A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA, in Healthy, HIV-Uninfected Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
PROTOCOL 
HVTN 119 
A phase 1 clinical trial to evaluate the safety and 
immunogenicity of pDNA vaccines expressing HIV 
M Group p24Gag conserved elements and/or p55Gag, 
administered with IL-12 pDNA by intramuscular 
electroporation, in healthy, HIV-uninfected adult 
participants 
DAIDS DOCUMENT ID 12061 
BB 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 PRODUCT(S) PROVIDED BY 
DAIDS, NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
Profectus BioSciences, Inc. 
Tarrytown New York, USA 
Ichor Medical Systems, Inc. 
San Diego, California, US 
February 17, 2017 
FINAL 
HVTN 119, Version1.0 

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HVTN119_v1.0_FINAL / Page 2 of 140 
Contents 
1 
Ethical considerations .............................................................................................. 4 
2 
IRB/EC review considerations ................................................................................. 6 
2.1 
Minimized risks to participants ..................................................................... 6 
2.2 
Reasonable risk/benefit balance .................................................................... 6 
2.3 
Equitable participant selection ....................................................................... 6 
2.4 
Appropriate informed consent ....................................................................... 7 
2.5 
Adequate safety monitoring ........................................................................... 7 
2.6 
Protect privacy/confidentiality ....................................................................... 7 
3 
Overview .................................................................................................................. 8 
3.1 
Protocol Team .............................................................................................. 11 
4 
Background ............................................................................................................ 12 
4.1 
Rationale for trial concept ........................................................................... 12 
4.2 
p24CE1/2 pDNA ......................................................................................... 15 
4.3 
p55gag pDNA ................................................................................................ 18 
4.4 
IL-12 pDNA adjuvant .................................................................................. 19 
4.5 
Electroporation (EP) .................................................................................... 20 
4.6 
Trial design rationale ................................................................................... 21 
4.7 
Plans for future product development and testing ....................................... 22 
4.8 
Preclinical safety studies .............................................................................. 22 
4.9 
Preclinical immunogenicity studies ............................................................. 23 
4.10 Clinical studies ............................................................................................ 35 
4.11 Potential risks of study products and administration ................................... 41 
5 
Objectives and endpoints ....................................................................................... 42 
5.1 
Primary objectives and endpoints ................................................................ 42 
5.2 
Secondary objectives and endpoints ............................................................ 42 
5.3 
Exploratory objectives ................................................................................. 43 
6 
Statistical considerations ........................................................................................ 45 
6.1 
Accrual and sample size calculations .......................................................... 45 
6.2 
Randomization ............................................................................................. 47 
6.3 
Blinding ....................................................................................................... 47 
6.4 
Statistical analyses ....................................................................................... 48 
7 
Selection and withdrawal of participants ............................................................... 53 
7.1 
Inclusion criteria .......................................................................................... 53 
7.2 
Exclusion criteria ......................................................................................... 55 
7.3 
Participant departure from vaccination schedule or withdrawal .................. 59 
8 
Study product preparation and administration ....................................................... 62 
8.1 
Vaccine regimen .......................................................................................... 62 
8.2 
Study product formulation ........................................................................... 63 
8.3 
Preparation of study products ...................................................................... 64 
8.4 
Administration ............................................................................................. 70 
8.5 
Acquisition of study products ...................................................................... 72 
8.6 
Pharmacy records......................................................................................... 72 
8.7 
Final disposition of study products .............................................................. 72 
9 
Clinical procedures ................................................................................................ 73 
9.1 
Informed consent ......................................................................................... 73 

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9.2 
Pre-enrollment procedures ........................................................................... 75 
9.3 
Enrollment and vaccination visits ................................................................ 76 
9.4 
Follow-up visits ........................................................................................... 78 
9.5 
Month 18 health contact .............................................................................. 79 
9.6 
HIV counseling and testing ......................................................................... 80 
9.7 
Contraception status..................................................................................... 82 
9.8 
Urinalysis ..................................................................................................... 82 
9.9 
Assessments of reactogenicity ..................................................................... 82 
9.10 Visit windows and missed visits .................................................................. 84 
9.11 Early termination visit ................................................................................. 84 
9.12 Pregnancy .................................................................................................... 84 
10 
Laboratory .............................................................................................................. 85 
10.1 HVTN CRS laboratory procedures .............................................................. 85 
10.2 Total blood volume ...................................................................................... 85 
10.3 Primary immunogenicity timepoints ........................................................... 85 
10.4 Endpoint assays: cellular ............................................................................. 85 
10.5 Endpoint assays: humoral ............................................................................ 86 
10.6 Genotyping .................................................................................................. 86 
10.7 Lab assay algorithm ..................................................................................... 86 
10.8 Exploratory studies ...................................................................................... 86 
10.9 Other use of stored specimens ..................................................................... 87 
10.10 Biohazard containment ................................................................................ 87 
11 
Safety monitoring and safety review ..................................................................... 88 
11.1 Safety monitoring and oversight .................................................................. 88 
11.2 Safety reporting ........................................................................................... 89 
11.3 Safety reviews .............................................................................................. 91 
11.4 Safety pause and prompt PSRT AE review ................................................. 92 
11.5 Review of cumulative safety data ................................................................ 93 
11.6 Study termination......................................................................................... 93 
12 
Protocol conduct .................................................................................................... 94 
12.1 Social impacts .............................................................................................. 95 
12.2 Compliance with NIH guidelines for research involving products containing 
recombinant or synthetic Nucleic Acid Molecules ...................................... 95 
12.3 Emergency communication with study participants .................................... 95 
13 
Version history ....................................................................................................... 97 
14 
Document references (other than literature citations) ............................................ 98 
15 
Acronyms and abbreviations ................................................................................ 100 
16 
Literature cited ..................................................................................................... 102 
Appendix A Sample informed consent form .................................................................. 112 
Appendix B Approved birth control methods (for sample informed consent form) ...... 131 
Appendix C Sample consent form for use of samples and information in other studies 132 
Appendix D Table of procedures (for sample informed consent form) ......................... 136 
Appendix E Laboratory procedures ............................................................................... 137 
Appendix F Procedures at HVTN CRS ......................................................................... 138 
Appendix G Adverse events of special interest .............................................................. 140 
 

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1 
Ethical considerations 
Multiple candidate HIV vaccines will need to be studied simultaneously in different 
populations around the world before a successful HIV preventive vaccine is found. 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) has 
addressed ethical concerns in the following ways: 
 
HVTN trials are designed and conducted to enhance the knowledge base necessary to 
find a preventive vaccine, using methods that are scientifically rigorous and valid, 
and in accordance with Good Clinical Practice (GCP) guidelines. 
 
HVTN scientists and operational staff incorporate the philosophies underlying major 
codes [1-3], declarations, and other guidance documents relevant to human subjects 
research into the design and conduct of HIV vaccine clinical trials. 
 
HVTN scientists and operational staff are committed to substantive community 
input—into the planning, conduct, and follow-up of its research—to help ensure that 
locally appropriate cultural and linguistic needs of study populations are met. 
Community Advisory Boards (CAB) are required by DAIDS and supported at all 
HVTN research sites to ensure community input.  
 
HVTN clinical trial staff counsel study participants routinely on how to reduce HIV 
risk. Participants who become HIV-infected during the trial are provided counseling 
on notifying their partners and about HIV infection according to local guidelines. 
Staff members will also counsel them about reducing their risk of transmitting HIV to 
others. 
 
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. 
 
The HVTN provides training so that all participating sites similarly ensure fair 
participant selection, protect the privacy of research participants, and obtain 
meaningful informed consent. During the study, participants will have their 
wellbeing monitored, and to the fullest extent possible, their privacy protected. 
Participants may withdraw from the study at any time. 
 
Prior to implementation, HVTN trials are rigorously reviewed by scientists who are 
not involved in the conduct of the trials under consideration.  
 
HVTN trials are reviewed by local and national regulatory bodies and are conducted 
in compliance with all applicable national and local regulations. 
 
The HVTN designs its research to minimize risk and maximize benefit to both study 
participants and their local communities. For example, HVTN protocols provide 
enhancement of participants’ knowledge of HIV and HIV prevention, as well as 
counseling, guidance, and assistance with any social impacts that may result from 
research participation. HVTN protocols also include careful medical review of each 

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research participant’s health conditions and reactions to study products while in the 
study.  
 
HVTN research aims to benefit local communities by directly addressing the health 
and HIV prevention needs of those communities and by strengthening the capacity of 
the communities through training, support, shared knowledge, and equipment. 
Researchers involved in HVTN trials are able to conduct other critical research in 
their local research settings. 
 
The HVTN values the role of in-country Institutional Review Boards (IRBs), Ethics 
Committees (ECs), and other Regulatory Entities (REs) as custodians responsible for 
ensuring the ethical conduct of research in each setting. 

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2 
IRB/EC review considerations 
US Food and Drug Administration (FDA) and other US federal regulations require 
IRBs/ECs/REs to ensure that certain requirements are satisfied on initial and continuing 
review of research (Title 45, Code of Federal Regulations (CFR), Part 46.111(a) 1-7; 21 
CFR 56.111(a) 1-7). The following section highlights how this protocol addresses each of 
these research requirements. Each HVTN Investigator welcomes IRB/EC/RE questions 
or concerns regarding these research requirements. 
2.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly informing 
participants about risks so that they can join in partnership with the researcher in 
recognizing and reporting harms; (b) respecting local/national blood draw limits; (c) 
performing direct observation of participants postvaccination and collecting information 
regarding side effects for several days postvaccination; (d) having staff properly trained 
in administering study procedures that may cause physical harm or psychological 
distress, such as blood draws, vaccinations, HIV testing and counseling and HIV risk 
reduction counseling; (e) providing HIV risk reduction counseling and checking on 
contraception use (for women); and (f) providing safety monitoring. 
2.2 
Reasonable risk/benefit balance 
45 CFR 46.111(a) 2 and 21 CFR 56.111(a) 2: Risks to subjects are reasonable in 
relation to anticipated benefits, if any, to subjects, and the importance of the 
knowledge that may reasonably be expected to result. 
In all public health research, the risk-benefit ratio may be difficult to assess because the 
benefits to a healthy participant are not as apparent as they would be in treatment 
protocols, where a study participant may be ill and may have exhausted all conventional 
treatment options. However, this protocol is designed to minimize the risks to participants 
while maximizing the potential value of the knowledge it is designed to generate.  
2.3 
Equitable participant selection  
45 CFR 46.111 (a) 3 and 21 CFR 56.111 (a) 3: Subject selection is equitable 
This protocol has specific inclusion and exclusion criteria for investigators to follow in 
admitting participants into the protocol. Participants are selected because of these criteria 
and not because of positions of vulnerability or privilege. Investigators are required to 
maintain screening and enrollment logs to document volunteers who screened into and 
out of the protocol and for what reasons. 

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2.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 & 5 and 21 CFR 56.111 (a) 4 & 5: Informed consent is sought 
from each prospective subject or the subject’s legally authorized representative as 
required by 45 CFR 46.116 and 21 CFR Part 50; informed consent is appropriately 
documented as required by 45 CFR 46.117 and 21 CFR 50.27 
The protocol specifies that informed consent must be obtained before any study 
procedures are initiated and assessed throughout the trial (see Section 9.1). Each site is 
provided training in informed consent by the HVTN as part of its entering the HVTN. 
The HVTN requires a signed consent document for documentation, in addition to chart 
notes or a consent checklist. 
2.5 
Adequate safety monitoring 
45 CFR 46.111 (a) 6 and 21 CFR 56.111 (a) 6: There is adequate provision for 
monitoring the data collected to ensure the safety of subjects. 
This protocol has extensive safety monitoring in place (see Section 11). Safety is 
monitored daily by HVTN Core and routinely by the HVTN 119 Protocol Safety Review 
Team (PSRT). In addition, the HVTN Safety Monitoring Board (SMB) periodically 
reviews study data. 
2.6 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate provisions to 
protect the privacy of subjects and maintain the confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or unreasonable 
intrusion into his/her private life and the right to control access to individually 
identifiable information about him/her. The term “privacy” concerns research participants 
or potential research participants as individuals whereas the term “confidentiality” is used 
to refer to the treatment of information about those individuals. This protocol respects the 
privacy of participants by informing them about who will have access to their personal 
information and study data (see Appendix A). 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 HVTN 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 HVTN and each study site participating in the 
protocol is required to have a standard operating procedure on how the staff members 
will protect the confidentiality of study participants. 

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3 
Overview 
Title 
A phase 1 clinical trial to evaluate the safety and immunogenicity of pDNA vaccines 
expressing HIV M Group p24Gag conserved elements and/or p55Gag, administered with IL-
12 pDNA by intramuscular electroporation, in healthy, HIV-uninfected adult participants 
Primary objectives 
 
To evaluate the safety and tolerability of the HIV-1 pDNA vaccines p24CE1/2 and 
p55gag administered with IL-12 pDNA by intramuscular injection with 
electroporation 
 
To compare the two pDNA prime/boost strategies with respect to breadth (defined as 
the number of targeted CEs) of CD4+ and CD8+ T-cell responses to conserved 
regions of the p24Gag protein  
Study products and routes of administration 
 
p24CE1/2 is a DNA plasmid (pDNA) that encodes 2 cassettes, p24CE1 and p24CE2, 
each consisting of 7 conserved element (CE) sequences from HIV-1 p24Gag separated 
by short amino acid spacers. The p24CE1 and p24CE2 proteins differ by 7 amino 
acids and together cover >98% of HIV-1 Group M sequences worldwide. The 
p24CE1 cassette is under the control of the human CMV promoter/enhancer and the 
bovine growth hormone (BGH) polyadenylation signal. The p24CE2 cassette is in the 
opposite transcriptional orientation and is under the control of the simian CMV 
promoter and the simian virus 40 (SV40) polyadenylation signal.  
 
p55gag refers to a DNA plasmid encoding an expression-optimized full length HIV-1 
p55Gag protein from the HIV-1 molecular clone HXB2 (Genbank NP_057850).  
 
IL-12 refers to GENEVAX® IL-12 DNA Plasmid (Profectus BioSciences, Inc., 
Tarrytown, New York, USA). The IL-12 pDNA adjuvant is a dual promoter plasmid 
that expresses the genes encoding human IL-12 proteins p35 and p40 under separate 
regulatory control. The p35 subunit is under the control of the human CMV 
promoter/enhancer and the SV40 polyadenylation signal. The p40 subunit is under 
the control of the simian CMV promoter and the BGH polyadenylation signal. The 
plasmid vaccines will be admixed with IL-12 pDNA to produce a single injectable 
solution delivered by intramuscular (IM) injection followed by electroporation. 
 
Placebo: Sodium Chloride for Injection, USP 0.9%. 
 
Intramuscular TriGrid Delivery System (TDS-IM) (Ichor Medical Systems, San 
Diego, California), a device for electroporation mediated intramuscular 
administration of DNA based-biologic candidates. 

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Table 3-1 Schema 
Study arm 
Number 
Dose  
(total) 
Month 0  
(Day 0) 
Month 1  
(Day 28) 
Month 3  
(Day 84) 
Month 6  
(Day 168) 
Group 1 
25 
4 mg 
2 mg 
p24CE1/2 
IL-12 
p24CE1/2 
IL-12 
p24CE1/2+ 
p55gag 
IL-12 
p24CE1/2+ 
p55gag 
IL-12 
3 
- 
Placebo 
Placebo 
Placebo 
Placebo 
Group 2 
25 
4 mg 
2 mg 
p55gag 
IL-12 
p55gag 
IL-12 
p55gag 
IL-12 
p55gag 
IL-12 
3 
- 
Placebo 
Placebo 
Placebo 
Placebo 
Total 
50+ 6 = 56 
 
 
 
 
 
Notes 
All injections will be delivered IM followed by electroporation (IM/EP). The doses 
shown will be divided between 2 injection sites, such that 2 mg p24CE1/2 or p55gag 
pDNA vaccine, or a mixture of 1 mg each, and 1 mg IL-12 pDNA, or placebo, will be 
given in each deltoid at every vaccination timepoint. 
Enrollment will proceed in both groups simultaneously and will be restricted to US 
HVTN Clinical Research Sites (CRSs). Across the participating CRSs, enrollment will be 
restricted to a maximum of 1 participant per day until 10 participants have been enrolled. 
The HVTN 119 Protocol Safety Review Team (PSRT) will review the cumulative safety 
data on each of these 10 participants, including at minimum local and systemic 
reactogenicity data reported for the first 72 hours postvaccination, and will determine 
whether it is safe to proceed with full enrollment in that group. 
Participants 
56 healthy, HIV-uninfected volunteers aged 18 to 50 years; 50 vaccinees, 6 placebo 
recipients 
Design 
Multicenter, randomized, placebo controlled, double-blind trial 
Duration per participant 
18 months (12 months of scheduled clinic visits (main study) and 1 follow-up contact) 
Estimated total study duration 
26 months (includes enrollment, planned safety holds, and follow-up) 
Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 

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Study product providers 
 
p24CE1/2 pDNA and p55gag pDNA: DAIDS, NIAID, NIH, DHHS (Bethesda, 
Maryland, USA) 
 
IL-12 pDNA adjuvant: Profectus BioSciences, Inc. (Tarrytown, New York, USA) 
 
Intramuscular TriGrid Delivery System (TDS-IM) EP Device: Ichor Medical 
Systems, Inc. (San Diego, California, USA) 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson Cancer 
Research Center (FHCRC) (Seattle, Washington, USA) 
Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), FHCRC (Seattle, 
Washington, USA) 
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) 
 
FHCRC/University of Washington (Seattle, Washington, USA) 
 
Vanderbilt University (Nashville, Tennessee, USA) 
Study sites 
HVTN Clinical Research Sites to be specified in the Site Announcement Memo 
Safety monitoring 
HVTN 119 PSRT; HVTN Safety Monitoring Board (SMB) 

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3.1 
Protocol Team 
Protocol leadership 
Chair 
Spyros Kalams 
Vanderbilt University 
615-322-8688 
spyros.a.kalams@vanderbilt.edu 
Statistician 
Allan DeCamp 
SCHARP, FHCRC 
206-667-6047 
adecamp@scharp.org 
Co-chair 
Hyman Scott 
Bridge HIV, SFDPH 
415-437-7438 
hyman.scott@sfdph.org 
Medical officer 
Mary Allen 
DAIDS, NIAID 
240-627-3036 
mallen@niaid.nih.gov 
Protocol 
Team leader 
Marnie Elizaga 
HVTN Core, FHCRC 
650-854-4984 
melizaga@fredhutch.org 
Laboratory lead 
Nicole Frahm 
HVTN Laboratory 
Program 
206-667-6268 
nfrahm@fredhutch.org 
Other contributors to the original protocol 
Core medical monitor 
Marnie Elizaga 
HVTN Core, FHCRC 
DAIDS protocol 
pharmacist 
Nayri Khairalla 
DAIDS, NIAID 
301-761-6659 
Vaccine developer 
representatives 
James I. Mullins 
University of Washington 
Clinical safety 
specialist 
Jill Zeller 
HVTN Core, FHCRC 
 
Barbara K. Felber 
National Institutes of Health 
Clinical trials 
manager 
Marianne Hansen 
HVTN Core, FHCRC 
 
George N. Pavlakis 
National Institutes of Health 
Clinical data 
manager 
Huguette Redinger 
SCHARP, FHCRC 
Adjuvant developer 
representative 
Susan Sciotto-Brown 
Profectus Biosciences 
HVTN program 
manager 
Gina Escamilla 
SCHARP, FHCRC 
Device developer 
representative 
Drew Hannaman 
Ichor Medical Systems 
DAIDS Project 
Officer 
Chris Butler 
DAIDS, NIAID 
Laboratory protocol 
operations manager 
On Ho 
HVTN Laboratory Program, 
FHCRC 
Protocol 
development 
manager 
Meg Trahey 
HVTN Core, FHCRC 
Regulatory affairs 
Laurie Rinn 
HVTN Core, FHCRC 
Community 
educator/recruiter 
Laura Michelson 
Fenway CRS 
Clinic coordinator 
Naomi Prashad 
Nashville CRS 
Community 
engagement unit 
representative 
Jim Maynard  
HVTN Core, FHCRC 
Community Advisory 
Board (CAB) members 
Ebony Gordon 
Nashville CAB 
Statistical research 
associate 
Erika Thommes 
SCHARP, FHCRC 
 
Fred Mazyck 
Boston-Fenway CAB 
Technical editor 
Erik Schwab 
HVTN Core, FHCRC 

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4 
Background 
4.1 
Rationale for trial concept 
The variability of HIV is a major stumbling block in vaccine design, since successful 
vaccines must protect against an ever-expanding universe of viral antigens. The plasticity 
of HIV allows for an enormous number of mutant strains that retain viability, which in 
turn allows the virus to escape from immune responses while preserving protein and 
overall viral function. The task of summarizing this diversity into immunogens of a 
manageable size is formidable. As a result, we are currently unable to produce HIV 
vaccines that predictably elicit broad, durable protective immunity. 
HIV vaccine immunogens have generally been derived from individual viral isolates. To 
maximize immunologic breadth, investigators have employed consensus and deduced 
ancestral sequences [4-6], as well as created antigenic combinations of common variants 
that evolve as a result of immune pressure (eg, mosaics [7-10] and similar structures 
[11,12]), with the goal of blocking common escape forms of viruses and thus effectively 
block immunological escape pathways. However, it may not be possible to vaccinate with 
all of the viral antigenic diversity required to block viable or transition escape forms of 
the virus—as rapid, sequential epitope evolution, including uncommon intermediates, is 
commonplace early in infection [13,14]. For example, a study of the recognition of the 
most common mutant forms of the HIV Nef protein (representing ~65% of the known 
variation of this protein), found that peptides were not recognized based on their 
frequency in the virus population [15]. Thus, the immunogen sequence diversity that may 
be required to block viable or transition escape mutants may be too large to accommodate 
for a single or a manageably sized variation inclusive vaccine. 
Another important concern is that presentation of variable epitopes, such as provided by a 
mosaic-like vaccine, would result in immunodominance (ie, hierarchical preference for 
recognition of one epitope of the vaccine over another, magnified by its presentation in 
different variant forms) or immunodominating responses (ie, suppression of some 
responses by others) by non-protective epitopes. Non-protective epitopes are those whose 
recognition is associated with a lack of virologic containment in vivo (eg, high viral load) 
or those that can readily escape without impairing viral fitness. Immunodominant 
epitopes with a high degree of conservation do not necessarily confer immune control of 
viral replication, as they may represent viral adaptation to human HLA types at the 
population level, and at minimal fitness cost [16-18]. It seems likely that if HIV segments 
were capable of mutating without limiting virus functionality, they would not contribute 
substantially to a vaccine’s protective response. We further suggest that variable epitopes 
can serve as immunodominant “decoys” that can absorb immune reactivity and 
potentially preclude responses against protective epitopes. For example, the most 
significant difference between HIV strains infecting vaccine vs. placebo recipients in the 
Step (HVTN 502) vaccine trial occurred within a region including the SLYNTVATL 
epitope in Gag [19], an immunodominant epitope, responses to which are not associated 
with diminution of viral load [20]. Although unproven, SLYNTVATL reactivity may 
therefore represent an immunodominant decoy response that is detrimental to vaccine 
efficacy [21].  
This trial will evaluate the safety and immunogenicity of a novel vaccine encoding 
“conserved elements” (CE) of the HIV-1 Gag core protein, p24Gag. The p24CE1/2 pDNA 
vaccine is composed exclusively of two gene segments (p24CE1 and p24CE2, on one 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 13 of 140 
plasmid, referred to as p24CE1/2 pDNA) expressing carefully selected portions of the 
HIV-1 capsid protein, p24Gag, the most abundant protein in HIV virions (Figure 4-1). 
p24Gag was chosen because of its availability as an immune target during infection, and 
because CTL responses to Gag, and in particular the p24Gag component of Gag, have been 
associated in numerous studies with greater control of HIV viremia [22-32]. The 
sequences expressed by p24CE1/2 pDNA correspond to the portions of p24Gag found in 
nearly every HIV-1 (M group) strain observed to date throughout the world. Unlike most 
of the HIV-1 genes and their encoded proteins, CE have rarely if at all been observed to 
mutate (for the most part they are composed of amino acids conserved in at least 98% of 
all HIV-1 infections), and represent components that are enriched with those essential to 
virus infectivity. 
The following observations guided the design of the p24CE1/2 pDNA vaccine: 
1. HIV mutates to sequences that contain ancestral amino acids (AA) when transmitted 
to a new host, essentially recovering a more fit state in the absence of the specific 
immune responses that shaped the viral genome in the previous host [33-35]. Hence, 
the p24CE1/2 vaccine is composed of conserved, ancestral, center of tree [6] 
sequences. 
2. CTL that target specific viral proteins have reproducible effects on viral load. 
Numerous studies have shown that robust Gag-specific CTL contain infection [22-
32], whereas CTL responses against the HIV-1 Pol protein generally do not correlate 
with levels of viremia, and responses against Env and the accessory proteins correlate 
with a lack of control of viremia [16-18,22,23]. 
3. Changes in conserved amino acids, especially in Gag, often but not always will 
debilitate or inactivate the virus [36-40]. In contrast, the majority of escape mutations 
in Env [36,39] or Nef [41] have a neutral or an enhancing impact on viral replication 
fitness. Hence, the p24CE1/2 pDNA vaccine is composed exclusively of conserved 
Gag protein elements. 
4. CTL recognition of some conserved epitopes of the virus are preferentially detected 
in long-term non-progressors and in those with strong virologic control, most notably 
those with HLA B*57, B*58 [42-47], and B*27 [42,46,48-51] alleles. These same 
epitopes are present in the p24CE1/2 vaccine, and importantly, they are also targets 
of immune responses in virologic “controllers” that do not possess these HLA 
proteins [52]. This illustrates the criticality of the viral protein sequence being 
targeted by the immune system, as opposed to the HLA type, in controlling infection. 
5. Viruses from “elite controllers” (ie, plasma HIV RNA <50 copies/mL in the absence 
of antiretroviral therapy) have impaired replication capacity both in acute/early 
[47,53] and in chronic infection [47,54]. 
6. Immunodominance of some epitopes can obscure or prevent reactivity against other, 
potentially protective epitopes, whereas responses to subdominant epitopes have been 
associated with better virologic control [55-57]. This suggests that an immunogen 
should not mimic the immunodominance elicited in most natural infections (B*57, 
B*58 and B*27 individuals being a notable exception). Hence, a focus on careful 
exclusion of these epitopes is likely to assist targeting of critical epitopes while 
removing potential immunodominant decoy responses.  
7. Some AA segments in HIV proteins are conserved throughout a given HIV-1 
subtype, the entire M group of HIV-1, and in some instances also in HIV-2 and SIV 
[56,58]. This is especially true for AA conserved since the beginning of the HIV 
pandemic, as opposed to those that have had HLA imprinting occur, with 

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immunologic escape mutants now comprising the most conserved AA state [37]. 
These segments make up the p24CE1/2 pDNA vaccine, are generally critical to viral 
function, and thus represent the Achilles’ heel of the virus. 
Recently a similar approach focusing on conserved elements is being taken, albeit with a 
heavy emphasis on Pol protein segments, in the European community [59]. Inclusion of 
conserved element approaches into the HVTN portfolio significantly broadens its 
scientific agenda. 
The focus of the study is a pDNA prime-boost vaccine regimen, comprising p24CE1/2 
pDNA prime followed by p24CE1/2+ p55gag pDNA booster vaccination. This regimen 
focuses the priming response to highly conserved, but subdominant epitopes, which we 
hypothesize will then be boosted, and possibly broadened by a combination of p24CE1/2 
vaccine, and full length gag in the booster vaccination. This strategy is expected to 
achieve significantly broader epitope recognition compared to a regimen of full-length 
gag pDNA vaccine given alone. 
This trial will be composed of 2 groups receiving different prime-boost regimens. Group 
1 will receive p24CE1/2 pDNA prime followed by co-delivery of p24CE1/2 pDNA and 
full-length gag pDNA (CE/CE+gag). Group 2 will receive prime and boost with the full-
length gag pDNA (gag/gag). The vaccines will be co-administered with IL-12 pDNA, 
and given with electroporation. Four vaccinations will be given in the series, with 
priming vaccinations at 0 and 1 month, and boost vaccinations given at 3 and 6 months. 
Cellular and humoral immune responses in vaccine recipients will be compared to a 
control set of individuals given placebo injections given with electroporation on the same 
schedule.  
In summary, we hypothesize that by targeting regions of the HIV-1 p24Gag protein that 
are invariable across Group M viruses, this vaccine approach may elicit specific immune 
responses linked to protection and viral control, rather than immune responses that may 
include decoy responses with detrimental effects or limited antiviral potential. 

HVTN 119, Version1.0 / February 17, 2017 
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Figure 4-1 Alignment of p24CE1, p24CE2 and p24Gag proteins. The schematic representation at 
the top of the figure shows the p55Gag and its proteolytic processing products including p24Gag 
protein. Below is the alignment of the amino acid (AA) sequences of the consensus p24Gag 
sequences of different HIV-1 clades and of the seven CE encoded by the p24CE1/2 pDNA vaccine. 
The AA sequences of the p24Gag of different HIV-1 clades (A, B, C), group M consensus, COT-M, 
and of the p24CE1 and p24CE2 proteins are shown. The CE1 to CE7 sequences with the single 
AA change per CE are indicated. 
4.2 
p24CE1/2 pDNA 
p24CE1/2 pDNA (Figure 4-2) is a dual promoter plasmid generated to express the 
p24CE1 gene from the human CMV promoter and the p24CE2 gene from the simian 
CMV promoter in the opposite transcriptional orientation. There are 7 CE segments of 
13, 18, 24, 20, 20, 14 and 18 amino acids in the p24CE pDNA vaccine[58]. One 
“toggled” amino acid is included in each of the 7 CE segments, resulting in two protein 
coding elements (p24CE1 and p24CE2) differing by a total of 7 codons, each sharing 127 
amino acids with p24Gag. Coding sequences were optimized to enhance expression in 
human cells [60-65]. The p24CE sequences represent 54% of p24Gag, including most 
extended coiled regions of the protein. CE regions include amino acids at p24Gag hexamer 
interfaces, which provide a structural rationale for their conservation, and CE are 
enriched with AA sites that if mutated to the second-most common AA found in the HIV 
database, nonetheless result in noninfectious virus [37,38].  
The plasmid also contains two polyadenylation signals (bovine growth hormone polyA 
signal for p24CE1 and the simian virus 40 polyA signal for p24CE2). Of note, the 
promoter and polyA signal for the p24CE1 gene are identical to the single gene 
expression vector used to express the p55Gag protein. Furthermore, the promoters and poly 
A signals are the same as used in the dual expression IL-12 pDNA plasmid to be used in 
the trial (although promoters and poly A signals were combined differently).  

