A Phase 1/2a Partially Double-blinded, Randomized Clinical Trial to Characterize the Safety and Immunogenicity of Clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 Alone, With MF59 Adjuvant, and With Alum Adjuvant in Healthy, HIV-uninfected Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
 
PROTOCOL 
HVTN 107 
A Phase 1/2a partially double-blinded, randomized 
clinical trial to characterize the safety and 
immunogenicity of clade C ALVAC-HIV (vCP2438) 
and Bivalent Subtype C gp120 alone, with MF59® 
adjuvant, and with alum adjuvant in healthy, HIV-
uninfected adult participants 
DAIDS DOCUMENT ID 12006 
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 
Sanofi Pasteur 
Swiftwater, Pennsylvania, USA 
 
GlaxoSmithKline Biologicals, S.A. 
Rixensart, Belgium 
 
NIH, NIAID, Vaccine Research Center (VRC) 
Bethesda, Maryland, USA 
 
May 4, 2017 
HVTN 107 
Version 3.0 

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Contents 
1 
Ethical considerations .............................................................................................. 5 
2 
IRB/EC review considerations ................................................................................. 7 
2.1 
Minimized risks to participants ..................................................................... 7 
2.2 
Reasonable risk/benefit balance .................................................................... 8 
2.3 
Equitable subject selection ............................................................................ 8 
2.4 
Appropriate informed consent ....................................................................... 8 
2.5 
Adequate safety monitoring ........................................................................... 8 
2.6 
Protect privacy/confidentiality ....................................................................... 9 
3 
Overview ................................................................................................................ 10 
3.1 
Protocol Team .............................................................................................. 14 
4 
Background ............................................................................................................ 15 
4.1 
Rationale for trial concept ........................................................................... 15 
4.2 
ALVAC-HIV (vCP2438)............................................................................. 19 
4.3 
Bivalent Subtype C gp120 ........................................................................... 21 
4.4 
MF59® adjuvant ........................................................................................... 22 
4.5 
Aluminum Hydroxide Suspension ............................................................... 23 
4.6 
Bivalent Subtype C gp120/MF59® for injection .......................................... 23 
4.7 
Bivalent Subtype C gp120 admixed with Aluminum Hydroxide Suspension 
for injection ................................................................................................. 24 
4.8 
Trial design rationale ................................................................................... 24 
4.9 
Plans for future product development and testing ....................................... 27 
4.10 Preclinical safety studies .............................................................................. 27 
4.11 Clinical studies ............................................................................................ 30 
4.12 Potential risks of study products and administration ................................... 46 
5 
Objectives and endpoints ....................................................................................... 48 
5.1 
Primary objectives and endpoints ................................................................ 48 
5.2 
Secondary objectives and endpoints ............................................................ 49 
5.3 
Exploratory objectives ................................................................................. 49 
6 
Statistical considerations ........................................................................................ 51 
6.1 
Accrual and sample size calculations .......................................................... 51 
6.2 
Randomization ............................................................................................. 54 
6.3 
Blinding ....................................................................................................... 54 
6.4 
Statistical analysis ........................................................................................ 55 
7 
Selection and withdrawal of participants ............................................................... 60 
7.1 
Inclusion criteria .......................................................................................... 60 
7.2 
Exclusion criteria ......................................................................................... 62 
7.3 
Participant departure from vaccination schedule or withdrawal .................. 65 
8 
Study product preparation and administration ....................................................... 68 
8.1 
Vaccine regimen .......................................................................................... 68 
8.2 
Study product formulation ........................................................................... 69 
8.3 
Preparation of study products ...................................................................... 70 
8.4 
Administration ............................................................................................. 72 
8.5 
Acquisition of study products ...................................................................... 73 
8.6 
Pharmacy records......................................................................................... 73 
8.7 
Final disposition of study products .............................................................. 73 

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9 
Clinical procedures ................................................................................................ 74 
9.1 
Informed consent ......................................................................................... 74 
9.2 
Pre-enrollment procedures ........................................................................... 76 
9.3 
Enrollment and vaccination visits ................................................................ 77 
9.4 
Follow-up visits ........................................................................................... 79 
9.5 
Innate immunity and mucosal sampling ...................................................... 80 
9.6 
Stool sampling ............................................................................................. 81 
9.7 
HIV counseling and testing ......................................................................... 82 
9.8 
Contraception status..................................................................................... 83 
9.9 
Urinalysis ..................................................................................................... 84 
9.10 Assessments of reactogenicity ..................................................................... 84 
9.11 Visit windows and missed visits .................................................................. 85 
9.12 Early termination visit ................................................................................. 86 
9.13 Pregnancy .................................................................................................... 86 
10 
Laboratory .............................................................................................................. 87 
10.1 HVTN CRS laboratory procedures .............................................................. 87 
10.2 Total blood volume ...................................................................................... 87 
10.3 Primary immunogenicity timepoint ............................................................. 87 
10.4 Endpoint assays: humoral ............................................................................ 87 
10.5 Endpoint assays: cellular ............................................................................. 88 
10.6 Innate immunity assays................................................................................ 88 
10.7 Genotyping .................................................................................................. 88 
10.8 Lab assay algorithm ..................................................................................... 89 
10.9 Exploratory studies ...................................................................................... 89 
10.10 Other use of stored specimens ..................................................................... 89 
10.11 Biohazard containment ................................................................................ 90 
11 
Safety monitoring and safety review ..................................................................... 91 
11.1 Safety monitoring and oversight .................................................................. 91 
11.2 Safety reporting ........................................................................................... 92 
11.3 Safety pause and prompt PSRT AE review ................................................. 95 
11.4 Review of cumulative safety data ................................................................ 96 
11.5 Study termination......................................................................................... 96 
12 
Protocol conduct .................................................................................................... 98 
12.1 Social impacts .............................................................................................. 98 
12.2 Compliance with NIH guidelines for research involving products containing 
recombinant DNA ....................................................................................... 99 
12.3 Specific regulatory considerations for Republic of South Africa and other 
Southern African countries .......................................................................... 99 
12.4 Emergency communication with study participants .................................... 99 
13 
Version history ..................................................................................................... 100 
14 
Document references (other than literature citations) .......................................... 104 
15 
Acronyms and abbreviations ................................................................................ 107 
16 
Literature cited ..................................................................................................... 110 
Appendix A Sample informed consent form .................................................................. 118 
Appendix B Injection schedule for sample informed consent form ............................... 136 
Appendix C Approved birth control methods (for sample informed consent form) ...... 137 
Appendix D Tables of procedures (for sample informed consent form) ........................ 138 

