A Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
 
PROTOCOL 
HVTN 130/HPTN 089 
A phase 1 clinical trial to evaluate the safety, tolerability, 
pharmacokinetics, and antiviral activity of combinations 
of monoclonal antibodies PGT121, PGDM1400, 10-1074, 
and VRC07-523LS administered via intravenous infusion 
in healthy, HIV-uninfected adult participants 
DAIDS DOCUMENT ID 38531 
IND ### 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 
Beth Israel Deaconess Medical Center 
Boston, Massachusetts, USA 
 
National Institute of Allergy and Infectious Diseases (NIAID), NIH, DHHS 
Bethesda, Maryland, USA 
 
Dale and Betty Bumpers Vaccine Research Center (VRC), NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
April 4, 2019 
HVTN 130/HPTN 089 
Version 1.0 

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Contents 
 
1 Overview ........................................................................................................................5 
1.1 
Protocol Team ................................................................................................8 
2 Ethical considerations ..................................................................................................10 
3 IRB/EC review considerations .....................................................................................12 
3.1 
Minimized risks to participants ....................................................................12 
3.2 
Reasonable risk/benefit balance ...................................................................12 
3.3 
Equitable participant selection .....................................................................13 
3.4 
Appropriate informed consent ......................................................................13 
3.5 
Adequate safety monitoring .........................................................................13 
3.6 
Protect privacy/confidentiality .....................................................................13 
4 Background ..................................................................................................................15 
4.1 
Rationale for trial concept ............................................................................16 
4.2 
Study products ..............................................................................................20 
4.3 
Trial design rationale ....................................................................................23 
4.4 
Plans for future product development and testing ........................................26 
4.5 
Preclinical studies .........................................................................................26 
4.6 
Clinical studies .............................................................................................30 
4.7 
Potential risks of study products and administration ...................................38 
5 Objectives and endpoints .............................................................................................42 
5.1 
Primary objectives and endpoints ................................................................42 
5.2 
Secondary objectives and endpoints ............................................................42 
5.3 
Exploratory objectives ..................................................................................43 
6 Statistical considerations ..............................................................................................45 
6.1 
Accrual and sample size calculations ...........................................................45 
6.2 
Randomization .............................................................................................49 
6.3 
Blinding ........................................................................................................50 
6.4 
Statistical analyses ........................................................................................50 
7 Selection and withdrawal of participants .....................................................................56 
7.1 
Inclusion criteria ...........................................................................................56 
7.2 
Exclusion criteria ..........................................................................................58 
7.3 
Participant departure from study product administration schedule or 
withdrawal (Group 4 only) ...........................................................................61 
8 Study product preparation and administration .............................................................65 
8.1 
Study product regimen .................................................................................65 
8.2 
Study product formulation ...........................................................................65 
8.3 
Preparation of study products .......................................................................66 
8.4 
Administration ..............................................................................................70 
8.5 
Acquisition of study products ......................................................................71 
8.6 
Pharmacy records .........................................................................................72 
8.7 
Final disposition of study products ..............................................................72 
9 Clinical procedures ......................................................................................................73 
9.1 
Informed consent ..........................................................................................73 

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9.2 
Pre-enrollment procedures ...........................................................................75 
9.3 
Enrollment and study product administration visits .....................................76 
9.4 
Follow-up visits ............................................................................................79 
9.5 
HIV counseling and testing ..........................................................................80 
9.6 
Contraception status .....................................................................................81 
9.7 
Urine testing .................................................................................................81 
9.8 
Assessments of Solicited AEs ......................................................................82 
9.9 
Visit windows and missed visits ..................................................................83 
9.10 Early termination visit ..................................................................................84 
9.11 Pregnancy .....................................................................................................84 
9.12 HIV infection during the study .....................................................................85 
10 Laboratory ....................................................................................................................86 
10.1 CRS laboratory procedures ..........................................................................86 
10.2 Total blood volume ......................................................................................86 
10.3 PGT121, PGDM1400, 10-1074, and VRC07-523LS concentrations ..........86 
10.4 Neutralizing antibody assay .........................................................................86 
10.5 ADA detection assay ....................................................................................87 
10.6 ADA functional assay ..................................................................................87 
10.7 Monoclonal Ab reaction assays ....................................................................87 
10.8 Exploratory studies .......................................................................................87 
10.9 Specimen storage and other use of specimens .............................................87 
10.10 Biohazard containment .................................................................................88 
11 Safety monitoring and safety review ...........................................................................89 
11.1 Safety monitoring and oversight ..................................................................89 
11.2 Safety reporting ............................................................................................90 
11.3 Safety reviews ..............................................................................................93 
11.4 Safety pause and prompt PSRT AE review..................................................94 
11.5 Review of cumulative safety data ................................................................95 
11.6 Study termination .........................................................................................96 
12 Protocol conduct ..........................................................................................................97 
12.1 Social impacts ..............................................................................................98 
12.2 Emergency communication with study participants ....................................98 
13 Version history .............................................................................................................99 
14 Document references (other than literature citations) ................................................100 
15 Acronyms and abbreviations......................................................................................102 
16 Literature cited ...........................................................................................................105 
Appendix A Sample informed consent form for Groups 1-3 .........................................112 
Appendix B Sample informed consent form for Group 4 ..............................................131 
Appendix C Approved birth control methods for persons assigned female sex at birth 
(for sample informed consent form) ...........................................................149 
Appendix D Sample consent form for use of samples and information in other studies 151 
Appendix E Schematic of IV infusions ..........................................................................155 

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Appendix F Tables of procedures (for sample informed consent forms) ......................156 
Appendix G Laboratory procedures for Groups 1 – 3 ....................................................157 
Appendix H Laboratory procedures for Group 4 ............................................................159 
Appendix I Procedures at CRS for Groups 1 – 3 ..........................................................161 
Appendix J Procedures at CRS for Group 4 ..................................................................162 
Appendix K HVTN low risk guidelines for the US ........................................................163 
Appendix L Protocol Signature Page .............................................................................165 

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1 
Overview 
Title  
A phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and 
antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 
10-1074, and VRC07-523LS administered via intravenous infusion in healthy, 
HIV-uninfected adult participants 
Primary objectives 
Primary objective 1 
To evaluate the safety and tolerability of PGT121 or PGDM1400 or 10-1074 
when administered in sequence via intravenous infusion (IV) with VRC07-523LS 
(2-mAb combinations), and of PGDM1400, PGT121, and VRC07-523LS 
administered in sequence via IV (3-mAb combination) 
Primary objective 2 
To evaluate the serum concentrations and pharmacokinetics (PK) of PGT121, 
PGDM1400, 10-1074, and VRC07-523LS after a single 2-mAb administration 
and after each PGDM1400, PGT121, VRC07-523LS 3-mAb administration  
Primary objective 3 
To evaluate the individual mAb-specific serum neutralizing activity of PGT121, 
PGDM1400, 10-1074, and VRC07-523LS after a single 2-mAb administration 
and after each PGDM1400, PGT121, VRC07-523LS 3-mAb administration  
Study products  
• PGT121: a human monoclonal antibody (mAb) that targets the HIV-1 V3 
glycan, centered on N332. It is provided by the Beth Israel Deaconess Medical 
Center and was manufactured under cGMP standards at Catalent Pharma 
Solutions (Madison, Wisconsin). Product is provided at 50 mg/mL as 10 mL 
glass vials with a 6 mL fill volume. 
• PGDM1400: a human mAb that targets the HIV-1 V2 glycan, centered on 
N160. It is provided by the Beth Israel Deaconess Medical Center and was 
manufactured under cGMP standards at Catalent Pharma Solutions (Madison, 
Wisconsin). Product is provided at 50 mg/mL as 10 mL glass vials with a 6 
mL fill volume. 
• 10-1074: a human mAb that targets the HIV-1 V3 glycan, centered on N332. 
It is provided by NIAID/NIH and was manufactured under cGMP standards at 

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MassBio (Boston, Massachusetts). Product is provided at 20 mg/mL as 50 mL 
glass vials with a 30 mL fill volume. 
• VRC-HIVMAB075-00-AB (VRC07-523LS): a human mAb that targets the 
HIV-1 CD4 binding site. It is provided by the VRC/NIAID/NIH and was 
manufactured under current Good Manufacturing Practice (cGMP) standards 
at the VRC Pilot Plant operated under contract by the Vaccine Clinical 
Materials Program, Leidos Biomedical Research, Inc. (Frederick, Maryland). 
Product is provided at 100 ± 10 mg/mL as 10 mL glass vials with a 6.25 ± 0.1 
mL fill volume and 3 mL glass vials with a 2.25 mL ± 0.1 mL fill volume. 
Table 1-1 Schema 
Study arm 
N 
Dose 
Route 
M0 
M4 
Group 1 
6 
20+20 mg/kg 
IV 
PGT121  
VRC07-523LS  
— 
 
 
 
 
 
 
Group 2 
6 
20+20 mg/kg 
IV 
PGDM1400  
VRC07-523LS  
— 
 
 
 
 
 
 
Group 3 
6 
20+20 mg/kg 
IV 
10-1074 
VRC07-523LS  
— 
 
 
 
 
 
 
Group 4* 
9 
20+20+20 mg/kg 
IV 
PGDM1400 
PGT121 
VRC07-523LS 
PGDM1400 
PGT121  
VRC07-523LS 
 
 
 
 
 
 
Total 
27 
 
 
 
 
IV = intravenous infusion. The mAbs are infused sequentially in the order shown. 
* Opening enrollment in Group 4 follows review of safety data for all participants in Groups 
1-3. Details described in Section 11.3.2. 
Participants 
27 healthy, HIV-1–uninfected volunteers aged 18 to 50 years 
Multicenter design 
Randomized by group in Groups 1-3; open label product administration in all 
groups 
Duration per participant 
12 months per participant in Groups 1-3; 16 months per participant in Group 4  
Estimated total study duration 
19 months (includes enrollment, planned safety holds, and follow-up) 

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Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
Study product providers 
• PGT121: Beth Israel Deaconess Medical Center (Boston, MA, USA) 
• PGDM1400: Beth Israel Deaconess Medical Center (Boston, MA, USA) 
• 10-1074: National Institute of Allergy and Infectious Diseases (NIAID), NIH, 
DHHS (Bethesda, MD, USA) 
• VRC07-523LS: Dale and Betty Bumpers Vaccine Research Center (VRC), 
NIAID, NIH, DHHS (Bethesda, MD, USA) 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Research Center (Fred Hutch) (Seattle, Washington, USA) 
HPTN Leadership Operations Center (LOC), FHI360 (Durham, North Carolina, 
USA) 
Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutch 
(Seattle, Washington, USA) 
HIV diagnostic laboratory 
University of Washington Virology Specialty Laboratory (UW-VSL) (Seattle, 
Washington, USA) 
Endpoint assay laboratories 
• Fred Hutchinson Cancer Research Center (Seattle, Washington, USA) 
• Duke University Medical Center (Durham, North Carolina, USA) 
• Dartmouth College (Hanover, New Hampshire, USA) 
• Vaccine Research Center – Immunology Testing Laboratory (Gaithersburg, 
Maryland, USA) 

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Study sites 
HVTN and HPTN Clinical Research Sites (CRSs) in the United States to be 
specified in the Site Announcement Memo 
Safety monitoring 
HVTN 130/HPTN 089 Protocol Safety Review Team (PSRT); HVTN Safety 
Monitoring Board (SMB) 
1.1 
Protocol Team 
Protocol leadership 
HVTN Chair Magdalena Sobieszczyk 
Columbia University 
Medical Center 
212-305-7185 
mes52@cumc.columbia.edu 
HPTN Chair Sharon Mannheimer 
Mailman School of Public 
Health, Columbia University 
212-939-2948 
sbm20@cumc.columbia.edu 
HVTN Protocol 
team leader 
Carmen Paez 
HVTN Core, Fred Hutch 
206-667-2881 
cpaez@fredhutch.org 
HPTN Protocol 
team lead 
Theresa Gamble 
HPTN LOC, FHI 360 
919-544-7040 
tgamble@fhi360.org 
HVTN 
Statistician 
Yunda Huang 
SCHARP, Fred Hutch 
206-667-5780 
yunda@scharp.org 
HPTN 
Statistician 
Brett Hanscom 
SCHARP, Fred Hutch 
206-667-4534 
bhanscom@fredhutch.org 
HVTN 
Laboratory lead 
David Montefiori 
HVTN Laboratory Program 
919-684-5278 
monte@duke.edu 
HPTN 
Laboratory lead 
Estelle Piwowar-Manning 
HPTN Laboratory Center 
410-614-6736 
epiwowa@jhmi.edu 
DAIDS Medical 
officer 
Jane Baumblatt 
DAIDS, NIAID 
301-761-7754 
jane.baumblatt@nih.gov 
DAIDS Medical 
officer 
David Burns 
DAIDS, NIAID 
301-435-8896 
david.burns@nih.gov 
Other contributors to the original protocol 
HVTN Core 
medical monitor 
Carmen Paez 
HVTN Core, Fred Hutch 
Consultative 
investigator 
Ken Mayer 
Fenway Health 
Study product 
developer 
representatives 
Lucio Gama 
VRC 
HVTN Statistical 
research associate 
Kyle Marshall 
SCHARP, Fred Hutch 
 Dan Barouch 
BIDMC 
HVTN Clinical 
safety specialist 
Jill Zeller 
HVTN Core, Fred Hutch 
 Boris Juelg 
BIDMC 
HVTN Clinical 
trials manager 
India Tindale 
HVTN Core, Fred Hutch 

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 Kathryn Stephenson 
BIDMC 
HPTN Prevention 
research specialist 
Michelle Robinson 
HPTN LOC, FHI 360 
 Michel Nussenzweig 
The Rockefeller Institute 
HPTN Senior 
Clinical research 
manager 
Bonnie Dye 
HPTN LOC, FHI 360 
 Marina Caskey 
The Rockefeller Institute 
HPTN 
Pharmacologist 
Julie Dumond 
University of North 
Carolina, Chapel Hill 
HVTN Laboratory 
Center 
representative 
Jennifer Hanke 
HVTN Laboratory 
Program, Fred Hutch 
HPTN Laboratory 
Program 
representative 
Paul Richardson 
HPTN Laboratory Center, 
Johns Hopkins University 
HVTN Laboratory 
Center 
representative 
John Hural  
HVTN Laboratory 
Program, Fred Hutch 
DAIDS protocol 
pharmacists 
Irene Rwakazina 
DAIDS, NIAID 
301-761-7269 
HVTN Regulatory 
affairs associate 
Laurie Rinn 
HVTN Core, Fred Hutch 
 Kelly Parsons 
DAIDS, NIAID 
240-669-5721 
Clinic coordinators Brett Gray 
Columbia University 
Medical Center 
SDMC Clinical 
data management 
manager 
Kristine Donaty 
SCHARP, Fred Hutch 
 Jun Avelino Loquere 
Harlem Prevention 
Center 
SDMC Lead 
clinical data 
manager 
Huguette Redinger 
SCHARP, Fred Hutch 
CRS pharmacist Kinara Yang 
Columbia University 
Medical Center 
SDMC Associate 
director of lab 
science 
April Randhawa 
SCHARP, Fred Hutch 
Community 
Advisory Board 
members 
Ebony Gordon 
Vanderbilt CAB 
HVTN Protocol 
development 
manager 
Carter Bentley 
HVTN Core, Fred Hutch 
 Kyle Warren 
Boston CAB 
HVTN Community 
engagement unit 
representative 
Gail Broder  
HVTN Core, Fred Hutch 
HPTN Community 
program associates 
Jontraye Davis 
HPTN LOC, FHI 360 
HVTN Community 
educator/recruiter 
Yi-Hao Jackie Wu 
Columbia, New York CRS 
 Abraham Johnson 
HPTN LOC, FHI 360 
HPTN Community 
educator/recruiter 
Christie Lyn Costanza 
Rutgers, NJMS CRS 
  
HVTN Technical 
editor 
Richa Chaturvedi 
HVTN Core, Fred Hutch 

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2 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of these clinical trials. The HIV Vaccine Trials Network 
(HVTN) and HIV Prevention Trials Network (HPTN) [hereafter referred to as the 
“Networks”] have addressed ethical concerns in the following ways: 
• Network trials are designed and conducted to enhance the knowledge base 
necessary to find new methods for the prevention of HIV infection, using 
methods that are scientifically rigorous and valid, and in accordance with 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) and/or other Good Clinical Practice 
(GCP) guidelines. 
• Network 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 
vaccine and prevention clinical trials. 
• Network 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 Network research sites to ensure community 
input. 
• Network 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 Networks require that all international Network 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 Networks. Participants who become HIV-infected during the trial are 
referred to medical practitioners to manage their HIV infection and to identify 
potential clinical trials they may want to join. 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 Networks provide 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 

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their wellbeing monitored, and to the fullest extent possible, their privacy 
protected. Participants may withdraw from the study at any time. 
• Prior to implementation, Network trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration.  
• Network trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
• The Networks design their research to minimize risk and maximize benefit to 
both study participants and their local communities. For example, Network 
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. Network protocols also 
include careful medical review of each research participant’s health conditions 
and reactions to study products while in the study.  
• Network 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 Network trials are able to conduct 
other critical research in their local research settings. 
• The Networks recognize the importance of institutional review and value 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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3 
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 Network 
Investigator welcomes IRB/EC/RE questions or concerns regarding these research 
requirements. 
The sections below address each of the review concerns by IRBs/ECs and any 
applicable REs regarding how the research will be conducted. 
3.1 
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 post study product 
administration and collecting information regarding side effects for several days 
post study product administration; (d) having staff properly trained in 
administering study procedures that may cause physical harm or psychological 
distress, such as blood draws, study product administrations, HIV testing and 
counseling and HIV risk reduction counseling; (e) providing HIV risk reduction 
counseling and checking on contraception use (for persons assigned female at 
birth); and (f) providing safety monitoring. 
3.2 
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.  

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3.3 
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. 
3.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 and 5 and 21 CFR 56.111 (a) 4 and 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 Networks as part of its 
entering the Network. The Networks require a signed consent document for 
documentation, in addition to chart notes or a consent checklist. 
3.5 
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 (see Section 11). Safety is 
monitored daily by HVTN clinical staff and routinely by the HVTN 130/HPTN 
089 PSRT. In addition, the HVTN SMB periodically reviews study data. 
3.6 
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 

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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, research participants in Network protocols are 
protected by a Certificate of Confidentiality from the US NIH, which can prevent 
disclosure of study participation even when that information is requested by 
subpoena. 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 
Networks. In some cases, a comparable confidentiality agreement process may be 
acceptable. 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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4 
Background 
Broadly neutralizing HIV-1 antibodies (bnAbs) occur in many HIV-1 infected 
individuals, usually after several years of infection (4). However, it remains a 
challenge to elicit them by vaccination because broad and potent HIV-1 
neutralization often requires unusual antibody characteristics, such as long 
hypervariable loops, autoreactivity with host antigens, interaction with glycans, 
and high levels of somatic mutation in the variable domains, which are important 
to facilitate binding to the highly glycosylated HIV-1 envelope protein (5-7). 
Thus, there is an interest in passive immunization with monoclonal antibodies 
(mAbs) modeled on these naturally-occurring bnAbs to prevent, treat, and 
potentially cure HIV-1 infection, as well as an interest in studying bnAbs to 
inform and expedite the development of HIV vaccines that may elicit such 
antibodies. 
Over the past decade, dozens of bnAbs have been identified and their HIV-1 
target sites and mechanisms of neutralization have been elucidated (5, 8-14). 
These efforts have informed the design of recombinant protein immunogens that 
can potentially elicit broadly neutralizing antibodies (12, 15-19) and they have set 
the stage for evaluation of these antibodies’ potential to contribute to HIV-1 
prevention (ie, passive immunization or antibody-mediated prevention), 
treatment, and possibly cure (20-24). Passive infusion studies in non-human 
primates (NHP) demonstrated that bnAbs were effective in protection against 
mucosal simian-human immunodeficiency virus (SHIV) challenge (25-32). 
Results from early phase human clinical trials using different classes of bnAbs, 
such as those targeting the CD4 binding site (VRC01 and 3BNC117) and the V3 
loop (10-1074 and PGT121), have been encouraging, demonstrating the potential 
for and challenges of developing anti-HIV-1 bnAbs as preventive and therapeutic 
agents (33-38). 
Passive immunization for prevention is a long-standing strategy that has been 
employed for more than 100 years against diverse disease targets and is still used 
for hepatitis A and B prophylaxis, for prevention of transplant-associated 
cytomegalovirus (CMV) infection, and as postexposure prophylaxis for rabies, 
measles, varicella zoster, and other infectious diseases (39-41). In 2016, VRC01 
advanced to the first prevention efficacy trials in HIV-uninfected individuals. In 
addition to assessing safety and PK data, these efficacy trials (HVTN 704/HPTN 
085 [NCT02716675] and HVTN 703/HPTN 081 [NCT02568215]) include 
assessment of non-neutralizing antiviral activity (ie, Fc effector functions), sieve 
analysis, and correlates analyses (42). These are important proof-of-concept trials 
to determine whether antibodies that neutralize HIV-1 in vitro and protect 
nonhuman primates from experimental SHIV challenge will protect against the 
acquisition of HIV infection in humans. They also aim to determine the protective 
titer as a critical parameter in designing future clinical trials.   
In HIV-1-infected patients, reductions in viral load have been observed after one 
infusion of a single bnAb, thus demonstrating the biological activity of HIV 

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bnAbs (35, 36, 43). A modest delay of viral rebound was also observed when 
bnAbs were infused after antiretroviral drugs were discontinued in previously 
suppressed HIV-infected individuals (44, 45). Improved neutralizing antibody 
activity in treated patients was also observed. However, viral resistant strains 
emerged rather quickly in most patients (34, 36, 43, 44, 46). Notably, recent tests 
of bnAb combinations have produced more durable viral suppression following 
analytical treatment interruption (38). 
4.1 
Rationale for trial concept 
The development of mAbs for the potential prevention and treatment of HIV is 
evolving rapidly. Multiple broadly neutralizing mAbs have been developed, each 
of which targets 1 of 5 known sites on the HIV-1 Env protein (see Figure 4-1). 
These mAbs display a broad range of neutralization potency and breadth and 
some of the more promising have been engineered for improved neutralization, 
manufacturability, stability, and serum half-life. Additional improvements 
continue to be made, including the construction of bi- and tri-specific mAbs. 
While relatively few HIV neutralizing mAbs are currently available for clinical 
evaluation, those that are available include some of the most broad and potent 
mAbs identified to date. Thus, the available products, though limited, provide 
opportunities to address important scientific questions through clinical evaluation.  
Since all bnAbs are limited in their breadth and potency, it is widely believed that 
some combination of complementary bnAbs will be required for effective HIV 
prophylaxis,  a proposition supported by NHP challenge studies showing that a 
combination of 2 bnAbs fully protected macaques against a mixed SHIV 
challenge when neither mAb administered alone was able to do so (47) (see 
Section 4.5.2.2).  
The bnAbs in this trial were selected for their neutralization potency, breadth of 
HIV-1 strain coverage, and their complementarity. As shown in Figure 4-1, 
PGT121, PGDM1400, 10-1074, and VRC07-523LS target different sites on the 
HIV trimer. They also differ in the potency with which they neutralize different 
HIV-1 virus strains and in the range and number of different strains that they 
neutralize, with desirable complementarity (Figure 4-2). When tested in vitro 
against multiclade panels of HIV-1 pseudoviruses, PGT121 and PGDM1400 
display limited coverage of viral strains (ie, breadth), but they also display 
outstanding potency, having among the lowest median IC50 and IC80 titers among 
all bnAbs identified to date (48) (see Sections 4.2.1 and 4.2.2). VRC07-523LS, a 
highly engineered derivative of the bnAb VRC01, displays somewhat lower 
potency than PGT121 or PGDM1400 but has outstanding breadth and an 
improved PK profile (see Section 4.2.4). The mAb 10-1074 targets the same V3 
supersite as PGT121 and exhibits a similar neutralization profile, thereby 
affording alternative choices for this site based on potential differences that might 
arise in mAb manufacturability, safety, tolerability and PK. 

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Figure 4-1: Antibody targets on the HIV-1 trimer (image by Stewart-Jones, Doria-Rose, 
Stuckey; adapted from (49, 50)) 
 
 
Figure 4-2 In vitro neutralization heat map of VRC07-523LS, PGT121, and PGDM1400 
measured on multiclade pseudovirus panel (n = 208)  
In vitro models suggest that administering these mAbs in combination will 
produce more potent and broader neutralization than administering any one mAb 
by itself (compare solid and dotted lines in Figure 4-3). Comparison of the solid 
lines in Figure 4-3 suggests that administering all 3 mAbs in combination may 
produce neutralization superior to any of 2 of the mAbs in combination. 
10E8 

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Figure 4-3 Predicted breadth and potency curves for PGT121, PGDM1400, VRC07-523LS and 
combinations of these mAbs against a panel of multiclade HIV isolates 
Indeed, modeling by Korber, Wagh, and colleagues based on in vitro data 
suggests that this may be among the best performing combination of mAbs 
currently available (51-53). Figure 4-4 depicts a comparison of the in vitro 
neutralization performance of VRC07-523LS + PGDM1400 + PGT121 against 
other combinations of 3 mAbs for protection against HIV-1 infection. Shown are 
predicted IC80 magnitude-breadth plots for VRC01-PGDM1400-10E8v4 
Trispecific, a wide variety of 3-bnAb combinations, and VRC07-523LS + 
10E8v4-V5R-100cF, which was identified as the best 2-bnAb combination. The 
figure on the far left shows data for the full global panel (n = 208), and the next 
figures show predicted performance against specific subtypes from this panel. The 
triple combination of VRC07-523LS + PGT121 + PGDM1400 is among the top 
performing combinations (among 56 triple bnAb combinations evaluated) when 
one considers all subtypes combined, subtype B alone, and subtype C alone, but is 
less effective against subtype AE, mainly because of poor coverage of this latter 
subtype by PGT121. The coverage of IC80 neutralization at 10 mcg/ml (3.3 
mcg/ml each bnAb) was 98.6% for the full virus panel, with 95.6-98.3% across 
subtypes. Importantly, the dual and triple mAb combinations to be evaluated here 
are far superior to VRC01 in vitro (Figure 4-4). 