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The CE segments are separated by linkers of 0-3 amino acids in length composed of 
Alanine, or Alanine and Lysine, or Alanine and Glycine. The total length of the proteins 
spans 157 AA including 17 AA of the GM-CSF signal peptide and 13 AA of linker 
sequences. It is known that inclusion of protease cleavage sites in DNA vaccines can 
enhance immunogenicity and preserve epitopes for HIV antigens [66]. The length and 
sequence of the linker sequences were therefore set based on the existing knowledge of 
cleavage specificities and peptide availability [67], as well as to avoid fortuitous 
junctional homologies with HIV and the human proteome, the latter determined by 
searching against the HIV and human proteome databases [68]. 
Production levels of p24CE proteins from the dual expression plasmid were 
indistinguishable from the combination of the two single vectors (unpublished). In studies 
performed in macaques, no differences in the levels of induced immune responses were 
noted using the single p24CE1/2 pDNA expressing p24CE1 and p24CE2 genes (N=10) 
versus the combination of two vectors, each expressing one of the two respective genes 
(N=6) (see Figure 4-5) [69-71]. 
 
 
Figure 4-2 Schematic of the p24CE1/2 pDNA (plasmid code 306H)  
For the clinical trial, the p24CE1/2 pDNA is produced at a concentration of 4 mg/mL, 
and is formulated in 30 mM citrate buffer pH 6.5 containing 150 mM NaCl, 0.01% 
ethylenediamine tetraacetic acid (EDTA) and 0.25% bupivacaine-HCl. The pDNA was 
manufactured by Ajinomoto Althea, San Diego, CA. The pDNA is formulated in 
bupivacaine, a local anesthetic that forms stable liposomal-like structures upon direct 
mixing with pDNA and further protects pDNA from degradation [72]. The p24CE1/2 
pDNA will be admixed with IL-12 pDNA, or with p55gag and IL-12 pDNA, to produce a 
single injectable solution. The p24CE1/2 pDNA has not been tested in humans. 
p24CE1/2 pDNA vaccine formulated in water given IM with EP has been tested in 
macaques monitored for >2 years without any adverse effects. 
The p24CE1/2 (plasmid 306H) and p55gag (plasmid 114H, see Section 4.3) pDNAs both 
use a plasmid backbone that is derived from pVR1012 [73] (Figure 4-3). The pVR1012 
plasmid backbone has also been used in DNA vaccine studies including the following: 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 17 of 140 
 
the gag-pol-nef plasmids VRC4413, VRC4305, VRC4311 (Vaccine Research Center, 
NIAID) for which biodistribution and toxicity studies were performed (BB-
IND10681 SN000);  
 
the p55gag plasmid DNA VRC4401 (Vaccine Research Center, NIAID; GenBank 
CS070894) that has been used in a clinical trial (NCT00123968) as part of the DNA 
vaccine HIVDNA016-00-VP. 
 
Figure 4-3 Comparison of plasmids derived from pVR1012. Plasmids VRC4413, VRC4305 and 
VRC4311 express gag-pol-nef using mammalian expression vector pVR1012. The plasmid 
backbone of p55gag (plasmid 114H) and p24CE1/2 (plasmid 306H) are also derived from pVR1012. 
Differences in pDP.CMVkan and pCMV.kan backbones are indicated in red (single nt change in the 
hCMV promoter, lack of CMV IE intron, 5 nt insertion between pUC and CMV promoter; 
pDP.CMVkan contains a cassette inserted within pUC that includes the simian CMV promoter and 
the SV40polyA signal sequence. Each vector has unique inserts. 
In summary, the pCMVkan and pDP.CMVkan plasmid backbones used in p24CE1/2 and 
p55gag pDNAs, respectively, and that of pVR1012 can be compared as follows: 
o identical BGH polyA signal,  
o identical kanamycin resistance gene 
o identical origin of replication, colE1 
o identical pUC nucleotide sequence between backbone segments 
with these differences: 
o one nucleotide difference in the human CMV promoter (745 nt): thymidine at 
position 362 in p55gag and p24CE1/2 pDNA instead of cytosine.  
o lack of the intronic sequence; according to our studies, splicing is not necessary for 
efficient expression of RNA-optimized genes; also, the presence of splice sites may 
generate alternatively spliced mRNAs encoding aberrant proteins 
o insertion of 5 nucleotides (TGGCC) at the junction of pUC plasmid and human CMV 
promoter in pCMVkan and pDP.CMVkan 
o presence of simian CMV promoter in the pDP.CMVkan derived plasmid p24CE1/2 
pDNA 

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o presence of SV40 polyA signal in the pDP.CMVkan derived plasmid p24CE1/2 
pDNA 
A variety of approaches have been taken to assure that CE immunogens present relevant 
T-cell epitopes to the immune system: 
1. To ensure that the epitopes in the CE vaccine could be processed appropriately for 
presentation by HLA, 40-mer peptides encompassing each CE as well as junctional 
regions were generated and subjected to proteolytic processing by human cell 
extracts. Fifteen of 16 known epitopes were identified as optimal or 1-3 AA extended 
degradation products in these assays (Le Gall et al., unpublished). 
2. To determine whether CE are conserved because they are immunologically silent 
(due to impaired presentation on HLA), or because they have functional significance, 
T-cell responses to p24Gag were evaluated in 50 HIV-1 infected subjects without 
protective HLA class I alleles [52]. These 50 individuals consisted of HIV-1 
controllers (<2,000 copies RNA/mL) and non-controllers (>50,000 copies RNA/mL) 
and excluded those with HLA*B27/57/58 alleles in order to focus development on 
immunogens for the majority of people without such favorable genetic backgrounds 
and, potentially, without the perhaps unique mechanisms of immune control [74] 
exhibited by HLA*B27/57/58 expressing individuals. For those without the 
aforementioned protective HLA alleles, recognition of HIV may be more likely to be 
obscured by immunodominant decoys and may benefit from directed targeting to 
structurally critical segments of the virus such as the CE. p24CE were found to be 
rich in epitopes, with >30 epitopes targeted by >40 different HLA class I molecules 
in the 50 subjects [52]. Interestingly, >70% of all responses to specific 10-mer 
peptides and their embedded optimally defined epitopes were observed in individuals 
not expressing the known restriction element [52], further supporting our approach to 
use CE rather than only known epitopes as immunogens. The 25 controllers tested 
preferentially recognized the TW10 and KK10 epitope regions, which were 
previously associated with control in B*57/B*58, and B*27 individuals, respectively, 
even though these controllers did NOT possess these “protective” alleles. Differential 
reactivity was also focused on a known B*14 DA9 epitope, again targeted by 
individuals that did not possess the B14 allele. In conclusion, the specific epitopes 
recognized, and not necessarily the HLA type, are critical for the control of infection. 
As the vaccine plasmids as well as the IL-12 plasmid are formulated in 0.25% 
bupivacaine, there is a risk of allergic reaction, including rash, urticaria, angioedema, 
bronchospasm, or anaphylaxis. Significant adverse experiences including cardiac arrest 
and death have occurred following intravenous delivery of bupivacaine. In most cases, 
this has followed use of bupivacaine at a dose of 1.6 mg/kg. Bupivacaine in this study is 
being administered IM at a dose of 2.5 mg/ml (maximum 2 ml, or 5 mg). A 50 kg person 
would receive a dose of 0.1 mg/kg per dose administered. Participants with a history of 
allergic reaction to amide-type local anesthetics (bupivacaine [Marcaine], lidocaine 
[Xylocaine], mepivacaine [Polocaine/Carbocaine], etidocaine [Duranest], prilocaine 
[Citanest, EMLA® cream]) will be excluded.  
4.3 
p55gag pDNA 
The p55gag pDNA (plasmid 114H) contains expression-optimized full length HIV-1 
p55gag gene from the HIV-1 molecular clone HXB2 (Genbank NP_057850) cloned into 
the pCMVkan plasmid between the human CMV promoter and the bovine growth 

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hormone polyA signal (Figure 4-4). The p55gag pDNA and the p24CE1/2 pDNA share the 
same plasmid backbone which is described above in Section 4.2. Like the p24CE1/2 
pDNA, the p55gag pDNA is formulated in bupivacaine.  
 
Figure 4-4 Schematic of p55gag pDNA 
p55gag pDNA is produced at a concentration of 4 mg/mL, in 30 mM citrate buffer pH 6.5 
containing 150 mM NaCl, 0.01% EDTA and 0.25% bupivacaine-HCl. The pDNA was 
manufactured by Ajinomoto Althea, San Diego, CA. The p55gag pDNA will be admixed 
with IL-12 pDNA or with p24CE1/2 and IL-12 pDNA to produce a single injectable 
solution. 
Related plasmids expressing HIV p55Gag have been tested in several clinical trials, 
including HVTN 060, 063, 070, 080, 087, and no significant adverse effects related to 
vaccine were reported. 
4.4 
IL-12 pDNA adjuvant 
The GENEVAX® IL-12 DNA plasmid is a dual promoter expression plasmid which 
expresses the genes encoding human IL-12 subunits p35 and p40 under separate 
regulatory control. The p35 subunit is under the control of the hCMV promoter/enhancer 
and the SV40 polyadenylation signal. The p40 subunit is under the control of the sCMV 
promoter and the BGH polyadenylation signal. The plasmid contains a chimeric 
kanamycin resistance gene and a pUC bacterial origin of replication. The IL-12 pDNA 
adjuvant is be produced at a concentration of 2 mg/mL and is formulated in 30 mM 
citrate buffer pH 6.5 containing 150 mM NaCl, 0.01% EDTA, and 0.25% bupivacaine- 
HCl. The plasmid is formulated in bupivacaine to enhance stability and facilitate entry 
into cells [72]. It was manufactured by Ajinomoto Althea, San Diego, CA. 
The IL-12 pDNA adjuvant will be given together with the p24CE1/2 pDNA, the p55gag 
pDNA and the p24CE1/2 and p55gag pDNA combination, respectively and will be 
delivered with electroporation (EP). HVTN 080, a phase 1 clinical trial, has demonstrated 

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the safety and immunogenicity of 3 mg PENNVAX™-B (gag, pol, env) vaccine (Inovio 
Pharmaceuticals, Inc.) with 1 mg IL-12 pDNA (Profectus BioSciences, Inc.) given by 
IM/EP [75]. In addition, recent work by Pavlakis, Felber and colleagues has shown 
induction of immunity with the proposed vector given with IL-12 pDNA EP in rhesus 
macaques, with superior CD4+ and CD8+ T-cell as well as Ab responses [76-78]. Other 
clinical trials (HVTN 087, IAVI B004) have shown reduced CD4+ T-cell response rates 
in groups given IL-12 pDNA, while CD8+ T-cell responses were equivalent or improved, 
compared to study arms without IL-12 pDNA [79,80]. The IL-12 pDNA adjuvant, 
GENEVAX® IL-12 DNA Plasmid, has been tested by the HVTN in 5 previous trials: 
HVTN 060 (DAIDS-ES ID 10057, BB IND#12367), HVTN 063 (DAIDS-ES ID 10058, 
BB IND#12439), HVTN 070 (DAIDS-ES ID 10490, BB IND#13449), HVTN 080 
(DAIDS-ES ID 10741, BB IND#14116), and HVTN 087 (DAIDS-ES ID 11673, BB 
IND#14976). Please refer to the Investigator’s Brochure (IB) for additional information. 
4.5 
Electroporation (EP) 
EP has been shown to be an efficient means to introduce DNA into cells [81]. EP is a 
technology in which a transient electric field is applied to the target tissue in order to 
enhance the cellular uptake of large molecules such as DNA. EP works by temporarily 
increasing the permeability of cell membranes. Although EP has been used 
experimentally in humans [82,83], EP remains investigational. Preclinical and phase 1 
studies have suggested that EP enhances the potency of pDNA vaccines [80,84-87]. Ichor 
Medical Systems has focused on the development of EP technology where the means for 
agent administration and electric field application are integrated into a fully automated 
administration device. The overarching goal of this approach, embodied in the Ichor 
TDS-IM, is to enable agent administration, placement of electrodes, and timing of EP 
delivery to be completed in a simple, user independent fashion. Each TDS-IM device 
consists of three components, a single use Application Cartridge housing the EP 
electrodes and the agent of interest, a handheld, multi-use Integrated Applicator, and a 
Pulse Stimulator. The TriGrid™ electrode array for intramuscular delivery consist of four 
electrodes arranged in two triangles to form a diamond shape around an integrated central 
injection needle. Correlation of the electrode configuration with the agent distribution 
pattern intrinsic to the target tissue ensures that the EP effect is induced only in tissues 
where the agent of interest has been distributed, improving tolerability and minimizing 
tissue disruption. To date, the TDS-IM has been used for IM delivery of DNA vaccines 
or placebo in over 20 human clinical studies totaling in more than 700 clinical trial 
participants. The device has been used for administration of pDNA doses of up to 4.0 mg 
per site and 8.0 mg overall. Use of the device has been associated with mild to moderate 
injection site reactions resolving within 24-72 hours. Other mild or moderate transient 
adverse events have included paresthesia or hypoesthesia in the injected limb, cutaneous 
bleeding, bruising, or hematoma, vasovagal reactions, flu-like symptoms, headache, 
fever, nausea, chills, dizziness, malaise, fatigue, arthralgia, myalgia, neuralgia, and CPK 
increase. One event of brief syncope has been reported in a person with pre-existing 
bradycardia. No serious pDNA or device related adverse events have been reported 
during these studies. Although the use of EP administration is associated with 
substantially more acute discomfort than a conventional injection, to date, study subjects 
have exhibited a high degree of compliance.  
HVTN 112 is a phase 1 trial to evaluate the safety, tolerability, and immunogenicity of a 
prime-boost regimen of HIV-1 nef/tat/vif, env pDNA vaccine delivered intramuscularly 
with electroporation and HIV-1 rVSV envC vaccine in healthy HIV-uninfected adult 

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HVTN119_v1.0_FINAL / Page 21 of 140 
participants (BB IND #16783, DAIDS-ES ID 11988). In HVTN 112, an event occurred 
in which the EP device was difficult to remove from a person’s arm, causing severe pain 
and stress. The participant was receiving injection with EP for the first time. Pain was 
managed with local anesthesia to allow device removal. After the event, the person had 
some pain, tenderness, and bruising, but did not have any serious adverse reactions, and 
quickly resumed normal activities. After investigation, the conclusion is that the device 
had functioned normally, but that in this case, there may have been an unusual mismatch 
between the device setting specified for the person’s arm skinfold measurement, and the 
person’s arm physique (ie, skin and deltoid muscle thickness) which led to contact 
between the injection needle and the underlying bone. This happened in one participant 
out of 15 in this study, and has not been previously reported with this device before, in 
over 700 other subjects, and over 3000 administrations. 
Please refer to the TDS-IM Investigator’s Brochure for additional information regarding 
the TDS-IM device. 
4.6 
Trial design rationale 
One major goal of the proposed phase 1 trial is to demonstrate that a DNA plasmid 
expressing the CE regions of p24Gag, given with IL-12 pDNA adjuvant and IM/EP 
delivery, has an acceptable safety profile. 
The proposed trial is also designed as a proof-of-concept demonstration that conserved 
elements of the viral p24Gag protein, normally subdominant in HIV infections, can be 
immunogenic, can induce levels of immune response comparable to full-length Gag, can 
potently shift the immunodominance of Gag epitopes from variable to conserved regions 
of the p24Gag protein when used in a CE/CE+gag prime/boost vaccination regimen, and 
can induce increased levels of polyfunctional and cytotoxic T cells directed to CE 
compared to the full-length Gag antigen administered as a pDNA vaccine. IL-12 pDNA 
delivered with plasmid DNA vaccines with EP may have an adjuvant effect on CD8+ 
responses and provide an advantage to the evaluation of immunogenicity of the 
p24CE1/2 and p55gag pDNA vaccines. 
4.6.1 
Dose (amount and number) 
The DNA vaccines (p24CE1/2, p55gag) will be given at 4 mg total dose per vaccination (2 
mg per deltoid). Doses of DNA vaccines previously given in HVTN studies with IM/EP 
have ranged from 3 mg to 8 mg. Multiple priming vaccinations are proposed to increase 
the likelihood of robust immune responses. 
GENEVAX® IL-12 DNA plasmid will be given at 2 mg total dose per vaccination (1 mg 
per deltoid). Doses of IL-12 pDNA adjuvant previously given in HVTN studies with 
IM/EP have ranged from 0.25 mg to 1.5 mg, with up to 1 mg given at a single injection 
site. 
In HVTN 080 (see Section 4.10.3), which showed an increase in ICS response rates (not 
statistically significant, possibly due to small sample sizes), 1 mg IL-12 pDNA was given 
at a single site, and well-tolerated. In other studies, the local dose of IL-12 pDNA was 
0.25 to 0.75 mg. An adjuvant effect appears to be dose dependent on the local IM dose, 
and 1 mg per injection site has been chosen for this study, to try to replicate the adjuvant 
effect seen in HVTN 080. IL-12 pDNA has not been associated with severe 

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reactogenicity or serious adverse events with up to 1.5 mg total dose per vaccination visit 
in these studies. We expect the minimal increase to 2 mg total dose (1 mg per injection 
site) to be safe and well tolerated both at the injection sites and systemically. 
4.6.2 
Prime-boost regimen 
A prime-boost regimen of 4 vaccinations will be given, with injections at 0, 1 (priming 
immunogen) and 3, 6 months (booster immunogen(s)). This schedule allows for 
comparison with other HVTN studies of DNA vaccines given with IM/EP, which 
vaccinated participants on schedules of 0, 1 and 3 months or 0, 1, 3 and 6 months. Group 
1 (CE/CE+gag) receives a combination of 2 immunogens for the boost. Group 2 
(gag/gag) receives one immunogen as both the prime and the boost. Partially 
heterologous boost vaccinations are proposed in Group 1 to further increase the 
likelihood of robust immune responses. 
4.6.3 
Choice of control 
Sodium Chloride for Injection, USP 0.9%, will serve as the placebo for the p24CE1/2 
pDNA vaccine, the p55gag pDNA vaccine, and IL-12 pDNA. Sodium Chloride for 
Injection, USP 0.9% is nonreactogenic and well tolerated. It will be delivered by IM/EP 
as a control for blinding purposes. It is possible that the presence of bupivacaine in the 
vaccines and adjuvant may reduce the pain of injection reported on the VAS relative to 
the saline control. This should not adversely affect the efficiency of blinding. 
4.7 
Plans for future product development and testing 
Positive results would prompt at least two avenues of future trials, towards evaluation of 
efficacy, either alone or in conjunction with other immunogens against other regions of 
the viral proteome, and for the development of additional CE immunogens corresponding 
to other regions of HIV-1 proteins and a therapeutic vaccine to target the highly 
conserved less exhausted epitopes of the HIV. 
4.8 
Preclinical safety studies 
During pre-IND review, the Center for Biologics Evaluation and Research concurred that 
preclinical safety studies with the p24CE1/2 pDNA and p55gag pDNA study products 
were not necessary based on previous nonclinical and clinical experience with similar 
products. DAIDS has developed significant nonclinical and clinical experience with 
pDNAs formulated in bupivacaine that contain gag inserts (multiple investigational 
products), and with IL-12 pDNA, including the use of intramuscular administration with 
electroporation to deliver a gag pDNA with IL-12 pDNA. In addition, the 3 
investigational plasmids to be studied have been evaluated in a macaque study that 
extended more than 2 years, using endotoxin-free DNA preparations purified with the 
Qiagen kit in the laboratory. This study not only demonstrated that the animals developed 
durable cellular and humoral immune responses, but also that no adverse effects were 
observed, either after the initial vaccination series or after an additional booster 
vaccination at approximately 2 years. Furthermore, the cGMP p24CE1/2 pDNA and 
p55gag pDNA preparations have been tested in an immunological and observational study 
in C57BL/6 mice (N=5/group). Mice were administered 20 micrograms of pDNA/mouse 
(2 vaccinations at 0 and 4 months and sacrificed 2 weeks later) via IM/EP. No adverse 

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effects were observed and the mice developed similar levels of antigen-specific cellular 
immune responses compared to mice vaccinated in parallel arms within the same study 
with the laboratory-produced endotoxin-free pDNAs. 
4.9 
Preclinical immunogenicity studies 
A variety of model systems were used to demonstrate that delivery of p24CE pDNA 
would induce strong immune responses. A series of proof-of-concept studies (Table 4-1), 
detailed in Sections 4.9.2 and 4.9.3, were conducted in mice and macaques. The vaccine 
concept aiming to focus the immune responses to the highly conserved CE sequences of 
the Gag capsid protein was developed and tested for HIV, and, using an analogous 
design, for SIV, which will allow in vivo testing of vaccine efficacy in a macaque 
challenge model. Briefly, these studies demonstrated that vaccination with CE pDNA 
induces potent immune responses to subdominant epitopes, which could not be achieved 
by vaccination with pDNA expressing the full-length Gag. Vaccine regimens including 
booster vaccinations with gag pDNA or co-delivery of CE+gag pDNA greatly augment 
the cytotoxic CE-specific responses, however the latter booster regimen maximizes the 
breadth of the responses to the otherwise subdominant CE epitopes. Thus, in preclinical 
trials, the regimen consisting of p24CE1/2 pDNA priming followed by co-delivery of 
CE+gag pDNA booster vaccination results in immune responses with greatest magnitude, 
breadth and cytotoxicity. This vaccine regimen has been selected for the clinical trial. 

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Table 4-1 Summary of preclinical immunogenicity studies 
Study  
number 
Product 
Schedule 
(months) 
Animal 
N 
(sex) 
pDNA Dose groups 
References 
Assay 
1 
HIV:  
p24CE1, p24CE2; p24CE1 + 
p24CE2; or p55gag; 
cGMP p24CE1/2; or 
cGMP p55gag 
0, 4 or 
0, 3, 6 
weeks 
C57BL/6, 
Balb/c mice 
~300 
(F) 
20 g 
[88] 
ICS, ELISA, 
Western 
2 
HIV: 
p24CE1+p24CE2+IL-12(P) 
0, 2* 
Indian (5)*, 
Chinese (1)* 
RM 
4 (M) 
2 (F) 
2 mg CE, 
0.2 mg IL-12 
[69,70] 
ICS, ELISA, 
Western 
3 
HIV: 
p24CE1/2+IL-12(P) 
0, 2 
Indian RM 
4 (M) 
2 mg CE, 
0.2 mg IL-12 
[69,70] 
ICS, ELISA, 
Western 
4 (continued 
from 2) 
HIV: 
p55gag +IL-12 (B) 
4 (B) 
 
 
1 mg gag, 
0.2 mg IL-12 (B) 
[89] 
ICS, ELISA, 
Western 
5 (continued 
from 3) 
HIV:  
 p55gag+IL-12 (B) 
4 (B) 
 
 
1 mg gag, 
0.2 mg IL-12 (B) 
[69,70] 
ICS, ELISA, 
Western 
6 
HIV: 
p24CE1/2+IL-12 (P)- 
p24CE1/2+p55gag+IL-12 (B) 
0, 1 (P)- 
4, 6 (B) 
Indian RM 
6 (M) 
4 mg CE, 
0.2 mg IL-12 (P)– 
2 mg CE, 
2 mg gag, 
0.2 mg IL-12 (B) 
[71] 
ICS 
7 
SIV: 
p27CE1+p27CE2+IL-12(P) 
0, 2, 4 
Indian RM 
13 (M) 
1 (F) 
2 mg CE, 
0.2 mg IL-12 
[71] 
ICS, ELISA, 
Western 
8 (6 animals, 
continued 
from 7) 
SIV: 
 gag+IL-12 (B) 
0, 2, 4 (P)- 
6 (B) 
Indian RM 
5 (M) 
1 (F) 
2 mg CE, 
0.2 mg IL-12 (P)– 
1 mg gag, 
0.2 mg IL-12 (B) 
[71] 
ICS, ELISA, 
Western 
9 
SIV: 
p27CE1+p27CE2+IL-12 (P)- 
p27CE1+p27CE2+ 
gag+IL-12 (B) 
0 (P)- 
2, 4, 6 (B) 
Indian RM 
6 (M) 
2 mg CE, 
0.2 mg IL-12 (P)– 
2 mg CE, 
2 mg gag, 
0.2 mg IL-12 (B) 
[71] 
ICS 
10 
HIV: 
p55gag+IL-12 
0, 2 
Indian RM 
4 
(3 M; 
1 F) 
2 mg p55gag, 
0.2 mg IL-12 
[69,70] 
ICS, ELISA, 
Western 
11 
 (continued 
from 10) 
HIV: 
p24CE1+p24CE2+IL-12(B) 
4 
 
 
2 mg CE, 
0.2 mg IL-12 
[69,70] 
ICS, ELISA, 
Western 
12 
HIV: 
p37gag 
0, 1, 2, 5.5, 6, 
6.5 
Indian RM 
3 
(2 M; 
1 F) 
 0.25 mg p37gag 
(0.5 mg at 5th 
vaccination) 
[76] 
ICS, ELISA, 
Western 
13 
HIV: 
p55gag 
0, 1, 3.5, 6, 9 
Indian RM 
4  
2 mg p55gag 
[89] 
ICS, ELISA, 
Western 
14 
SIV: 
gag+IL-12 
0, 2 
Indian RM 
 24 
(19 M; 
5 F) 
0.25 mg p57gag 
0.25 mg MCP-p39 gag 
0.1 mg IL-12 
[71] 
ICS, ELISA, 
Western 
15 
SIV: 
gag+IL-12 
0, 2, 4, 6 
Indian RM 
 2 (F) 
0.5 mg p57gag 
0.5 mg MCP-p39 gag 
0.1 mg IL-12 
[71] 
ICS, ELISA, 
Western 
16 
SIV: 
gag+IL-12 
0, 1, 4.5 
Indian RM 
 3 (M) 
0.5 mg p57gag 
0.5 mg MCP-p39 gag 
0.1 mg IL-12 
[71] 
ICS, ELISA, 
Western 
17 
SIV: 
gag+IL-12 
0, 3, 6 
Indian RM 
 2 (M) 
0.5 mg p57gag 
0.5 mg MCP-p39 gag 
0.1 mg IL-12 
[71] 
ICS, ELISA, 
Western 
(P) prime; (B) boost; (RM) rhesus macaque; IL-12, macaque IL-12 pDNA. All product administrations were at 2 sites 
with IM/EP except study 13 which was IM only.  
*One animal in each group (M437, P314) had earlier been vaccinated with a poorly immunogenic variant of p24CE 
pDNA which expressed an unmodified p24CE protein without the GM-CSF leader sequence, and then received 3 
priming vaccinations at 0, 1 and 2 months with p24CE1 and p24CE2 plasmids as used for the other animals, but 
without macaque IL-12 pDNA adjuvant. These animals received the gag pDNA booster vaccinations at 8 and 9 
months. 

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4.9.1 
Immunogenicity of p24CE ex vivo 
Transfection of CE-encoding RNA into human dendritic cells derived from HIV-
seronegative individuals was used to present p24CE1 antigen to autologous naïve T cells 
in order to generate primary human immune T-cell responses to CE ex vivo. Levels of 
CD4+ and CD8+ T-cell responses comparable to that of the full-length Gag protein were 
generated, even though only the p24CE1 protein (without p24CE2) was used as 
immunogen [90] (and unpublished). 
4.9.2 
Immunogenicity of p24CE DNA in mice 
Study 1 (Table 4-1): Balb/c, C57BL/6, and HLA-transgenic C57BL/6 mice (expressing 
human HLA A*02 or B*07) [88] were immunized with pDNA expressing CE or full-
length Gag. Different leader sequences were used to alter intracellular trafficking of the 
CE immunogens, thus manipulating protein localization, stability, and also the nature of 
elicited immune responses. The GM-CSF leader was chosen to move forward into human 
studies. Immunization of C57BL/6 mice with full-length p55gag pDNA induced poor 
CD4+ T-cell mediated responses against CE, and to only 2 of the 7 CE segments. In 
contrast, vaccination with p24CE1 and p24CE2 pDNAs induced cross-clade reactive, 
robust T-cell responses to 4 of the 7 CE. The CE-induced responses were multifunctional 
and composed of both CD4+ and CD8+ T cells with mature cytotoxic phenotypes. In 
contrast, p55gag pDNA induced immune responses recognized the CE only weakly or not 
at all. p24CE pDNA vaccination also induced humoral immune responses similar in 
magnitude to those induced by p55gag pDNA, which recognize the virus encoded p24Gag 
protein. Similarly, p55gag pDNA induced humoral immune responses did not recognize 
the CE. Together, p24CE pDNA vaccine induces cellular and humoral immune responses 
that are only poorly or not induced by full-length gag DNA vaccination. 
In addition to testing laboratory-purified plasmids, C57BL/6 mice were also vaccinated 
with the Althea produced cGMP p24CE1/2 and p55gag pDNA preparations. This study 
showed the expected induction of antigen-specific T cell responses, recapitulating 
previously reported findings [83]. The immune responses induced with the cGMP DNAs 
paralleled those obtained with laboratory-produced pDNA preparations. These data 
support qualification of these cGMP plasmid preparations for the clinical trial. 
4.9.3 
Immunogenicity of p24CE DNA in macaques 
Strong immunogenicity induced by the p24CE1/2 pDNA was also demonstrated in 
Rhesus macaques [69-71], and novel prime-boost regimens were developed to maximize 
magnitude, breadth and the generation of cytotoxic T cell responses recognizing the CE. 
Studies 2 and 3 (Table 4-1): These studies were conducted in macaques which received 
vaccinations with a combination of the two HIV p24CE1and p24CE2 single expression 
vectors (study 2) or with the dual expression vector p24CE1/2 (study 3) to examine the 
immunogenicity of the CE immunogen. The animals received 2 vaccinations (0 and 2 
months), except for 2 animals (M437, P314) that were primed at 0, 2, and 4 months. 
Cellular immune responses were measured in blood at 2 weeks after the last vaccination 
by stimulation of PBMC with peptides spanning the 7 CE (Figure 4-5), and compared 
with results from study 6, in which animals were primed with the dual expression vector 
p24CE1/2 pDNA at months 0 and 1 (Table 4-1). 
 