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Appendix E Sample consent form for use of samples and information in other studies 140 
Appendix F Laboratory procedures (Groups 1, 2, and 4) .............................................. 144 
Appendix G Laboratory procedures (Groups 1, 2, and 4 – innate and mucosal subset) 145 
Appendix H Laboratory procedures (Group 3) .............................................................. 146 
Appendix I Laboratory procedures (Group 3 – innate and mucosal subset) ................ 147 
Appendix J Procedures at HVTN CRS (Groups 1, 2, and 4) ........................................ 148 
Appendix K Procedures at HVTN CRS (Groups 1, 2, and 4 – innate and mucosal subset) 
 
 
 ................................................................................................................... 149 
Appendix L Procedures at HVTN CRS (Group 3) ........................................................ 151 
Appendix M Procedures at HVTN CRS (Group 3 – innate and mucosal subset) .......... 152 
Appendix N Adverse events of special interest .............................................................. 154 
Appendix O Protocol Signature Page ............................................................................. 155 
 

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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, in accordance with Good 
Participatory Practices (GPP) and all local and national guidelines. Specifically, the 
HVTN leadership is aware of the Guidelines for Good Clinical Practice in the 
Conduct of Clinical Trials with Human Participants in South Africa Section 2.4 
“Communication and Community Involvement” and the South African Medical 
Research Council’s Guidelines on Ethics for Medical Research: HIV Preventive 
Vaccine Research (particularly section 5, Community Participation) and works to 
implement both guidelines generally and those sections specifically. 
 
HVTN clinical trial staff counsel study participants routinely on how to reduce HIV 
risk. Participants who become HIV-infected during the trial are provided counseling 
on notifying their partners and about HIV infection according to local guidelines. 
Staff members will also counsel them about reducing their risk of transmitting HIV to 
others. 
 
The HVTN requires that all international HVTN sites lacking national plans for 
providing antiretroviral therapy (ART) develop plans for the care and treatment of 
participants who acquire HIV infection during a trial. Each plan is developed in 
consultation with representatives of host countries, communities from which 
potential trial participants will be drawn, sponsors, and the HVTN. Participants will 
be referred to programs for ART provision when the appropriate criteria for starting 
ART are met. If a program is not available at a site and ART is needed, a privately 
established fund will be used to pay for access to treatment to the fullest extent 
possible. 
 
The HVTN provides training so that all participating sites similarly ensure fair 
participant selection, protect the privacy of research participants, and obtain 
meaningful informed consent. During the study, participants will have their 
wellbeing monitored, and to the fullest extent possible, their privacy protected. 
Participants may withdraw from the study at any time. 

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 
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 
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 recognizes the importance of institutional review and values the role of in 
country Institutional Review Boards (IRBs) and Ethics Committees (ECs) 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 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 questions or 
concerns regarding these research requirements. 
This trial is being conducted in Southern Africa, with partial funding from the US NIH. 
Due to this, the trial is subject to both US and local regulations and guidelines on the 
protection of human research subjects and ethical research conduct. Where there is a 
conflict in regulations or guidelines, the regulation or guideline providing the maximum 
protection of human research subjects will be followed. 
In compliance with the Guidelines For Good Practice In The Conduct Of Clinical Trials 
In Human Participants In South Africa (“South African GCPs”), each research location in 
South Africa has a South African-based Principal Investigator (PI) who is qualified to 
conduct (and supervise the conduct of) the research; and the research addresses an 
important South African health need for an HIV vaccine in line with the national strategic 
plan for South Africa and the national South African HIV vaccine plan. In addition, the 
investigators take responsibility for the conduct of the study and the control of the study 
products, including obtaining all appropriate South African regulatory and ethical 
reviews of the research. Each participating site has a standard operating procedure for 
ensuring that participants have the necessary information to make a decision whether or 
not to consent to the research.  
The sections below address each of the review concerns by IRBs/ECs regarding how the 
research will be conducted. 
2.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly informing 
participants about risks so that they can join in partnership with the researcher in 
recognizing and reporting harms; (b) respecting local/national blood draw limits; (c) 
performing direct observation of participants 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. 

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

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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 addition, each staff member at each study site in this protocol signs a 
Confidentiality Agreement 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 1/2a partially double-blinded, randomized clinical trial to characterize the safety 
and immunogenicity of clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 
alone, with MF59® adjuvant, and with alum adjuvant in healthy, HIV-uninfected adult 
participants 
Primary objective(s) 
Primary objective 1 
To compare the humoral immune responses induced by ALVAC-HIV (vCP2438) prime 
with 2 ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59® boosts or 2 
ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120 admixed with Aluminum 
Hydroxide Suspension boosts in HIV-uninfected participants 
Primary objective 2:  
To compare the humoral immune responses induced by ALVAC-HIV (vCP2438) prime 
with 2 ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59® boosts to the 
regimen with 3 ALVAC-HIV (vCP2438) + Bivalent Subtype C /MF59® vaccinations in 
HIV-uninfected participants 
Primary objective 3 
To evaluate the safety and tolerability of each vaccine regimen through the Month 6.5 
timepoint 
Study products and routes of administration 
 
ALVAC-HIV (vCP2438): ALVAC-HIV (vCP2438) expresses the gene products 
ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 
transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) 
and gag and pro (clade B LAI strain). It is formulated as a lyophilized vaccine for 
injection at a viral titer ≥ 1 × 106 cell culture infectious dose (CCID)50 and < 1 × 108 
CCID50 (nominal dose of 107 CCID50) and is reconstituted with 1 mL of sterile 
sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single 
dose. 
 
Bivalent Subtype C gp120/MF59®: Bivalent Subtype C gp120/MF59® consists of 2 
subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 
Env, each at a dose of 100 mcg, mixed with MF59® adjuvant (an oil-in-water 
emulsion) and delivered as a 0.5 mL IM injection. 
 
Bivalent Subtype C gp120 admixed with Aluminum Hydroxide Suspension: 
Bivalent Subtype C gp120 admixed with Aluminum Hydroxide Suspension consists 
of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C 

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gp120 Env, each at a dose of 100 mcg, admixed with Aluminum Hydroxide 
Suspension (~625 mcg aluminum content) and delivered as a 0.5 mL IM injection. 
 