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Figure 4-4 Comparison of the in vitro performance of VRC07-523LS + PGDM1400 + PGT121 
against a Trispecific bnAb and combinations of 3 bnAbs under clinical development for 
passive protection against acquisition of HIV-1 infection 
Based on preliminary PK data, VRC07-523LS has a longer half-life than PGT121 
(Figure 4-5); likewise, PGDM1400, similarly lacking the “LS” modification, is 
also expected to have a shorter half-life than VRC07-523LS. However, it is 
important to note that PGT121 and PGDM1400 are more potent against the HIV 
strains they neutralize than is VRC07-523LS, potentially mitigating, at least in 
part, their shorter half-lives. 
 
Figure 4-5: Serum concentrations (mcg/mL) for VRC01LS at 5 mg/kg and VRC07-523LS at 
either 1 mg/kg or 5 mg/kg compared to PGT121 at 3 mg/kg following a single IV infusion in 
humans. 
Like PGT121, 10-1074 targets the potential N-linked glycosylation site at 
Asn332gp120 and the C-terminal base of the Env variable region 3 (V3) loop. 
Also like PGT121, 10-1074 exhibits potent neutralizing activity, including broad 
reactivity against transmitted founder viruses (see Section 4.2.3) (36).  

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Early product development assessment of the mAbs proposed for combination in 
this trial has revealed an attractive product profile, including safety and 
tolerability in early human trials (see Section 4.6). Thus, it is scientifically sound 
to evaluate VRC07-523LS, PGT121, 10-1074, and PGDM1400 together in a 
phase 1 human clinical trial to assess safety (including anti-drug antibodies 
[ADA]), PK, and functional activity, and to establish an experimental platform in 
preparation for further clinical testing of mAb combinations. In addition, testing 
mAbs (10-1074, PGT121) that target the same epitope will provide early 
information about the safety, tolerability, PK, and antiviral activity of each mAb 
in combination with VRC07-523LS. This information will expand the options for 
optimizing future combination products and is similar to the approach taken to 
development of combination therapies for HIV. Because of limited availability of 
10-1074, 10-1074 and VRC07-523LS will only be evaluated in combination, 
while a regimen comprising PGDM1400, PGT121, and VRC07-523LS, a 3-mAb 
combination, will be evaluated in Group 4. The combination of these 3 mAbs 
with distinct epitope specificities will provide valuable experience assessing the 
potential additive, synergistic, or antagonistic properties of 3 bnAbs administered 
sequentially at the same study visit.  
The overarching aims guiding this study are to characterize the safety, tolerability, 
and PK of mAbs when administered in combination; and to describe whether, in 
humans, there is an increase in neutralization potential with combination mAbs 
and whether neutralization varies by antibody and site of binding. Given NHP 
data, in vitro modeling data, and experience from the antiretroviral field (51, 52), 
it is likely that a combination of multiple antibodies targeting different key 
epitopes on the viral envelope may be necessary for efficacy and thus testing 
different mAb combinations is an important first step. Even though newer, LS 
formulations of mAbs such as PGDM1400, PGT121, and 10-1074 will be tested 
in future studies, testing whether neutralization breadth and potency can be 
augmented with multiple mAbs is an important first step. Furthermore, these data 
will start generating information about interchangeability of mAbs targeting the 
V3-N332 glycan with respect to neutralization, ADA, and PK.  
Taken together, data collected in this protocol will contribute significantly to 
future analyses and to the design of future studies seeking to optimize mAb 
combinations for HIV-1 prevention. 
4.2 
Study products 
4.2.1 
PGT121 
PGT121 is a broadly neutralizing mAb that was identified from African donor 17 
of the IAVI Protocol G cohort. It is a human mAb that targets the V3 glycan-
dependent epitope region of the HIV-1 virus. This epitope on the gp120 outer 
domain includes both protein and glycans and is centered on the conserved 
residue N332 (54-56). Using a 162-pseudovirus panel, representative of all major 

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HIV-1 circulating clades, PGT121 had a 10-fold higher median neutralizing 
potency than mAbs PG9, VRC01, or PGV04 and a 100-fold higher potency than 
2G12, b12, or 4E10 (48). While PGT121 neutralized a smaller percentage of the 
panel of pseudoviruses than VRC01 at an IC50 < 50 mcg/mL (63% for PGT121 
vs. 93% for VRC01), it exhibited high potency against the sensitive strains, with 
neutralization of 44% of the 162-virus panel at an IC50 < 0.1 mcg/mL. This 
percentage is almost twice the neutralization under the same conditions as PG9, 
VRC01, PGV04 and 20–40 times more neutralizing than 2G12, b12, and 4E10, all 
of which have been investigated previously in passive protection studies (48, 57, 
58). 
4.2.2 
PGDM1400 
PGDM1400 is a broadly neutralizing mAb that was recently identified from 
African donor 84 of the IAVI Protocol G cohort. PGDM1400 is a human mAb 
that interacts with glycans in the region of N160 on the V2 loop of gp120 Env 
(57). The PGDM1400 antibody is highly quaternary-structure dependent and was 
discovered by using a recombinant HIV envelope trimer, BG505 SOSIP.664 
gp140, as an affinity reagent (57). It is exceptionally broad and potent, with 83% 
global coverage at a median IC50 of 0.003 mcg/mL, and is, therefore, 10 to 100-
fold more potent than the previous best in class CD4bs antibodies VRC01, 
VRC07, and 3BNC117 (47, 48, 57, 58). 
PGDM1400 and PGT121 are complementary in their coverage of global viral 
isolates. In combination they neutralize 98-99% of global HIV-1 viruses tested in 
a 106-pseudovirus panel and have unparalleled potency with a median IC50 of 
0.007 mcg/mL (57). 
4.2.3 
10-1074 
10-1074 is a human mAb that was isolated at the Rockefeller University from an 
African donor who was infected with a clade A HIV-1 virus and who displayed 
high titer serum neutralization activity (59). Like PGT121-123, 10-1074 
recognizes an epitope on the gp120 V3 outer domain that includes both protein 
and glycans, centered on the conserved residue N332 (60, 61).  
When tested against large panels of HIV-1 pseudoviruses in TZM.bl 
neutralization assays in vitro, 10-1074 neutralizes 65% of 306 strains comprising 
13 subtypes and 88.5% of 26 clade B strains at an average IC80 of 0.18 mcg/mL 
and 0.13 mcg/mL, respectively (36) (Figure 4-6). When tested against primary 
HIV-1 isolates from 179 persons with HIV-1 infection (77 off and 102 on ART) 
living in the US and Germany, 77.7% of cultures were neutralized, with a mean 
IC80 of 0.67 mcg/mL (36). 

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Figure 4-6 Summary of 10-1074 neutralizing in vitro activity based on 306 HIV-1 pseudotyped 
viruses comprising 13 subtypes and recombinant forms. Mean IC80 values are color-coded 
(dark red: < 0.1 mcg/mL; light red: 0.1 – 0.49 mg/mL; orange 0.5 – 1 mcg/mL; n.d.: not 
determined) [(36) Suppl] 
4.2.4 
VRC07-523LS 
The VRC, at the NIAID-NIH developed VRC07-523LS, a human mAb that 
targets the HIV-1 CD4 binding site. A similar antibody, VRC01, also targeting 
the CD4 binding site, is currently in clinical trials for both HIV-1 prevention (IND 
113,611 and IND 125,494) and therapeutic (IND 126,001, IND 126,664, and IND 
113,017) indications. VRC01 was originally isolated from a subject infected with 
HIV-1 for more than 15 years whose immune system controlled the virus without 
ART (62, 63). Through advances in B-cell immunology, cloning, and structure-
guided optimization techniques, numerous HIV-1 neutralizing mAbs, including 
VRC07 (“07” denotes sequential numbering when discovered), VRC07-523 
(“523” denotes sequential numbering when the engineered variant was generated), 
and later VRC07-523LS (“LS” denotes 2 amino acid mutations), were isolated 
and subsequently engineered to have potency and breadth greater than those of 
earlier antibodies (27). 
The VRC07 (wild-type) heavy chain was identified by 454 deep sequencing based 
on its similarity to the VRC01 mAb and paired with the VRC01 (wild-type) light 
chain. The mutations that together define the 523 designation are a glycine to 
histidine mutation at residue 54 of the heavy chain, a deletion of the first two 
amino acids, glutamate and isoleucine, from the light chain, and a valine to serine 
mutation at the third amino acid residue of the light chain (27). 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. The LS mutation was introduced by site-directed 
mutagenesis to increase the binding affinity for the neonatal Fc-receptor (FcRn); 
this mutation increases the recirculation of functional immunoglobulin G (IgG) 
(31, 64), thus, increasing plasma half-life. 

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VRC07-523LS was found to be 5- to 8-fold more potent than VRC01, with an 
inhibitory concentration (IC50) < 50 mcg/mL against 96% of HIV-1 pseudoviruses 
representing the major circulating HIV-1 clades, and an IC50 < 1 mcg/mL against 
92% of HIV-1 viruses tested (27). In addition, it displayed minimal levels of 
autoreactivity. 
4.3 
Trial design rationale 
The safety, tolerability, pharmacokinetics, and antiviral activity of the mAbs 
included in this trial are being evaluated, individually and in some combinations, 
in ongoing clinical trials (see Section 4.6). Currently, data for VRC07-523LS 
from VRC 605 (NCT03015181) are being analyzed. The HVTN 127/HPTN 087 
study (NCT03387150), which enrolled participants from February to October 
2018, is gathering additional data on this mAb. T001 (NCT02960581) is assessing 
PGT121 alone, while T002 (NCT03205917) is gathering data on PGDM1400 
alone as well as in combination with PGT121. The 10-1074 mAb has been 
evaluated in several phase 1 studies, alone and when administered along with 
another mAb, 3BNC117 (23, 36-38). 
This clinical trial is designed to evaluate the safety and tolerability profile of three 
different mAbs, each combined with VRC07-523LS. In Groups 1-3, they will be 
administered in dual combinations via IV. In Group 4, safety and tolerability of 3 
mAbs (PGDM1400, PGT 121, and VRC07-523LS) administered via IV will be 
evaluated. Additionally, this trial will provide an opportunity to evaluate serum 
mAb concentrations and to assess (in humans) the neutralization profile of these 
combinations. 
Combinations of VRC07-523LS with PGT121 and/or PGDM1400 or 10-1074 
have not yet been evaluated in humans. This study is designed to gather safety 
information on the dual combination groups (PGT121+VRC07-523LS in Group 
1, PGDM1400+VRC07-523LS in Group 2, and 10-1074+VRC07-523LS in 
Group 3) before the triple combination Group 4 (PGDM1400+PGT121+VRC07-
523LS) begins enrolling. 
Enrollment in Groups 1-3 across all participating CRSs will be restricted to a 
maximum of 1 participant per day until all 6 participants have been enrolled in 
each group. Cumulative safety data will be reviewed on a daily basis by HVTN 
clinical safety staff (ie, Clinical Safety Specialist nurses and physicians) and 
reviewed at least weekly by the HVTN 130/HPTN 089 PSRT.  
At least 2 weeks after the final participant in Groups 1, 2, and 3 completes the 
Day 0 infusion, the HVTN 130/HPTN 089 PSRT’s safety review will determine if 
Group 4 may begin to enroll. The HVTN 130/HPTN 089 PSRT will request an 
ad-hoc review of the data by the HVTN SMB in the instance that serious safety 
events are identified before proceeding to Group 4 (see Section 11.3.3). 

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Following approval by the PSRT, Group 4 will begin to enroll. Enrollment will be 
restricted to a maximum of one participant per day for the first 6 participants. 
Cumulative safety data will be reviewed daily by HVTN clinical safety staff (ie, 
Clinical Safety Specialist nurses and physicians) and reviewed at least weekly by 
the HVTN 130/HPTN 089 PSRT. 
At least 2 weeks after the 6th participant in Group 4 completes the Day 0 infusion, 
the HVTN 130/HPTN 089 PSRT’s safety review will determine if study product 
may be administered to the remaining participants in Group 4 (see Section 
11.3.3). Cumulative safety data will be reviewed daily by HVTN clinical safety 
staff (ie, Clinical Safety Specialist nurses and physicians) and reviewed at least 
weekly by the HVTN 130/HPTN 089 PSRT. 
4.3.1 
Dose and schedule 
The proposed doses and intervals for Groups 1, 2, and 3 are based on preclinical 
and clinical studies of PGT121, PGDM1400, 10-1074, and VRC07-523LS. The 
choice of 20 mg/kg dose aligns with ongoing protocols using VRC07-523LS. 
Data from human studies of VRC01 (65, 66) and VRC01LS (67), and preclinical 
and clinical studies of VRC07-523LS, including VRC605 and HVTN 127/HPTN 
087 were used to determine the doses and intervals for VRC07-523LS in this trial. 
Similarly, administration doses and intervals for PGT121and PGDM1400 are 
based on data from the T001 and T002 clinical trials. The YCO-0899 
(NCT02824536) and MCA-0885 (NCT02511990) trials provided the data for the 
10-1074 doses selected for this study (see Section 4.6.3).  
The dosing schedule in Group 4 was selected based on the PK modeling of each 
individual mAb contained in the combinations, assuming no drug-drug PK 
interactions. Predicted serum concentrations of PGT121 and VRC07-523LS 
following multiple IV infusions at 20 mg/kg every 8 to 20 weeks were generated 
through Monte Carlo simulations of 1000 hypothetical trial participants based on 
population PK models of PK data for PGT121, IV PGDM1400, and VRC07-
523LS as of June 2018 (Figure 4-7).  

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Figure 4-7: Predicted PGDM1400, PGT121 and VRC07-523LS concentration with multiple 8- 
to 20-weekly IV infusions at 20mg/kg. Shown are median (solid lines), 5th and 95th percentiles 
(shaded areas) of predicted drug levels with values truncated at half of the lower limit of 
quantification – 0.12 mcg/mL (PGDM1400), 0.25 mcg/mL (PGT121) or 1.1/2 mcg/mL (VRC07-
523LS).  
In these simulations, the body weights of the hypothetical trial participants were 
randomly drawn with replacement from the sample of body weights collected in 
the HVTN 104 study of VRC01 in US sites, some of which will be used in this 
study (65, 66). In addition, linear PK was assumed for the mAbs so that PK 
parameters estimated based on single-dose settings carried forward to multiple-
dose settings. The PK parameters used in the simulations were estimated based on 
observed serum concentration data for PGDM1400 at 3 and 10 mg/kg following a 
single IV infusion, for PGT121 at 3, 10, and 30 mg/kg following a single IV 
infusion and at 3 mg/ kg following a single SC injection, and for VRC07-523LS 
at 5, 20, and 40 mg/kg following a single IV infusion, at 20 mg/ kg following 
three 12-weekly IV infusions, at 5mg/ kg following a single and at 5 mg/kg 
following three 12-weekly SC injections. The mean and variance of log-
transformed serum concentrations were computed after each IV infusion. 
Specifically, at 16 weeks after the second IV infusion at a dose level of 20 mg/kg, 
the serum concentrations (mean ± SD) were predicted to be 1.6 ± 0.5 for 
PGDM1400, 1.8 ± 0.5 for PGT121, and 3.4 ± 0.6 for VRC07-523LS. The chance 
of having a VRC07-523LS serum concentration > 1 mcg/mL at 48 weeks post the 
second IV infusion at 20 mg/kg is predicted to be about 24%. Given the IC50 and 

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IC80 data of the mAbs, these PK simulation results suggest that the proposed study 
design should be able to attain desirable serum concentration levels over time that 
confer sufficient neutralization against diverse panels of viruses (see Section 4.1). 
Thus, based on currently available data, in Group 4, a dosing interval of every 16 
weeks was selected to have high probability of achieving a trough above 1 
mcg/mL for all study mAbs. This threshold of 1 mcg/mL is the limit of detection 
of the currently used anti-idiotypic enzyme-linked immunosorbent assay (ELISA) 
for mAb serum concentrations. 
Substantial safety data have already been collected over several trials on products 
related to VRC07-523LS, including VRC01 and VRC01LS. These studies have 
demonstrated the safety and tolerability of the IV of the individual mAbs at doses 
similar to or greater than those proposed in this study. For example, in VRC 606 
(NCT02599896), the doses for VRC01LS in HIV-uninfected participants ranged 
between 1 and 40 mg/kg for IV administrations. Moreover, in multiple studies, 
including VRC 601, VRC 602, HVTN 104, RV397, RV398, A5340, A5342, and 
P1112, doses for VRC01 in HIV-uninfected and/or HIV-infected participants 
ranged between 1 and 40 mg/kg for IV administrations. 
Given the reassuring safety profile of VRC07-523LS, PGT121, PGDM1400, 10-
1074, and similar mAbs given via IV in previous studies and ongoing trials 
evaluating these mAbs either individually or in combination (see Section 4.6), 
placebo recipients are not included in this trial.  
4.4 
Plans for future product development and testing 
In light of the genetic diversity of HIV-1, it is prudent to consider using a 
combination approach. HVTN 130/HPTN 089 is the first in a series of studies that 
will evaluate whether combining mAbs that target different epitopes on HIV is 
additive or synergistic (or potentially antagonistic) with respect to PK and 
neutralization breadth and potency. It is expected that future studies will evaluate 
mAb combinations incorporating “LS” formulations of these antibodies; this 
study will generate reference data against which to compare the performance of 
these LS formulations. In addition, these data will help inform the design of future 
mAb studies.  
4.5 
Preclinical studies  
4.5.1 
Preclinical studies of PGT121  
PGT121 has been assessed in a non-Good Laboratory Practice (GLP) 
pharmacokinetic rat study, a GLP in vitro tissue cross-reactivity (TCR) study, and 
a GLP repeat dose toxicity study in rats. In the repeat dose toxicity study, animals 
were given 30 mg/kg or 300 mg/kg intravenously or 30 mg/kg subcutaneously at 
weekly intervals over a 28-day period. There were minor disturbances in the 
plasma proteins with higher total protein, albumin, and globulin resulting in a 

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lower albumin/globulin ratio. There was also transient local microscopic 
inflammation (fibrosis, mixed cell inflammation) at the injection site following 
subcutaneous administration, which increased in severity and/or incidence 
compared to the control animals. The findings resolved after a 4-week treatment-
free period. The no-observed-adverse-effect-level (NOAEL) for intravenous 
administration was 300 mg/kg and for subcutaneous injection was 30 mg/kg, 
which were the highest dose levels administered. 
PGT121 can neutralize a wide array of HIV-1 viruses in vitro and can treat and 
prevent SHIV in the NHP model. Complete protection from different strains of 
SHIV was shown with 20 mg/kg and protection in most animals at levels of 5 
mg/kg, 1 mg/kg, and 0.2 mg/kg (29). PGT121 administered at 10mg/kg to SHIV-
infected animals resulted in rapid virologic control to undetectable levels by day 7 
followed by viral rebound between day 42 and day 56 in 3 of the 4 animals after 
antibody levels declined to undetectable. One animal exhibited long-term control 
(26). 
See the Investigator’s Brochure (IB) for further details. 
4.5.2 
Preclinical studies of PGDM1400  
PGDM1400 has been assessed in a non-GLP pharmacokinetic rat study, a GLP in 
vitro TCR, and a GLP repeat dose toxicity study in rats.  
In the repeat dose toxicity study, administration of PGDM1400 alone or in 
combination with PGT121 by once weekly subcutaneous or intravenous injection 
for one month (total of 5 injections) at 30 mg/kg/dose, and alone by once weekly 
intravenous injection at 300 mg/kg/dose, resulted in slightly higher plasma 
proteins in males, and a higher incidence of hemorrhage at the subcutaneous 
injection sites that had received PGDM1400. Neither of these findings was 
considered adverse, and they were not observed after a one-month recovery 
(treatment-free) period. No clinical signs or local reactions were noted at the 
injection sites that were considered to be related to the administration of 
PGDM1400 alone or in combination with PGT121. Body weight, food 
consumption, hematology, coagulation and urine volume and composition were 
unaffected by treatment with PGDM1400 alone or in combination. The NOAEL 
for intravenous administration was 300 mg/kg and for subcutaneous injection was 
30 mg/kg, which were the highest dose levels administered.  
4.5.2.1 
Preclinical challenge study of PGDM1400 
PGDM1400 was evaluated against a novel challenge stock, SHIV-325c, 
developed specifically for NHP challenge studies of PGDM1400, CAP256, and 
related variants and PGDM1400 demonstrated protection at low doses. As shown 
in Figure 4-8 below, rhesus macaques received a single IV infusion of 
PGDM1400 (n = 5 at 2 mg/kg; n = 5 at 0.4 mg/kg; n = 4 at 0.08 mg/kg) 24 hours 
before high dose intrarectal challenge with SHIV-325c. All animals in the control 
group were infected between days 7 and 28. In the 2 mg/kg group, one of five 

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animals receiving PGDM1400 became infected on Day 28; in the 0.4 mg/kg 
group, no animals became infected; in the 0.08 mg/kg group, three of four animals 
receiving PGDM1400 were infected. The average serum antibody concentrations 
in animals administered PGDM1400 at doses of 2, 0.4, and 0.08 mg/kg were 6.9, 
2.5, and 0.22 mcg/mL, respectively, at the time of challenge. The half-life of 
PGDM1400 was calculated for the 2, 0.4, and 0.08 mg/kg groups to be 7.7 days, 
6.7 days, and 6.3 days, respectively (47).  
See IB for further details. 
 
Figure 4-8: Protective efficacy of PGDM1400 against SHIV-325c in rhesus macaques. Plasma 
viral RNA (as log vRNA copies/mL) is shown for animals that received: (A) saline control; (B) 
PGDM1400 (2mg/kg); (C) PGDM1400 (0.4 mg/kg); (D) PGDM1400 (0.08 mg/kg). The assay 
sensitivity limit was >50 RNA copies/mL 
4.5.2.2 
Preclinical challenge study of PGT121 and PGDM1400 
Administration of both PGT121 and PGDM1400 in NHP challenge with a 
combination of SHIV-SF162P3 (sensitive in vitro to PGT121, resistant to 
PGDM1400) and SHIV-325c (sensitive in vitro to PGDM1400, resistant to 
PGT121) demonstrated protection with the combination of the two mAbs, but not 
with either mAb alone, as reflected in Figure 4-9 (47).  
 

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Figure 4-9: Protective efficacy of the combination of PGT121 + PGDM1400 against a mixed 
SHIV challenge in rhesus monkeys. Five animals per group received an intravenous single 
dose of PGDM1400, PGT121, the combination of PGT121 + PGDM1400, or saline (Sham) 
before being rectally challenged with a high dose of both SHIV-SF162P3 and SHIV-325C. 
Graphs depict the log plasma viral RNA copies/mL after mixed challenge with SHIV-SF162P3 
and SHIV-325C. Red line indicates median values. Detection limit is 50 copies/mL. 
4.5.3 
Preclinical studies of 10-1074  
In addition to therapeutic and preventive pharmacology studies in humanized 
mice (68), the potential of 10-1074 to prevent SHIV infection was evaluated in 
rhesus macaques (69, 70). A total of 10 rhesus macaques were administered a 
single IV infusion of 10-1074 at 0.2 mg/kg (n = 2), 1 mg/kg (n = 2), 5 mg/kg 
(n = 2), or 20 mg/kg (n = 2) dose levels, and challenged intrarectally with SHIV-
AD8 or SHIV-CL7 (1000 TCID50) 1 day later. As shown in Table 4-1, passive 
transfer of 5 mg/kg of 10-1074 protected 2 of 2 animals from SHIV-AD8. When 
challenged with SHIV-CL7, 1 of 2 animals treated with 1 mg/kg of 10-1074 was 
protected. 
 
Table 4-1 10-1074 protection against high dose SHIV challenge in rhesus macaques 
 
Protected animals after challenge 
Dose (mg/kg) 
SHIV AD8 
R5 SHIV CL7 AD8 
20 
2/2 
2/2 
5 
2/2 
NA 
1 
0/2 
1/2 
0.2 
NA 
0/2 
Another NHP study was performed to evaluate the efficacy of a single IV dose 
(20 mg/kg) of 10-1074 in blocking repeated weekly low dose virus challenge of 
the clade B SHIV AD8 (10 TCID50) (71). Compared to control animals, which 
required 2 to 6 challenges (median = 3 weeks) for infection, a single 10-1074 
infusion was protective for a median of 12.5 weeks (range 7 to 23 weeks). The 

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animals were also monitored for safety and no clinical signs were reported after 
the animals received 10-1074 infusion, including no evidence of altered behavior, 
decreased appetite, fluctuation in body weight, or development of respiratory or 
gastrointestinal signs.  
See the IB for more details. 
4.5.4 
Preclinical studies of VRC07-523LS  
VRC07-523LS has been assessed in several preclinical safety studies evaluating 
potential off-target binding, TCR, toxicity, and local tolerance.  
VRC07-523LS was found to be 5- to 8-fold more potent than VRC01, with an 
inhibitory concentration (IC50) < 50 mcg/mL against 96% of HIV-1 pseudoviruses 
representing the major circulating HIV-1 clades, and an IC50 < 1 mcg/mL against 
92% of HIV-1 viruses tested. In addition, it displayed minimal levels of 
autoreactivity.  
In vivo proof-of-concept studies showed that VRC07-523LS is about 5-fold more 
potent than VRC01LS in Rhesus macaques and displays a longer half-life (9.8 
days) than VRC07 (4.9 days) after a single dose of mAb at 10 mg/kg administered 
IV (27). 
See the IB for further details. 
4.6 
Clinical studies 
4.6.1 
Clinical studies of PGT121 
T001 is a phase 1 randomized placebo-controlled clinical trial of the safety, 
pharmacokinetics, and antiviral activity of PGT121 in HIV-uninfected and HIV-
infected adults. The study design is shown below in Table 4-2. 