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Figure 4-5 p24CE pDNA vaccine is immunogenic in macaques. Macaques (N=16) were 
vaccinated with a mixture of p24CE1&p24CE2 pDNA (N=6) or the dual expression vector 
p24CE1/2 (N=10; 4 animals from study 3 and 6 animals from study 6). The pDNA vaccine for all 
animals, except M437 and P314, also contained 0.2 mg macaque IL-12 pDNA. The frequency of 
CE-specific IFN-γ+ T cells was measured two weeks after the last priming vaccination using CE-
specific peptide pools composed of a mixture of 15-mer overlapping by 11 AA and 10-mer peptides 
overlapping by 9 AA covering both p24CE1 and p24CE2 proteins. The CE-specific CD4+ (open 
bars, labeled CD4) and CD8+ (filled bars, labeled CD8) T cells are shown. 
All animals developed CE-specific cellular responses, as measured by IFN-γ production, 
with a frequency ranging from 0.1% to 0.8% of total T cells in blood (Figure 4-5). These 
responses were elicited by both CD4+ and CD8+ T cells, of both central (CD28+, CD95+) 
and effector memory phenotype (CD28-, CD95+), and included cytotoxic and 
polyfunctional CE-specific T cells, as defined by their granzyme B content, ability to 
secrete two cytokines (IFN-γ and TNF-α) and ability to degranulate (CD107a). Both the 
combination of individual p24CE1 and p24CE2 pDNAs (study 2) and the dual expression 
plasmid p24CE1/2 (studies 3 and 6) induced similar CE-specific responses. 
Mapping of the CE-specific responses showed a response breadth of 1-3 CE per animal 
(median = 3). Thus, the p24CE pDNA vaccine induced a broader response than the gag 
DNA vaccine, which elicited CE-specific T cell responses in only ~50% of the animals 
with a narrower response breadth of 0-3 CE per animal (median = 0). The breadth of the 
CE-specific responses obtained by the 2 vaccine regimens is depicted in Figure 4-6, 
where the percentage of the vaccinated animals recognizing each specific CE is shown. 

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Figure 4-6. Increased breadth of immune responses in the p24CE pDNA vaccinated 
macaques. Animals were vaccinated with p24CE pDNA (N=16; Table 4-1 studies 2, 3, and 6 after 
2 vaccinations, except 2 animals which received 3 vaccinations) or gag pDNA (N=11; Table 4-1 
studies 10, 12, 13; 2-6 vaccinations) and T cell responses to individual CE were mapped. The plot 
shows the % responders to each CE induced by the gag pDNA (grey bars) and CE pDNA (red 
bars). The bars show the percentage of the vaccinated animals recognizing each specific CE. 
Furthermore, analysis of humoral responses mimics those of the cellular responses, with 
only the CE pDNA vaccine being able to induce responses recognizing the CE. 
Studies 4 and 5 (Table 4-1): The animals from studies 2 and 3 were enrolled into follow-
up studies (studies 4 and 5, respectively) where they received a p55gag pDNA booster 
vaccination administered 2 months after the final priming vaccination. Despite the poor 
ability to induce de novo CE-specific immunity, p55gag pDNA booster vaccination 
significantly increased (p=0.0115) the IFN-γ+ CE-specific T cells (reaching up to ~3% of 
the total T cell population) (Figure 4-7) and the CE-specific polyfunctional cytotoxic T 
cells (as measured by 4 functions; p = 0.0068; Figure 4-8). 
 
Figure 4-7 Boosting of p24CE pDNA-primed macaques with p55gag pDNA increases CE-
specific cellular responses. The p24CE pDNA primed macaques received a p55gag pDNA 
booster vaccination. Frequency of total CE-specific IFN-γ+ T cells before and after the boost is 
shown. CE-specific responses in the ten p24CE pDNA vaccinated animals (studies 2 and 3) were 
measured 2 weeks after the last prime and 2 weeks after receiving a single booster vaccination 
with 1 mg of p55gag pDNA. PBMC were stimulated with a mixture of 15-mer peptides (overlapping 

HVTN 119, Version1.0 / February 17, 2017 
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by 11 AA) and 10-mer peptides (overlapping by 9 AA) spanning the 7 CE. P value is from paired t 
test. 
 
Figure 4-8 Increased frequency of polyfunctional cytotoxic CE-specific T cell responses by 
the p24CE pDNA prime-p55gag pDNA booster vaccination regimen. Frequency of total CE-
specific polyfunctional (4 functions: IFN-γ+ TNF-α+ CD107a+ GzmB+) CE-specific T cells before and 
after the p55gag pDNA booster vaccination. Polyfunctional (granzyme B+, IFN-γ+ TNF-+ and 
CD107a+) CE-specific responses were measured 2 weeks after the prime and 2 weeks after the 
boost using a mixture of peptides spanning the seven CE. P value is from paired t test. 
This observation supports the notion that CE-containing peptides are indeed processed 
from the p55Gag protein and are presented as peptides to the immune system, but are 
poorly immunogenic, potentially due to immunological interference with dominant 
responses from other Gag epitopes in variable regions. Therefore, these data demonstrate 
that the immunodominance hierarchy can be significantly altered by p24CE pDNA 
priming vaccination, focusing responses onto otherwise subdominant epitopes. A vaccine 
regimen that includes p24CE pDNA prime and p55gag pDNA boost vaccination results in 
CE-specific T cell responses characterized by increased magnitude and cytotoxicity but 
no increase in the CE response breadth. Furthermore, p55gag pDNA boost expanded the 
response and included responses against both highly conserved and variable regions 
outside of CE with a skewing to the highly conserved regions.  
In addition to cellular immune responses, vaccination with p24CE plasmids induced 
robust antibody responses in macaques [70]. These antibody responses recognized linear 
CE epitopes and the intact p24CE proteins, whereas the full-length Gag immunogen 
failed to elicit responses that recognized CE (studies 2 and 3). Furthermore, humoral 
responses to CE were greatly enhanced by a full-length Gag booster vaccination (studies 
4 and 5). Thus, the CE pDNA vaccine induces potent cellular and humoral immune 
responses to subdominant epitopes that are greatly augmented by the p55gag pDNA 
booster vaccination. 
Together, studies 4 and 5 demonstrate that the immunodominance exerted by variable 
Gag epitopes was lost in the presence of pre-existing CE-specific responses. Thus, p24CE 
pDNA as the priming immunogen resulted in broadened responses, including against the 
subdominant highly conserved epitopes, and avoided eliciting immunodominant 
responses against potentially “decoy” epitopes, while focusing responses to CE, for 
which few viable escape pathways may exist. 

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Study 6 (Table 4-1): This study was modeled after study 9 (see below), the latter of 
which was performed earlier, using analogous molecules from SIV, and corresponded to 
the most effective protocol found to induce the broadest recognition of SIV Gag CE. 
Study 6 included 2 priming vaccinations (0, 1 month) with HIV p24CE1/2 pDNA (Figure 
4-5) followed by 2 booster vaccinations (4, 6 months) with co-delivery of 
p24CE1/2+p55gag pDNA (Figure 4-9). All vaccinations included macaque IL-12 pDNA. 
The priming vaccination induced robust CE-specific responses (median 0.3% of T cells), 
which were significantly increased by each booster vaccination, reaching maximal 
responses after the 2nd booster vaccination (median 1.5% of T cells) (Figure 4-9). 
 
Figure 4-9 CE pDNA prime-CE+gag pDNA boost. (A) The cartoon depicts the HIV CE pDNA 
prime/CE+gag pDNA booster vaccination regimen. (B) Cellular immune responses were measured 
2 weeks after the 2nd prime and 2 weeks after each booster vaccination. P values are from paired t 
test. (C) Frequency of CE-specific IFN-γ+ T cell responses for individual macaques is shown for 
CD4+ (open bars) and CD8+ (filled bars) T cells after the 2nd CE+gag pDNA booster vaccination. 
The CE-specific responses were mediated both by CD4+ and CD8+ T cells with a skewing 
towards CD8+ T cell responses (Figure 4-9). This vaccination regimen also induced 
highly cytotoxic CE-specific IFN-+ T cells with a frequency of >89% of granzyme B+. 
The responses to individual CE were measured using CE-specific peptide sub-pools. The 
CE+gag pDNA booster vaccine showed that all CE were recognized and induced a 
broader response compared to the gag pDNA only booster vaccine (Figure 4-10). 

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Figure 4-10 Increased CE recognition induced by the CE/CE+gag pDNA vaccine. Comparison 
of the breadth of the responses per CE induced by the CE prime/gag pDNA prime-boost (green; 
from studies 4 and 5) and CE prime/ CE+gag pDNA prime-boost vaccine (red, study 6). The bars 
show the percentage of the vaccinated animals recognizing each specific CE. 
The breadth of the response, measured by the number of CE recognized per animal, was 
compared among groups which received different CE based vaccines [CE pDNA only 
(studies 2 and 3), CE/gag pDNA (studies 4 and 5) and CE/CE+gag pDNA (study 6) 
(Figure 4-11). The CE+gag pDNA booster vaccination induced responses with 
significantly increased breadth (2-6 CE per animal), compared to CE or CE/gag pDNA 
vaccines with 1-3 or 1-4 CE per animal (see above studies 4 and 5), with no difference 
among these groups. All CE based pDNA vaccines induced broader responses than the 
HIV p55gag pDNA only vaccine, which induced responses to 0-2 CE per animal. 

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Figure 4-11 Increased breadth of the HIV CE-specific responses induced by a CE/CE+gag 
pDNA vaccine regimen. A comparison of the CE breadth using different vaccine regimens is 
shown. For details see Table 4-1. The plot shows the number of CE recognized by each macaque 
immunized with HIV gag pDNA only (studies 10, 12, 13), HIV CE pDNA only (studies 2, 3, 6 using 
the priming data only), CE pDNA prime/gag pDNA booster vaccination (studies 4, 5) or CE pDNA 
prime/CE+gag pDNA booster vaccination (study 6). The total number of vaccinations and 
separately the number of vaccinations including p24CE pDNA are given. The median number of 
CE recognized, the range of CE responses, and the number of animals analyzed are indicated. P 
values are from an ANOVA (Dunnett’s test). Peptide-stimulated samples were considered positive 
if the responses were 2-fold higher than that of the unstimulated medium only control and greater 
than 0.01 after subtracting the medium control value. Samples were acquired on a LSR II or 
Fortessa flow cytometer (BD Biosciences, San Jose, CA), and the data were analyzed using 
FlowJo software (Tree Star, Inc., Ashland, OR). 
Priming with HIV p24CE pDNA is critical to induce immune responses to subdominant 
epitopes, and inclusion of the p24CE pDNA together with a plasmid expressing the full-
length immunogen (study 6) as a boost is the most effective protocol to induce desirable 
responses with greatest breadth, magnitude and cytotoxic capability. Importantly, study 6 
using HIV vaccine constructs recapitulated the SIV vaccine data (study 9). Hence, this 
vaccine regimen is proposed for the clinical trial. 

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4.9.4 
Immunogenicity of SIV p27CE DNA in macaques 
By analogy to the HIV CE immunogens, molecules derived from SIV p27Gag were 
designed (p27CE1 and p27CE2) and tested in macaques [71]. The findings of the SIV 
p27CE studies (studies 7-9) recapitulated those of the HIV CE (studies 2-6), each 
supporting the observation that a priming vaccination with CE pDNA focuses responses 
to subdominant epitopes, allowing a change of the immunodominance hierarchy and 
leading to increased breadth and cytotoxicity. 
Study 7 (Table 4-1): Macaques received 3 vaccinations with a combination of p27CE1 
and p27CE2 pDNA at 0, 2 and 4 months, with macaque IL-12 pDNA. Analysis of the 
vaccine-induced immunity demonstrated that all 14 macaques developed CE-specific 
cellular responses ranging from 0.03–0.8% of CE-specific IFN-γ+ T lymphocytes in 
blood. All 7 CE were immunogenic (range 1-4 CE/animal; Figure 4-12). This is in 
contrast to gag pDNA vaccinated macaques which induced CE-specific responses in 
~50% of animals targeting significantly fewer CE (range 0-3 CE/animal). 
 
Figure 4-12 Comparison of breadth of CE-specific T cell responses in p27CE pDNA and gag 
pDNA vaccinated animals. CE-specific T cell responses were mapped to individual CE. The plot 
shows the range and median of the CE responses among the two groups. P value is from unpaired 
t test. 
p27CE pDNA vaccination elicited CE-specific T cells with a significant fraction of 
cytotoxic (IFN-γ+, granzyme B+, CD107a+) T cells among both the CD4+ and CD8+ T cell 
subsets. Thus, these findings mirror the data from HIV p24CE vaccine described in 
studies 2 and 3. 
Study 8 (Table 4-1): Six of the macaques primed with SIV CE pDNA (from study 7) 
received a gag pDNA booster vaccination given with macaque IL-12 pDNA. The gag 
pDNA booster vaccination significantly increased the magnitude of the CE-specific 
responses (p=0.031). These data recapitulate the potent augmentation of HIV p24CE 
primed T cell responses upon a boost with HIV gag pDNA expressing the full-length 
protein (studies 3 and 4), demonstrating that the immunodominance hierarchy could be 
altered by CE priming. In addition, the responses after the SIV gag pDNA boost were 
significantly higher (p=0.048) compared to the responses obtained after the p27CE 
pDNA priming vaccination, similar to observations from the HIV p24CE prime-gag 
DNA boost studies (studies 4 and 5). The gag pDNA booster vaccination (study 8) 
resulted in recognition of 1-4 CE per animal with a similar response breadth as found in 
the p27CE pDNA only primed animals. Thus, gag pDNA booster vaccination increased 
the magnitude of the CE-specific responses without broadening CE recognition. 

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Therefore, SIV p27CE pDNA and HIV p24CE pDNA priming vaccinations share the 
unique feature of effectively inducing immune responses to subdominant Gag epitopes, 
which is only inefficiently achieved by vaccination with pDNAs expressing full-length 
SIV Gag or HIV Gag. 
Study 9 (Table 4-1): A second vaccine concept was tested in which macaques (N=6) 
received a single SIV p27CE pDNA priming vaccination followed by 3 booster 
vaccinations comprised of a co-delivered mixture of p27CE+gag pDNA, plus macaque 
IL-12 pDNA. The booster vaccination greatly induced robust CE-specific responses, 
reaching up to ~1.8% IFN-+ T cells in blood. No further increase in magnitude of the 
responses was observed between the 2nd and the 3rd boost, demonstrating that two 
CE+gag pDNA booster vaccinations are sufficient to maximize the magnitude of the 
primed CE-specific responses using this vaccine regimen. 
Both booster vaccines (gag pDNA and p27CE+gag pDNA) induced overall similar levels 
of CE-specific T cell responses (studies 8 and 9). However, the p27CE+gag pDNA 
booster vaccination (study 9) significantly expanded the breadth of CE-specific cellular 
responses (Figure 4-13) to 4-7 CE per animal (Figure 4-14).  
 
Figure 4-13 Breadth of CE responses comparing the two prime-boost regimens. Responses 
to individual CE were mapped in the 2 vaccine groups. The % responders per CE are plotted. 
p27CE prime-gag pDNA boost (CE/gag; N=6; blue bars; front row) from study 8 and p27CE prime-
p27CE+gag pDNA boost (CE/CE+gag; N=6; red bars; back row) from study 9 are compared. 
 

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Figure 4-14 Comparison of breadth of CE-specific T cell responses among the 3 groups of 
macaques vaccinated with p27CE pDNA based vaccine regimens. CE-specific T cell 
responses were mapped to individual CE using macaques described in studies 7-9. The plot shows 
the range and median of the CE responses among the 3 groups. P values are from ANOVA 
(Dunnett’s test). 
Thus, the detailed analysis of the responses to individual CE induced by these two 
booster vaccination regimens (studies 8 and 9) revealed a fundamental difference in 
breadth, although the magnitude of CE-specific T cell responses induced by both vaccine 
regimens is similar. 
The frequency of the cytotoxic T cells (granzyme B+) induced in the different CE-based 
vaccination regimens was also examined. Of note, gag pDNA vaccinated macaques 
which also developed CE-specific responses (N=18) showed significantly (p=0.014) 
higher frequency of granzyme B+ p27Gag-specific T cells than the ~50% of macaques 
(N=13) which failed to induce CE-specific responses (Figure 4-15, left panel), suggesting 
that the T cells targeting the CE are functionally more cytotoxic than those targeting the 
variable regions. This notion is supported by the findings that all protocols in which 
p27CE pDNA was included as prime induced significantly higher frequency of cytotoxic 
T cell responses than those induced by the gag pDNA vaccination (studies 2-6) (Figure 
4-15, right panel). 

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Figure 4-15 Comparison of cytotoxicity of SIV Gag-specific T cell responses with different 
vaccine regimens. The frequency of Gag-specific granzyme B+ IFN-+ T cell responses was 
measured in the different vaccine groups. Left panel: Macaques vaccinated with gag pDNA were 
grouped according to their ability to mount T cell responses recognizing CE. P value is from t-test. 
Right panel: The cytotoxicity of Gag responses is compared among all the gag pDNA vaccinated 
animals and the animals which received a CE based pDNA vaccine (CE only, or CE prime-gag 
pDNA boost or CE prime- p27CE+gag pDNA boost) (right panel). The median is indicated. P 
values are from ANOVA (Dunnett’s test). 
Overall, priming with CE pDNA and boosting with a mixture of CE and gag pDNA is the 
most efficient protocol to induce CE responses with the broadest coverage, and the 
subdominant epitopes encoded by the CE immunogen elicit T cell responses of higher 
functional relevance (more cytotoxic). Data from both the macaques vaccinated with 
p27CE pDNA and the subset of gag DNA vaccinated animals which developed CE-
specific responses show a link between CE immunity and CTL responses. Thus, the use 
of CE pDNA priming vaccine is critical to efficiently induce potent CTL responses to 
subdominant epitopes. 
4.10 
Clinical studies 
4.10.1 
Clinical studies of p24CE1/2 pDNA 
This is a first-in-human study for the p24CE1/2 pDNA vaccine. 
4.10.2 
Clinical studies of p55gag pDNA 
DAIDS has developed significant clinical experience with pDNAs that contain gag 
inserts (multiple variants), including the use of intramuscular administration with 
electroporation to deliver a gag pDNA with IL-12 pDNA. These trials include: HVTN 
060, 063, 070, 080 and 087. 

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4.10.3 
Clinical studies of HIV-1 DNA vaccines given with GENEVAX® IL-12 pDNA adjuvant 
IM with Electroporation 
Table 4-2 Summary of clinical studies of HIV-1 DNA vaccines with GENEVAX® IL-12 DNA 
plasmid and EP in healthy HIV-uninfected adults 
Study number/ 
clinicaltrials.gov 
identifier 
Study 
population 
Test article(s) 
Trial design / route of delivery/ schedule / N (vaccinee/placebos) 
HVTN 080/ 
NCT00991354 
HIV-
uninfected 
healthy 
adults 
- PENNVAX®-
B pDNA 
GENEVAX® 
IL-12 pDNA 
 
Grp 1:  3 mg PV-B alone, IM/EP, month 0, 1, 3 
 
N = 10/2 
Grp 2: 3 mg PV-B + 1 mg IL-12 pDNA, IM/EP, month 0, 1, 3 
 
N = 10/2 
Grp 3: 3 mg PV-B + 1 mg IL-12 pDNA, IM/EP, month 0, 1, 3 
 
N = 20/4 
 
IAVI study 
B004/ 
NCT01496989 
HIV-
uninfected 
healthy 
adults 
- HIV-MAG 
pDNA + 
GENEVAX® 
IL-12 pDNA 
- Ad35 
GRIN/ENV 
Grp 1:  3 mg HIV-MAG pDNA, IM/EP, month 0, 1, 2 
 
2 × 1010 vp Ad35 GRIN/ENV, IM, month 6 
 
N = 12/3 
Grp 2: 3 mg HIV-MAG + 0.1 mg IL-12 pDNA, IM/EP, month 0, 1, 2 
 
2 × 1010 vp Ad35 GRIN/ENV, IM, month 6 
 
N = 12/3 
Grp 3: 3 mg HIV-MAG + 1 mg IL-12 pDNA, IM/EP, month 0, 1, 2 
 
2 × 1010 vp Ad35 GRIN/ENV, IM, month 6 
 
N = 12/3 
Grp 4: 3 mg HIV-MAG + 1 mg IL-12 pDNA, IM/EP, month 0 
 
2 × 1010 vp Ad35 GRIN/ENV, IM, month 4 
 
N = 12/3 
Grp 5: 2 × 1010 vp Ad35 GRIN/ENV, IM, month 0 
 
3 mg HIV-MAG + 1 mg IL-12 pDNA, IM/EP, month 6 
 
N = 12/3 
HVTN 087/ 
NCT01578889 
HIV-
uninfected 
healthy 
adults 
- HIV-MAG 
pDNA + 
GENEVAX® 
IL-12 pDNA 
- rVSV HIV gag 
Grp 1:  3 mg HIV-MAG pDNA alone, IM/EP, month 0, 1, 3 
 
1 × 108 PFU rVSV HIV gag, IM, month 6 
 
N = 22/3 
Grp 2: 3 mg HIV-MAG + 0.25 mg IL-12 pDNA, IM/EP, month 0, 1, 3 
 
1 × 108 PFU rVSV HIV gag, IM, month 6 
 
N = 22/3 
Grp 3: 3 mg HIV-MAG + 1 mg IL-12 pDNA, IM/EP, month 0, 1, 3 
 
1 × 108 PFU rVSV HIV gag, IM, month 6 
 
N = 22/3 
Grp 4: 3 mg HIV-MAG + 1.5 mg IL-12 pDNA, IM/EP, month 0, 1, 3 
 
1 × 108 PFU rVSV HIV gag, IM, month 6 
 
N = 22/3 
In HVTN 080, healthy HIV-uninfected volunteers received 3 mg PENNVAX®-B (gag, 
pol, env) with or without 1 mg IL-12 pDNA by IM injection followed by in vivo EP 
(IM/EP) (CELLECTRA® EP system) at a single injection site. In this study, adjuvant 
activity was seen with IL-12 pDNA. While the difference was not statistically significant, 
in HVTN 080 the proportion of volunteers making a vaccine-specific CMI response was 
almost 2-fold greater in the group that received Profectus’ GENEVAX® IL-12 pDNA 
adjuvant given with EP compared to the small group receiving no IL-12 pDNA (see 
Figure 4-16, Figure 4-17).  

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Figure 4-16 HIV-specific CD4+ T cell ICS responses in HVTN 080 
 
Figure 4-17 HIV-specific CD8+ T-cell ICS responses in HVTN 080 
In HVTN 087, several dose levels of IL-12 pDNA (GENEVAX® IL-12 DNA plasmid) 
were tested for adjuvant activity, with HIV-MAG (HIV-1 gag/pol and HIV-1 nef/tat/vif, 
env) pDNA vaccine delivered IM/EP with the Ichor TDS-IM EP Device. In HVTN 087 
the healthy HIV-uninfected volunteers received the HIV-MAG pDNA vaccine given with 
0, 0.25, 1 and 1.5 mg IL-12 pDNA IM/EP divided equally across two injection sites. The 
HIV-MAG pDNA vaccinations were followed by a VSV HIV gag boost. The results of 

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HVTN 087 with regards to the adjuvant activity of IL-12 pDNA suggest that the highest 
dose of IL-12 pDNA was associated with an increased magnitude of CD8+ T-cell 
responses following the VSV HIV gag boost, compared with group 1, which did not 
receive IL-12 pDNA (p = 0.0185, Figure 4-19). The ability to see statistically significant 
differences between the study arms was limited by the small sample sizes.  
 
Figure 4-18 HIV-specific CD4+ T-cell ICS responses in HVTN 087 

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Figure 4-19 HIV-specific CD8+ T-cell ICS responses in HVTN 087  
However, the highest CD4+ T-cell response rate to DNA vaccination (pre-VSV boost) 
was seen in group 1, without IL-12 pDNA (Figure 4-18). Given the ability of IL-12 to 
shift vaccine-specific immunity toward a Th1 response, IL-12 pDNA as an adjuvant 
could contribute to CD8+ cellular immune responses to the p24CE1/2 pDNA vaccine.  
IAVI has presented results of its B004 study, which also tested multiple injections of 
HIV-MAG and GENEVAX® IL-12-4532 DNA IM/EP (Ichor TDS-IM EP Device) in 
healthy volunteers [7]. The study tested the groups shown in Table 4-3. The vaccine 
regimens tested were adequately safe with no SAEs or AEs that were probably or 
definitely related to vaccine. The vaccine regimens in the 3 study groups shown were 
similarly rated with respect to tolerability. 
With respect to cellular responses assessed by IFN-γ ELISpot, at baseline there were no 
responders. After the 3 pDNA priming injections, response rates among vaccinees were 
82% (9/11) in Group 1, 64% (7/11) in Group 2, and 42% (5/12) in Group 3. After the 
Ad35-GRIN/ENV boost, response rates among vaccinees were 73% (8/11) in Group 1, 
82% (9/11) in Group 2, and 89% (8/9) in Group 3. Samples from 8 participants in each 
group were also assessed with 7-color ICS to assess expression of IL-2, TNF-α, and 
IFN-γ in response to peptides matched to the HIV-MAG vaccine. Groups 1-3 had similar 
CD4+ and CD8+ T-cell response rates and magnitudes, and the polyfunctionality profiles 
were similar. An ELISA assay for HIV-specific antibodies to Env A and Env B (matched 
to the HIV-MAG vaccine) and p24Gag did not detect any HIV-specific antibodies 
following the DNA primes in any group. In summary, the vaccine regimens tested were 
immunogenic, but there was no clear indication of enhancement of immunogenicity of 
HIV-MAG by IL-12 DNA in this small trial. One shortcoming of this data is that the 
participants were not all evaluated for CD8+ responses with ICS. It is not clear how the 
specific participant samples were selected for ICS assay, or how responses would have 
differed if measured by the HVTN laboratory assays.  

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Table 4-3 B004 schema 
Study 
arm 
N 
Month  
(Week)  
0 (0) 
Month  
(Week)  
1 (4) 
Month  
(Week)  
2 (8) 
Month  
(Week) 
6 (24) 
 
 
 
 
 
 
Group 1 
12 
HIV-MAG 
HIV-MAG 
HIV-MAG 
Ad35-GRIN/ENV 
3 
Placebo 
Placebo 
Placebo 
Placebo 
 
 
 
 
 
 
Group 2 
12 
HIV-MAG+ 
IL-12 pDNA 
0.1 mg 
HIV-MAG+ 
IL-12 pDNA 
0.1 mg 
HIV-MAG+ 
IL-12 pDNA 
0.1 mg 
Ad35-GRIN/ENV 
3 
Placebo 
Placebo 
Placebo 
Placebo 
 
 
 
 
 
 
Group 3 
12 
HIV-MAG+ 
IL-12 pDNA 
1 mg 
HIV-MAG+ 
IL-12 pDNA 
1 mg 
HIV-MAG+ 
IL-12 pDNA 
1 mg 
Ad35-GRIN/ENV 
3 
Placebo 
Placebo 
Placebo 
Placebo 
Note: HIV-MAG 3 mg delivered IM by EP. GENEVAX® IL-12 DNA plasmid co-administered 
with HIV-MAG delivered IM by EP. Ad35-GRIN/ENV 2×1010 vp delivered IM by standard 
needle injection. 
The HVTN is also evaluating PENNVAX®-GP (Gag, Pol, Env) pDNA Vaccine and IL-
12 plasmid (INO-9012, Inovio Pharmaceuticals, Inc. Plymouth Meeting, Pennsylvania, 
USA), delivered via intradermal or IM/EP (CELLECTRA® EP system) in HVTN 098 
(BB IND #16398, held by DAIDS). In that study, for IM delivery, the dose of 
PENNVAX®-GP is 8 mg and the dose of the Inovio IL-12 plasmid is 1 mg, at a single 
injection site. The study is ongoing. No SAEs related to vaccination have been reported. 
Injection site pruritus has been reported by 19.1% of participants and presyncope 
following the vaccination procedure in 5.3%. Another IL-12 pDNA (pUMVC3-hIL-12-
NGVL3, City of Hope Center for Biomedicine and Genetics, Duarte, CA) has been given 
in doses up to 5.8 mg per administration delivered with EP directly into melanoma 
tumors, with no dose limiting systemic toxicities noted [91]. Hence, we do not anticipate 
any significant systemic or local adverse effects related to the use of IL-12 pDNA IM 
with EP at the proposed dose. 
Taken together, the studies suggest that IL-12 pDNA delivered with plasmid DNA 
vaccines with EP may have a dose-dependent adjuvant effect on CD8+ responses. IL-12 
pDNA has been given at doses up to 1 mg at a single injection site with IM/EP and up to 
1.5 mg total IM/EP at one visit (2 injection sites). Given the focus of this study on 
evaluating cellular immune responses, IL-12 pDNA may provide an advantage to the 
evaluation of immunogenicity of the p24CE and p55gag pDNA vaccines. 

