315
D197-211
D253-
26715
D351-
36515
D442-456 D526-540
Week:
W–2
W0
W1-2
W5-6
W8
W9-10
W12
W13-14
W15-16
W16
W19-20
W24
W25-26
W29-30
W37-38
W51-52
W64-65
W76-77
Procedure
Ship to1, 2
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
Inf#1
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HSV-1/2
Local lab
Local lab
SST
5mL
—
—
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 8
UW-VSL/
HSML-NICD
UW-VSL/
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
—
10
—
—
—
—
10
—
10
20
—
—
50
Safety Labs21
CBC/ Diff / platelets
Local lab
Local lab
EDTA
5mL
5
—
—
5
—
—
—
—
—
—
—
—
—
—
—
5
—
—
—
15
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
5
—
—
—
—
—
—
—
—
—
—
—
5
—
—
—
15
Hormone Levels
Hormone panel19
Local lab
Local lab
SST
8.5mL
—
—
—
8.5
8.5
—
—
—
8.5
—
—
8.5
—
8.5
—
8.5
8.5
—
—
60
STI Serology
Syphilis10
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Drug Levels/Detection
VRC01LS Ab levels
CSR
NVITAL/FHCRC
SST
8.5mL
—
—
y
y
y
—
y
—
y
—
—
y
—
y
—
y
y
—
—
0
Immunogenicity Assays
Host genetics 6
CSR
FHCRC
ACD
8.5mL
—
—
z
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
Anti-VRC01LS Ab levels
CSR
VRC/NVITAL
SST
8.5mL
—
—
y
y
—
—
—
—
—
—
—
—
—
—
—
—
y
—
—
0
Functional humoral 
assays9
CSR
Duke
SST
8.5mL
—
—
y
y
y
—
y
—
y
—
—
y
—
y
—
y
y
—
—
0
STORAGE
Serum storage
CSR
—
SST
8.5mL
—
—
76.5
51
51
—
51
—
51
—
—
51
—
51
—
51
51
—
—
485
PBMC storage
CSR
—
ACD
8.5mL
—
—
51W
—
—
—
—
—
34W
—
—
—
—
34W
—
—
34W
—
—
153
Visit total
25
0
133
75
65
0
51
0
109
0
0
65
0
109
0
85
119
0
0
832
56-Day total16
 
25
25
158
232
297
272
190
116
224
224
160
224
65
173
173
85
119
0
0
URINE COLLECTION
Urine dipstick17, 21
Local lab
Local lab
X
—
—
X
—
—
—
—
—
—
—
—
—
—
—
X
—
—
—
Pregnancy Test7, 21
Local lab
Local lab
X
—
X
X
X
—
X
—
X
—
—
X
—
X
—
X
X
—
—
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea11
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
Trichomonas vaginalis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
Bacterial vaginosis 12
Local lab
Local lab
X
—
—
—
—
—
—
—
X
—
—
—
—
X
—
—
X
—
—
Yeast13
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
MUCOSAL BIOPSY COLLECTION14
Colorectal
Total Biopsies
VRC01LS Ab levels
TBD
VRC/FHCRC
—
—
—
1
1
—
—
—
2
—
—
2
—
1
—
2
1
—
—
IHC
TBD
FHCRC
—
—
—
1
1
—
—
—
—
—
—
—
—
1
—
—
1
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
0
0
2
2
0
0
0
2
0
0
2
0
2
0
2
2
0
0
14
Cervical
VRC01LS Ab levels
TBD
VRC/FHCRC
—
—
—
1
1
—
—
—
2
—
—
2
—
1
—
2
1
—
—
IHC
TBD
FHCRC
—
—
—
1
1
—
—
—
—
—
—
—
—
1
—
—
1
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
0
0
2
2
0
0
0
2
0
0
2
0
2
0
2
2
0
0
14
Vaginal
VRC01LS Ab levels
TBD
VRC/FHCRC
—
—
—
1
1
—
—
—
2
—
—
2
—
1
—
2
1
—
—
IHC
TBD
FHCRC
—
—
—
1
1
—
—
—
—
—
—
—
—
1
—
—
1
—
—
Infectivity
FHCRC/CHIL
FHCRC/CHIL
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
0
0
0
2
2
0
0
0
2
0
0
2
0
2
0
2
2
0
0
14
MUCOSAL SECRETION COLLECTION14
Semen
CSR
VRC/Duke
X18
—
—
X
X
—
X
—
X
—
—
X
—
X
—
X
X
—
—
Cervical Secretions
CSR
VRC/Duke
X18
—
—
X
X
—
X
—
X
—
—
X
—
X
—
X
X
—
—
Rectal Secretions
CSR
VRC/Duke
X18
—
—
X
X
—
X
—
X
—
—
X
—
X
—
X
X
—
—
Screening 
visit3
Total
Visit total colorectal biopsies20
Visit total cervical biopsies20
Visit total vaginal biopsies20
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 171 of 188 
 