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Table 4-2: T001 study schema 
 
The hypothesis in this ongoing study is that PGT121 administration will be safe 
by both IV and SC routes. The secondary hypothesis is that PGT121 will be 
detectable in human sera with a definable half-life. As of June 2018, accrual is 
complete in Groups 1A-1C (HIV-uninfected, 3-30 mg/kg, IV route), Group 1D 
(HIV-uninfected, 3 mg/kg, SC route), as well as in Groups 2A (HIV-infected, 3 
mg/kg, IV route) and 2B (HIV-infected, 10 mg/kg, IV route). Blinded interim 
safety data as of June 2018 included all accumulated safety data through week 24 
post investigational product administration for Groups 1A, 1B, 1C, 1D, 2A, and 
2B. After intravenous administration of 3 mg/kg, 10 mg/kg or 30 mg/kg, there 
was short-lived, mild or moderate local and systemic reactogenicity. After 
subcutaneous administration of 3 mg/kg, there was short-lived, mild local 
reactogenicity but no systemic reactogenicity. There have been no related SAEs. 
There has been one unrelated SAE (hospital admission for orthopedic surgery). 
To date, there have been no study safety pauses for AEs and product 
administrations have been generally well tolerated.  
Safety data for Groups 1A, 1B, and 1C was reviewed by the independent Safety 
Monitoring Committee (SMC) in January 2018. There were no dose limiting 
toxicities (DLTs), defined as: (1) any grade 3 or greater reactogenicity, or any 
adverse events judged by the study investigators as at least possibly related to 
investigational product; or (2) any SAE considered at least possibly related to 
investigational product), and maximum tolerated dose (MTD) was not reached. 
The SMC recommended to proceed with enrollment of Group 3 at the maximum 
dose of 30 mg/kg PGT121. 

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PGT121 concentrations have been measured in Group 1A (HIV-uninfected, 3 
mg/kg, IV route), Group 1B (HIV-uninfected, 10 mg/kg, IV route) and Group 1C 
(HIV-uninfected, 30 mg/kg, IV route) by validated anti-idiotype PK and TZM-bl 
neutralization assays through week 15 postinfusion. As shown in Figure 4-10, the 
medium half-life of PGT121 during the elimination phase was 23 days, with the 
half-life ranging from 19 to 26 days. PGT121 neutralizing antibody (nAb) 
concentrations to X2088_c9 and CNE30 pseudoviruses were significantly and 
positively correlated with the PGT121 binding Ab concentrations. See the IB for 
more details. 
 
Figure 4-10: PGT121 binding antibody concentrations in Group 1A (HIV uninfected, 3 
mg/kg), Group 1B (HIV uninfected, 10 mg/kg) and Group 1C (HIV uninfected, 30 mg/kg). 
4.6.2 
Clinical studies of PGDM1400 and combination of PGT121 and 
PGDM1400 
T002 is a phase 1 randomized placebo-controlled clinical trial of the safety, 
pharmacokinetics, and antiviral activity of PGDM1400 as well as the combination 
of PGDM1400+PGT121 in HIV-uninfected and HIV-infected adults. The study 
design is shown below in Table 4-3 

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Table 4-3: T002 study schema 
 
Blinded interim safety data as of October 2018 included all accumulated safety 
data between 2 and 24 weeks post investigational product administration for 
Groups 1A (24 weeks), 1B (24 weeks), 1C (16-24 weeks), and 2A (20-24 weeks), 
2B (8-16 weeks), and 2C (4-8 weeks). After intravenous administration of 3 
mg/kg, 10 mg/kg, and 30 mg/kg of PGDM1400 and after administration of 3+3 
mg/kg, 10+10 mg/kg, and 30+30 mg/kg of PGDM1400 and PGT121, there was 
short-lived, mild or moderate local and systemic reactogenicity. There have been 
no related SAEs. To date, there have been no study safety pauses for AEs and 
product administrations have been generally well tolerated.  
PGDM1400 concentrations have been measured in Group 1A, 1B, and 1C (HIV-
uninfected, 3, 10, and 30 mg/kg, IV route, respectively) by validated anti-idiotype 
PK assays through week 4-24 postinfusion. The preliminary medium half-life of 
PGDM1400 during the elimination phase is 21 days. 
As of October 2018, accrual is complete in Groups 1A, 1B, and 1C (HIV-
uninfected, PGDM1400 at 3, 10 and 30 mg/kg, respectively, IV route) and in 
Group 2A, 2B, and 2C (HIV uninfected, PGDM1400+PGT121 at 3+3, 10+10 and 
30+30 mg/kg, respectively, IV route). The external SMC reviewed the safety data 
on October 17, 2018. There were no DLTs, defined as: (1) any grade 3 or greater 
reactogenicity, or any adverse events judged by the study investigators as at least 

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possibly related to investigational product; or (2) any SAE considered at least 
possibly related to investigational product), and MTD was not reached. The SMC 
recommended to proceed with enrollment of Group 3 at the maximum dose of 30 
mg/kg PGDM1400 and 30 mg/kg PGT121. Enrollment into Group 3 (HIV-
infected viremic) is ongoing and it is estimated to be completed at the end of 
March 2019. 
 
Figure 4-11 PGDM1400 binding antibody concentrations in Group 1A (HIV uninfected, 3 
mg/kg), Group 1B (HIV uninfected, 10 mg/kg), and Group 1C (HIV uninfected, 30 mg/kg) 
See the IB for more details. 
4.6.3 
Clinical studies of 10-1074 
As of November 2018, 10-1074 had been administered to 92 study participants at 
doses ranging from 3 mg/kg to 30 mg/kg (32 HIV-uninfected and 49 HIV-
infected). 10-1074 has been generally well tolerated at all dose levels tested (ie, 3, 
10, and 30 mg/kg).  
In a first-in-human, open label, dose-escalation study of 10-1074 (protocol MCA-
0885, NCT02511990, see Figure 4-12), 33 participants (19 HIV-infected and 14 
HIV-uninfected) were given 1 IV infusion at 3, 10, and 30 mg/kg. Six participants 
received 10 mg/kg and 21 received 1 infusion at 30 mg/kg. All study participants 
were followed to 24 weeks. 10-1074 was generally safe and well tolerated at the 
doses tested. A total of 57 adverse events were reported during a follow-up period 
of 6 months, 88% of these were of grade 1 severity. The most commonly reported 
adverse event deemed possibly related to the study drug was transient, mild 
headache. There were no serious adverse events, or grade 3 related adverse 
events.  
 

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Figure 4-12 MCA-0885 schema 
Two phase 1 clinical trials of the combination of the CD4 binding site bnAb 
3BNC117 plus 10-1074, administered intravenously, are currently underway. In 
one study (protocol YCO-0899, NCT02824536, see Figure 4-13) HIV-uninfected 
individuals received 1-3 doses of the antibody combination at 3 or 10 mg/kg or 
placebo. A total 24 of participants enrolled in the study, and 18 received the 
3BNC117 and 10-1074 combination (the study is placebo-controlled and remains 
blinded). In the second study (protocol MCA-0906, NCT02825797, see Figure 
4-14), HIV-infected individuals receive 1 to 3 doses of 3BNC117 and 10-1074 
combination at 10 or 30 mg/kg each or placebo. Fifteen study participants 
discontinue ART and receive up to 3 infusions of the mAbs at weeks 0, 3, and 6. 
To date, 34 individuals enrolled (30 received the antibody combination and 4 
received placebo). Of those, 12 received 3 infusions of 30 mg/kg, administered 3 
weeks apart, and 3 received 3 infusions of 30 mg/kg, 2 weeks apart. 
There have been no SAEs, and the safety profile of the 3BNC117 plus 10-1074 
combination is similar to what was observed with either antibody alone. Most 
reported AE’s were graded as mild (77%), and the most commonly reported AEs 
were upper respiratory infection, headache, and malaise/fatigue 
 
Figure 4-13 YCO-0899 schema 
 

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Figure 4-14 MCA-0906 Schema 
See the IB for additional details. 
4.6.4 
Clinical studies of VRC07-523LS 
4.6.4.1 
VRC 605 
A phase 1 open-label, dose-escalation study of VRC07-523LS, VRC 605 
(NCT03015181), is underway in healthy, HIV-uninfected adults to evaluate the 
safety and pharmacokinetics of 1 to 3 administrations of the antibody. The doses 
being evaluated are a single administration of 1 mg/kg and 5 mg/kg IV and SC, 
and 20 mg/kg and 40 mg/kg IV, and three administrations (q 12 weeks) of 5 
mg/kg SC and 20 mg/kg IV VRC07-523LS (Table 4-4).  
Study objectives include evaluating the safety and tolerability of the study 
regimen and the pharmacokinetics of each dose level, determining the presence or 
absence of detectable ADA to VRC07-523LS, and evaluating for evidence of 
functional activity of VRC07-523LS. 

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Table 4-4 VRC 605 study schema 
Group 
Participants 
Administration Schedule 
Day 0 
Week 12 
Week 24 
1 
3 
1 mg/kg IV 
 
 
2 
3 
5 mg/kg IV 
 
 
3 
3 
5 mg/kg SC 
 
 
4 
3 
20 mg/kg IV 
 
 
5 
3 
40 mg/kg IV 
 
 
6 
5 
5 mg/kg SC 
5 mg/kg SC 
5 mg/kg SC 
7 
5 
20 mg/kg IV 
20 mg/kg IV 
20 mg/kg IV 
Total 
25 
 
IV = intravenous infusion 
SC = subcutaneous injection 
The study is fully enrolled and study product administration is complete. There 
have been no serious adverse events (SAEs) or safety pauses and product 
administrations have been generally well tolerated, with no reports of grade 3 or 
higher related adverse events deemed related to the study product. Figure 4-15 
depicts preliminary PK data that suggests pharmacokinetics similar to those of 
VRC01-LS. 
 
 
Figure 4-15 Serum concentrations of VRC07-523LS (from VRC 605) after 3 IV infusions of 20 
mg/kg. (Confidential–interim and preliminary) 
4.6.4.2 
HVTN 127/HPTN 087 
The follow-up study HVTN 127/HPTN 087 (NCT03387150) is a randomized 
phase 1 clinical trial that evaluates the safety and serum concentrations of 
VRC07-523LS administered in multiple doses and routes to healthy, HIV-
uninfected adults.  

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Table 4-5 HVTN 127/HPTN 087 (Version 2.0) study schema 
Group 
N 
Route 
Dose 
VRC07-523LS administration schedule 
W0 
W16 
W32 
W48 
W64 
1 
20 
IV 
2.5 mg/kg 
X 
X 
X 
X 
X 
2 
20 
IV 
5 mg/kg 
X 
X 
X 
X 
X 
3 
20 
IV 
20 mg/kg 
X 
X 
X 
X 
X 
4 
20 
SC 
2.5 mg/kg 
X 
X 
X 
X 
X 
5 
20 
SC 
5 mg/kg 
X 
X 
X 
X 
X 
6 
20 
IM 
2.5 mg/kg 
X 
X 
X 
X 
X 
4 
Placebo 
X 
X 
X 
X 
X 
Total 
124 
IV = intravenous infusion 
SC = subcutaneous injection 
IM = intramuscular injection 
Between February and October 2018, HVTN 127/HPTN 087 enrolled a total of 
124 healthy, HIV-uninfected adult participants to receive multiple administrations 
of VRC07-523LS via IV, SC, or IM routes (IM added in protocol version 2.0; 4 
IM participants receive placebo). The primary objectives of the study are to assess 
safety and tolerability of repeated IV, SC, or IM administrations of VRC07-
523LS, and to characterize serum concentration over time for different doses, 
schedules, and routes of administration. Additional objectives include building a 
population PK model of VRC07-523LS and determining whether ADA emerge in 
response to repeated administrations of the antibody. 
No Grade 3 or higher AEs deemed related to VRC07-523LS and no serious 
adverse events (SAEs) have been reported in HVTN 127/HPTN 087. The 
majority of participants have reported no local or systemic Solicited AEs and no 
Unsolicited AEs. The few reported Unsolicited AEs have been Grade 1 (mild) and 
the few reported Solicited AEs have been Grade 1 (mild) or Grade 2 (moderate).  
See the IB for more details. 
4.7 
Potential risks of study products and administration 
There is early phase human experience with administration of VRC07-523LS. 
VRC 605 was evaluating the safety and pharmacokinetics of 1 to 3 
administrations of VRC07-523LS prior to the start of HVTN 127/HPTN 087. In 
addition, the similar CD4-binding site mAb, VRC01, has been given to more than 
3000 participants in several phase 1 and phase 2b clinical trials. More than 10,000 
infusions of 10 mg/kg and 30 mg/kg VRC01 have been given to HIV-uninfected 
adults in HVTN 703/HPTN 081 and HVTN 704/HPTN 085. Additionally, both 
VRC01 and VRC01LS are being tested in an ongoing phase 1 study (HVTN 116). 

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As of January 2018, the VRC605 study is fully enrolled. Twenty-five of 26 
subjects received at least 1 dose of VRC07-523LS (12 SC and 25 IV 
administrations). One subject withdrew prior to receiving the study product. There 
have been no SAEs and no safety pauses for AEs. Overall, 15 of 25 subjects who 
received the product (60%) have had at least one AE with the maximum severity 
being grade 1 for 7 subjects, grade 2 for 6 subjects, grade 3 for 1 subject and 
grade 4 for 1 subject. The grade 3 AE was for an elevated creatinine 56 day after 
the last product administration. This was most likely related to dehydration 
following exercise. The creatinine value was determined to be a grade 3 based on 
the DAIDS Grading Table parameter of an increase of 1.5 to 2 times the baseline 
value, which was still well within the institutional normal range. The grade 4 AE 
was for elevated liver enzymes likely related to a starting a concomitant 
medication, fluoxetine, known to cause hepatoxicity, and not related to VRC07-
523LS. VRC07-523LS administrations were discontinued for this subject due to 
the concomitant illness. While the subject was being followed for safety, liver 
enzymes tests fluctuated again after starting citalopram which reinforced that the 
event was most likely caused by an underlying sensitivity to selective serotonin 
reuptake inhibitor (SSRI) medications. This grade 4 laboratory abnormality was 
not considered life-threatening, as it was not clinically significant as there were no 
hospitalization, jaundice, coagulopathy, bleeding, or ascites. Six mild or moderate 
AEs were assessed as related to study product including mild dizziness, 4 
occasions of infusion reactions (1 mild and 3 moderate, reported for 2 subjects), 
and mild abdominal pain. All AEs assessed as related to the study product have 
resolved without residual effects.  
Two subjects developed infusion reactions shortly after IV product 
administration. Symptoms were typical of infusion reactions observed with other 
monoclonal antibodies (72). No atypical symptoms or delayed symptoms were 
seen. Specifically, one subject enrolled in the 40mg/kg IV group experienced a 
moderate infusion reaction with chills, rigors, fever, myalgia, and headache 
beginning 15 minutes after completion of the infusion. The subject was treated 
with acetaminophen and ibuprofen. All symptoms resolved within 12 hours. 
Another subject in the 20mg/kg IV group experienced 3 separate infusion 
reactions (n=2 moderate, n=1 mild) after each product infusion. The subject 
experienced nausea, chills, rigors, malaise, tachycardia, headache, myalgia, and 
arthralgia. Symptoms began 15 minutes to 1 hour after completion of each 
product administration and completely resolved within 12 hours. The subject was 
treated with acetaminophen and ibuprofen. 
Human experience with PGDM1400 and PGT121 is limited to the T001 and T002 
clinical trials. As of June 2018, T001 and T002 accrual is ongoing, and there have 
been no related SAEs. There has been one unrelated SAE (hospital admission for 
orthopedic surgery) in T001. To date, there have been no study safety pauses for 
AEs and product administrations have been generally well tolerated. 
As of November 2018, 10-1074 has been administered to 92 participants either 
alone or in combination with 3BNC117 in the MCA-0885, YCO-0899, MCA-

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0906, and MCA-965 protocols. 10-1074 has been generally safe and well 
tolerated at the doses tested. The majority of the reported AEs were graded mild 
and there have been no SAEs or study safety pauses in either of these clinical 
trials. 
Experience is accruing with each of these mAbs alone and in dual combination 
mentioned above (Section 4.6) but the current study evaluating 3 mAbs together 
will be a first in human.  
Overall, the side effects of mAbs are mild and can include fever, flushing, chills, 
rigors, nausea, vomiting, diarrhea, pain, pruritus, rash, urticaria, angioedema, 
headache, dizziness, shortness of breath, bronchospasm, tachycardia, hypotension, 
hypertension, and chest pain. There can also be a risk of infection from mAbs 
targeting human cytokines or human cell antigens, but this is not expected with a 
mAb targeting a viral antigen (73).  
Additional reactions such as tumor lysis syndrome and cytokine release syndrome 
have been previously described with chimeric and humanized Abs, usually with 
mAbs targeting human antigens. Cytokine release syndrome has been described 
with human mAbs targeting lymphocyte cell-surface antigens. Serious allergic 
reactions such as anaphylaxis, angioedema, bronchospasm, hypotension, and 
hypoxia are rare and often associated with mAbs targeting human proteins or with 
non-human mAbs. These mAb-related events typically occur within the first 24 
hours of administration. Cytokine release syndrome typically occurs within the 
first few hours of administration, and usually with the first administration when 
the largest number of target cells expressing antigen are present. Reactions related 
to the rate of infusion have been described for several FDA-licensed mAbs. 
Cytokine release syndrome can be effectively managed by temporarily holding 
the administration, administering anti-histamines, and restarting the IV infusion at 
a slower rate (74). 
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, characterized by urticaria, fever, lymph node enlargement, and 
joint pains. These symptoms may not appear until several days to a few weeks 
after the exposure to the mAb and are noted to be more common with chimeric 
types of mAb (73, 75). 
Other potential side effects of mAbs include thrombocytopenia, autoimmune 
diseases, cancer, dermatitis, and cardiotoxicity (73). 
Since PGT121, PGDM1400, 10-1074, and VRC07-523LS all target a viral 
antigen rather than human cell surface antigens and are human mAbs, serious 
infusion reactions are expected to be rare. 

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There is a possibility that receipt of the study products will cause a reactive result 
on some currently available HIV test kits, especially if testing occurs close to 
study product administration timepoints (see Section 9.5.1). 
To date, the clinical trial safety experience with VRC01-class mAbs has been 
reassuring. In HVTN 104, IV administration of VRC01 was generally well-
tolerated with mild pain and/or tenderness commonly reported at the site of the IV 
infusion. Mild to moderate systemic reactogenicity symptoms were reported by 
VRC01 recipients following at least one of the infusions, but there was no clear 
relationship with frequency or severity to the dose of VRC01 (66). The ongoing 
efficacy trials HVTN 704/HPTN 085 and HVTN 703/HPTN 081 have 
accumulated significant additional VRC01 clinical experience; however, as these 
trials remain blinded, they do not yet contribute to the unblinded VRC01 safety 
profile. 
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 irritation (called phlebitis), or 
blood clot. Risk will be minimized by using sterile technique and universal 
precautions. Blood drawing may also cause anemia. 
Risks of intravenous infusion: The placement of an intravenous 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 local skin prior to catheter 
placement and through the use of infection control practices during infusion. The 
risk of product contamination will be minimized by the use of aseptic technique in 
the pharmacy and universal precautions during product administration.  

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5 
Objectives and endpoints 
5.1 
Primary objectives and endpoints 
Primary objective 1 
To evaluate the safety and tolerability of PGT121 or PGDM1400 or 10-1074 
when administered in sequence via IV with VRC07-523LS (2-mAb 
combinations), and of PGDM1400, PGT121, and VRC07-523LS administered in 
sequence via IV (3-mAb combination) 
Primary endpoint 1 
Local and systemic Solicited AEs, laboratory measures of safety, Unsolicited 
AEs, and SAEs  
Early discontinuation of administration and reason(s) for discontinuation and 
early study termination 
Primary objective 2 
To evaluate the serum concentrations and pharmacokinetics of PGT121, 
PGDM1400, 10-1074 and VRC07-523LS after a single 2-mAb administration and 
after each PGDM1400, PGT121, VRC07-523LS 3-mAb administration  
Primary endpoint 2 
Serum concentrations of PGT121, PGDM1400, 10-1074, and VRC07-523LS at 
prespecified timepoints among participants who received all scheduled product 
administrations  
Primary objective 3 
To evaluate the individual mAb-specific serum neutralizing activity of PGT121, 
PGDM1400, 10-1074 and VRC07-523LS after a single 2-mAb administration and 
after each PGDM1400, PGT121, VRC07-523LS 3-mAb administration 
Primary endpoint 3 
Magnitude of serum neutralizing activity measured with mAb-specific Env-
pseudotyped viruses in TZM-bl cells at prespecified timepoints among 
participants who received all scheduled product administrations 
5.2 
Secondary objectives and endpoints 
Secondary objective 1 

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To correlate serum concentrations of PGT121, PGDM1400, 10-1074, and 
VRC07-523LS with corresponding virus neutralization titers in serum 
Secondary endpoints 1 
Serum concentrations of PGT121, PGDM1400, 10-1074, and VRC07-523LS at 
prespecified timepoints for all participants in all groups regardless of how many 
product administrations and how much product they received  
Magnitude of serum neutralizing activity measured with Env pseudotyped viruses 
in TZM-bl cells at prespecified timepoints for all participants in all groups 
regardless of how many product administrations and how much product they 
received 
Secondary objective 2 
To determine whether the mAbs maintain their expected combined magnitude and 
breadth of serum neutralizing activity after a single 2-mAb administration 
(Groups 1-3) and after each 3-mAb administration (Group 4) as predicted by the 
known magnitude and breadth of neutralization of the corresponding mAb 
combinations as non-infused clinical products 
Secondary endpoint 2 
Magnitude of neutralizing activity against a panel of Env pseudotyped reference 
viruses in TZM-bl cells at selected timepoints for all participants in all groups 
regardless of how many product administrations and how much product they 
received 
Secondary objective 3 
To determine whether ADA are present and whether there is a correlation among 
PGT121, PGDM1400, 10-1074, and VRC07-523LS concentrations and ADA 
titers in serum samples 
Secondary endpoint 3 
Serum PGT121, PGDM1400, 10-1074, and VRC07-523LS concentrations and 
ADA titers in each group measured at prespecified timepoints for all participants 
in all groups regardless of how many product administrations and how much 
product they received 
5.3 
Exploratory objectives 
Exploratory objective 1 

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To determine whether any confirmed positive ADA samples have functional 
activity that impacts the neutralizing activity of PGT121, PGDM1400, 10-1074, 
and VRC07-523LS 
Exploratory objective 2 
To further evaluate non-neutralizing antiviral activities, additional assays (eg, 
antibody dependent cell mediated cytotoxicity [ADCC], antibody dependent 
cellular phagocytosis [ADCP], virion capture) may be performed for activities 
that PGT121, PGDM1400, 10-1074, and VRC07-523LS are shown to exhibit in 
vitro 
Exploratory objective 3 
To develop predictive population PK models and to assess PK, drug-drug 
interaction, and neutralization drug-drug interaction among PGT121, PGDM1400, 
10-1074, and VRC07-523LS 
Exploratory objective 4 
To conduct analyses related to furthering the understanding of HIV, monoclonal 
antibodies, immunology, vaccines, and clinical trial conduct 

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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling 27 healthy, HIV-uninfected adult participants in 
four treatment groups. Groups 1, 2, and 3 entail IV administration of VRC07-
523LS along with either PGT121, PGDM1400, or 10-1074; Group 4 entails 2 IV 
administrations of PGDM1400, PGT121, and VRC07-523LS. Groups 1 through 3 
will be open label, open to enrollment simultaneously and randomized at a 1:1:1 
ratio with n = 6 participants per group. Enrollment of Group 4 with n = 9 
participants will follow the review of safety data in Groups 1-3. To ensure that 
both persons assigned male sex at birth and persons assigned female sex at birth will 
be adequately represented, the trial will enroll at least approximately 40% of each. 
Since enrollment is concurrent with receiving the first study product 
administration, all participants will provide some safety data. However, for mAb 
concentration and antiviral analyses, it is possible that data may be missing for 
various reasons, such as participants terminating from the study early, problems in 
shipping specimens, or high assay background. For this reason, the sample size 
calculations in Section 6.1.2 account for 15% enrolled participants having missing 
data for the primary lab endpoint at a given timepoint. As a reference, 
immunogenicity data from 17 phase 1 and 2 phase 2a HVTN vaccine trials, which 
began enrolling after June 2005 (data as of September 2014), indicate that 17% is 
a reasonable estimate for the rate of missing data at a given timepoint. In HVTN 
104 (phase 1 trial of VRC01), approximately 10-15% of mAb concentration data 
were missing at the primary timepoints. 
6.1.1 
Sample size calculations for safety 
The goal of the safety evaluation for 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 each treatment group of size n = 6, there is a 90% 
chance of observing at least 1 event if the true rate of such an event is 31.9% or 
more; and there is a 90% chance or more of observing no events if the true rate is 
1.7% or less. For Group 4 of size n = 9, there is at least a 90% chance of 
observing at least 1 event if the true rate of such an event is 22.6% or more; and 
there is at least a 90% chance of observing no events if the true rate is 1.2% or 
less. For Groups 1-3 combined with n = 18, there is at least a 90% chance of 
observing at least 1 event if the true rate of such an event is 12.0% or more; and 
there is at least a 90% chance of observing no events if the true rate is 0.6% or 
less. For all active double- and triple-mAb treatment groups combined, with 
n = 27, there is at least a 90% chance of observing at least 1 event if the true rate 
of such an event is 8.2% or more; and there is at least a 90% chance of observing 
no events if the true rate is 0.4% or less. As a reference, in HVTN vaccine trials 

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from April 2008 through March 2018, about 1.7% of participants who received 
placebos experienced an SAE. 
Binomial probabilities of observing 0, 1 or more, and 2 or more events among 
arms of sizes 6, 9, 18, and 27 are presented in Table 6-1 for a range of possible 
true adverse event rates. These calculations provide a more complete picture of 
the sensitivity of this study design to identify potential safety problems with 
sequential administration of VRC07-523LS with either PGT121, PGDM1400, or 
10-1074, or sequential administration of VRC07-523LS, PGT121, and 
PGDM1400. 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
groups of size 6, 9, 18, and 27 for different true event rates 
Group size 
True event rate (
%) 
Pr(0/n1) 
Pr(1+/n1) 
Pr(2+/n1) 
6 
1 
0.94 
0.06 
<0.01 
4 
0.78 
0.22 
0.02 
10 
0.53 
0.47 
0.11 
20 
0.26 
0.74 
0.34 
30 
0.12 
0.88 
0.58 
9 
1 
0.91 
0.09 
<0.01 
4 
0.69 
0.31 
0.05 
10 
0.39 
0.61 
0.23 
20 
0.13 
0.87 
0.56 
30 
0.04 
0.96 
0.80 
18 
1 
0.84 
0.16 
0.01 
4 
0.48 
0.52 
0.16 
10 
0.15 
0.85 
0.55 
20 
0.02 
0.98 
0.90 
30 
<0.01 
>0.99 
0.99 
27 
1 
0.76 
0.24 
0.03 
4 
0.33 
0.67 
0.29 
10 
0.06 
0.94 
0.77 
20 
<0.01 
>0.99 
0.98 
30 
<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 adverse event rate 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 (76). If none of the 27 participants in all treatment groups experiences 
a safety event, the 95% 2-sided upper confidence bound for the true rate of such 
events in the total treated population is 12.5%. For each individual antibody 
treatment arm of n = 6 or 9, the 2-sided upper confidence bound for this rate is 
39.0% and 29.9%, respectively. 