Bivalent Subtype C gp120: Bivalent Subtype C gp120 consists of 2 subtype C 
recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at 
a dose of 100 mcg, mixed with sodium chloride for injection, 0.9% and delivered as a 
0.5 mL IM injection.  
Table 3-1 Schema 
Group 
N 
(total) 
N 
(innate/mucosal 
subset) 
Dose of each 
protein 
component 
Injection schedule in Months (Days) 
M0 (D0) 
M1 (D28) 
M3 (D84) 
M6 (D168) 
M12 (D364) 
1 
36 
18 
100 mcg 
ALVAC-HIV 
(vCP2438) 
ALVAC-HIV 
(vCP2438) 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120/MF59® 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120/MF59® 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120/MF59® 
2 
36 
18 
100 mcg 
ALVAC-HIV 
(vCP2438) 
ALVAC-HIV 
(vCP2438) 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120 
admixed with 
Aluminum 
Hydroxide 
Suspension 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120 
admixed with 
Aluminum 
Hydroxide 
Suspension 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120 
admixed with 
Aluminum 
Hydroxide 
Suspension 
3 
36 
18 
100 mcg 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120/MF59® 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120/MF59® 
— 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120/MF59® 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120/MF59® 
4 
24 
18 
100 mcg 
ALVAC-HIV 
(vCP2438) 
ALVAC-HIV 
(vCP2438) 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120 
ALVAC-HIV 
(vCP2438) + 
Bivalent 
Subtype C 
gp120 
Total 
132 
72 
 
Participants 
132 healthy, HIV-1–uninfected volunteers aged 18 to 40 years 
Design 
Multicenter, randomized, controlled, (partially) double-blind trial 
Duration per participant 
18 months of scheduled clinic visits  
Estimated total study duration 
21 months (includes enrollment and follow-up) 

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Study sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
Study product providers 
 
ALVAC-HIV (vCP2438): Sanofi Pasteur (Swiftwater, Pennsylvania, USA) 
 
Bivalent Subtype C gp120: GlaxoSmithKline Biologicals, S.A. (GSK Vaccines) 
(Rixensart, Belgium) 
 
MF59®:: GlaxoSmithKline Biologicals, S.A. (GSK Vaccines) (Rixensart, Belgium) 
 
Aluminum Hydroxide Suspension: NIH, NIAID, Vaccine Research Center 
(Frederick, Maryland, USA) 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson Cancer 
Research Center (FHCRC) (Seattle, Washington, USA) 
Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), FHCRC (Seattle, 
Washington, USA) 
HIV diagnostic laboratory 
HIV Sero-Molecular Laboratory–National Institute for Communicable Diseases (HSML-
NICD) (Johannesburg, South Africa)  
Endpoint assay laboratories 
Cape Town HVTN Immunology Laboratory (CHIL) (Cape Town, South Africa)  
Duke Human Vaccine Institute (DHVI), Duke University Medical Center (Durham, 
North Carolina, USA)  
Neutralizing Antibody (nAb) Assay Laboratory, Duke University Medical Center 
(Durham, North Carolina, USA)  
FHCRC/University of Washington (Seattle, Washington, USA) 
South Africa Immunology Laboratory and National Institute for Communicable Diseases 
(SAIL-NICD) (Johannesburg, South Africa) 
Study sites 
HVTN Clinical Research Sites HVTN (CRSs) in Southern Africa to be specified in the 
Site Announcement Memo 

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Safety monitoring 
HVTN 107 PSRT; HVTN SMB 

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3.1 
Protocol Team 
Protocol leadership 
Chair 
Paul Goepfert 
University of 
Alabama, Birmingham 
205-975-5667 
paulg@uab.edu 
Statistician 
Zoe Moodie 
SCHARP, FHCRC 
206-667-7077 
zoe@scharp.org 
Cochair 
Kathy Mngadi 
CAPRISA 
27-031-260-1927 
mngadik@caprisa.org 
Medical officer 
Laura Polakowski 
DAIDS, NIAID 
240-627-3040 
laura.polakowski@nih.gov 
Protocol Team 
leader 
Nicole Grunenberg 
HVTN Core, FHCRC 
206-667-2043 
ngrunenb@fhcrc.org 
Lab lead 
Erica Andersen-Nissen  
CHIL, HCRISA 
+27 (0)21 202 2224 
eanderse@hcrisa.org.za 
Other contributors to the original protocol 
Core medical 
monitor 
Nicole Grunenberg 
HVTN Core, 
FHCRC 
DAIDS protocol pharmacist 
Irene Rwakazina  
DAIDS, NIAID 
301-761-7269 
Regional medical 
liaison 
Simba Takuva 
HCRISA 
Statistical research associate 
Xue Han 
SCHARP, FHCRC 
Vaccine developer 
representative 
Sanjay Phogat 
Sanofi Pasteur 
Clinical safety specialist 
Jill Zeller 
HVTN Core, FHCRC 
 
Carlos 
DiazGranados 
Sanofi Pasteur 
Clinical trials manager 
Michelle Nebergall 
HVTN Core, FHCRC 
 
Marguerite 
Koutsoukos 
GSK Vaccines 
SDMC Clinical data 
manager 
Ingrid Durrenberger 
SCHARP, FHCRC 
 
Olivier van der 
Meeren 
GSK Vaccines 
SDMC Senior clinical data 
manager 
Gina Escamilla 
SCHARP, FHCRC 
Laboratory 
Program 
representative 
On Ho 
HVTN Laboratory 
Program, FHCRC 
DAIDS Project Officer 
Michael Pensiero 
DAIDS, NIAID 
Regulatory affairs 
Laurie Rinn 
HVTN Core, 
FHCRC 
Protocol development 
manager 
Carter Bentley 
HVTN Core, FHCRC 
Clinic coordinator 
Diantha Pillay 
CAPRISA 
Community engagement unit 
representative 
Nandi Luthuli  
HVTN Core, FHCRC 
Community 
Advisory Board 
(CAB) members 
Thoko Norah 
Sifunda 
PHRU 
Community 
educator/recruiter 
Londiwe Luthuli 
CAPRISA 
 
