A Phase 1 Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Monoclonal Antibody PGT121.414.LS Administered Alone and in Combination With VRC07-523LS Via Intravenous or Subcutaneous Infusions in Healthy, HIV-uninfected Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

PROTOCOL 
HVTN 136/HPTN 092 
A phase 1 dose-escalation clinical trial to evaluate the 
safety, tolerability, pharmacokinetics, and antiviral 
activity of the monoclonal antibody PGT121.414.LS 
administered alone and in combination with  
VRC07-523LS via intravenous or subcutaneous 
infusions in healthy, HIV-uninfected adult participants 
DAIDS DOCUMENT ID 38634 
IND TBD HELD BY DAIDS 
CLINICAL TRIAL SPONSORED BY 
Division of AIDS (DAIDS) 
National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
Department of Health and Human Services (DHHS) 
Bethesda, Maryland, USA 
STUDY PRODUCTS PROVIDED BY 
Dale and Betty Bumpers Vaccine Research Center (VRC), NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
October 8, 2019 
Final 
HVTN 136/HPTN 092 
Version 1.0 

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Contents 
1 Overview ........................................................................................................................5 
1.1 
Protocol Team ................................................................................................9 
2 Ethical considerations ..................................................................................................11 
3 IRB/EC review considerations .....................................................................................13 
3.1 
Minimized risks to participants ....................................................................13 
3.2 
Reasonable risk/benefit balance ...................................................................13 
3.3 
Equitable participant selection .....................................................................14 
3.4 
Appropriate informed consent ......................................................................14 
3.5 
Adequate safety monitoring .........................................................................14 
3.6 
Protect privacy/confidentiality .....................................................................14 
4 Background ..................................................................................................................16 
4.1 
Rationale for trial concept ............................................................................17 
4.2 
Study products ..............................................................................................22 
4.3 
Trial design rationale ....................................................................................24 
4.4 
Plans for future product development and testing ........................................28 
4.5 
Preclinical studies .........................................................................................29 
4.6 
Clinical studies .............................................................................................35 
4.7 
Potential risks of study products and administration ...................................44 
5 Objectives and endpoints .............................................................................................47 
5.1 
Primary objectives and endpoints ................................................................47 
5.2 
Secondary objectives and endpoints ............................................................48 
5.3 
Exploratory objectives ..................................................................................49 
6 Statistical considerations ..............................................................................................50 
6.1 
Accrual and sample size calculations ...........................................................50 
6.2 
Randomization .............................................................................................53 
6.3 
Blinding ........................................................................................................53 
6.4 
Statistical analyses ........................................................................................54 
7 Selection and withdrawal of participants .....................................................................60 
7.1 
Inclusion criteria ...........................................................................................60 
7.2 
Exclusion criteria ..........................................................................................62 
7.3 
Participant departure from study product administration schedule or 
withdrawal (Part B) ......................................................................................65 
8 Study product preparation and administration .............................................................69 
8.1 
Study product regimen .................................................................................69 
8.2 
Study product formulation ...........................................................................70 
8.3 
Preparation of study products .......................................................................70 
8.4 
Administration ..............................................................................................74 
8.5 
Acquisition of study products ......................................................................75 
8.6 
Pharmacy records .........................................................................................76 
8.7 
Final disposition of study products ..............................................................76 
9 Clinical procedures ......................................................................................................77 
9.1 
Informed consent ..........................................................................................77 

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9.2 
Pre-enrollment procedures ...........................................................................79 
9.3 
Enrollment and study product administration visits .....................................81 
9.4 
Follow-up visits ............................................................................................83 
9.5 
HIV counseling and testing ..........................................................................84 
9.6 
Contraception status .....................................................................................85 
9.7 
Urine testing .................................................................................................86 
9.8 
Assessments of Solicited AEs ......................................................................86 
9.9 
Visit windows and missed visits ..................................................................88 
9.10 Early termination visit ..................................................................................88 
9.11 Pregnancy .....................................................................................................88 
9.12 HIV infection during the study .....................................................................88 
10 Laboratory ....................................................................................................................90 
10.1 CRS laboratory procedures ..........................................................................90 
10.2 Total blood volume ......................................................................................90 
10.3 PGT121.414.LS and VRC07-523LS concentrations ...................................90 
10.4 Neutralizing antibody assay .........................................................................91 
10.5 Monoclonal Ab reaction assays ....................................................................91 
10.6 Exploratory studies .......................................................................................91 
10.7 Specimen storage and other use of specimens .............................................92 
10.8 Biohazard containment .................................................................................92 
11 Safety monitoring and safety review ...........................................................................93 
11.1 Safety monitoring and oversight ..................................................................93 
11.2 Safety reporting ............................................................................................94 
11.3 Safety reviews ..............................................................................................97 
11.4 Safety pause and prompt PSRT AE review................................................100 
11.5 Review of cumulative safety data ..............................................................101 
11.6 Study termination .......................................................................................102 
12 Protocol conduct ........................................................................................................103 
12.1 Social impacts ............................................................................................104 
12.2 Emergency communication with study participants ..................................104 
13 Version history ...........................................................................................................105 
14 Document references (other than literature citations) ................................................106 
15 Acronyms and abbreviations......................................................................................108 
16 Literature cited ...........................................................................................................111 
Appendix A Sample informed consent form for Part A (Groups 1-4) ...........................119 
Appendix B Sample informed consent form for Part B (Groups 5 and 6) .....................138 
Appendix C Approved birth control methods for persons assigned female sex at birth 
(for sample informed consent form) ...........................................................158 
Appendix D Sample consent form for use of samples and information in other studies 159 
Appendix E Schematic of IV infusions and SC infusions ..............................................163 
Appendix F Table of procedures for Part A Groups 1-3 (for sample informed consent 
form) ...........................................................................................................164 

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Appendix G Table of procedures for Part A Group 4 (for sample informed consent form)
 165 
Appendix H Table of procedures for Part B Group 5 (for sample informed consent form)
 166 
Appendix I Table of procedures for Part B Group 6 (for sample informed consent form)
 167 
Appendix J Laboratory procedures for Part A – Groups 1, 2, and 3 .............................168 
Appendix K Laboratory procedures for Part A – Group 4 .............................................170 
Appendix L Laboratory procedures for Part B – Group 5 ..............................................172 
Appendix M Laboratory procedures for Part B – Group 6 ..............................................174 
Appendix N Procedures at CRS for Part A Groups 1 – 3 ...............................................176 
Appendix O Procedures at CRS for Part A Group 4 ......................................................177 
Appendix P Procedures at CRS for Part B Group 5 .......................................................178 
Appendix Q Procedures at CRS for Part B Group 6 .......................................................180 
Appendix R HVTN low risk guidelines for the US ........................................................182 
Appendix S Visit Windows for Part A Groups 1-3 ........................................................184 
Appendix T Visit Windows for Part A Group 4 .............................................................185 
Appendix U Visit Windows for Part B Group 5 .............................................................186 
Appendix V Visit Windows for Part B Group 6 .............................................................187 
Appendix W Protocol Signature Page .............................................................................188 
 
 

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1 
Overview 
Title 
A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, 
pharmacokinetics, and antiviral activity of the monoclonal antibody 
PGT121.414.LS administered alone and in combination with VRC07-523LS via 
intravenous or subcutaneous infusions in healthy, HIV-uninfected adult 
participants 
Primary objectives 
Primary objective 1 
To evaluate the safety and tolerability of the PGT121.414.LS monoclonal 
antibody (mAb) when administered alone via intravenous (IV) or subcutaneous 
(SC) infusion (Part A) and of PGT121.414.LS and VRC07-523LS administered 
consecutively via IV or SC routes at and after each product administration visit 
(Part B). 
Primary objective 2 
To evaluate the serum concentrations and pharmacokinetic (PK) properties of 
PGT121.414.LS after a single administration (Part A) and of PGT121.414.LS and 
VRC07-523LS after consecutive administration of the pair of mAbs at and after 
each of 3 quarterly visits (Part B).  
Primary objective 3 
To evaluate the individual mAb-specific serum neutralizing activity of 
PGT121.414.LS after a single administration (Part A) and of PGT121.414.LS and 
VRC07-523LS after consecutive administration of the pair of mAbs at and after 
each of 3 quarterly visits (Part B). 
 

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Study products 
• PGT121.BIJ414.LS (referenced and labeled as PGT121.414.LS) is a human 
mAb that targets the HIV-1 V3 glycan, centered on N332. It is a derivative of 
PGT121 that was engineered for improved manufacturing, stability and in 
vivo elimination half-life by Just Biotherapeutics in collaboration with Dan 
Barouch and the Collaboration for AIDS Vaccine Discovery (CAVD) 
investigators. The drug substance was manufactured under current Good 
Manufacturing Practice (cGMP) standards at Just Biotherapeutics under 
contract to DAIDS’s Vaccine Translational Research Branch (VTRB). The 
drug product was filled and released by the Dale and Betty Bumpers Vaccine 
Research Center (VRC) and Vaccine Clinical Materials Program (VCMP), 
Leidos Biomedical Research, Inc., Frederick, MD. Product is provided at 100 
mg/mL as 10 mL glass vials with a 4.75 mL fill volume. 
• VRC-HIVMAB075-00-AB (VRC07-523LS) is a human mAb that targets the 
HIV-1 CD4 binding site. It was developed by the VRC/NIAID/NIH and 
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, MD. 
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 
Number 
Dose 
Route 
Month 0  
(Day 0) 
Month 4  
(Day 112) 
Month 8  
(Day 224) 
Part A 
 
 
 
 
 
 
Group 
1* 
3 
3 mg/kg 
IV 
PGT121.414.LS 
— 
— 
Group 
2a* 
3 
10 mg/kg 
IV 
PGT121.414.LS 
— 
— 
Group 
3b* 
3 
30 mg/kg 
IV 
PGT121.414.LS 
— 
— 
Group 
4b* 
3 
5 mg/kg 
SC 
PGT121.414.LS 
— 
— 
Part B 
 
 
 
 
 
 
Group 
5c 
10 
20 mg/kg 
+  
20 mg/kg 
IV 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
Group 
6c 
10 
5 mg/kg 
+ 
5 mg/kg 
SC 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
Total 
32 
 
 
 
 
 
 
 

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Notes 
IV = intravenous infusion; SC = subcutaneous infusion. Infusions are given sequentially in the 
order shown. 
a Enrollment in Group 2 begins following review of safety data for participants in Group 1. 
b Enrollment in Groups 3 and 4 begins concurrently following review of safety data for 
participants in Groups 1 and 2. 
c Enrollment in Groups 5 and 6 begins concurrently following review of safety data for 
participants in Part A. Details described in Section 11.3  
*Additional participants may be enrolled to ensure the availability of 2-week safety data from at 
least 3 participants 
Participants 
32 healthy, HIV-1–uninfected volunteers aged 18 to 50 years 
Multicenter design 
Part A: dose escalation, first in human, open-label IV or SC product 
administration with randomization into Groups 3 and 4 
Part B: randomized, open-label IV or SC product administration 
Duration per participant 
Part A: 8 months per participant in Groups 1, 2 and 3; 6 months per participant in 
Group 4; 16 months per participant in Part B. 
Estimated total study duration 
24 months (includes enrollment, planned safety holds, and follow-up) 
Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
Study product providers 
• PGT121.414.LS: Dale and Betty Bumpers Vaccine Research Center (VRC), 
NIAID, NIH, DHHS (Bethesda, MD, USA) 
• VRC07-523LS: Dale and Betty Bumpers Vaccine Research Center (VRC), 
NIAID, NIH, DHHS (Bethesda, MD, USA) 
Core operations 
HIV Vaccine Trials Network (HVTN) Leadership Group/Core Operations Center, 
Fred Hutchinson Cancer Research Center (Fred Hutch) (Seattle, Washington, 
USA) 

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HIV Prevention Trials Network (HPTN) Leadership Operations Center (LOC), 
FHI 360 (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 
• Duke University Medical Center (Durham, North Carolina, USA) 
• Fred Hutch/University of Washington (Seattle, Washington, USA) 
• Dartmouth College (Hanover, New Hampshire, USA)  
Study sites 
HVTN and HPTN Clinical Research Sites (CRSs) in the United States to be 
specified in the Site Announcement Memo 
Safety monitoring 
HVTN 136/HPTN 092 Protocol Safety Review Team (PSRT); HVTN Safety 
Monitoring Board (SMB) 

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1.1 
Protocol Team 
Protocol leadership 
HVTN Chair Srilatha Edupuganti 
Emory University 
404-712-1434 
sedupug@emory.edu 
HPTN Chair Christopher Hurt 
UNC Chapel Hill 
919-966-2789 
christopher_hurt@med.unc.edu 
BIDMC 
Chair 
Kathryn Stephenson 
BIDMC, Harvard University 
617-735-4556 
kstephen@bidmc.harvard.edu 
  
HVTN 
Protocol 
team leader 
Carmen Paez 
HVTN Core, Fred Hutch 
206-667-2881 
cpaez@fredhutch.org 
HPTN 
Protocol 
team leader 
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 
HVTN 
Jane Baumblatt 
DAIDS, NIAID 
301-761-7754 
jane.baumblatt@nih.gov 
DAIDS 
Medical 
officer 
HPTN 
Wairimu Chege 
DAIDS, NIAID 
240-292-4786 
wairimu.chege@nih.gov 
Other contributors to the original protocol 
HVTN Core medical 
monitor 
Carmen Paez 
HVTN Core, Fred Hutch 
HVTN Clinical safety 
specialist 
Sophie Hasan 
HVTN Core, Fred Hutch 
Consultants Bette Korber 
Los Alamos National 
Laboratory 
HPTN Prevention 
research specialist 
Michelle Robinson 
HPTN LOC, FHI 360 
 Kshitij Wagh 
Los Alamos National 
Laboratory 
HPTN Senior Clinical 
research manager 
Bonnie Dye 
HPTN LOC, FHI 360 
Study product 
developer 
representatives 
Lucio Gama 
VRC 
HPTN Pharmacologist Julie Dumond 
UNC Chapel Hill 
 Dan Barouch 
BIDMC 
HVTN DAIDS protocol 
pharmacist 
Justine Beck 
DAIDS, NIAID 
301-761-5288 
 Nandini Sane 
DAIDS, NIAID 
HVTN Statistical 
research associate 
Xue Han 
SCHARP, Fred Hutch 
 Jennifer Grossman 
DAIDS, NIAID 
  

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HVTN Laboratory 
Program 
representative 
Jen Hanke  
HVTN Laboratory 
Program, Fred Hutch 
HPTN Laboratory 
Program representative 
Vanessa Cummings 
HPTN Laboratory 
Center, Johns Hopkins 
University 
HVTN Clinical trials 
manager 
Carissa Karg 
HVTN Core, Fred Hutch 
SDMC Clinical data 
management manager 
Kristine Donaty 
SCHARP, Fred Hutch 
HVTN Regulatory 
affairs associate 
Laurie Rinn 
HVTN Core, Fred Hutch 
SDMC Associate 
director of lab science 
April Randhawa 
SCHARP, Fred Hutch 
Clinic coordinators Miriam Chicurel-Bayard 
UNC Chapel Hill 
  
 Shashikala Nagar 
Emory Hope Clinic 
HVTN Protocol 
development manager 
Ramey Fair 
HVTN Core, Fred Hutch 
HVTN Community 
Advisory Board 
member 
Hakeem White 
Emory Hope Clinic CAB 
HPTN Community 
program manager 
Jonathan Lucas 
HPTN LOC, FHI 360 
HPTN Community 
Advisory Board 
member 
W Scott Cooley 
UNC Chapel Hill CAB 
HPTN community 
educator/recruiter 
Noshima Darden-Tabb 
UNC Chapel Hill 
HVTN Community 
engagement unit 
representative 
Gail Broder 
HVTN Core, Fred Hutch 
HVTN Technical editor Richa Chaturvedi 
HVTN Core, Fred Hutch 
HVTN community 
educator/recruiter 
Machel Hunt 
Emory Hope Clinic 
  
 

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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 136/HPTN 
092 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 
(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 
In 2017, more than 35 million people were living with HIV, and 1.8 million 
people were newly infected with the virus (4). While many countries have 
achieved progress toward leveling HIV incidence over the past several years, 
micro-epidemics of infection continue to occur in all regions, even in countries 
with robust public health infrastructure. Effective biomedical interventions are 
urgently needed to reduce HIV acquisition. A vaccine is the preferred intervention 
(5) but remains a major challenge. Antiretroviral treatment can decrease HIV 
transmission (6) and the use of pre-exposure prophylaxis (PrEP) can decrease 
acquisition (7), but both interventions face limitations due to adherence, side 
effects and the logistics and costs of implementation (8). Alternative interventions 
are being considered that use passively administered, long-acting antiretroviral 
drugs or neutralizing antibodies (nAb) for prevention (9-14) 
Passive immunization for prevention of infectious diseases has been employed for 
more than 100 years, most often as postexposure prophylaxis against hepatitis A 
and B, rabies, measles, and varicella zoster virus (15). Palivizumab, a monoclonal 
antibody (mAb) directed against the F protein of respiratory syncytial virus 
(RSV), has been used for nearly 2 decades as RSV prophylaxis in preterm and 
other high-risk infants (16-18). Administration of palivizumab serves as a model 
for the use of mAbs to block a mucosally-acquired infection. 
The most promising approach for applying passive immunization to HIV-1 
involves broadly neutralizing antibodies (bnAbs). These naturally occurring 
antibodies (Abs) may be isolated from many HIV-1–infected individuals, usually 
after at least several years of infection (19), and feature unusual characteristics, 
such as long hypervariable loops, an ability to overcome host tolerance control, 
interaction with glycans, and high levels of somatic mutation in the variable 
domains facilitating binding to the highly glycosylated HIV-1 envelope protein 
(20-22). These distinctive features are selected for during natural infection and co-
evolution of the virus and antibodies in an infected host; potency and 
heterologous breadth is acquired over long term iterative cycles of immune 
escape, epitope diversification, and antibody adaptation to resistant variants (23).  
While it is challenging to emulate these processes by vaccination, using bnAbs to 
inform and expedite the development of HIV vaccines may eventually enable 
elicitation of such antibodies by immunization (24-29). Meanwhile, there is great 
interest in studying passive immunization with monoclonal antibodies (mAbs) 
modeled on these naturally-occurring bnAbs to prevent, treat, and potentially cure 
HIV-1 infection.  
Until recently, these antibodies were few in number, targeted a narrow spectrum 
of HIV strains and Env epitopes, and were not potent enough for practical use. 
Since 2012, the field has changed dramatically: new developments in antigen-
specific memory B cell sorting and high throughput single-cell polymerase chain 
reaction (PCR) amplification have led to the isolation of new monoclonal 
antibodies with extraordinary potency and breadth (11, 12, 30). 