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Table 6-2 Two-sided 95% confidence intervals for the probability of observing a safety event 
based on observing a particular rate of safety endpoints for arms of size 6, 9, 18, and 27 
Observed event
 rate 
95% 
Confidence  
interval (%) 
0/6 
(0.0, 39.0) 
1/6 
(3.0, 56.4) 
2/6 
(9.7, 70.0) 
 
 
0/9 
(0.0, 29.9) 
1/9 
(2.0, 43.5) 
2/9 
(6.3, 54.7) 
 
 
0/18 
(0.0, 17.6) 
1/18 
(1.0, 25.8) 
2/18 
(3.1, 32.8) 
 
 
0/27 
(0.0, 12.5) 
1/27 
(0.7, 18.3) 
2/27 
(2.1, 23.4) 
6.1.2 
Sample size calculations for serum mAb concentrations  
Primary objective 2 of this study is to evaluate serum concentrations of VRC07-
523LS, PGT121, PGDM1400, and 10-1074 at several timepoints (ie, 
pharmacokinetics) following IV administration of these mAbs. This objective is 
descriptive in nature and will be accomplished by estimating the mean serum 
concentration of each mAb within each treatment group at specific timepoints 
following each administration. The precision with which a true mean 
concentration can be estimated from observed data depends on the standard 
deviation (SD) of the measurements and the sample size. Table 6-3 displays two-
sided 95% confidence intervals (CIs) for the mean mAb concentration for several 
values of the observed average mAb concentration. The construction of these 
confidence intervals assumed sample sizes of n = 5 and 7 per arm, reflecting a 
missingness rate of 15%, compared to a planned treatment group size of 6 and 9 
participants, respectively. The calculations assumed that log-transformed serum 
concentrations are approximately normally distributed. To account for the small 
sample sizes, a t-distribution was used to construct CIs. For instance, with an 
observed mean loge serum level of loge(10 mcg/mL) and assuming a standard 
deviation of 0.5 for their log-transformed values, a two-sided 95% confidence 
interval for the true mean mAb concentration level is (5.4, 18.6) and (6.3, 15.9) 
(in loge(mcg/mL)) with an effective sample size of 5 and 7 participants, 
respectively. Of note, a SD of less than 1.0 was generally observed in the log-
transformed serum concentrations of VRC01 at various timepoints post IV 
infusions or SC injections of VRC01 in HVTN104 (65). 

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Table 6-3 Two-sided 95% confidence intervals based on observing a particular average loge 
mAb concentration in participants in any of the active arms, taking 15% attrition into 
consideration (n = 5 or 7) 
Observed 
average loge-
mAb 
concentration 
(loge mcg/mL) 
SD of loge-
mAb 
concentration 
(loge 
mcg/mL) 
95% confidence interval (mcg/mL) 
n = 5 
n = 7 
loge(0.5) 
0.5 
(0.3, 0.9) 
(0.3, 0.8) 
loge(1) 
(0.5, 1.9) 
(0.6, 1.6) 
loge(3) 
(1.6, 5.6) 
(1.9, 4.8) 
loge(5) 
(2.7, 9.3) 
(3.1, 7.9) 
loge(10) 
(5.4, 18.6) 
(6.3, 15.9) 
loge(20) 
(10.7, 37.2) 
(12.6, 31.8) 
loge(30) 
(16.1, 55.8) 
(18.9, 47.6) 
loge(40) 
(21.5, 74.4) 
(25.2, 63.5) 
loge(50) 
(26.9, 93) 
(31.5, 79.4) 
loge(100) 
(53.7, 186) 
(63, 158.8) 
loge(250) 
(134.4, 465.1) 
(157.4, 397) 
loge(500) 
(268.7, 930.2) 
(314.9, 794) 
loge(1000) 
(537.5, 1860.5) 
(629.8, 1587.9) 
loge(0.5) 
1.0 
(0.1, 1.7) 
(0.2, 1.3) 
loge(1) 
(0.3, 3.5) 
(0.4, 2.5) 
loge(3) 
(0.9, 10.4) 
(1.2, 7.6) 
loge(5) 
(1.4, 17.3) 
(2, 12.6) 
loge(10) 
(2.9, 34.6) 
(4, 25.2) 
loge(20) 
(5.8, 69.2) 
(7.9, 50.4) 
loge(30) 
(8.7, 103.8) 
(11.9, 75.6) 
loge(40) 
(11.6, 138.5) 
(15.9, 100.9) 
loge(50) 
(14.4, 173.1) 
(19.8, 126.1) 
loge(100) 
(28.9, 346.1) 
(39.7, 252.1) 
loge(250) 
(72.2, 865.3) 
(99.1, 630.4) 
loge(500) 
(144.5, 1730.7) 
(198.3, 1260.7) 
loge(1000) 
(288.9, 3461.4) 
(396.6, 2521.5) 
6.1.3 
Sample size calculations for serum neutralization activity  
Primary objective 3 of this study is to evaluate serum neutralization titers of 
VRC07-523LS, PGT121, PGDM1400, and 10-1074 against Env-pseudotyped 
viruses specific to each mAb at several timepoints following IV administrations. 
This objective is also descriptive in nature, and will be accomplished by 
estimating, within each treatment group, the mean serum neutralization titers of 
each mAb against the specific virus. The precision with which a true mean 
neutralization titer can be estimated from observed data depends on the SD of the 
measurements and the sample size. Table 6-4 displays two-sided 95% confidence 
intervals for the mean neutralization titer for several values of the observed 
average ID50 or ID80 neutralization titer. The construction of these confidence 
intervals assumed sample sizes of n = 5, and 7 per group, reflecting an attrition 

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rate of 15% compared to the planned treatment group size of 6 and 9 participants, 
respectively. The calculations assumed that log-transformed neutralization titers 
are approximately normally distributed. To account for the small sample sizes, a t-
distribution was used to construct CIs. For instance, with an observed mean titer 
of loge(50) and assuming a standard deviation of 0.5 for their log-transformed 
values, a two-sided 95% confidence interval for the true mean neutralization titer 
is (26.9, 93) and (31.5, 79.4) with an effective sample size of 5 and 7 participants, 
respectively. Of note, based on neutralization data against a global panel of 11 
pseudoviruses in six participants in HVTN104, an SD of approximately 1.0 was 
observed in the loge-transformed ID50 titers at various timepoints post IV 
infusions of VRC01(65). 
Table 6-4 Two-sided 95% confidence intervals based on observing a particular average loge-
neutralization titer in participants in any of the active arms, taking 15% attrition into 
consideration (n = 5 or 7) 
Observed average 
loge neutralization 
titer 
SD of loge 
neutralization titer 
95% confidence interval 
n = 5 
n = 7 
loge(5) 
0.5 
(2.7, 9.3) 
(3.1, 7.9) 
loge(20) 
(10.7, 37.2) 
(12.6, 31.8) 
loge(50) 
(26.9, 93) 
(31.5, 79.4) 
loge(100) 
(53.7, 186) 
(63, 158.8) 
loge(250) 
(134.4, 465.1) 
(157.4, 397) 
loge(500) 
(268.7, 930.2) 
(314.9, 794) 
loge(1000) 
(537.5, 1860.5) 
(629.8, 1587.9) 
loge(5) 
1.0 
(1.4, 17.3) 
(2, 12.6) 
loge(20) 
(5.8, 69.2) 
(7.9, 50.4) 
loge(50) 
(14.4, 173.1) 
(19.8, 126.1) 
loge(100) 
(28.9, 346.1) 
(39.7, 252.1) 
loge(250) 
(72.2, 865.3) 
(99.1, 630.4) 
loge(500) 
(144.5, 1730.7) 
(198.3, 1260.7) 
loge(1000) 
(288.9, 3461.4) 
(396.6, 2521.5) 
6.2 
Randomization  
A participant’s randomization assignment will be computer generated and 
provided to the CRS pharmacist through a Web-based randomization system. 
Groups 1, 2, and 3 will be randomized in blocks to ensure balance across groups. 
The enrollment of Group 4 will be contingent on safety data from Groups 1-3 and 
hence Group 4 will not be randomized with Groups 1-3.  

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6.3 
Blinding 
Participants and CRS staff will be unblinded to participant group assignments. 
Laboratory program staff will remain blinded during sample analysis. 
6.4 
Statistical analyses 
All safety data from enrolled participants will be analyzed according to the initial 
randomization assignment regardless of how many study product administrations 
they received. In the rare instance that a participant receives the wrong treatment 
at a specific study product administration time, the Statistical Analysis Plan (SAP) 
will address how to analyze the participant’s safety data. Analyses of safety data 
are modified intent-to-treat (MITT) in that individuals who are randomized but 
not enrolled do not contribute data and hence are excluded. Because of the brief 
length of time between randomization and enrollment—typically no more than 4 
working days—very few such individuals are expected. The primary analysis of 
mAb concentration and neutralizing activity data are per-protocol (PP) in that 
only individuals who receive the expected mAb combination at the expect dose 
level within the expected visit window contribute data. Secondary analysis will 
also involve the MITT cohort. 
Analyses for primary endpoints will be performed using SAS and R. Additional 
software may be used to perform non-compartmental PK and population PK 
analyses (eg, NONMEM). All other descriptive and inferential statistical analyses 
will be performed using SAS, StatXact, or R statistical software. 
No formal multiple comparison adjustments will be employed for multiple 
primary or secondary endpoints. However, multiplicity adjustments will be made 
for certain primary or secondary endpoint assays, as discussed below, when the 
assay endpoint is viewed as a collection of hypotheses (eg, testing multiple 
pseudoviruses to determine a positive antiviral activity response). Unless 
otherwise noted, all statistical tests will be 2-sided and will be considered 
statistically significant if p < 0.05. 
6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, serum 
mAb concentrations, neutralization, and ADA for primary- and secondary-
objective analyses. 
6.4.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using 
descriptive statistics. 

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6.4.3 
Safety/tolerability analysis 
Since enrollment is concurrent with receiving the first study product 
administration, all participants will have received at least 1 product administration 
and therefore will provide some safety data. 
6.4.3.1 
Solicited AEs 
The number and percentage of participants experiencing each type of Solicited 
AE 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 Solicited AEs 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. Kruskal-Wallis tests will be used to test for 
differences in severity between arms. 
6.4.3.2 
SAEs and Unsolicited AEs 
Unsolicited 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 Unsolicted 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 Unsolicited 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 study product administration, and 
number of study product administrations received.  
6.4.3.3 
Local laboratory values  
Box plots 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 
box plot will show the first quartile, the median, and the third quartile. Outliers 
(values outside the box plot) will also be plotted. If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted. 
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 
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (version specified in SSP/SAP) will be tabulated by treatment arm for each 

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poststudy product administration timepoint. Reportable clinical laboratory 
abnormalities without an associated clinical diagnosis will also be included in the 
tabulation of AEs described above. 
6.4.3.4 
Reasons for study product administration discontinuation 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 
Serum concentration and PK analysis 
6.4.4.1 
Primary analyses of serum concentrations 
The primary analysis of serum concentration and pharmacokinetics of the 
evaluated mAbs (Primary bjective 2) will be restricted to participants who 
received all scheduled administrations per-protocol. Serum concentrations that 
appear unreliable, or from specimens collected outside of the visit window, or 
from HIV-infected participants postinfection may be excluded. The primary 
analysis of serum concentration will be descriptive and will be performed 
separately for each mAb. A non-compartmental pharmacokinetic analysis will be 
performed on the concentration data. Pharmacokinetic parameters may include, 
but are not limited to: area-under-the-curve (AUC), maximum concentration 
(Cmax), time to Cmax (Tmax), clearance (CL), volume of distribution (Vd), terminal 
elimination rate constant (λz) and the terminal half-life (T1/2). Data will be 
summarized by group and overall for CL, Vd, and T1/2. Graphical displays of the 
data (eg, boxplots, scatterplots, histograms, spaghetti plots) will be generated to 
visually explore distributional properties of the data as well as potential pairwise 
associations. These summary statistics and graphical displays may be produced 
for each treatment arm and each timepoint separately. 
6.4.4.2 
Exploratory analyses of serum concentrations via population PK models 
Population PK (popPK) models of each mAb may be developed to describe the 
overall kinetics of serum concentration and the variation of the kinetics between 
and within healthy, HIV-uninfected adults based on non-linear mixed effects 
models. Data from all enrolled participants will be analyzed regardless of how 
many administrations and how much mAb dose they received (MITT analysis). 
Serum concentration data from specimens collected outside of the visit window 
may be included in popPK analyses that account for the actual specimen 
collection time, and the actual time and dose amount of each product 
administration. Since the exact date of HIV infection is unknown, any serum level 
data from blood draws 4 weeks prior to an infected participant’s last seronegative 
sample and thereafter may be excluded. All data from HIV-infected participants 
who have no seronegative samples postenrollment may be excluded from the 
analysis. 

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The popPK models will describe the pharmacokinetics of each mAb at the 
individual level using a compartmental approach. Based on a previous population 
PK analysis of the serum concentrations of VRC01 (65), we anticipate that a two-
compartmental model can characterize the kinetics of the serum concentrations of 
the mAbs. In the event the modeling assumptions appear violated, we will 
consider other compartmental models. Comparisons of PK parameters across 
treatment groups will be performed using either likelihood ratio or Wald tests. 
Estimates of metrics of interest as a function of the PK parameters, including half-
life and steady state concentration will be derived from these analyses. 
6.4.5 
Analysis of neutralization activity and correlation with serum 
concentrations 
6.4.5.1 
Primary and secondary analyses of serum neutralization titers 
The primary analysis of serum neutralization titers against each mAb-specific 
virus will be restricted to participants who received all scheduled administrations 
per-protocol. Serum neutralization titers that appear unreliable, or from specimens 
collected outside of the visit window, or from HIV-infected participants 
postinfection may be excluded. This analysis of serum neutralization titers will be 
descriptive and will be performed separately for each mAb. To address Secondary 
objective 3, at each specified timepoint, the area-under-the-magnitude-breadth 
curve (AUC-MB) to a panel of viral isolates (77) will be computed for each 
participant with evaluable neutralization ID50 or ID80 data, as described in (78). 
Magnitude–Breadth (M-B) curves may be employed to display individual- and 
group-level response breadth as a function of magnitude. Response breadth is 
defined as the percentage of viruses in the panel with neutralization titer above 
certain thresholds. Two choices are to compare the M-B curves among arms, as 
follows: a non-parametric Wilcoxon rank sum test on the subject-specific area-
under-the M-B curve (AUC M-B) or a Kolmogorov-Smirnov type test on the 2 
group-average M-B curves. Simulations can be used to obtain 2-sided p-values for 
the latter test. Second, a weighted-average score-like variable may be constructed 
to account for the correlations between virus isolates as an integrated magnitude 
of responses to multiple isolates. Similar group comparison methods described in 
the first approach may be adopted. Details of either approach will be described in 
the SAP. 
6.4.5.2 
Secondary analyses of correlations between serum concentrations and 
serum neutralization levels 
To address Secondary objective 1, data from all enrolled participants will be 
analyzed regardless of how many administrations and how much mAb dose they 
received (MITT analysis). Besides descriptive analyses of the correlations, 
pharmacodynamics (PD) models based on either linear or non-linear mixed 
effects models may be performed to characterize the correlation between serum 
concentration (observed or popPK model-predicted) and serum neutralization 
against each virus or the AUC-MB of serum neutralization against the panel. 
Similar to the popPK analysis, data from specimens collected outside of the visit 

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window may be included in the PK/PD analyses that account for the actual 
specimen collection time, and the actual time and dose amount of each product 
administration. Since the exact date of HIV infection is unknown, any serum 
concentration data from blood draws 4 weeks prior to an infected participant’s last 
seronegative sample and thereafter may be excluded. All data from HIV-infected 
participants who have no seronegative samples postenrollment may be excluded 
from the analysis. 
6.4.6 
Analysis of ADA and other functional activities in serum 
For the analysis of ADA (Secondary objective 4), data from enrolled participants 
will be used regardless of how many administrations they received (MITT). For 
Exploratory objectives regarding non-neutralizing anti-viral functionality, data 
from all enrolled participants will be used. Assay results that are unreliable or 
from HIV-infected participants postinfection will be excluded. Additional 
exploratory analyses examining the impact of ADA on PK will be described in 
the SAP. 
Univariate and bivariate descriptive analyses of continuous assay data (eg, 
ADCC) will be performed using mean, median, standard deviation, range, 
skewness, Spearman’s and Pearson’s correlation coefficients, for example. 
Graphical displays of the data based on appropriate techniques (eg, boxplots, 
histograms, kernel density estimates, probability plots, two- or three-dimensional 
scatterplots, spaghetti plots) will be generated to visually explore distributional 
properties of the data as well as potential pairwise associations. Statistics and 
graphical displays will be produced for each treatment arm across timepoints. 
Comparisons of continuous assay data between treatment groups or timepoints 
will be primarily performed using nonparametric rank-based tests, the Wilcoxon 
rank-sum test, or Friedman nonparametric two-way analysis of variance 
(ANOVA). In the event the data appear normally distributed, the results of these 
tests may be compared to those produced by parametric tests (eg, two-sample t-
tests with unequal variances). Appropriate data transformations (eg, square-root, 
logarithmic) may be applied prior to testing hypotheses in order for key 
distributional assumptions [eg, normality, homoscedasticity (ie, constancy of 
variance)] to be satisfied. 
Analyses of categorical variables (eg, binary) will be conducted by constructing 
frequency tables. One such table will be produced for each treatment group and 
each timepoint. Crude response rates will be presented with their corresponding 
95% confidence interval estimates calculated using the score test method (72). 
Associations between categorical variables will be assessed using Fisher’s exact, 
Barnard’s exact, or Chi-squared tests. 
Analysis of longitudinal data may be performed using mixed effects models or 
generalized estimating equations (GEE). These approaches allow describing 

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outcome responses over several timepoints while accounting for potential inter-
subject heterogeneity. 
To achieve unbiased statistical estimation and inferences with nonparametric tests 
and generalized linear models fit by GEE methods, missing data need to be 
missing completely at random (MCAR). MCAR assumes that missingness does 
not depend on any observed or unobserved data (ie, the observed data is just a 
random sample of all the potential data). When missingness is negligible (eg, less 
than 20%), statistical methods (eg, nonparametric tests and GEE methods) based 
on the MCAR assumption can be used with limited impact on the analysis. 
When the frequency of missing data is more substantial, methods that require the 
MCAR assumption may give misleading results. In this situation, statistical 
analyses will be performed based on appropriate modeling assumptions and 
adjusted using weighting methods, or combined with imputation, under the 
assumption that the missing data are missing at random (MAR). MAR assumes 
that the probability of an observation being missing only depends on the observed 
responses or covariates. Thus, this assumption is less stringent than the MCAR 
assumption. Weighting adjustments (eg, weighted GEE) and imputation methods 
are valid under MAR. We will consider including any of the available baseline 
predictors of the missing outcomes as covariates in statistical models. Please see 
Little and Rubin [(79), Chapters 1, 3, and 6] for elaborate definitions and 
examples of missing data mechanisms and Ibrahim et al (80) for a review of 
missing data methods in clinical studies. 
Generalized linear models for response rates will use a binomial error distribution 
and for quantitative endpoints, a normal error distribution. We will assess 
repeated functional measurement using linear mixed effects models. If functional 
activity outcomes are left- and/or right- censored, we will use Hughes’ (73) linear 
mixed effects models to accommodate censoring. In addition, exploratory 
analyses of repeated functional measurements may be done using weighted GEE 
(74) methods, which are valid under MAR. We will again consider including any 
of the available baseline predictors of the missing outcomes as covariates in 
statistical models.  
6.4.7 
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 
or laboratory endpoint assessments.  
6.4.7.1 
Safety 
During the course of the trial, analyses of safety data will be prepared 
approximately every 4 months for review by the SMB. Ad hoc safety reports may 
also be prepared for SMB review at the request of the HVTN 130/HPTN 089 
PSRT.  

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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 information available at the time of 
enrollment, including results of screening 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 other endpoints 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. Access to a participating CRS and willingness to be followed for the planned 
duration of the study 
3. Ability and willingness to provide informed consent 
4. Assessment of understanding: volunteer demonstrates understanding of this 
study and completes a questionnaire prior to first study product administration 
with verbal demonstration of understanding of all questionnaire items answered 
incorrectly 
5. Agrees not to enroll in another study of an investigational research agent until 
completion of the last required protocol clinic visit 
6. Good general health as shown by medical history, physical exam, and screening 
laboratory tests 
HIV-Related Criteria: 

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7. Willingness to receive HIV test results 
8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction 
counseling 
9. Assessed by the clinic staff as being at “low risk” for HIV infection and 
committed to maintaining behavior consistent with low risk of HIV exposure 
through the last required protocol clinic visit (see Appendix K) 
Laboratory Inclusion Values 
Hemogram/Complete Blood Count 
10. Hemoglobin ≥ 11.0 g/dL for volunteers who were assigned female sex at birth, 
≥13.0 g/dL for volunteers who were assigned male sex at birth. For transgender 
participants who have been on feminizing hormone therapy for more than 6 
consecutive months, determine hemoglobin eligibility based on the gender with 
which they identify (ie, a transgender female who has been on hormone therapy 
for more than 6 consecutive months should be assessed for eligibility using the 
hemoglobin parameters for persons assigned female sex at birth). 
11. White blood cell count = 2,500 to 12,000 cells/mm3 
12. WBC differential either within institutional normal range or with site clinician 
approval 
13. Platelets = 125,000 to 550,000/mm3 
Chemistry 
14. Chemistry panel: ALT < 1.25 times the institutional upper limit of normal; 
creatinine ≤ institutional upper limit of normal 
Virology 
15. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-
approved enzyme immunoassay (EIA) or chemiluminescent microparticle 
immunoassay (CMIA). 
16. Negative Hepatitis B surface antigen (HBsAg)  
17. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV 
polymerase chain reaction (PCR) if the anti-HCV is positive 
Urine 
18. Negative or trace urine protein 

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Reproductive Status 
19. Volunteers who were assigned female sex at birth: negative serum or urine beta 
human chorionic gonadotropin (β-HCG) pregnancy test performed prior to study 
product administration on the day of initial study product administration. Persons 
who are NOT of reproductive potential due to having undergone total 
hysterectomy or bilateral oophorectomy (verified by medical records), are not 
required to undergo pregnancy testing. 
20. Reproductive status: A volunteer who was assigned female sex at birth must: 
• Agree to use effective contraception 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 one of the 
following methods: 
 Condoms (male or female) with or without a spermicide, 
 Diaphragm or cervical cap with spermicide, 
 Intrauterine device (IUD), 
 Hormonal contraception,  
 Tubal ligation, 
 Any other contraceptive method approved by the HVTN 130/HPTN 089 
PSRT 
 Successful vasectomy in any partner assigned male sex at birth 
(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 reached menopause (no 
menses for 1 year) or having undergone hysterectomy or bilateral 
oophorectomy; 
• Or be sexually abstinent. 
21. Volunteers who were assigned female sex at birth 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. 
7.2 
Exclusion criteria 
General 
1. Weight > 115 kg  

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2. Blood products received within 120 days before first study product 
administration, unless eligibility for earlier enrollment is determined by the 
HVTN 130/HPTN 089 PSRT 
3. Investigational research agents received within 30 days before first study 
product administration 
4. Intent to participate in another study of an investigational research agent or 
any other study that requires non-Network HIV antibody testing during the 
planned duration of the HVTN 130/HPTN 089 study  
5. Pregnant or breastfeeding 
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 130/HPTN 089 
PSRT will determine eligibility on a case-by-case basis. 
7. Previous receipt of humanized or human mAbs, whether licensed or 
investigational; the HVTN 130/HPTN 089 PSRT will determine eligibility on a 
case-by-case basis. 
8. Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-
523LS, PGT121, PGDM1400, or 10-1074 
Immune System  
9. Immunosuppressive medications received within 30 days before first study 
product administration (Not exclusionary: [1] corticosteroid nasal spray; [2] 
inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated 
dermatological condition; or [4] a single course of oral/parenteral prednisone or 
equivalent at doses < 20 mg/day and length of therapy < 14 days.) 
10. Serious adverse reactions to VRC07-523LS, PGT121, PGDM1400, or 10-1074 
formulation components (acetate, sucrose, polysorbate 80, histidine, and sorbitol; 
see Section 8.2), including history of anaphylaxis and related symptoms such as 
hives, respiratory difficulty, angioedema, and/or abdominal pain 
11. Immunoglobulin received within 90 days before first study product 
administration, unless eligibility for earlier enrollment is determined by the 
HVTN 130/HPTN 089 PSRT (for mAb see criterion 7 above) 
12. Autoimmune disease (Not excluded from participation: Volunteer with mild, 
stable and uncomplicated autoimmune disease that does not require 
immunosuppressive medication and that, in the judgment of the site investigator, 
is likely not subject to exacerbation and likely not to complicate Solicited and 
Unsolicited AE assessments) 

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13. Immunodeficiency 
Clinically significant medical conditions  
14. 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 inability 
to establish venous or sub-cutaneous access. 
• 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 (eg, chronic urticaria or recent injection or infusion 
with evidence of residual inflammation) for which signs or symptoms could 
be confused with reactions to the study product, or 
• Any condition specifically listed among the exclusion criteria. 
15. Any medical, psychiatric, occupational, or skin condition (eg, tattoos) that, in 
the judgment of the investigator, would interfere with, or serve as a 
contraindication to, protocol adherence, assessment of safety, Solicited AEs, or a 
volunteer’s ability to give informed consent 
16. 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. 
17. Current anti-tuberculosis (TB) therapy 
18. 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: 
• 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 had either of the following: 

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 Greater than 1 exacerbation of symptoms treated with oral/parenteral 
corticosteroids; 
 Needed emergency care, urgent care, hospitalization, or intubation for 
asthma. 
19. Diabetes mellitus type 1 or type 2 (Not exclusionary: type 2 cases controlled with 
diet alone or a history of isolated gestational diabetes) 
20. 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. 
21. Bleeding disorder diagnosed by a clinician (eg, factor deficiency, coagulopathy, 
or platelet disorder requiring special precautions) 
22. 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.) 
23. 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. 
24. Asplenia: any condition resulting in the absence of a functional spleen 
25. History of hereditary angioedema, acquired angioedema, or idiopathic 
angioedema 
7.3 
Participant departure from study product administration schedule or 
withdrawal (Group 4 only) 
This section concerns an individual participant’s departure from the study product 
administration schedule. Pause rules for the trial are described in Section 11.4. 