Lindiwe Mbhele 
UKZN 
Technical editor 
Erik Schwab 
HVTN Core, FHCRC 
 

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4 
Background 
4.1 
Rationale for trial concept 
The RV144 HIV vaccine trial in Thailand, which evaluated a heterologous regimen of 2 
doses of ALVAC-HIV (vCP1521) followed by the 2 doses of ALVAC-HIV plus 
AIDSVAX® clades B/E gp120 protein, was the first clinical HIV vaccine trial to 
demonstrate efficacy in the prevention of HIV acquisition [4].The RV144 trial results 
have triggered a suite of clinical trials designed to deepen understanding of the 
mechanism of protection and ultimately to develop a licensable product appropriate to 
regions with significant HIV burden. Specifically, several trials are planned in the clinical 
testing of an HIV vaccine regimen similar to that tested in RV144 but adapted for the 
Southern African region, that is, with a clade C viral vector vaccine insert and clade C 
subunit proteins. This trial will directly compare the differences in elicited immune 
response between aluminum hydroxide and MF59® as adjuvants in the RV144-like 
vaccine regimen modified for the Southern African region. It will also evaluate 
concurrent administration of the viral vector and clade C subunit proteins with MF59® 
from Month 0.  
With approximately 6.1 million people living with HIV as of 2012 [5], South Africa’s 
epidemic remains the largest in the world and Sub-Saharan Africa bears the preponderant 
burden of the HIV epidemic with almost 70% of all infections worldwide [6]. The vast 
majority of newly acquired infections in this region occur during unprotected 
heterosexual intercourse.  
ART was introduced into the public sector in South Africa in 2003 and, as of 2012, 
approximately 2.2 million people were on treatment, representing 80% of people 
requiring ART [7]. While universal access to antiretroviral HIV treatment is a global 
ideal and progress toward this goal has been made [7], in many regions of Sub-Saharan 
Africa limited access and other barriers to care continue to undermine the prevention 
potential of widespread ART [8]. Moreover, the cost and health care burden of delivering 
ever-increasing amounts of treatment in resource constrained settings pose significant 
challenges and drives the quest for effective prevention of infection [9-12]. In addition, 
while studies conducted over the past few years have confirmed the promise of 
antiretroviral chemoprophylaxis, adherence to drug regimens, a critical factor in their 
effectiveness, has proved problematic in several recent clinical trials [13-15]. Clearly, 
effective methods for preventing the acquisition and transmission of HIV-1 are urgently 
needed for this region, and it remains well recognized that the way to eradicate a global 
viral epidemic is to design, mass-produce, and then systematically vaccinate the target 
population with an effective prophylactic vaccine [16].  
4.1.1 
The RV144 trial  
The RV144 trial was conducted by the US Military HIV Research Program and the 
Thailand Ministry of Health in a community-based sample of more than 16,000 HIV-1 
uninfected participants in Thailand; results were published in 2009 [4]. This study 
enrolled individuals aged 18 to 30 years with varying degrees of HIV risk. The clinical 
trial evaluated the heterologous prime-boost combination of canarypox prime ALVAC-
HIV (vCP1521) (>106 CCID50), expressing clade E env and clade B gag and pro, 
followed by the AIDSVAX® clades B/E gp120 protein boost (300 mcg of each protein 
[600 mcg total] formulated with 600mcg of alum adjuvant). These products were based 
on viruses commonly circulating in Thailand at the time. This vaccine regimen 

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demonstrated 31.2% efficacy when compared with placebo (51 and 74 cases in the 
vaccines and placebo recipients, respectively; p = 0.04) at 3.5 years [4]. Although 
evaluation of vaccine efficacy at 12 months post vaccination was not included in the pre-
specified analysis, substantially greater reduction in acquisition was observed in the first 
year postvaccination (estimated 60.5%, 95% confidence interval [CI] 22%-80%) with the 
vaccine effect waning over time to 31% cumulative reduction in HIV acquisition through 
3.5 years [17]. 
4.1.2 
Correlates of risk (CoR) in RV144 
To better understand how the RV144 vaccine regimen reduced the risk of HIV infection, 
a large consortium of independent laboratories worked together systematically to ensure 
maximal information could be derived from samples obtained from participants who 
were vaccinated but became infected compared with those who had been vaccinated but 
who were uninfected at the end of the trial. A case control study was performed on 41 
infected vaccine recipients, 205 uninfected vaccine recipients (1:5) and 40 placebo 
recipients (20 infected and 20 uninfected) within the RV 144 clinical trial to identify CoR 
[18]. Among the 6 primary immunological variables selected for the correlates analysis 
(5 different antibody [Ab] responses and CD4+ T-cell cytokine production) that were 
measured at the 2 weeks after the final vaccination visit (ie, at or near peak 
immunogenicity), 2 immune CoR of HIV acquisition were identified among vaccine 
recipients in the RV144 case control study. The first was the presence of immunoglobulin 
G (IgG) Ab that bound to a scaffolded gp70 V1V2 recombinant protein; this variable 
correlated inversely with infection rate (ie, higher V1V2 Ab→lower infection rate). The 
second was plasma Env-specific binding immunoglobulin A (IgA), which correlated 
directly with infection rate (ie, higher IgA to Env→higher infection rate). The other 4 
primary variables correlated inversely with infection rate, but only when the level of IgA 
binding was low. This observation engendered the hypothesis that IgA might interfere 
with protective IgG effector functions, as had been observed previously with some other 
pathogens. In support of this possibility, it was noted that vaccinees who produced serum 
IgA to the first conserved region of Env protein (C1) had a significantly higher risk of 
infection than vaccinees without these antibodies. It was further noted that the C1 region 
of gp120 contains an epitope that can be a target on the surface of virus-infected cells for 
antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC). The 
researchers concluded that if the protection conferred by V1V2 IgG antibodies could be 
confirmed, then a vaccine that could induce high levels of those antibodies along with 
low levels of monomeric Env-specific IgA antibodies might be more efficacious. 
Notably, despite the positive correlation of Env-specific IgA with infection risk in the 
RV144 study, neither low levels of V1V2 Ab nor high levels of Env-specific IgA were 
associated with higher rates of infection than those found in the placebo group [18]. 
Recently, several studies have further enhanced our understanding of the efficacy seen in 
RV144. Rolland and colleagues demonstrated a sieve effect in the vaccine recipients,  
specifically that the vaccine induced better protection against viruses that matched the 
vaccine sequence at position 169 in the V2 loop of Env [19]. These data further 
substantiate the importance of antibodies directed against this region in protecting against 
infection [18]. Yates and colleagues noted that Env V1V2-specific IgG3 was the 
immunoglobulin subclass showing the strongest correlation with prevention of HIV 
acquisition in RV144 [20]. Chung and colleagues demonstrated that the IgG3 subclass 
was much better at engaging Fc-mediated effector responses when compared to the other 
subclasses, thereby providing a possible mechanism explaining the association of Env 
V1V2 IgG3 with a lower rate of HIV acquisition [21]. In addition, Tomaras and 
colleagues confirmed that IgA antibodies to the C1 region of Env did indeed block IgG 