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In 2016, VRC01 advanced to the first prevention efficacy trials in HIV-uninfected 
individuals. In addition to assessing safety and PK, the Antibody Mediated 
Prevention (AMP) Trials (HVTN 704/HPTN 085 [NCT02716675] and HVTN 
703/HPTN 081 [NCT02568215]) include assessment of neutralizing and non-
neutralizing antiviral activity (ie, Fc effector functions), neutralization and genetic 
sieve analyses, and correlates analyses (31). These important proof-of-concept 
trials will help us determine whether antibodies that neutralize HIV-1 in vitro and 
protect nonhuman primates (NHPs) from experimental simian-human 
immunodeficiency virus (SHIV) challenge will protect against the acquisition of 
HIV infection in humans. They also aim to determine the protective titer – a 
critical parameter in designing future clinical trials of passive immunization and 
vaccines. 
As of 2019, dozens of bnAbs have been identified, and their HIV-1 target sites 
and mechanisms of neutralization have been elucidated (20, 21, 23, 24, 32, 33). 
These efforts have set the stage for evaluation of these antibodies’ potential to 
contribute to HIV-1 prevention, treatment, and possibly cure (25-29). Passive 
infusion studies in NHPs demonstrated that bnAbs were effective in protection 
against mucosal SHIV challenge (34-43) and broadly neutralizing investigational 
mAb products can reduce HIV RNA levels in humans (43-50). Results from 
early-phase human clinical trials using different classes of bnAbs, such as those 
targeting the CD4 binding site (eg, VRC01 and 3BNC117) and a glycan-
dependent epitope at the base of the V3 loop (eg, 10-1074 and PGT121), have 
been encouraging, demonstrating the potential for and challenges of developing 
anti-HIV-1 bnAbs as preventive and therapeutic agents (41, 44-47, 49-51). 
4.1 
Rationale for trial concept 
The development of mAb investigational products for the potential prevention and 
treatment of HIV is evolving rapidly. Multiple mAbs have been developed, each 
of which target 1 of 6 known sites on the HIV-1 Env protein (Figure 4-1): 
1. the CD4-binding site,  
2. V2-apex region of gp120, 
3. V3-glycan region of gp120,  
4. the membrane-proximal external region (MPER) of gp41,  
5. the gp120-gp41 interface/gp41 fusion peptide,  
6. glycan-dependent epitopes in the center of the gp120 silent face (52).  
These mAb products display a broad range of neutralization potency and breadth 
and some of the more promising molecules have been engineered for improved 
neutralization, manufacturability, stability, and serum half-life. Additional 
improvements continue to be made, including the construction of engineered, 
chimeric bi- and tri-specific mAbs (53-55). While relatively few HIV neutralizing 
mAbs are currently available for clinical evaluation, those that are include some 
of the broadest and most potent mAbs identified to date. Thus, the available 
products, though limited, provide opportunities to address important scientific 

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questions through clinical evaluation and to plan for follow-up efficacy trials of 
passively delivered mAbs.  
 
Figure 4-1 Antibody targets on the HIV-1 trimer (image by Stewart-Jones, Doria-Rose, 
Stuckey; adapted from (56, 57)) 
As mentioned above, the VRC01 AMP trials are important proof-of-concept trials 
to demonstrate whether bnAbs can prevent HIV infection, and to gain insights 
into the potency needed for prevention. However, we recognize that much 
stronger and broader neutralization will be required to counter the genetic 
variability of HIV across diverse geographic locations. Indeed, models that 
combine in vitro neutralizing activity and NHP protection data predict that 2 or 
more of the best bnAbs may be needed, either as a combination of individual 
bnAbs, as bi- or tri-specific bnAbs, or both (13). 
The overarching aims guiding this study are to characterize the safety, tolerability, 
and PK of 2 broadly-neutralizing mAb investigational products, VRC07-523LS 
(CD4-binding site) and PGT121.414.LS (V3-glycan), when co-administered IV 
and SC, and to describe whether there is an increase in neutralization potential in 
humans with this mAb combination as predicted by the in vitro neutralizing 
activity of the corresponding non-infused clinical products. The data collected in 
this protocol will contribute significantly to future analyses that aim to combine 
LS versions of 3 broadly-neutralizing mAbs to optimize prevention efficacy. 
Our long-term goal is to clinically test the combination of VRC07-523LS, 
PGT121.414.LS and PGDM1400LS because of the superior in vitro neutralization 
profiles across all major global subtypes (see below). If efficacious, this 
combination would likely be developed as a global product. Data collected in this 
protocol will contribute significantly to this end goal. 
It is reasonable to ask why we are working to advance these specific mAbs from 
among the various options available. CD4-binding site bnAbs are likely going to 
serve as the “backbone” of any mAb combination approach, owing to their 
exceptional breadth. VRC01 has detectable inhibitory concentration (IC80) 
responses for 80% of the 403 globally sampled pseudoviruses summarized in 

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Figure 4-2, with a median IC80 of 1.75 mcg/mL. Ongoing clinical studies have 
begun to assess VRC07-523LS, which has substantially improved performance in 
vitro, neutralizing up to 97% of circulating strains, with a median IC80 of only 
0.162 mcg/mL. Among all of the diverse pseudoviruses with neutralization data 
collected in the Los Alamos Immunology database (Compile, Analyze and Tally 
nAb Panels [CATNAP]), 59% (412 of 704) have an IC50 < 1 mcg/mL using 
VRC01, while 91% (365/402) have an IC50 < 1 mcg/mL using VRC07-523LS 
(www.hiv.lanl.giv/components/sequence/HIV/neutralization/index.html). 
V3-glycan and V2-apex bnAbs have a narrower breadth than CD4-binding site 
bnAbs, but their potency often exceeds CD4-binding site Abs for a subset of 
viruses (Figure 4-2). V3-glycan and V2-apex bnAbs are also complementary in 
coverage (42), individually neutralizing 50-70% of viruses – whereas combined, 
they neutralize >90% of viruses at IC50 < 1 mcg/mL. Studies of in vitro 
neutralization have shown that a triple combination of CD4-binding site + V2-
apex + V3-glycan bnAbs outperforms “best-in-class” single and dual bnAbs, 
while the addition of a fourth bnAb provides minimal additional benefit in terms 
of enhancing the predicted combined IC50 values (13, 14, 58). Such a triple 
combination also increases the chance that at least 2 of the 3 antibodies in the 
combination will be simultaneously active (dual coverage) on any given strain. 
This in turn diminishes the chance for rapid selection of immune escape variants 
following exposure. Dual coverage also accounts for differences in PK among the 
antibodies, and for differences in the neutralization profiles of circulating viruses 
and the complex viral quasispecies encountered at transmission (42), to improve 
the probability that at least 1 bnAb will be active at an effective concentration 
over an extended period of time between dosing intervals. 
With respect to other “categories” of bnAbs, those targeting the gp120-gp41 
interface/fusion peptide and the gp120 silent face are not currently being pursued 
for passive prevention but remain of interest for vaccine design (59). Such 
antibodies may have benefits in clade A and B epidemics (60) MPER bnAbs 
exhibit promising potency and breadth but often possess lipid-binding properties 
that could have undesirable effects. In a recent trial, the lead MPER bnAb clinical 
candidate, 10E8VLS, had a disappointing PK profile, and 1 participant who 
received subcutaneous injections experienced severe erythema and panniculitis at 
the injection site, resulting in suspension of the trial (61). It is possible that MPER 
or fusion peptide-targeting bnAbs may eventually be useful as clinical products, 
but are currently not ready for evaluation.  

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Figure 4-2 Magnitude, breadth and dual coverage predictions for PGT121, PGDM1400, 
VRC07-523LS and combinations of these 3 mAbs against a multiclade panel of HIV isolates. 
VRC01 is shown as reference to AMP. (A) The top row shows cumulative coverage (%) of 
pseudoviruses at a given IC80 for single bnAbs and their 2 and 3 bnAb combinations. The bottom 
row shows cumulative coverage (%) of pseudoviruses neutralized by at least 2 bnAbs in the 2 or 3 
bnAb combinations as a function of combination IC80 titers. (B) IC80 titers for individual bnAbs and 
their 2 and 3 combinations for the full dataset and for individual subtypes of interest. Rows indicate 
pseudoviruses and columns indicate IC80 titers for a given bnAb or combination. For each panel, 
the ordering of viruses is the same between single bnAbs and 2/3 bnAb combinations. USA = 
United States, RSA = South Africa. (C) IC80 titers for VRC01 and VRC07-523LS are shown as 
heatmaps, as in (B). Pseudoviruses are grouped according to subtypes of interest, with "Other" 
indicating all other subtypes in the dataset. 
PGT121.414.LS was recently assayed by the VRC against a multiclade panel of 
208 viruses and shown to be equivalent to PGT121 against most but not all of the 
viruses (Figure 4-3). In some cases PGT121.414.LS had diminished potency 
against a subset of viruses that are least sensitive to PGT121, whereas it gained 
potency against a subset of viruses that are most sensitive to PGT121. Despite 
these differences, there was excellent overall concordance between the 2 
antibodies (r2= 0.736 and 0.776 for IC50 and IC80 values, respectively, 

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p<0.0001). These findings support the use of PGT121 neutralization data to 
predict PGT121.414.LS activity. 
As shown in Figure 4-3, PGT121 displays limited breadth but has outstanding 
potency against the viruses that are neutralized, having among the lowest median 
IC50 and IC80 titers among all bnAbs identified to date (30) (see Section 4.2.1). 
VRC07-523LS, a highly engineered derivative of the bnAb VRC01, displays 
somewhat lower potency than PGT121 but has outstanding breadth and an 
improved PK profile (see Section 4.2.2). 
 
Figure 4-3 Comparison of in vitro neutralizing activity of PGT121 and PGT121.414.LS against 
a multiclade pseudovirus panel (n=208). 50 mcg/mL was the highest concentration tested and is 
used as the cut-off for negative neutralization. Dotted line shows median IC50 and IC80 of all 
viruses (including those not neutralized). Solid line shows median IC50 and IC80 of viruses 
sensitive to neutralization (excluding those not neutralized). Data courtesy of the Vaccine Research 
Center, NIH. 
Modeling by Korber, Wagh, and colleagues, using PGT121 in vitro data and the 
predicted neutralizing activity of PGT121.414.LS based on PGT121 data, suggests 
that the addition of PGT121.414.LS provides enhanced breadth and potency of 
heterologous variants relative to VRC07-523LS alone. In particular, 22 of the 403 
pseudoviruses tested for neutralization had no detectable sensitivity to VRC07-
523LS, and of these 9 were sensitive to PGT121. Perhaps more importantly, for 37% 
of the 403 pseudoviruses tested, PGT121 was more potent than VRC07-523LS, so it 
often makes a very substantial contribution to the overall potency of the combination 
(Figure 4-3). The combination of VRC07-523LS + PGT121.414.LS is predicted to 
provide no dual coverage of CRF01 because of broad resistance of this subtype to 
PGT121. PGT121 also has far more limited activity against clade A and CRF02, 
common viral lineages in west and central Africa. Thus, while in vitro neutralizing 
activity suggests that VRC01-523LS + PGT121.414.LS has potential for success in 
subtype B populations where both antibodies tend to be highly active (Figure 4-2) the 
addition of a V2-apex class antibody (eg, PGDM1400LS), because of complementary 
coverage with PGT121.414.LS and complementary potency with VRC07-523LS, 
would be the best candidate for a third bnAb addition.  
Early product development assessment of the PGT121 and  
VRC07-523LS mAbs has revealed an attractive product profile, including safety 

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and tolerability in early human trials (10, 45-47). Given the available safety and 
tolerability data of these 2 mAbs, it is scientifically sound to evaluate 
PGT121.414.LS alone and in combination with VRC07-523LS in a phase 1 
human clinical trial to assess safety (including anti-drug antibodies [ADA]), PK, 
and functional activity, and to contribute to the development of an experimental 
platform for a triple bnAb combination. This approach for optimizing future 
combination products is similar to the approach taken to develop combination 
therapies for HIV. The combination of these 2 mAbs with distinct epitope 
specificities will provide valuable experience assessing the potential additive, 
synergistic, or antagonistic properties of 2 bnAbs administered sequentially at the 
same study visit.  
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. 
4.1.1 
Cross-network implementation 
DAIDS has requested that its two major prevention trial networks—the HVTN 
and the HPTN—work together in the rapid development of HIV-directed bnAbs 
for both the advancement of vaccine research and HIV prevention purposes. This 
priority program leverages the historical partnership between the HVTN and the 
VRC (a major developer of anti-HIV bnAbs) and other commercial developers, 
the strong portfolio of biomedical-based HIV prevention trials that the HVTN and 
HPTN have developed over the past 2 decades, the multidisciplinary expertise of 
investigators in each network, and the networks’ complementary laboratory and 
statistical expertise. In addition, the two networks have complementary CRSs that 
allow for rapid enrollment of participants, worldwide. The engagement of CRSs 
from both networks, particularly in early phase trials, accelerates recruitment, 
diversifies the trial cohort, and builds capacity for the conduct of future bnAb 
efficacy trials. 
4.2 
Study products 
4.2.1 
PGT121.414.LS 
PGT121.BIJ414.LS (referenced and labeled as PGT121.414.LS) was produced by 
Just Biotherapeutics in collaboration with Dan Barouch (Beth Israel Deaconess 
Medical Center), and collaborative engagement of CAVD investigators. The drug 
substance was manufactured under cGMP standards at Just Biotherapeutics under 
contract to DAIDS’s Vaccine Translational Research Branch (VTRB). The drug 
product was filled and released for the Dale and Betty Bumpers Vaccine Research 
Center (VRC) by the Vaccine Clinical Materials Program (VCMP), Leidos 
Biomedical Research, Inc., Frederick, MD. The PGT121.414.LS mAb is an 
engineered variant of PGT121. It contains a total of 8 residue modifications to 
improve various aspects of manufacturing, stability and in vivo elimination half-
life. Six of the modifications are in the Fragment crystallizable (Fc) region, 

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providing increased conformational stability leading to improved manufacturing 
characteristics including low pH stability and an improved storage stability 
profile. The 2 modifications in the Fc region of each heavy chain are the Xencor 
Xtend LS modifications helping provide a significantly reduced elimination half-
life in vivo (62, 63). The magnitude and breadth of neutralizing activity of 
PGT121.414.LS and its PGT121 in vitro were shown to be nearly equivalent 
against a multiclade panel of Env-pseudotyped viruses (Figure 4-3).  
The bnAb, PGT121, was identified from African donor 17 of the International 
AIDS Vaccine Initiative (IAVI) Protocol G cohort. It 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 (64-66). Using a 162-pseudovirus panel, representative of all major 
HIV-1 circulating clades, the 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 (30). 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 (30, 
67, 68). 
4.2.2 
VRC07-523LS (VRC-HIVMAB075-00-AB) 
VRC07-523LS is a human mAb targeting the HIV-1 CD4 binding site, developed 
by NIAID-NIH at the VRC. 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 (69, 70). 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), were isolated and 
subsequently engineered to have potency and breadth greater than those of earlier 
antibodies (36). This protocol will use VRC07-523LS (“523” denotes sequential 
numbering when the engineered variant was generated; “LS” denotes 2 amino 
acid mutations). 
The VRC07 (wild-type) heavy chain was identified by 454 deep sequencing based 
on its similarity to VRC01 and was then engineered to pair it 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 2 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 (36). The LS 
designation in VRC07-523LS specifies methionine to leucine (L) and asparagine 
to serine (S) (M428L/N434S, referred to as LS) changes within the C-terminus of 

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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) 
(40, 62), thus, increasing plasma half-life. 
VRC07-523LS was found to be 5- to 8-fold more potent than VRC01, with an 
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 (36). In addition, it displayed minimal levels of autoreactivity. 
4.3 
Trial design rationale 
This is the first clinical study of the PGT121.414.LS mAb. This phase 1, dose-
escalation, open-label clinical trial is aiming to examine the safety, tolerability, 
dose, and pharmacokinetics of PGT121.414.LS with and without  
VRC07-523LS, a CD4 binding site mAb. The hypothesis is that PGT121.414.LS 
alone and paired with VRC07-523LS will be safe for administration to healthy 
adults by both the IV and SC routes. 
In Part A of the study, PGT121.414.LS will be administered via IV infusion at 3, 
10, or 30 mg/kg (Groups 1-3) or via SC infusion at 5 mg/kg (Group 4). Each 
group in Part A will have 3 participants. At each of 3 visits in Part B of the study, 
participants will receive consecutive administration of PGT121.414.LS followed 
by VRC07-523LS, at 20 mg/kg IV each per dose (Group 5) or 5 mg/kg SC each 
per dose (Group 6). Each group in Part B will have 10 participants, yielding a 
total sample size for Parts A and B of 32. Participants will be followed for 32 
weeks after the last study product administration via IV infusion and 24 weeks 
after the last study product administration via SC infusion. 
Cumulative safety data will be reviewed on a daily basis by Network clinical 
safety staff (ie, Clinical Safety Specialist nurses and physicians) and reviewed at 
least weekly by the HVTN 136/HPTN 092 Protocol Safety Review Team (PSRT) 
for all participants in all groups. There will be a planned safety hold to evaluate 
safety at least 2 weeks after product administration in all groups (see Section 
11.3.1 and Table 11-1). 
The HVTN 136/HPTN 092 PSRT will request an ad hoc review of the data by the 
HVTN SMB in the instance that serious safety events are identified during the 
planned safety holds (see Section 11.3). 
Ideally, this study will demonstrate that PGT121.414.LS alone and in 
combination with VRC07-523LS is safe and well-tolerated when given 
intravenously and subcutaneously, and that the half-life of PGT121.414.LS is 
significantly extended compared to PGT121, as well as unchanged by co-
administration with VRC07-523LS. The study aims to evaluate if sera from 
infused participants retain the same neutralizing breadth in vitro as PGT121 alone 
and in combination with VRC07-523LS. 

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This protocol is part of a series of protocols gathering data to determine the best 
mAb combinations to be used in a future efficacy trial. The doses and dosing 
intervals selected for this trial will allow for comparability with other clinical 
trials evaluating VRC07-523LS and PGT121 both of which are being 
administered alone and in different combinations. Existing clinical trials 
evaluating VRC07-523LS and PGT121 either alone or in combination are 
summarized in Table 4-1. 
Table 4-1 Summary of bnAb clinical trials that evaluate VRC07-523LS and PGT121 alone or 
in combination. 
Study 
bnAb 
Dose (mg/kg) and 
Route 
Interval(weeks) 
VRC605 
VRC07-523LS 
1,5,20,40 IV  
Single dose 
 
 
5 SC 
Single dose 
 
 
5 SC 
Q12 
 
 
20 IV 
Q12 
HVTN 127/ 
HPTN 087 
VRC07-523LS 
2.5,5,20 IV 
Q16 
2.5,5 SC 
Q16 
 
 
2.5 IM 
Q16 
IAVI T001 
PGT121 
3,10,30 IV 
Single dose 
 
 
3 SC 
Single dose 
IAVI T002 
PGT121+PGDM1400 
3+3 IV 
Single dose 
 
 
10+10 IV 
Single dose 
 
 
30+30 IV 
Single dose 
IAVI T003 
PGT121+VRC07-523LS 
30+30 IV 
Single dose 
 
PGT121+VRC07-523LS+ 
PGDM1400 
20+20+20 IV 
Single dose 
HVTN 130/ 
HPTN 089 
PGT121+VRC07-523LS 
20+20 IV 
Single dose 
 
PGT121+PGDM1400+ 
VRC07-523LS 
20+20+20 IV 
Q16 
IV = intravenous infusion 
SC = subcutaneous injection 
IM = intramuscular injection 
The safety, tolerability, pharmacokinetics, and antiviral activity of VRC07-523LS 
and PGT121 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 (see Section 4.6).  
Additionally, IAVI T001 (NCT02960581) is assessing PGT121 alone, IAVI T002 
(NCT03205917) is gathering data on PGT121 administered in combination with 
PGDM1400 (10, 45-47) and IAVI T003 (NCT03721510) is evaluating PGT121 
administered in either a dual combination with VRC07-523LS or a triple 
combination with VRC07-523LS and PGDM1400 (see Section 4.6). 