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4.11 
Potential risks of study products and administration 
Table 4-4 Summary of potential risks of study products and administration 
Common 
 Mild transient cutaneous bleeding, bruising/ecchymosis 
 Mild to moderate injection site pain, tenderness, pruritus, erythema, 
or swelling/induration/edema 
 Malaise/fatigue, myalgia, or headache in the first few days following 
injection 
Less common 
 Severe injection site pain or tenderness 
 Transient paresthesia or hypoesthesia in the injected limb 
 Fever, chills, flu-like syndrome, arthralgia, rash, nausea, or dizziness 
in the first few days following injection  
 Vasovagal reaction/lightheadedness/dizziness related to the injection 
procedure 
 Transient changes in clinical laboratory values 
 Injection site hematoma, laceration, bruising/ecchymosis, other 
transient lesions, itching, or bleeding related to the injection 
procedure 
 A vaccine-induced positive HIV antibody test result 
Uncommon or rare 
 Severe localized injection site reaction, such as sterile abscess or 
secondary bacterial infection  
 Allergic reaction, including rash, urticaria, angioedema, 
bronchospasm, or anaphylaxis 
 Muscle damage at the injection site 
 Injection needle contact with the bone 
 Difficulty removing EP device 
 Syncope 
Theoretical risks 
 Autoimmune disease or cancer  
 Electrical injury with EP 
 Disruption of function of implanted electronic medical devices with 
EP 
 Exacerbation of cardiac arrhythmias with EP  
 Effects on a participant’s response to an approved HIV vaccine 
administered in the future 
 Effects on susceptibility to HIV, if the participant is exposed to HIV  
 Effects on the course of HIV infection/disease, if the participant is 
infected with HIV 
 Effects on the fetus and on pregnancy 

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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 HIV-1 pDNA vaccines p24CE1/2 and p55gag 
administered with IL-12 pDNA by intramuscular injection with electroporation 
Primary endpoints 1: 
 
Frequency and severity of local injection/EP site and systemic reactogenicity signs 
and symptoms 
 
Frequency of AEs categorized by MedDRA body system, MedDRA preferred term, 
severity and assessed relationship to study products. Detailed description of all AEs 
meeting DAIDS criteria for expedited reporting 
 
The distribution of values of safety laboratory measures at baseline and at follow-up 
visits post vaccination 
 
Number of participants with early discontinuation of vaccinations and reason for 
discontinuation 
 
Magnitude of local injection/EP site pain as measured by a visual analog scale 
 
Distribution of responses to questions regarding acceptability of study injection 
procedures 
Primary objective 2:  
To compare the two pDNA prime/boost strategies with respect to breadth (defined as the 
number of targeted CEs) of CD4+ and CD8+ T-cell responses to conserved regions of the 
p24Gag protein  
Primary endpoint 2:  
The number of targeted CEs by CD4+ and CD8+ T-cell responses measured by ICS 2 
weeks after the second and fourth vaccinations 
5.2 
Secondary objectives and endpoints 
Secondary objective 1: 
To determine the effect of the different prime/boost regimens on the magnitude and 
polyfunctionality of T-cell responses induced by the different priming vaccinations 

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Secondary endpoint 1: 
Rate, magnitude and polyfunctionality of CD4+ and CD8+ T-cell responses measured by 
ICS to p24CE and HIV Gag, 2 weeks after the second and fourth vaccinations 
Secondary objective 2: 
To determine the effect of the different prime/boost regimens on the specificity of T-cell 
responses induced by the different primes 
Secondary endpoint 2: 
Epitope specificity of T-cell responses measured by IFN- ELISpot to p24CE and HIV 
Gag, 2 weeks after the second and fourth vaccinations 
Secondary objective 3: 
To evaluate the humoral immunogenicity of the HIV-1 pDNA vaccines p24CE1/2 and 
p55gag administered alone, in combination, or sequentially by intramuscular injection 
with electroporation 
Secondary endpoint 3: 
Rate and magnitude of humoral immune responses to Gag measured 2 weeks after the 4th 
vaccination by binding antibody multiplex assay 
Secondary objective 4: 
To determine the frequency of circulating Tfh in response to each vaccination regimen 
Secondary endpoint 4: 
Rate and magnitude of CD4+ cTfh measured by ICS 
5.3 
Exploratory objectives 
Exploratory objective 1: 
To further evaluate immunogenicity of the different vaccine regimens, additional 
immunogenicity assays may be performed, including on samples from other time points, 
based on the HVTN Laboratory Assay Algorithm 
Exploratory objective 2: 
To determine the frequency of plasmablasts in response to each vaccination regimen 
Exploratory objective 3: 
To evaluate the breadth of the T cell receptor repertoire induced after pDNA vaccination 
by electroporation 

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Exploratory objective 4: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, and clinical trial conduct 

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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling 56 healthy, HIV-uninfected adult participants, aged 18 
to 50 years. 
To ensure that both men and women will be adequately represented in the trial, the trial 
will enroll at least approximately 40% of each sex overall. Hence, when approximately 
33 participants of one sex are enrolled, recruitment of persons born of that sex will stop. 
Since enrollment is concurrent with receiving the first study vaccination, all participants 
will provide some safety data. However, for immunogenicity analyses, it is possible that 
data may be missing for various reasons, such as participants terminating from the study 
early, problems in shipping specimens, low cell viability of processed peripheral blood 
mononuclear cells (PBMCs) or high background. 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 day 182. For this reason, the sample size calculations in Section 6.1.2 account for 4 
enrolled participants receiving vaccine having missing data for each study arm at the 
primary immunogenicity endpoint. 
6.1.1 
Sample size calculations for safety 
The goal of the safety evaluation for this study is to identify safety concerns associated 
with product administration. Sample size calculations for safety are expressed in terms of 
the ability to detect AEs requiring expedited reporting to DAIDS. 
The ability of the study to detect serious adverse events (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 vaccine arm 
of the study (n =25), there is a 90% chance of observing at least 1 event if the true rate of 
such an event is 8.8% or more; and there is a 90% chance of observing no events if the 
true rate is 0.4% or less. As a reference, in HVTN vaccine trials from December 2000 
through September 2010, about 4% of participants who received placebos experienced an 
SAE. 
Probabilities of observing 0, 1 or more, and 2 or more events among arms of size 25 are 
presented in Table 6-1 for a range of possible true adverse event rates. These calculations 
provide a more complete picture of the sensitivity of this study design to identify 
potential safety problems with the vaccine. 

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Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
arms of size 25, for different true event rates 
True event rate (%) 
Pr(0/25) 
Pr(1+/25) 
Pr(2+/25) 
1 
77.8 
22.2 
2.6 
4 
36 
64 
26.4 
5 
27.7 
72.3 
35.8 
10 
7.2 
92.8 
72.9 
20 
0.4 
99.6 
97.3 
30 
<0.1 
>99.9 
99.8 
40 
<0.1 
>99.9 
>99.9 
 
An alternative way of describing the statistical properties of the study design is in terms 
of the 95% confidence interval for the true rate of an adverse event based on the observed 
data. Table 6-2 shows the 2-sided 95% confidence intervals for the probability of an 
event based on a particular observed rate. Calculations are done using the score test 
method [92]. For a given vaccine arm, if none of the 25 participants receiving a vaccine 
regimen experience a safety event, the 95% 2-sided upper confidence bound for the true 
rate of such events in the total vaccinated population is 13.3%. 
Table 6-2 Two-sided 95% confidence intervals based on observing a particular rate of safety 
endpoints for arms of size 25 
Observed event rate 
95% CI 
0/25 
[0.0, 13.3] 
1/25 
[0.2, 19.5] 
2/25 
[2.2, 25.0] 
6.1.2 
Sample size calculations for immunogenicity 
For comparing the CD4+ and CD8+ T-cell endpoints between the 2 vaccine regimens, 
the primary analysis uses head-to-head superiority comparisons. The comparison will be 
performed separately for each of the primary breadth and secondary magnitude T-cell 
subset endpoints. No multiplicity adjustments are made for the multiple comparisons 
given the utility to favor higher power at the expense of a higher accepted false positive 
rate. 
Figure 6-1 below summarizes power available for superiority testing. For these 
calculations, we assume 17% missing data (n=21 evaluable endpoints from each arm). 
Sample size calculations for breadth of response are based on data from the HVTN 083 
trial and assume a beta-binomial distribution. Sample size calculations for ICS magnitude 
assume normally distributed magnitudes after natural log transformation with standard 
deviation = 1. The assumptions for the sample size calculations for ICS magnitude are 
based on the data from the HVTN 080 trial. Superiority test power is based on the Mann-
Whitney U test with 2-sided p-value <0.05 as statistically significant. 
If mean CE breadth in the vaccine recipients in Group 1 is 0.2 (0.5) then the study has 
80% power to detect superiority in Group 2 if the true CE breadth the 2nd group is at least 
1.0 (1.5). A 2.5 fold-change in the vaccine recipients from Group 2 versus Group 1 is 
required to have 80% power to detect superiority in the T-cell response magnitude. 

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Figure 6-1 Power to detect superiority in CE Breadth and ICS Magnitude. Power calculations 
for the breadth of response were run under two different scenarios. In the first panel power 
the mean CE Breadth is assumed to be 0.2 for the vaccine recipients in Group 1 while the second 
panel assumes a mean CE Breadth of 0.5. In the third panel power calculations are shown for the 
magnitude of response. The x-axis in the first two panels is the CE Breadth for the vaccine 
recipients in Group 2 and for the third panel it the x-axis is the fold change in ICS response 
magnitude for vaccine recipients from Group 2 versus Group 1. Power curves are shown for N=20, 
25, and 30 vaccine recipients per Group and account for 17% missing immunogenicity data. 
6.2 
Randomization 
The randomization sequence will be obtained by computer-generated random numbers 
and provided to each HVTN CRS through a Web-based randomization system. The 
randomization will be done in blocks to ensure balance across arms. At each institution, 
the pharmacist with primary responsibility for dispensing study products is charged with 
maintaining security of the treatment assignments (except in emergency situations as 
specified in the HVTN MOP). 
6.3 
Blinding 
Participants and site staff (except for site pharmacists) will be blinded as to participant 
treatment arm assignments (ie, blinded to both group and vaccine/control status). Study 
product assignments are accessible to those HVTN CRS pharmacists, DAIDS protocol 

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pharmacists and contract monitors, and SDMC staff who are required to know this 
information in order to ensure proper trial conduct. Any discussion of study product 
assignment between pharmacy staff and any other HVTN CRS staff is prohibited. The 
HVTN SMB members also are unblinded to treatment assignment in order to conduct 
review of trial safety.  
When a participant leaves the trial prior to study completion, the participant will be told 
he or she must wait until all participants are unblinded to learn his or her treatment 
assignment.  
Emergency unblinding decisions will be made by the site investigator. If time permits, 
the HVTN PSRT should be consulted before emergency unblinding occurs. 
6.4 
Statistical analyses 
This section describes the final study analyses, unblinded as to treatment arm assignment. 
All data from enrolled participants will be analyzed according to the initial randomization 
assignment regardless of how many vaccinations they received. In the rare instance that a 
participant receives the wrong treatment at a specific vaccination time, the Statistical 
Analysis Plan will address how to analyze the participant’s safety data. Analyses are 
modified intent-to-treat in that individuals who are randomized but not enrolled do not 
contribute data and hence are excluded. Because of blinding and the brief length of time 
between randomization and enrollment—typically no more than 4 working days—very 
few such individuals are expected. 
Analyses for primary endpoints will be performed using SAS and R. 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 safety 
endpoints, multiple primary immunogenicity endpoints, or secondary endpoints. 
However, multiplicity adjustments will be made for certain immunogenicity assays, as 
discussed below, when the assay endpoint is viewed as a collection of hypotheses (eg, 
testing multiple peptide pools to determine a positive response). 
6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, and 
immunogenicity for primary- and secondary-objective analyses. 
6.4.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using descriptive 
statistics. 
6.4.3 
Safety/tolerability analysis 
Since enrollment is concurrent with receiving the first vaccination, all participants will 
have received at least 1 vaccination and therefore will provide some safety data. 

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6.4.3.1 
Reactogenicity 
The number and percentage of participants experiencing each type of reactogenicity sign 
or symptom will be tabulated by severity and treatment arm and the percentages 
displayed graphically by arm. For a given sign or symptom, each participant’s 
reactogenicity will be counted once under the maximum severity for all injection 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 
AEs and SAEs 
AEs will be summarized using MedDRA System Organ Class and preferred terms. 
Tables will show by treatment arm the number and percentage of participants 
experiencing an AE within a System Organ Class or within preferred term category by 
severity or by relationship to study product. For the calculations in these tables, a 
participant with multiple AEs within a category will be counted once under the maximum 
severity or the strongest recorded causal relationship to study product. Formal statistical 
testing comparing arms is not planned since interpretation of differences must rely 
heavily upon clinical judgment. 
A listing of SAEs reported to the DAIDS Regulatory Support Center (RSC) Safety Office 
will provide details of the events including severity, relationship to study product, time 
between onset and last vaccination, and number of vaccinations received. A separate 
listing will do the same for AEs of special interest (AESI). AESI for this protocol include 
but are not limited to autoimmune disorders; a sample list of AESI is provided in 
Appendix G. 
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 time point, as well as changes from baseline for post-enrollment 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 will be tabulated by treatment arm for 
each post-vaccination time point. 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 vaccination discontinuation and early study termination 
The number and percentage of participants who discontinue vaccination and who 
terminate the study early will be tabulated by reason and treatment arm. 

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6.4.4 
Immunogenicity analysis 
6.4.4.1 
General approach 
For the statistical analysis of immunogenicity endpoints, data from enrolled participants 
will be used according to the initial randomization assignment regardless of how many 
injections they received. Additional analyses may be performed, limited to participants 
who received all scheduled injections per protocol. Assay results that are unreliable, from 
specimens collected outside of the visit window, or from HIV-infected participants 
postinfection are excluded. Since the exact date of HIV infection is unknown, any assay 
data from blood draws 4 weeks prior to an infected participant’s last seronegative sample 
and thereafter may be excluded. If an HIV-infected participant does not have a 
seronegative sample postenrollment, then all data from that participant may be excluded 
from the analysis. 
Discrete categorical assay endpoints (eg, response rates) will be analyzed by tabulating 
the frequency of positive response for each assay by antigen and treatment arm at each 
timepoint for which an assessment is performed. Crude response rates will be presented 
with their corresponding 95% confidence interval estimates calculated using the score 
test method [92]. Because of the small numbers of control participants in each group, no 
adjustment will be made to the vaccine arm estimates for the false positive rates in the 
control arms. Fisher’s exact tests will be used to compare the response rates of any 2 
vaccine arms, with a significant difference declared if the 2-sided p-value is ≤ 0.05. 
For quantitative assay data (eg, percentage of positive cells from the ICS assay or mean 
fluorescence intensity from the binding antibody multiplex assay), graphical and tabular 
summaries of the distributions by antigen, treatment arm, and timepoint will be made. For 
all primary and secondary immunogenicity endpoints, box plots and plots of estimated 
reverse cumulative distribution curves will be used for graphical display of all of the 
study arms. Typically, the results will be shown for each vaccine arm and for the set of 
control arms pooled into one group.  
The differences between treatment groups at 2 weeks post the 2nd and 4th vaccination 
timepoints will be tested with a nonparametric Wilcoxon rank sum test if the data are not 
normally distributed and with a 2-sample t-test if the data appear to be normally 
distributed. 
Some immunologic assays have underlying continuous or count-type readouts that are 
dichotomized into responder/nonresponder categories (eg, ICS and BAMA). If treatment 
arm differences for these assays are best summarized by a mixture model, then 
Lachenbruch’s test statistic [93] will be used to evaluate the composite null hypothesis of 
equal response rates in the 2 arms and equal response distributions among responders in 
the 2 such arms. This test statistic equals the square of a binomial Z-statistic for 
comparing the response rates plus the square of a Wilcoxon statistic for comparing the 
response distributions in the subgroup of responders. A permutation procedure is used to 
obtain a 2-sided p-value. For estimation, differences in response rates between arms will 
be estimated using the methods described above, and in the subgroup of positive 
responders, differences in location parameters between arms will be estimated using the 
methods described above.  
More sophisticated analyses employing repeated measures methodology (eg, linear mixed 
models or marginal mean models fit by generalized estimating equations) may be utilized 

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to incorporate immune responses over several timepoints and to test for differences over 
time. However, inference from such analyses would be limited by the small sample size 
of this study. All statistical tests will be 2-sided and will be considered statistically 
significant if p  0.05. 
Based upon previous HVTN trials, missing 17% of immunogenicity results for a specific 
assay is common due to study participants terminating from the study early, problems in 
shipping specimens, or low cell viability of processed peripheral blood mononuclear cells 
(PBMCs). To achieve unbiased statistical estimation and inferences with standard 
methods applied in a complete-case manner (only including participants with observed 
data in the analysis), missing data need to be missing completely at random (MCAR). 
Following the most commonly used definition, MCAR assumes that the probability of an 
observation being missing does not depend on any participant characteristics (observed or 
unobserved). When missing data are minimal (specifically if no more than 20% of 
participants are missing any values), then standard complete-case methods will be used, 
because violations of the MCAR assumption will have little impact on the estimates and 
hypothesis tests.  
If a substantial amount of immunogenicity data is missing for an endpoint (at least 1 
value missing from more than 20% of participants), then using the methods that require 
the MCAR assumption may give misleading results. In this situation, analyses of the 
immunogenicity endpoints at a specific timepoint will be performed using parametric 
generalized linear models fit by maximum likelihood. These methods provide unbiased 
estimation and inferences under the parametric modeling assumptions and the assumption 
that the missing data are missing at random (MAR). MAR assumes that the probability of 
an observation being missing may depend upon the observed responses and upon 
observed covariates, but not upon any unobserved factors. Generalized linear models for 
response rates will use a binomial error distribution and for quantitative endpoints, a 
normal error distribution. For assessing repeated immunogenicity measurement, linear 
mixed effects models will be used. If the immunological outcomes are left- and/or right- 
censored, then the linear mixed effects models of Hughes [94] will be used, because they 
accommodate the censoring. In addition, secondary analyses of repeated immunogenicity 
measurements may be done using weighted GEE [95] methods, which are valid under 
MAR. All of the models described above in this paragraph will include as covariates all 
available baseline predictors of the missing outcomes.  
6.4.4.2 
Analysis of CD4+ and CD8+ T-cell response as measured by the ICS assay  
The analysis of CD4+ and CD8+ T-cell response rates as measured by the ICS assay will 
be evaluated and compared as described under the general approach. For each T-cell 
subset, the positivity call for each peptide pool will include a multiple comparison 
adjustment for the number of peptide pools used in the assay. In general, the Mixture 
Models for Single-cell Assays (MIMOSA) statistical framework [96] and/or the Fisher’s 
exact test-based positivity criteria will be used. Details of the positivity criteria will be 
discussed in the SAP. The magnitude of marginal response will be analyzed as described 
for quantitative data in the general approach section. For each T-cell subset, graphs will 
be used to display the background-subtracted magnitudes for each participant by protein, 
treatment arm and timepoint. Statistical testing comparing the magnitudes will be based 
on positive responders only. The polyfunctionality of ICS responses will also be analyzed 
as a secondary endpoint. Besides descriptive plots of the magnitude of polyfunctional 
responses, the COMPASS (Combinatorial Polyfunctionality analysis of Antigen-Specific 
T-cell Subsets) statistical framework will also be used to perform joint modelling of 

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multiple T-cell subsets of different cytokine combinations using the functionality score 
(FS) and the polyfunctionality score (PFS) to summarize the multi-parameter ICS 
responses.  
6.4.4.3 
Analysis of multiplexed immunoassay data 
The analysis of response rates and response magnitudes will be evaluated and compared 
as described under the general approach. 
6.4.5 
Analyses prior to end of scheduled follow-up visits 
Any analyses conducted prior to the end of the scheduled follow-up visits should not 
compromise the integrity of the trial in terms of participant retention or safety or 
immunogenicity endpoint assessments. In particular, early unblinded analyses by 
treatment assignment require careful consideration and should be made available on a 
need to know basis only. 
6.4.5.1 
Safety 
During the course of the trial, unblinded analyses of safety data will be prepared 
approximately every 4 months during the main study, as defined in Section 3, for review 
by the SMB. Ad hoc safety reports may also be prepared for SMB review at the request 
of the HVTN PSRT. The HVTN leadership must approve any other requests for 
unblinded safety data prior to the end of the scheduled follow-up visits. 
6.4.5.2 
Immunogenicity 
An unblinded statistical analysis by treatment assignment of a primary immunogenicity 
endpoint may be performed when all participants have completed the corresponding 
primary immunogenicity visit and data are available for analysis from at least 80% of 
these participants. Similarly, an unblinded statistical analysis by treatment assignment of 
a secondary or exploratory immunogenicity endpoint may be performed when all 
participants have completed the corresponding immunogenicity visit and data are 
available for analysis from at least 80% of these participants. However, such analyses for 
a secondary or exploratory immunogenicity endpoint will only take place after at least 
one of the primary immunogenicity endpoints of the same class (humoral or cell-
mediated) or, if no primary endpoint of the same class, at least one of the primary 
immunogenicity endpoints reaches the aforementioned threshold. The Laboratory 
Program will review the analysis report prior to distribution to the protocol chairs, 
DAIDS, vaccine developer, and other key HVTN members and investigators. 
Distribution of reports will be limited to those with a need to know for the purpose of 
informing future trial-related decisions. The HVTN leadership must approve any other 
requests for HVTN immunogenicity analyses prior to the end of the scheduled follow-up 
visits. 

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7 
Selection and withdrawal of participants 
Participants will be healthy, HIV uninfected (seronegative) adults who comprehend the 
purpose of the study and have provided written informed consent. Volunteers will be 
recruited and screened; those determined to be eligible, based on the inclusion and 
exclusion criteria, will be enrolled in the study. Final eligibility determination will 
depend on results of laboratory tests, medical history, physical examinations, and answers 
to self-administered and/or interview questions.  
Investigators should always use good clinical judgment in considering a volunteer’s 
overall fitness for trial participation. Some volunteers may not be appropriate for 
enrollment even if they meet all inclusion/exclusion criteria. Medical, psychiatric, 
occupational, or other conditions may make evaluation of safety and/or immunogenicity 
difficult, and some volunteers may be poor candidates for retention. 
The DNA vaccine and adjuvant used in this study will be given with EP. Volunteers may 
not participate if they have certain metal implants, a surgical or traumatic metal implant 
in the upper limb and/or shoulder, or a history of cardiac arrhythmias. 
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 HVTN 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; 
completes a questionnaire prior to first vaccination with verbal demonstration of 
understanding of all questionnaire items answered incorrectly 
5. Agrees not to enroll in another study of an investigational research agent prior to 
completion of last required protocol visit (excludes annual health contact visit) 
6. Good general health as shown by medical history, physical exam, and screening 
laboratory tests 
HIV-Related Criteria: 
7. Willingness to receive HIV test results 

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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. 
Laboratory Inclusion Values 
Hemogram/CBC 
10. Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for 
volunteers who were born male 
11. White blood cell count = 3,300 to 12,000 cells/mm3 
12. Total lymphocyte count ≥ 800 cells/mm3 
13. Remaining differential either within institutional normal range or with site physician 
approval 
14. Platelets = 125,000 to 550,000/mm3 
Chemistry 
15. Chemistry panel: ALT, AST, and alkaline phosphatase < 1.25 times the institutional 
upper limit of normal; CPK ≤ 2.0 times the institutional upper limit of normal; creatinine 
≤ institutional upper limit of normal. 
Virology 
16. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-approved 
enzyme immunoassay (EIA). 
17. Negative Hepatitis B surface antigen (HBsAg)  
18. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase 
chain reaction (PCR) if the anti-HCV is positive 
Urine 
19. Normal urine: 
 
Negative urine glucose, and 
 
Negative or trace urine protein, and 
 
Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a 
microscopic urinalysis with red blood cells levels within institutional normal range). 

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Reproductive Status 
20. Volunteers who were born female: negative serum or urine beta human chorionic 
gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial 
vaccination. 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. 
21. Reproductive status: A volunteer who was born female must: 
 
Agree to consistently 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, or 
 
Any other contraceptive method approved by the HVTN PSRT 
 
Successful vasectomy in the male partner (considered successful if a volunteer 
reports that a male partner has [1] documentation of azoospermia by microscopy, 
or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite 
sexual activity postvasectomy); 
 
Or not be of reproductive potential, such as having reached menopause (no menses 
for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal 
ligation; 
 
Or be sexually abstinent. 
22. Volunteers who were born female must also agree not to seek pregnancy through 
alternative methods, such as artificial insemination or in vitro fertilization until after the 
last required protocol clinic visit 
7.2 
Exclusion criteria 
General 
1. Allergy to amide-type local anesthetics (bupivacaine [Marcaine], lidocaine [Xylocaine], 
mepivacaine [Polocaine/Carbocaine], etidocaine [Duranest], prilocaine [Citanest, 
EMLA® cream]) 
2. Blood products received within 120 days before first vaccination  
3. Deltoid skin fold measurement by caliper > 40 mm 
4. Investigational research agents received within 30 days before first vaccination 

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5. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age > 45, 
systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current 
smoker, known hyperlipidemia 
6. Intent to participate in another study of an investigational research agent or any other 
study that requires non-HVTN HIV antibody testing during the planned duration of the 
study  
7. Pregnant or breastfeeding 
8.  Active duty and reserve US military personnel 
Vaccines and other Injections 
9. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received 
control/placebo in an HIV vaccine trial, the HVTN PSRT will determine eligibility on a 
case-by-case basis. 
10. Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine 
trial. Exceptions may be made for vaccines that have subsequently undergone licensure 
by the FDA. For volunteers who have received control/placebo in an experimental 
vaccine trial, the HVTN PSRT will determine eligibility on a case-by-case basis. For 
volunteers who have received an experimental vaccine(s) greater than 5 years ago, 
eligibility for enrollment will be determined by the HVTN PSRT on a case-by-case basis. 
11. Live attenuated vaccines other than influenza vaccine, received within 30 days before 
first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and 
rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever) 
12. Influenza vaccine or any vaccines that are not live attenuated vaccines and were 
received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A 
or B) 
13. Allergy treatment with antigen injections within 30 days before first vaccination or 
that are scheduled within 14 days after first vaccination  
Immune System  
14. Immunosuppressive medications received within 168 days before first vaccination. 
(Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical 
corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of 
oral/parenteral corticosteroids at doses < 2 mg/kg/day and length of therapy < 11 days 
with completion at least 30 days prior to enrollment.) 
15. Serious adverse reactions to vaccines or to vaccine components, including history of 
anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, 
and/or abdominal pain. (Not excluded from participation: a volunteer who had a 
nonanaphylactic adverse reaction to pertussis vaccine as a child.)  
16. Immunoglobulin received within 60 days before first vaccination 
17. Autoimmune disease  

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18. Immunodeficiency 
Clinically significant medical conditions  
19. Untreated or incompletely treated syphilis infection 
20. 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 injections or blood draws, 
 
A condition that requires active medical intervention or monitoring to avert grave 
danger to the volunteer’s health or well-being during the study period, 
 
A condition or process for which signs or symptoms could be confused with reactions 
to vaccine, or 
 
Any condition specifically listed among the exclusion criteria below. 
21. Any medical, psychiatric, occupational, or other condition that, in the judgment of the 
investigator, would interfere with, or serve as a contraindication to, protocol adherence, 
assessment of safety or reactogenicity, or a volunteer’s ability to give informed consent 
22. 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. 
23. Current anti-tuberculosis (TB) prophylaxis or therapy 
24. Asthma exclusion criteria: 
Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as 
defined in the most recent National Asthma Education and Prevention Program (NAEPP) 
Expert Panel report).  
Exclude a volunteer who: 
 
Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or 
 
Uses moderate/high dose inhaled corticosteroids, or 
 
In the past year has either of the following: 
 
Greater than 1 exacerbation of symptoms treated with oral/parenteral 
corticosteroids; 

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 
 Needed emergency care, urgent care, hospitalization, or intubation for asthma. 
25. Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not 
excluded: history of isolated gestational diabetes.) 
26. Thyroidectomy, or thyroid disease requiring medication during the last 12 months 
27. 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. 
28. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) 
29. 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) 
30. Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer 
has used medications in order to prevent or treat seizure(s) at any time within the past 3 
years. 
31. Asplenia: any condition resulting in the absence of a functional spleen 
32. History of hereditary angioedema, acquired angioedema, or idiopathic angioedema. 
33. Presence of implanted electronic medical device (eg, cochlear implant, pacemaker, 
implantable cardioverter defibrillator) 
34. Presence of surgical or traumatic metal implant at the intended site of administration 
(including the deltoid muscles and/or overlying skin) 
35. Sinus bradycardia (defined as < 50 bpm on exam) or a history of cardiac arrhythmia: 
eg, supraventricular tachycardia, atrial fibrillation, or frequent ectopy. 
NOTE: Sinus arrhythmia is not excluded. 

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7.3 
Participant departure from vaccination schedule or withdrawal 
This section concerns an individual participant’s departure from the vaccination schedule. 
Pause rules for the trial as a whole are described in Section 11.4. 
For information on procedures following EP difficulties, see Sections 9.3.1 and 9.3.2. 
7.3.1 
Delaying vaccinations for a participant 
Under certain circumstances, a participant’s scheduled vaccination will be delayed. The 
factors to be considered in such a decision include but are not limited to the following: 
 
Within 45 days prior to any study injection  
 
Receipt of blood products or immunoglobulin 
 
Within 30 days prior to any study injection 
 
Receipt of live attenuated vaccines other than influenza vaccine  
 
Receipt of allergy treatment with antigen injections 
 
Within 14 days prior to any study injection 
 
Receipt of influenza vaccine or any vaccines that are not live attenuated vaccines 
(eg, pneumococcal)  
 
Pre-vaccination abnormal vital signs or clinical symptoms that may mask assessment 
of vaccine reaction. 
Vaccinations should not be administered outside the visit window period specified in the 
Study Specific Procedures. 
In order to avoid vaccination delays and missed vaccinations, participants who plan to 
receive licensed vaccines or allergy treatments should be counseled to schedule receipt of 
these substances, when possible, outside the intervals indicated above. The effects of 
these substances on safety and immunogenicity assessments and their interactions with 
study vaccines are unknown. Therefore, if circumstances allow, these substances should 
also be avoided in the 2 week interval between a study vaccination and completion of the 
2 week post vaccination follow-up visit. 
7.3.2 
Participant departure from vaccination schedule 
Every effort should be made to follow the vaccination schedule per the protocol. If a 
participant misses a vaccination and the visit window period for the vaccination has 
passed, that vaccination cannot be given. The participant should be asked to continue 
study visits. The participant should resume the vaccination schedule with the next 
vaccination unless there are circumstances that require further delay or permanent 
discontinuation of vaccination (see Sections 7.3.1 and 7.3.3).  

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7.3.3 
Discontinuing vaccination for a participant 
Under certain circumstances, an individual participant’s vaccinations will be permanently 
discontinued. Specific events that will result in stopping a participant’s vaccination 
schedule include: 
 
Co-enrollment in a study with an investigational research agent (rare exceptions 
allowing for the continuation of vaccinations may be granted with the unanimous 
consent of the HVTN PSRT). 
 
Clinically significant condition (ie, a condition that affects the immune system or for 
which continued vaccinations and/or blood draws may pose additional risk), 
including but not limited to the following: 
 
Pregnancy (regardless of outcome); 
 
Any grade 4 local or systemic reactogenicity symptom, lab abnormality, or AE 
that is subsequently considered to be related to study products. 
 
Any grade 3 lab abnormality or other clinical AE (exception: fever or vomiting 
and subjective local and systemic symptoms) that is subsequently considered to 
be related to study products; or 
 
Clinically significant type 1 hypersensitivity reaction associated with study 
vaccination. Consultation with the HVTN PSRT is required prior to subsequent 
vaccinations following any type 1 hypersensitivity reaction associated with study 
vaccination; or 
 
Investigator determination in consultation with Protocol Team leadership (eg, for 
repeated nonadherence to study staff instructions). 
Such participants 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. 
In addition, vaccinations will be stopped for participants diagnosed with HIV infection. 
HIV-infected participants will not continue in the trial (see Section 7.3.4). 
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 HVTN CRS is not 
possible, 
 
HVTN CRS determines that the participant is lost to follow-up,  
 
Participant becomes HIV infected, or 

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 
Investigator decides, in consultation with Protocol Team leadership, to terminate 
participation (eg, if participant exhibits inappropriate behavior toward clinic staff). 
 
Any condition where termination from the study is required by applicable 
regulations. 