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binding and effector functions in RV144 vaccinees [22]. In sum, these CoR studies point 
to the importance of functional Ab responses, directed against a specific region of Env, in 
mediating the differing rates of HIV acquisition observed in RV144. They lay the 
groundwork for directing immune analyses planned for future HIV vaccine clinical trials.  
4.1.3 
Rationale for the proposed study 
Based in large part on the successes seen in the RV144 trial, the HVTN is extending the 
efficacy studies to Southern Africa using a vaccine regimen that is similar to that tested in 
RV144, with HVTN 100 being the first phase 1-2 trial evaluating ALVAC-HIV 
(vCP2438) prime with ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59® 
boosts. The ALVAC-HIV vector in this trial is the same as was tested in RV144 but 
encodes a subtype C envelope protein to better match the HIV subtype most prevalent in 
Southern Africa. Similarly the protein boost will consist of bivalent recombinant subtype 
C gp120 monomers. Additionally, MF59® has been selected as the protein adjuvant 
because it has generated superior Ab responses in vaccines against influenza, hepatitis B, 
and HIV [23-28]. For HIV in particular, MF59®, given together with a gp120/HIV-1SF2 
HIV protein vaccine candidate, elicited higher HIV specific immune responses than alum 
[23,24,27].  
Vaccines adjuvanted with MF59® elicit higher magnitude systemic immune responses 
than do the same vaccines adjuvanted with alum and, as noted previously, the reduction 
in risk of HIV infection seen in RV144 was greatest when the systemic antibody 
responses were of highest magnitude (following the final dose of the vaccine up to 
around 6 months thereafter) [17]. For this reason, the HVTN is interested in eliciting 
antibody responses more rapidly and maintaining them for longer periods of time. 
Regarding the capacity to raise antibody responses rapidly, the HVTN 096 study 
demonstrated that a recombinant pox vector or plasmid DNA (pDNA) given concurrently 
with recombinant gp120 at all vaccination timepoints induced antibody responses more 
rapidly than priming with a pox vector or pDNA and waiting to boost with recombinant 
protein at months 3 and 6 [29]. Moreover, in HVTN 096 the lowest levels of vaccine-
specific serum IgA responses were seen in participants who received an HIV recombinant 
NYVAC vector expressing gp120 concurrently with AIDSVAX® B/E at all vaccinations 
[29]. In contrast, those who were primed with recombinant NYVAC followed by a 
NYVAC/gp120 dual boost had higher serum IgA responses to vaccine-matched antigens. 
Whether such a finding is reproducible, whether it has functional consequences similar to 
those observed in the RV144 trial, and whether it extends to the ALVAC-HIV + Bivalent 
Clade C gp120/MF59® vaccine regimens remain to be determined. 
Quicker production of higher magnitude antibody responses that may also be more 
durable would seem desirable, especially if potential interference from less helpful 
immune responses can be minimized. However, several recent studies have called into 
question whether higher magnitude systemic immune responses necessarily translate into 
superior vaccine efficacy.  
In particular, a recent study by Franchini and colleagues, using the non-human primate 
(NHP) model of HIV infection, made an unexpected and relevant observation [30]. In 
this preclinical study, NHP were assigned to receive the RV144 vaccine regimen using 
simian immunodeficiency virus (SIV) instead of the HIV inserts. One group received 
alum (n = 27), as given in the RV144 study, while another group received MF59® in the 
place of alum (n = 27). A third group served as a placebo control (n = 47). As expected, 
the systemic Ab responses achieved greater magnitude in the MF59® group. NHP were 

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then challenged intra-rectally with SIVmac251 four weeks after the final immunization. 
Surprisingly, the only protection seen was in the alum group, with an estimated vaccine 
efficacy or 44% in preventing SIV infection at each challenge, similar to the reduction in 
HIV infection seen among vaccinees in RV144. The MF59® group was not protected 
against infection, and similar to the RV144 Study, there was no effect on viral load in the 
infected primates. Dr. Franchini and colleagues have subsequently analyzed the mucosal 
immune responses and found that despite increased total envelope-specific IgG 
antibodies in the rectal mucosa of the MF59® NHP, the V2-specific antibodies were 
decreased compared to the alum group. They also analyzed the expression of the gut 
mucosal homing marker 47 on plasmablasts in the peripheral blood and noted that the 
MF59® group had decreased expression of this marker compared to the alum group. 
In another NHP study, Franchini and colleagues compared immune responses elicited by 
an RV144-like ALVAC-SIV prime and ALVAC-SIV plus gp120 with alum boost to the 
responses elicited by regimens with the RV144-like SIV vaccines primed by plasmid 
DNA and adenovirus serotype 26 (Ad26) SIV vaccines [31]. While the Ad26-primed 
regimen showed the highest magnitude Ab responses in blood and mucosal secretions 
(including V1V2 binding antibodies [the CoR in RV144]), superior neutralization of 
Tier-1–like SIV strains, and generally superior T-cell responses, this regimen performed 
poorly against serial SIVmac251 intrarectal challenges begun 4 weeks after the last 
vaccination, showing no significant difference from the control group. The investigators 
concluded that increased immunogenicity does not necessarily translate into increased 
efficacy. 
These surprising and unanticipated results in nonclinical studies call into question the 
blanket assumption that higher magnitude immune response equate with improved 
vaccine efficacy. However, there are several caveats that must be considered. First of all, 
NHP studies have not always translated to similar results in humans [32,33]. 
Furthermore, the first NHP study described above was not a single study but instead data 
compiled from 2 separate studies, neither of which was randomized. Moreover, the small 
number of studied monkeys makes broad conclusions difficult; as does the fact that a 
rectal challenge was used. The latter may not be pertinent in a population where the 
majority of infections are expected to occur as a result of heterosexual transmission. 
Finally, the NHP were challenged 4 weeks following the final vaccination, which likely 
does not adequately represent the timing that would occur in humans. A longer period 
between vaccination and challenge would allow for optimal maturation of the immune 
response the quality of which is likely to be different at 4 weeks than at 4-6 months 
following the final boost [34]. One of the best examples of this phenomenon is seen with 
the attenuated SIV vaccine where efficacy is not seen until several months following the 
final vaccination [35]. 
The previously cited analyses of clinical samples by Yates et al [20] and Chung et al [21] 
arrived at similar conclusions based on comparisons of Ab titers elicited by the modestly 
efficacious RV144 regimen and by repeated doses (up to 7) of the same AIDSVAX® 
vaccine in clinical trial VAX003, which was also conducted in Thailand, albeit among a 
higher risk cohort of persons who inject drugs. Both groups found that, in terms of most 
of the Ab responses measured, including binding Abs to V1V2, the VAX003 vaccine 
regimen outperformed the RV144 vaccine regimen. However, the apparently superior Ab 
responses in VAX003 did not translate into vaccine efficacy, as none was observed in 
that trial [36]. As noted, these studies direct attention toward specific Ab subtypes and 
subclasses associated with Fc-mediated effector responses. 