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Furthermore, the HVTN 130/HPTN 089 study is designed to gather safety 
information on the dual combination groups (PGT121+VRC07-523LS) and in the 
triple combination Group (PGDM1400+PGT121+VRC07-523LS). The HVTN 
130/HPTN 089 protocol opened in July 2019 (see Section 4.6). 
4.3.1 
Dose, schedule and route of administration 
The doses and dosing schedule to be used in the HVTN 136/HPTN 092 clinical 
trial were selected based on prior clinical experience with VRC07-523LS and 
PGT121, as well as on PK modeling using nonclinical and clinical data for 
VRC07-523LS and PGT121. 
The proposed doses for Groups 1, 2, and 3 in Part A (3, 10 and 30 mg/kg IV), 
were selected based on previously tested doses of PGT121 in preclinical studies 
and in the IAVI T001 and IAVI T002 clinical trials. Because PGT121.414.LS is 
formulated in higher concentrations than PGT121, it is possible to administer a 
higher dose (5 vs. 3 mg/kg) via the SC route. 
Part A has a dose-escalation design, starting at the same low dose of antibody (3 
mg/kg IV) that was used as a starting dose in IAVI T001, the first in human trial 
of PGT121.  
In Part B, dosing is scheduled every 16 weeks based on preclinical and clinical 
data of VRC07-523LS and PGT121. The choice of 20 mg/kg dose IV and 5 
mg/kg SC aligns with ongoing protocols using VRC07-523LS either alone 
(VRC605 and HVTN 127/HPTN 087) or in combination with PGT121 (IAVI 
T003 and HVTN 130/HPTN 089). 
The doses of VRC07-523LS in Part B were selected using model-based 
predictions of this mAb serum concentration over time following IV and SC 
administrations of VRC07-523LS. Predictions were generated through 
simulations of PK data on VRC07-523LS serum concentrations based on a PK 
model of the VRC605 study. Moreover, dose and dosing intervals of 16 weeks in 
Groups 5 and 6 were selected to have high probability of achieving a trough 
above 1 mcg/mL for VRC07-523LS and likely for PGT121.414.LS (Figure 4-5), 
where 1 mcg/mL was shown to provide excellent coverage of the bnAb 
combination against a broad panel of viruses in vitro (Figure 4-2). 
An additional benefit to testing low doses of PGT121.414.LS, particularly the 5 
mg/kg SC dose, is to collect PK data at low concentrations where this product 
may still have antiviral activity. Data from the IAVI T001 trial have shown that 
the antibody PGT121 has very high potency in humans, with suppression of virus 
in HIV infected individuals (off all antiretrovirals) at concentrations 
< 0.7 mcg/mL. Therefore, it would be important to know the PK parameters of the 
antibody at these very low concentrations. This window of the concentration-time 
profile is more likely to be captured following low dose administrations, given the 
more frequent sampling following product administration. Characterizing low 
concentrations could be missed following the high dose administration as these 

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are likely to occur when sampling is sparse, with the possibility that 
concentrations fall below the limit of quantification between visits. 
Moreover, Figure 4-4 shows the predicted serum concentrations of VRC07-523LS 
following multiple IV infusions at 20 mg/kg or multiple SC injections at 5 mg/kg 
every 8 to 20 weeks. These concentrations were simulated based on population 
PK models using PK data observed in VRC605 for VRC07-523LS.  
 
Figure 4-4 Predicted VRC07-523LS concentration with multiple 8- to 20-weekly IV infusions 
at 20 mg/kg or SC injections at 5 mg/kg. Shown are median (solid lines), 5th and 95th percentiles 
(shaded areas) of predicted drug levels with values truncated at 0.55 mcg/mL. 
In these simulations, the body weights of 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 (71, 72). In addition, linear PK was assumed for the VRC07-523LS 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 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 

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SC injections. The mean and variance of log-transformed serum concentrations 
were computed after each IV infusion. Specifically, after the third IV infusion of 
VRC07-523LS at a dose level of 20 mg/kg, the mean serum concentrations were 
predicted to be 28.5, 9.0, and 2.8 mcg/mL, respectively at 16, 24, and 32 weeks 
post infusion. After the third SC injection at a dose level of 5 mg/kg, the mean 
serum concentration was predicted to be 3.9, and 1.2 mcg/mL, respectively, at 16 
and 24 weeks post injection. In addition, the chance of observing trough serum 
concentrations that are greater than 1 mcg/mL at 16 weeks post product 
administration is >95% for both 20 mg/kg IV and 5 mg/kg SC VRC07-523LS. 
Given the IC50 and 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 6.1). Thus, based on currently available data, in 
Groups 5 and 6, a dosing interval of every 16 weeks was selected to have high 
probability of achieving a trough above 1 mcg/mL for VRC07-523LS, and likely 
for PGT121.414.LS. 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 administration of each of these 
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, and similar mAbs 
given via IV and SC routes 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 
This protocol is part of a path to an efficacy trial of a triple bnAb combination 
comprising CD4-binding site + V2-apex + V3-glycan bnAbs. The CD4 binding 
bnAb (VRC07-523LS) will serve as the “backbone” for future dual- and triple-
combination mAb regimens. This protocol complements HVTN 130/HPTN 089 
in a series of studies that will evaluate synergism and antagonism between mAbs 
targeting different epitopes on HIV, with respect to PK, neutralization breadth, 
and potency. HVTN 130/HPTN 089 is testing the combination of VRC07-523LS 
and non-LS versions of PGT121 and PGDM1400. It is expected that future 
studies will evaluate mAb combinations incorporating LS-modified versions of all 
3 antibodies in preparation for a planned efficacy trial. HVTN 136/HPTN 092 

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will provide the foundation for combining LS versions of 2 bnAbs to different 
epitopes as a platform for adding the LS version of a third complementary bnAb 
in the future. The third planned bnAb, PGDM1400LS, is not expected to be ready 
for first-in-human (FIH) clinical testing until mid-to-late 2020. In the meantime, it 
is important to establish the behavior of VRC07-523LS and PGT121.414.LS 
when co-administered intravenously and subcutaneously, to determine whether 
co-administration alters the expected safety, tolerability, PK and neutralizing 
activity of the products compared to when they are administered as single agents.  
Other mAb interventions for HIV-1 in the clinical pipeline include:  
1. Trispecific antibody SAR441236 (Sanofi), incorporating Fab portions of 
VRC01, 10E8v4, and PGDM1400 along with an LS modification, which will 
undergo phase 1 clinical testing in HVTN 129/HPTN 088  
2. Bispecific 10E8.4/iMab (ADARC/Gates) that began phase 1 testing in early 
2019 
3. Dual combination of 3BNC117LS (CD4-binding site) and 10-1074LS (V3-
glycan) slated to begin phase 1/2 testing in the second half of 2019 
(Rockefeller University/IAVI/Gates), and 
4. Dual combination of VRC07-523LS and CAP256LS for South Africa, 
(VRC/CAPRISA).  
The unique dual combination of VRC07-523LS + PGT121.414.LS in HVTN 
136/HPTN 092 will provide critical information to guide future trials of mAbs 
incorporating LS-modified versions of a V2-apex bnAb (eg, PGDM1400LS). This 
triple combination is expected to have favorable safety, tolerability and PK, and to 
be superior to VRC01 for protection efficacy against multiple genetic subtypes of 
HIV-1 in different parts of the world. 
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 study (TCR), 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 
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 simian human immunodeficiency virus (SHIV) in the NHP model. 

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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. 
PGT121 administered at 10 mg/kg to SHIV-infected animals resulted in rapid 
virological 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 (73). 
4.5.2 
Preclinical studies of PGT121.414.LS 
Preclinical studies of PGT121.414.LS include: humanized FcRn mouse PK, NHP 
PK, repeat dose toxicity and Tissue Cross Reactivity. 
4.5.2.1 
Pharmacokinetic study of PGT121.414.LS in human FcRn transgenic mice 
The Vaccine Research Center (VRC), NIAID, NIH evaluated the in vivo 
pharmacokinetic profile of PGT121.414.LS in three human FcRn transgenic mice 
(74-76). In this study, we tested PGT121.414.LS (lot #S-20190121-1) produced 
from a stably transfected CHO cell line. The antibody was given at a single bolus 
dose of 10 mg/kg via the intravenous route. The levels of antibody in the sera of 
these animals at various time points up to 28 days after administration were then 
quantitated by an anti-PGT121 idiotype based ELISA method. Figure 4-5 shows 
the sera levels of PGT121.414.LS in each animal, with levels maintained above 
10 mcg/mL up to day 9 post infusion in all animals. After day 9, the sera levels of 
PGT121.414.LS steeply dropped to below the detection limit in 2 out of the 3 
animals indicative of an anti-drug antibody (ADA) response against 
PGT121.414.LS in those animals. The third animal showed a longer persistence 
of the antibody in the sera with levels dropping below the detection limit at day 
28 post infusion. 
 
Figure 4-5. Sera levels of PGT121.414.LS antibody in three human FcRn transgenic mice 
administered 10 mg/kg of the antibody via the intravenous route. 
 

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The pharmacokinetic parameters were calculated using a non-compartment model 
in the WinNonLin software package and are presented in Table 4-2. The average 
half-life was calculated to be 3.61 days with a range of 2.53 to 4.59 days. The 
average AUC (Area Under the Curve) was calculated to be 332 Day*mcg/mL 
with a range of 312 to 368 Day*mcg/mL. The average clearance was calculated to 
be 15.13 mL/Day/kg with a range of 13.58 to 15.99 mL/Day/kg. 
Table 4-2. In vivo pharmacokinetic parameters for PGT121.414.LS in human FcRn 
transgenic mice 
Antibody 
Animal ID 
Half-life 
AUC 
Clearance 
Day 
Day*mcg/mL 
mL/Day/kg 
PGT121.414LS 
2283 
4.59 
368 
13.58 
2284 
3.70 
315 
15.82 
2285 
2.53 
312 
15.99 
Average 
3.61 
332 
15.13 
Standard error 
0.46 
14 
0.60 
4.5.2.2 
Pharmacokinetic study of PGT121.414.LS in rhesus macaques 
The VRC evaluated the in vivo pharmacokinetic profile of PGT121.414.LS in 
four male and two female rhesus macaques. In this study, we tested 
PGT121.414.LS (lot #S-20190121-1) produced from a stably transfected CHO 
cell line. The antibody was given at a single bolus dose of 10 mg/kg via either the 
subcutaneous (n=3) or intravenous route (n=3). The levels of antibody in the sera 
of these animals at various time points up to 105 days after administration were 
then quantitated by an anti-PGT121 idiotype based ELISA method. Figure 4-6 
shows the sera levels of PGT121.414.LS in each animal. The initial sera antibody 
levels were higher when the antibody was given IV compared to SC, but by day 2 
the sera antibody levels were similar in all animals irrespective of route and 
followed similar distribution over time Also, sera antibody levels were maintained 
above 5mcg/mL for up to 105 days after dosing in all animals irrespective of 
route. In addition, none of the animals developed any anti-drug antibody 
responses against PGT121.414.LS in this study, as there were no steep drops in 
sera antibody levels over time 
 

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Figure 4-6. Sera levels of PGT121.414.LS antibody in six rhesus macaques administered at 
10 mg/kg of the antibody via either the subcutaneous (SC) or intravenous (IV) route. 
The pharmacokinetic parameters were calculated using a non-compartment model 
in the WinNonLin software package and are presented in Table 4-3. The average 
half-life for PGT121.414.LS was 28.4 days for the IV route and 27.8 days for the 
SC route, which were very similar to each other, with a range of 26.6 days to 
31.9 days. The AUC was slightly higher for the IV route (4710 day*mcg/mL) 
than for the SC route (3617 day*mcg/mL) due to the higher initial peak observed 
in the serum levels for the IV route compared to the SC route. The clearance was 
similar between the 2 routes (2.24 mL/day/kg for IV versus 2.61 mL/day/kg for 
SC). 

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HVTN136-HPTN092_v1.0_FINAL / Page 33 of 188 
Table 4-3. In vivo pharmacokinetic parameters for PGT121.414.LS in rhesus macaques 
Route 
Animal ID 
Half-life 
AUC 
Clearance 
(days) 
(day*mcg/mL) 
(mL/day/kg) 
IV 
0DG 
26.80 
4221 
2.22 
IV 
DGFH 
26.65 
3702 
2.54 
IV 
DGKX 
31.91 
4586 
1.96 
Average 
28.45 
4170 
2.24 
Standard error 
1.73 
257 
0.17 
SC 
09Z 
30.13 
4223 
2.15 
SC 
DGDW 
27.73 
3353 
2.78 
SC 
DGFK 
25.53 
3274 
2.90 
Average 
27.80 
3617 
2.61 
Standard error 
1.33 
304 
0.23 
Abbreviations: AUC, area under the curve; IV, intravenous; SC, subcutaneous.  
4.5.2.3 
GLP repeat dose IV or SC of PGT121.414.LS in rats 
PGT121.414.LS was tested in a GLP-compliant study to determine the potential 
toxicity and toxicokinetics of the mAb in Sprague Dawley rats after three IV or 
SC dose administrations at 10-day intervals (on Days 1, 11, and 21) followed by a 
recovery period. No clinically significant findings were noted in the toxicology 
study. The study details and results are included in the IB. 
4.5.2.4 
PGT121.414.LS Tissue Cross Reactivity (TCR) study 
PGT121.414.LS was tested in a GLP-compliant study to determine the potential 
cross reactivity of the mAb in human tissue cryosections. The TCR study was 
conducted using a panel of normal human tissue cryosections from 3 separate 
donors, according to recommendations in the Points to Consider in the 
Manufacture and Testing of Monoclonal Antibody Products for Human Use 
(CBER 1997) and consistent with ICH guidance S6(R1). No clinically significant 
findings were noted in the tissue cross reactivity study. The study details and 
results are included in the IB. 
4.5.2.5 
4.5.2.5 PGT121.414.LS preclinical functional studies 
PGT121.414.LS was recently assayed against a multiclade panel of 208 Env-
pseudoviruses at the VRC (Table 4-4 below). As expected it had less breadth than 
VRC07-523LS and VRC01 but was approximately 4-times more potent than 
VRC07-523LS and 10-times more potent than VRC01 against the viruses that 
were neutralized. 

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Table 4-4. Neutralization data of mAbs assayed against VITL/VRC Multiclade Panel 
 
See Investigator’s Brochure for further details. 
4.5.3 
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 
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 
intravenously (36). 
See the IB for further details. 
VITL/VRC Multiclade Panel
IC50
PGT121 
.414 LS
PGT121
VRC01
VRC01.23
VRC07-
523-LS
N6-LS
10-1074
PGDM 
1400
10E8v4
# Viruses
208
208
208
208
208
208
208
208
208
% VS Neutralized
IC50 <50ug/ml
58
65
90
96
96
98
63
80
98
IC50 <10ug/ml
55
64
89
96
96
97
63
79
98
IC50 <1.0ug/ml
50
56
72
94
92
95
60
75
71
IC50 <0.1ug/ml
44
44
17
73
53
63
42
60
15
For Sensitive Viruses Only:
Median IC50
0.022
0.040
0.328
0.041
0.081
0.069
0.054
0.014
0.463
Geometric Mean
0.044
0.072
0.339
0.042
0.088
0.072
0.060
0.024
0.419
For All Viruses:
Median IC50
0.904
0.352
0.392
0.042
0.086
0.071
0.204
0.043
0.468
Geometric Mean
0.868
0.691
0.548
0.055
0.116
0.081
0.724
0.107
0.470
IC80
PGT121 
.414 LS
PGT121
VRC01
VRC01.23
VRC07-
523-LS
N6-LS
10-1074
PGDM 
1400
10E8v4
# Viruses
208
208
208
208
208
208
208
208
208
% VS Neutralized
IC80 <50ug/ml
50
59
89
96
96
97
60
74
98
IC80 <10ug/ml
50
56
83
96
94
96
59
72
89
IC80 <1.0ug/ml
45
49
46
90
83
88
52
63
26
IC80 <0.1ug/ml
36
29
2
45
23
23
26
44
3
For Sensitive Viruses Only:
Median IC80
0.051
0.099
0.959
0.107
0.238
0.221
0.126
0.047
2.31
Geometric Mean
0.076
0.154
1.06
0.120
0.257
0.231
0.157
0.069
1.91
For All Viruses:
Median IC80
33.3
1.50
1.24
0.117
0.257
0.235
0.884
0.201
2.36
Geometric Mean
1.89
1.68
1.63
0.151
0.323
0.270
1.57
0.394
2.06

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4.6 
Clinical studies 
4.6.1 
Clinical studies of PGT121 
4.6.1.1 
IAVI T001 
IAVI 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 4-5. 
Table 4-5: IAVI T001 study schema 
 
The hypothesis in IAVI T001 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 March 2019, accrual is complete in 
Groups 1A-1C (HIV-uninfected, 3-30 mg/kg, IV route), Group 1D (HIV-
uninfected, 3 mg/kg, SC route), Groups 2A-2C (HIV-infected on ART, 3-30 
mg/kg, IV route) and 2B (HIV-infected, 10 mg/kg, IV route), and Group 3A  
(HIV-infected not on ART, 30 mg/kg IV route). There are 2 remaining slots open 
for enrollment in Group 3D (HIV-infected off ART with low viral load). Among 
all participants, there was short-lived, mild or moderate local and systemic 
reactogenicity. There were no HIV infections, pregnancies or deaths. One 
participant discontinued early after 10 weeks of follow up. There has been 1 
serious adverse event (SAE) that was assessed as not related. The SAE was a case 
of pre-patellar bursitis occurring 2 months after administration of the 

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investigational product for which the participant was hospitalized for surgical 
treatment and IV antibacterials administration for methicillin-sensitive 
Staphylococcus aureus infection. There have been 41 non-serious adverse events, 
of which 28 were assessed as not related, 9 were assessed as unlikely related 
(urinary tract infection grade 1, fatigue grade 2, nasal congestion grade 1, 
headache grade 1, abdominal pain grade 1, CD4+ T-cells decreased grade 1, 
bruising grade 1, neutropenia grade 1, haematuria grade 1), 4 were assessed as 
possibly related (gastroenteritis grade 2, fatigue grade 1, fatigue grade 2, headache 
grade 1). There were no probably related or definitely related adverse events. 
There were no dose limiting toxicities (DLTs), defined as 1) any grade 3 or 
greater reactogenicity or adverse event 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. 
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 
4-7, 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. 
 