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8 
Study product preparation and administration 
CRS pharmacists should consult the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks for standard pharmacy operations. The protocol schema is 
shown in Table 3-1. See the Investigator’s Brochures for further information about study 
products. 
8.1 
Vaccine regimen 
The schedule of vaccination is shown in Section 3 and additional information is given 
below.  
Group 1 
All vaccine regimens including placebo will be administered intramuscularly using the 
Ichor Medical System intramuscular TriGrid TM Delivery System (TDS-IM) 
electroporation (EP) device. 
Treatment 1 (T1): 
p24CE1/2 DNA plasmid 2 mg admixed with GENEVAX® IL-12 
DNA plasmid 1 mg administered as 1 mL IM in left deltoid  
AND 
p24CE1/2 DNA plasmid 2 mg admixed with GENEVAX® IL-12 
DNA plasmid 1 mg administered as 1 mL IM in right deltoid at 
Months 0 and 1. 
THEN 
p24CE1/2 DNA plasmid 1 mg admixed with p55gag DNA plasmid 1 
mg and GENEVAX® IL-12 DNA plasmid 1 mg administered as 1 
mL IM in left deltoid 
AND 
p24CE1/2 DNA plasmid 1 mg admixed with p55gag DNA plasmid 1 
mg and GENEVAX® IL-12 DNA plasmid 1 mg administered as 1 
mL IM in right deltoid at Months 3 and 6. 
Control 1 (C1): 
Placebo for p24CE1/2 + IL-12 pDNA is Sodium Chloride for 
Injection, USP 0.9%, administered as 1 mL IM in left deltoid  
AND 
1 mL IM in right deltoid at Months 0 and 1. 

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THEN 
Placebo for p24CE1/2 + p55gag + IL-12 pDNA is Sodium Chloride 
for Injection, USP 0.9%, administered as 1 mL IM in left deltoid  
AND 
1 mL IM in right deltoid at Months 3 and 6. 
Group 2 
All vaccine regimens including placebo will be administered intramuscularly using the 
Ichor Medical System intramuscular TriGrid TM Delivery System (TDS-IM) 
electroporation (EP) device. 
Treatment 2 (T2): 
p55gag DNA plasmid 2 mg admixed with GENEVAX® IL-12 DNA 
plasmid 1 mg administered as 1 mL IM in left deltoid  
AND 
p55gag DNA plasmid 2 mg admixed with GENEVAX® IL-12 DNA 
plasmid 1 mg administered as 1 mL IM in right deltoid at Months 0, 
1, 3, and 6. 
Control 2 (C2):  
Placebo for p55gag + IL-12 pDNA is Sodium Chloride for Injection, 
USP 0.9%, administered as 1 mL IM in left deltoid  
AND 
1 mL IM in right deltoid at Months 0, 1, 3 and 6. 
8.2 
Study product formulation  
p24CE1/2 pDNA [Labeled as p24CE1/2 pDNA 4 mg/mL]  
p24CE1/2 pDNA is a clear, colorless solution in a 2 mL single use vial. Each 2 mL vial 
contains 0.7 ± 0.1 mL p24CE1/2 pDNA at a concentration of 4 mg/mL in 30 mM citrate 
buffer pH 6.5 containing 150 mM NaCl, 0.01% EDTA, and 0.25% bupivacaine-HCl.  
It must be stored at -20˚C. 
The product is contraindicated in participants with known hypersensitivity to 
bupivacaine. 

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p55gag pDNA [Labeled as p55 Gag pDNA 4 mg/mL]  
The p55gag pDNA is a clear, colorless solution in a 2 mL single use vial. Each 2 mL vial 
contains 0.7 ± 0.1 mL p55gag pDNA at a concentration of 4 mg/mL in 30 mM citrate 
buffer pH 6.5 containing 150 mM NaCl, 0.01% EDTA, and 0.25% bupivacaine-HCl.  
It must be stored at -20˚C. 
The product is contraindicated in participants with known hypersensitivity to 
bupivacaine. 
GENEVAX® IL-12 DNA Plasmid (GENEVAX® IL-12-4532, WLV-103M, IL-12 pDNA, 
IL-12 plasmid) 
GENEVAX® IL-12 DNA plasmid is a clear colorless solution in a 2 mL single use vial. 
Each 2 mL vial contains 1 ± 0.1 mL of IL-12 pDNA at a concentration of 2 mg/mL in 30 
mM citrate buffer pH 6.5 containing 150 mM NaCl, 0.01% EDTA and 0.25% 
bupivacaine-HCl.  
The product should be stored at 2 to 8C. 
The product is contraindicated in participants with known hypersensitivity to 
bupivacaine. 
8.3 
Preparation of study products 
 
p24CE1/2 + IL-12 pDNA (Group 1) 
8.3.1
Two vials of p24CE1/2 pDNA (4 mg/mL), 2 vials of IL-12 pDNA (2 mg /mL), and 1 
empty sterile vial (5 mL) will be needed to prepare the 2 syringes. Prior to dispensing, the 
pharmacist will remove 2 vials of p24CE1/2 pDNA from the freezer and allow to thaw at 
room temperature for 15-30 minutes until no crystals are observed. The pharmacist will 
remove 2 vials of IL-12 pDNA from the refrigerator. Gently swirl and invert the vials for 
at least 10 inversions (do not shake vigorously). 
The vials should be visually inspected prior to use. If the vial contains material different 
from its description above, do not use the vial and contact the protocol pharmacist. Prior 
to mixing the study products, the pharmacist will also inspect the sterile pouches 
containing the TriGrid™ Application Cartridges for integrity and verify the Cartridges 
have not passed expiration. If any tears or gaps in the sterile pouch are noted or if the 
expiration date has been reached, the Application Cartridge should be placed in 
quarantine and the protocol pharmacist should be informed. Note: In the event that the 
Cartridge Cap has become detached from the Cartridge in the sterile pouch, the 
Cartridge may still be used if the Cartridge Cap can be replaced without contaminating 
the patient contact portion of the Cartridge. 
 
Using aseptic technique, the pharmacist will withdraw the 0.6 ml from each of 
the 2 vials of p24CE1/2 pDNA (4 mg/mL) with a 1 mL low void 25 Ga syringe 
(low dead space syringe; see HVTN 119 Study Specific Procedures) and inject 
them into an empty mixing sterile vial. This mixing vial, now containing 1.2 mL 
of p24CE1/2 pDNA, will be set aside.  

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 
Using aseptic technique, the pharmacist will then withdraw 0.6 mL from each of 
the 2 vials containing IL-12 pDNA (2 mg /mL) with a 1 mL syringe and inject 
them directly into the mixing vial containing 1.2 mL of p24CE1/2 pDNA. The 
pharmacist will mix the vial containing 2.4 mL of the mixture of p24CE1/2 
pDNA + GENEVAX® IL-12 DNA plasmid. Gently swirl and invert the mixing 
vial containing the vaccine for at least 10 inversions (do not shake vigorously). 
 
Using two new 3 mL syringes (BD# 309585, 309657, or Ichor approved) each 
fitted with a 22 Ga x 1.5" needle (BD# 305156, or Ichor approved), the 
pharmacist will withdraw 1 mL of the mixed preparation from the mixing vial 
into each syringe, and affix each syringe with a new 22 Ga x 1.5" needle, and 
attached into an Application Cartridge as directed in the HVTN 119 Study 
Specific Procedures. 
Note: Use the syringe tabs to insert the syringe into the Application Cartridge. Do not 
depress the syringe plunger during insertion of the syringe into the Application Cartridge 
as this will cause the agent to be injected into the Cartridge. 
Caution: During the syringe loading procedure, do not physically touch the syringe 
needle or cause it to come in contact with a non-sterile surface. Note that, although the 
inside of the Application Cartridge is sterile, contact between the syringe needle and the 
inner housing of the Application Cartridge should be avoided to the extent possible. 
Contact between the syringe needle and Application Cartridge could result in 
deformation of the syringe needle and increased discomfort for the subject upon 
insertion. If contamination and/or deformation of the injection needle is suspected, 
replace the injection needle with a new BD 22 Ga x 1.5" injection needle (BD model 
305156 or Ichor approved). To prevent loss of dosage make sure to withdraw agent from 
needle before replacing. 
 
Each Application Cartridge will have the Participant’s ID number written on it 
using a Sharpie or other similar pen. The cartridge will then be placed back in the 
pouch that it was removed from and the pouch will be labeled as “HVTN 119 
study product or placebo 1 mL.” 
 
The pouch containing the syringe must be labeled with a 4-hour expiration date 
from the time the vial is removed from the refrigerator/freezer. The label must 
also contain the words “Administer as soon as possible.”  
 
One of the syringes must also be labeled for administration in RIGHT deltoid and 
the second syringe must be labeled for administration in the LEFT deltoid.  
Any unused portion of reconstituted vials or expired prefilled syringes is disposed of in 
accordance with institutional or pharmacy policy.  
 
Placebo for p24CE1/2 + IL-12 pDNA (Group 1) 
8.3.2
One vial containing Sodium Chloride for Injection, USP 0.9% will be needed to prepare 
the two syringes. The vial should be visually inspected prior to use. The pharmacist will 
also inspect the sterile pouches containing the TriGridTM Application Cartridges for 
integrity and verify the Cartridges have not passed expiration. If any tears or gaps in the 
sterile pouch are noted or if the expiration date has been reached, the Application 
Cartridge should be placed in quarantine and the protocol pharmacist should be informed. 

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Note: In the event that the Cartridge Cap has become detached from the Cartridge in the 
sterile pouch, the Cartridge may still be used if the Cartridge Cap can be replaced 
without contaminating the patient contact portion of the Cartridge. 
 
Using aseptic technique, the pharmacist, using two new 3 mL syringes (BD# 
309585, 309657, or Ichor approved) each fitted with a 22 Ga x 1.5" needle (BD# 
305156 or Ichor approved), will withdraw 1 mL of the Sodium Chloride for 
Injection, USP 0.9% into each syringe and insert the syringe with an identical 
new needle attached into the Application Cartridge as directed in the HVTN 119 
Study Specific Procedures.  
Note: Use the syringe tabs to insert the syringe into the Application Cartridge. Do not 
depress the syringe plunger during insertion of the syringe into the Application Cartridge 
as this will cause the agent to be injected into the Cartridge. 
Caution: During the syringe loading procedure, do not physically touch the syringe 
needle or cause it to come in contact with a non-sterile surface. Note that, although the 
inside of the Application Cartridge is sterile, contact between the syringe needle and the 
inner housing of the Application Cartridge should be avoided to the extent possible. 
Contact between the syringe needle and Application Cartridge could result in 
deformation of the syringe needle and increased discomfort for the subject upon 
insertion. If contamination and/or deformation of the injection needle is suspected, 
replace the injection needle with a new BD 22 Ga x 1.5" injection needle (BD model 
305156 or Ichor approved). To prevent loss of dosage make sure to withdraw agent from 
needle before replacing. 
 
Each Application Cartridge will have the Participant’s ID number written on it 
using a Sharpie or other similar pen. The cartridge will then be placed back in the 
pouch that it was removed from and the pouch will be labeled as “HVTN 119 
study product or placebo 1mL.” 
 
The pouch containing the syringe must be labeled with a four-hour expiration 
date from the time the vial is removed from the refrigerator. The label must also 
contain the words “Administer as soon as possible.”  
 
One of the syringes must also be labeled for administration in RIGHT deltoid and 
the second syringe must be labeled for administration in the LEFT deltoid.  
Any unused portion of reconstituted vials or expired prefilled syringes is disposed of in 
accordance with institutional or pharmacy policy. 
 
p24CE1/2 + p55gag + IL-12 pDNA (Group 1) 
8.3.3
One vial of p24CE1/2 pDNA (4 mg/mL), 1 vial of p55gag pDNA (4 mg/mL), 2 vials of 
IL-12 pDNA (2 mg/mL) and one empty 5 mL sterile vial (for mixing) will be needed to 
prepare the dose. Prior to dispensing, the pharmacist will remove one vial of p24CE1/2 
pDNA and one vial of p55gag pDNA from the freezer and allow to thaw at room 
temperature for 15 to 30 minutes until no crystals are observed. The pharmacist will 
remove 2 vials of IL-12 pDNA from the refrigerator. Gently swirl and invert the vials 
containing vaccine for at least 10 inversions (do not shake vigorously). 

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The vials should be visually inspected prior to use. If the vial contains material different 
from its description above, do not use the vial and contact the protocol pharmacist. Prior 
to mixing the study products, the pharmacist will also inspect the sterile pouches 
containing the TriGrid™ Application Cartridges for integrity and verify the Cartridges 
have not passed expiration. If any tears or gaps in the sterile pouch are noted or if the 
expiration date has been reached, the Application Cartridge should be placed in 
quarantine and the protocol pharmacist should be informed. Note: In the event that the 
Cartridge Cap has become detached from the Cartridge in the sterile pouch, the 
Cartridge may still be used if the Cartridge Cap can be replaced without contaminating 
the patient contact portion of the Cartridge. 
 
Using aseptic technique, the pharmacist will withdraw 0.6 ml from the vial 
containing p24CE1/2 pDNA (4 mg/mL) with a 1 mL low void 25 Ga syringe 
(low dead space syringe; see HVTN 119 Study Specific Procedures) and inject 
this into the mixing vial. This mixing vial, now containing 0.6 mL of p24CE1/2 
pDNA, will be set aside.  
 
Using aseptic technique, the pharmacist will withdraw 0.6 ml from the vial 
containing p55gag pDNA (4 mg/mL) with a 1 mL low void 25 Ga syringe (low 
dead space syringe; see HVTN 119 Study Specific Procedures) and inject this into 
the mixing vial that contains p24CE1/2 pDNA. This mixing vial, now containing 
1.2 mL of p24CE1/2 pDNA + p55gag pDNA will be set aside.  
 
Using aseptic technique, the pharmacist will then withdraw 0.6 mL from each of 
the 2 vials containing IL-12 pDNA (2 mg /mL) with a 1 mL syringe and inject 
them directly into the mixing vial containing 1.2 mL of p24CE1/2 pDNA+ 
p55gagpDNA. The pharmacist will mix the vial containing 2.4 mL of the mixture 
of p24CE1/2 pDNA + p55gag
 pDNA +GENEVAX® IL-12 DNA plasmid. Gently 
swirl and invert the mixing vial containing the vaccine mixture for at least 10 
inversions (do not shake vigorously). 
 
Using two new 3 mL syringes (BD# 309585, 309657, or Ichor approved) each 
fitted with a 22 Ga x 1.5" needle (BD# 305156 or Ichor approved), the 
pharmacist will withdraw 1 mL of the mixed preparation from the mixing vial 
into each syringe, and insert each syringe with an identical new needle attached 
into an Application Cartridge as directed in the HVTN 119 Study Specific 
Procedures. 
Note: Use the syringe tabs to insert the syringe into the Application Cartridge. Do not 
depress the syringe plunger during insertion of the syringe into the Application Cartridge 
as this will cause the agent to be injected into the Cartridge. 
Caution: During the syringe loading procedure, do not physically touch the syringe 
needle or cause it to come in contact with a non-sterile surface. Note that, although the 
inside of the Application Cartridge is sterile, contact between the syringe needle and the 
inner housing of the Application Cartridge should be avoided to the extent possible. 
Contact between the syringe needle and Application Cartridge could result in 
deformation of the syringe needle and increased discomfort for the subject upon 
insertion. If contamination and/or deformation of the injection needle is suspected, 
replace the injection needle with a new BD 22 Ga x 1.5" injection needle (BD model 
305156 or Ichor approved). To prevent loss of dosage make sure to withdraw agent from 
needle before replacing. 

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HVTN119_v1.0_FINAL / Page 68 of 140 
 
Each Application Cartridge will have the Participant’s ID number written on it 
using a Sharpie or other similar pen. The cartridge will then be placed back in the 
pouch that it was removed from and the pouch will be labeled as “HVTN 119 
study product or placebo 1mL.” 
 
The pouch containing the syringe must be labeled with a four-hour expiration 
date from the time the vial is removed from the refrigerator. The label must also 
contain the words “Administer as soon as possible.”  
 
One of the syringes must also be labeled for administration in RIGHT deltoid and 
the second syringe must be labeled for administration in the LEFT deltoid.  
Any unused portion of reconstituted vials or expired prefilled syringes is disposed of in 
accordance with institutional or pharmacy policy. 
 
Placebo for p24CE1/2+ p55gag + IL-12 pDNA (Group 1) 
8.3.4
One vial containing Sodium Chloride for Injection, USP 0.9% will be needed to prepare 
the two syringes. The vial should be visually inspected prior to use. The pharmacist will 
also inspect the sterile pouch containing the TriGridTM Application Cartridge for integrity 
and verify the Cartridge has not passed expiration. If any tears or gaps in the sterile pouch 
are noted or if the expiration date has been reached, the Application Cartridge should be 
placed in quarantine and the protocol pharmacist should be informed. Note: In the event 
that the Cartridge Cap has become detached from the Cartridge in the sterile pouch, the 
Cartridge may still be used if the Cartridge Cap can be replaced without contaminating 
the patient contact portion of the Cartridge. 
 
Using aseptic technique, the pharmacist, using two new 3 mL syringes (BD# 
309585, 309657, or Ichor approved) each fitted with a 22 Ga x 1.5" needle (BD# 
305156 or Ichor approved), will withdraw 1 mL of the Sodium Chloride for 
Injection, USP 0.9% into each syringe and insert the syringe with an identical 
new needle attached into the Application Cartridge as directed in the HVTN 119 
Study Specific Procedures.  
Note: Use the syringe tabs to insert the syringe into the Application Cartridge. Do not 
depress the syringe plunger during insertion of the syringe into the Application Cartridge 
as this will cause the agent to be injected into the Cartridge. 
Caution: During the syringe loading procedure, do not physically touch the syringe 
needle or cause it to come in contact with a non-sterile surface. Note that, although the 
inside of the Application Cartridge is sterile, contact between the syringe needle and the 
inner housing of the Application Cartridge should be avoided to the extent possible. 
Contact between the syringe needle and Application Cartridge could result in 
deformation of the syringe needle and increased discomfort for the subject upon 
insertion. If contamination and/or deformation of the injection needle is suspected, 
replace the injection needle with a new BD 22 Ga x 1.5" injection needle (BD model 
305156 or Ichor approved). To prevent loss of dosage make sure to withdraw agent from 
needle before replacing. 
 
Each Application Cartridge will have the Participant’s ID number written on it 
using a Sharpie or other similar pen. The cartridge will then be placed back in the 

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pouch that it was removed from and the pouch will be labeled as “HVTN 119 
study product or placebo 1 mL.” 
 
The pouch containing the syringe must be labeled with a 4-hour expiration date 
from the time the vial is removed from the refrigerator/freezer. The label must 
also contain the words “Administer as soon as possible.”  
 
One of the syringes must also be labeled for administration in RIGHT deltoid and 
the second syringe must be labeled for administration in the LEFT deltoid.  
Any unused portion of reconstituted vials or expired prefilled syringes is disposed of in 
accordance with institutional or pharmacy policy. 
Any unused portion of entered vials or expired prefilled syringes should be disposed of in 
accordance with institutional or pharmacy policy. 
 
p55gag + IL-12 pDNA (Group 2) 
8.3.5
Two vials of p55gag pDNA (4 mg/mL), 2 vials of IL-12 pDNA (2 mg /mL), and 1 empty 
sterile vial (5 mL) will be needed to prepare the 2 syringes. Prior to dispensing, the 
pharmacist will remove 2 vials of p55gag pDNA from the freezer and allow thaw at room 
temperature for 15-30 minutes until no crystals are observed. The pharmacist will remove 
2 vials of IL-12 pDNA from the refrigerator. Gently swirl and invert the vials for at least 
10 inversions (do not shake vigorously). 
The vials should be visually inspected prior to use. If the vial contains material different 
from its description above, do not use the vial and contact the protocol pharmacist. Prior 
to mixing the study products, the pharmacist will also inspect the sterile pouches 
containing the TriGrid™ Application Cartridges for integrity and verify the Cartridges 
have not passed expiration. If any tears or gaps in the sterile pouch are noted or if the 
expiration date has been reached, the Application Cartridge should be placed in 
quarantine and the protocol pharmacist should be informed. Note: In the event that the 
Cartridge Cap has become detached from the Cartridge in the sterile pouch, the 
Cartridge may still be used if the Cartridge Cap can be replaced without contaminating 
the patient contact portion of the Cartridge. 
 
Using aseptic technique, the pharmacist will withdraw 0.6 mL from each of the 2 
vials of p55gag pDNA (4 mg/mL) with a 1 mL low void 25 Ga syringe (low dead 
space syringe; see HVTN 119 Study Specific Procedures) and inject this into the 
mixing vial. This mixing vial, now containing 1.2 mL of p55gagpDNA, will be set 
aside.  
 
Using aseptic technique, the pharmacist will then withdraw 0.6 mL from each of 
the 2 vials containing IL-12 pDNA (2 mg /mL) with a 1 mL syringe and inject 
them directly into the mixing vial containing 1.2 mL of p55gag pDNA. Now the 
mixing vial contains 2.4 mL of the mixture of p55gag pDNA + GENEVAX® IL-
12 DNA plasmid. The pharmacist will gently swirl and invert the mixing vial 
containing the vaccine mixture for at least 10 inversions (do not shake 
vigorously). 
 
Using two new 3 mL syringes (BD# 309585, 309657, or Ichor approved) each 
fitted with a 22 Ga x 1.5" needle (BD# 305156, or Ichor approved), the 

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pharmacist will withdraw 1 mL of the mixed preparation from the mixing vial 
into each syringe, and insert each syringe with an identical new needle attached 
into an Application Cartridge as directed in the HVTN 119 Study Specific 
Procedures. 
Note: Use the syringe tabs to insert the syringe into the Application Cartridge. Do not 
depress the syringe plunger during insertion of the syringe into the Application Cartridge 
as this will cause the agent to be injected into the Cartridge. 
Caution: During the syringe loading procedure, do not physically touch the syringe 
needle or cause it to come in contact with a non-sterile surface. Note that, although the 
inside of the Application Cartridge is sterile, contact between the syringe needle and the 
inner housing of the Application Cartridge should be avoided to the extent possible. 
Contact between the syringe needle and Application Cartridge could result in 
deformation of the syringe needle and increased discomfort for the subject upon 
insertion. If contamination and/or deformation of the injection needle is suspected, 
replace the injection needle with a new BD 22 Ga x 1.5" injection needle (BD model 
305156 or Ichor approved). To prevent loss of dosage make sure to withdraw agent from 
needle before replacing. 
 
Each Application Cartridge will have the Participant’s ID number written on it 
using a Sharpie or other similar pen. The cartridge will then be placed back in the 
pouch that it was removed from and the pouch will be labeled as “HVTN 119 or 
placebo 1 mL.” 
 
The pouch containing the syringe must be labeled with a 4-hour expiration date 
from the time the vial is removed from the refrigerator/freezer. The label must 
also contain the words “Administer as soon as possible.”  
 
One of the syringes must also be labeled for administration in RIGHT deltoid and 
the second syringe must be labeled for administration in the LEFT deltoid.  
Any unused portion of reconstituted vials or expired prefilled syringes is disposed of in 
accordance with institutional or pharmacy policy.  
8.4 
Administration 
Any administrator of study product will be blinded to the individual participant’s 
treatment assignment. At sites where registered pharmacists are legally authorized to 
administer drug, the HVTN CRS may choose to have a blinded HVTN CRS pharmacist 
administer the vaccinations. 
Administration of vaccine or placebo for all groups consists of 2 injections, 1 each in left 
and right medial deltoids using the Ichor Medical Systems Intramuscular TriGrid 
Delivery System (TDS-IM) EP device at Months 0, 1, 3 and 6. 
The TDS-IM device will be used as directed by Ichor Medical Systems, Inc. (Please refer 
to the TDS-IM User Manual for further instruction). The TDS-IM has three components: 
The TDS-IM Pulse Stimulator, the Integrated Applicator (reusable) and the Application 
Cartridge (single-use). The Application Cartridge is the only patient contact component 
of the system. Only use Becton Dickinson 3.0 mL sterile syringe (BD# 309585, 309657, 

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HVTN119_v1.0_FINAL / Page 71 of 140 
or Ichor approved) and Becton Dickinson 22 Ga x 1.5" injection needle (BD# 305156 or 
Ichor approved) with the Application Cartridge. 
The used TDS-IM Application Cartridge should be disposed of in accordance with 
institutional policy in the clinic. It should NOT be returned to pharmacy. 
To accommodate differences in skin thickness, a slidable depth control gauge allows 
adjustment of injection depth to one of three settings: 12, 17, or 22 millimeters (mm) 
from the skin surface. The corresponding depth of electrode insertion for these settings is 
15, 20, and 25 mm respectively. Prior to applying the EP procedure, the participant’s skin 
to muscle thickness must be assessed for each arm separately. This may be assessed once, 
at any time prior to the first injection with EP for a participant, and is not required prior 
to each procedure. However the skin fold thickness should be reassessed for a participant 
whose body weight has changed by 10% since the previous skin fold thickness 
assessment. The skin fold thickness for each arm is recorded in the participant study 
chart. The Application Cartridge penetration depth will be set prior to each procedure 
according to these measurements. 
To assess the thickness of the skin and subcutaneous tissue use your thumb and forefinger 
to “pinch” the skin and subcutaneous tissue overlying the muscle at the administration 
site together and measure the fold thickness using skin calipers or other suitable 
measurement device. Based on this measurement, use the chart below to select the 
appropriate depth setting on the Application Cartridge for each arm. Record the skin fold 
thickness for each arm in the participant study chart. The selected depth setting on the 
Cartridge is indicated by the number of indicator lines visible on Cartridge (see Table 
8-1). 
Table 8-1 Selection of device depth setting 
Range of Measured 
skin fold Thickness 
[mm] 
Device Depth 
Selection 
Number of 
indicator lines 
visible 
< 14 mm 
A 
3 
14-23 mm 
B 
2 
24-40 mm 
C 
1 
>40 mm 
Exclude from 
protocol 
Exclude from 
protocol 
To ensure intramuscular injection, proper selection of the injection site as well as 
assessment and setting of the injection depth are important factors in procedure 
administration. In particular, care should be taken in specific subjects or subject 
populations with low muscle mass (eg, sarcopenia) to ensure that an administration site 
with adequate muscle thickness (eg, vastus lateralis) is selected for injection. Specifically, 
any selected administration site should have sufficient muscle mass to accommodate the 
1 inch / 25 mm maximum penetration depth of the device. 

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8.5 
Acquisition of study products 
p24CE1/2 pDNA and p55gag pDNA will be provided by DAIDS, NIAID, NIH, DHHS.  
GENEVAX® IL-12 DNA plasmid will be provided by Profectus BioSciences, Inc.  
The TriGrid™ Delivery System and TriGrid™ Application Cartridge (electroporation 
array), will be provided by Ichor Medical Systems. 
The placebo (Sodium Chloride for Injection, USP 0.9%) will not be provided through the 
protocol but must be purchased by the site. 
The syringes and needles used for the preparation and delivery of the study products, 
including the 3 mL syringes (BD #309585, 309657, or Ichor approved) and Becton 
Dickinson 22 Ga x1½" needles (BD #305156 or Ichor approved) will not be provided 
through the protocol and must be purchased by the site. 
Once an HVTN CRS is protocol registered, the pharmacist can obtain study products 
from the NIAID Clinical Research Products Management Center (CRPMC) by following 
the ordering procedures given in Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks. 
8.6 
Pharmacy records 
The HVTN CRS pharmacist is required to maintain complete records of all study 
products. The pharmacist of record is responsible for maintaining randomization codes 
and randomization confirmation notices for each participant in a secure manner. 
8.7 
Final disposition of study products 
All unused study products must be returned to the CRPMC after the study is completed 
or terminated unless otherwise instructed by the CRPMC. The procedures and relevant 
form are included in the Pharmacy Guidelines and Instructions for DAIDS Clinical Trials 
Networks.  

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

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Protocol-specific consent forms 
9.1.2
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. A 
sample protocol-specific consent form for the main study is located in Appendix A. A 
separate sample consent form for other uses of specimens is located in Appendix C. 
Each HVTN CRS is responsible for developing a protocol-specific consent form(s) for 
local use, based on the sample protocol-specific consent forms in Appendix A and 
Appendix C. 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 the International Conference on Harmonisation (ICH) E6, 
Good Clinical Practice: Consolidated Guidance 4.8.  
Study sites are strongly encouraged to have their local CABs review their 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 form includes instructions throughout the document for 
developing specific content. 
Sites should follow the instructions in the Protocol-specific Official Memo distributed 
along with this protocol regarding when they may begin using their site-specific protocol 
consent forms. 
Regarding protocol registration, sites should follow procedures outlined in the current 
version of the DAIDS Protocol Registration Manual. 
 
Assessment of Understanding 
9.1.3
Study staff are 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 HIV vaccine 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 

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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 
vaccination 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; 
 
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; 
 
Deltoid skin fold measurement (Section 8.4) 
 
Assessment of concomitant medications the volunteer is taking, including 
prescription and nonprescription drugs, vitamins, topical products, 
alternative/complementary medicines (eg, herbal and health food supplements), 
recreational drugs, vaccinations, and allergy shots; 
 
Laboratory tests as defined in the inclusion and exclusion criteria, including: 
 
Screening HIV test, 
 
HBsAg, 
 
Anti-HCV antibodies, 
 
Syphilis test, 
 
CBC with differential and platelets, 
 
Chemistry panel (ALT, AST, alkaline phosphatase, creatinine, and CPK), 
 
Urine dipstick (as described in Section 9.8). and 
 
Urine or serum pregnancy test (participants who were born female)  
 
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); 

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 
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 9.6; and 
 
Discussion of pregnancy prevention. A pregnant or breastfeeding person may not be 
enrolled in this trial. Specific criteria and assessment of contraception and pregnancy 
status are described in study inclusion criteria. Discussion of pregnancy prevention 
includes advising a participant who was born female and who reports no current 
sexual activity that could lead to that participant becoming pregnant to have a plan to 
begin adequate birth control. This plan would be put to use if, during the study, the 
participant becomes sexually active in a way that could lead to that participant 
becoming pregnant.  
 
Use of screening results from another HVTN study 
9.2.1
If a participant screens for an HVTN study at the same HVTN CRS but then does not join 
that study, screening results from that effort may be applied to the screening for this 
protocol, as long as the screening was done under participant consent, the participant has 
signed a consent form to begin screening for this study, and the tests were conducted 
within the time periods specified in the eligibility criteria (see Sections 7.1 and 7.2). 
9.3 
Enrollment and vaccination visits 
Enrollment is simultaneous with first vaccination. The time interval between 
randomization and enrollment should not exceed 4 working days. The HVTN CRS 
registers the participant by scheduling the day 0 visit (enrollment) via the Web-based 
randomization system, and requests the randomization assignment. Circumstances may 
require a participant’s enrollment visit to be changed. This may exceed the 4-day 
randomization time limit. 
At all vaccination visits, the following procedures are performed before vaccination: 
 
Abbreviated physical examination, including weight, vital signs, and a symptom-
directed evaluation by history and/or appropriate physical exam based on participant 
self-reported symptoms or complaints; 
 
Assessment of baseline reactogenicity parameters; 
 
Assessment of concomitant medications (as described in Section 9.2); 
 
Assessment of any new or unresolved AEs/intercurrent illnesses; and 
 
Urine or serum pregnancy test (for participants who were born female). Persons who 
are NOT of reproductive potential due to having undergone total 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 
vaccination may proceed, vaccination is prepared and administered (see Sections 8.3 and 
8.4). 