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7.3.1 
Delaying study product administrations for a participant  
Under certain circumstances, a participant’s scheduled study product 
administration will be delayed. Refer to the HVTN 130/HPTN 089 SSP for 
further guidance regarding which procedures to conduct in these instances. The 
factors to be considered in such a decision include but are not limited to the 
following: 
• Within 7 days prior to study product administration  
 Receipt of systemic glucocorticoids (eg, prednisone or other 
glucocorticoids) or other immunomodulators (other than nonsteroidal anti-
inflammatory drugs [NSAIDs]) 
• Preinfusion abnormal vital signs or clinical symptoms that may mask 
assessment of study product reactions 
• Intercurrent illness that is assessed by the site principal investigator (or 
designee) to require delaying product administration. The investigator may 
consult the HVTN 130/HPTN 089 PSRT. 
• Pregnancy: study product administration will be stopped while a participant is 
pregnant. If the participant is no longer pregnant (as defined by 2 consecutive 
negative tests) or breast-feeding and study product administration can be 
performed within an appropriate visit window, study product administration 
may resume with unanimous consent of the HVTN 130/HPTN 089 PSRT. 
Do not administered study product outside the Visit 9 window specified in the 
Section 9.9. If the study product administration is not completed within this visit 
window, the participant should continue with remaining study visits. 
7.3.2 
Discontinuing study product administration for a participant  
Under certain circumstances, an individual participant’s study product 
administrations will be permanently discontinued. Specific events that will result 
in stopping a participant’s study product-administration schedule include: 
• Co-enrollment in a study with an investigational research agent (rare 
exceptions allowing for the continuation of study product administrations may 
be granted with the unanimous consent of the HVTN 130/HPTN 089 PSRT) 
• Clinically significant condition (ie, a condition that affects the immune system 
or for which continued study product administrations and/or blood draws may 
pose additional risk), including but not limited to the following: 
 HIV infection 
 Any grade 4 local or systemic Solicited or Unsolicited AE that is 
subsequently considered to be related to study product administration 

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 Grade 3 clinical AE that is subsequently considered to be related to study 
product administration with the exception of fever, vomiting, and 
subjective local and systemic symptoms. For grade 3 infusion site 
erythema and/or induration, upon review, the HVTN 130/HPTN 089 
PSRT may allow continuation of study product.  
 Any grade 3 or 4 lab abnormality confirmed by a repeated value that is 
subsequently considered to be related to study product; 
 SAE that is subsequently considered to be related to study product 
administration 
 Clinically significant hypersensitivity or mAb reaction including, but not 
limited to, type 1 hypersensitivity reaction, urticaria, or serum sickness 
associated with study product administration. Consultation with the 
HVTN 130/HPTN 089 PSRT is required prior to subsequent study product 
administrations following any hypersensitivity reaction associated with 
study product administration 
• 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 (see 
HVTN 130/HPTN 089 SSP). 
Participants diagnosed with HIV infection during the study should be encouraged 
to participate in follow-up visits as indicated in Section 9.12.  
7.3.3 
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 CRS is not 
possible, 
• CRS determines that the participant is lost to follow-up,  
• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff), or 

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• Any condition where termination from the study is required by applicable 
regulations. 

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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 Section 1. See the IB for further information about study 
products. 
8.1 
Study product regimen 
The schedule of study product administration is shown in Section 1 and additional 
information is given below.  
Group 1 
Treatment 1 (T1): PGT121 20 mg/kg AND VRC07-523LS 20 mg/kg to be 
administered IV sequentially in this order at Month 0. 
Group 2 
Treatment 2 (T2): PGDM1400 20 mg/kg AND VRC07-523LS 20 mg/kg to be 
administered IV sequentially in this order at Month 0. 
Group 3 
Treatment 3 (T3): 10-1074 20 mg/kg AND VRC07-523LS 20 mg/kg to be 
administered IV sequentially in this order at Month 0. 
Group 4 
Treatment 4 (T4): PGDM1400 20 mg/kg AND PGT121 20 mg/kg AND VRC07-
523LS 20 mg/kg to be administered IV sequentially in this order at Month 0 and 
Month 4. 
8.2 
Study product formulation  
8.2.1 
PGT121 (Labeled as PGT121) 
PGT121 will be supplied as 10 mL single-use glass vials with 6 mL fill volume, at 
a concentration of 50 mg/mL. Upon thaw, each vial contains a clear, colorless to 
slightly yellow solution for injection, which is essentially free from foreign 
particles. The formulation buffer is composed of 20 mM acetate, 9% w/v sucrose, 
and 0.008% w/v polysorbate 80 at pH 5.2 in Water for Injection (WFI). It does 
not contain a preservative.  
The product is stored frozen at -25 ºC to - 15 ºC. The study product is described in 
further detail in the IB. 

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8.2.2 
PGDM1400 (Labeled as PGDM1400) 
PGDM1400 will be supplied as 10 mL single-use glass vials with a 6 mL fill 
volume, at a concentration of 50 mg/mL. Upon thaw, each vial contains a clear, 
colorless to slightly yellow solution for injection, which is essentially free from 
foreign particles. The formulation buffer is composed of 20 mM Acetate, 9% w/v 
Sucrose, 0.008% w/v Polysorbate 80 at pH 5.2 in WFI. It does not contain a 
preservative. 
The product is stored frozen at -25°C to -15°C. The study product is described in 
further detail in the IB. 
8.2.3 
10-1074 (Labeled as 10-1074) 
10-1074 will be supplied as 50 mL single-use glass vials with a 30 mL fill 
volume, at a concentration of 20 mg/mL. Upon thaw, each vial contains a clear, 
colorless to yellow liquid, which is essentially free of visible particles. The 
formulation buffer is composed of Potassium Phosphate, Monobasic, NF, BP, EP 
0.20 mg; Sodium Phosphate, Monobasic, Monohydrate, USP, BP, EP 0.25 mg; 
Sodium Chloride, USP, FCC 8.00 mg; Potassium Chloride, USP, FCC 0.20 mg; 
Sodium Phosphate, Dibasic, Heptahydrate, USP, EP 1.67 mg; Polysorbate 80 
(plant derived), NF, EP, JP 0.10 mg; and WFI Quality water, USP, q.s. to 1 mL. It 
does not contain a preservative. 
The product is stored at 2°C to 8°C. The study product is described in further 
detail in the IB. 
8.2.4 
VRC07-523LS (Labeled as VRC07-523LS HIV MAb Drug Product VRC-
HIVMAB075-00-AB) 
VRC07-523LS will be supplied as 10 mL single-use glass vials with a 6.25 ± 0.1 
mL fill volume and 3 mL single-use glass vials with a 2.25 mL ± 0.1 mL fill 
volume, at a concentration of 100 ± 10 mg/mL. Each vial contains 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 50 
mM histidine, 50 mM sodium chloride, 5% sucrose, and 2.5% sorbitol at pH 6.8. 
Vials do not contain a preservative. 
VRC07-523LS product label designates the long-term storage as -35ºC to -15 ºC 
(-31 ºF to 5 ºF). The study product is described in further detail in the IB. 
8.3 
Preparation of study products 
Prior to preparation of the first infusion (enrollment visit), a new prescription will 
be sent to the pharmacy. The prescription MUST contain the participant’s weight 
based upon the participant’s weight at the most recent visit where weight was 
measured (this includes screening). If this information is NOT on the prescription, 

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the prescription will be returned to the clinic from the pharmacy to be completed 
appropriately prior to the pharmacist beginning preparation of study product. 
Subsequent visit weights (based upon the participant’s weight at the most recent 
visit where weight was measured) must be communicated to the pharmacy in 
writing prior to the day of the visit. Any changes in weight of more than 10% 
(between the prior weight and the weight on the day of the infusion visit) will 
require an updated visit weight communication to the pharmacy in writing so that 
product can be prepared based on that weight change.  
Pharmacists should keep in mind that the preparation instructions below are 
considered medium risk per USP 38 General Chapter Physical Tests / <797> 
Pharmaceutical Compounding - Sterile, and should follow the requirements of 
their country, their institution, and their pharmacy regulatory authority regarding 
these procedures. 
Any unused portion of study product will not be used for another participant. Any 
empty vials, unused portion of entered vials, or unused solution which contains 
study product should be discarded in a biohazard containment bag and incinerated 
or autoclaved in accordance with institutional or pharmacy policy.  
8.3.1 
PGT121 
8.3.1.1 
Thawing instructions 
1. Remove PGT121 vial(s) from freezer and thaw in a room temperature water 
bath or in a clean beaker/container of water at room temperature, ensuring the 
vial(s) are not submerged. Swish vial(s) in the water to help facilitate thawing. 
2. Once thawed, mix vial contents by gently inverting vial(s) five times. 
8.3.1.2 
PGT121 intravenous infusion preparation 
1. Calculate the total dose (mg) of PGT121 required based on the participant’s 
weight (in kg). Obtain the minimum number of thawed PGT121 vials, as well 
as an appropriately sized IV container (bag/glass bottle) containing 100 mL of 
Sodium Chloride for Injection, 0.9% USP that will also permit the addition of 
the required calculated volume of PGT121.  
2. Using an 18G needle, withdraw the calculated volume of PGT121 into a 
sterile syringe. 
3. Using aseptic technique, add the withdrawn volume of PGT121 to the IV 
container with 100 mL of Sodium Chloride for Injection. 9.9% USP. Record 
this as the study product preparation time. Assign a 4-hour expiration 
from this time. 
4. Gently mix the prepared IV container. Ensure there are no visible particulates 
in the IV container.  

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8.3.2 
PGDM1400  
8.3.2.1 
Thawing instructions 
1. Remove PGDM1400 vials from freezer and thaw in a room temperature water 
bath or in a clean beaker/container of water at room temperature, ensuring the 
vials are not submerged. Swish vial(s) in the water to help facilitate thawing. 
2. Once thawed, mix vial contents by gently inverting vial(s) five times. 
8.3.2.2 
PGDM1400 intravenous infusion preparation 
1. Calculate the total dose (mg) of PGDM1400 required based on the 
participant’s weight (in kg). Obtain the minimum number of thawed 
PGDM1400 vials, as well as an appropriately sized IV container (bag/glass 
bottle) containing 100 mL of Sodium Chloride for Injection, 0.9% USP, that 
will also permit the addition of the required calculated volume of PGDM1400.  
2. Using an 18G needle, withdraw the calculated volume of PGDM1400 into a 
sterile syringe. 
3. Using aseptic technique, add the withdrawn volume of PGDM1400 to the IV 
container with 100 mL of Sodium Chloride for Injection 0.9% USP. Record 
this as the study product preparation time. Assign a 4-hour expiration 
from this time. 
4. Gently mix the prepared IV container. Ensure there are no visible particulates 
in the IV container. 
8.3.3 
10-1074  
8.3.3.1 
10-1074 intravenous infusion preparation 
1. Calculate the total dose (mg) of 10-1074 required based on the participant’s 
weight (in kg). Remove the minimum number of 10-1074 vials from 
refrigerated storage, as well as an appropriately sized IV container (bag/glass 
bottle) containing 100 mL of Sodium Chloride for Injection, 0.9% USP, that 
will also permit the addition of the required calculated volume of 10-1074.  
2. Using aseptic technique, add the withdrawn volume of 10-1074 to the IV 
container with 100 mL of Sodium Chloride for Injection, 0.9% USP. Record 
this as the study product preparation time. Assign a 24-hour expiration 
from this time. 
3. After product preparation, 10-1074 should be administered within 24 hours, if 
stored at room temperature. 

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8.3.4 
VRC07-523LS 
VRC07-523LS is a highly concentrated protein solution and may develop white, 
opaque to translucent particles after thawing. 
8.3.4.1 
Thawing instructions  
1. Thaw vial(s) for a minimum of 1 hour at controlled room temperature 
(maximum 27°C) after removing from the freezer.  
2. Keep the material at room temperature during the entire preparation period 
until use, up to the maximum storage times described in # 4 below.  
3. Prior to preparation for administration, swirl vials for 30 seconds to resuspend 
any visible particles, avoid foaming. DO NOT SHAKE THE VIALS. If 
particles are observed, return the vials to 2°C to 8°C storage. If the 
particles re-dissolve within the maximum storage times described in # 4 
below, they may be used for product preparation. If particles continue to be 
observed, do not use the vials.  
4. Thawed vials may be stored for up to 24 hours at controlled room temperature 
(maximum 27°C) and/or up to 2 weeks (14 days) at 2°C to 8°C. Product may 
not be stored in direct sunlight. If stored at 2 ºC to 8 ºC, vials must be 
equilibrated at controlled room temperature (maximum 27 ºC) for a minimum 
of 30 minutes and may be held at room temperature for up to 8 hours prior to 
product preparation. 
8.3.4.2 
VRC07-523LS intravenous infusion preparation 
1. Calculate the total dose (mg) of VRC07-523LS required based on the 
participant’s weight (in kg). Remove the minimum number of thawed particle-
free VRC07-523LS vials from storage, as well as an appropriately sized IV 
container (bag/glass bottle) containing 100 mL of Sodium Chloride for 
Injection, 0.9% USP, that will also permit the addition of the required 
calculated volume of VRC07-523LS.  
2. Gently swirl thawed vials for 30 seconds, avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright at all times until ready to withdraw 
the contents. Do not invert the vials during inspection.  
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.4.1.  
4. Using aseptic technique, add the calculated volume of VRC07-523 LS to the 
IV container with 100 mL of Sodium Chloride for Injection, 0.9 USP. Record 
this as the study product preparation time.  

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5. The prepared VRC07-523LS IV container may be stored at 2°C to 8°C up to 
48 hours or at controlled room temperature (maximum 27°C) for a maximum 
of 4 hours total including the infusion time. Product may not be stored in 
direct sunlight. If stored at 2°C to 8°C, prepared product must be equilibrated 
at controlled room temperature (maximum 27°C) for a minimum of 30 
minutes prior to product administration.  
8.3.5 
Labeling of Study Product 
Label the study product as follows:  
• Participant identifier(s)  
• Participant weight (in kg) 
• Study product name  
• Total dose (mg)  
• Final volume (mL) 
• Infusion time  
• Beyond use date and time  
• Any additional information required by jurisdiction  
8.4 
Administration 
The container prepared by the pharmacy will include the weight that was used for 
preparation of the study product. The clinician responsible for administration will 
check the container label and confirm that the participant identifier(s) is/are 
correct and that the weight listed on the container label is within 10% of the 
participant’s current actual weight. A filter must be used for product 
administration. Filters must comply with the specifications described in the 
HVTN 130/HPTN 089 SSP. When the filter is added to the tubing, prime the 
administration set with normal saline for injection. 
In Groups 1-3, 2 separate IV containers each containing one study product will be 
administered sequentially. In Group 4, 3 separate containers, each containing one 
study product, will be administered sequentially.  

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8.4.1 
PGT121  
PGT121 will be administered IV over 60 minutes at the Month 0 visit. For 
participants in Group 4, the subsequent infusion at the Month 4 visit may be 
administered IV over 30 minutes. 
8.4.2 
PGDM1400  
PGDM1400 will be administered IV over 60 minutes at the Month 0 visit. For 
participants in Group 4, the subsequent infusion at the Month 4 visit may be 
administered IV over 30 minutes. 
8.4.3 
10-1074  
10-1074 will be administered IV over 60 minutes at the Month 0 visit. 
8.4.4 
VRC07-523LS  
VRC07-523LS will be administered IV over 60 minutes at the Month 0 visit. For 
participants in Group 4, the subsequent infusion at the Month 4 visit may be 
administered IV over 15-30 minutes. 
8.5 
Acquisition of study products 
PGT121 is provided by Beth Israel Deaconess Medical Center (Boston, MA, 
USA). 
PGDM1400 is provided by Beth Israel Deaconess Medical Center (Boston, MA, 
USA). 
10-1074 is provided by the National Institute of Allergy and Infectious Diseases 
(NIAID), NIH, DHHS (Bethesda, MD, USA).  
VRC07-523LS is provided by Dale and Betty Bumpers Vaccine Research Center 
(VRC), NIAID, NIH, DHHS (Bethesda, MD, USA). 
Once a CRS is protocol registered, the pharmacist can obtain study products from 
the NIAID Clinical Research Products Management Center (CRPMC) by 
following the ordering procedures outlined in Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks. 
Filters, tubing, and 0.9% sodium chloride for injection will be locally sourced by 
the site. Please refer to the study product considerations section of the HVTN 
130/HPTN 089 SSPs for product specific reference numbers.  

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8.6 
Pharmacy records 
The 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 
For US clinical research sites, all unused study products must be returned to the 
CRPMC after the study is completed or terminated unless otherwise instructed by 
the study sponsor. For non-US clinical research sites, all unused study products 
must be destroyed after the study is completed or terminated unless otherwise 
instructed by the study sponsor. The procedures 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 I and Appendix J. 
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 informed consent form (ICF) documents that a participant (1) has been 
informed about the potential risks, benefits, and alternatives to participation, and 
(2) is willing to participate in the study. Informed consent encompasses all written 
or verbal study information CRS staff provide to the participant, before and 
during the trial. CRS staff will obtain informed consent of participants according 
to HVTN and HPTN 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, 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. 
A CRS may employ recruitment efforts prior to the participant consenting. For 
example, some 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. CRSs must submit recruitment and prescreening materials to their 
IRB/EC and any applicable 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 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 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 
prevention clinical trial. In this way, CRS staff can continually screen potential 
participants and, when needed, proceed quickly to obtain protocol-specific 

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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. 
Sample protocol-specific consent forms for the main study are located in 
Appendix A and Appendix B. A separate sample consent form for other uses of 
specimens is located in Appendix D. 
Each 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, 
Appendix B, and Appendix D. The consent form(s) must be developed in 
accordance with requirements of the following: 
• CRS’s IRB/EC and any applicable REs, 
• CRS’s institution, and 
• Elements of informed consent as described in Title 45, CFR Part 46 and 
Title 21 CFR, Part 50, and in ICH E6, Good Clinical Practice: 
Consolidated Guidance 4.8.  
Study sites are strongly encouraged to have their local CABs review their sites-
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 forms include instructions for developing specific 
content. 
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 is responsible for ensuring that participants fully understand the study 
before enrolling them. This process involves reviewing the informed 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 clinical 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. 

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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 study product administration on day 0. 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 (see 
Appendix K).  
• 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; and skin 
• 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 
• Laboratory tests including: 
 Screening HIV 
 Hepatitis B surface antigen (HBsAg), 
 Anti-HCV Abs, 
 Syphilis, 
 Complete Blood Count (CBC) with differential, 
 Chemistry panel (alanine aminotransferase [ALT], creatinine), 
 Urine dipstick (urinalyses if indicated; see Section 9.7), 

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 Urine or serum pregnancy test (volunteers who were assigned female sex 
at birth); persons who are not of reproductive potential due to having 
undergone total hysterectomy with bilateral oophorectomy (verified by 
medical records) are not required to undergo pregnancy testing; 
• Administration of behavioral risk assessment questionnaire 
• Obtaining of 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 9.5 
• 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 assigned 
female sex at birth 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. 
9.2.1 
Use of screening results from another HVTN or HPTN study 
If a participant screens for an HVTN or HPTN study at the same 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 (see Sections 7.1 and 7.2). 
9.3 
Enrollment and study product administration visits 
Enrollment is simultaneous with first study product administration. The CRS 
requests the randomization assignment via a Web-based randomization system. In 
general, the time interval between randomization and enrollment should not 
exceed 4 working days. However, circumstances may require a participant’s 
enrollment visit to be changed. This may exceed the 4-day randomization time 
limit. 

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At all study product administration visits, the following procedures are performed 
before study product administration: 
• 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 Solicited AEs; 
• Assessment of concomitant medications (as described in Section 9.2); 
• Assessment of any new AEs/intercurrent illnesses; and 
• Clinical laboratory tests including: 
 CBC with differential; 
 Chemistry panel (see Section 9.2), and 
 Urine or serum pregnancy test (for participants who were assigned female 
sex at birth). Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing; 
Following completion of all procedures in the preceding list, and if results 
indicate that study product administration may proceed, study product is 
administered (see Sections 8.3 and 8.4). 
Administration of all infusions during a study product administration visit must be 
accomplished within 1 calendar day. 
Immediately following study product administration, the participant remains in 
the clinic for observation for 1 hour. At the end of this 1-hour observation period, 
samples are drawn for PK testing (see Appendix G and Appendix H). 
See the HVTN 130/HPTN 089 SSP for details regarding infusion visit protocols 
and subsequent infusion observation and Solicited AE assessment procedures that 
CRSs must follow. The site will make arrangements to be in contact with the 
participant following the Solicited AE period (as described in Section 9.8 and the 
HVTN 130/HPTN 089 SSP). 
The following procedures will be performed at all study product administration 
visits. These procedures may be performed prior to or following study product 
administration:  
• Risk reduction counseling (as described in Section 9.5);  

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• For participants capable of becoming pregnant, contraception status 
assessment (as described in Section 9.2 and 9.6). In persons who are 
confirmed pregnant, contraception status assessment is not required; 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). 
The following procedure will be performed at all infusion visits following study 
product administration: 
•  Acceptability questionnaire. 
Additional procedures will be performed at scheduled visits as specified in 
Appendix I and Appendix J: 
• Specimen collection (should be completed per Appendix G and Appendix H). 
• HIV infection assessment including pretest counseling and HIV testing. 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, 
9.3.1 
Managing infusion reactions 
Since PGT121, PGDM1400, 10-1074, and VRC07-523LS are human mAbs that 
target a viral antigen rather than human cell surface antigens, serious mAb 
reactions are expected to be rare. Nevertheless, participants will be closely 
monitored in the clinic during study product administration and during a post-
infusion observation period. CRS staff are trained to recognize suspected mAb 
reactions and to provide immediate medical care consistent with CRS SOP. 
Medications used to treat mAb reactions may include: acetaminophen, 
antihistamines, and corticosteroids. CRSs are also equipped with additional 
emergency medical supplies to provide immediate medical interventions and are 
near medical emergency services. Should the need arise, CRSs may transfer the 
participant, once stabilized, to a tertiary care center for further management.  
The following procedures should be performed after a mAb reaction: 
• mAb reaction clinical assessment; 
• mAb reaction blood collection. 
For detailed instructions regarding management of mAb reactions see the HVTN 
130/HPTN 089 SSP.  