Figure 4-7: 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). 
4.6.1.2 
IAVI T002 
T002 is a phase 1, randomized, placebo-controlled clinical trial of the safety, 
pharmacokinetics, and antiviral activity of PGDM1400 as well as the combination 
Group 1B
10 mg/kg IV
Group 1A
3 mg/kg IV
Group 1C
30 mg/kg IV

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of PGDM1400 and PGT121 in HIV-uninfected and HIV-infected adults. The 
study design is shown in Table 4-6. 
Table 4-6: IAVI T002 study schema 
 
Blinded interim safety data as of March 2019 includes all accumulated safety data 
for 24 weeks post investigational product administration for Groups 1A-C and 
2A-C. 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 adverse events (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 (Figure 4-8). 
As of March 2019 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 Safety Monitoring 

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Committee (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 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 PGDM1400 and 30 mg/kg PGT121. Enrollment into Group 3 (HIV-
infected viremic) began in November 2018 and it is estimated to be completed at 
the end of June 2019. 
 
Figure 4-8 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). 
LLOQ indicates lower limit of quantitation. 
4.6.1.3 
IAVI T003 
IAVI T003 is a phase 1/2a, open-label clinical trial of the safety, tolerability, 
pharmacokinetics, and antiviral activity of PGT121, VRC07-523LS and 
PGDM1400 in HIV-uninfected and HIV-infected adults. The study design is 
shown below in Table 4-7. 
 
0
5 0
1 0 0
1 5 0
0 .1
1
1 0
1 0 0
1 0 0 0
1 0 0 0 0
P G D M 1 4 0 0 µ g /m l
1A
T1
1
LLOQ
3 mg/kg IV
10 mg/kg IV
30 mg/kg IV

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Table 4-7: IAVI T003 study schema 
 
Notes: ART: Antiretroviral Therapy; ATI: Analytical Treatment Interruption (starting on Day 2 after 
participants complete their full course of ART for Day1 an after first IV infusion on Day 0); IV: intravenous; 
N/A: not applicable. 
As of March 2019, PGT121 has been administered in combination with VRC07-
523LS to 3 participants in the IAVI T003 trial. There have been no Grade 3 or 
higher local or systemic reactions, or related adverse events. One participant 
reported transient Grade 1 light-headedness on the same day as study product 
administration.  
4.6.2 
Clinical studies of VRC07-523LS 
4.6.2.1 
VRC 605 
VRC 605 is a phase 1, open-label, dose-escalation study of VRC07-523LS 
(NCT03015181) in healthy, HIV-uninfected adults to evaluate the safety and 
pharmacokinetics of 1 to 3 administrations of the antibody. The study is fully 
enrolled and study product administration is complete. The doses evaluated were 
a single administration of 1 mg/kg and 5 mg/kg IV and SC, 20 mg/kg and 40 
mg/kg IV, and 3 administrations (q 12 weeks) of 5 mg/kg SC and 20 mg/kg IV 
VRC07-523LS (Table 4-8).  
Study objectives included 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 4-8 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 
In VRC 605, a total of 41 administrations of VRC07-523LS occurred during the 
study. VRC07-523LS was safe and well tolerated, with no SAEs or dose-limiting 
toxicities. All reported local and systemic reactogenicity was mild to moderate in 
severity. Six AEs were determined to be possibly related to VRC07-523LS 
administration. One participant in group 5 exhibited grade 1 dizziness on the day 
of infusion, and 1 in group 7 reported grade 1 abdominal pain the day after 
infusion. Two volunteers (one each in groups 5 and 7) displayed either grade 1 or 
grade 2 infusion reactions following each administration, with symptoms typical 
of those observed following receipt of monoclonal antibodies: fever, chills, 
myalgia, nausea, and headache. Sera collected from the group 7 participant after 
each infusion showed an elevation of serum cytokines including Tumor necrosis 
factor alpha (TNF-a), Interleukin (IL)-6, and IL-13. Importantly, the levels of 
histamine, tryptase, Interferon gamma (IFN-g), sIL-2R, IL-1b, IL-2, IL-4, IL-5, 
IL-8, IL-10, IL-12, and IL-17 remained within normal levels, and the reaction 
grade decreased in this participant from grade 2 during the first two infusions to 
grade 1 during the final infusion. There were no symptoms of hypotension, 
urticaria, bronchospasm, or other symptoms of severe infusion reactions. Both 
volunteers were treated symptomatically with acetaminophen and ibuprofen. All 
symptoms resolved within 12 hours without increased monitoring required. 
Interim PK based on preliminary data suggest the average compartmental half-life 
of VRC07-523LS is 33 ±10 days, with an estimated 28-day trough after one 5 
mg/kg SC injection calculated at 27 (SD = 12) mcg/mL. 
Figure 4-9 displays interim and confidential VRC07-523LS PK data from VRC 
605. 
 
 
 

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Figure 4-9 (Top) Serum concentration of VRC01LS (from VRC 606) and of VRC07-523LS 
(from VRC 605) after a single SC injection of 5 mg/kg for each product. (Middle) Serum 
concentrations of VRC01 LS (from VRC 606) and of VRC07-523LS (from VRC 605) after 3 SC 
injections of 5 mg/kg for each product. (Bottom) Serum concentrations of VRC07-523LS 
(from VRC 605) after 3 IV infusions of 20 mg/kg. (Confidential–interim and preliminary; VRC 
study team personal communication) 
4.6.2.2 
HVTN 127/HPTN 087 
HVTN 127/HPTN 087 (NCT03387150) is a randomized phase 1 clinical trial 
evaluating the safety and serum concentrations of VRC07-523LS administered in 
multiple doses via different routes to healthy, HIV-uninfected adults (Table 4-9).  

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Table 4-9 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 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 ADAs emerge 
in response to repeated administrations of the antibody. 
One Grade 3 elevated alanine aminotransferase (ALT) deemed related to VRC07-
523LS has been reported; the remaining AEs deemed related have been grade 1 
(mild) or grade 2 (moderate). No related SAEs have been reported as of May 
2019. Four mAb reactions have been reported in three participants, including: (1) 
grade 1 generalized pruritus in a participant in Group 2 (5 mg/kg IV) after her 
first infusion; (2) grade 1 generalized pruritus in a participant in Group 5 (5 mg/kg 
SC) after the second series of SC injections; and (3) two infusion related reactions 
in a participant in Group 3 (20 mg/kg IV)- the first occurred after his first infusion 
and was grade 2 and characterized by chills, myalgia, arthralgia, malaise/fatigue, 
nausea and headache and the second occurred after his second infusion and was 
grade 1 and characterized by malaise/fatigue, chills and myalgia. 
4.6.2.3 
HVTN 128 
HVTN 128 is a randomized, phase 1 clinical trial that evaluates the safety, 
tolerability and pharmacokinetics of VRC07-523LS in the sera and mucosae of 
healthy, HIV-uninfected adults (Table 4-10).  

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Table 4-10 HVTN 128 (Version 1.0) study schema 
Group 
N* 
Route 
VRC07-
523LS Dose 
Product administration  
schedule 
D0 
D112 
D224 
W0 
W16 
W32 
1 
12 
IV 
10 mg/kg 
X 
X 
X 
2 
12 
IV 
30 mg/kg 
X 
X 
X 
Total 
24 
 
 
 
 
 
IV = intravenous infusion 
N* = number of participants receiving at least one product infusion 
As of May 2019, ten IV infusions of VRC07-523LS have been administered in 
the HVTN 128 trial. Four mAb reactions after first product administration have 
been reported in four participants including: (1) grade 1 facial flushing in a 
participant who enrolled into Group 2 (30 mg/kg IV); (2) grade 2 generalized 
pruritus in a participant in Group 2 (30 mg/kg IV); (3) grade 1 oropharyngeal 
itching in a participant who was randomized to Group 1 (10 mg/kg IV); and (4) 
grade 1 mAb reaction characterized by mild tachycardia, nausea, chills and 
headache in a participant enrolled in Group 1 (10 mg/kg IV). No other AEs 
deemed related or related SAEs to VRC07-523LS have been reported.  
4.6.2.4 
HVTN 130/HPTN 089 
HVTN 130/HPTN 089 is a randomized, phase 1 clinical trial that will evaluate the 
safety, tolerability and serum concentrations of PGT121, PGDM1400, 10-1074 
and VRC07-523LS when given sequentially in single and multiple doses via IV 
administration to healthy, HIV-uninfected adults (Table 4-11). This study opened 
in July 2019. 

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Table 4-11 HVTN 130/HPTN 089 (Version 1.0) study 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.  
4.7 
Potential risks of study products and administration 
General Risks of mAbs: 
Overall, the side effects of mAbs (including for indications other than HIV) 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 since PGT121.414.LS and VRC07-523LS target viral 
antigens rather than human cell surface antigens and are human mAbs, serious 
infusion reactions are expected to be rare (77). 
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 used in the treatment of rheumatological 
disorders and cancer. 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 nonhuman 
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 (78). 

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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 (77, 79). 
Other potential side effects of mAbs include thrombocytopenia, autoimmune 
diseases, cancer, dermatitis, and cardiotoxicity (77). 
Risks of the study product(s): 
Experience is accruing with each of the PGT121 and VRC07523-LS mAbs alone 
and in combinations mentioned above (Section 4.6) but HVTN 136/HPTN 092 
evaluating PGT121.414.LS alone and in combination with VRC07-523LS will be 
a first-in-human for the LS-modified form of PGT121. Human experience with 
PGT121 is limited to the IAVI T001, T002, and T003 clinical trials.  
As of March 2019, the IAVI T001, T002, and T003 trials accrual is ongoing, and 
there have been no related SAEs. There has been 1 unrelated SAE (hospital 
admission for orthopedic surgery and IV antibacterial treatment for pre-patelar 
bursitis) in T001. To date, there have been no study safety pauses for AEs and 
product administrations have been generally well tolerated. 
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 1 of the infusions, but there was no clear 
relationship with frequency or severity to the dose of VRC01 (72). SC 
administration of VRC01 was generally well-tolerated and associated with mild to 
moderate local pain and/or tenderness, but there was no difference in the 
frequency or severity between VRC01 recipients and placebo recipients. 
Erythema and/or induration at the SC injection sites were generally less than 25 
cm2 whether VRC01 or placebo was injected (72). No hypersensitivity reactions 
or cytokine release syndrome symptoms were reported in HVTN 104 (72).  
The ongoing efficacy trials HVTN 704/HPTN 085 and HVTN 703/HPTN 081 
have accumulated significant additional VRC01 clinical experience. More than 
20,000 infusions of 10 mg/kg and 30 mg/kg VRC01 have been given to more than 
5000 HIV-uninfected adults in both trials. However, as these trials remain 
blinded, they do not yet contribute to the unblinded VRC01 safety profile. 
Early-phase human experience with administration of VRC07-523LS has been 
reassuring in the VRC605 and HVTN127/ HPTN 087 trials (see Section 4.6.2). 
The majority of participants have reported no local or systemic Solicited AEs and 
no Unsolicited AEs. Severe reactions associated with mAb administration, such as 

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acute anaphylaxis, serum sickness, anti-drug antibodies, and increased risk of 
infections have not been observed to date in trials of VRC01-class mAbs. 
Risk of HIV seroreactivity: 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). 
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, phlebitis, or blood clot. Risk will 
be minimized by using sterile technique and universal precautions. Blood drawing 
may also cause anemia. 
Risks of IV 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. 
Risks of SC infusion: SC administration can result in pain, nodule formation, local 
edema, and possible infection. The risk of infection from SC administration will 
be minimized through skin decontamination of the skin prior to needle insertion. 
The risk of product contamination will be the same as for IV administration and 
will be minimized through the use of aseptic technique during product preparation 
and 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 the PGT121.414.LS monoclonal 
antibody (mAb) when administered alone via intravenous (IV) or 
subcutaneous (SC) infusion (Part A) and of PGT121.414.LS and VRC07-
523LS administered consecutively via IV or SC routes at and after each 
product administration visit (Part B) 
Primary endpoints 1 
• Local and systemic solicited AEs, laboratory measures of safety, and 
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 pharmacokinetic (PK) properties 
of PGT121.414.LS after a single administration (Part A) and of 
PGT121.414.LS and VRC07-523LS after consecutive administration of 
the pair of mAbs at and after each of 3 quarterly visits (Part B) 
Primary endpoint 2 
• Serum concentrations of PGT121.414.LS 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 
PGT121.414.LS after a single administration (Part A) and of 
PGT121.414.LS and VRC07-523LS after consecutive administration of 
the pair of mAbs at and after each of 3 quarterly visits (Part B). 
Primary endpoint 3 
• Magnitude of serum neutralizing activity measured with mAb-specific 
Env-pseudotyped viruses in TZM-bl cells from samples obtained at 
prespecified timepoints among participants who received all scheduled 
product administrations 

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5.2 
Secondary objectives and endpoints 
Secondary objective 1 
• To correlate serum concentrations of PGT121.414.LS and VRC07-523LS 
with corresponding virus neutralization titers in serum 
Secondary endpoints 1 
• Serum concentrations of PGT121.414.LS 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 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 2 
• To determine whether the mAbs maintain their expected combined 
magnitude and breadth of serum neutralizing activity as predicted by the 
known magnitude and breadth of neutralization of the corresponding mAb 
combinations as non-infused clinical products in vitro 
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, and for the clinical product assayed at the 
same time. 
Secondary objective 3 
• To determine whether ADA are present and whether there is a correlation 
between PGT121.414.LS and VRC07-523LS concentrations and ADA 
titers in serum samples 
Secondary endpoint 3 
• Serum PGT121.414.LS and VRC07-523LS concentrations and ADA titers 
measured at prespecified timepoints for all participants in all groups 
regardless of how many product administrations and how much product 
they received 

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5.3 
Exploratory objectives 
Exploratory objective 1: 
To determine whether any confirmed positive ADA samples have functional 
activity that impacts the neutralizing activity of PGT121.414.LS 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 PGT121.414.LS 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 PGT121.414.LS and 
VRC07-523LS 
Exploratory objective 4 
To conduct analyses related to predicting serum neutralization over time against a 
set of potentially exposing viruses in a future efficacy trial for ranking and down-
selecting bnAb regimens 
Exploratory objective 5 
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 32 healthy, HIV-uninfected adult participants. In 
Part A of the study, PGT121.414.LS will be administered as a single IV infusion 
at 3, 10, or 30 mg/kg (Groups 1-3) or a 5 mg/kg SC dose (Group 4) with n=3 
participants per group. Groups 1 and 2 will enroll sequentially, and Groups 3 and 
4 will be randomized in a 1:1 ratio. In Part B of the study, participants will receive 
3 doses of PGT121.414.LS + VRC07-523LS at 20 mg/kg IV each per dose 
(Group 5) or 5 mg/kg SC each per dose (Group 6). Groups 5 and 6 will be 
randomized in a 1:1 ratio with n=10 participants per group. All groups 1-6 are 
open-label. 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. In Part A, each of Groups 1-4 will enroll at least 
one person of each sex assigned at birth. In Part B, each Groups 5-6 will enroll at 
least four people of each sex assigned at birth. 
Since enrollment is concurrent with receiving the first product administration, all 
participants will provide some safety data. However, 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 account for 20% of 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 15% of mAb concentration data 
were missing at the primary timepoints. 
6.1.1 
Sample size calculations for safety 
This study is primarily descriptive. 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 = 3 in Part A, there is a 90% or more chance of observing at least 1 event if the 
true rate of such an event is 53.6% or more; and there is a 90% or more chance of 
observing no events if the true rate is 3.4% or less. For IV infusion Groups 1-3 
combined with n=9 in Part A, there is a 90% chance or more of observing at least 
1 event if the true rate is 22.6% or more; and there is a 90% chance or more of 
observing no events if the true rate is 1.2% or less. For Groups 1-4 combined with 
n=12 in Part A, there is 90% chance or more of observing at least 1 event if the 
true rate is 17.5% or more; and there is a 90% chance or more of observing no 
events if the true rate is 0.9% or less. For each group of size n=10 in Part B, there 
is 90% or more chance of observing at least 1 event if the true rate of such an 

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event is 20.6% or more; and there is 90% or more chance of observing no events 
if the true rate is 1.1% or less. For Groups 5 and 6 combined with n=20 in Part B, 
there is 90% or more chance of observing at least 1 event if the true rate of such 
an event is 11.0% or more; and there is 90% or more chance of observing no 
events if the true rate is 0.5% or less. As a reference, in HVTN vaccine trials from 
December 2000 through April 2014, about 4% of participants who received 
placebos experienced an SAE. 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
groups of size 3, 9, 12, and 20 for different true event rates 
Group 
size 
True event rate (%) 
Pr(0/n1) 
Pr(1+/n1) 
Pr(2+/n1) 
3 
1 
0.97 
0.03 
<0.01 
4 
0.88 
0.12 
<0.01 
10 
0.73 
0.27 
0.03 
20 
0.51 
0.49 
0.10 
30 
0.34 
0.66 
0.22 
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 
12 
1 
0.89 
0.11 
0.01 
4 
0.61 
0.39 
0.08 
10 
0.28 
0.72 
0.34 
20 
0.07 
0.93 
0.73 
30 
<0.01 
>0.99 
0.91 
20 
1 
0.72 
0.28 
0.04 
4 
0.27 
0.73 
0.37 
10 
0.03 
0.97 
0.84 
20 
<0.01 
>0.99 
0.99 
30 
<0.01 
>0.99 
>0.99 
6.1.2 
Sample size calculations for serum mAb concentrations  
Primary objective 2 of this study is to evaluate serum concentrations of VRC07-
523LS and PGT121.414.LS at several timepoints (ie, pharmacokinetics) 
following IV or SC 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 6-2 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 = 8 per arm, reflecting a missingness rate of 20%, 
compared to a planned treatment group size of 10 participants. The calculations 

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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 (6.6, 15.2) (in mcg/mL) with an effective sample size of 8 
participants. 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 infusions of VRC01 in HVTN104 (71). 
Table 6-2 Two-sided 95% confidence intervals based on observing a particular average loge 
mAb concentration in Part B participants, taking 15% attrition into consideration (n = 8/arm) 
Observed average loge-mAb 
concentration (loge mcg/mL) 
SD of loge-mAb concentration 
(loge mcg/mL) 
95% confidence 
interval (mcg/mL) 
loge(1) 
0.5 
(0.7, 1.5) 
loge(10) 
(6.6, 15.2) 
loge(50) 
(32.9, 75.9) 
loge(100) 
(65.8, 151.9) 
loge(500) 
(329.2, 759.5) 
loge(1000) 
(658.4, 1518.9) 
loge(1) 
1.0 
(0.4, 2.3) 
loge(10) 
(4.3, 23.1) 
loge(50) 
(21.7, 115.4) 
loge(100) 
(43.3, 230.7) 
loge(500) 
(216.7, 1153.6) 
loge(1000) 
(433.4, 2307.2) 
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 and PGT121.414.LS, against Env-pseudotyped viruses specific to 
each mAb at several timepoints following IV or SC 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 6-3 displays two-sided 95% confidence intervals for 
the mean neutralization titer for several values of the observed average infectious 
dose (ID)50 or ID80 neutralization titer. The construction of these confidence 
intervals assumed sample sizes of n = 8 per group, reflecting an attrition rate of 
20% compared to the planned treatment group size of 10 participants, 