Footnotes: 
Grayed out visits are not applicable to this group  
1 CSR = central specimen repository 
2 HVTN Laboratory Program includes laboratories at UW-VSL, FHCRC, Duke, NVITAL, VRC, CHIL, and HSML-NICD. UW-VSL = University of Washington Virology Specialty Laboratory 
(Seattle, Washington, USA); FHCRC = Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke = Duke University Medical Center (Durham, North Carolina, USA); NVITAL = 
NIAID Vaccine Immune T-Cell Antibody Laboratory(Gaithersburg, Maryland, USA); VRC = Vaccine Research Center (Bethesda, Maryland, USA); CHIL = Cape Town HVTN Immunology 
Laboratory (Cape Town, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory, National Institute for Communicable Diseases (Johannesburg, South Africa). 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to infusion #1. 
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment). 
6 Genotyping may be performed on enrolled participants using cryopreserved PBMC collected at baseline. 
7 Pregnancy test may be performed on blood specimens. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical records), are not required 
to undergo pregnancy testing. 
8 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 17 above. If a 
participant has a confirmed diagnosis of HIV-infection, do not collect blood for HIV diagnostic testing (see Section 9.14). 
9 Functional humoral assays may include nAb, ADCC, virion capture, and phagocytosis assays. 
10 Syphilis testing will be done by serology. 
11 Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and when clinically indicated. 
12 Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
13 Cervical/vaginal swabs will be collected from females for yeast only when clinically indicated. 
14 Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. 
15 Mucosal biopsy collections must be at least 28 days from the previous biopsy collection. 
16 The total 56-day blood collection includes 5mL maximum blood loss per biopsy collection visit. 
17 And microscopy if needed. 
18 Mucosal secretion specimens will be collected as part of screening. They may be collected up to the infusion at visit 3. 
19 Hormone panel (persons born female only) is defined in Sections 9.3 (enrollment visits) and 9.5 (follow-up visits). 
20 The visit total indicates the total number of colorectal, cervical, or vaginal biopsies collected per visit. 
21 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be collected. 
w = 5 x 1mL aliquots of ACD plasma will be harvested for storage during PBMC processing; no separate blood draw is needed. 
y = SST blood collected for serum storage will also cover specimen needs for the VRC01 drug level, anti-VRC01 Ab level, and functional humoral assays; no separate blood draw is needed. 
z = ACD blood collected for PBMC storage will also cover specimen needs for host genetics assay; no separate blood draw is needed. 
TBD = to be determined. 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 172 of 188 
Appendix L 
Procedures at HVTN CRS for Group 1 and Group 2 
Visit: 
01a 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-14 
D0 
D1-15 
D29-43 
D56 
D57-71 
D84 
D85-99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-
14 
W15-
16 
W16 
W19-20 
W24 
W25-26 
W29-30 
W37-38 
W51-52 
W64-65 
W76-77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf1 
 
 
Inf2 
 
 
 
 
Inf3 
 
Inf4 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if 
used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
Risk reduction counselingb 
X 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
Pregnancy prevention 
assessmentc 
X 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
Behavioral risk assessmentd 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
X 
X 
— 
— 
— 
Confirm eligibility and obtain 
demographics  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Randomizee 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
Social impact assessment 
questionnaire 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
Acceptability questionnaire 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
— 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
Intercurrent illness/adverse 
experience 
— 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
HIV infection assessmentf 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
X 
— 
— 
— 
Confirm HIV test results 
provided to participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
X 
Mucosal biopsy collectiong 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Colorectal 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
— 
— 
— 
Cervical 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
— 
— 
— 
Vaginal 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
— 
— 
— 
Mucosal secretion collectiong 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Semen 
— 
X 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
X 
X 
X 
— 
— 
— 
Cervical secretions 
— 
X 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
X 
X 
X 
— 
— 
— 
Rectal secretions 
— 
X 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
X 
X 
X 
— 
— 
— 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 173 of 188 
 