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Administration of all injections during a vaccination visit must be accomplished within 1 
calendar day. 
Immediately following vaccination, the participant remains in the clinic for observation. 
Participant pain will be assessed using a Visual Analog Scale (VAS) immediately 
following EP, then again 5-7 minutes and 25-60 minutes following vaccination (as 
described in Section 9.9.3). An initial reactogenicity assessment is made at a target of 30 
minutes after injection, with an acceptable range of 25-60 minutes. Before leaving the 
clinic, the participant is given the postvaccination memory tool and is instructed on how 
to complete it. The site will make arrangements to be in contact with the participant 
during the reactogenicity period (as described in Section 9.9). 
The following procedures will be performed at all vaccination visits. These procedures 
may be performed prior to or following vaccination:  
 
Risk reduction counseling (as described in Section 9.6);  
 
Pregnancy prevention assessment (as described in Section 9.2 and 9.7); 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). 
Additional procedures will be performed at scheduled visits as specified in Appendix E 
and Appendix F:  
 
Administration of the social impact assessment questionnaire (types of impacts 
assessed involve personal relationships, health insurance, life insurance, educational 
or employment opportunities, housing, immigration, or travel); 
 
Administration of a questionnaire that asks the participant about any HIV testing he 
or she may have received outside of the study. Participants will also be asked whether 
they believe they received the active vaccine or the control; 
 
HIV infection assessment including pre-test counseling. A subsequent follow-up 
contact is conducted to provide post-test counseling and to report results to 
participant; 
 
Confirm that participants received HIV test results from previous visit. If not, provide 
test results and post-test counseling as appropriate; and 
 
Specimen collection (should be completed prior to vaccination). 
 
EP device applied without vaccination 
9.3.1
All vaccinations will be given with the Ichor TDS-IM EP device. If the device was 
applied, but neither electroporation nor study product (vaccine or placebo) was received, 
and the participant is willing, additional attempts may be made within the vaccination 
window. For the Month 0 visit, any additional attempts are expected to take place within 
4 days of randomization, unless a longer window is approved by the PSRT. For 
subsequent timepoints, if a participant does not receive study agent (vaccine or placebo, 

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with or without EP) in at least one arm within the vaccination window, that participant 
will have missed that vaccination. 
At the Month 0 visit, if the participant had the Ichor TDS-IM EP device applied to the 
participant’s arm but the participant was not able to receive any injection of study product 
at the enrollment visit, the participant is not considered enrolled into the study, and is 
referred to as a “device-only participant”. Refer to the HVTN 119 Study Specific 
Procedures for additional instructions and for the CRFs to be completed. Receipt of study 
product (ie, any volume of vaccine or placebo, with or without EP) in at least one arm 
constitutes enrollment. 
The CRS staff should contact each device-only participant approximately 14 days after 
initial application of the device in order to assess any new or unresolved AEs that may 
have occurred in the interim. This contact does not require a clinic visit, unless medically 
indicated. As the device-only participant was not enrolled in the trial, no further visits or 
study procedures are required, except for AE reporting of events associated with the 
application of the EP device, which should be reported to the SDMC on the appropriate 
CRF. In addition, AEs requiring expedited reporting should be reported to the DAIDS 
RSC Safety Office as described in Section 11.2.3. 
 
When a vaccination attempt results in vaccination without EP 
9.3.2
If a study product injection (ie, any volume of vaccine or placebo) is given without EP 
due to human error or device malfunction, this event will be recorded/documented for 
that arm, and vaccinations should continue as scheduled. 
9.4 
Follow-up visits 
The following procedures are performed at all scheduled follow-up visits: 
 
Risk reduction counseling (as described in Section 9.6);  
 
Pregnancy prevention assessment (as described in Section 9.2 and 9.7); and 
 
Assessment of new or unresolved social impacts (site staff will ask participant about 
the status of any unresolved social impacts and if s/he has experienced any new 
social impacts as a result of the trial participation); 
 
Assessment of new or continuing concomitant medications (as described in Section 
9.2); and 
 
Assessment of new or unresolved AEs/intercurrent illnesses. 
Additional procedures will be performed at scheduled follow-up visits as specified in 
Appendix E and Appendix F:  
 
Administration of an EP acceptability questionnaire; 
 
Administration of behavioral risk assessment questionnaire; 

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 
Administration of the social impact assessment questionnaire (types of impacts 
assessed involve personal relationships, health insurance, life insurance, educational 
or employment opportunities, housing, immigration, or travel); 
 
Administration of a questionnaire that asks the participant about any HIV testing he 
or she may have received outside of the study. Participants will also be asked whether 
they believe they received the active vaccine or the control; 
 
HIV infection assessment including pre-test counseling. A subsequent follow-up 
contact is conducted to provide post-test counseling and to report results to 
participant; 
 
Confirm that participants received HIV test results from previous visit. If not, provide 
test results and post-test counseling as appropriate; 
 
Abbreviated physical examination including weight, vital signs, and a symptom-
directed evaluation by history and/or appropriate physical exam based on participant 
self-reported symptoms or complaints; 
 
Complete physical examination, including weight, vital signs, and clinical 
assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; heart; chest; 
abdomen; extremities; neurological function; and skin; 
 
Specimen collection; 
 
Clinical laboratory tests including: 
 
CBC with differential, 
 
Chemistry panel (see Section 9.2), and 
 
Urine dipstick (urinalysis if appropriate; see Section 9.8); and 
 
Urine or serum pregnancy test (for participants who were born female). 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. 
9.5 
Month 18 health contact 
CRS staff will contact study participants at their Month 18 timepoint to collect the 
information listed below. Clinic visits will only be required if HIV confirmatory testing is 
necessary (see Section 9.6.1); however, a clinic visit may be arranged for other reasons. 
 
Confirmation of vital status; if deceased, attempt to learn cause and date of death 
 
If participant is alive, record any of the following events: 
 
New AEs related to study product(s), including: 
o Life threatening adverse experiences; 

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o Persistent or significant disability/incapacity; 
o Hospitalizations and reasons; 
o Other important medical events that may jeopardize the participant or 
may require intervention to prevent 1 of the other outcomes listed above; 
o New chronic conditions requiring more than 30 days of medical 
intervention or medication; 
o Other related AEs. 
 
AESI (Section 11.2.2). A sample list of AESI is provided in Appendix G. AESI 
are reported regardless of relationship to study product(s); 
 
New diagnosis of HIV infection; and 
 
Pregnancies and outcomes, including congenital anomalies/birth defects. 
All such events will be recorded and adverse events will be assessed for relationship to 
study products. A safety monitoring team reviews reports from these contacts quarterly. 
This monitoring team comprises a DAIDS Medical Officer, Core medical monitor, and a 
clinical safety specialist (CSS). Other questions may be added by the HVTN 119 Protocol 
Team for exploratory endpoints. 
 
Interim contacts 
9.5.1
CRSs may report safety information obtained at a contact other than the annual contact. 
These contacts are reported as interim visits. 
9.6 
HIV counseling and testing 
HIV counseling will be performed in compliance with the CDC’s guidelines or other 
local guidelines for HIV counseling and referral. HIV testing will be performed in 
accordance with the current HVTN HIV testing algorithm following enrollment. 
Participants will be counseled routinely during the trial on the avoidance of HIV infection 
and on the potential negative social impacts of testing antibody positive due to the 
vaccine. They will also be counseled on the risks of HIV antibody testing outside of the 
HVTN CRSs and will be discouraged from doing so during study participation and/or 
during any period of vaccine-induced positive serology. 
Study staff will take particular care to 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. Such testing has become more likely due to the 
CDC’s revised guidelines for HIV counseling and testing, as well as policy changes in 
many countries to make HIV testing more frequent and routine. CRS staff should 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 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 

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reported to local public health authorities. CRS staff should also inform participants of 
the need to maintain study blinding by getting HIV testing only at the study CRS. 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 vaccine clinical trial and should only be tested at the study CRS. 
Potential participants identified as being HIV infected during screening are not enrolled. 
All participants who become HIV infected during the study will be terminated from this 
study. Potential and enrolled participants identified as HIV infected will be referred for 
medical treatment, counseling, and management of the HIV infection. These individuals 
may also be referred to appropriate ongoing clinical trials or observational studies. 
 
Distinguishing intercurrent HIV infection from vaccine-induced positive serology 
9.6.1
The study product may elicit an antibody response to HIV proteins. Therefore, vaccine-
induced positive serology may occur in this study. Several precautionary measures will 
be taken to distinguish intercurrent HIV infection from vaccine-induced positive 
serology. These precautionary measures include: 
 
Participants will have physical examinations at visits specified in Appendix F. Signs 
or symptoms of an acute HIV infection syndrome, an intercurrent illness consistent 
with HIV-1 infection, or probable HIV exposure would prompt a diagnostic workup 
per the HVTN algorithm for Recent Exposure/Acute Infection Testing to determine 
HIV infection. 
 
HIV testing will be performed at multiple timepoints throughout the study (see 
Appendix F). The Laboratory Program (or approved diagnostic laboratory) will 
follow the HVTN HIV testing algorithm (as described in the HVTN Laboratory 
Manual of Operations), which is able to distinguish vaccine-induced antibody 
responses from actual HIV infections.  
 
All participants can receive HIV-1 diagnostic testing from the site following their last 
scheduled visit until they are told that they did not receive an HIV vaccine or that 
they do not have vaccine-induced seropositivity. 
 
All participants who received vaccine product and who have vaccine-induced 
positive or indeterminate HIV-1 serology (as measured by the standard anti-HIV 
antibody screening tests) at or after the study is unblinded will be offered poststudy 
HIV-1 diagnostic testing (per the HVTN poststudy HIV-1 testing algorithm) 
periodically and free of charge as medically/socially indicated (approximately every 
6 months) unless or until HIV Ab testing is no longer the standard test in clinical 
settings.  
 
VISP registry  
9.6.2
Experimental HIV vaccines may induce antibody production to HIV antigens, producing 
reactive results on commercially available HIV test kits. This is called “vaccine-induced 
seropositivity” (VISP) (see Section 9.6.1). In order to provide post-study HIV testing to 
distinguish between VISP and HIV infection, and to mitigate potential social harms 
resulting from VISP in HIV vaccine recipients who are not infected with HIV, the HVTN 
has created a VISP registry. Following study unblinding, the registry will allow trained 
staff to verify that an individual has received an HIV vaccine, and therefore has the 

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potential for VISP. Information in the VISP registry will not be used for research. Rather, 
the registry exists to support provision of post-study testing and counseling services to 
HIV vaccine recipients. The registry contains the names of all study participants, unless 
they request that their names be removed. 
9.7 
Contraception status 
Contraception status is assessed and documented at every scheduled clinic visit for a 
participant who was born female and who is sexually active in a way that could cause that 
participant to become pregnant. Prior to enrollment and throughout the study, staff will 
ask participants to verbally confirm their use of adequate contraceptive methods. A 
participant who was born female and is sexually active in a way that could cause that 
participant to become pregnant should be reminded at all scheduled clinic visits of the 
importance of using contraception and should be referred to specific counseling, 
information, and advice as needed. (Specific contraception requirements are listed in 
Section 7.1). This reminder should be documented in the participant’s study record. 
Self-reported infertility—including having reached menopause (no menses for 1 year) or 
having undergone hysterectomy, bilateral oophorectomy, or tubal ligation—must be 
documented in the participant’s study record. 
9.8 
Urinalysis 
Dipstick testing may be performed in the clinic or the lab, as long as the required 
elements (glucose, protein, and hemoglobin) are tested. The examination is performed on 
urine obtained by clean catch. 
If the screening dipstick is transiently abnormal due to menses or infection, document this 
issue in the participant’s source documentation. For infection, provide appropriate 
treatment and/or referral. Following resolution, repeat the dipstick and, if within the 
eligibility limits specified in the protocol, the participant may be enrolled. 
Follow-up urinalysis should be deferred if a participant is menstruating, but should be 
performed as soon as possible. If a follow-up dipstick is abnormal due to a participant’s 
menstrual period, document in the comment section of the case report form (CRF) and 
repeat the dipstick once the participant is no longer menstruating. A micro-urinalysis is 
not required. 
9.9 
Assessments of reactogenicity 
For all participants, baseline assessments are performed before and reactogenicity 
assessments are performed after each vaccination. All reactogenicity symptoms are 
followed until resolution and graded according to the Division of AIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 
2014, except as noted in Section 11.2.2. 
The reactogenicity assessment period is 7 full days following each vaccination per the 
assessment schedule shown in Table 9-1. Participants are instructed to record symptoms 

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using a postvaccination memory tool. Contact between the participant and the site staff 
should take place at least once between 1-3 days postvaccination, and for events that arise 
during the period between vaccination and the next scheduled visit. In general, a 
participant who self-reports any postvaccination reaction greater than mild is seen by a 
clinician within 48 hours after onset, unless the reaction is improving and/or has 
completely resolved. Clinic staff will follow new or unresolved reactogenicity symptoms 
present at day 7 to resolution. 
Reactogenicity events are reported using CRFs that correspond to the time of assessment 
in Table 9-1. Reactogenicity assessments include assessments of systemic and local 
symptoms, vaccine-related lesions, and lymph nodes. Events not listed on a CRF, or with 
an onset after the reactogenicity assessment period (day of vaccination and 7 full days 
after), or those meeting SAE/adverse events requiring expedited reporting to DAIDS 
criteria, are recorded on an adverse experience log form. 
Table 9-1 Schedule of reactogenicity assessments 
Day 
Time 
Performed by 
0a 
Baseline: before vaccination 
HVTN CRS staff 
 
Early: 25-60 minutes after vaccination 
HVTN CRS staff 
 
Between early assessment and 11:59pm day 0 
HVTN CRS staff or participant 
1-7b 
Between 12:00am and 11:59pm on the respective 
day 
HVTN CRS staff or participant 
a Day of vaccination 
b New or unresolved reactogenicity symptoms present on day 7 are followed until resolution 
 
Assessment of systemic and local symptoms 
9.9.1
Systemic symptoms include increased body temperature, malaise and/or fatigue, myalgia, 
headache, chills, arthralgia, nausea, and vomiting. Local symptoms include pain and/or 
tenderness proximal to the injection site. The daily maximum severity reached for each 
symptom during the assessment period is reported.  
Body temperature is measured by oral or infrared thermometry and reported in degrees 
Celsius. If temperature is measured in Fahrenheit, the conversion to Celsius should be 
documented in the participant’s chart note. A measurement is taken once daily during the 
assessment period and should be repeated if participant is feeling feverish. 
 
Assessment of injection site 
9.9.2
Typical injection site reactions are erythema/redness and induration/swelling. The 
maximum horizontal and maximum vertical measurements for all injection site reactions 
are recorded. 
All injection site reactions are monitored until resolution. Areas greater than 25 cm2 are 
followed daily; otherwise, the frequency of follow-up is based on clinician judgment. 
 
Visual Analog Scale (Pain Scale) 
9.9.3
Participant pain will be assessed using a VAS immediately following EP, then again 5-7 
minutes and 25-60 minutes following vaccination. A VAS is a horizontal line, 10 cm in 
length, anchored by word descriptors at each end (“no pain” and “worst pain”). The VAS 
score is determined by measuring in centimeters from the left hand end of the line to the 
point that the patient marks, 0 cm being no pain and 10 cm being maximum pain.  

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Assessment of lymph nodes 
9.9.4
This assessment is required only when reactogenicity assessments are performed by 
HVTN CRS staff, not by the participant. 
Only the proximally draining lymph nodes are assessed (eg, axillary nodes on the same 
side of the body for injections given in the deltoid). Lymph nodes are first evaluated for 
enlargement and tenderness. If they are found to be enlarged, measurements are taken to 
determine the size (widest diameter) of the enlarged node(s). 
9.10 
Visit windows and missed visits 
Visit windows are defined in HVTN 119 Study Specific Procedures. For a visit not 
performed within the window period, a Missed Visit form is completed. If the missed 
visit is one that required safety assessments or local safety labs, HVTN CRS staff should 
attempt to bring the participant in for an interim visit as soon as possible. 
Procedures performed at an interim visit are usually toxicity/safety assessments 
(including local safety labs) and HIV testing. With the exception of HIV testing, these 
procedures are performed only if they were required at the missed visit or if clinically 
indicated. HIV testing may be performed as deemed appropriate by the study staff. Blood 
samples for immunogenicity assays are not typically collected at interim visits. 
If a missed visit required vaccination, please refer to Section 7.3.2 and Section 7.3.3 for 
resolution. 
9.11 
Early termination visit 
In the event of early participant termination, site staff should consider if the following 
assessments are appropriate: a final physical examination, clinical laboratory tests 
(including urine dipstick, CBC with differential, and chemistry panel), pregnancy testing, 
social impact assessment, and HIV test. 
9.12 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more injections of 
study product will be given, but remaining visits and study procedures should be 
completed unless medically contraindicated or applicable regulations require termination 
from the study. In case of required termination, enrollment in an observational study 
should be offered to the participant. 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. 

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10 
Laboratory 
10.1 
HVTN CRS laboratory procedures 
The HVTN Site Processing Lab Instructions and study-specific procedures (SSP) provide 
further guidelines for operational issues concerning the clinical and processing 
laboratories. The manual includes guidelines for general specimen collection, special 
considerations for phlebotomy, specimen labeling, whole blood processing, HIV 
screening/diagnostic testing, and general screening and safety testing. 
Tube types for blood collection are specified in Appendix E. For tests performed locally, 
the local lab may assign appropriate tube types. 
In specific situations, the blood collection tubes may be redirected to another laboratory 
or may require study-specific processing techniques. In these cases, laboratory special 
instructions will be posted on the protocol-specific section of the HVTN website. 
10.2 
Total blood volume 
Required blood volumes per visit are shown in Appendix E. 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 
Primary immunogenicity timepoints 
The primary immunogenicity timepoints in this study are at visits 6 (day 42) (ie, 2 weeks 
after the 2nd vaccination visit) and 11 (day 182) (ie, 2 weeks after the 4th vaccination 
visit). Endpoint assays for humoral and cellular responses are performed on participants 
at the primary immunogenicity timepoints and may be performed at baseline. Depending 
on the number of responders observed, assays for humoral and cellular responses may be 
performed on participants at other timepoints; the schedule is shown in Appendix E. 
10.4 
Endpoint assays: cellular 
10.4.1 
Flow cytometry 
Flow cytometry will be used to examine vaccine-specific CD4+ and CD8+ T-cell 
responses following stimulation of PBMCs with synthetic HIV peptides that span the 
proteins encoded by the vaccine construct, including pools covering individual CE 
regions. ICS parameters will include cytokines such as IFN-γ, IL-2, and TNF-α, and may 
include other cytokines and phenotypic markers to identify T cells of specific 
functionality (such as Th2 and Tfh). Markers of cytotoxic potential (eg, granzyme B) 
must also be included. Data will be reported as percentages of CD4+ or CD8+ T cells 

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responding to a specific peptide pool. Additional cell surface markers, cytokines, or 
functional markers may also be analyzed. 
10.4.2 
IFN-γ ELISpot (Epitope Mapping) 
Ex vivo HIV-specific T-cells will be assessed by IFN-γ ELISpot for epitope mapping. To 
this end, PBMCs will be stimulated overnight with synthetic peptide pools that span the 
proteins encoded by the vaccine constructs, including separate pools containing only CE 
peptides. Samples with positive responses in this first round of testing will then be tested 
in a second round using individual peptides comprised in the pools to identify responses 
to individual epitopes. Data will be reported as the number of spot-forming cells (SFC) 
per 106 cells recognizing a specific peptide or peptide pool. 
10.5 
Endpoint assays: humoral 
10.5.1 
HIV-1 multiplex antibody assay 
IgG antibodies to Clade B Gag and p24CE will be assessed on plasma/serum samples 
from study participants taken at the primary immunogenicity timepoint and baseline. 
Specimens from other timepoints as well as other HIV antigens may also be assayed 
based on the results of the initial assay.  
10.6 
Genotyping 
Molecular human leukocyte antigen (HLA) typing may be performed on enrolled 
participants using cryopreserved PBMC collected at baseline, initially on specimens from 
participants who demonstrate vaccine-induced T-cell responses at post vaccination 
timepoints. Other participants (including control recipients) may be HLA-typed to 
support future studies of immunological interest at the discretion of the HVTN 
Laboratory Program. Other markers, such as genes associated with immune responses or 
HIV-1disease progression may also be assessed.  
10.7 
Lab assay algorithm 
The Lab Assay Algorithm lists assays to characterize cellular, humoral, and innate 
immune responses as well as host genetics that may be conducted to determine endpoints 
in HVTN vaccine trials. The type of assay(s) employed will be dependent on the response 
obtained by the primary immunogenicity assays at relevant time points. Please note that 
the Lab Assay Algorithm will be updated periodically to include new assays. 
10.8 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV immunology 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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T-cell repertoire  
10.8.1
Specimens collected at primary immunogenicity timepoints may be compared to those 
collected at baseline in order to examine evolution of vaccine-induced immune responses 
by HIV-specific CD4+ T helper cells. Studies that can be performed include detailed T 
cell receptor alpha beta T cell receptor usage, mapping of epitope-specific responses after 
transfection of TCR alpha and beta chains into reporter cell lines, and transcriptome 
analysis of epitope-specific T cells. 
10.9 
Other use of stored specimens 
The HVTN stores specimens from all study participants indefinitely, unless a participant 
requests that specimens be destroyed or if required by IRB/EC, or RE. 
Other use of specimens is defined as studies not described in the protocol. 
This research may relate to HIV, vaccines, the immune system, and other diseases. This 
could include limited genetic testing and, potentially, genome-wide studies. This research 
is done only to the extent authorized in each study site’s informed consent form, or as 
otherwise authorized under applicable law. Other testing on specimens will occur only 
after review and approval by the HVTN, the IRB/EC of the researcher requesting the 
specimens, and the CRS’s IRBs/ECs if required. 
The protocol sample informed consent form is written so that the participant either 
explicitly allows or does not allow their samples to be used in other research when they 
sign the form. Participants who initially agree to other use of their samples may rescind 
their approval once they enter the study; such participants will remain in this study and 
their samples will only be used for the studies described in this protocol. If a participant 
decides against allowing other research using his or her samples, or at any time rescinds 
prior approval for such other use, the study site investigator or designee must notify 
HVTN Regulatory Affairs in writing. In either case, HVTN Regulatory Affairs directs the 
HVTN Lab Program not to use samples from these participants for such other uses.  
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on other use of specimens. 
10.10 
Biohazard containment 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, and blood products, appropriate precautions will be 
employed by all personnel in the drawing of blood and shipping and handling of all 
specimens for this study, as currently recommended by the CDC and the NIH or other 
applicable agencies. 
All dangerous goods materials, including Biological Substances, Category A or Category 
B, must be transported according to instructions detailed in the International Air 
Transport Association Dangerous Goods Regulations. 

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11 
Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
 
HVTN 119 PSRT 
11.1.1
The HVTN 119 PSRT is composed of the following members: 
 
DAIDS medical officer representative, 
 
Protocol chair and cochair, 
 
Protocol Team leader, 
 
Core medical monitor, and 
 
Clinical safety specialist. 
The clinician members of HVTN 119 PSRT are responsible for decisions related to 
participant safety. 
The Protocol Team clinic coordinator, clinical data manager, vaccine and device 
developer representatives, clinical trial manager, and others may also be included in 
HVTN 119 PSRT meetings. 
 
HVTN SMB 
11.1.2
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, and 
experts in HIV vaccine research that, collectively, has experience in the conduct and 
monitoring of vaccine trials. Members of the SMB are not directly affiliated with the 
protocols under review.  
The SMB reviews safety data, unblinded as to treatment arm, approximately every 4 
months. The reviews consist of evaluation of cumulative reactogenicity events, AE, 
laboratory safety data, and individual reports of adverse events requiring expedited 
reporting to DAIDS. To increase the sensitivity for detecting potential safety problems, 
the SMB will review safety data aggregated across multiple protocols that use the same 
or similar vaccine candidates. The SMB conducts additional special reviews at the 
request of the HVTN 119 PSRT.  
Study sites will receive SMB summary minutes and are responsible for forwarding them 
to their IRB/EC and any applicable RE. 
 
SDMC roles and responsibilities in safety monitoring  
11.1.3
The roles and responsibilities of the SDMC in relation to safety monitoring include: 
 
Maintaining a central database management system for HVTN clinical data; 

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 
Providing reports of clinical data to appropriate groups such as the HVTN 119 PSRT 
and HVTN SMB (see Section 11.1.2); 
 
HVTN Core roles and responsibilities in safety monitoring 
11.1.4
 
Daily monitoring of clinical data for events that meet the safety pause and HVTN 
119 PSRT AE review criteria (see Section 11.4); 
 
Notifying HVTN CRSs and other groups when safety pauses or planned holds are 
instituted and lifted (see Section 11.4); 
 
Querying HVTN CRSs for additional information regarding reported clinical data; 
and 
 
Providing support to the HVTN 119 PSRT. 
11.2 
Safety reporting 
 
Submission of safety forms to SDMC 
11.2.1
Sites must submit all safety forms (eg, reactogenicity, adverse experience, urinalysis, 
local lab results, concomitant medications) before the end of the next business day after 
receiving the information. The forms should not be held in anticipation of additional 
information at a later date. If additional information is received at a later date, the forms 
should be updated and resubmitted before the end of the next business day after receiving 
the new information. 
 
AE reporting 
11.2.2
An AE is any untoward medical occurrence in a clinical investigation participant 
administered a study product/procedure(s) and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an investigational study product/procedure(s), whether or not 
related to the investigational study product/procedure(s). All AEs are graded according to 
the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events, Version 2.0, November 2014, available on the RSC website at http://rsc.tech-
res.com/docs/default-source/safety/daids_ae_grading_table_v2_nov2014.pdf, except: 
 
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 119 Study Specific 
Procedures); 
 
Injection Site Erythema or Redness and Injection Site Induration or Swelling will not 
consider interference with usual social and functional activities such that: 
 
Grade 1 is: 2.5 to < 5 cm in diameter OR 6.25 to < 25 cm2 surface area; 
 
Grade 2 is: ≥ 5 to < 10 cm in diameter OR ≥ 25 to < 100 cm2 surface area; 
 
Grade 3 is: ≥ 10 cm in diameter OR ≥ 100 cm2 surface area OR Ulceration OR 
Secondary infection OR Phlebitis OR Sterile abscess OR Drainage; 

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 
Grade 4 is: Potentially life-threatening consequences (eg, abscess, exfoliative 
dermatitis, necrosis involving dermis or deeper tissue); 
 
The grading of Insomnia events will consider the criteria within the Insomnia 
parameter as well as the general AE functional table such that: 
 
Grade 1 is: Mild difficulty falling asleep, staying asleep, or waking up early 
causing no or minimal interference with usual social and functional activities 
with intervention not indicated; 
 
Grade 2 is: Moderate difficulty falling asleep, staying asleep, or waking up early, 
causing greater than minimal interference with usual social and functional 
activities with intervention indicated; 
 
Grade 3 is: Severe difficulty falling asleep, staying asleep, or waking up early, 
causing inability to perform usual social & functional activities with intervention 
or hospitalization indicated. 
If a definition of insomnia falls between 2 grades, the final grading will be selected based 
on the degree of interference with usual social and functional activities caused by the 
symptoms. 
All AEs are reported to the SDMC on the appropriate CRF. Clinic staff should evaluate 
every AE to determine if (1) the AE meets the requirements for expedited reporting to 
DAIDS (Section 11.2.3) and (2) if the AE meets the criteria for a safety pause/prompt AE 
review (Section 11.4) and (3) if the AE is an AESI. A sample list of AESI is provided as 
Appendix G. 
Sites are expected to notify the CSS of any serious safety concern requiring their 
attention (see Table 11-1). Telephone numbers and email addresses are found on the 
protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn119). Concerns requiring immediate attention 
should be communicated by calling the clinical safety phone. 
In the case of email notification, the CSS will reply during working hours (US Pacific 
Time) to confirm that the email has been received and reviewed. If email service is not 
available, the HVTN CRS should notify the CSS of the event by telephone, then submit 
CRFs. 
In addition, site investigators are required to submit AE information in accordance with 
IRB/EC and any applicable RE requirements. 
 