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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 (32.9, 75.9) with an effective sample size of 8 participants. Of note, based on 
neutralization data against a global panel of 11 pseudoviruses in 6 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 (71). 
Table 6-3 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 
loge(10) 
0.5 
(6.6, 15.2) 
loge(50) 
(32.9, 75.9) 
loge(100) 
(65.8, 151.9) 
loge(500) 
(329.2, 759.5) 
loge(1000) 
(658.4, 1518.9) 
loge(10) 
1.0 
(4.3, 23.1) 
loge(50) 
(21.7, 115.4) 
loge(100) 
(43.3, 230.7) 
loge(500) 
(216.7, 1153.6) 
loge(1000) 
(433.4, 2307.2) 
6.2 
Randomization 
There will be no randomization for Groups 1 and 2 as they will be enrolled 
sequentially for dose escalation. Contingent on safety data from Groups 1 and 2, 
Groups 3 and 4 will be randomized and enrolled simultaneously. Contingent on 
data from Groups 1-4, Groups 5 and 6 will be randomized in blocks to ensure 
balance across groups for simultaneous enrollment. A participant’s randomization 
assignment will be computer generated and provided to the CRS pharmacist 
through a Web-based randomization system.  
6.3 
Blinding 
Participants and CRS staff will be unblinded to participant group assignments. 
Laboratory program staff will be unblinded to whether a sample is from Part A or 

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Part B, but will remain blinded to treatment assignment within Part A or Part B 
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, and when necessary account for the actual 
specimen collection time, and the actual time and dose amount of each product 
administration. 
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 two-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 reported 
more than once, 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 Unsolicited 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 Study Specific Procedures [SSP]/Statistical Analysis 
Plan [SAP]) will be tabulated by treatment arm for each poststudy product 

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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 Objective 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. Individual-level two-
compartmental models may also be considered. 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 post enrollment 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 (71), we anticipate that a two-
compartmental model can characterize the kinetics of the serum concentrations of 
the mAbs. In the event that 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 post 
infection 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 (80) will be computed for each 
participant with evaluable neutralization ID50 or ID80 data, as described in (81). 
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 two-sided p-values 
for the latter test. In addition, 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 post enrollment 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 post infection 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, and 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 test, 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 intra-
subject correlation. 
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 (82), Chapters 1, 3, and 6] for elaborate definitions and examples 
of missing data mechanisms and Ibrahim et al (83) 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’ (84) linear 
mixed effects models to accommodate censoring. In addition, exploratory 
analyses of repeated functional measurements may be done using weighted GEE 
(85) 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 136/HPTN 092 
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 
 
 

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HIV-Related Criteria: 
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 Q).  
Laboratory Inclusion Values 
Hemogram/Complete Blood Count 
10. Hemoglobin ≥ 11.0 g/dL for participants who were assigned female sex at birth, 
≥13.0 g/dL for participants 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 cells/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 

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18. Negative or trace urine protein 
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 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, or 
▪ Any other contraceptive method approved by the HVTN 136/HPTN 092 
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, 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 

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1. Weight > 115 kg  
2. Blood products received within 120 days before first study product 
administration, unless eligibility for earlier enrollment is determined by the 
HVTN 136/HPTN 092 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 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 136/HPTN 092 
PSRT will determine eligibility on a case-by-case basis. 
7. Previous receipt of humanized or human mAbs, whether licensed or 
investigational; the HVTN 136/HPTN 092 PSRT will determine eligibility on a 
case-by-case basis. 
8. Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-
523LS, or PGT121  
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 or PGT121.414.LS 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 136/HPTN 092 PSRT (for mAb see criterion 7 above) 
12. Autoimmune disease (Not excluded from participation: Participant with mild, 
stable and uncomplicated autoimmune disease that does not require 
immunosuppressive medication and that, in the judgment of the site investigator, 

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is likely not subject to exacerbation and likely not to complicate Solicited and 
Unsolicited AE assessments) 
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 subcutaneous 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 
participant’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).  
19. Exclude a volunteer who: 
• Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or 
• Uses moderate/high-dose, inhaled corticosteroids, or 

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• In the past year has either of the following: 
▪ Greater than 1 exacerbation of symptoms treated with oral/parenteral 
corticosteroids; 
▪ Needed emergency care, urgent care, hospitalization, or intubation for 
asthma. 
20. Diabetes mellitus type 1 or type 2 (Not excluded: type 2 cases controlled with 
diet alone or a history of isolated gestational diabetes.) 
21. 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. 
22. Bleeding disorder diagnosed by a clinician (eg, factor deficiency, coagulopathy, 
or platelet disorder requiring special precautions) 
23. 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) 
24. Seizure disorder: History of seizure(s) within past 3 years. Also exclude if 
volunteer has used medications in order to prevent or treat seizure(s) at any time 
within the past 3 years. 
25. Asplenia: any condition resulting in the absence of a functional spleen 
26. History of generalized urticaria, angioedema, or anaphylaxis. 
7.3 
Participant departure from study product administration schedule or 
withdrawal (Part B) 
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 (Part B only) 
Under certain circumstances, a participant’s scheduled study product 
administration will be delayed. Refer to the HVTN 136/HPTN 092 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 136/HPTN 092 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 136/HPTN 092 PSRT. 
7.3.2 
Participant departure from study product administration schedule 
Every effort should be made to follow the study product-administration schedule 
per the protocol. If a participant misses a study product administration and the 
visit window period for the study product administration has passed, that study 
product administration cannot be given. The participant should be asked to 
continue study visits. For Groups 5 and 6 in Part B, the participant should resume 
the study product administration schedule with the next study product 
administration unless there are circumstances that require further delay or 
permanent discontinuation of study product administration (see Sections 7.3.3 and 
7.3.4). 
7.3.3 
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 136/HPTN 092 PSRT) 

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• 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 
▪ 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 136/HPTN 092 
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 136/HPTN 092 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 136/HPTN 092 SSP). 
Participants diagnosed with HIV infection during the study should be encouraged 
to participate in follow-up visits as indicated in Section 9.12. 
7.3.4 
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,  

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• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff), or 
• 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 Table 1-1. See the IB for further information about study 
products. 
8.1 
Study product regimen 
The schedule of study product administration is shown in Table 1-1 and additional 
information is given below. 
Group 1 
Treatment 1 (T1): PGT121.414.LS 3 mg/kg to be administered IV at Month 0 
Group 2 
Treatment 2 (T2): PGT121.414.LS 10 mg/kg to be administered IV at Month 0 
Group 3 
Treatment 3 (T3): PGT121.414.LS 30 mg/kg to be administered IV at Month 0 
Group 4 
Treatment 4 (T4): PGT121.414.LS 5 mg/kg to be administered via SC infusion at 
Month 0 
Group 5 
Treatment 5 (T5): PGT121.414.LS 20 mg/kg AND VRC07-523LS 20 mg/kg to 
be administered IV sequentially in this order at Month 0, Month 4, and Month 8 
Group 6 
Treatment 6 (T6): PGT121.414.LS 5 mg/kg AND VRC07-523LS 5 mg/kg to be 
administered via SC infusion sequentially in this order at Month 0, Month 4, and 
Month 8 

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8.2 
Study product formulation 
8.2.1 
PGT121.414.LS [Labeled as PGT121.414.LS Drug Product (VRC-
HIVMAB0107-00-AB)] 
PGT121.414.LS will be supplied as 10 mL single-use glass vials with a 4.75 mL 
fill volume, at a concentration of 100 mg/mL. Each vial contains a clear, colorless 
to yellow, preservative free, sterile solution for injection. The formulation buffer 
is composed of acetate, sucrose, polysorbate 80 at pH of 5.2. 
PGT121.414.LS product label designates the long-term storage as -35°C to -15°C 
(-31°F to 5°F). 
8.2.2 
VRC07-523LS Labeled as VRC07-523LS HIV MAb (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 isotonic, preservative free, sterile solution essentially free of 
visible particles; some opaque or translucent particles may be present. The 
formulation buffer is composed of histidine, sodium chloride, sucrose, and 
sorbitol at pH 6.8. Vials do not contain a preservative. 
VRC07-523LS product label designates the long-term storage as -35°C to -15°C 
(-31°F to 5°F). 
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, 
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 must follow appropriate aseptic technique and sterile preparation 
procedures as outlined in United States Pharmacopeia (USP) <797> 
Pharmaceutical Compounding – Sterile Preparations, utilizing a pharmacy 
biosafety cabinet/isolator or better. Local regulations and site institutional policies 
and procedures for use of personal protective equipment such as gloves, gowns, 

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masks, and safety glasses, must be followed. Pharmacists 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 prepared study product 
should be discarded in a biohazard container and disposed of in accordance with 
institutional or pharmacy policy. 
8.3.1 
PGT121.414.LS  
8.3.1.1 
Thawing instructions 
1. Thaw vial(s) at room temperature and hold for at least 30 minutes post-thaw 
(no ice crystals present). Vials must not be moved directly from the freezer to 
storage at 2°C to 8°C. 
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 some 
white to translucent particles continue to be observed, vials may be used for 
the preparation of the IV or SC product. 
4. Thawed vials may be stored for up to 24 hours at room temperature 
(maximum 27°C). If vials are not used within that time, they may be 
refrigerated for up to 2 weeks (14 days) at 2°C to 8°C and should be used 
within 8 hours of any subsequent return to room temperature (maximum 
27°C).  Refrigerated product must be equilibrated at room temperature 
(maximum 27°C) for a minimum of 30 minutes prior to use.   
8.3.1.2 
PGT121.414.LS intravenous infusion preparation 
1. Calculate the total dose (mg) of PGT121.414.LS required based on the 
participant’s weight (in kg) and treatment dose of 3 mg/kg, 10 mg/kg, 20 
mg/kg, or 30 mg/kg. Remove the minimum number of thawed 
PGT121.414.LS 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 PGT121.414.LS. 
2. Gently swirl thawed vials for 30 seconds, avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright until ready to withdraw the contents. 
Do not invert the vials during inspection. 
3. Using aseptic technique, remove the air from the IV container and then add 
the calculated volume of PGT121.414.LS to the IV container with 100 mL of 

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Sodium Chloride for Injection, 0.9 % USP. Record this as the study product 
preparation time. 
4. The prepared PGT121.414.LS product may be stored at 2°C to 8°C up to 24 
hours or at room temperature (maximum 27°C) for a maximum of 4 hours, 
including the administration time.  If stored at 2°C to 8°C, prepared product 
must be equilibrated at room temperature (maximum 27°C) for a minimum of 
30 minutes prior to product administration.  
8.3.1.3 
PGT121.414.LS subcutaneous infusion preparation 
1. Calculate the total (mg) of PGT121.414.LS required based on the participant’s 
weight (in kg) and the treatment group of 5 mg/kg. Remove the minimum 
number of thawed PGT121.414.LS vials from storage. 
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT SHAKE 
VIALS. Keep the vials upright until ready to withdraw the contents. Do not 
invert the vial during inspection. 
3. Using aseptic technique, withdraw the calculated volume of PGT121.414.LS 
from the vial(s) into the final container using a 5 micron filter needle (see 
HVTN 136/HPTN 092 SSP for needle/filter specifications and details). A new 
filter needle must be used for each container. Discard the filter needle prior to 
dispensing. Record this as the study product preparation time. 
4. The prepared PGT121.414.LS product may be stored at 2°C to 8°C up to 24 
hours or at room temperature (maximum 27°C) for a maximum of 4 hours, 
including the administration time.  If stored at 2°C to 8°C, prepared product 
must be equilibrated at room temperature (maximum 27°C) for a minimum of 
30 minutes prior to product administration. 
8.3.2 
VRC07-523LS 
VRC07-523LS is a highly concentrated protein solution and may develop white, 
opaque to translucent particles after thawing. 
8.3.2.1 
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, 

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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. 
8.3.2.2 
VRC07-523LS intravenous infusion preparation 
1. Calculate the total dose (mg) of VRC07-523LS required based on the 
participant’s weight (in kg) and treatment dose of 20 mg/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 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 8.3.2.1. 
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. 
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, 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. 
8.3.2.3 
VRC07-523LS subcutaneous infusion preparation 
1. Calculate the total (mg) of VRC07-523LS required based on the participant’s 
weight (in kg) and the treatment group of 5 mg/kg. Remove the minimum 
number of thawed particle-free VRC07-523LS vials from storage. 
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT SHAKE 
VIALS. Keep the vials upright until ready to withdraw the contents. Do not 
invert the vial during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.2.1. 

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4. Using aseptic technique, withdraw the calculated volume of VRC07-523LS 
from the vial(s) into the final container using a 5 micron filter needle (see 
HVTN 136/HPTN 092 SSP for needle/filter specifications and details). A new 
filter needle must be used for each container. Discard the filter needle prior to 
dispensing. Record this as the study product preparation time. 
5. The prepared VRC07-523LS syringe(s) may be stored at 2°C to 8°C for up to 
24 hours or at room temperature (maximum 30°C) for a maximum of 4 hours, 
including the administration time. Product may not be stored in direct 
sunlight. If stored at 2°C to 8°C, prepared product must be equilibrated at 
room temperature (maximum 30°C) for a minimum of 30 minutes prior to 
product administration. 
8.3.3 
Labeling of study products 
Label the study product as follows:  
• Participant identifier(s)  
• Participant weight (in kg) 
• Study product name  
• Total dose (mg)  
• Final volume (mL) 
• Route (IV or SC) 
• Infusion time 
• Beyond use date and time  
• Any additional information required by jurisdiction  
8.4 
Administration 
The weight that was used for preparation of the study product, will be included on 
the study product label prepared by the pharmacy. The clinician responsible for 
administration will check the study product 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. 
In Group 5, two separate IV containers each containing 1 study product will be 
administered sequentially, PGT121.414.LS first followed by VRC07-523LS. 
In Group 6, two separate preparations each containing 1 study product will be 
administered sequentially, PGT121.414.LS SC infusion first followed by VRC07-
523LS SC infusion. 

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8.4.1 
PGT121.414.LS (Intravenous Infusion) 
PGT121.414.LS will be administered IV over approximately 30 to 60 minutes. A 
1.2 micron in-line filter must be used for IV product administration. Filters must 
comply with the specifications described in the HVTN 136/ HPTN 092 SSP. 
Once the in-line filter is added to the tubing, prime the administration set with 
Sodium Chloride Injection, 0.9% USP. Refer to the HVTN 136/HPTN 092 SSP 
for further information on IV administration. 
8.4.2 
PGT121.414.LS (Subcutaneous Infusion) 
PGT121.414.LS will be administered via SC infusion at a rate of 15 mL/hr. A 
suitable needle for SC infusion should be affixed to the prepared product prior to 
administration. 
8.4.3 
VRC07-523LS (Intravenous Infusion) 
VRC07-523LS will be administered IV over approximately 15 to 60 minutes. A 
1.2 micron in-line filter must be used for IV product administration. Filters must 
comply with the specifications described in the HVTN 136/ HPTN 092 SSP. 
Once the in-line filter is added to the tubing, prime the administration set with 
0.9% Sodium Chloride Injection, USP. Refer to the HVTN 136/HPTN 092 SSP 
for further information on IV administration. 
8.4.4 
VR07-523LS (Subcutaneous Infusion) 
VRC07-523LS will be administered via subcutaneous infusion at a rate of 15 
mL/hr. A needle suitable for SC infusion should be affixed to the prepared 
product prior to administration. 
8.5 
Acquisition of study products 
PGT121.414.LS is provided by Dale and Betty Bumpers Vaccine Research Center 
(VRC), 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. 
Filter needles, in-line 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 136/HPTN 092 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. 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 N, Appendix O, 
Appendix P, and Appendix Q. 
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 
entity/body that has the power to regulate which includes authorities that review 
submitted clinical data and those that conduct inspections. These are sometimes 
referred to as competent authorities. These are entities/bodies whose 
approval/authorization/acknowledgment of a clinical trial is required for 
conducting a clinical trial. Any organization whose approval is required prior to a 
CRS's participation in DAIDS funded and/or Sponsored Clinical Trial. Includes 
but not limited to approvals from state/national health systems and administrative 
bodies, drug agencies etc. (DAIDS adopted from ICH E6).” CRSs are responsible 
for knowing the requirements of their applicable REs. 

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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 
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. 

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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. 
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 R).  
• 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 
 

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• 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), 
▪ 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). 

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9.3 
Enrollment and study product administration visits 
Enrollment is simultaneous with first study product administration. The study 
group assignment (all groups) and treatment assignment (Groups 3 and 4 in Part 
A and Groups 5 and 6 in Part B) will be provided via a Web-based system (see 
Section 6.2). 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. 
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 2 hours. Samples are drawn 1 hour after the last 
product administration  (see Appendix J, Appendix K, Appendix L, and Appendix 
M). 
See the HVTN 136/HPTN 092 SSP for details regarding study product 
administration visit procedures and subsequent study product observation and 

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Solicited AE assessment procedures that CRSs must follow. The site will make 
arrangements to be in contact with the participant during or following the 
Solicited AE period (as described in Section 9.8 and the HVTN 136/HPTN 092 
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);  
• 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. 
• PK Specimen collection (see Appendix J, Appendix K, Appendix L, and 
Appendix M)  
Additional procedures will be performed at scheduled visits as specified in, 
Appendix N, Appendix O, Appendix P, and Appendix Q: 
• Specimen collection (should be completed per Appendix J, Appendix K, 
Appendix L, and Appendix M). 
• 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 PGT121.414.LS 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 postinfusion observation 
period. CRS staff are trained to recognize suspected mAb reactions and to provide 
immediate medical care consistent with the HVTN 136/HPTN 092 SSP. 

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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 management of mAb reactions see the HVTN 136/HPTN 092 SSP 
9.4 
Follow-up visits 
The following procedures are performed at scheduled follow-up visits as specified 
in Appendix N, Appendix O, Appendix P, and Appendix Q: 
• Risk reduction counseling (as described in Section 9.5);  
• For participants capable of becoming pregnant, contraception status 
assessment (as described in Section 9.2 and 9.6). In persons who are pregnant, 
contraception status assessment is not required; 
• 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); 
• 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; 

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• 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 J, Appendix K, 
Appendix L, and Appendix M); 
• Clinical laboratory tests including: 
▪ CBC with differential, 
▪ Chemistry panel (see Section 9.2);  
▪ 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.  

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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 anti-HIV mAbs 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 136/HPTN 092 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 
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 N, Appendix O, Appendix P, and Appendix Q 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. 

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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 
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 Manual of Operations (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 during and after the 3-day Solicited AE assessment 
period, or sooner if indicated. See the HVTN 136/HPTN 092 SSP for further 
details. In general, a participant who self-reports any poststudy product 
administration reaction(s) 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 

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administration and 3 full days after), or those meeting SAE/Unsolicited AEs 
requiring expedited reporting to DAIDS criteria, are recorded on an AE Log. 
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. Additionally, in participants receiving SC infusions, local pruritus 
will be assessed. The daily maximum severity reached for each symptom during 
the assessment period is reported (see HVTN 136/HPTN 092 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 sites 
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. 