Grayed out visits are not applicable to this group  
a Screening may occur over the course of several contacts/visits up to and including visit 02, prior to biopsy collections. 
b Includes transmission risk reduction counseling for HIV-infected participants. 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d Not applicable to HIV-infected participants. 
e Participants will be randomized prior to the first infusion, ideally within 4 days. See Section 6.2. 
f Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. If a participant has a confirmed 
diagnosis of HIV infection, do not perform HIV infection assessment. 
g Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. Mucosal biopsy collections must 
be at least 28 days from the previous biopsy collection. 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 174 of 188 
Procedures at HVTN CRS for Group 1 and Group 2 continued 
Visit: 
01 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-14 
D0 
D1-15 
D29-43 
D56 
D57-71 
D84 
D85-99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-
14 
W15-
16 
W16 
W19-
20 
W24 
W25-
26 
W29-
30 
W37-
38 
W51-
52 
W64-
65 
W76-
77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf1 
 
 
Inf2 
 
 
 
 
Inf3 
 
Inf4 
 
 
 
 
 
 
 
Local lab assessmentsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening HIV test 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Syphilis, HBV, HCV 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
HSV 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Pap smearb 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Blood hormone levelsc 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
— 
— 
— 
Urine collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
Pregnancy (urine or serum HCG)d 
X 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Safety labsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC, differential 
X 
— 
— 
X 
— 
— 
X 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
Chemistry panel  
X 
— 
— 
X 
— 
— 
X 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
Rectal swab collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Cervical/vaginal swab collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Trichomonas vaginalisf 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Bacterial vaginosisf 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Yeastg 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Study product administration 
proceduresh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV infusioni 
— 
— 
X 
— 
— 
X 
— 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
Reactogenicity assessmentsj 
— 
— 
X 
— 
— 
X 
— 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 175 of 188 
 
Grayed out visits are not applicable to this group  
a For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests will be collected (see Appendix H). 
b Only for volunteers born female, per Sections 7.1 and 9.6. If collection of a pap smear is required, this may be done at any time provided the results are available prior to the 
collection of cervical samples. 
c Only collected in persons born female. 
d For a participant who was born female, pregnancy test must be performed on the day of every infusion and every biopsy prior to infusion or biopsy collections. Pregnancy test to 
determine initial eligibility will be performed at screening. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. Serum pregnancy tests may be used to confirm the results of, or substitute for, a urine pregnancy test. 
e Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and 
when clinically indicated. 
f Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
g Cervical/vaginal swabs will be collected from females for yeast only if clinically indicated.  
 
h Not applicable to HIV-infected participants. 
i Blood draws required at infusion visits must be performed prior to administration of study product; however, it is not necessary to have results prior to administration, except for 
results of a serum pregnancy test, if indicated. Lab tests may be drawn within the 3 days prior to infusion.  
j Reactogenicity assessments performed daily for at least 3 days postinfusion (see Section 9.10). 
 
 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 176 of 188 
Appendix M 
Procedures at HVTN CRS for Group 3 
Visit: 
01a 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-14 
D0 
D1-15 
D29-43 
D56 
D57-71 
D84 
D85-99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-14 
W15-16 
W16 
W19-20 
W24 
W25-26 
W29-30 
W37-38 
W51-52 
W64-65 
W76-77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf1 
 
 
 
 
Inf2 
 
 
 