Expedited reporting of adverse events to DAIDS 
11.2.3
Requirements, definitions and methods for expedited reporting of AEs are outlined in 
Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to 
DAIDS (DAIDS EAE Manual), which is available on the RSC website at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting. 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 reporting to DAIDS. In the event of system outages or technical 
difficulties, expedited AE reports may be submitted via the DAIDS EAE Form. For 

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questions about DAERS, please contact CRMSsupport@niaid.nih.gov or from within the 
DAERS application itself.  
For questions about expedited AE reporting, please contact the RSC 
(DAIDSRSCSafetyOffice@tech-res.com).  
The study products for which expedited reporting are required are:  
 
p24CE1/2 pDNA or placebo 
 
p55gag pDNA or placebo 
 
IL-12 pDNA or placebo 
 
Intramuscular TriGrid Delivery System (TDS-IM) electroporation device  
While the participant is in the main study reporting period (See Section 3), the SAE 
Reporting Category will be used.  
If the participant has completed the main study (visit 13, Month 12) and is in the “follow-
up health contact” reporting period (see Section 3) the SUSAR Reporting Category will 
be used (In addition, please note, per Section 9.5, all adverse events that are serious are 
collected on the month 18 Health Contact Event Log and reported to SCHARP.) 
After the participant has completed the month 18 health contact and is off study, sites 
must report SUSARS if the study site staff becomes aware of the events on a passive 
basis (eg, from publicly available information) 
The NIAID/DAIDS will report all unexpected SAEs related to the study products 
observed in this clinical trial to the FDA in accordance with 21 CFR 312.32 (IND Safety 
Reports). However, because safety is a primary study endpoint, the Sponsor Medical 
Officer will not routinely be unblinded to study treatment assignment when there is an 
assessment of relatedness of the SAE with the study product(s); and the safety report will 
be sent to the FDA based on the blinded attribution assessment. 
If the PSRT believes unblinding of the site PI to treatment assignment will assist with the 
clinical management of the SAE, the PSRT will consult the independent HVTN SMB for 
a recommendation. In the event the HVTN SMB determines that unblinding is indicated, 
the SMB will inform the site physician of the participant’s treatment assignment in such a 
manner as to maintain the study blind of the PSRT and study team. For additional impact 
and management of SAEs on the study, refer to Section 11.4. 
11.3 
Safety reviews 
 
Initial safety evaluation 
11.3.1
Enrollment across all participating HVTN CRSs will be restricted to a maximum of 1 
participant per day and restricted to US sites until 10 participants have been enrolled. The 
HVTN 119 PSRT will review the cumulative safety data including at minimum local and 
systemic reactogenicity data reported for the first 72 hours postvaccination on each of 

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these 10 participants, and will determine whether it is safe to proceed with full 
enrollment.  
11.4 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and vaccinations will be held until 
further notice. The AEs that will lead to a safety pause or prompt HVTN 119 PSRT AE 
review are summarized in Table 11-1. Vaccinations 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 119 PSRT, participant safety may be threatened. Criteria for an 
individual participant’s departure from the schedule of vaccinations are listed in Section 
7.3. 
Table 11-1 AE notification and safety pause/AE review rules 
Event and 
relationship to study 
products 
Severity 
HVTN CRS actiona 
HVTN Core action 
SAE, related 
Grade 5 or 
Grade 4 
Phone immediately, email 
and submit forms 
immediately 
Immediate pause 
SAE, not related 
Grade 5 
Phone immediately, email 
and submit forms 
immediately 
Immediate HVTN 119 
PSRT notification 
SAE, related 
Grade 3 
Email and submit forms 
immediately 
Prompt HVTN 119 PSRT 
AE review to consider 
pause 
AEb, related 
Grade 4 or 
3 
Email and submit forms 
immediately 
Prompt HVTN 119 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/hvtn119). 
b Does not include subjective reactogenicity symptoms (injection site pain, tenderness, fatigue/malaise, myalgia, arthralgia, chills, headache, 
nausea). 
For all safety pauses, HVTN Core notifies the HVTN 119 PSRT, HVTN Regulatory 
Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), DAIDS Regulatory Affairs 
Branch (RAB), DAIDS Safety and Pharmacovigilance Team (SPT), and participating 
HVTN CRSs. When an immediate safety pause is triggered, HVTN Core notifies the 
SMB.  
Once a trial is paused, the HVTN 119 PSRT reviews safety data and decides whether the 
pause can be lifted or permanent discontinuation of vaccination is appropriate, consulting 
the SMB if necessary. HVTN Core notifies the participating HVTN CRSs, HVTN 
Regulatory Affairs, DAIDS PAB, DAIDS RAB, and DAIDS SPT of the decision 
regarding resumption or discontinuation of study vaccinations. Based on the HVTN 119 
PSRT assessment, DAIDS RAB notifies the FDA as needed. 
If an immediate HVTN 119 PSRT notification or prompt HVTN 119 PSRT AE review is 
triggered, HVTN Core notifies the HVTN 119 PSRT as soon as possible during working 
hours (US Pacific Time)—or, if the information was received during off hours, by the 
morning of the next work day. If a prompt HVTN 119 PSRT AE review cannot be 

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completed within 72 hours of notification (excluding weekends and US federal holidays), 
an automatic safety pause occurs. 
The HVTN requires that each CRS submit to its IRB/EC and any applicable RE protocol-
related safety information (such as IND safety reports, notification of vaccine holds due 
to the pause rules, and notification of other unplanned safety pauses). CRSs must also 
follow all applicable RE reporting requirements. 
In addition, all other AEs are reviewed routinely by the HVTN 119 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 HVTN CRSs. Events are 
tracked by internal reports until resolution.  
 
Daily review 
11.5.1
Blinded 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 119 PSRT AE review criteria. 
 
Weekly review 
11.5.2
During the injection phase of the trial, the HVTN 119 PSRT reviews clinical safety 
reports on a weekly basis and conducts calls to review the data as appropriate. After the 
injections and the final 2-week safety visits are completed, less frequent reporting and 
safety reviews may be conducted at the discretion of the HVTN 119 PSRT. HVTN Core 
reviews reports of clinical and laboratory AEs. Events identified during the review that 
are considered questionable, inconsistent, or unexplained are referred to the HVTN CRS 
clinic coordinator for verification. 
11.6 
Study termination 
This study may be terminated early by the determination of the HVTN 119 PSRT, a 
pertinent national regulatory authority, NIH, Office for Human Research Protections 
(OHRP), FDA, or vaccine developer(s). In addition, the conduct of this study at an 
individual HVTN CRS may be terminated by the determination of the IRB/EC and any 
applicable RE. 

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12 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICHe6), and according to DAIDS and HVTN 
policies and procedures as specified in the HVTN Manual of Operations, DAIDS Clinical 
Research Policies and Standard Procedures Documents including procedures for the 
following: 
 
Protocol registration, activation, and implementation; 
 
Informed consent, screening, and enrollment; 
 
Study participant reimbursement; 
 
Clinical and safety assessments; 
 
Safety monitoring and reporting; 
 
Data collection, documentation, transfer, and storage; 
 
Participant confidentiality; 
 
Study follow-up and close-out; 
 
Unblinding of staff and participants; 
 
Quality control; 
 
Protocol monitoring and compliance; 
 
Advocacy and assistance to participants regarding negative social impacts associated 
with the vaccine trial; 
 
Risk reduction counseling;  
 
Specimen collection, processing, and analysis;  
 
Ancillary studies, and 
 
Destruction of specimens. 
Any policies or procedures that vary from DAIDS and HVTN standards or require 
additional instructions (eg, instructions for randomization specific to this study) will be 
described in the HVTN 119 Study Specific Procedures.  

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12.1 
Social impacts 
Participants in this study risk experiencing discrimination or other personal problems, 
resulting from the study participation itself or from the development of VISP. The HVTN 
CRS is obliged to provide advocacy for and assistance to participants regarding these 
negative social impacts associated with the vaccine trial. If HVTN CRS staff have 
questions regarding ways to assist a participant dealing with a social impact, a designated 
NIAID or HVTN Core representative can be contacted.  
Social harms are tabulated by the SDMC and are subjected to descriptive analysis. The 
goal is to reduce their incidence and enhance the ability of study staff to mitigate them 
when possible. 
Summary tables of social impact events will be generated weekly, and made available for 
review by the protocol chairs, protocol team leader, and the designated NIAID 
representative. 
12.2 
Compliance with NIH guidelines for research involving products 
containing recombinant or synthetic Nucleic Acid Molecules 
Because this study is evaluating products containing recombinant or synthetic DNA, it 
must comply with regulations set forth in the NIH Guidelines for Research Involving 
Recombinant or Synthetic Nucleic Acid Molecules (April 2016). Information about the 
study must be submitted to site Institutional Biosafety Committees (IBCs) and 
Institutional Review Boards/Ethics Committees (IRBs/ECs). IBCs and IRBs/ECs must 
provide a written assessment of whether Recombinant DNA Advisory Committee (RAC) 
review is warranted. In exceptional cases that meet specific criteria outlined in the NIH 
Guidelines Appendix M-I-B, IBCs and IRBs/ECs assessment can include a request for 
RAC review. Regardless of the potential for RAC review, the HVTN and DAIDS will 
register the protocol with the NIH Office of Scientific Policy (OSP). The Protocol Team, 
jointly with Profectus BioSciences, Inc., will prepare the NIH OSP registration 
documents. 
Investigators at each site are responsible for obtaining IBC approval per NIH Guidelines 
section IV-B7-a-(1). IBC review and approval must be documented by the investigator 
and submitted as part of DAIDS’s initial protocol registration for this trial before 
participants are enrolled at the site. If this protocol is amended, investigators should 
follow the requirements of their IBC. 
The HVTN and DAIDS will ensure that reporting requirements to NIH OSP, as outlined 
in Appendix M-I-C-1.Initiation of the Clinical Investigation, Appendix M-I-C-
2.Additional Clinical Trial Sites. Appendix M-I-C-3.Annual Reports and Appendix M-I-C-
4.Safety Reporting are satisfied per the NIH Guidelines. 
12.3 
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.  

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When such communication is needed, the CRS will request that its IRB/EC and any 
applicable RE expedite review of the message. If this review cannot be completed in a 
timeframe consistent with the urgency of the required communication, the site should 
contact the participant first, and then notify the IRB/EC and any applicable RE of the 
matter as soon as possible. 

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13 
Version history 
The Protocol Team may modify the original version of the protocol. Modifications are 
made to HVTN protocols via clarification memos, letters of amendment, or full protocol 
amendments.  
The version history of, and modifications to, Protocol HVTN 119 are described below. 
Protocol history and modifications 
Date: February 17, 2017 
Protocol version: 1.0 
Protocol modification: 
Original protocol 
 

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14 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant to the 
conduct of this study, include: 
 
Assessment of Understanding. Accessible through the HVTN protocol-specific 
website. 
 
Current CDC Guidelines. Revised Recommendations for HIV Testing of Adults, 
Adolescents, and Pregnant Women in Health-Care Settings. Available at 
http://www.cdc.gov/mmwr/PDF/rr/rr5514.pdf.  
 
Division of AIDS (DAIDS) Clinical Research Policies and Standard Procedures 
Documents. Available at https://www.niaid.nih.gov/research/daids-clinical-research-
policies-standard-procedures 
 
Division of AIDS Protocol Registration Manual. Available at 
https://www.niaid.nih.gov/sites/default/files/documents/prmanual.pdf 
 
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events. Version 2.0, November 2014. Available at http://rsc.tech-
res.com/docs/default-source/safety/daids_ae_grading_table_v2_nov2014.pdf 
 
The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 2.0, 
January 2010. Available at http://rsc.tech-res.com/clinical-research-sites/safety-
reporting/manual 
 
HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
 
HVTN 119 Special Instructions. Accessible through the HVTN protocol-specific 
website. 
 
HVTN 119 Study Specific Procedures. Accessible through the HVTN protocol-
specific website. 
 
HVTN 119 Site Lab Instructions. Accessible through the HVTN protocol-specific 
website. 
 
HVTN Laboratory Manual of Operations. Accessible through the HVTN website. 
 
HVTN Manual of Operations. Accessible through the HVTN website. 
 
Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
http://www.iata.org/publications/dgr/Pages/index.aspx 
 
Lab assay algorithm 

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HVTN119_v1.0_FINAL / Page 99 of 140 
 
HVTN algorithm for diagnosis of HIV infections. Part of the HVTN Laboratory 
Manual of Operations (see above). 
 
International Conference on Harmonisation (ICH) E6 (R1), Guideline for Good 
Clinical Practice: Section 4.8, Informed consent of trial subjects. Available at 
http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html 
 
Participants’ Bill of Rights and Responsibilities. Accessible through the HVTN 
website. 
 
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid 
Molecules. Available at 
http://osp.od.nih.gov/sites/default/files/resources/NIH_Guidelines.pdf 
 
NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical Research. 
Available at http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-01-053.html. 
 
Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks, July 
2008. 
 
Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials. Available at https://www.niaid.nih.gov/research/daids-clinical-site-
implementation-operations 
 
Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=5
0 
 
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 
AA 
amino acid 
Ab 
antibody 
AE 
adverse event 
AESI 
AEs of special interest 
ALT 
alanine aminotransferase 
ANOVA 
analysis of variance 
AST 
aspartate aminotransferase 
β-HCG 
beta human chorionic gonadotropin 
BMI 
body mass index 
CAB 
Community Advisory Board 
CBC 
complete blood count 
CDC 
US Centers for Disease Control and Prevention 
CE 
conserved elements 
CFR 
Code of Federal Regulations 
CI 
confidence intervals 
CPK 
creatine phosphokinase 
CRF 
case report form 
CRPMC 
NIAID Clinical Research Products Management Center 
CRS* 
clinical research site 
CTL 
cytotoxic T lymphocyte 
DAERS 
DAIDS Adverse Experience Reporting System 
DAIDS 
Division of AIDS (US NIH) 
DHHS 
US Department of Health and Human Services 
DSMB 
NIAID Data and Safety Monitoring Board 
EAE 
adverse events requiring expedited reporting to DAIDS 
EC 
Ethics Committee 
EDTA 
ethylenediamine tetraacetic acid 
EIA 
enzyme immunoassay 
ELISA 
enzyme-linked immunosorbent assay 
ELISpot 
enzyme-linked immunospot 
EP 
electroporation 
FDA 
US Food and Drug Administration 
FHCRC 
Fred Hutchinson Cancer Research Center 
GCP 
Good Clinical Practice 
GEE 
generalized estimating equation 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 

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HVTN 
HIV Vaccine Trials Network 
IB 
Investigator’s Brochure 
IBC 
Institutional Biosafety Committee 
ICH 
International Conference on Harmonisation 
ICS 
intracellular cytokine staining 
IFN-γ 
interferon gamma 
IM 
intramuscular 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IUD 
intrauterine device 
MAR 
missing at random 
MCAR 
missing completely at random 
MMR 
measles, mumps, and rubella 
NIAID 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
US National Institutes of Health 
OSP 
NIH Office of Scientific Policy 
OHRP 
US Office for Human Research Protections 
OPV 
oral polio vaccine 
PAB 
DAIDS Pharmaceutical Affairs Branch 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
pDNA 
plasmid DNA 
PI 
Principal Investigator 
PSRT 
Protocol Safety Review Team 
RAB 
DAIDS Regulatory Affairs Branch 
RAC 
NIH Recombinant DNA Advisory Committee 
RE 
regulatory entity 
RSC 
DAIDS Regulatory Support Center 
SAE 
serious adverse event 
SCHARP Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
statistical and data management center 
SFC 
spot-forming cell 
SIV 
simian immunodeficiency virus 
SMB 
Safety Monitoring Board 
SPT 
DAIDS Safety and Pharmacovigilance Team 
SV40 
simian virus 40 
TB 
tuberculosis 
UW-VSL University of Washington Virology Specialty Laboratory 
VISP 
Vaccine induced seropositivity 
VRC 
Vaccine Research Center (NIAID) 
* CRSs were formerly referred to as HIV Vaccine Trial Units (HVTUs). Conversion to 
use of the term CRS is in process, and some HVTN documents may still refer to HVTUs. 

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16 
Literature cited 
 
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circulating subtype B envelope. J Virol 2005;79:11214-24. 
 
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tier of AIDS vaccine design. Expert Rev Vaccines 2004;3:S151-S159. 
 
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Consensus and ancestral state HIV vaccines. Science 2003;299:1515-8. 
 
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Haynes B, Letvin NL, Walker BD, Hahn BH, Korber BT. Polyvalent vaccines for 
optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med 
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Appendix A Sample informed consent form 
Title: A phase 1 clinical trial to evaluate the safety and immunogenicity of pDNA 
vaccines expressing HIV M Group p24Gag conserved elements and/or p55Gag, 
administered with IL-12 pDNA by intramuscular electroporation, in healthy, HIV-
uninfected adult participants 
HVTN protocol number: HVTN 119 
Site: [Insert site name] 
Thank you for your interest in our research study. Please read this consent form or ask 
someone to read it to you. If you decide to join the study, we will ask you to sign or make 
your mark on this form. We will offer you a copy to keep. We will ask you questions to 
see if we have explained everything clearly. You can also ask us questions about the 
study.  
Research is not the same as treatment or medical care. The purpose of a research study is 
to answer scientific questions. 
About the study 
The HIV Vaccine Trials Network (HVTN) and [Insert site name]  are doing a study to 
test HIV vaccines. HIV is the virus that causes AIDS. 
About 56 people will take part in this study at multiple sites. The researcher in charge of 
this study at this clinic is [Insert name of site PI]. The US National Institutes of Health 
(NIH) is paying for the study.  
This study is testing HIV vaccines, and another study product called an adjuvant. The 
study will also test an experimental device, called an electroporation (EP) device, which 
delivers these products with a small electrical pulse. We will explain these terms in later 
sections. 
1. We are doing this study to answer several questions. 
 
Are the study products safe to give to people? 
 
Are people able to take the study products given with the EP device without 
becoming too uncomfortable?  
 
How do people’s immune systems respond to the study products? (Your immune 
system protects you from disease.) 
2. The study products cannot give you HIV. 
The study products are not made from actual HIV. It is impossible for the study products 
to give you HIV. Also, they cannot cause you to give HIV to someone else. 

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3. We do not know if the study products will decrease, increase, or not change your 
risk of becoming infected with HIV if you are exposed to the virus. 
Sites: Any change to the language in this section requires approval from HVTN 
Regulatory Affairs. 
Several studies have tested whether HIV vaccines can reduce the risk of getting HIV 
from another person. In some studies, people who got the vaccine seemed to have the 
same risk of getting HIV as people who did not get the vaccine. In one study, people who 
got the vaccine seemed to have a lower risk of getting HIV than people who did not get 
the vaccine. In studies with a different vaccine, some people who got the vaccine had a 
higher risk of getting HIV than people who did not get the vaccine.  
This study differs from the studies in which people who got the vaccine had a higher or 
lower risk of getting HIV. The study staff can tell you about the differences.  
We do not know whether the vaccines in this study will affect your risk of getting HIV 
from another person. The risk could be higher, lower, or unchanged. It’s very important 
to avoid exposure to HIV during and after the study. We will tell you how to avoid HIV. 
4. These study products are experimental. 
The study products are called p24CE1/2 vaccine, p55gag vaccine, and IL-12 pDNA 
adjuvant. From here on, we will call them “the study vaccines” and “the study adjuvant”. 
These study products are experimental. That means we do not know whether the study 
products will be safe to use in people, or whether they will work to prevent HIV 
infection. These study products are used only in research studies.  
There is also a placebo in this study. A placebo is a substance that does not contain 
vaccine. The placebo for the study vaccines is sterile salt water. 
The study vaccines are provided by the Division of AIDS (DAIDS). The study adjuvant 
is provided by Profectus BioSciences, Inc.  
The study vaccines are DNA vaccines that contain DNA made in the laboratory. DNA is 
a natural substance in the body that tells the body to make proteins. Proteins are natural 
substances that the body uses to build and maintain itself, as well as protect itself against 
disease. The DNA in the study vaccines tells the body to make proteins, or pieces of 
proteins, that are found in HIV. Your body’s immune system may respond to these 
proteins by helping your immune cells recognize and respond to infection. Some of these 
immune cells make antibodies, which fight infection. 
So far, experimental DNA vaccines in people have produced mostly weak immune 
responses. Sometimes vaccines work better when they are combined with another 
substance that helps to alert the immune system. These substances are called adjuvants. 
In this study, the study vaccines are always given with the study adjuvant. The study 
adjuvant is made of DNA that tells the body to make IL-12, a normal protein in the body 
that helps immune cells work together and makes them multiply. 
One of the study vaccines, the p24CE1/2 vaccine, has not been given to people before. It 
has been tested in mice and monkeys without causing health problems. Even if something 
looks like it is safe or works in animals, it may not be true for people.  

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Vaccines very similar to the p55gag study vaccine have been given to about 300 people in 
4 different studies. Some of these studies also included the study adjuvant. No serious 
health problems were found that were related to those study products. 
General risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, headache, dizziness, 
and feeling tired. Vaccines can also cause pain, redness, swelling, or itching where you 
got the injection. Most people can still do their planned activities after getting a vaccine. 
Rarely, people experience side effects that limit their normal activities or make them go 
to the doctor. 
Rarely, a vaccine can cause an allergic reaction, including a rash, hives, or difficulty 
breathing. Allergic reactions can be life-threatening. You should tell us if you have ever 
had a bad reaction to any injection or vaccine. 
Very rarely, a vaccine causes an autoimmune disease in a person, or makes an 
autoimmune disease worse. An autoimmune disease happens when your immune 
system attacks your own body, instead of attacking an infection. 
Risks of the study products: 
This section lists the side effects of the study products that we know about. There may be 
others that we don’t yet know about, even serious ones. We will tell you if we learn about 
any new side effects. 
The study vaccines and the study adjuvant are made with an anesthetic (a pain reliever) 
called bupivacaine. Bupivacaine helps DNA get into the muscle. It is similar to the 
numbing medicine used by dentists. Some people have an allergy to bupivacaine or 
similar products that are sometimes used by dentists or in anesthetic skin creams. For this 
reason we will ask if you have ever had an allergic reaction to one of these anesthetics 
before enrolling you in the study.  
Possible risks related to the study vaccines include muscle damage at the site of the 
injection, the production of antibodies which might react with normal body tissues and 
cause an autoimmune disease, and insertion of the study product’s DNA into the body’s 
DNA.  
Since 1995, thousands of people have received experimental DNA vaccines for diseases 
such as hepatitis, human papilloma virus (HPV, also known as genital warts), and HIV. 
In these people, the DNA vaccines have not caused serious side effects. We expect the 
risks of the study vaccines in this study to be similar to those of other DNA vaccines.  
In earlier studies of the study adjuvant given at lower doses, there were no severe 
reactions or serious health problems. We do not know if participants in this study will 
have similar experiences to those seen in earlier studies. 
However, with the study products, there may be new side effects that we don’t know 
about. 

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5. The study vaccines and study adjuvant are given using electroporation. 
Besides adjuvants, another way to improve immune responses to DNA vaccines is to use 
electroporation (EP). EP uses an electric pulse to briefly open tiny pores in the cells. The 
DNA can enter the cells through these pores. EP has been used for many years in the 
laboratory to get DNA or other substances into cells. Recently, a study showed that EP 
increased immune responses to another experimental DNA vaccine. 
EP is done in this study using a device called the Intramuscular TriGrid Delivery System. 
It was developed by Ichor Medical Systems, Inc. From now on we will call it “the EP 
device.” EP in people is an experimental procedure, and the EP device is an experimental 
device. The EP device is only used in people in research studies. The EP device gives an 
electrical pulse into the arm muscle where the injection is given.  
This electrical pulse is delivered to the muscle through 4 thin needles at the same time as 
the study products or placebo are given. The EP device has been tested in more than 700 
people in other studies with DNA vaccines and placebos. There were no serious side 
effects. 
In other studies, different DNA vaccines and an IL-12 pDNA adjuvant were given into 
the muscle with EP to 148 people. However this is the first time these particular study 
products will be given to people with EP. 
Risks of electroporation (EP): 
EP will cause brief muscle spasms during the procedure. In previous studies using EP, 
people felt initial pain that ranged from mild to severe. For most people, the pain eased 
quickly. EP can also cause soreness, a small amount of bleeding, bruising, redness, 
swelling, itching, or hardness/stiffness in the upper arm where you get the injection.  
Minor damage to muscle cells is also possible.  
Five percent of people (5%) felt lightheaded or faint after an injection with EP, and felt 
better after lying down. While uncommon, the EP device may cause infection at the part 
of your body where you got the injection. Rarely, people have reported numbness or a 
tingling sensation in their arm lasting several minutes. A standard injection with needle 
and syringe can also have these side effects.  
It is possible that the EP device may not work as expected, such as not giving the study 
products or placebo or the electrical pulse. If this happens, we may ask if we can try 
again.  
In one study, during a person’s first injection, the injection needle came in contact with 
bone, and the EP device was hard to remove, which caused severe pain and stress. A 
local anesthetic had to be used to ease the removal. This has happened once, in more than 
3500 injections using this EP device.  
Having the procedure or thinking about it may cause some stress and anxiety. If you feel 
anxious, please tell us and we will try to help you.  
Because EP could possibly interfere with implanted electronic medical devices such as 
pacemakers or defibrillators or make certain heart problems worse, we will ask whether 

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you have a history of irregular heartbeat (arrhythmias). We will also make sure you don’t 
have any metal implants in the upper part of your body. 
We do not know if EP will change the risks for any of the study products. We do not 
know all the risks of EP because it has only been used in a limited number of people 
before this study and not with these study products. 
Joining the study 
6. It is completely up to you whether or not to join the study.  
Take your time in deciding. If it helps, talk to people you trust, such as your doctor, 
friends or family. If you decide not to join this study, or if you leave it after you have 
joined, your other care at this clinic and the benefits or rights you would normally have 
will not be affected. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
biomedical 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. 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 7 if you use a separate screening consent that covers these procedures. 
7. 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) 
 
Gently pinching the skin of your upper arm to measure the skin thickness for EP 
injections 
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 hepatitis and syphilis. We will ask you about medications you are taking. We will 
ask you about behaviors that might put you at risk for getting HIV. If you were born 
female, we will test you for pregnancy.  
We will review the screening results with you. The screening results may show you are 
not eligible to join the study, even if you want to.  
(Sites: adapt the following section so it is applicable to the care available at your site) 

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8. 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. 
9. If you were born female and could become pregnant, you must agree to use birth 
control to join this study. 
Site: If you want to include Appendix B, 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 
products could affect the developing baby. You must agree to use effective birth control 
from 21 days before your first injection until 6 months after your last study injection. 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: 
10. You will come to the clinic for scheduled visits about [#] times over 
[Insert period of time]. 
Site: Insert number of visits and range of visit lengths. (There is site-specific variation in 
screening protocols and in the number of possible follow-up visits between protocol-
mandated visits.) 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the main study ends (for example, to tell you about the study 
results). 
11. We will give you [Site: Insert compensation] for each study visit you complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for female participants who 
could become pregnant). 
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. 

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12. We will give you either the study products or a placebo.  
Not everyone in this study will get the study products. Some people will get a placebo, a 
substance that does not contain study vaccine or study adjuvant. We will compare the 
results from people who got the placebo with results from people who got the study 
products. In this study, the placebo is sterile salt water. 
You have around a 6-in-7 chance of getting the study products. Site: Modify the 
randomization metaphor in the next sentence as appropriate to your local culture. 
Whether you get the study products or the placebo is completely random, like flipping a 
coin.  
We have no say in whether you get the study products or the placebo. We will not know 
which one you are getting, and neither will you. Only the pharmacist at this clinic will 
have this information while the study is going on.  
You will have to wait until everyone completes their final study visits to find out whether 
you got the study products or the placebo. This could be several years. But, if you have a 
serious medical problem and need to know what you got before the end of the study, we 
can tell you. 
13. We will give you the study products on a schedule. 
You will be in one of 2 groups. You will get 2 injections of the study products or placebo, 
one in each upper arm. This will happen 4 times during the study. All injections will be 
given with EP. 
Site: If a picture version of the injection schedule has been provided in a separate 
protocol appendix, you may insert it below in place of (or in addition to) the text version 
or give it as a separate document to volunteers if you believe it will be helpful to them. 
You are not required to do either. 
 

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Injection Schedule 
Group 
First Injection 
Visit 
1 month  
later 
3 months 
later 
6 months 
later 
1 
p24CE1/2 vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
p24CE1/2 
vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
p24CE1/2 
vaccine 
+ 
p55gag vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
p24CE1/2 
vaccine 
+ 
p55gag vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
2 
p55gag vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
p55gag vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
p55gag vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
p55gag vaccine 
+ 
study adjuvant 
 
OR  
 
placebo 
 
For all injections, the EP device is pressed against your upper arm firmly. You will feel 
some pressure against your arm. Once the EP device is set in place, the clinic staff will 
activate it and you will hear two clicks. At this point the needles are inserted into your 
arm. For most people, this does not hurt but gives a sensation of pressure. After the 
needles have been inserted, there will be a 3 to 4 second delay. During this time, the 
study products or placebo are being injected into your arm. After the injection, a very 
small amount of electricity is sent to the muscle. The electrical signal will last for about a 
half second. This procedure will be done once in each upper arm.  
You will feel a strong movement in your arm muscle, which is often painful. The level of 
pain varies from person to person. Some people describe the feeling like a punch in the 
arm. The intensity of that feeling dies down within a minute or two. On rare occasions, 
people have reported a mild tingling immediately after EP in their arm or fingers lasting 
for a few seconds up to several minutes. After EP, your arm may be sore for a few days.  
We will ask you to rate any pain you feel on a scale. 
At each injection visit, you will have to wait in the clinic for about a half hour after your 
injections to see how you are feeling. Then for that night and for 7 more days, you will 
need to keep track of how you are feeling and if you have any symptoms. Within 3 days 
of your injections, we will contact you or ask you to contact us and let us know how you 
are doing. You should always contact us if you have any issues or concerns after 
receiving an injection. If you have a problem, we will continue to check on you until it 
goes away. 
14. In addition to giving you the study products, we will:  
 
Do regular HIV testing, as well as counseling on your results and on how to avoid 
getting HIV; 

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 
Do physical exams; 
 
Do pregnancy tests if you were born female;  
 
Ask questions about your health, including medications you may be taking; 
 
Ask questions about any personal problems or benefits you may have from being in 
the study; 
 
Ask questions about your experience with EP; and  
 
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 10 mL and 336 mL (2 teaspoons to about 1½ cups). Your body 
will make new blood to replace the blood we take out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate blood 
in the US can give a total of about 500 mL in an 8-week period.”). Modify the example 
for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix [#], Table of procedures (for informed consent form) in this section 
or distribute it as a separate sheet if it is helpful to your study participants. You are not 
required to do either. 
We will be looking for side effects. We will review the results of these procedures and 
tests with you at your next visit, or sooner if necessary. If any of the results are important 
to your health, we will tell you.  
15. We will counsel you on avoiding HIV infection. 
We will ask you personal questions about your HIV risk factors such as sexual behavior, 
alcohol, and drug use. We will talk with you about ways to keep your risk of getting HIV 
low.  
16. We will test your samples for this study. 
We will send your samples (without your name) to labs approved by the HVTN for this 
study, which are located in the United States. Researchers at these labs will test your 
samples to see how your immune system responds to the study products. In rare cases, 
some of your samples may be sent to labs approved by the HVTN in other countries for 
research related to this study. 
Researchers may also do genetic testing related to this study on your samples. Your genes 
are passed to you from your birth parents. They affect how you look and how your body 
works. The differences in people’s genes can help explain why some people get a disease 
while others do not. These types of genetic tests involve some of your genes, not all of 
your genes (your genome). The researchers will study the genes related to the immune 
system and HIV and those that affect how people get HIV.  