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9.9 
Visit windows and missed visits 
 Visit windows are shown in Appendix S, Appendix T, Appendix U, and 
Appendix V. For a visit window not performed within the window period, a 
Missed Visit form is completed. 
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 136/HPTN 092 SSP.  
If a missed visit required study product administration or if study product 
administration must be permanently discontinued, please refer to Sections 7.3.1 
and 7.3.3 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 
the participant is no longer pregnant, refer to Section 7.3.1.  
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 

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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 
136/HPTN 092 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 N, Appendix O, Appendix P, and 
Appendix Q). 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 Site Lab Instructions and HVTN 136/HPTN 092 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 J, Appendix K, 
Appendix L, and Appendix M. 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 J, Appendix K, 
Appendix L, and Appendix M. 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 
PGT121.414.LS and VRC07-523LS concentrations 
PGT121.414.LS 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 PGT121.414.LS 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. 

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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 
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 and PGT121.414.LS. 
These viruses will be selected from a global panel and/or clade-specific panels 
(80, 86) and may be modified by site-directed mutagenesis to be capable of 
measuring the activity of each mAb individually. 
10.4.1 
ADA detection assay 
A tiered testing approach will be used to identify and characterize ADAs that may 
arise. Anti-PGT121.414.LS and VRC07-523LS antibody detection assays will be 
performed on serum samples from study participants at indicated timepoints. 
Samples will be evaluated with a sensitive screening assay in Tier 1. Samples 
showing positive responses in the screening assay will be evaluated in a 
confirmatory assay of specificity. Specific, or Tier 2 positive responses will be 
characterized by titration (Tier 3). 
10.4.2 
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 and PGT121.414.LS neutralizing activity against a qualified 
virus in the TZM-bl assay. 
10.5 
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 
136/HPTN 092 SSP for more information. 
10.6 
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, cryopreserved samples may be used to perform additional assays to 
support standardization and validation of existing or newly developed methods.  

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10.7 
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.  
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. 
10.8 
Biohazard containment 
As the transmission of HIV and other blood-borne pathogens can occur through 
contact with contaminated needles, blood, and blood products, appropriate 
precautions will be employed by all personnel in the drawing of blood 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 136/HPTN 092 PSRT 
The HVTN 136/HPTN 092 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 the HVTN 136/HPTN 092 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 136/HPTN 092 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 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 136/HPTN 092 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: 
• Maintaining a central database management system for clinical data; 

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• Providing reports of clinical data to appropriate groups such as the HVTN 
136/HPTN 092 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 136/HPTN 092 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 136/HPTN 092 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 
product/procedure(s), whether or not related to the investigational study 
product/procedure(s). See the HVTN 136/HPTN 092 SSP for further details 
regarding Solicited and Unsolicited AEs.  

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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 
136/HPTN 092 SSP); 
• Infusion Site Erythema or Redness and Infusion 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 136/HPTN 092 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 11-2). Telephone numbers and email 
addresses are found on the protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn136hptn092). Concerns requiring 
immediate attention should be communicated by calling the clinical safety phone. 
In the case of email notification, clinical safety staff will reply within 1 business 
day. Serious events that meet pause rule criteria will be addressed immediately (as 
outlined in Table 11-2). If email service is not available, the CRS should notify 
clinical safety staff of the event by telephone, and then submit CRFs. 

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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:  
• PGT121.414.LS 
• VRC-HIVMAB075-00-AB (VRC07-523LS) 
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.  
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). 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. 

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11.3 
Safety reviews 
11.3.1 
Safety Considerations for Part A 
Enrollment in Group 1 and Group 2 will be stepwise by group. Enrollment will 
start with Group 1 and will be restricted to a maximum of 1 participant per day 
across all participating CRSs until a total of 3 participants have been enrolled. In 
addition to monitoring participant safety throughout the study period, the HVTN 
136/HPTN 092 PSRT will review all cumulative safety data available up to and 
including 2 weeks post product administration. Upon PSRT determination that it 
is safe to proceed, enrollment in Group 2 will begin (see Table 11-1). 
Enrollment in Group 2 will be restricted to a maximum of 1 participant per day 
across all participating CRSs until a total of 3 participants have been enrolled. In 
addition to monitoring participant safety throughout the study period, the HVTN 
136/HPTN 092 PSRT will review all cumulative safety data available up to and 
including 2 weeks post product administration. Upon PSRT determination that it 
is safe to proceed, enrollment in Groups 3 and 4 will begin (see Table 11-1). 
If any Grade 3 or higher AEs deemed related to study product are reported in 
Groups 1 or 2, the HVTN SMB will perform an additional review of these safety 
data to make the final determination based on safety before proceeding to Groups 
3 and 4. 
Groups 3 and 4 will be enrolled simultaneously. Enrollment will be restricted to a 
maximum of 1 participant per day from either of the 2 groups across all 
participant CRSs until a total of 3 participants in each group have been enrolled.  
11.3.2 
Safety evaluation for opening enrollment in Part B 
In addition to monitoring participant safety throughout the study period, the 
HVTN 136/HPTN 092 PSRT will review all cumulative safety data available 
from Groups 1 through 4 up to and including the 2-week visit after study product 
administration. Based on the assessment of these safety data, the HVTN 
136/HPTN 092 PSRT will make a decision regarding the appropriateness of 
opening enrollment in Part B. The HVTN SMB may perform an additional review 
of these safety data to make the final determination based on safety for 
proceeding to Part B (see Table 11-1).  
If any Grade 3 or higher AEs deemed related to study product are reported in 
Groups 1, 2, 3 or 4, the HVTN SMB will perform an additional review of these 
safety data to make the final determination based on safety for proceeding to Part 
B. 
11.3.3 
Safety considerations for Part B 
Groups 5 and 6 will enroll simultaneously. Enrollment will be restricted to a 
maximum of 1 participant per day from either of the 2 groups across all 

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participant CRSs until a total of 3 participants in each group have been enrolled. 
In addition to monitoring participant safety throughout the study period, the 
HVTN 136/HPTN 092 PSRT will review cumulative safety data available on the 
first 6 participants in Part B (3 participants from Group 5 and 3 participants from 
Group 6) up to and including the 2-week visit after the first study product 
administration to determine whether the remaining participants in Groups 5 and 6 
can be enrolled (see Table 11-1).  
If any Grade 3 or higher AEs deemed related to study product are reported in the first 
3 participants in Group 5 or Group 6, 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 7 participants in Group 5 and Group 6. 
The HVTN 136/HPTN 092 PSRT may consult with the HVTN SMB on an ad hoc 
basis for any of the previously described evaluations. 

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Table 11-1 Summary of planned safety holds 
Planned 
Safety Hold 
Timepoint/Data Reviewed 
Actions 
Planned 
Safety Hold 
#1 
Part A 
Begins 2 weeks after the 3rd participant 
receives study product in Group 1. 
 
Review of all cumulative safety data 
available for the 3 participants in 
Group 1 up to and including the 2-
week visit after the study product 
administration. 
 
The PSRT will make a decision based 
on these safety data regarding the 
appropriateness of beginning 
enrollment in Group 2 from a safety 
perspective. 
  
Planned 
Safety  
Hold #2 
Part A 
Begins 2 weeks after the 3rd participant 
receives study product in Group 2. 
 
Review of all cumulative safety data 
available for the 3 participants in 
Group 2 up to and including the 2-
week visit after the study product 
administration. 
 
The PSRT will make a decision based 
on these safety data regarding the 
appropriateness of beginning 
enrollment in Groups 3 and 4 from a 
safety perspective. 
 
Planned 
Safety 
Hold #3 
Part A 
Begins 2 weeks after all participants 
receive study product in Group 3 and 
Group 4 (total of 6 participants). 
 
Review of all cumulative safety data 
available for: 
• 
The 6 participants in Groups 3 
and 4 up to and including the 
2-week visit after the first 
product administration. 
• 
All participants in Part A. 
 
The PSRT will make a decision based 
on all the safety data from all 
participants included in Part A 
regarding the appropriateness of 
beginning enrollment in Part B from a 
safety perspective. 
 
Planned 
Safety 
Hold #4 
Part B 
Begins 2 weeks after a total of 6 
participants receive study product in 
Part B (3 participants in Group 5 and 3 
participants in Group 6). 
  
Review of all cumulative safety data 
available for the 6 participants in 
Groups 5 and Group 6 up to and 
including the 2-week visit after the first 
study product administration. 
 
The PSRT will make a decision based 
on these safety data regarding the 
appropriateness of continuing 
enrollment and subsequent product 
administrations in Groups 5 and 6 
from a safety perspective. 
 

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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 136/HPTN 092 PSRT AE review are summarized in Table 11-2. 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 136/HPTN 092 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 11-2 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/hvtn136hptn092). 
b HVTN CSS or HVTN Core designee 
c Does not include subjective Solicited AEs (infusion site pain and/or tenderness, fatigue/malaise, myalgia, 
arthralgia, nausea, chills, headache, non-exertional dyspnea, generalized pruritus, local pruritus [SC infusion 
only], facial flushing, and unexplained diaphoresis). 
For all safety pauses, HVTN Core notifies the HVTN 136/HPTN 092 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 136/HPTN 092 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 
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 136/HPTN 
092 PSRT assessment, DAIDS RAB notifies the FDA as needed. 

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If an immediate HVTN 136/HPTN 092 PSRT notification or prompt HVTN 
136/HPTN 092 PSRT AE review is triggered, HVTN Core notifies the HVTN 
136/HPTN 092 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 136/HPTN 092 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 136/HPTN 092 
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 136/HPTN 092 PSRT AE review criteria. 
11.5.2 
Weekly review 
During the study product administration phase of the trial, the HVTN 136/HPTN 
092 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 136/HPTN 092 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 136/HPTN 
092 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 136/HPTN 092 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 N, Appendix O, 
Appendix P, and Appendix Q). 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 136/HPTN 092 are 
described below. 
Protocol history and modifications 
Date: October 8, 2019 
Protocol version: Version 1.0 
Protocol modification: 
 
Original protocol 

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14 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant 
to the conduct of this study, include: 
• Assessment of Understanding. Accessible through the HVTN protocol-
specific website. 
• Current 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 136/HPTN 092 Special Instructions. Accessible through the HVTN 
protocol-specific website. 

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HVTN136-HPTN092_v1.0_FINAL / Page 107 of 188 
• HVTN 136/HPTN 092 Study Specific Procedures. Accessible through the 
HVTN protocol-specific website. 
• HVTN 136/HPTN 092 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 
AMP 
 
Antibody Mediated Prevention 
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 
CAB 
 
Community Advisory Board 
CATNAP  
Compile, Analyze and Tally NAb Panels 
CAVD 
 
Collaboration for AIDS Vaccine Discovery 
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 
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 
Fc 
 
Fragment crystallizable 
FcRn 
 
Fc-receptor 
FDA 
 
US Food and Drug Administration 
Fred Hutch 
Fred Hutchinson Cancer Research Center 
GCP 
 
Good Clinical Practice 

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GEE 
 
generalized estimating equation 
GLP 
 
Good Laboratory Practice 
HBsAg 
 
hepatitis B surface antigen 
HCV 
 
hepatitis C virus 
HPTN 
 
HIV Prevention Trials Network 
HVTN 
 
HIV Vaccine Trials Network 
IAVI 
 
International AIDS Vaccine Initiative 
IB 
 
Investigator’s Brochure 
IC 
 
inhibitory concentration 
ICF 
 
informed consent form 
ICH 
 
International Council on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ID 
 
infectious dose 
IgG 
 
immunoglobulin G 
IL 
 
Interleukin 
IM 
 
intramuscular 
IND 
 
Investigational New Drug 
INF 
 
Interferon 
IoR 
 
Investigator of Record 
IRB 
 
Institutional Review Board 
IUD 
 
intrauterine device 
IV 
 
intravenous 
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 
MPER 
 
membrane-proximal external region 
MTD 
 
maximum tolerated dose 
nAb 
 
neutralizing antibody 
NAEPP 
 
National Asthma Education and Prevention Program 
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 

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PAB 
 
DAIDS Pharmaceutical Affairs Branch 
PCR 
 
polymerase chain reaction 
PD 
 
pharmacodynamics 
PK 
 
pharmacokinetic 
popPK 
 
population PK (pharmacokinetic) 
PP 
 
per-protocol 
PrEP 
 
pre-exposure prophylaxis 
PSRT 
 
Protocol Safety Review Team 
RAB 
 
DAIDS Regulatory Affairs Branch 
RE 
 
regulatory entity 
RSC 
 
DAIDS Regulatory Support Center 
RSV 
 
respiratory syncytial virus 
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 
SUSAR 
 
sudden unexpected serious adverse reaction 
TB 
 
tuberculosis 
TCR 
 
tissue cross reactivity 
Tmax 
 
time to Cmax 
TNF 
 
Tumor necrosis factor 
USP 
 
United States Pharmacopeia 
UW-VSL  
University of Washington Virology Specialty Laboratory 
VCMP 
 
and Vaccine Clinical Materials Program 
Vd 
 
volume of distribution 
VRC 
 
Vaccine Research Center (NIAID) 
VTRB 
 
Vaccine Translational Research Branch 
 

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16 
Literature cited 
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2. The National Commission for the Protection of Human Subjects of 
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and Guidelines for the Protection of Human Subjects of Research. 1979 
4/18/1979. 
3. Council for International Organizations of Medical Sciences (CIOMS). 
International ethical guidelines for biomedical research involving human 
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4. UNAIDS. UNAIDS Data 2018 2018 [Available from: 
http://www.unaids.org/en/resources/documents/2018/unaids-data-2018. 
5. Fauci AS. An HIV Vaccine Is Essential for Ending the HIV/AIDS Pandemic. 
JAMA. 2017;318(16):1535-6. 
6. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, 
Kumarasamy N, et al. Antiretroviral Therapy for the Prevention of HIV-1 
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7. Elion R, Coleman M. The preexposure prophylaxis revolution: from clinical 
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8. Fauci AS, Marston HD. Ending the HIV-AIDS Pandemic--Follow the 
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9. Pegu A, Hessell AJ, Mascola JR, Haigwood NL. Use of broadly neutralizing 
antibodies for HIV-1 prevention. Immunol Rev. 2017;275(1):296-312. 
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HIV-1 Prevention or Immunotherapy. N Engl J Med. 2016;375(21):2019-21. 
11. Cohen YZ, Caskey M. Broadly neutralizing antibodies for treatment and 
prevention of HIV-1 infection. Curr Opin HIV AIDS. 2018;13(4):366-73. 
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13. Wagh K, Seaman MS, Zingg M, Fitzsimons T, Barouch DH, Burton DR, et 
al. Potential of conventional & bispecific broadly neutralizing antibodies for 
prevention of HIV-1 subtype A, C & D infections. PLoS Pathog. 
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15. Graham BS, Ambrosino DM. History of passive antibody administration for 
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16. Homaira N, Rawlinson W, Snelling TL, Jaffe A. Effectiveness of 
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17. Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal 
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Infection in High-risk Infants. Pediatrics. 1998;102(3):531-7. 
18. Simoes EA. Immunoprophylaxis of respiratory syncytial virus: global 
experience. Respir Res. 2002;3 Suppl 1:S26-33. 
19. Stamatatos L, Morris L, Burton DR, Mascola JR. Neutralizing antibodies 
generated during natural HIV-1 infection: good news for an HIV-1 vaccine? 
Nat Med. 2009;15(8):866-70. 
20. Mascola JR, Haynes BF. HIV-1 neutralizing antibodies: understanding 
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Appendix A 
Sample informed consent form for Part A 
(Groups 1-4) 
Title: A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, 
pharmacokinetics, and antiviral activity of the monoclonal antibody 
PGT121.414.LS administered alone and in combination with VRC07-523LS via 
intravenous or subcutaneous infusion in healthy, HIV-uninfected adult 
participants 
Protocol number: HVTN 136/HPTN 092 
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. 
Key Information 
These are some of the things you should know about this study: 
• The purpose of the study is to understand how well antibodies against HIV 
work when given alone and combined with other antibodies. We also want to 
see if the antibodies are safe to give to people and do not make them too 
uncomfortable.  
• If you choose to join, we will ask you to come to several study visits over 
about 6-8 months. At one of these visits you will get the study antibody in a 
vein (by IV infusion) or under the skin (by subcutaneous infusion, called SC). 
We will take blood from you at each study visit to see how your body 
responds to the study antibody and how much antibody is in your blood. We 
will test you for HIV and other sexually transmitted infections (STIs) and 
pregnancy (if applicable). We will ask you to complete questionnaires (many 
with questions of a personal nature) and you will have physical exams.  
• Some general risks of antibodies include fever, chills, shaking, nausea, 
vomiting, pain, headache, dizziness, fatigue, flushing, trouble breathing, high 
or low blood pressure, itchiness and rash. There may be other side effects that 
we don’t yet know about, even serious ones. Because this is the first time the 
study antibody is being given to people, we do not know what all of the risks 
may be. We think that the risks will be similar to these general risks. 
• We do not expect the study antibody to benefit you in any way.  

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• Whether to take part in this study is your choice. You do not have to take part 
in the study and you are free to stop at any time. 
• The rest of this form provides a more complete description of this study. 
Please read it carefully. 
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 a 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 in a vein (by IV infusion) or under the skin (by subcutaneous 
infusion, called SC). 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 32 people will take part in this study at multiple clinics. 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 2 parts of this study, Part A and Part B. In Part A, we will give different 
doses of one of the study antibodies by IV or SC. People in Part A will only get 
the study antibody one time. There will be about 12 people in Part A. When we 
know that there were no serious health problems in Part A, we will decide 
whether or not to do Part B. If we decide to do Part B, we will give about 20 more 
people a combination of both study antibodies by IV or SC. We will give these 
antibodies three times. 
You are being invited to join Part A of the study. 
1. We are doing this study to answer several questions. 
• Is the study antibody safe to give to people? 
• Are people able to take the study antibody without becoming too 
uncomfortable? 
• How much of the study antibody remains in the body as time passes? 
• How does the body’s response change depending on how the study antibody is 
given?  