 
Inf3 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if 
used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
— 
— 
Risk reduction counselingb 
X 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
— 
Pregnancy prevention 
assessmentc 
X 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
— 
Behavioral risk assessmentd 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
X 
— 
Confirm eligibility and obtain 
demographics  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Randomizee 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
— 
Social impact assessment 
questionnaire 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
Acceptability questionnaire 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
Concomitant medications 
X 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/adverse 
experience 
— 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
— 
HIV infection assessmentf 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
X 
— 
X 
— 
Confirm HIV test results 
provided to participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
X 
— 
X 
Mucosal biopsy collectiong 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Colorectal 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
— 
Cervical 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
X 
(X)h  
— 
Vaginal 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
X 
(X)h  
— 
Mucosal secretion collectiong 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Semen 
— 
X 
— 
X 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
— 
Cervical secretions 
— 
X 
— 
X 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
— 
Rectal secretions 
— 
X 
— 
X 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
— 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 177 of 188 
 
Grayed out visits are not applicable to this group  
a Screening may occur over the course of several contacts/visits up to and including visit 02, prior to biopsy collections. 
b Includes transmission risk reduction counseling for HIV-infected participants. 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d Not applicable to HIV-infected participants. 
e Participants will be randomized prior to the first infusion, ideally within 4 days. See Section 6.2. 
f Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
g Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. Mucosal biopsy collections must 
be at least 28 days from the previous biopsy collection. 
h These biopsies will only be collected if the participant has missed prior collection visit(s). 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 178 of 188 
Procedures at HVTN CRS for Group 3 continued 
Visit: 
01 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-14 
D0 
D1-15 
D29-43 
D56 
D57-71 
D84 
D85-99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-14 
W15-16 
W16 
W19-20 
W24 
W25-26 
W29-30 
W37-38 
W51-52 
W64-65 
W76-77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf1 
 
 
 
 
Inf2 
 
 
 
 
Inf3 
 
 
 
 
 
 
 
Local lab assessmentsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening HIV test 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Syphilis, HBV, HC 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
HSV 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Pap smearb 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Blood hormone levelsc 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
— 
Urine collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
Pregnancy (urine or serum 
HCG)d 
X 
X 
X 
X 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
— 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
Safety labsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC, differential 
X 
— 
— 
X 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
Chemistry panel  
X 
— 
— 
X 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
Rectal swab collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
Cervical/vaginal swab 
collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrheae  
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
Trichomonas vaginalisf 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
Bacterial vaginosisf 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
Yeastg 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Study product administration 
proceduresh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV infusioni 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
Reactogenicity assessmentsj 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 179 of 188 
 
a For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests will be collected (see Appendix I). 
Grayed out visits are not applicable to this group  
b Only for volunteers born female, per Sections 7.1 and 9.6. If collection of a pap smear is required, this may be done at any time provided the results are available prior to the 
collection of cervical samples. 
c Only collected in persons born female. 
d For a participant who was born female, pregnancy test must be performed on the day of every infusion and every biopsy prior to infusion or biopsy collections. Pregnancy test to 
determine initial eligibility will be performed at screening. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. Serum pregnancy tests may be used to confirm the results of, or substitute for, a urine pregnancy test. 
e Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and 
when clinically indicated. 
f Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
g Cervical/vaginal swabs will be collected from females for yeast only if clinically indicated. 
h Not applicable to HIV-infected participants. 
i Blood draws required at infusion visits must be performed prior to administration of study product; however, it is not necessary to have results prior to administration, except for 
results of a serum pregnancy test, if indicated. Lab tests may be drawn within the 3 days prior to infusion. 
j Reactogenicity assessments performed daily for at least 3 days postinfusion (see Section 9.10). 
 
 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 180 of 188 
Appendix N 
Procedures at HVTN CRS for Group 4 
Visit: 
01a 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-14 
D0 
D1-15 
D29-43 
D56 
D57-71 
D84 
D85-99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-14 
W15-16 
W16 
W19-20 
W24 
W25-26 
W29-30 
W37-38 
W51-52 
W64-65 
W76-77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf#1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if 
used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Abbreviated physical exam 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
Risk reduction counselingb 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Pregnancy prevention 
assessmentc 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Behavioral risk assessmentd 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Confirm eligibility, obtain 
demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Social impact assessment 
questionnaire 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Acceptability questionnaire 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Concomitant medications 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Intercurrent illness/adverse 
experience 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
HIV infection assessmente 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Confirm HIV test results 
provided to participant 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
Mucosal biopsy collectionf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Colorectal 
— 
— 
— 
X 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Cervical 
— 
— 
— 
X 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Vaginal 
— 
— 
— 
X 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Mucosal secretion collectiong 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Semen 
Xg 
— 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Cervical secretions 
Xg 
— 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Rectal secretions 
Xg 
— 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 181 of 188 
 