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9.4 
Follow-up visits 
The following procedures are performed at scheduled follow-up visits as specified 
in Appendix I and Appendix J: 
• Risk reduction counseling (as described in Section 9.5);  
• Contraception status assessment (as described in Section 9.2 and 9.6); and 
• Administration of behavioral risk assessment questionnaire 
• 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 (as described in 
Section 9.2); and 
• Assessment of new or unresolved Unsolicited AEs/intercurrent illnesses; 
• 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); 
• HIV infection assessment including pretest counseling and HIV testing. 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 (should be completed per Appendix G and Appendix H); 
• Clinical laboratory tests including: 
 CBC with differential, 
 Chemistry panel (see Section 9.2), and 

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 Urine dipstick (urinalysis if appropriate; see Section 9.7); and 
 Urine or serum pregnancy test (for participants who were assigned female 
sex at birth). Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. During follow-up 
in persons who are confirmed pregnant, pregnancy testing is not required, 
unless clinically indicated. 
9.4.1 
Interim contacts 
CRSs may report safety information obtained at a contact other than the regularly 
scheduled visits. These contacts are reported as interim visits. 
9.5 
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 protocol-specific 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 HIV-infected will be 
referred for medical treatment, counseling, and management of the HIV infection. 
With respect to enrolled participants who become HIV-infected, see Section 9.12. 
It is theoretically possible that an anti-HIV mAb may suppress viral replication, 
which can reduce the ability to detect HIV, even if a person is actually infected.  
An anti-HIV mAb is not likely to directly reduce or inhibit the assays used to 
detect HIV-1 infection. 
9.5.1 
Study product-related seroreactivity 
Tests of human plasma containing VRC07-523LS have been conducted using a 
variety of commercially available HIV test kits. At high plasma concentrations, 
reactive or indeterminate results have been observed on some test kits. See the 
HVTN 130/HPTN 089 SSP for further detail. Thus, there is a possibility that 
receipt of the study product will cause a reactive result on some currently 
available HIV test kits, especially if testing occurs close to study product 
administration timepoints. 
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 

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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.  
9.6 
Contraception status 
Contraception status is assessed and documented at clinic visits indicated in 
Appendix I and Appendix J for a participant who was assigned female sex at birth 
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 assigned female sex at birth 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. 
Self-reported infertility—including having reached menopause (no menses for 1 
year) or having undergone hysterectomy or bilateral oophorectomy—must be 
documented in the participant’s study record. 
9.7 
Urine testing 
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. 
menstruation) or infection, document this issue in the participant’s source 
documentation. For infection, provide appropriate treatment and/or referral and 
document this in the participant’s chart. Following resolution, repeat the dipstick 
and, if within the eligibility limits specified in the protocol, the participant may be 
enrolled. 
Follow-up visit dipstick testing should be deferred if a participant is menstruating 
but should be performed as soon as possible. If a follow-up dipstick is abnormal 

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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. If a follow-up visit dipstick or 
micro-urinalysis is abnormal due to infection, provide appropriate treatment 
and/or referral and document this in the participant's source documentation. See 
the Urinalysis Sample Collection, Interpretation, Management, and Reporting 
section in the Ab MOP for further details. 
9.8 
Assessments of Solicited AEs 
For all participants, baseline assessments are performed before and Solicited AE 
assessments are performed after each study product administration. All Solicited 
AEs 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 Solicited AE assessment period is 3 full days following each study product 
administration per the assessment schedule shown in Table 9-1. Participants are 
instructed to record symptoms using a Participant Diary. CRS staff and the 
participant will be in contact after the 3-day Solicited AE assessment period, or 
sooner if indicated. See the HVTN 130/HPTN 089 SSP for further details. In 
general, a participant who self-reports any poststudy product administration 
reaction greater than mild is seen by a clinician within 48 hours after onset, unless 
the reaction is improving and/or has completely resolved. Clinic staff will follow 
new or unresolved Solicited AEs present at day 3 to resolution. 
Solicited AEs are reported using CRFs that correspond to the time of assessment 
in Table 9-1. Solicited AE assessments include assessments of systemic and local 
symptoms, and study product-related lesions. Events not listed on a CRF, or with 
an onset after the Solicited AE assessment period (day of study product 
administration and 3 full days after), or those meeting SAE/Unsolicited AEs 
requiring expedited reporting to DAIDS criteria, are recorded on an AE Log.  

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Table 9-1 Schedule of Solicited AE assessments 
Day 
Time 
Performed by 
0a 
Baseline: before study product 
administration 
CRS clinician 
 
Early: 25-60 minutes after study product 
administration 
CRS clinician 
 
Between early assessment and 11:59pm 
day 0 
CRS clinician or participant 
1-3b 
Between 12:00am and 11:59pm on the 
respective day 
CRS clinician or participant 
a Day of study product administration 
b New or unresolved Solicited AEs present on day 3 are followed until resolution 
9.8.1 
Assessment of systemic and local symptoms 
Systemic symptoms to be assessed as Solicited AEs in this trial include increased 
body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, 
nausea, urticaria, non-exertional dyspnea, non-exertional tachycardia (assessed by 
CRS staff, not the participant), generalized pruritus, facial flushing, and 
unexplained diaphoresis. Local symptoms include pain and/or tenderness at the 
infusion site. The daily maximum severity reached for each symptom during the 
assessment period is reported (see HVTN 130/HPTN 089 SSP).  
Body temperature is measured by oral or infrared thermometry. All temperatures 
must be measured by non-axillary thermometry. This includes temperatures taken 
in the clinic, as well as temperatures taken by participants during the Solicited AE 
period. 
Temperature is 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. 
9.8.2 
Assessment of infusion site 
Typical infusion site reactions are erythema/redness and induration/swelling. The 
maximum diameter measurement for all infusion site reactions is recorded. 
All infusion site reactions are monitored until resolution. Areas with diameters 
greater than 5 cm are followed daily; otherwise, the frequency of follow-up is 
based on clinician judgment. 
9.9 
Visit windows and missed visits 
Target visit windows for follow-up visits have been chosen to ensure the viability 
of robust PK calculations and cross-protocol comparison. As such, Visits 3 and 4 
should be done on Day 3 and 6 on target days; target windows for Visit 5 through 
visits 24 weeks after the final infusion (ie, Visit 11 for Groups 1-3 and Visit 13 

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for Group 4) are ± 3 days. The target window expands to ± 7 days for all 
remaining follow-up visits. The target window for the second infusion visit in 
Group 4 (Visit 9) is ±7 days. Broader allowable visit windows are shown below: 
• For Groups 1-3: Visit 3 (-2, +1 day(s)), Visit 4 (±2 days), Visits 5, 6, 7, 9, 
and 11 (±7 days), and Visits 12, 13, and 14 (±14 days) 
• For Group 4: Visit 3 (-2, +1 day(s)), Visit 4 (±2 days), Visits 5, 6, 7, 8, 10, 
11, 12, and 13 (±7 days), and Visits 9, 14, 15, and 16 (±14 days) 
All follow-up visits should take place within the target visit windows. The 
expanded allowable visit windows may be utilized only if the visit cannot be 
scheduled within the target visit window. Visits scheduled outside the allowable 
visit windows are considered protocol deviations. Visit windows are defined in 
greater detail in the HVTN 130/HPTN 089 SSP. 
If a participant misses a scheduled visit, the CRS staff should attempt to bring the 
participant in as soon as possible to complete the required safety assessments and 
other procedures. The procedures for documenting missed visits and out of 
window visits are described in the HVTN 130/HPTN 089 SSP. 
If a missed visit required study product administration or if study product 
administration must be permanently discontinued, please refer to Section 7.3.2 for 
resolution. 
9.10 
Early termination visit 
In the event of early participant termination, site staff should attempt to complete 
the following assessments, as appropriate: a final physical examination, clinical 
laboratory tests (including urine dipstick, CBC with differential, and chemistry 
panel), pregnancy testing, social impact assessment, and HIV test (note, for 
persons who are confirmed pregnant, pregnancy testing is not required, unless 
clinically indicated). For participants who have a confirmed diagnosis of HIV 
infection, see Section 9.12. 
9.11 
Pregnancy 
If a participant becomes pregnant during the course of the study, infusions of 
study product will not be given, but remaining visits and study procedures should 
be completed unless medically contraindicated or applicable regulations require 
termination from the study. During follow-up in persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated. 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. Pregnancies and pregnancy outcomes will be reported. If 

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the participant is no longer pregnant, refer to Section 7.3.1. If the participant is no 
longer pregnant, refer to Section 7.3.2. 
See Pregnancy Management and Reporting section of the Ab MOP for further 
details. 
9.12 
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 or their last scheduled protocol clinic visit, whichever 
comes first. Follow-up duration for participants diagnosed with HIV infection 
may be adjusted in consultation with the CRS investigator and the HVTN 
130/HPTN 089 PSRT (eg, to avoid interference with participant initiation of HIV 
treatment). At postinfection follow-up visits, only specimens required for 
protocol-specified safety laboratory tests, urinalysis, and pregnancy tests will be 
collected (note: for persons who are confirmed pregnant, pregnancy testing is not 
required, unless clinically indicated); in addition, some clinic procedures may be 
modified or discontinued (see Appendix G, Appendix H, Appendix I, and 
Appendix J). These individuals may also be referred to appropriate ongoing 
clinical trials or observational studies. 
See the HIV Infection section in the Ab MOP for further details. 

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10 
Laboratory 
10.1 
CRS laboratory procedures 
The HVTN 130/HPTN 089 Site Lab Instructions and HVTN 130/HPTN 089 SSP 
provide further guidelines for operational issues concerning the clinical and 
processing laboratories. These documents include 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 G and Appendix H, 
and. For tests performed locally, the local lab may assign appropriate tube types. 
Of note, all assays described below are performed as research assays and are not 
approved for use in medical care. Results from these assays are not made 
available to participants or medical professionals to guide treatment decisions. 
10.2 
Total blood volume 
Required blood volumes per visit are shown in Appendix G and Appendix H. 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. The 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. 
10.3 
PGT121, PGDM1400, 10-1074, and VRC07-523LS concentrations 
PGT121, PGDM1400, 10-1074, and VRC07-523LS concentrations will be 
measured in serum collected at prespecified timepoints. A quantitative 
immunoassay will be used to determine the concentration of each mAb. Ultra-
sensitive bead-based analyses enable a broad dynamic range and higher sensitivity 
(eg, for the anti-idiotype mAb, 5C9, the lower limit of quantification is 
approximately 50 pg/mL). The operational sensitivity of the quantitative assays 
will be determined for the clinical grade PGT121, PGDM1400, 10-1074, and 
VRC07-523LS used for this study. For multiplexed PK measurements, 
interference testing will be included as part of the qualification/validation. The 
mAb concentrations may be normalized relative to total protein. 
10.4 
Neutralizing antibody assay 
HIV-1–specific nAb assays will be performed on serum samples from study 
participants taken at post administration timepoint(s) and at baseline. The TZM-bl 

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assay will test neutralization of a panel of mAb-specific viruses (one virus per 
mAb). The assay will also test the neutralization of a panel of viruses that exhibit 
a range of known sensitivities to mAbs VRC07-523LS, PGDM1400, PGT121, 
and 10-1074. These viruses will be selected from a global panel and/or clade-
specific panels (77, 81) and may be modified by site-directed mutagenesis to be 
capable of measuring the activity of each mAb individually. 
10.5 
ADA detection assay 
A tiered testing approach will be used to identify and characterize ADAs that may 
arise. Anti-PGT121, PGDM1400, 10-1074, and VRC07-523LS antibody 
detection assays (screening, confirmatory, and/or titration) will be performed on 
serum samples from study participants at indicated timepoints. 
10.6 
ADA functional assay 
A functional ADA assay will be used to characterize any positive activity that is 
observed in the ADA detection assay. Functional activity will measure a reduction 
in VRC07-523LS, PGDM1400, PGT121 and 10-1074 neutralizing activity against 
a qualified virus in the TZM-bl assay. 
10.7 
Monoclonal Ab reaction assays 
To investigate mAb reactions, serum samples collected after the onset of reaction 
may be tested to measure levels of certain markers (eg, tryptase, complement 
components [C3 and C4], and cytokines). ADA detection and functional assays, 
as described above, may be performed on serum samples taken prior to the study 
product administration associated with the reaction. Refer to the HVTN 
130/HPTN 089 SSP for more information. 
10.8 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV immunology, antibody mediated prevention, or vaccines. In 
addition, samples may be used to perform additional assays to support 
standardization and validation of existing or newly developed methods.  
10.9 
Specimen storage and other use of specimens  
The Networks store specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if required by IRB/EC, or RE.  

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Other use of specimens is defined as studies not covered by the protocol or the 
informed consent form for the main study (see Appendix D).  
This research may relate to HIV, vaccines, monoclonal antibodies, the immune 
system, and other diseases. This could include 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 research on specimens (“other use”) will occur only after review and 
approval by the HVTN, the HPTN, the IRB/EC of the researcher requesting the 
specimens, and the CRS’s IRBs/ECs/REs if required.  
As part of consenting for the study, participants document their initial decision to 
allow or not allow their specimens to be used in other research, and they may 
change their decision at any time. The participant’s initial decision about other 
use of their specimens, and any later change to that decision, is recorded by their 
CRS in a Web-based tool that documents their current decisions for other use of 
their specimens. The Networks will only allow other research to be done on 
specimens from participants who allow such use.  
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on specimen storage or 
other use of specimens. 
10.10 
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 and 
shipping and handling of all specimens for this study, as currently recommended 
by the CDC and the NIH or other applicable agencies. 
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 130/HPTN 089 PSRT 
The HVTN 130/HPTN 089 PSRT is composed of the following members: 
• DAIDS medical officer representatives 
• Protocol chairs 
• Protocol Team leaders 
• Core medical monitor 
• Clinical safety specialist 
The clinician members of HVTN 130/HPTN 089 PSRT are responsible for 
decisions related to participant safety. 
The Protocol Team clinic coordinator, clinical data manager, study product 
developer representative, clinical trial manager, clinical research manager, and 
others may also be included in HVTN 130/HPTN 089 PSRT meetings. 
11.1.2 
HVTN SMB 
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, 
and experts in HIV vaccine and drug research that, collectively, has experience in 
the conduct and monitoring of vaccine, mAb, and other drug 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 Solicited AEs, 
Unsolicited AEs, laboratory safety data, and individual reports of adverse events 
requiring expedited reporting to DAIDS. The SMB conducts additional special 
reviews at the request of the HVTN 130/HPTN 089 PSRT.  
Study sites will receive SMB summary minutes and are responsible for 
forwarding them to their IRB/EC and any applicable RE. 
11.1.3 
Roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring 
include: 

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• Maintaining a central database management system for clinical data; 
• Providing reports of clinical data to appropriate groups such as the HVTN 
130/HPTN 089 PSRT and HVTN SMB (see Section 11.1.2); 
The roles and responsibilities of the HVTN Clinical Safety Specialist (CSS) or 
HVTN Core designee in relation to safety monitoring include: 
• Daily monitoring of clinical data for events that meet the safety pause and 
HVTN 130/HPTN 089 PSRT AE review criteria (see Section 11.4); 
• Notifying CRSs and other groups when safety pauses or planned holds are 
instituted and lifted (see Section 11.4); 
• Querying CRSs for additional information regarding reported clinical data; 
and 
• Providing support to the HVTN 130/HPTN 089 PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
Site staff must submit all safety forms (eg, Solicited AEs, Unsolicited AEs, 
urinalysis, local lab results, and concomitant medications) before the end of the 
next business day, excluding federal or bank holidays. 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. For the case of a longer site holiday closure, site staff must submit 
the data by the end of the 5th day (local time) after receiving the information even 
if this day is a holiday.  
For example: If the site becomes aware of an AE on Thursday (Day 0), the site 
must submit the data by the end of the next business day, on Friday. If there is a 
longer site holiday closure, then this AE must be reported no later than the end of 
the fifth day, Monday (Day 4). If Monday is a holiday as well, all safety forms 
still need to be submitted by the end of Monday (Day 4). 
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 

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product/procedure(s), whether or not related to the investigational study 
product/procedure(s). See the  HVTN 130/HPTN 089 SSP for further details 
regarding Solicited and Unsolicited AEs.  
The study Unsolicited AE reporting period comprises the entire study period for 
each individual participant (from enrollment through the last scheduled clinic visit 
or participant early termination from the study). 
All AEs are graded according to the Division of AIDS (DAIDS) Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 
2.1, July 2017, available on the RSC website at https://rsc.niaid.nih.gov/clinical-
research-sites/daids-adverse-event-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 
130/HPTN 089 SSP); 
• Infusion or Injection Site Erythema or Redness and Infusion or Injection Site 
Induration or Swelling will not consider surface area and interference with 
usual social and functional activities such that: 
 Grade 1 is: 2.5 to < 5 cm in diameter; 
 Grade 2 is: ≥ 5 to < 10 cm in diameter; 
 Grade 3 is: ≥ 10 cm in diameter 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); 
• mAb reactions not represented in the DAIDS Table to be graded per the 
“infusion related reaction” row from the Common Terminology Criteria for 
Adverse Events (CTCAE) from the US DHHS (Version 5.0. Published 
November 27, 2017, available at 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctca
e_v5_quick_reference_5x7.pdf; see also HVTN 130/HPTN 089 SSP) 
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 (see Section 11.2.3); (2) if the AE meets the 
criteria for a safety pause/prompt AE review (see Section 11.4). 
Sites are expected to notify HVTN clinical safety staff 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/hvtn130hptn089). Concerns requiring 
immediate attention should be communicated by calling the clinical safety phone. 

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In the case of email notification, clinical safety staff will reply within one 
business day. Serious events that meet pause rule criteria will be addressed 
immediately (as outlined in Table 11-1). If email service is not available, the CRS 
should notify clinical safety staff of the event by telephone, and 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 https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-
reporting-adverse-events-daids. The SAE Reporting Category will be used for this 
study.  
The internet-based DAIDS Adverse Experience Reporting System (DAERS) must 
be used for expedited AE (EAE) 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 
https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting. 
For questions about DAERS, please contact CRMSsupport@niaid.nih.gov or 
from within the DAERS application itself. 
For questions about EAE reporting, please contact the DAIDS RSC Safety Office 
at (DAIDSRSCSafetyOffice@tech-res.com). 
The study products for which expedited reporting are required are:  
• VRC-HIVMAB075-00-AB (VRC07-523LS) 
• PGT121 
• PGDM1400 
• 10-1074 
While the participant is in the study, the SAE Reporting Category will be used.  
After the end of trial participation for that participant, unless otherwise noted, 
only Suspected, Unexpected Serious Adverse Reactions (SUSARs) 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.  

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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). However, because safety is a primary study endpoint, the 
Sponsor Medical Officer will not routinely be unblinded to study treatment 
assignment when there is an assessment of relatedness of the SAE with the study 
product(s); and the safety report will be sent to the FDA based on the blinded 
attribution assessment. In addition, the NIAID/DAIDS or designee(s) will prepare 
and file expedited reports to other appropriate regulatory authorities within the 
timelines required by pertinent national regulatory agencies.  
CRS Investigators of Record (IoRs)/designees will submit AE information and 
any other relevant safety information to their IRBs/ECs in accordance with 
IRB/EC requirements. 
11.3 
Safety reviews 
11.3.1 
Initial safety evaluation 
Enrollment in Group 1-3 across all participating CRSs will be restricted to a 
maximum of 1 participant per day until 6 participants have been enrolled in each 
group. The HVTN 130/HPTN 089 PSRT will review the cumulative safety data 
including at minimum local and systemic Solicited AE data reported for the first 
72 hours post study product administration on each of these 18 participants.  
11.3.2 
Safety evaluation for opening enrollment in Group 4  
In addition to monitoring participant safety throughout the study period, the 
HVTN 130/HPTN 089 PSRT will review all cumulative safety data available 
from Groups 1 through 3 up to and including the 2-week visit after the first study 
product administration. Based on the assessment of this safety data, the HVTN 
130/HPTN 089 PSRT will make a decision regarding the appropriateness of 
opening enrollment in Group 4. The HVTN SMB may perform an additional 
review of this safety data to make the final determination based on safety for 
proceeding to Group 4. 
If any Grade 3 or higher AEs deemed related to study product are reported in 
Groups 1, 2 or 3, the HVTN SMB will perform an additional review of these 
safety data to make the final determination based on safety for proceeding to 
Group 4.  
11.3.3 
Safety considerations for Group 4 
In addition to monitoring participant safety throughout the study period, the 
HVTN 130/HPTN 089 PSRT will review cumulative safety data available on the 
first 6 participants in Group 4 up to and including the 2-week visit after the first 
study product administration to determine whether the remaining participants in 
Group 4 can be enrolled. If any Grade 3 or higher AEs deemed related to study 

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product are reported in Group 4, the HVTN SMB will perform an additional review 
of these safety data to make the final determination based on safety for proceeding 
with enrollment of the remaining 3 participants in Group 4. The HVTN 130/HPTN 
089 PSRT may consult with the HVTN SMB on an ad hoc basis for these 
evaluations. 
11.4 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and study product 
administration 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 130/HPTN 089 PSRT AE review are summarized in Table 11-1. Study 
product administrations 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 130/HPTN 089 PSRT, participant safety may be threatened. Criteria for an 
individual participant’s departure from the schedule of study product 
administrations are listed in Section 7.3. 
Table 11-1 AE notification and safety pause/AE review rules 
Event and 
relationship to study 
products 
Severity 
CRS action a 
HVTN Core action b 
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 PSRT notification 
SAE, related 
Grade 3, 2, or 1 
Email and submit forms 
immediately 
Immediate PSRT notification and 
prompt PSRT AE review to 
consider pause 
AEc, related 
Grade 4 or 3 
Email and submit forms 
immediately 
Immediate PSRT notification and 
prompt 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/hvtn130hptn089). 
b HVTN CSS or HVTN Core designee 
c Does not include subjective Solicited AEs (infusion site pain, tenderness, fatigue/malaise, myalgia, 
arthralgia, chills, headache, non-exertional dyspnea, generalized pruritus, facial flushing, and unexplained 
diaphoresis). 
For all safety pauses, HVTN Core notifies the HVTN 130/HPTN 089 PSRT, 
HVTN Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), 
DAIDS Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance 
Team (SPT), and participating CRSs. When an immediate safety pause is 
triggered, HVTN Core notifies the SMB.  
Once a trial is paused, the HVTN 130/HPTN 089 PSRT reviews safety data and 
decides whether the pause can be lifted or permanent discontinuation of study 
product administration is appropriate, consulting the SMB if necessary. HVTN 

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Core notifies the participating CRSs, HVTN Regulatory Affairs, DAIDS PAB, 
DAIDS RAB, and DAIDS SPT of the decision regarding resumption or 
discontinuation of study product administrations. Based on the HVTN 130/HPTN 
089 PSRT assessment, DAIDS RAB notifies the FDA as needed. 
If an immediate HVTN 130/HPTN 089 PSRT notification or prompt HVTN 
130/HPTN 089 PSRT AE review is triggered, HVTN Core notifies the HVTN 
130/HPTN 089 PSRT as soon as possible during working hours (local time)—or, 
if the information was received during off hours, by the morning of the next 
workday. If a prompt HVTN 130/HPTN 089 PSRT AE review cannot be 
completed within 72 hours of notification (excluding weekends and US federal 
holidays), an automatic safety pause occurs. 
The HVTN and HPTN require that each CRS submit to its IRB/EC and any 
applicable RE protocol-related safety information (such as IND safety reports, 
notification of study-product holds due to the pause rules, unanticipated problems 
involving risks to participants or others, 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 130/HPTN 089 
PSRT (see Section 11.5.2). 
11.5 
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 CRSs. Events 
are tracked by internal reports until resolution.  
11.5.1 
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 130/HPTN 089 PSRT AE review criteria. 
11.5.2 
Weekly review 
During the study product administration phase of the trial, the HVTN 130/HPTN 
089 PSRT reviews clinical safety reports on a weekly basis and conducts calls to 
review the data as appropriate. Following the visit 4 weeks after the final study 
product administration, less frequent reporting and safety reviews may be 
conducted at the discretion of the HVTN 130/HPTN 089 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 CRS clinic coordinator for verification. 

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11.6 
Study termination 
This study may be terminated early by the determination of the HVTN 130/HPTN 
089 PSRT, FDA, NIH, Office for Human Research Protections (OHRP), or study 
product developer(s). In addition, the conduct of this study at an individual 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, HVTN 
and HPTN policies and procedures as specified in the network-specific Manuals 
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; 
• Unblinding of staff and participants; 
• Quality control; 
• Protocol monitoring and compliance; 
• Advocacy and assistance to participants regarding negative social impacts 
associated with the trial; 
• Risk reduction counseling;  
• Specimen collection, processing, and analysis;  
• Exploratory and ancillary studies and sub-studies, and 
• Destruction of specimens. 
Any policies or procedures that vary from DAIDS, HVTN, or HPTN standards or 
require additional instructions (eg, instructions for randomization specific to this 
study) will be described in the HVTN 130/HPTN 089 SSP.  

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12.1 
Social impacts 
It is possible that participants’ involvement in the study could result in social 
impacts. For example, a participant’s involvement in the study could become 
known to others, and a social harm may result (ie, because participants could be 
perceived as being HIV infected or at “high risk” for HIV infection). Participants 
could be treated unfairly, or could have problems being accepted by their families 
and/or communities. Alternatively, a social benefit may result (eg, a participant 
could feel good helping others). 
Social harms are negative social impact events and social benefits are positive 
social impact events that a participant reports as affecting them as a result of 
being involved in a research study. It is not the researcher’s opinion of how they 
perceive an event has affected a participant. Social impacts will be collected and 
reported on CRFs during scheduled visits (see Appendix I and Appendix J). A 
social harm that is reported by the participant and judged by the IoR/designee to 
be serious or unexpected will be reported to the responsible site’s IRB at least 
annually, or according to their individual requirements. In the event that a 
participant reports a social harm, every effort will be made by study staff to 
provide appropriate care and counseling to the participant as necessary, and/or 
referral to appropriate resources for the safety and wellbeing of the participant. 
While maintaining participant confidentiality, study sites may engage their CAB 
in exploring the social context surrounding instances of social harms to minimize 
the potential occurrence of such an impact. 
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 can contact the participant without IRB/EC approval if 
such communication is necessary to avoid imminent harm to the study participant. 
The CRS must 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 Network protocols via clarification memos, letters of 
amendment, or full protocol amendments.  
The version history of, and modifications to, Protocol HVTN 130/HPTN 089 are 
described below. 
Protocol history and modifications 
Date: March 18, 2019 
Protocol version: 1.0 
Protocol modification: NA 
 

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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 Centers for Disease Control (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.  
 Revised Guidelines for HIV Counseling, Testing, and Referral. Available 
at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5019a1.htm 
• 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 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-
tables 
• The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 
2.0, January 2010. Available at https://rsc.niaid.nih.gov/clinical-research-
sites/manual-expedited-reporting-adverse-events-daids 
• Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. 
Published November 27, 2017. Available at 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctca
e_v5_quick_reference_5x7.pdf 
• HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
• HPTN Certificate of Confidentiality 
• HVTN 130/HPTN 089 Special Instructions. Accessible through the HVTN 
protocol-specific website. 