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2. The study antibody cannot give you HIV. 
The study antibody is not made from actual HIV. It is impossible for the antibody 
to give you HIV. Also, it 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 
getting HIV if you are exposed to the virus. 
3. This study antibody is experimental. 
The formal name of the study antibody given in Part A is PGT121.414.LS. From 
here on, we will call it the study antibody. It is an experimental product. That 
means we do not know if it will be safe to use in people, or if it will work to 
prevent HIV infection. The study antibody is used only in research studies. This is 
the first study testing this antibody in people. 
The study antibody was developed by researchers with the Collaboration for 
AIDS Vaccine Discovery (CAVD).  
In laboratory studies, the study antibody attached to HIV. It also prevented 
infection by many strains of HIV from around the world. 
In animal studies, the study antibody protected animals from infection with the 
animal viruses that are very similar to HIV. The study antibody has also been 
tested for safety in the laboratory and in animals and it did not cause health 
problems. Even if something looks like it is safe or works in animals, it may not 
be true for people.  
We do not know if the study antibody will prevent HIV when given to people. It 
will take many studies to learn if it will be useful for HIV prevention. This study 
will not answer that question. 
Risks of the study antibody: 
PGT121.414.LS 
Because this is the first time the antibody is being given to people, we do not 
know what all of the risks may be. We think that the risks will be similar to the 
general risks described below. 
PGT121 
A similar study antibody called PGT121 was changed to make it last longer in the 
body, and that new version is what we will use in this study. PGT121 is being 
tested in a study with HIV-positive and HIV-negative participants. As of March 
2019, about 28 HIV-negative people and 20 HIV-positive people have gotten 
different doses of it.by IV infusions and SC injections, sometimes in combination 
with other experimental antibodies. Ten other people have gotten a placebo (a 
liquid with no antibody in it). This study is still going on and we don’t know who 

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got the study antibody and who got a placebo, or what the safety results are. 
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 
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 you 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 

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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 personal questions about your HIV 
risk factors such as sexual behavior, alcohol, and drug use. 
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 

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6. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
7. If you were 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 antibody could affect the developing baby. You must agree to use 
effective birth control from 21 days before your infusion until your participation 
in the study ends. 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 6-8 
months. 
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. After you get the study antibody, we 
will ask you to come to the clinic for follow up visits on the next day, 2 days later, 
3 days later, 6 days later, and 2 weeks later to draw your blood. We will do this so 
that we can look at how your body responds to the study antibody. We will also 
look at how much of the antibody is in your blood. 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] 

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Site: Insert any costs to participants (eg, birth control costs for participants assigned 
female sex at birth 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 the study antibody by IV infusion or SC infusion.  
There are 4 groups in Part A of this study, called Group 1, 2, 3 and 4. Everyone in 
Part A will get the study antibody one time in different doses. People in Groups 1, 
2 and 3 will get the study antibody by IV infusion. People in Group 4 will get the 
study antibody by SC infusion. 
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. The infusion will take about one 
hour.  
When getting a subcutaneous infusion, a sterile needle is put under the skin on 
your abdomen or thigh. A pump similar to an IV pump is used to control how fast 
the study antibody is injected through the needle. You will get one infusion of the 
study antibody. The infusion will take about 30 minutes  
People in Group 1 will be enrolled first, and the safety will be reviewed before 
enrollment starts in Group 2. Safety for Group 2 will be reviewed before 
enrollment begins in Groups 3 and 4. Enrollment in Groups 3 and 4, and whether 
you get the study antibody by IV or SC, is completely random, like flipping a 
coin. We have no say in how people are assigned to Groups 3 and 4. Neither do 
you. 
11.  You will get an IV infusion or SC infusion of the study antibody at the first 
visit during the study. 
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. 
 
Group 
Number of 
Participants 
Dose 
Study antibody 
At enrollment 
1 
3 
Low 
PGT121.414.LS 
IV infusion 
2 
3 
Medium 
PGT121.414.LS 
IV infusion 
3 
3 
High 
PGT121.414.LS 
IV infusion 
4 
3 
Low 
PGT121.414.LS 
SC infusion 
 

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You will have to wait in the clinic for at least 2 hours after the infusion to see if 
there are any problems. While you are waiting, we will collect a blood sample one 
hour after the infusion. Then that night and for 3 more days, you will need to keep 
track in a diary about how you are feeling and if you have any symptoms. We will 
review the diary with you at each visit after getting the study antibody. You will 
turn in the diary at the day 6 visit. Contact the clinic staff if you have any issues 
or concerns. If you have a problem, we will continue to check on you until it goes 
away. 
12. In addition to giving you the study antibody, 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 130 mL (a little less than 2 tablespoons 
to a little more 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 and Appendix G, 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.  

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13. We will counsel you on avoiding HIV. 
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 antibody. 
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 antibody. 
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 get HIV, 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 antibody.  
The 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 and HPTN 
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 

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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 and HPTN 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. The key to the code 
will stay at this clinic. It will not be shared with the HVTN, HPTN or other 
researchers. Your name will not be part of the information. However, some 

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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. There may be other unknown risks. 
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], 
• Beth Israel Deaconess Medical Center (as part of the Protocol Safety Review 
Team), 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. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. 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.). If your site does not have public health or legal reporting 
requirements, you may delete the last sentence in the paragraph above, along with 
the bullets below. 
• [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 

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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 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 contract 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 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 if you choose. We 
will discuss your study options with you. We will counsel you about having HIV 

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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 and receiving SC infusions:  
In this study, we will do some routine medical procedures. These include taking 
blood from you and giving SC infusions to people in Group 4. These procedures 
can cause bruising, pain, fainting, soreness, redness, swelling, itching, a sore, 
bleeding, blood clots, forming a bump under the skin, and (rarely) muscle 
damage, or infection where you got the SC infusion. Giving blood can cause 
swelling of the vein where the needle is placed, or 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 another study antibody, VRC07-523LS, that will be used in Part B of 
this study. 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 study antibody being used in Part A. 

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Although it has not been seen so far, getting the study antibody 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 your true HIV status. They can also tell if 
someone does not have HIV. 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 US 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 antibody 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. 

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We do not know how the study antibody 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 antibody 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 or other methods to prevent HIV. 
However, if the study antibody or a related product 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 protect 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 

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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, the HVTN has a process to decide if it 
is related to the study antibody 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 15 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 Part B 
(Groups 5 and 6) 
Title: A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, 
pharmacokinetics, and antiviral activity of the monoclonal antibody 
PGT121.414.LS administered alone and in combination with VRC07-523LS via 
intravenous or subcutaneous infusions in healthy, HIV-uninfected adult 
participants 
Protocol number: HVTN 136/HPTN 092 
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. 
Key Information 
These are some of the things you should know about this study: 
• The purpose of the study is to understand how well antibodies against HIV 
work when given alone and combined with other antibodies. We also want to 
see if the antibodies are safe to give to people and do not make them too 
uncomfortable.  
• If you choose to join, we will ask you to come to several study visits over 
about 14-16 months. At 3 of these visits you will get combinations of the 
study antibodies in a vein (by IV infusion) or under the skin (by subcutaneous 
infusion, called SC). We will take blood from you at each study visit to see 
how your body responds to the study antibodies and how much antibodies are 
in your blood. We will test you for HIV and other sexually transmitted 
infections (STIs) and pregnancy (if applicable). We will ask you to complete 
questionnaires (many with questions of a personal nature) and you will have 
physical exams.  
• Some general risks of antibodies include fever, chills, shaking, nausea, 
vomiting, pain, headache, dizziness, fatigue, flushing, trouble breathing, high 
or low blood pressure, itchiness and rash. There may be other side effects that 
we don’t yet know about, even serious ones. We think that the risks will be 
similar to these general risks. 
• We do not expect the study antibody to benefit you in any way.  

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• Whether to take part in this study is your choice. You do not have to take part 
in the study and you are free to stop at any time. 
The rest of this form provides a more complete description of this study. Please 
read it carefully. 
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 a 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 in a vein (by IV infusion) or under the skin (by subcutaneous 
infusion, called SC). 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 32 people will take part in this study at multiple clinics. 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 2 parts of this study, Part A and Part B. In Part A, we gave different 
doses of one of the study antibodies by IV and SC. People in Part A got the study 
antibody one time. There were about 12 people in Part A and the results showed 
that it is safe to move ahead with Part B of the study. In Part B, we will give about 
20 more people a combination of both study antibodies by IV and SC. We will 
give the antibodies three times. 
You are being invited to join Part B of the study. 
1. We are doing this study to answer several questions. 
• Are the study antibodies safe to give to people together? 
• Are people able to take the study antibodies without becoming too 
uncomfortable? 
• How much of the study antibodies remain in the body as time passes? 
• How does the body’s response change depending on how the study antibodies 
are given? 

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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 getting HIV if you are exposed to the virus. 
3. These study antibodies are experimental. 
The formal names of the study antibodies are PGT121.414.LS and VRC07-
523LS. 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. This is the first study testing PGT121.414.LS in 
people. VRC07-523LS has been tested in a small number of people in previous 
studies. This is the first study in people using this combination of antibodies. 
The 2 study antibodies were developed by researchers with the Collaboration for 
AIDS Vaccine Discovery (CAVD) (PGT121.414.LS) and at the Dale and Betty 
Bumpers Vaccine Research Center in Bethesda, Maryland (VRC07-523LS). 
In laboratory studies, these study antibodies attached to HIV. They also prevented 
infection by many strains of HIV from around the world. Each of the study 
antibodies was strongest against different strains of HIV. When combined in lab 
tests, they were able to protect human cells from almost all global strains of HIV. 
In animal studies, the study antibodies protected 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, and they did not cause 
health problems. Even if something looks like it is safe or works in animals, it 
may not be true for people. 
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 HIV 
prevention. This study will not answer that question. 
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 this combination, even serious ones. We will tell you about any new 
information that might change your willingness to stay in this study. 
PGT121.414.LS 
Because this is the first time the antibody is being given to people, we do not 
know what all of the risks may be. We think that the risks will be similar to the 
general risks described below. 

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PGT121 
A similar study antibody called PGT121 was changed to make it last longer in the 
body, and that new version is what we will use in this study. PGT121 is being 
tested in a study with HIV-positive and HIV-negative participants. As of March 
2019, about 28 HIV-negative people and 20 HIV-positive people have gotten 
different doses of it by IV infusions and injections, sometimes in combination 
with other experimental antibodies. Ten other people have gotten a placebo (a 
liquid with no antibody in it). This study is still going on and we don’t know who 
got the study antibody and who got a placebo, or what the safety results are. 
VRC07-523LS 
The VRC07-523LS study antibody was given to 25 people by SC injection or IV 
infusion in a study 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. They were given Tylenol and Ibuprofen, and the 
symptoms went away within 12 hours. 
As of October 2018, about 120 more people have gotten this study antibody by IV 
or SC 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, the antibody has 
not made people too uncomfortable or caused serious health problems so far. 
A similar study antibody called VRC01 has been given in 20,000 infusions to 
more than 5000 adults in several studies. Many of these studies are still going on 
and we don’t know who got the study antibody and who got a placebo. After 
receiving VRC01, many people said they had mild pain, itching, or redness where 
the IV infusion or SC injection was given to them. Some of these people said they 
felt like they had the flu afterward, but this feeling lasted a few hours at the most. 
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. 

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• 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 the antibodies in this 
study or 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 or with 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 
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: 

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• 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 personal questions about your HIV 
risk factors such as sexual behavior, alcohol, and drug use. 
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. 
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 your 
participation in the study ends. 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: 

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8. You will come to the clinic for scheduled visits about [#] times over 14-16 
months. 
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. After you get the study antibodies, we 
will ask you to come to the clinic for follow-up visits 1 day later (Group 5 
enrollment visit only), 3 days later, 6 days later, and 2 weeks later (Groups 5 and 
6) 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. Visits where you get the study antibodies 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 participants assigned 
female sex at birth 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 a combination of two study antibodies by IV infusion or SC 
infusion.  
There are 2 groups in Part B of this study called Group 5 and 6. Everyone in Part 
B will get both study antibodies 3 times during the study. People in Group 5 will 
get the antibodies by IV infusion. People in Group 6 will get the antibodies by SC 
infusion. 
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 

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antibody (total of about 2 hours). Other IV infusions will take about 30 minutes 
for each study antibody (total of about 1 hour). 
When getting a subcutaneous infusion, a sterile needle is put under the skin on 
your abdomen or thigh. A pump similar to an IV pump is used to control how fast 
the study antibody is injected through the needle. We will administer each 
antibody as a separate infusion, so you will get 2 infusions of the study antibodies. 
Each infusion will take about 30 minutes in all visits.  
Which group you are in and whether you get the study antibody by IV or SC is 
completely random, like flipping a coin. We have no say in which group you are 
assigned to. Neither do you. 
11. We will give you the study antibodies on a schedule. 
You will get an IV infusion or SC infusion of the study antibodies at three visits 
during the study.  
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 
Participants 
Study antibodies 
At 
enrollment 
At 4 
Months 
At 8 
Months 
5 
10 
PGT121.414.LS 
+ VRC07-523LS 
IV infusion 
IV infusion 
IV infusion 
6 
10 
PGT121.414.LS 
+ VRC07-523LS 
SC infusion  
SC infusion  
SC infusion 
 
You will have to wait in the clinic for at least 2 hours after each infusion to see if 
there are any problems. While you are waiting, we will collect a blood sample one 
hour after the infusions. Then that night and for 3 more days, you will need to 
keep track in a diary about how you are feeling and if you have any symptoms. 
We will review the diary with you at each visit after getting the study antibody. 
You will turn in the diary at the day 6 visit. Contact the clinic staff if you have 
any issues or concerns. If you have a problem, we will continue to check on you 
until it goes away. 
12. In addition to giving you the study antibodies, we will: 
• Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV 
• Do physical exams 
• Do pregnancy tests if you were assigned female sex at birth 

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• 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 120 mL (a little less than 2 tablespoons 
to about 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 H and Appendix I, 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. 
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. 

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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 get HIV, 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 antibodies.  
The 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 and HPTN 
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 and HPTN 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. The key to the code 
will stay at this clinic. It will not be shared with the HVTN, HPTN, or other 
researchers. 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. There may be other unknown risks. 
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 

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• 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. 
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, Beth Israel Deaconess 
Medical Center (as part of the Protocol Safety Review Team), 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. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. 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.). If your site does not have public health or legal reporting 
requirements, you may delete the last sentence in the paragraph above, along with 
the bullets below. 
• [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 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 contract 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 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 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 if you choose. We 
will discuss your study options with you. We will counsel you about having HIV 
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 (Group 5 and 6) and receiving SC infusions (Group 6):  
In this study, we will do some routine medical procedures. These include taking 
blood from you and giving you SC infusions. These procedures can cause 
bruising, pain, fainting, soreness, redness, swelling, itching, a sore, bleeding, 
blood clots, forming a bump under the skin, and (rarely) muscle damage, or 
infection where you got the SC infusion. Giving blood can cause swelling of the 
vein where the needle is placed, or a low blood cell count (anemia), making you 
feel tired. 
Risks of getting an IV infusion (Group 5): 
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. 

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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 study antibody. 
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 your true HIV status. They can also tell if 
someone does not have HIV. 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 or other methods to prevent HIV. 
However, if the study antibody or a related product 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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HVTN136-HPTN092_v1.0_FINAL / Page 154 of 188 
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 protect 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, the HVTN has 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. 

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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 15 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. 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 156 of 188 
 
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: 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
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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 your participation in the study ends. 
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, 
• 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 dose-escalation clinical trial to evaluate the safety, tolerability, 
pharmacokinetics, and antiviral activity of the monoclonal antibody 
PGT121.414.LS administered alone and in combination with VRC07-523LS via 
intravenous or subcutaneous infusions in healthy, HIV-uninfected adult 
participants 
Protocol number: HVTN 136/HPTN 092 
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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HVTN136-HPTN092_v1.0_FINAL / Page 160 of 188 
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 and HPTN 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. The key to the 
code will stay at this clinic. It will not be shared with the HVTN, or other 
researchers. 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 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 161 of 188 
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 US 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 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 162 of 188 
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. 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
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Appendix E 
Schematic of IV infusions and SC infusions 
 
 
 
 
 
 

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Appendix F 
Table of procedures for Part A Groups 1-3 (for sample informed consent form) 
 
 
 
Time after infusion  
Procedure 
Screening 
visit(s) 
Day 0 
1 day 
2 days 
3 days 
6 days 
2 weeks 
1 month 
2 months 
4 months 
6 months 
8 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 
Table of procedures for Part A Group 4 (for sample informed consent form) 
 
 
 
Time after infusion  
Procedure 
Screening 
visit(s) 
Day 0 
1 day 
2 days 
3 days 
6 days 
2 weeks 
1 month 
2 months 
4 months 
6 months 
SC 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. 
 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 166 of 188 
Appendix H 
Table of procedures for Part B Group 5 (for sample informed consent form) 
 
 
 
Time after first infusion  
Procedure 
Screening visit(s) 
Day 0 
1 day 
3 days 
6 days 
2 weeks 
1 month 
2 months 
3 months 
4 months 
5 months 
6 months 
7 months 
8 months 
9 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. 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 167 of 188 
Appendix I 
Table of procedures for Part B Group 6 (for sample informed consent form) 
 
 
 
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 
7 months 
8 months 
9 months 
10 months 
1 year 
1 year & 2 months 
SC 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. 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 168 of 188 
Appendix J 
Laboratory procedures for Part A – Groups 1, 2, and 3 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Day:
Screening 
visit3
D0
D1
D2
D3
D6
D14
D28
D56
D84
D112
D140
D168
D196
D224
Week:
W0
W2
W4
W8
W12
W16
W20
W24
W28
W32
Study Product 
Administration
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. capacity)4
PGT121.414.LS
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 diagnostics 7
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
—
—
10
—
—
—
20
30
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
PGT121.414.LS concentration
CSR
HVTN Labs
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
y
y
y
—
y
—
—
—
—
0
Non-neutralizing antiviral 
assays
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
y
y
—
y
—
—
—
—
0
Anti-Drug Antibody (ADA)
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
y
—
—
—
y
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
y
—
—
—
y
0
Ab Reaction11
Tryptase / C3 and C4 
Complement / Cytokines
CSR
ARUP
SST
8.5mL
—
See footnote 12
—
—
—
—
—
See 
footnote 12
—
See 
footnote 
12
—
See 
footnote 12
0
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs
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
42.5
42.5
42.5
42.5
—
42.5
—
42.5
—
42.5
510
Visit total
25
95
52.5
42.5
52.5
42.5
52.5
42.5
52.5
0
62.5
0
52.5
0
72.5
645
56-Day total13
 
25
120
172.5
215
267.5
310
362.5
405
457.5
95
115
62.5
115
52.5
125
URINE COLLECTION10
Urine dipstick8
Local lab
Local lab
X
—
—
—
—
—
X
—
—
—
—
—
—
—
—
Pregnancy test6
Local lab
Local lab
X
X
—
—
—
—
—
—
—
—
—
—
X
—
—
See footnote 12
 