Grayed out visits are not applicable to this group  
a Screening may occur over the course of several contacts/visits up to and including day 0 prior to infusion. 
b Includes transmission risk reduction counseling for HIV-infected participants. 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d Not applicable to HIV-infected participants. 
e Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
f Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. Mucosal biopsy collections must 
be at least 28 days from the previous biopsy collection. 
g Mucosal secretion specimens will be collected as part of screening. They may be collected up to the infusion at visit 3. 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 182 of 188 
Procedures at HVTN CRS for Group 4 continued 
Visit: 
01 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-14 
D0 
D1-15 
D29-43 
D56 
D57-71 
D84 
D85-99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-14 
W15-16 
W16 
W19-20 
W24 
W25-26 
W29-30 
W37-38 
W51-52 
W64-65 
W76-77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf#1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Local lab assessmentsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening HIV test 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Syphilis, HBV, HCV 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
HSV 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Pap smearb 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Blood hormone levelsc 
— 
— 
— 
X 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Urine collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
Pregnancy (urine or serum 
HCG)d 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Safety labsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
— 
— 
— 
— 
— 
 
CBC, differential 
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
Chemistry panel  
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
Rectal swab collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
— 
— 
— 
— 
— 
 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Cervical/vaginal swab collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
— 
— 
— 
— 
— 
 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Trichomonas vaginalisf 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Bacterial vaginosisf 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Yeastg 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Study product administration 
proceduresh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV infusioni 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Reactogenicity assessmentsj 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 183 of 188 
 
Grayed out visits are not applicable to this group  
a For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests will be collected (see Appendix J). 
b Only for volunteers born female, per Sections 7.1 and 9.6. If collection of a pap smear is required, this may be done at any time provided the results are available prior to the 
collection of cervical samples. 
c Only collected in persons born female. 
d For a participant who was born female, pregnancy test must be performed on the day of infusion prior to infusion and on the day of every biopsy prior to biopsy collections. 
Pregnancy test to determine initial eligibility may be performed at screening, but must also be done on day 0 prior to first infusion. Persons who are NOT of reproductive potential 
due to having undergone bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. Serum pregnancy tests may be used to confirm the 
results of, or substitute for, a urine pregnancy test. 
e Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and 
when clinically indicated. 
f Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
g Cervical/vaginal swabs will be collected from females for yeast only if clinically indicated. 
h Not applicable to HIV-infected participants. 
i Blood draws required at the infusion visit must be performed prior to administration of study product; however, it is not necessary to have results prior to administration, except 
for results of a serum pregnancy test, if indicated. Lab tests may be drawn within the 3 days prior to infusion. 
j Reactogenicity assessments performed daily for at least 3 days postinfusion (see Section 9.10). 
 
 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 184 of 188 
Appendix O 
Procedures at HVTN CRS for Group 5 
Visit: 
01a 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-
14 
D0 
D1-
15 
D29-
43 
D56 
D57-
71 
D84 
D85-
99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-
14 
W15-
16 
W16 
W19-20 
W24 
W25-26 
W29-30 
W37-38 
W51-52 
W64-65 
W76-77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf#1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
Abbreviated physical exam 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
Risk reduction counselingb 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Pregnancy prevention assessmentc 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Behavioral risk assessmentd 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
X 
— 
— 
— 
Confirm eligibility, obtain demographics, 
randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Acceptability questionnaire 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
— 
Concomitant medications 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Intercurrent illness/adverse experience 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
HIV infection assessmente 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
X 
X 
— 
— 
— 
Confirm HIV test results provided to 
participant 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
X 
Mucosal biopsy collectionf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Colorectal 
— 
— 
— 
X 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Cervical 
— 
— 
— 
X 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Vaginal 
— 
— 
— 
X 
X 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Mucosal secretion collectiong 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
— 
 
 
 
 
 
Semen 
Xg 
— 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Cervical secretions 
Xg 
— 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Rectal secretions 
Xg 
— 
— 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 185 of 188 
 
Grayed out visits are not applicable to this group  
a Screening may occur over the course of several contacts/visits up to and including day 0 prior to infusion. 
b Includes transmission risk reduction counseling for HIV-infected participants. 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d Not applicable to HIV-infected participants. 
e Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
f Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria specified in the SSP. Mucosal biopsy collections must 
be at least 28 days from the previous biopsy collection 
g Mucosal secretion specimens will be collected as part of screening. They may be collected up to the infusion at visit 3. 
 