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• HVTN 130/HPTN 089 Study Specific Procedures. Accessible through the 
HVTN protocol-specific website. 
• HVTN 130/HPTN 089 Site Lab Instructions. Accessible through the HVTN 
protocol-specific website. 
• HVTN Manual of Operations. Accessible through the HVTN website. 
• Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
https://www.iata.org/publications/dgr/Pages/index.aspx 
• Lab assay algorithm (available upon request) 
• International Council on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6, 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. 
• National Institutes of Health (NIH) Policy on Reporting Race and Ethnicity 
Data: Subjects in Clinical Research. Available at 
https://grants.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 
ADA 
 
anti-drug antibodies 
ADCC 
 
antibody dependent cell mediated cytotoxicity 
ADCP 
 
antibody dependent cellular phagocytosis 
AE 
 
adverse event 
ALT 
 
alanine aminotransferase 
ANOVA  
analysis of variance 
ART 
 
antiretroviral therapy 
AUC 
 
area-under-the-curve 
AUC-MB  
area-under-the-magnitude-breadth curve 
β-HCG 
 
beta human chorionic gonadotropin 
bnAb 
 
broadly neutralizing HIV-1 antibody 
BP 
 
British Pharmacopoeia 
CAB 
 
Community Advisory Board 
CBC 
 
complete blood count 
CDC 
 
US Centers for Disease Control and Prevention 
CFR 
 
Code of Federal Regulations 
cGMP 
 
current Good Manufacturing Practice 
CI 
 
confidence interval 
Cmax  
 
maximum concentration 
CMV 
 
cytomegalovirus 
CRF 
 
case report form 
CRPMC 
 
NIAID Clinical Research Products Management Center 
CRS 
 
clinical research site 
CSS 
 
Clinical Safety Specialist 
DAERS 
 
DAIDS Adverse Experience Reporting System 
DAIDS 
 
Division of AIDS (US NIH) 
DHHS 
 
US Department of Health and Human Services 
DLT 
 
dose limiting toxicity 
EAE 
 
adverse events requiring expedited reporting to DAIDS 
EC 
 
Ethics Committee 
ELISA 
 
enzyme-linked immunosorbent assay 
EP 
 
European Pharmacopoeia 
FCC 
 
Food Chemical Codex 
FcRn 
 
Fc-receptor 
FDA 
 
US Food and Drug Administration 

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Fred Hutch 
Fred Hutchinson Cancer Research Center 
GCP 
 
Good Clinical Practice 
GEE 
 
generalized estimating equation 
GLP 
 
Good Laboratory Practice 
HBsAg 
 
hepatitis B surface antigen 
HCV 
 
hepatitis C virus 
IB 
 
Investigator’s Brochure 
IC 
 
inhibitory concentration 
ICF 
 
informed consent form 
ICH 
 
International Council on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IgG 
 
immunoglobulin G 
IND 
 
Investigational New Drug 
IoR 
 
Investigator of Record 
IRB 
 
Institutional Review Board 
IUD 
 
intrauterine device 
IV 
 
intravenous 
JP 
 
Japanese Pharmacopoeia 
LOC 
 
Leadership Operations Center 
mAb 
 
monoclonal antibody 
MAR 
 
missing at random 
M-B 
 
Magnitude-Breadth 
MCAR 
 
missing completely at random 
MITT 
 
modified intent-to-treat 
MOP 
 
Manual of Operations 
MTD 
 
maximum tolerated dose 
nAb 
 
neutralizing antibody 
NAEPP 
 
National Asthma Education and Prevention Program 
NF 
 
(US) National Formulary 
NHP 
 
nonhuman primate 
NIAID 
 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
 
US National Institutes of Health 
NOAEL 
 
no-observed-adverse-effect-level 
NSAID 
 
non-steroidal anti-inflammatory drugs 
OHRP 
 
US Office for Human Research Protections 
PAB 
 
DAIDS Pharmaceutical Affairs Branch 
PCR 
 
polymerase chain reaction 
PD 
 
pharmacodynamics 
PK 
 
pharmacokinetic 

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popPK 
 
population PK (pharmacokinetic)  
PP 
 
per-protocol 
PSRT 
 
Protocol Safety Review Team 
RAB 
 
DAIDS Regulatory Affairs Branch 
RE 
 
regulatory entity 
RSC 
 
DAIDS Regulatory Support Center 
SAE 
 
serious adverse event 
SAP 
 
Statistical Analysis Plan 
SC 
 
subcutaneous  
SCHARP  
Statistical Center for HIV/AIDS Research and Prevention 
SD 
 
standard deviation 
SDMC 
 
statistical and data management center 
SHIV 
 
simian-human immunodeficiency virus 
SMB 
 
Safety Monitoring Board 
SMC 
 
Safety Monitoring Committee 
SPT 
 
DAIDS Safety and Pharmacovigilance Team 
SSP 
 
Study Specific Procedures 
SSRI 
 
selective serotonin reuptake inhibitor 
SUSAR 
 
sudden unexpected serious adverse reaction 
TB 
 
tuberculosis 
TCR 
 
tissue cross reactivity 
Tmax 
 
time to Cmax 
USP 
 
United States Pharmacopeia 
UW-VSL  
University of Washington Virology Specialty Laboratory 
Vd 
volume of distribution 
VRC 
Vaccine Research Center (NIAID) 
WFI 
Water for Injection 
 

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16 
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Appendix A 
Sample informed consent form for Groups 1-
3 
Title: A phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics, 
and antiviral activity of combinations of monoclonal antibodies PGT121, 
PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion 
in healthy, HIV-uninfected adult participants 
Protocol number: HVTN 130/HPTN 089 
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), the HIV Prevention Trials Network 
(HPTN) and [Insert site name]  are doing a study to test the combination of 
different antibodies against HIV. 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 these procedures below. Officially approved antibodies have been 
used successfully to prevent or treat some other health problems, such as a virus 
that causes respiratory infections in infants. 
About 27 people will take part in this study at multiple sites. 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.  
There are a total of 4 groups in this study. About 18 people total will take part in 
Groups 1, 2, and 3. After we see the safety results from Groups 1-3, we will 
decide whether or not to do Group 4. If we decide to do Group 4, 9 more people 
will join. 
You are being invited to join Group 1, 2, or 3 of the study. 
1. We are doing this study to answer several questions. 
• Are the study antibodies safe to give to people in combinations? 

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• Are people able to take the study antibodies without becoming too 
uncomfortable? 
• How much of the antibodies remains in the body as time passes? 
• How does the body’s response to the antibodies change depending on the 
combination given? 
2. The study antibodies cannot give you HIV. 
The study 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. 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 study antibodies are experimental. 
The formal names of the study antibodies are VRC07-523LS, PGDM1400, 
PGT121, and 10-1074. From here on, we will call them the study antibodies. 
They are experimental products. That means we do not know if they will be safe 
to use in people, or if they will work to prevent HIV infection. These study 
antibodies are used only in research studies. 
The different study antibodies were developed by researchers at the Dale and 
Betty Bumpers Vaccine Research Center in Bethesda, Maryland, the Beth Israel 
Deaconess Medical Center in Boston, Massachusetts, and the Rockefeller Institute 
in New York, New York. 
In laboratory studies, these study antibodies attached to and prevented infection 
by many kinds of HIV viruses from around the world. Each of the study 
antibodies was strongest against different varieties of HIV viruses. When 
combined in lab tests, they were able to prevent almost all varieties of HIV from 
infecting human cells. 
In animal studies, the study antibodies prevented animals from infection with 
animal viruses that are very similar to HIV. The study antibodies have also been 
tested for safety in the laboratory and in animal studies.  
We do not know if the study antibodies will prevent HIV infection when given to 
people. It will take many studies to learn if they will be useful for prevention of 
HIV infection. This study will not answer these questions. 
These study antibodies have been tested in small numbers of people in previous 
studies. Although there are other ongoing studies using these antibodies 
individually and in other combinations, there have been no studies in people using 
the same combinations of two antibodies as in this study. There have not been any 
serious health problems in any of these studies so far. 

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Risks of the study antibodies: 
This section lists the side effects we know about when the antibodies are given 
individually. There may be side effects that we don’t yet know about, or side 
effects from these combinations, even serious ones. We will tell you about any 
new information that might change your willingness to stay in this study. 
VRC07-523LS 
The VRC07-523LS study antibody was given by injection or intravenous infusion 
(IV) to 25 people in a clinical trial at the NIH Clinical Center in Bethesda, 
Maryland. Two people who got the study antibody by IV had chills, fever, nausea, 
body aches, rapid heartbeat, and headache. These feelings went away within 12 
hours. 
As of October 2018, about 120 more people have gotten this study antibody by IV 
or injection in a clinical trial called HVTN 127/HPTN 087. This study is taking 
place at clinics in the US and in Switzerland. In this study, this antibody has not 
made people too uncomfortable or caused serious health problems so far. 
A similar study antibody called VRC01 has been given to more than 3000 adults 
in several studies. Many of these studies are still going on and we don’t know 
which people got the study antibodies and which got a placebo (a liquid with no 
antibody in it). After receiving the IV infusion or injection, many people said they 
had mild pain, itching, or redness where the antibody or placebo was given to 
them. Some of these people said they felt like they had the flu after getting the IV 
or injections, but this feeling lasted a few hours at most. 
PGT121 
The PGT121 study antibody is being tested in a study with HIV-positive and 
HIV-negative participants. As of July 2018, about 20 HIV-negative people and 14 
HIV-positive people have gotten different doses of the study antibody by IV 
infusions and injections. Eight other people have gotten a placebo. There have 
been no serious health problems in any of the participants, and people have not 
found getting this study antibody or placebo too uncomfortable. 
PGDM1400 and PGT121 
The PGDM1400 study antibody is being tested by itself and in combination with 
the PGT121 study antibody. As of October 2018, 9 HIV-negative people have 
gotten PGDM1400 and 9 more HIV-negative people have gotten both 
PGDM1400 and PGT121. Six other people in this study have gotten a placebo. In 
this study people get the different doses of the study antibodies or a placebo by IV 
infusion. No serious health problems have been reported so far. 
10-1074 

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The 10-1074 study antibody has been tested by itself and in combination with 
another study antibody. As of November 2018, 32 HIV-negative people have 
gotten different doses of 10-1074 by IV infusion. The most common problems 
people reported were upper respiratory tract infections (colds) and headaches. 
Only a few of these problems were possibly related to getting the study antibody. 
Most problems were mild. 
General risks of antibodies: 
There are different types of antibodies officially approved for use in preventing or 
treating other diseases. From all of these uses of antibodies, we know that most 
side effects happen within the first 24 hours. Those antibodies have caused fever, 
chills, shaking, nausea, vomiting, pain, headache, dizziness, fatigue, flushing, 
trouble breathing, high or low blood pressure, itchiness, rash, hives, lip or face 
swelling, diarrhea, racing heartbeat, or chest pain.  
Rarely, some antibodies have caused serious reactions that may be life-
threatening. These reactions may include: 
• Anaphylaxis – a physical reaction that may include hives or rash, swelling in 
the mouth and face, low blood pressure, and difficulty breathing, possibly 
leading to low blood oxygen. This may occur soon after getting an antibody. 
• Serum Sickness – a physical reaction that includes developing hives or a rash, 
fever, big lymph nodes, muscle and joint pains, chest discomfort and shortness 
of breath. This may occur several days to a few weeks after getting an 
antibody. 
These rare reactions have not been seen in other studies with similar experimental 
antibodies. 
Please tell us if you have ever experienced reactions similar to anaphylaxis or 
serum sickness, and the cause of the reactions if you remember. 
Rarely, antibodies officially approved 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 
antibodies in this study with or similar experimental antibodies.  
Antibodies given to a person usually do not last in the body more than a few 
months. One of the goals of this study is to see how long the study antibodies will 
stay in the body. We don’t know yet how long they will last, but it may be several 
months.  

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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 prevention 
studies now or in the future. You cannot be in this study while you are in another 
study where you get a study product. Being in more than one study may not be 
safe.  
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 see how easy it might be to start an IV 
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, 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 assigned female sex at birth, we will test you for pregnancy. If you 
have had your uterus or ovaries removed (a hysterectomy or oophorectomy), 
verified by medical records, you are not required to have a pregnancy test.  
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.  

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Site: adapt the following section so it is applicable to the care available at your site 
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 assigned female sex at birth and could become pregnant, you 
must agree to use 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 study antibodies could affect the developing baby. You must agree to use 
effective birth control from 21 days before your infusion until 12 months after 
your study product administration. 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 [#] times over about a 
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.) 
Most of the visits will be 1-2 months apart. We will also ask you to come to the 
clinic about 3 days, 6 days, and 2 weeks after the infusion visit to draw your 
blood. We will do this so that we can look at how your body responds to the study 
antibodies. We will also look at how much of the antibodies are in your blood. 
The infusion visit can last from [#] to [#] hours. Follow-up 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 main study ends (for example, to tell you about the 
study results). 

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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: Include the following paragraph: 
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 some combination of two of the study antibodies.  
People in Groups 1, 2, and 3 will get an IV infusion with different combinations 
of 2 study antibodies.  
When getting an IV infusion, a sterile needle is used to place a small plastic tube 
into a vein in your arm. The tube is connected to a small container of fluid that 
contains the study antibody. Each antibody is in a separate container. An IV pump 
controls how fast the fluid drips from the container, through the tube, into your 
arm. The infusion will take about one hour for each study antibody (total of 2 
hours). 
Which group you are in and which antibody combination you get is completely 
random, like flipping a coin. We have no say in which group you are assigned to. 
Neither do you. You will know which antibody combination you will get. 
11. We will give you the study antibodies on a schedule. 
You will get the antibodies in a vein in your arm at one visit during the study. The 
antibodies will be given one at a time. 
Site: A picture of IV infusion placement has been provided in Appendix E. You may 
insert it below or give it as a separate document to volunteers if you believe it will be 
helpful to them. You are not required to do either. 
 

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Infusion Schedule 
Group 
Number of 
Participants 
Study Antibodies 
IV Infusion 
1 
6 
PGT121 and  
VRC07-523LS 
At enrollment 
 
2 
6 
PGDM1400 and 
VRC07-523LS 
3 
6 
10-1074 and  
VRC07-523LS  
You will have to wait in the clinic for at least an hour after the infusion to see if 
there are any problems. We will collect a blood sample one hour after the IV. 
Then that night and for 3 more days, you will need to keep track of how you are 
feeling and if you have any symptoms. We will ask about how to contact you. We 
will contact you about 3 days after the infusion visit to ask how you have been 
feeling. 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 the study products, 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 assigned female sex at birth 
• 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 
• Ask questions about your experience getting infusions 
• Take urine and blood samples. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 25 mL and 100 mL (a little less than 2 tablespoons 
to a little less than ½ cup). Your body will make new blood to replace the blood 
we take out. Please tell us if you have blood drawn for other purposes during this 
study.  
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. 

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Site: Insert Appendix AF, Tables 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 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.  
14. We will test your samples to see how your immune system responds to the 
study antibodies. 
We will send your samples (without your name) to labs approved by the HVTN 
and HPTN for this study, which are located in the United States. In rare cases, 
some of your samples may be sent to labs approved by the HVTN and HPTN in 
other countries for research related to this study. 
The samples will be tested to: 
• Measure how much antibody is in your blood, and 
• See how your immune system responds to the study antibodies. 
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. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only the genes related to the immune system and HIV and those that 
affect how people get HIV. 
If you become HIV positive, 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).  
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests.  
When your samples are no longer needed for this study, the HVTN will continue 
to store them with your permission. 

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Site: Delete next section if using separate consent for use of samples and information 
in other studies 
15. When samples are no longer needed for this study, the HVTN and HPTN 
may want to use them in other studies and share them with other 
researchers.  
These samples are called “extra samples”. The HVTN and HPTN will only allow 
your extra samples to be used in other studies if you agree to this. You will mark 
your decision at the end of this 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. 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: Revise the previous sentence to 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 or HPTN sell my samples and information? No, but the HVTN 
and HPTN may share your samples with other researchers. Once we share your 
samples and information, we may 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 information, their research plan must be approved 
by the HVTN and HPTN. 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 HVTN, HPTN or other researchers? The 
samples and information will be labeled with a code number. Your name will not 

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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, monoclonal antibodies, the immune 
system and other diseases.  
Researchers may also do genetic testing on your samples.  
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 extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and 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 and information may be published. 
No publication will use your name or identify you personally. 
16. 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. 

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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, 
• Any regulatory agency that reviews clinical trials, 
• [Insert name of local IRB/EC] , 
• [Insert name of local and/or national regulatory authority as appropriate], 
• The Dale and Betty Bumpers Vaccine Research Center, the Beth Israel 
Deaconess Medical Center, the Rockefeller Institute, and people who work for 
them, 
• The HVTN, HPTN 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 

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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. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
17. We may stop your infusion or 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: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• you get HIV, 
• 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 infusion, we may ask you to stay in the study to complete other 
study procedures. 
18. We will not give you an infusion if you become pregnant.  
However, if you become pregnant after your infusion, 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. 
19. If you get infected with HIV during the study, we will take fewer samples, 
and we will help you get care and support. 
We will encourage you to stay in the study for up to 4 months 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 

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support and medical care. Site: Modify the following sentence as appropriate. We 
will not provide or pay for any of your HIV care directly.  
Other Risks 
20. 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 giving blood:  
Collection of blood samples can cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore, bleeding, blood clots, and (rarely) muscle damage, or 
infection. Taking blood can cause a low blood cell count (anemia), making you 
feel tired. 
Risks of getting an IV infusion: 
Getting an infusion 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. 
Personal problems/discrimination/testing HIV antibody positive: 
Some people who join HVTN and HPTN 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 have used 
several common HIV antibody tests to test samples of blood containing different 
amounts of one of the study antibodies, VRC07-523LS. These tests show that 
very high levels of this antibody in the blood can cause positive or uncertain 
results on a few brands of HIV tests. Such high levels might exist for a short time 
after a person gets the study antibody. This means that for a few days after getting 
the antibody, certain HIV tests might say a person is infected with HIV when they 
really aren’t. We don’t know if the different brands of tests will have similar 
results for the other antibodies. 
Although it has not been seen so far, getting the study antibodies may cause 
common HIV antibody tests to show that someone is HIV-negative, even if they 
are actually infected. 

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Because of these risks, you should 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 not HIV infected. We do not expect you to have any problems with 
HIV testing after the study ends because the antibodies do not last in the body for 
that long. 
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: 
It is unlikely, but the genetic tests done on your samples 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.  
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 study 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 study antibodies might affect your HIV infection or how 
long it takes to develop AIDS. 
We do not know how the study antibodies will affect a pregnant participant or a 
developing baby.  

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Benefits 
21. The study may not benefit you. 
We do not expect that getting the study antibodies will 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 
study antibody or a vaccine later gets approved and sold, there are no plans to 
share any money with you.  
Your rights and responsibilities 
22. 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 
23. 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: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text 
24. 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 

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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 study 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.  
Some of the study product providers may pay medical costs for study-related 
injuries that are determined to be caused by their own study antibodies. If 
provider funds are not available or are not enough, or if the injury is determined to 
be caused by study procedures, the HVTN has limited funds to pay medical costs 
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/or 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, independent experts will be asked to review the decision. You always 
have the right to use the court system if you are not satisfied. 
Questions  
25. 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 or title 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 or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. 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 or title and telephone number of person on IRB/EC] , at the 
committee. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 

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Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
26. In Section 14 of this form, we told you about possible other uses of your extra 
samples and 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 and HPTN keep track of your decision 
about how your samples and information can be used. You can change your 
mind after signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to 
HIV, HIV prevention, the immune system, and other diseases. This may include 
genetic testing.  
OR 
 
 
I agree to the option above and also to allow my extra samples and 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 or genome wide studies.  
 
27. 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. 

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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 entire discussion of this consent form. 
 
 

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Appendix B 
Sample informed consent form for Group 4 
Title: A phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics, 
and antiviral activity of combinations of monoclonal antibodies PGT121, 
PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion 
in healthy, HIV-uninfected adult participants 
Protocol number: HVTN 130/HPTN 089 
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), the HIV Prevention Trials Network 
(HPTN) and [Insert site name]  are doing a study to test the combination of 
different antibodies against HIV. 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 these procedures below. Officially approved antibodies have been 
used successfully to prevent or treat some other health problems, such as a virus 
that causes respiratory infections in infants. 
About 27 people will take part in this study at multiple sites. 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.  
There are a total of 4 groups in this study. About 18 people participated in Groups 
1, 2, and 3. The results showed that it is safe to move ahead with Group 4, so 9 
more people will join. 
You are being invited to join Group 4 of the study. 
1. We are doing this study to answer several questions. 
• Are the study antibodies safe to give to people in combinations? 
• Are people able to take the study antibodies without becoming too 
uncomfortable? 

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• How much of the antibodies remains in the body as time passes? 
• How does the body’s response to the antibodies change depending on the dose 
and combination given? 
• Does the method of giving the antibodies change the body’s response? 
2. The study antibodies cannot give you HIV. 
The study 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. 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 study antibodies are experimental. 
The formal names of the study antibodies are VRC07-523LS, PGDM1400, and 
PGT121. From here on, we will call them the study antibodies. They are 
experimental products. That means we do not know if they will be safe to use in 
people, or if they will work to prevent HIV infection. These study antibodies are 
used only in research studies. 
The different study antibodies were developed by researchers at the Dale and 
Betty Bumpers Vaccine Research Center in Bethesda, Maryland, the Beth Israel 
Deaconess Medical Center in Boston, Massachusetts, and the Rockefeller Institute 
in New York, New York. 
In laboratory studies, these study antibodies attached to and prevented infection 
by many kinds of HIV viruses from around the world. Each of the study 
antibodies was strongest against different varieties of HIV viruses. When 
combined in lab tests, they were able to prevent almost all varieties of HIV from 
infecting human cells. 
In animal studies, the study antibodies prevented animals from infection with 
animal viruses that are very similar to HIV. The study antibodies have also been 
tested for safety in the laboratory and in animal studies.  
We do not know if the study antibodies will prevent HIV infection when given to 
people. It will take many studies to learn if they will be useful for prevention of 
HIV infection. This study will not answer these questions. 
These study antibodies have been tested in combinations of two Groups 1 through 
3 of this study, as well as in small numbers of people in previous studies. 
Although there are other ongoing studies using these antibodies individually and 
in other combinations, there have been no studies in people using the same 
combinations of three antibodies as in this study. There have not been any serious 
health problems in any of these studies so far. 

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Risks of the study antibodies: 
This section lists the side effects we know about when the antibodies are given 
individually. There may be side effects that we don’t yet know about, or side 
effects from the combinations, even serious ones. We will tell you about any new 
information that may change your willingness to stay in this study. 
VRC07-523LS 
The VRC07-523LS study antibody was given by injection or intravenous infusion 
(IV) to 25 people in a clinical trial at the NIH Clinical Center in Bethesda, 
Maryland. Two people who got the study antibody by IV had chills, fever, nausea, 
body aches, rapid heartbeat, and a headache. These feelings went away within 12 
hours. 
As of October 2018, about 120 more people have gotten this study antibody by IV 
or injection in a clinical trial called HVTN 127/HPTN 087. This study is taking 
place at clinics in the US and in Switzerland. In these studies, this antibody has 
not made people too uncomfortable or caused serious health problems so far.  
A similar study antibody called VRC01 has been given to more than 3000 adults 
in several studies. Many of these studies are still going on and we don’t know 
which people got the study antibodies and which got a placebo (a liquid with no 
antibody in it). After receiving the IV infusion or injection, many people said they 
had mild pain, itching, or redness where the antibody or placebo was given to 
them. Some of these people said they felt like they had the flu after getting the IV 
or injections, but this feeling lasted a few hours at most. 
PGT121 
The PGT121 study antibody is being tested in a study with HIV-positive and 
HIV-negative participants. As of July 2018, about 20 HIV-negative people and 14 
HIV-positive people have gotten the different doses of the study antibody by IV 
infusions and injections. Eight other people have gotten a placebo. There have 
been no serious health problems in any of the participants, and people have not 
found getting this study antibody or placebo too uncomfortable. 
PGDM1400 and PGT121 
The PGDM1400 study antibody is being tested by itself and in combination with 
the PGT121 study antibody. As of October 2018, 9 HIV-negative people have 
gotten PGFM1400 and 9 more HIV-negative people have gotten both PGDM1400 
and PGT121. Six other people in this study have gotten a placebo. In this study 
people get the different doses of the study antibody or a placebo by IV infusion. 
No serious health problems have been reported so far. 
General risks of antibodies: 

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There are different types of antibodies officially approved for use in preventing or 
treating other diseases. From all of these uses of antibodies, we know that most 
side effects happen within the first 24 hours. Those antibodies have caused fever, 
chills, shaking, nausea, vomiting, pain, headache, dizziness, flushing, trouble 
breathing, high or low blood pressure, itchiness, rash, hives, lip or face swelling, 
diarrhea, racing heartbeat, or chest pain.  
Rarely, some antibodies have caused serious reactions that may be life-
threatening. These reactions may include: 
• Anaphylaxis – a physical reaction that may include hives or rash, swelling in 
the mouth and face, low blood pressure, and difficulty breathing, possibly 
leading to low blood oxygen. This may occur soon after getting an antibody 
• Serum Sickness – a physical reaction that includes developing hives or a rash, 
fever, big lymph nodes, muscle and joint pains, chest discomfort and shortness 
of breath. This may occur several days to a few weeks after getting an 
antibody 
These rare reactions have not been seen in other studies with similar experimental 
antibodies. 
Please tell us if you have ever experienced reactions similar to anaphylaxis or 
serum sickness, and the cause of the reactions if you remember. 
Rarely, antibodies officially approved 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 
antibodies in this study with or similar experimental antibodies.  
Antibodies given to a person usually do not last in the body more than a few 
months. One of the goals of this study is to see how long the study antibodies will 
stay in the body. We don’t know yet how long they will last, but it may be several 
months.  
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 prevention 
studies now or in the future. You cannot be in this study while you are in another 

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study where you get a study product. Being in more than one study may not be 
safe.  
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 
• Looking at your skin 
• Listening to your heart and lungs 
• Feeling your abdomen (stomach and liver) 
• Checking your veins to see how easy it might be to start an IV 
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, 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 assigned female sex at birth, we will test you for pregnancy. If you 
have had your uterus or ovaries removed (a hysterectomy or oophorectomy), 
verified by medical records, you are not required to have a pregnancy test.  
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.  
Site: adapt the following section so it is applicable to the care available at your site 
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. 