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If you become HIV infected, the researchers may look at all of the genes of the virus 
found in your samples. The researchers will use this information to learn more about HIV 
and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of them over 
time, so that they can continue to contribute to this study.  
Tests done on your samples are for research purposes only. The labs will not give the 
results to you or this clinic, and the results will not become part of your study record. 
When your samples are no longer needed for this study, the HVTN will continue to store 
them. 
Site: Delete next section if using separate consent for use of samples and information in 
other studies 
17. When samples are no longer needed for this study, the HVTN wants to keep them 
for use in other studies by HVTN or other researchers. We will call these “extra 
samples.” 
This section gives you information so you can decide if you want your extra samples and 
information used in other studies. You will mark your decision at the end of the form. If 
you have any questions, please ask.  
Do I have to agree? No. You are free to say yes or no, or to change your mind after you 
sign this form. At your request, we will destroy all extra samples that we have. Your 
decision will not affect your being in this study or have any negative consequences here.  
Where are the samples stored? Extra samples are stored in a secure central place called a 
repository. Your samples will be stored in the HVTN repository in the United States. 
How long will the samples be stored? There is no limit on how long your extra samples 
will be stored. [Site: insert limits if your regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, there is 
no plan to share any money with you. The researcher is not likely to ever know who you 
are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. They are 
not part of your medical record. The studies are only being done for research purposes. 
Will the HVTN sell my samples and information? No, but the HVTN may share your 
samples with other researchers. Once we share your samples and information, we will not 
be able to get them back. 
How do other researchers get my samples and information? When a researcher wants to 
use your samples and/or information, their research plan must be approved by the HVTN. 
Also, the researcher’s institutional review board (IRB) or ethics committee (EC) will 
review their plan. [Site: If review by your institution’s IRB/EC/RE is also required, insert 
a sentence stating this.] IRBs/ECs protect the rights and well-being of people in research. 

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If the research plan is approved, the HVTN will send your samples to the researcher’s 
location.  
What information is shared with other researchers? The samples and limited information 
will be labeled with a code number. Your name will not be part of the information. 
However, some information that we share may be personal, such as your race, ethnicity, 
sex, health information from the study, and HIV status. We may share information about 
the study product you received and how your body responded to the study product.  
What kind of studies might be done with my extra samples and information? The studies 
will be related to HIV, vaccines, the immune system and other diseases.  
Researchers may also do genetic testing on your samples.  
If you become HIV infected, the researchers may look at all of the genes of the virus 
found in your samples. The researchers will use this information to learn more about HIV 
and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of them over 
time, so that they can continue to contribute to this study.  
If you agree, your samples could also be used for genome wide studies. In these studies, 
researchers will look at all of your genes (your genome). The researchers compare the 
genomes of many people, looking for common patterns of genes that could help them 
understand diseases. The researchers may put the information from the genome-wide 
studies into a protected database so that other researchers can access it. Usually, no one 
would be able to look at your genome and link it to you as a person. However, if another 
database exists that also has information on your genome and your name, someone might 
be able to compare the databases and identify you. If others found out, it could lead to 
discrimination or other problems. The risk of this is very small. 
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
 
Researchers who use your stored samples and limited information for other research 
 
Government agencies that fund or monitor the research using your samples or 
information 
 
The researcher’s Institutional Review Board or Ethics Committee 
 
The people who work with the researcher  
All of these people will do their best to protect your information. The results of any new 
studies that use your extra samples or information may be published. No publication will 
use your name or identify you personally. 
18. We will do our best to protect your private information. 
US sites: Check HIPAA authorization for conflicts with this section. 

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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. 
Sites: Any change to the following boxed text requires approval from HVTN Regulatory 
Affairs.  
We do need to share your name with the HVTN in case you need proof in the future that 
you participated in an HIV vaccine study. The HVTN will keep your name in a secure 
file with these items:  
 The name of your study  
 Your age or date of birth  
 Your study ID number  
 What study product(s) you received  
There are no HIV test results kept in this file. The HVTN will not share any information 
that could identify you without your agreement. The HVTN will remove your name from 
the file if you do not want it there. 
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, 
 
[Insert name of local IBC], 
 
[Insert name of local IRB/EC] , 
 
[Insert name of local and/or national regulatory authority as appropriate], 
 
Profectus BioSciences, Inc. and people who work for them, 
 
Ichor Medical Systems, Inc. and people who work for them, 
 
The HVTN and people who work for them,  
 
The HVTN Safety Monitoring Board, and 
 
The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 

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We cannot guarantee absolute privacy. At this clinic, we have to report the following 
information:  
Site: Include any public health or legal reporting requirements. Bulleted examples should 
include all appropriate cases (reportable communicable disease, risk of harm to self or 
others, etc.). 
 
[Item 1] 
 
[Item 2] 
 
[Item 3] 
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. 
Sites: The text below may not be deleted or changed, per FDA requirement. 
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. 
19. We may stop your injections or take you out of the study at any time. We may do 
this even if you want to stay in the study and even if you were scheduled for more 
injections.  
This may happen if: 
 
you do not follow instructions, 
 
we think that staying in the study might harm you, 
 
you get HIV, 
 
you enroll in a different research study where you get another study product, or 
 
the study is stopped for any reason. 
If we stop your injections, we may ask you to stay in the study to complete other study 
procedures. 

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20. We will stop your injections if you become pregnant during the study.  
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. 
21. If you get infected with HIV during the study, we will help you get care and support. 
You will not be able to stay in this study. We will counsel you about your HIV infection 
and about telling your partner(s). We will tell you where you can get support and medical 
care, and if there are other studies you may want to join. Site: Modify the following 
sentence as appropriate. We will not provide or pay for any of your HIV care directly.  
Other Risks 
22. 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 routine medical procedures:  
In this study, we will do some routine medical procedures. These are taking blood and 
giving injections. These procedures can cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore, bleeding, and (rarely) muscle damage or infection where you got 
the injection. Taking blood can cause a low blood cell count (anemia), making you feel 
tired. 
Personal problems/discrimination/testing HIV antibody positive: 
About 10 to 20% of people who join HVTN studies report personal problems or 
discrimination because of joining an HIV vaccine 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.  
The body makes antibodies to fight or prevent infection. Most vaccines cause the body to 
make antibodies as a way of preventing infection. Your body may make antibodies to 
HIV because you received HIV study vaccines. The study vaccines may cause you to test 
positive on some types of HIV antibody tests, even if you are not infected with HIV. This 
is called vaccine-induced seropositivity (VISP). VISP means that after you get the study 
vaccines, a routine HIV test done outside this clinic may say you have HIV, even if you 
don’t. For this reason, you should plan to get HIV tests only at this clinic during the 
study. Our tests can tell the difference between true HIV infection and a positive result 
that is caused by the study vaccines. 
If you have a positive test result caused by the study vaccines at any time, we can arrange 
free HIV testing for as long as you need it. If this happens, we do not know how long you 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 126 of 140 
will test positive due to the study vaccines. If you receive a positive HIV test result and 
we determine it is because you have HIV, we will refer you for follow-up care. 
It is unlikely, but you could test negative at the end of the study and positive some time 
later, even though you don’t have HIV. This could happen if different HIV tests come 
into use. We will give you a phone number to call for more information.  
Site: Modify the following paragraph if applicable.  
If someone believes you are infected with HIV even if you are not, you could face 
discrimination and other problems. For example, in some countries, you could be denied 
medical or dental care, employment, insurance, a visa, or entry into the military. If you do 
have a positive HIV antibody test caused by the study vaccines, you will not be able to 
donate blood or organs. Your family and friends may treat you differently. We will give 
you a brochure that tells you more about testing HIV positive because of an HIV vaccine, 
and how you can avoid some of these problems. 
If you become pregnant during or after the study and have VISP, we don't know if the 
antibodies could be passed to your baby. We know that this happens with other vaccines, 
like tetanus vaccine. These antibodies from the mother are not a danger to the baby, and 
they go away over time. For most babies antibodies from the mother last for about six 
months. 
You should always tell the delivery staff if you have VISP. However, you may still be 
tested for HIV using the antibody test when you deliver your baby. If your test is positive 
and the delivery staff believes you have an HIV infection, your baby may be started on 
antiretroviral treatment when it is not needed. If this happens, we can arrange for you and 
the baby to have a test that can tell the difference between true HIV infection and a VISP 
result. If you or the baby continue to have VISP, we can arrange this testing for free for 
as long as it is needed. 
Embarrassment/anxiety:  
You may feel embarrassed when we ask about your HIV risks, such as having sex and 
using drugs. Also, waiting for your HIV test results or other health test results could 
make you feel anxious. You could feel worried if your test results show that you are 
infected with HIV. If you feel embarrassed or anxious, please tell us and we will try to 
help you. 
Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk is very 
low, it is possible that your personal information could be given to someone who should 
not have it. If that happened, you could face discrimination, stress, and embarrassment. 
We can tell you more about how we will protect your personal information if you would 
like it.  
Risks of genetic testing: 
The genetic testing could show you may be at risk for certain diseases. If others found 
out, it could lead to discrimination or other problems. However, it is almost impossible 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 127 of 140 
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 vaccines 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 vaccines might affect your HIV infection or how long it takes to develop 
AIDS. 
We do not know if getting these study vaccines will affect how you respond to any future 
approved HIV vaccine. It could be that a future HIV vaccine may not work as well for 
you because you got the study vaccines. Currently, no HIV vaccine has been approved 
for use.  
We do not know how the study vaccines will affect a pregnant participant or a developing 
baby.  
Benefits 
23. The study may not benefit you. 
We do not know whether getting the study products might benefit you in any way. 
However, being in the study might still help you in some ways. The counseling that you 
get as part of the study may help you avoid getting HIV. The lab tests and physical exams 
that you get while in this study might detect health problems you don’t yet know about.  
This study may help in the search for a vaccine to prevent HIV. However, if the study 
products or EP device later become approved and sold, there are no plans to share any 
money with you.  
Your rights and responsibilities 
24. 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 
25. Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this clinic and 
your legal rights will not be affected, but it is important for you to let us know.  

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We will ask you to come back to the clinic one last time for a physical exam, and we may 
ask to take some blood and urine samples. We will also ask about any personal problems 
or benefits you have experienced from being in the study. We believe these steps are 
important to protecting your health, but it is up to you whether to complete them. 
Injuries 
Sites: Do not make changes to the following section without obtaining approval from 
HVTN Regulatory Affairs at vtn.core.reg@hvtn.org. 
26. If you get sick or injured during the study, contact us immediately. 
Your health is important to us. (Sites: adjust the following 2 sentences if applicable to the 
care available at your site) We will tell you about the care that we can give here. For the 
care that we cannot provide, we will explain how we will help you get care elsewhere. 
If you become sick or injured in this study, there is a process to decide if it is related to 
the study products, EP device 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.  
The HVTN has limited funds to pay medical costs that it determines are reasonable. 
There may be other ways that study-related injuries can be funded. We can give you more 
information, if you would like. (Sites: insert locale- appropriate medical insurance 
language in the following sentence) If the injury is not study related, then you and your 
health insurance will be responsible for treatment costs. 
Some injuries are not physical. For example, you might be harmed emotionally by being 
in an HIV vaccine study. Or you might lose wages because you cannot go to work. 
However, there are no funds to pay for these kinds of injuries, even if they are study 
related. 
You may disagree with the decision about whether your injury is study related. If you 
wish, the HVTN will ask independent experts to review the decision. You always have 
the right to use the court system if you are not satisfied. 
Health contact visit 
27. After your clinic visits end, we will contact you 18 months after your first injection.  
We will contact you by phone, email, or text message [Site: Modify mode of contact as 
appropriate; consult IRB/EC if necessary] around 18 months after your first injection to 
ask questions about your health. If you prefer to answer these questions in person, you 
can come to the clinic to do this. 
If we have any concerns about your health, we may need to have more contact with you. 
You are also welcome to contact us at any time if you have concerns about your health 
related to being in the study.  
If we ask you to come to the clinic, we will give you [Site: Insert compensation amount] 
for each visit. This amount is to cover the costs of [Site: Insert text]. 

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HVTN119_v1.0_FINAL / Page 129 of 140 
If someone outside this study clinic told you that you are infected with HIV, we will ask 
you to come back to the clinic for another HIV test. We will draw about 15 mL (1 
tablespoon) of blood. We may ask you to come back more than once for this testing. 
Because we will want to contact you once after the main study, please tell us if your 
contact information changes, if you are moving away, or if you do not want us to contact 
you anymore. 
You can tell us at any time that you don’t want us to contact you after the main study. If 
you do so, you will not lose any benefits or rights you would normally have. 
All other information that is discussed earlier in this consent also applies to the 18 month 
health contact. 
Questions  
28. If you have questions or problems at any time during your participation in this 
study, use the following important contacts. 
If you have questions about this study, contact 
[name and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, or problems or concerns 
about how you are being treated in this study, contact 
[name/title/phone of person on IRB or other appropriate organization]. 
If you want to leave this study, contact 
[name and telephone number of the investigator or other study staff]. 
 Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and information in 
other studies 
29. In Section 17 of this form, we told you about possible other uses of your extra 
samples and limited information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN keeps track of your decision about how your 
samples and information can be used. 
 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 130 of 140 
 
I allow my extra samples combined with limited information to be used for other 
studies related to HIV, vaccines, the immune system, and other diseases. This may 
include genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples combined with limited 
information to be used in genome-wide studies. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes not 
allowing genetic testing, growing more of my cells, or genome-wide studies.  
 
30. If you agree to join this study, you will need to sign or make your mark below. 
Before you sign or make your mark on this consent form, make sure of the 
following: 
 
You have read this consent form, or someone has read it to you. 
 
You feel that you understand what the study is about and what will happen to you if 
you join. You understand what the possible risks and benefits are. 
 
You have had your questions answered and know that you can ask more. 
 
You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the signature 
block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process. 
 

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Appendix B Approved birth control methods (for sample 
informed consent form) 
You should not become pregnant during the study because we do not know how the study 
products could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first injection until 
6 months after your last study injection.  
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 female partner or partners; 
 
You only have oral sex; or, 
 
You are sexually abstinent (no sex at all). 
Remember: If you are having sex, you need to use male or female condoms to protect 
yourself from HIV infection. 
If you join the study, we will test you for pregnancy at some visits, including before each 
study injection. 

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Appendix C Sample consent form for use of samples and 
information in other studies 
Title: A phase 1 clinical trial to evaluate the safety and immunogenicity of pDNA 
vaccines expressing HIV M Group p24Gag conserved elements and/or p55Gag, 
administered with IL-12 pDNA by intramuscular electroporation, in healthy, HIV-
uninfected adult participants 
HVTN protocol number: HVTN 119 
Site: [Insert site name] 
When samples are no longer needed for this study, the HVTN wants to keep them for use 
in other studies. We will call these “extra samples.” 
This form gives you information so you can decide if you want your extra samples and 
information used in other studies. You will mark your decision at the end of the form. If 
you have any questions, please ask.  
1. Do I have to agree?  
No. You are free to say yes or no, or to change your mind after you sign this form. At 
your request, we will destroy all extra samples that we have. Your decision will not affect 
your being in this study or have any negative consequences here.  
2. Where are the samples stored?  
Extra samples are stored in a secure central place called a repository. Your samples will 
be stored in the HVTN repository in the United States. 
3. How long will the samples be stored?  
There is no limit on how long your extra samples will be stored. [Site: insert limits if your 
regulatory authority imposes them.] 
4. Will I be paid for the use of my samples?  
No. Also, a researcher may make a new scientific discovery or product based on the use 
of your samples. If this happens, there is no plan to share any money with you. The 
researcher is not likely to ever know who you are. 
5. Will I benefit from allowing my samples to be used in other studies?  
Probably not. Results from these other studies are not given to you, this clinic, or your 
doctor. They are not part of your medical record. The studies are only being done for 
research purposes. 
6. Will the HVTN sell my samples and information?  
No, but the HVTN may share your samples with other researchers. Once we share your 
samples and information, we will not be able to get them back. 

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7. How do other researchers get my samples and information?  
When a researcher wants to use your samples and/or information, their research plan 
must be approved by the HVTN. Also, the researcher’s institutional review board (IRB) 
or ethics committee (EC) will review their plan. [Site: If review by your institution’s 
IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs protect the rights 
and well-being of people in research. If the research plan is approved, the HVTN will 
send your samples to the researcher’s location. 
8. What information is shared with other researchers?  
The samples and limited information will be labeled with a code number. Your name will 
not be part of the information. However, some information that we share may be 
personal, such as your race, ethnicity, gender, health information from the study, and HIV 
status. We may share information about the study product you received and how your 
body responded to the study product.  
9. What kind of studies might be done with my extra samples and information?  
 
The studies will be related to HIV, vaccines, the immune system and other diseases.  
Researchers may also do genetic testing related to this study on your samples.  
If you become HIV infected, the researchers may look at all of the genes of the virus 
found in your samples. The researchers will use this information to learn more about HIV 
and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of them over 
time, so that they can continue to contribute to this study. 
If you agree, your samples could also be used for genome wide studies. In these studies, 
researchers will look at all of your genes (your genome). The researchers compare the 
genomes of many people, looking for common patterns of genes that could help them 
understand diseases. The researchers may put the information from the genome-wide 
studies into a protected database so that other researchers can access it. Usually, no one 
would be able to look at your genome and link it to you as a person. However, if another 
database exists that also has information on your genome and your name, someone might 
be able to compare the databases and identify you. If others found out, it could lead to 
discrimination or other problems. The risk of this is very small. 
10. What are the risks of genetic testing?  
The genetic testing could show you may be at risk for certain diseases. If others found 
out, it could lead to discrimination or other problems. However, it is almost impossible 
for you or others to know your test results from the genetic testing. The results are not 
part of your study records and are not given to you.  
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. 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 134 of 140 
GINA does not help or protect you against discrimination by companies that sell life, 
disability or long-term care insurance.  
11. Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
 
Researchers who use your stored samples and limited information for other research 
 
Government agencies that fund or monitor the research using your samples or 
information 
 
The researcher’s Institutional Review Board or Ethics Committee 
 
The people who work with the researcher  
All of these people will do their best to protect your information. The results of any new 
studies that use your extra samples or information may be published. No publication will 
use your name or identify you personally. 
Questions  
12. If you have questions or problems about allowing your samples and information to 
be used in other studies, use the following important contacts. 
If you have questions about the use of your samples or information or if you want to 
change your mind about their use, contact 
[name and telephone number of the investigator or other study staff]. 
If you think you may have been harmed because of studies using your samples or 
information, contact [name and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, contact 
[name/title/phone of person on IRB or other appropriate organization]. 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 135 of 140 
13. Please choose only one of the options below and write your initials or make your 
mark in the box next to it. Whatever you choose, the HVTN keeps track of your 
choice about how your samples and information can be used. 
 
I allow my extra samples combined with limited information to be used for other 
studies related to HIV, vaccines, the immune system, and other diseases. This may 
include genetic testing and keeping my cells growing over time.  
OR 
 
 
I agree to the option above and also to allow my extra samples combined with limited 
information to be used in genome wide studies. 
 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes not 
allowing genetic testing, growing more of my cells, or genome wide studies.  
 
 
 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the signature 
block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the consent process

HVTN 119, Version1.0 / February 17, 2017 
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Appendix D Table of procedures (for sample informed consent form) 
 
 
 
Time after first injection visit (in months) 
Procedure 
Screening 
visit(s) 
First injection 
visit 
0.5 
1 
1.25 
1.5 
3 
3.5 
6 
6.25 
6.5 
9 
12 
182 
Injection 
 
√ 
 
√ 
 
 
√ 
 
√ 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
Urine test 
√ 
 
√ 
 
 
 
 
 
 
 
√ 
 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Pregnancy test (participants 
born female)1 
√ 
√ 
 
√ 
 
 
√ 
 
√ 
 
 
√ 
 
 
HIV testing & pretest 
counseling 
√ 
 
 
 
 
 
√ 
 
√ 
 
 
√ 
√ 
 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Health contact 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
1Persons who had a total hysterectomy (removal of the uterus verified by medical records) or removal of both ovaries (verified by medical records), are not required to have a 
pregnancy test. 
2Visit at 18 months is a health contact visit. 
 
 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 137 of 140 
Appendix E Laboratory procedures 
 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
1410
Day:
D0
D14
D28
D35
D42
D84
D98
D168
D175
D182
D273
D364
D546
Week:
W0
W2
W4
W5
W6
W12
W14
W24
W25
W26
W39
W52
W78
Month:
M0
M0.5
M1
M1.25
M1.5
M3
M3.5
M6
M6.25
M6.5
M9
M12
M18
VAC1
VAC2
VAC3
VAC4
Procedure
Ship to1
Tube4
Tube size (vol. 
capacity)4
BLOOD COLLECTION
Screening or diagnostic assays
     Screening HIV test
Local Lab
Local Lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
     HBsAg/anti-HCV
Local Lab
Local Lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
     Syphilis
Local Lab
Local Lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
5
     HIV diagnostics9
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
—
—
10
—
10
—
—
10
209
—
50
Safety labs
     CBC/ Diff/ platelets
Local lab
Local lab
EDTA
5mL
5
—
5
—
—
5
—
5
—
5
—
5
—
—
30
     Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
5
—
—
5
—
5
—
—
5
5
—
—
30
Immunogenicity assays 6
     Host genetics7
CSR
HVTN Labs
ACD
8.5mL
—
17
—
—
—
—
—
—
—
—
—
—
—
—
17
     Cellular assays
          ICS
CSR
HVTN Labs
ACD
8.5mL
—
42.5
—
—
—
42.5
—
—
—
—
42.5
—
68
—
195.5
          pTfh
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
42.5
—
—
—
—
42.5
—
—
—
—
85
          Epitope mapping
CSR
HVTN Labs
ACD
8.5mL
—
—
—
—
—
59.5
—
—
—
—
127.5
—
—
—
187
          T-cell repertoire
CSR
Vanderbilt
ACD
8.5mL
—
25.5
—
—
—
—
—
25.5
—
—
25.5
—
25.5
—
102
     Humoral assays
          Binding Ab
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
8.5
—
—
—
—
8.5
—
8.5
—
34
Specimen storage
     PBMC
CSR
ACD
8.5mL
—
42.5
—
—
25.5
68
—
85
—
25.5
85
—
85
—
416.5
     Plasma
CSR
ACD
8.5mL
—
z
—
—
z
z
—
z
—
z
z
—
z
—
0
     Serum
CSR
SST
8.5mL
—
17
—
—
8.5
17
—
17
—
8.5
17
—
17
—
102
Visit total
25
153
10
0
76.5
205.5
10
137.5
10
81.5
311
20
224
0
1264
56-Day total
25
178
188
188
264.5
470
292
353
10
91.5
402.5
20
224
0
URINE COLLECTION
      Urine dipstick11
Local lab
Local lab
X
—
X
—
—
—
—
—
—
—
X
—
—
—
      Pregnancy test8
Local lab
Local lab
X
X
—
X
—
—
X
—
X
—
—
X
—
—
Screening 
visit3
Assay Location2
Total
Tube volume (mL)
 
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). Non-HVTN laboratory: Vanderbilt (Nashville, Tennessee, USA). 
3Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination.  
4Local labs may assign appropriate alternative tube types for locally performed tests. 
5Chemistry panels are defined in Section 9.2 (pre-enrollment) and Section 9.4 (postenrollment). 
6Immunogenicity assays will be performed at M0 (for binding Ab assay), and M1.5 and M6.5. Based on the number of responders observed at these timepoints, lab assays may be performed on participants for humoral and cellular responses at other time 
points. 
7Genotyping may be performed on enrolled participants using cryopreserved PBMC collected at baseline, initially in participants who demonstrate vaccine-induced T-cell responses at postvaccination timepoints. 
8For a participant born female, pregnancy test must be performed on the day of vaccination with negative results received prior to vaccination. 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. 
9At an early termination visit for a withdrawn or terminated participant (see Section 9.11), blood should be drawn for HIV diagnostic testing, as shown for visit 13 above. 
10For information concerning the Month 18 health contact, see Section 9.5. Clinic visits are not required except that any participant reporting a diagnosis of HIV infection from testing outside the HVTN will be asked to come to the clinic to collect 
specimens for HIV testing with HVTN HIV diagnostic algorithms. 
11And microscopy if needed. 
z= Up to 10 x 1mL aliquots of ACD plasma will be harvested for storage during PBMC processing; no separate blood draw is needed.  

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 138 of 140 
Appendix F 
Procedures at HVTN CRS  
Visit: 
011 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
148 
Post 
Day: 
 
D0 
D14 
D28 
D35 
D42 
D84 
D98 
D168 
D175 
D182 
D273 
D364 
D546 
 
Month: 
 
M0 
M0.5 
M1 
M1.25 
M1.5 
M3 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M18 
 
Procedure 
Scr. 
VAC1 
 
VAC2 
 
 
VAC3 
 
VAC4 
 
 
 
 
 
 
Study procedures2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
Risk reduction counseling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Pregnancy prevention assessment3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Behavioral risk assessment 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
Confirm eligibility, obtain demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
— 
X 
— 
— 
Outside testing and belief questionnaire 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Intercurrent illness/adverse experience 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
HIV infection assessment4 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
X 
X 
— 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
X 
X 
— 
Visual Analog Pain Scale (Pain Assessment) 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Acceptability questionnaire 
— 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
Local lab assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
Pregnancy (urine or serum HCG)5 
X 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
X 
— 
— 
— 
CBC, differential 
X 
— 
X 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
— 
— 
Chemistry panel (see Section 9.2) 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
X 
X 
— 
— 
— 
Syphilis, Hepatitis B, Hepatitis C 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Vaccination procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination6 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
Reactogenicity assessments7 
— 
X 
— 
X 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 139 of 140 
Visit: 
011 
02 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
148 
Post 
Day: 
 
D0 
D14 
D28 
D35 
D42 
D84 
D98 
D168 
D175 
D182 
D273 
D364 
D546 
 
Month: 
 
M0 
M0.5 
M1 
M1.25 
M1.5 
M3 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M18 
 
Procedure 
Scr. 
VAC1 
 
VAC2 
 
 
VAC3 
 
VAC4 
 
 
 
 
 
 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant  
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
2 For specimen collection requirements see Appendix E. 
3 Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
4 Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
5 For a participant who was born female, pregnancy test must be performed on the day of vaccination prior to vaccination. Pregnancy test to determine initial eligibility may be performed at screening, but must also be done on Day 0 prior to first vaccination. 
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. Serum pregnancy test may be used to confirm the results 
of, or substitute for, a urine pregnancy test. 
6 Blood draws required at vaccination visits must be performed prior to administration of study product, however it is not necessary to have results prior to administration, except for results of a serum pregnancy test, if indicated. Lab tests may be drawn 
within the 3 days prior to vaccination. 
7 Reactogenicity assessments performed daily for at least7 days postvaccination (see Section 9.9). 
8 For information concerning the Visit 14 health contact, see Section 9.5. Clinic visits are not required, except that any participant reporting a diagnosis of HIV infection will be asked to come to the clinic so that HIV status can be confirmed.

HVTN 119, Version1.0 / February 17, 2017 
HVTN119_v1.0_FINAL / Page 140 of 140 
Appendix G 
Adverse events of special interest 
AEs of special interest (AESI) for this protocol include but are not limited to autoimmune disorders; 
representative examples of AESI are listed below. Updates to AESI will be provided as an appendix 
to the HVTN 119 Study Specific Procedures. 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
 
Cranial nerve disorders, including 
paralyses/paresis (eg Bell’s palsy)  
 
Optic neuritis 
 
Multiple sclerosis 
 
Transverse myelitis 
 
Guillain-Barré syndrome, including 
Miller Fisher syndrome and other 
variants 
 
Acute disseminated 
encephalomyelitis, including site 
specific variants: eg non-infectious 
encephalitis, encephalomyelitis, 
myelitis, myeloradiculoneuritis 
 
Myasthenia gravis, including 
Lambert-Eaton myasthenic 
syndrome  
 
Immune-mediated peripheral 
neuropathies and plexopathies, 
(including chronic inflammatory 
demyelinating polyneuropathy, 
multifocal motor neuropathy and 
polyneuropathies associated with 
monoclonal gammopathy). 
 
Narcolepsy 
 
Systemic lupus erythematosus and 
associated conditions 
 
Systemic scleroderma (Systemic 
sclerosis), including diffuse 
systemic form and CREST 
syndrome 
 
Idiopathic inflammatory 
myopathies, including 
dermatomyositis  
 
Polymyositis  
 
Antisynthetase syndrome 
 
Rheumatoid arthritis, and associated 
conditions including juvenile 
chronic arthritis and Still’s disease 
 
Polymyalgia rheumatica 
 
Spondyloarthritis, including 
ankylosing spondylitis, reactive 
arthritis (Reiter's Syndrome) and 
undifferentiated spondyloarthritis  
 
Psoriatic arthropathy 
 
Relapsing polychondritis 
 
Mixed connective tissue disorder 
 
Psoriasis 
 
Vitiligo 
 
Erythema nodosum 
 
Autoimmune bullous skin diseases 
(including pemphigus, pemphigoid 
and dermatitis herpetiformis) 
 
Alopecia areata 
 
Lichen planus 
 
Sweet’s syndrome 
 
Localized Scleroderma (Morphea)  
 
Cutaneous lupus erythematosus 
 
Metabolic disorders 
 
Addison’s disease 
 
Autoimmune thyroiditis (including 
Hashimoto thyroiditis) 
 
Diabetes mellitus type I 
 
Grave's or Basedow’s disease 
Vasculitides 
Blood disorders 
Others 
 
Large vessels vasculitis including: 
giant cell arteritis such as 
Takayasu’s arteritis and temporal 
arteritis.  
 
Medium sized and/or small vessels 
vasculitis including: polyarteritis 
nodosa, Kawasaki's disease, 
microscopic polyangiitis, Wegener’s 
granulomatosis, Churg-Strauss 
syndrome (allergic granulomatous 
angiitis), Buerger’s disease 
(thromboangiitis obliterans), 
necrotizing vasculitis and anti-
neutrophil cytoplasmic antibody 
(ANCA) positive vasculitis (type 
unspecified), Henoch-Schonlein 
purpura, Behcet’s syndrome, 
leukocytoclastic vasculitis. 
 
Autoimmune hemolytic anemia 
 
Autoimmune thrombocytopenia 
 
Antiphospholipid syndrome 
 
Pernicious anemia 
 
Autoimmune aplastic anemia 
 
Autoimmune neutropenia  
 
Autoimmune pancytopenia 
 
Gastrointestinal disorders 
 
Celiac disease 
 
Crohn’s disease 
 
Ulcerative colitis 
 
Ulcerative proctitis 
 
Liver disorders 
 
Autoimmune cholangitis 
 
Autoimmune hepatitis 
 
Primary biliary cirrhosis 
 
Primary sclerosing cholangitis 
 
Autoimmune glomerulonephritis 
(including IgA nephropathy, 
glomerulonephritis rapidly 
progressive, membranous 
glomerulonephritis, 
membranoproliferative 
glomerulonephritis, and 
mesangioproliferative 
glomerulonephritis) 
 
Ocular autoimmune diseases 
(including autoimmune uveitis and 
autoimmune retinopathy) 
 
Autoimmune 
myocarditis/cardiomyopathy 
 
Sarcoidosis 
 
Stevens-Johnson syndrome 
 
Sjögren’s syndrome 
 
Idiopathic pulmonary fibrosis 
 
Goodpasture syndrome 
 
Raynaud’s phenomenon