HVTN 116, Version 2.0 / August 3, 2018 
HVTN116_v2-0_FINAL.docx / Page 186 of 188 
Procedures at HVTN CRS for Group 5 continued 
Visit: 
01 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D-14 
D0 
D1-15 
D29-43 
D56 
D57-71 
D84 
D85-99 
D99-
113 
D112 
D127-
141 
D168 
D169-
183 
D197-
211 
D253-
267 
D351-
365 
D442-
456 
D526-
540 
 
Week: 
 
W-2 
W0 
W1-2 
W5-6 
W8 
W9-10 
W12 
W13-14 
W15-16 
W16 
W19-20 
W24 
W25-26 
W29-30 
W37-38 
W51-52 
W64-65 
W76-77 
 
Month: 
 
 
M0 
 
 
M2 
 
M3 
 
 
M4 
 
M6 
 
 
 
 
 
 
 
Procedure 
Scr. 
 
Inf#1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Local lab assessmentsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening HIV test 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Syphilis, HBV, HCV 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
HSV 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Pap smearb 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Blood hormone levelsc 
 
 
 
X 
X 
 
 
 
X 
 
 
X 
 
X 
 
X 
X 
 
 
 
Urine collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
Pregnancy (urine or serum 
HCG)d 
X 
— 
X 
X 
X 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
X 
— 
— 
— 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Safety labsa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC, differential 
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
Chemistry panel  
X 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
Rectal swab collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Cervical/vaginal swab collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrheae 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Trichomonas vaginalisf 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Bacterial vaginosisf 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
Yeastg 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Study product administration 
proceduresh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV infusioni 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Reactogenicity assessmentsj 
— 
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X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
 
 

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Grayed out visits are not applicable to this group  
a For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests will be collected (see Appendix K). 
b Only for volunteers born female, per Sections 7.1 and 9.6. If collection of a pap smear is required, this may be done at any time provided the results are available prior to the 
collection of cervical samples. 
c Only collected in persons born female. 
d For a participant who was born female, pregnancy test must be performed on the day of infusion prior to infusion and on the day of every biopsy prior to biopsy collections. 
Pregnancy test to determine initial eligibility may be performed at screening, but must also be done on day 0 prior to first infusion. Persons who are NOT of reproductive potential 
due to having undergone bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. Serum pregnancy tests may be used to confirm the 
results of, or substitute for, a urine pregnancy test. 
e Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal swabs in females; testing will occur at indicated visits and 
when clinically indicated. 
f Cervical/vaginal swabs will be collected from females for bacterial vaginosis and Trichomonas vaginalis at the indicated visits and when clinically indicated. 
g Cervical/vaginal swabs will be collected from females for yeast only if clinically indicated. 
h Not applicable to HIV-infected participants. 
i Blood draws required at the infusion visit must be performed prior to administration of study product; however, it is not necessary to have results prior to administration, except 
for results of a serum pregnancy test, if indicated. Lab tests may be drawn within the 3 days prior to infusion. 
j Reactogenicity assessments performed daily for at least 3 days postinfusion (see Section 9.10). 
 
 

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Appendix P 
Protocol Signature Page 
A phase 1 clinical trial to evaluate the safety, pharmacokinetics, and anti-viral 
activity of VRC-HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB 
(VRC01LS) in the serum and mucosa of healthy, HIV-uninfected adult 
participants 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (US) Health and Human Service regulations (45 
CFR 46); applicable U.S. Food and Drug Administration regulations; standards of 
the International Conference on Harmonization Guideline for Good Clinical 
Practice (E6); Institutional Review Board/Ethics Committee determinations; all 
applicable in-country, state, and local laws and regulations; and other applicable 
requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
DAIDS Protocol Number: HVTN 116 
DAIDS Protocol Version: HVTN 116, Version 2.0 
Protocol Date: August 3, 2018