Greyed out visits are not applicable to these groups. 
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: ARUP Laboratories (Salt Lake City, Utah, USA). 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 169 of 188 
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 administration with negative 
results received prior to administration. Persons who have undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
7At 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 15 above. If a 
participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.12). 
8And microscopy if needed 
9.Syphilis testing will be done by serology 
10For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be collected. 
11To investigate Ab administration-related clinical 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 136/HPTN 092 SSP for more information. 
12SST blood will be collected at specific timepoints after the onset of any Ab reaction. Refer to the HVTN 136/HPTN 092 SSP for more information. 
13The 56-day total blood volume does not include up to 34mL SST blood collected for any Ab reaction; however, the 56-day limit is not exceeded at any visit by the possible collection of SST blood 
for an Ab reaction. 
14Of 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 Ab reactions); no separate blood draw is needed. 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 170 of 188 
Appendix K 
Laboratory procedures for Part A – Group 4 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
Day:
Screening 
visit3
D0
D1
D2
D3
D6
D14
D28
D56
D84
D112
D140
D168
Week:
W0
W2
W4
W8
W12
W16
W20
W24
Study Product 
Administration
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. capacity)4
PGT121.414.LS
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 diagnostics 7
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
—
—
—
—
10
—
20
30
Safety labs10
CBC/ Differential
Local lab
Local lab
EDTA
5mL
5
5
5
—
5
—
5
—
5
—
5
—
5
40
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
5
—
5
—
5
—
5
—
5
—
5
40
Drug concentrations/detection
PGT121.414.LS concentration
CSR
HVTN Labs
SST
8.5mL
—
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
—
y
—
—
0
Non-neutralizing antiviral assays
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
y
y
—
y
—
—
0
Anti-Drug Antibody (ADA)
ADA detection assays (screening, confirmatory, 
titration)
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
y
—
—
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
y
—
—
0
Ab Reaction11
0
Tryptase / C3 and C4 Complement / Cytokines
CSR
ARUP
SST
8.5mL
—
See footnote 12
—
—
—
—
—
See 
footnote 12
—
See 
footnote 12
0
ADA detection assays (screening, confirmatory, 
titration)
CSR
HVTN Labs
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
42.5
42.5
42.5
42.5
—
42.5
—
42.5
468
Visit total
25
95
52.5
42.5
52.5
42.5
52.5
42.5
52.5
0
62.5
0
72.5
593
56-Day total13
 
25
120
172.5
215
267.5
310
362.5
405
457.5
95
115
62.5
135
URINE COLLECTION10
Urine dipstick8
Local lab
Local lab
X
—
—
—
—
—
X
—
—
—
—
—
—
Pregnancy test6
Local lab
Local lab
X
X
—
—
—
—
—
—
—
—
X
—
—
See footnote 12
 
Greyed out visit are not applicable to these groups. 
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: ARUP Laboratories (Salt Lake City, Utah, USA). 
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. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 171 of 188 
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 administration with negative 
results received prior to administration. 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 13 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 Ab administration-related clinical 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 136/HPTN 092 SSP for more information. 
12 SST blood will be collected at specific time points after the onset of any Ab reaction. Refer to the SSP for more information. 
13 The 56-day total blood volume does not include up to 34mL SST blood collected for any Ab reaction; however, the 56-day limit is not exceeded at any visit by the possible collection of SST blood 
for an Ab reaction. 
14 Of this volume, 17mL of SST blood will be collected 1 hour after the end of study product administration (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; no separate blood draw is needed. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 172 of 188 
Appendix L 
Laboratory procedures for Part B – Group 5 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Day:
Screening 
visit3
D0
D1
D2
D3
D6
D14
D28
D56
D84
D112
D140
D168
D196
D224
D252
D280
D336
D392
D448
Week:
W0
W2
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W48
W56
W64
Study Product 
Administration #1
Study Product 
Administration #2
Study Product 
Administration #3
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
PGT121.414.LS +
VRC07-523LS
PGT121.414.LS +
VRC07-523LS
PGT121.414.LS +
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 diagnostics 7
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
5
5
5
80
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
—
—
—
—
5
5
5
5
5
5
5
5
5
5
5
5
5
5
80
Drug concentrations/detection
PGT121.414.LS, VRC07-
523LS concentrations
CSR
HVTN Labs
SST
8.5mL
—
y
y
—
y
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
y
y
y
y
y
y
y
—
—
0
Non-neutralizing antiviral 
assays
CSR
HVTN Labs
SST
8.5mL
—
y
y
—
y
y
y
y
y
—
y
y
y
y
y
y
y
y
—
—
0
Anti-Drug Antibody (ADA)
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs
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
Ab 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 
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
—
—
See footnote y
—
—
—
See footnote y
—
—
—
—
—
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
—
—
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
42.5
5114
42.5
42.5
42.5
5114
42.5
42.5
42.5
42.5
42.5
824.5
Visit total
 
25
95
42.5
0
42.5
42.5
52.5
52.5
52.5
52.5
71
52.5
52.5
53
71
52.5
52.5
62.5
52.5
72.5
1049.5
56-Day total13
 
25
120
163
163
205
248
300
353
405
157.5
176
176
176
105
124
176
176
115
115
125
URINE COLLECTION10
 
 
 
 
 
 
 
Urine dipstick8
Local lab
Local lab
X
—
—
—
—
—
X
—
—
—
—
X
—
—
—
X
—
—
—
—
Pregnancy test6
Local lab
Local lab
X
X
—
—
—
—
—
—
—
—
X
—
—
—
X
—
—
—
X
—
See footnote 12
 
Greyed out visits are not applicable to this group. 
1CSR = central specimen repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA) 
2HVTN 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: ARUP Laboratories (Salt Lake City, Utah, USA) 
3Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration.  
4Local labs may assign appropriate alternative tube types for locally performed tests. 
5Chemistry panels are defined in Section 9.2 (pre-enrollment).  
6For 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 administration with negative 
results received prior to administration. Persons who have undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 173 of 188 
7At 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 20 above. If a 
participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.12). 
8And microscopy if needed. 
9Syphilis testing will be done by serology.  
10For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be collected. 
11To investigate Ab administration-related clinical 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 136/HPTN 092 SSP for more information. 
12SST blood will be collected at specific timepoints after the onset of any Ab reaction. Refer to the HVTN 136/HPTN 092 SSP for more information. 
13The 56-day total blood volume does not include up to 51mL SST blood collected for any Ab reaction; however, the 56-day limit is not exceeded at any visit by the possible collection of SST blood 
for an Ab 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 Ab reactions); no separate blood draw is needed. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 174 of 188 
Appendix M 
Laboratory procedures for Part B – Group 6 
 
Greyed out visits are not applicable to this group. 
1CSR = central specimen repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA) 
2HVTN Laboratories include: Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, North Carolina, USA); Dartmouth College (Hanover, 
New Hampshire, USA). 
3Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration.  
4Local labs may assign appropriate alternative tube types for locally performed tests. 
5Chemistry panels are defined in Section 9.2 (pre-enrollment).  
6For 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 administration with negative 
results received prior to administration. Persons who have undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Day:
Screening 
visit3
D0
D1
D2
D3
D6
D14
D28
D56
D84
D112
D140
D168
D196
D224
D252
D280
D336
D392
Week:
W0
W2
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W48
W56
Study Product 
Administration #1
Study Product 
Administration #2
Study Product 
Administration #3
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
PGT121.414.LS +
VRC07-523LS
PGT121.414.LS +
VRC07-523LS
PGT121.414.LS +
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 diagnostics 7
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
5
5
75
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
—
—
—
—
5
5
5
5
5
5
5
5
5
5
5
5
5
75
Drug concentrations/detection
PGT121.414.LS, VRC07-
523LS concentrations
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
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
y
y
y
y
y
y
—
0
Non-neutralizing antiviral 
assays
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
y
y
y
y
y
—
y
y
y
y
y
y
y
y
—
0
Anti-Drug Antibody (ADA)
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
y
—
—
y
y
—
—
y
y
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
—
—
—
y
—
—
y
y
—
—
y
y
0
Ab 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 
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
—
—
See footnote y
—
—
—
See footnote y
—
—
—
—
0
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
—
—
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
5114
42.5
42.5
42.5
42.5
739.5
Visit total
 
25
95
0
0
42.5
42.5
52.5
52.5
52.5
52.5
71
52.5
52.5
104
71
52.5
52.5
62.5
72.5
1005.5
56-Day total13
 
25
120
120
120
163
205
258
310
363
157.5
176
176
176.0
156
175
227
176
115
135
URINE COLLECTION10
 
 
 
 
 
 
 
Urine dipstick8
Local lab
Local lab
X
—
—
—
—
—
X
—
—
—
—
X
—
—
—
X
—
—
—
Pregnancy test6
Local lab
Local lab
X
X
—
—
—
—
—
—
—
—
X
—
—
—
X
—
—
X
—
See foootnote 12

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 175 of 188 
7At 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 19 above. If a 
participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic testing (see Section 9.12). 
8And microscopy if needed. 
9Syphilis testing will be done by serology. 
10For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be collected. 
11To investigate Ab administration-related clinical 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 136/HPTN 092 SSP for more information. 
12SST blood will be collected at specific time points after the onset of any Ab reaction. Refer to the SSP for more information. 
13The 56-day total blood volume does not include up to 51mL SST blood collected for any Ab reaction; however, the 56-day limit is not exceeded at any visit by the possible collection of SST blood 
for an Ab reaction. 
14Of this volume, 17mL of SST blood will be collected 1 hour after the end of study product administration (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; no separate blood draw is needed. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 176 of 188 
Appendix N 
Procedures at CRS for Part A Groups 1 – 3 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
Post 
Day: 
 
D0 
D1 
D2 
D3 
D6 
D14 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
 
Week: 
 
W0 
W0 
W0 
W0 
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
 
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 
X 
X 
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 
— 
Contraception status assessment5 
X 
X 
— 
— 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
X 
— 
Social impact assessment 
— 
X 
— 
— 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
X 
— 
Behavioral risk assessment questionnaire6 
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 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
Sample Collection8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
— 
X 
— 
Greyed out visits are not applicable to these groups. 
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 136/HPTN 092 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 J. 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 177 of 188 
Appendix O 
Procedures at CRS for Part A Group 4 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
Post 
Day: 
 
D0 
D1 
D2 
D3 
D6 
D14 
D28 
D56 
D84 
D112 
D140 
D168 
 
Week: 
 
W0 
W0 
W0 
W0 
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
 
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 
X 
X 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
X 
— 
— 
— 
Risk reduction counseling4 
X 
X 
— 
— 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
Contraception status assessment5 
X 
X 
— 
— 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
Social impact assessment 
— 
X 
— 
— 
— 
— 
X 
X 
X 
— 
X 
— 
X 
— 
Behavioral risk assessment questionnaire6 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Concomitant medications 
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 
— 
HIV infection assessment7 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
Sample Collection8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
X 
— 
X 
— 
Greyed out visits are not applicable to these groups. 
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 137/HPTN 092 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 K. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 178 of 188 
Appendix P 
Procedures at CRS for Part B Group 5 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
10 
113 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Post 
Day: 
 
D0 
D1 
D2 
D3 
D6 
D14 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D336 
D392 
D448 
 
Week: 
 
W0 
W0 
W0 
W0 
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W48 
W56 
W64 
 
Procedure 
Scr 
Inf 1 
 
 
 
 
 
 
 
 
Inf 2 
 
 
 
Inf 3 
 
 
 
 
 
 
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 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Solicited AE assessment4 
— 
X 
X 
— 
X 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Abbreviated physical exam 
— 
X 
X 
— 
X 
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 
X 
X 
— 
Contraception status assessment6 
X 
X 
— 
— 
— 
— 
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 
X 
X 
X 
X 
X 
X 
— 
Behavioral risk assessment questionnaire7 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
Concomitant medications 
X 
X 
X 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/Unsolicited adverse 
experience 
— 
X 
X 
— 
X 
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 
X 
X 
X 
— 
Greyed out visits are not applicable to this group. 
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 136/HPTN 092 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. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 179 of 188 
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 L. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 180 of 188 
Appendix Q 
Procedures at CRS for Part B Group 6 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
10 
113 
12 
13 
14 
15 
16 
17 
18 
19 
Post 
Day: 
 
D0 
D1 
D2 
D3 
D6 
D14 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D336 
D392 
 
Week: 
 
W0 
W0 
W0 
W0 
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W48 
W56 
 
Procedure 
Scr 
Inf 1 
 
 
 
 
 
 
 
 
Inf 2 
 
 
 
Inf3 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Confirm eligibility, obtain 
demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Infusion4 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Solicited AE assessment4 
— 
X 
— 
— 
X 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Abbreviated physical exam 
— 
X 
— 
— 
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 
X 
— 
Contraception status assessment6 
X 
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 
X 
X 
X 
X 
X 
— 
Behavioral risk assessment 
questionnaire7 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
 
X 
— 
Social impact assessment 
questionnaire 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Concomitant medications 
X 
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 
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 
X 
— 
Greyed out visits are not applicable to this group. 
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 136/HPTN 092 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. 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 181 of 188 
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 M. 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 182 of 188 
Appendix R 
HVTN low risk guidelines for the US 
 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 183 of 188 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 184 of 188 
Appendix S 
Visit Windows for Part A Groups 1-3 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Day 
Target 
Day 
Upper 
Target Day 
Upper 
Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
- 
02.0 
Enrollment¹ 
Infusion 
- 
- 
0 
- 
- 
03.0 
1 day post infusion 
- 
- 
1 
- 
- 
04.0 
2 days post infusion  
- 
- 
2 
- 
- 
05.0 
3 days post infusion 
- 
- 
3 
- 
- 
06.0 
 
6 days post infusion 
-2 
- 
6 
- 
+2 
07.0 
2 weeks post infusion 
-7 
-3 
14 
+3 
+7 
08.0 
4 weeks post infusion 
-7 
-3 
28 
+3 
+7 
09.0 
8 weeks post infusion 
-7 
-3 
56 
+3 
+7 
10.0 
 
 
 
 
 
 
11.0 
16 weeks post infusion 
-7 
-3 
112 
+3 
+7 
12.0 
 
 
 
 
 
 
13.0 
24 weeks post infusion 
-7 
-3 
168 
+3 
+7 
14.0 
 
 
 
 
 
 
15.0 
Final Visit 
32 weeks post infusion 
-14 
-7 
224 
+7 
+14 
¹Screening should be conducted within 56 days of Enrollment (Infusion.) 
 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 185 of 188 
Appendix T 
Visit Windows for Part A Group 4 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Day 
Target 
Day 
Upper 
Target Day 
Upper 
Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
- 
02.0 
Enrollment¹ 
Infusion 
- 
- 
0 
- 
- 
03.0 
1 day post infusion 
- 
- 
1 
- 
- 
04.0 
2 days post infusion  
- 
- 
2 
- 
- 
05.0 
3 days post infusion 
- 
- 
3 
- 
- 
06.0 
 
6 days post infusion 
-2 
- 
6 
- 
+2 
07.0 
2 weeks post infusion 
-7 
-3 
14 
+3 
+7 
08.0 
4 weeks post infusion 
-7 
-3 
28 
+3 
+7 
09.0 
8 weeks post infusion 
-7 
-3 
56 
+3 
+7 
10.0 
 
 
 
 
 
 
11.0 
16 weeks post infusion 
-7 
-3 
112 
+3 
+7 
12.0 
 
 
 
 
 
 
13.0 
Final Visit 
24 weeks post infusion 
-7 
-3 
168 
+3 
+7 
¹Screening should be conducted within 56 days of Enrollment (Infusion). 
 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 186 of 188 
Appendix U 
Visit Windows for Part B Group 5 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Day 
Target 
Day 
Upper 
Target Day 
Upper 
Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
- 
02.0 
Enrollment¹ 
Infusion #1 
- 
- 
0 
- 
- 
03.0 
1 day post infusion #1² 
- 
- 
1 
- 
- 
04.0 
  
- 
- 
 
- 
- 
05.0 
3 days post infusion #1² 
- 
- 
3 
- 
- 
06.0 
 
6 days post infusion #1² 
-2 
- 
6 
- 
+2 
07.0 
2 weeks post infusion #1² 
-7 
-3 
14 
+3 
+7 
08.0 
4 weeks post infusion #1² 
-7 
-3 
28 
+3 
+7 
09.0 
8 weeks post infusion #1² 
-7 
-3 
56 
+3 
+7 
10.0 
12 weeks post infusion #1² 
-7 
-3 
84 
+3 
+7 
11.0 
Infusion #2 
-14 
-7 
112 
+7 
+14 
12.0 
4 weeks post infusion #2² 
-7 
-3 
140 
+3 
+7 
13.0 
8 weeks post infusion #2² 
-7 
-3 
168 
+3 
+7 
14.0 
12 weeks post infusion #2² 
-7 
-3 
196 
+3 
+7 
15.0 
Infusion #3 
-14 
-7 
224 
+7 
+14 
16.0 
4 weeks post infusion #3² 
-7 
-3 
252 
+3 
+7 
17.0 
8 weeks post infusion #3² 
-7 
-3 
280 
+3 
+7 
18.0 
16 weeks post infusion #3² 
-7 
-3 
336 
+3 
+7 
19.0 
24 weeks post infusion #3² 
-7 
-3 
392 
+3 
+7 
20.0 
Final Visit 
32 weeks post infusion #3² 
-14 
-7 
448 
+7 
+14 
¹Screening should be conducted within 56 days of Enrollment (Infusion #1). 
²Postinfusion visits are scheduled according to date of the prior infusion visit. 
 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 187 of 188 
Appendix V 
Visit Windows for Part B Group 6 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Day 
Target 
Day 
Upper 
Target Day 
Upper 
Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
- 
02.0 
Enrollment¹ 
Infusion #1 
- 
- 
0 
- 
- 
03.0 
 
- 
- 
 
- 
- 
04.0 
 
- 
- 
 
- 
- 
05.0 
3 days post infusion #1² 
- 
- 
3 
- 
- 
06.0 
 
6 days post infusion #1² 
-2 
- 
6 
- 
+2 
07.0 
2 weeks post infusion #1² 
-7 
-3 
14 
+3 
+7 
08.0 
4 weeks post infusion #1² 
-7 
-3 
28 
+3 
+7 
09.0 
8 weeks post infusion #1² 
-7 
-3 
56 
+3 
+7 
10.0 
12 weeks post infusion #1² 
-7 
-3 
84 
+3 
+7 
11.0 
Infusion #2 
-14 
-7 
112 
+7 
+14 
12.0 
4 weeks post infusion #2² 
-7 
-3 
140 
+3 
+7 
13.0 
8 weeks post infusion #2² 
-7 
-3 
168 
+3 
+7 
14.0 
12 weeks post infusion #2² 
-7 
-3 
196 
+3 
+7 
15.0 
Infusion #3 
-14 
-7 
224 
+7 
+14 
16.0 
4 weeks post infusion #3² 
-7 
-3 
252 
+3 
+7 
17.0 
8 weeks post infusion #3² 
-7 
-3 
280 
+3 
+7 
18.0 
 16 weeks post infusion #3² 
-7 
-3 
336 
+3 
+7 
19.0 
Final Visit 
24 weeks post infusion #3² 
-7 
-3 
392 
+3 
+7 
¹Screening should be conducted within 56 days of Enrollment (Infusion #1). 
²Postinfusion visits are scheduled according to date of the prior infusion visit. 
 
 

HVTN 136/HPTN 092 Version 1.0 / October 8, 2019 
HVTN136-HPTN092_v1.0_FINAL / Page 188 of 188 
Appendix W Protocol Signature Page 
A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, 
pharmacokinetics, and antiviral activity of the monoclonal antibody 
PGT121.414.LS administered alone and in combination with  
VRC07-523LS via intravenous or subcutaneous infusions in healthy, HIV-
uninfected adult participants 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (US) Health and Human Service regulations (45 
CFR 46); applicable U.S. Food and Drug Administration regulations; standards of 
the International Conference on Harmonization Guideline for Good Clinical 
Practice (E6); Institutional Review Board/Ethics Committee determinations; all 
applicable in-country, state, and local laws and regulations; and other applicable 
requirements (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 136/HPTN 092 
DAIDS Protocol Version: Version 1.0 
Protocol Date: October 8, 2019