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7. If you were assigned female sex at birth and could become pregnant, you 
must agree to use 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 study antibodies could affect the developing baby. You must agree to use 
effective birth control from 21 days before your first infusion until 12 months 
after your last infusion 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 [#] times over about a 
year and a half. 
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.) 
Most of the visits will be 1-2 months apart. We will also ask you to come to the 
clinic about 3 days, 6 days, and 2 weeks after the first infusion visit to draw your 
blood. We will do this so that we can look at how your body responds to the study 
antibodies. We will also look at how much of the study antibodies are in your 
blood. Infusion visits can last from [#] to [#] hours. Follow-up 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 main 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: Include the following paragraph: 
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. 

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You do not have to pay anything to be in this study. 
10. We will give you a combination of three study antibodies.  
When getting an IV infusion, a sterile needle is used to place a small plastic tube 
into a vein in your arm. The tube is connected to a small container of fluid that 
contains the study antibody. An IV pump controls how fast the fluid drips from 
the container, through the tube, into your arm. Each antibody is in a separate 
container. At the first visit, the infusion will take about one hour for each study 
antibody (total of about 3 hours). Other IV infusions will take about 30 minutes 
for each study antibody (total of about 1.5 hours). 
11. We will give you the study antibodies on a schedule. 
You will get antibodies at two visits during the study. The infusions will go into a 
vein in your arm. The antibodies will be given one at a time. 
Site: A picture of IV infusion placement has been provided in Appendix E. You may 
insert it below or give it as a separate document to volunteers if you believe it will be 
helpful to them. You are not required to do either. 
 
Infusion schedule 
Group 
Number 
of 
people 
Study 
Antibodies 
Infusion (at 
enrollment) 
Infusion 
(Month 4) 
4 
9 
PGDM1400, 
PGT121, and 
VRC07-523LS 
IV 
IV 
After each set of infusions, you will have to wait in the clinic for at least an hour 
to see if there are any problems. We will collect a blood sample one hour after the 
IV. Then that night and for 3 more days, you will need to keep track of how you 
are feeling and if you have any symptoms. We will ask about how to contact you. 
We will contact you about 3 days after each infusion visit to ask how you have 
been feeling. 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 the study products, 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 assigned female sex at birth 
• 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 
• Ask questions about your experience getting infusions 
• Take urine and blood samples. 
When we take blood, the amount will depend on the lab tests we need to do. It 
will be some amount between 25 mL and 100 mL (a little less than 2 tablespoons 
to a little less than ½ cup). Your body will make new blood to replace the blood 
we take out. Please tell us if you have blood drawn for other purposes during this 
study.  
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, Tables 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 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.  
14. We will test your samples to see how your immune system responds to the 
study antibodies. 
We will send your samples (without your name) to labs approved by the HVTN 
and HPTN for this study, which are located in the United States. In rare cases, 
some of your samples may be sent to labs approved by the HVTN and HPTN in 
other countries for research related to this study. 
The samples will be tested to: 
• Measure how much antibody is in your blood, and 
• See how your immune system responds to the study antibodies. 
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 

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and how your body works. The differences in people’s genes can help explain 
why some people get a disease while others do not. The genetic testing will only 
involve some of your genes, not all of your genes (your genome). The researchers 
will study only 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).  
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests.  
When your samples are no longer needed for this study, the HVTN will continue 
to store them with your permission. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 
15. When samples are no longer needed for this study, the HVTN and HPTN 
may want to use them in other studies and share them with other 
researchers.  
These samples are called “extra samples”. The HVTN and HPTN will only allow 
your extra samples to be used in other studies if you agree to this. You will mark 
your decision at the end of this 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. 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: Revise the previous sentence to 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. 

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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 or HPTN sell my samples and information? No, but the HVTN 
and HPTN may share your samples with other researchers. Once we share your 
samples and information, we may 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 information, their research plan must be approved 
by the HVTN and HPTN. 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 HVTN, HPTN or other researchers? The 
samples and 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, monoclonal antibodies, the immune 
system and other diseases.  
Researchers may also do genetic testing on your samples.  
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 extra samples and information for other research 

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• Government agencies that fund or monitor the research using your extra 
samples and 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 and information may be published. 
No publication will use your name or identify you personally. 
16. 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, 
• Any regulatory agency that reviews clinical trials, 
• [Insert name of local IRB/EC] , 
• [Insert name of local and/or national regulatory authority as appropriate], 
• The Dale and Betty Bumpers Vaccine Research Center, the Beth Israel 
Deaconess Medical Center, the Rockefeller Institute, and people who work for 
them, 
• The HVTN, HPTN and people who work for them,  
• The HVTN Safety Monitoring Board and 
• The US Office for Human Research Protections. 

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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. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
17. 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 get HIV, 

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• 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. 
18. We will stop your infusions if you become pregnant.  
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. 
19. If you get infected with HIV during the study, we will stop your infusions and 
take fewer samples, and we will help you get care and support. 
We will encourage you to stay in the study for up to 4 months after your last 
infusion visit 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. Site: Modify the following 
sentence as appropriate. We will not provide or pay for any of your HIV care 
directly.  
Other Risks 
20. 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 giving blood:  
Collection of blood samples can cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore, bleeding, blood clots, and (rarely) muscle damage or 
infection. Taking blood can cause a low blood cell count (anemia), making you 
feel tired. 
Risks of getting an IV infusion: 
Getting an infusion 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. 
Personal problems/discrimination/testing HIV antibody positive: 

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Some people who join HVTN and HPTN 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 have used 
several common HIV antibody tests to test samples of blood containing different 
amounts of one of the study antibodies, VRC07-523LS. These tests show that 
very high levels of this antibody in the blood can cause positive or uncertain 
results on a few brands of HIV tests. Such high levels might exist for a short time 
after a person gets the study antibody. This means that for a few days after getting 
the antibody, certain HIV tests might say a person is infected with HIV when they 
really aren’t. We don’t know if the different brands of tests will have similar 
results for the other antibodies. 
Although it has not been seen so far, getting the study antibodies may cause 
common HIV antibody tests to show that someone is HIV-negative, even if they 
are actually infected. 
Because of these risks, you should 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 not HIV infected. We do not expect you to have any problems with 
HIV testing after the study ends because the antibodies do not last in the body for 
that long. 
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: 

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It is unlikely, but the genetic tests done on your samples 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.  
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 study 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 study antibodies might affect your HIV infection or how 
long it takes to develop AIDS. 
We do not know how the study antibodies will affect a pregnant participant or a 
developing baby.  
Benefits 
21. The study may not benefit you. 
We do not expect that getting the study antibodies will 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 
study antibody or a vaccine later gets approved and sold, there are no plans to 
share any money with you.  
Your rights and responsibilities 
22. 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. 

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Leaving the study 
23. 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: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text 
24. 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 study 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.  
Some of the study product providers may pay medical costs for study-related 
injuries that are determined to be caused by their own study antibodies. If 
provider funds are not available or are not enough or if the injury is determined to 
be caused by study procedures,  the HVTN has limited funds to pay medical costs 
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/or 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, independent experts will be asked to review the decision. You always 
have the right to use the court system if you are not satisfied. 
Questions  
25. 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 or title 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 or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. 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 or title and telephone number of person on IRB/EC] , at the 
committee. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
26. In Section 14 of this form, we told you about possible other uses of your extra 
samples and 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 and HPTN keep track of your decision 
about how your samples and information can be used. You can change your 
mind after signing this form. 
 

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I allow my extra samples and information to be used for other studies related to 
HIV, HIV prevention, the immune system, and other diseases. This may include 
genetic testing.  
OR 
 
 
I agree to the option above and also to allow my extra samples and 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 or genome wide studies.  
 
27. 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: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 
 

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Appendix C 
Approved birth control methods for persons 
assigned female sex at birth (for sample informed 
consent form) 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs at vtn.core.reg@hvtn.org. You can remove the box around the text. 
You should not become pregnant during the study because we do not know how 
the study antibody could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first study 
infusion until 12 months after your last infusion.  
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 reached menopause, with no menstrual periods for one year; 
• You have had a hysterectomy (your uterus removed); 
• 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 partner(s) assigned female sex at birth; 
• You only have oral sex; or, 

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• You are sexually abstinent (no sex at all). 
Remember: If you are having sex, male and female condoms are the only birth 
control methods that also provide protection against HIV and other sexually 
transmitted infections. 
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 
Sample consent form for use of samples and 
information in other studies 
Title: A phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics, 
and antiviral activity of combinations of monoclonal antibodies PGT121, 
PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion 
in healthy, HIV-uninfected adult participants 
Protocol number: HVTN 130/HPTN 089 
Site: [Insert site name] 
When samples are no longer needed for this study, the HVTN and HPTN may 
want to use them in other studies and share them with other researchers. These 
samples are called “extra samples”. The HVTN will only allow your extra 
samples to be used in other studies if you agree to this. You will mark your 
decision at the end of this 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. 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: Revise the 
previous sentence to 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. 
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. 

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6. Will the HVTN or HPTN sell my samples and information?  
No, but the HVTN and HPTN may share your samples with other researchers. 
Once we share your samples and information, we may 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 information, their research plan 
must be approved by the HVTN and HPTN. 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 HVTN, HPTN or other researchers?  
The samples and 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, monoclonal antibodies, the immune 
system and other diseases.  
Researchers may also do genetic testing on your samples.  
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, but your name and other personal information will not be included. 
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. There may be other unknown risks. 
10. What are the risks of genetic testing?  
It is unlikely, but the genetic tests done on your samples 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 

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test results from the genetic testing. The results are not part of your study records 
and are not given to you.  
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 extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and 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 and information may be published. 
No publication will use your name or identify you personally. 
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 or title 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 or title and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, contact 
[name or title and telephone number of person on IRB/EC . 
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 and HPTN 

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keep track of your choice about how your samples and information can be 
used. You can change your mind after signing this form. 
 
I allow my extra samples and information to be used for other studies related to 
HIV, HIV prevention, the immune system, and other diseases. This may include 
genetic testing.  
OR 
 
 
I agree to the option above and also to allow my extra samples and 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 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 entire discussion of this consent form. 

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Appendix E 
Schematic of IV infusions 
 
 

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Appendix F 
Tables of procedures (for sample informed 
consent forms) 
Groups 1 – 3 
 
 
 
Time after infusion  
Procedure 
Screening 
visit(s) 
Day 0 
3 days 
6 days 
2 weeks 
1 month 
2 months 
4 months 
6 months 
8 months 
10 months 
1 year 
IV infusion  
 
√ 
 
 
 
 
 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
 
 
√  
 
 
 
 
 
 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants 
assigned female sex at birth)* 
√ 
√ 
 
 
 
 
 
 
 
 
√ 
 
HIV testing and pretest 
counseling** 
√ 
 
 
 
 
 
 
√ 
 
√ 
 
√ 
Risk reduction counseling 
√ 
√ 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire(s) 
√ 
√ 
 
 
 
 
 
 
√ 
 
 
√ 
 
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), are not 
required to have a pregnancy test.' 
** We will contact you with results of HIV testing. 
Group 4  
 
 
 
Time after first infusion  
Procedure 
Screening visit(s) 
Day 0 
3 days 
6 days 
2 weeks 
1 month 
2 months 
3 months 
4 months 
5 months 
6 months 
8 months 
10 months 
1 year 
1 year & 2 months 
1 year & 4 months 
IV infusion  
 
√ 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
 
 
√ 
 
 
 
 
√ 
 
 
 
 
 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test 
(participants assigned 
female sex at birth)* 
√ 
√ 
 
 
 
 
 
 
√ 
 
 
 
 
 
√ 
 
HIV testing and pretest 
counseling** 
√ 
 
 
 
 
 
 
 
√ 
 
 
√ 
 
√ 
 
√ 
Risk reduction counseling 
√ 
√ 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire(s) 
√ 
√ 
 
 
 
 
 
 
√ 
 
√ 
 
 
√ 
 
√ 
 
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), are not 
required to have a pregnancy test. 
** We will contact you with results of HIV testing. 

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Appendix G 
Laboratory procedures for Groups 1 – 3 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Day:
Screening 
visit3
D0
D3
D6
D14
D28
D56
D84
D112
D140
D168
D224
D280
D336
Week:
W0
W2
W4
W8
W12
W16
W20
W24
W32
W40
W48
Study Product Administration
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. capacity)4
PGT121 OR PGDM1400
OR 10-1074,
+ VRC07-523LS
Total
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Syphilis9
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics7
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
10
—
—
10
—
20
40
Safety labs10
CBC/ Differential
Local lab
Local lab
EDTA
5mL
5
5
—
—
5
—
5
—
5
—
5
5
5
5
45
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
—
—
5
—
5
—
5
—
5
5
5
5
45
Drug concentrations/detection
PGT121, PDGM1400, 10-
1074, VRC07-523LS 
concentrations
CSR
HVTN Labs / VITL
SST
8.5mL
—
y
y
y
y
y
y
—
y
—
y
y
y
y
0
Humoral assays
HIV-1 neutralizing Ab 
CSR
HVTN Labs
SST
8.5mL
—
y
y
—
—
y
y
—
y
—
—
—
—
—
0
Non-neutralizing antiviral 
assays
CSR
HVTN Labs
SST
8.5mL
—
y
y
—
—
y
y
—
y
—
—
—
—
—
0
Anti-Drug Antibody (ADA)
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs / VITL
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
y
y
y
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
y
y
y
0
mAb Reaction11
Tryptase / C3 and C4 
Complement / Cytokines
CSR
ARUP
SST
8.5mL
—
See footnote 12
—
—
—
See 
footnote 
12
—
0
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs / VITL
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
—
—
—
—
—
—
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
—
—
—
—
—
—
0
STORAGE
Serum 
CSR
—
SST
8.5mL
—
8514
42.5
42.5
42.5
43
42.5
—
42.5
—
42.5
42.5
42.5
42.5
510
Visit total
25
95
42.5
42.5
52.5
42.5
52.5
0
62.5
0
52.5
62.5
52.5
72.5
655
56-Day total13
 
25
120
162.5
205
257.5
300
352.5
95
115
62.5
115
115
115
125
URINE COLLECTION10
Urine dipstick8
Local lab
Local lab
X
—
—
—
X
—
—
—
—
—
—
—
—
—
Pregnancy test6
Local lab
Local lab
X
X
—
—
—
—
—
—
—
—
—
—
X
—
See footnote 12
See footnote 12
 
1 CSR = central specimen repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA); Dartmouth College (Hanover, 
New Hampshire, USA). 
 Non-HVTN laboratories: VITL = Vaccine Research Center - Immunology Testing Laboratory (Gaithersburg, Maryland, USA); ARUP Laboratories (Salt Lake City, Utah, USA). 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 158 of 165 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
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 For a participant who was born female (ie, assigned female sex at birth), pregnancy test must be performed on urine or blood specimens on the day of study product infusion with negative results 
received prior to infusion. Persons who have undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
7 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.10), 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 9.12). 
8 And microscopy if needed. 
9 Syphilis testing will be done by serology. 
10 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis, and pregnancy tests will be collected. 
11 To investigate mAb reactions, assays may be performed on serum samples taken prior to the study product administration associated with the reaction and collected after the onset of reaction. Refer 
to the HVTN 130/HPTN 089 SSP for more information. 
12 SST blood will be collected at specific timepoints after the onset of any mAb reaction. Refer to the HVTN 130/HPTN 089 SSP for more information. 
13 The 56-day blood total volume does not include up to 51mL SST blood collected for any mAb reaction; however, the 56-day limit is not exceeded at any visit by the possible collection of SST 
blood for a mAb reaction. 
14 Of this volume, 17mL of SST blood will be collected 1 hour after the end of the infusion (see Section 9.3). 
y = SST blood collected for serum storage will also cover specimen needs for drug concentrations, HIV-1 neutralizing Ab assays, non-neutralizing antiviral assays, and ADA detection and functional 
assays (including for any mAb reactions); no separate blood draw is needed. 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 159 of 165 
Appendix H 
Laboratory procedures for Group 4 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Day:
Screening 
visit3
D0
D3
D6
D14
D28
D56
D84
D112
D140
D168
D224
D280
D336
D392
D448
Week:
W0
W2
W4
W8
W12
W16
W20
W24
W32
W40
W48
W56
W64
Study Product 
Administration #1
Study Product 
Administration #2
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
PGDM1400 +
PGT121 +
VRC07-523LS
PGDM1400 +
PGT121 +
VRC07-523LS
Total
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Syphilis9
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics7
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
10
—
—
10
—
10
—
20
50
Safety labs10
CBC/ Differential
Local lab
Local lab
EDTA
5mL
5
5
—
—
5
—
5
5
5
5
5
5
5
5
5
5
65
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
—
—
5
—
5
5
5
5
5
5
5
5
5
5
65
Drug concentrations/detection
PGT121, PDGM1400, 
VRC07-523LS 
concentrations
CSR
HVTN Labs / VITL
SST
8.5mL
—
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
0
Humoral assays
HIV-1 neutralizing Ab 
CSR
HVTN Labs
SST
8.5mL
—
y
y
—
—
y
y
—
y
y
y
y
—
—
—
—
0
Non-neutralizingantiviral 
assays
CSR
HVTN Labs
SST
8.5mL
—
y
y
—
—
y
y
—
y
y
y
y
—
—
—
—
0
Anti-Drug Antibody (ADA)
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs / VITL
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
y
y
y
y
y
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
y
—
—
y
y
y
y
y
0
mAb Reaction11
Tryptase / C3 and C4 
Complement / Cytokines
CSR
ARUP
SST
8.5mL
—
See footnote 12
—
—
0
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs / VITL
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
See footnote y
—
—
—
—
—
—
—
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
See footnote y
—
—
—
—
—
—
—
0
STORAGE
Serum 
CSR
—
SST
8.5mL
—
8514
42.5
42.5
42.5
42.5
42.5
42.5
5114
42.5
42.5
42.5
42.5
42.5
42.5
42.5
688.5
Visit total
 
25
95
42.5
42.5
52.5
42.5
52.5
52.5
71
52.5
52.5
62.5
52.5
62.5
52.5
72.5
883.5
56-Day total13
 
25
120
162.5
205
257.5
300
352.5
147.5
176
176
176
115
115
115
115
125
URINE COLLECTION10
 
 
 
 
 
Urine dipstick8
Local lab
Local lab
X
—
—
—
X
—
—
—
—
X
—
—
—
—
—
—
Pregnancy test6
Local lab
Local lab
X
X
—
—
—
—
—
—
X
—
—
—
—
—
X
—
See footnote 12
 
1 CSR = central specimen repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2 HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA); Dartmouth College (Hanover, 
New Hampshire, USA). 
 Non-HVTN laboratories: VITL = Vaccine Research Center - Immunology Testing Laboratory (Gaithersburg, Maryland, USA); ARUP Laboratories (Salt Lake City, Utah, USA). 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 160 of 165 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
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 For a participant who was born female (ie, assigned female sex at birth), pregnancy test must be performed on urine or blood specimens on the day of study product infusion with negative results 
received prior to infusion. Persons who have undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
7 At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.10), blood should be drawn for HIV diagnostic testing, as shown for visit 16 above. If a 
participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.12). 
8 And microscopy if needed. 
9 Syphilis testing will be done by serology. 
10 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis, and pregnancy tests will be collected. 
11 To investigate mAb reactions, assays may be performed on serum samples taken prior to the study product administration associated with the reaction and collected after the onset of reaction. Refer 
to the HVTN 130/HPTN 089 SSP for more information. 
12 SST blood will be collected at specific timepoints after the onset of any mAb reaction. Refer to the HVTN 130/HPTN 089 SSP for more information. 
13 The 56-day total blood volume does not include up to 51mL SST blood collected for any mAb reaction; however, the 56-day limit is not exceeded at any visit by the possible collection of SST 
blood for a mAb reaction. 
14 Of this volume, 17mL of SST blood will be collected 1 hour after the end of the infusion (see Section 9.3). 
y = SST blood collected for serum storage will also cover specimen needs for drug concentrations, HIV-1 neutralizing Ab assays, non-neutralizing antiviral assays, and ADA detection and functional 
assays (including for any mAb reactions); no separate blood draw is needed. 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 161 of 165 
Appendix I 
Procedures at CRS for Groups 1 – 3  
 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
Post 
Day: 
 
D0 
D3 
D6 
D14 
D28 
D56 
 
D112 
 
D168 
D224 
D280 
D336 
 
Week: 
 
W0 
 
 
W2 
W4 
W8 
 
W16 
 
W24 
W32 
W40 
W48 
 
Procedure 
Scr 
Inf  
 
 
 
 
 
 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
X 
— 
Confirm eligibility, obtain demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Infusion 
— 
X 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Solicited AE assessment3 
— 
X 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
— 
— 
Risk reduction counseling4 
X 
X 
— 
— 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
— 
Contraception status assessment5 
X 
X 
— 
— 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
— 
Social impact assessment 
— 
X 
— 
— 
— 
— 
X 
 
X 
 
X 
X 
X 
X 
 
Behavioral risk assessment questionnaire6 
X 
— 
— 
— 
— 
— 
— 
 
— 
 
X 
— 
— 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
 
— 
 
X 
— 
— 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
— 
 
— 
 
— 
— 
— 
— 
— 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
— 
Intercurrent illness/Unsolicited AE assessment 
— 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
— 
HIV infection assessment7 
X 
— 
— 
— 
— 
— 
— 
 
X 
 
— 
X 
— 
X 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
 
— 
 
X 
— 
X 
— 
X 
Sample Collection8 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
2 Specimens collected at Day 0 may be obtained within the 14 days prior to study product administration, except for a pregnancy test, which must be performed on urine or blood specimens within 24 
hours prior to study product administration with negative results received prior to study product administration. 
3 Solicited AE assessments performed daily for at least 3 days following study product administration. CRS staff to contact participant to review and report Solicited AEs following the Solicited AE 
period (see the HVTN 130/HPTN 089 SSP). 
4 Includes transmission risk reduction counseling for HIV-infected participants. 
5 Contraception status assessment is required only for participants who were assigned female sex at birth and who are capable of becoming pregnant. 
6 Not applicable to HIV-infected participants. 
7 Includes pretest counseling and HIV testing. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. Not applicable for participants diagnosed 
with HIV infection. 
8 For specimen collection requirements, see Appendix G. 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 162 of 165 
Appendix J 
Procedures at CRS for Group 4  
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
093 
10 
11 
12 
13 
14 
15 
16 
Post 
Day: 
 
D0 
D3 
D6 
D14 
D28 
D56 
D84 
D112 
D140 
D168 
D224 
D280 
D336 
D392 
D448 
 
Week: 
 
W0 
 
 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W32 
W40 
W48 
W56 
W64 
 
Procedure 
Scr 
Inf 1 
 
 
 
 
 
 
Inf 2 
 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Confirm eligibility, obtain demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Infusion4 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
Solicited AE assessment4 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Risk reduction counseling5 
X 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Contraception status assessment6 
X 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Social impact assessment 
— 
X 
— 
— 
— 
— 
X 
— 
X 
— 
X 
X 
X 
X 
X 
X 
— 
Behavioral risk assessment questionnaire7 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/Unsolicited adverse experience 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
HIV infection assessment8 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
X 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
X 
— 
X 
Sample collection9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
2 Specimens collected at Day 0 may be obtained within the 14 days prior to study product administration, except for a pregnancy test, which must be performed on urine or blood specimens within 24 
hours prior to study product administration with negative results received prior to study product administration. 
3 Blood draws required at study product administration 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 with the 3 days prior to study product administration. 
4 Solicited AE assessments performed daily for at least 3 days following study product administration. CRS staff to contact participant to review and report Solicited AEs following the Solicited AE 
period (see the HVTN 130/HPTN 089 SSP). 
5 Includes transmission risk reduction counseling for HIV-infected participants. 
6 Contraception status assessment is required only for participants who were assigned female sex at birth and who are capable of becoming pregnant. 
7 Not applicable to HIV-infected participants. 
8 Includes pretest counseling and HIV testing. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. Not applicable for participants diagnosed 
with HIV infection. 
9 For specimen collection requirements, see Appendix H. 
 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 163 of 165 
Appendix K 
HVTN low risk guidelines for the US 
 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 164 of 165 
 

HVTN 130/HPTN 089 Version 1.0 / April 4, 2019 
HVTN130_HPTN089_v1.0_FINAL.docx / Page 165 of 165 
Appendix L 
Protocol Signature Page 
 
A phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and 
antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-
1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-1 
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 (eg, 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 130/HPTN 089 
DAIDS Protocol Version: Version 1.0 
Protocol Date: April 4, 2019