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In light of these preclinical and clinical findings, it is important for the HVTN to 
determine the extent to which they apply to the vaccine/adjuvant combinations being 
evaluated in this study. For instance, while the MF59® adjuvant increases overall Ab 
responses in the systemic circulation, how do the adjuvants differ in terms of specific 
systemic immune responses elicited (eg, IgG3) and also in terms of innate and mucosal 
responses? To help answer these questions, this study will evaluate both the magnitude 
and the quality of the immune responses elicited in association with these adjuvants, both 
systemically and in the mucosa. 
While the mechanism for SIV protection in the NHP study in the alum arm remains 
unclear, a leading hypothesis is that the mucosal antibody responses were quantitatively 
and qualitatively different when comparing the two adjuvants. Although we are able to 
measure some surrogate markers of mucosal homing using samples derived from blood, 
these are indirect measurements, which may not correlate well with the actual mucosal 
levels of vaccine-induced antibody responses. Furthermore, the quality of the mucosal 
antibody response (specificity, isotype, protein glycosylation, etc.) can only be attained 
from samples taken at the mucosal site. Even though mucosal responses are more labor 
intensive to evaluate and collecting these samples requires more time and effort on the 
part of the participant, our judgment, based on this information, is that the potential 
scientific information gained from these samples outweighs these expressed concerns. 
The mucosal compartment as a primary portal of entry for HIV-1 plays a critical role in 
HIV transmission and early events after HIV infection [37]. Hence, understanding 
vaccine-induced mucosal immune responses is an important goal of HIV vaccine 
research. As observed in some NHP studies, vaccine-induced systemic immune responses 
may not necessarily predict or correlate with responses at the mucosa, highlighting the 
importance of assessing immune responses in both compartments. In 1 NHP study, for 
example, protection from vaginal virus challenge was associated with vaccine induced 
Ab responses in the mucosal compartment that were not detected in blood [38]. For these 
reasons, this study will explore rectal, semen, and cervical humoral mucosal responses in 
a subset of participants from each group.  
In addition, the current study will evaluate the immune responses elicited by an 
unadjuvanted vaccine regimen as an active control. It is expected that improved immune 
responses with the adjuvanted regimens in this trial will provide support for the use of 
adjuvants as components of vaccine regimens planned for testing in later-stage clinical 
research and development.  
While similar vaccine regimens adjuvanted with alum and with MF59® have been 
conducted and are ongoing in Thailand and in South Africa, these tests remain separated 
in time and space with samples having been and being tested in different labs with 
different assays being employed. Therefore, it remains important to compare the two 
adjuvants directly in a single study in Southern Africa, the geographic location of planned 
future efficacy studies. In addition, this study will help inform interpretation of results 
from other planned studies and will give insights into future trial designs to improve 
vaccine efficacy. 
4.2 
ALVAC-HIV (vCP2438) 
ALVAC-HIV (vCP2438) is a preparation of live, attenuated recombinant canarypox-
derived virus expressing products from the HIV-1 env gp120 (clade C), env gp41 TM 

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(clade B), gag (clade B), and protease (clade B) coding sequences and cultured in 
primary chicken embryo fibroblasts (CEFs). 
4.2.1 
Constructs 
The original strain of canarypox virus (Rentschler strain) was attenuated by serial 
passages on CEFs. The attenuated virus was plaque isolated and designated as ALVAC. 
Details of the manufacturing process are provided in the ALVAC-HIV (vCP2438) 
Investigator’s Brochure (IB). 
The inserted HIV-1 gene sequences are:  
 
The region of the env gene encoding the extracellular Env gp120 moiety of the 
96ZM651 strain of HIV-1 linked to the sequence encoding the HIV-1 TM anchor 
sequence of gp41 (28 amino acids) from HIV-1 strain LAI. The env gene 
sequence is under the control of the vaccinia virus H6 promoter. 
 
The gag gene encoding the entire Gag protein and a portion of the pol sequences 
of the LAI strain of HIV-1 sufficient to encode the protease function. The 
gag/protease gene sequences are under the control of the same vaccinia virus I3L 
promoter. 
Table 4-1 ALVAC-HIV (vCP2438) Construct Summary Table 
Inserted gene 
Strain 
Promoter 
Insertion Locus 
env (gp120 + gp41 TM) 
96ZM651 (gp120) 
LAI (gp41 TM) 
H6 (vaccinia) 
C6 
gag + pro 
LAI 
I3L (vaccinia) 
C6 
4.2.2 
Formulation characteristics 
ALVAC-HIV (vCP2438) is formulated as a lyophilized vaccine for injection and is 
reconstituted with 1.0 mL of sterile sodium chloride solution (NaCl 0.4%) for injection as 
a single dose. The composition of 1 dose of ALVAC-HIV (vCP2438) is provided in 
Table 4-2. 

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Table 4-2 Composition of ALVAC-HIV (vCP2438) 
Ingredient 
Amount in 1 dose 
Function 
ALVAC-HIV (vCP2438) 
≥ 1 x 106 CCID50 and  
< 1 × 108 CCID50 
Immunogen 
Tris-HCl 
0.3 mg 
Buffer 
Lactose-monohydrate 
26.325 mg 
Component of lactoglutamate stabilizer 
L-Glutamic acid 
0.278 mg 
Component of lactoglutamate stabilizer 
NaH2PO4.2H2O 
0.15 mg 
Component of lactoglutamate stabilizer 
K2HPO4 
0.55 mg 
Component of lactoglutamate stabilizer 
KOH 
0.1 mg 
Component of lactoglutamate stabilizer 
Sucrose 
50 mg 
Component of freeze-drying stabilizer 
Sodium glutamate monohydrate 
5.5325 mg 
Component of freeze-drying stabilizer 
HCl 
1.8 mg 
Component of freeze-drying stabilizer 
Non-essential amino acids 
1.628 mg 
Component of freeze-drying stabilizer 
Essential amino acids 
4.46 mg 
Component of freeze-drying stabilizer 
4.2.3 
Manufacturing 
ALVAC-HIV (vCP2438) Bulk Drug Substance is manufactured by IDT Biologika 
GmbH, Am Pharmapark, Dessau-Rosslau, Germany, under contract to Sanofi Pasteur. 
ALVAC-HIV (vCP2438) Drug Product is manufactured at the Sanofi Pasteur SA, facility 
located in Marcy l’Etoile, France. The diluent used for reconstitution is manufactured at 
the Sanofi Pasteur Inc. facility located in Swiftwater, Pennsylvania (USA). 
ALVAC-HIV (vCP2438) is produced by inoculating the virus seed into cultured primary 
CEFs derived from eggs produced by specific pathogen free (SPF) flocks. 
The manufacturing process for ALVAC-HIV (vCP2438) is similar to the manufacturing 
process for ALVAC-HIV (vCP1521) used in RV144. 
4.3 
Bivalent Subtype C gp120 
4.3.1 
Constructs 
Bivalent Subtype C gp120, manufactured by Novartis Vaccines at Rentschler 
Biotechnologie (Laupheim, Germany), consists of two separate subtype C recombinant 
monomeric proteins, TV1.C gp120 and 1086.C gp120. These recombinant gp120s 
represent the HIV Env surface glycoprotein containing the receptor binding domain. Each 
gp120 is modified from its wild type full-length form (gp160) by replacement of the 
native signal sequence and deletion of the entire gp41 C-terminal portion of the 
glycoprotein containing the TM and cytoplasmic domains. The combination of the 2 
subtype C gp120 proteins and the MF59® is referred to as Bivalent Subtype C 
gp120/MF59®. The combination of the 2 subtype C gp120 proteins and Aluminum 
Hydroxide Suspension is referred to as Bivalent Subtype C gp120 admixed with 
Aluminum Hydroxide Suspension. 

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4.3.2 
Manufacturing and formulation 
Each protein is expressed in Chinese hamster ovary (CHO) cells under conditions 
favorable for secretion of monomeric protein. Following fermentation, each protein is 
extensively purified as described briefly below.  
Following clone selection, a fed batch cell culture at 500L or 1000L scale is employed for 
cell propagation. Once the cells reach optimum cell density, the culture is harvested and 
purified using standard methods. Harvest clarification was performed using a series of 
depth filters followed by bioburden reduction using a sterilizing-grade filter. The harvest 
was collected in single use disposable bags and purified including further enrichment for 
monomer. Additonal processing utilizes multiple filtration steps and a series of 
chromatography steps that remove process related impurities.  
Both TV1.C and 1086.C bulk drug substances are stored frozen at not more than -60°C. 
The formulations are similar for both drug substances, containing Env antigen, sodium 
citrate, and sodium chloride, pH 6.5-7.0. Each of the HIV gp120 proteins as final 
products are tested for pH, appearance, identity, strength (concentration), purity, potency, 
as well as safety and content uniformity following US Pharmacopoeia methods where 
applicable. 
The qualitative composition per dose of each subtype C gp120 vaccine protein is 
provided in Table 4-3. 
Table 4-3 Qualitative composition of Subtype C gp120 drug substances vials 
Ingredient 
Function 
gp120 protein 
Sodium Citrate, Dihydrate 
Citric Acid, Monohydrate 
Sodium Chloride 
Water for injections 
active 
buffer 
buffer 
tonicity modifying agent 
solvent 
Additional information is provided in the Bivalent Subtype C gp120/MF59® IB. 
4.4 
MF59® adjuvant  
The Novartis MF59® adjuvant is an oil-in-water emulsion with a squalene internal oil 
phase and a citrate buffer external aqueous phase. Two non-ionic surfactants, sorbitan 
trioleate and polysorbate 80, serve to stabilize the emulsion. The qualitative composition 
is shown in the table below.  

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Table 4-4 Qualitative composition of MF59® 
Name of Ingredients 
Function 
Squalene 
oil phase 
Polysorbate  
surfactant 
Sorbitan Trioleate 
surfactant 
Sodium Citrate, dihydrate 
buffer 
Citric Acid, monohydrate 
buffer 
Water for Injection 
aqueous phase 
Nitrogen 
inert gas 
The full dose of MF59® utilized in the marketed Fluad® vaccine (containing 9.75 mg of 
squalene) will be utilized for formulation with subtype C recombinant envelope gp120 
proteins (described above). 
Additional information is provided in the Bivalent Subtype C gp120/MF59® IB. 
4.5 
Aluminum Hydroxide Suspension  
The Aluminum Hydroxide Suspension is provided by the NIH, NIAID, Vaccine Research 
Center, utilizing Rehydragel HPA from ChemTrade Logistics (Berkeley Heights, New 
Jersey, USA), diluted with sterile water for injection to a concentration of 5 mg of 
aluminum per mL and vialed under aseptic conditions consistent with cGMP regulations.  
Additional information is provided in the Bivalent Subtype C gp120 admixed with 
Aluminum Hydroxide Suspension IB Supplement. 
4.6 
Bivalent Subtype C gp120/MF59® for injection 
A final dose of 100 mcg of each recombinant Env protein will be mixed with MF59® 
adjuvant. The composition of1 dose of the resulting vaccine is shown in Table 4-5. 
Table 4-5 Composition of 0.5 mL dose of Bivalent Subtype C gp120/MF59® for injection 
Ingredient  
Amount in 1 dose  
Function  
Drug Substances  
TV1.C gp120 protein  
1086.C gp120 protein  
100 mcg  
100 mcg  
active  
active  
Adjuvant (MF59®)  
Squalene  
9.75 mg  
oil phase  
Polysorbate  
1.175 mg  
surfactant  
Sorbitan Trioleate  
1.175 mg  
surfactant  
Excipients  
Sodium Citrate, Dihydrate  
Citric Acid, Monohydrate  
Sodium Chloride  
Water for injections  
1.39 mg  
0.051 mg  
4.38 mg  
qs to 0.5 mL  
buffer  
buffer  
tonicity modifying agent  
solvent  

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4.7 
Bivalent Subtype C gp120 admixed with Aluminum Hydroxide 
Suspension for injection 
A final dose of 100 mcg of each recombinant Env protein will be admixed with 
Aluminum Hydroxide Suspension. The composition of 1 dose of the resulting vaccine is 
shown in Table 4-6. 
Table 4-6 Composition of 0.5 mL dose of Bivalent Subtype C gp120 admixed with Aluminum 
Hydroxide Suspension for injection 
Ingredient  
Amount in 1 dose  
Function  
Drug Substances  
TV1.C gp120 protein  
1086.C gp120 protein  
100 mcg  
100 mcg  
active  
active  
Adjuvant  
Aluminum hydroxide  
625 mcg aluminum 
adjuvant  
Excipients  
Sodium Citrate, Dihydrate  
Citric Acid, Monohydrate  
Sodium Chloride  
Water for injections  
1.39 mg  
0.051 mg  
4.38 mg  
qs to 0.5 mL  
buffer  
buffer  
tonicity modifying agent  
solvent  
4.8 
Trial design rationale 
The primary objective of the study is to compare the humoral immune responses induced 
by the MF59®- and alum-adjuvanted vaccine regimens; while the unadjuvanted group is 
included to provide information about the added value of the adjuvants. Therefore, a 
smaller sample size for the unadjuvanted controls is sufficient. Other important questions 
to be answered in this study are to compare the quality, magnitude, kinetics, and duration 
of the humoral and T-cell responses depending on the adjuvant used or whether ALVAC 
and proteins are co-adminstered during early vaccinations. The subset of participants who 
will provide innate immunity and mucosal samples will include 18 participants from each 
of the vaccine regimens.  
Group assignments are randomized to provide unbiased estimates of the safety and 
immunogenicity parameters of the different study arms. In addition, Groups 1, 2, and 4 
are double blinded to study arm assignment. Because Group 3 has a different vaccination 
schedule and because blood draws for innate immunity assays occur at different 
timepoints from the other 3 groups in the trial, it would not be possible to include Group 
3 in the blind without imposing an excessive number of unnecessary clinic visits, placebo 
injections, and (possibly) invasive study procedures on all trial participants. For this 
reason, a decision was taken to not include Group 3 in the blind.  
4.8.1 
Dose (amount and number) 
ALVAC-HIV (vCP2438): Viral titer ≥ 1 × 106 CCID50 and < 1 × 108 CCID50 (nominal 
dose of 107 CCID50) lyophilized vaccine to be reconstituted for IM injection. 
This study will utilize doses of ALVAC-HIV that are within the same range as was used 
for the RV144 study. The ALVAC-HIV (vCP1521) dose targeted for study RV144 was > 

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106 CCID50. The actual ALVAC-HIV titers from the 12 vaccine lots used in the RV144 
study ranged from 107.06 CCID50 to 107.41 CCID50. 
Titers of the ALVAC-HIV (vCP205) construct used in studies ranged from 105.6 CCID50 
to 106.85 CCID50. A dose response analysis was conducted with samples collected on 
Days 98 and 182 in the AIDS Vaccine Evaluation Group (AVEG) 022, 022A, 027, 032, 
033, 034 and 034A studies. In summary, these data indicate that while there is not a 
positive dose-response relationship between ALVAC-HIV and cytotoxic T lymphocyte 
(CTL) responses, use of the lower titer is not optimal for induction of nAb responses. 
Therefore, many clinical studies in humans have targeted an ALVAC dose > 106 CCID50. 
HVTN 039 is the only study that has compared the safety and immunogenicity of 
ALVAC-HIV (vCP1452) given at the standard dose (107.25 CCID50) to a dose 5.6 times 
higher (108 CCID50), and placebo [39]. The high-dose ALVAC-HIV (vCP1452) resulted 
in unacceptable levels of reactogenicity, without evidence of improved immunogenicity. 
Although extrapolation of these findings to other ALVAC-HIV vaccines requires caution, 
the study suggested that an ALVAC-HIV dose < 108 CCID50 is desirable.  
For the Bivalent Subtype C gp120/MF59® vaccine component, the two gp120 subtype C 
proteins (TV1.C gp120 and 1086.C gp120) will be admixed with the oil-in-water 
emulsion MF59®  by the Pharmacist at each CRS prior to IM administration of a 0.5 mL 
injection containing 100 mcg of each protein plus MF59® adjuvant. 
For the Bivalent Subtype C gp120 admixed with Aluminum Hydroxide Suspension 
vaccine component, the two gp120 subtype C proteins (TV1.C gp120 and 1086.C gp120) 
will be admixed with Aluminum Hydroxide Suspension by the Pharmacist at each CRS 
prior to IM administration of a 0.5 mL injection containing 100 mcg of each protein plus 
alum adjuvant. 
For the Bivalent Subtype C gp120 without adjuvant vaccine component, the two gp120 
subtype C proteins (TV1.C gp120 and 1086.C gp120) will be admixed by the Pharmacist 
at each CRS prior to IM administration of a 0.5 mL injection containing 100 mcg of each 
protein plus diluent. 
Bivalent Subtype C gp120 vaccine has not yet been administered to humans. The 
200 mcg total dose was selected based on previous clinical experience. Limited dose 
range studies performed with Novartis (formerly Chiron) a combination of subtype B SF2 
gp120 and subtype E gp120 protein candidates indicated that 50 mcg and 100 mcg doses 
(ie,150 mcg total) with MF59® adjuvant were immunogenic and well tolerated [40]. 
Using the same dose of each protein (100 mcg) in all active arms will allow head-to-head 
comparisons between groups without introducing variability in protein content. 
4.8.2 
Schedule 
This trial will use the same vaccination schedule used in RV144, in HVTN 097 (which is 
administering the RV144 vaccine regimen in a South African study population), and the 
primary vaccine regimen in the HVTN 100 trial, which will administer the ALVAC-HIV 
(vCP2438) + Bivalent Subtype C gp120/MF59® vaccine regimen in South Africa. 
Considerations underlying selection of this schedule for RV144 are described in Section 
4.11.4.1.  

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Furthermore, in light of the lower IgA responses seen in HVTN 096 when recombinant 
NYVAC and AIDSVAX B/E were co-administered at all time points, we will also 
evaluate the concurrent administration of ALVAC-HIV (vCP2438) + Bivalent Subtype C 
gp120/MF59® in a separate group. This latter schedule will administer the vaccines at 
months 0, 1, and 6 to determine if longer interval of the third boost will allow a 
maturation of antibody responses as seen for influenza vaccines [34]. In addition, data 
from HVTN 096 shows that antibody responses peaked after the third protein 
administration in the groups with protein co-administered at every vaccination.  
4.8.3 
Prime-boost regimen 
In Groups 1, 2, and 4, this trial will employ the same strategy as RV144, that is, utilizing 
the ALVAC vector as a prime and the ALVAC vector/protein dual component boost. 
Group 3 participants will receive the ALVAC vector/protein dual component 
concurrently at Months 0, 1, 6, and 12. The HIV Env inserts in the ALVAC vector differ 
from those in RV144 in that they encode subtype C Env to more closely match the viral 
strains present in the Southern Africa region [41-44]. As noted above, ALVAC-HIV 
(vCP2438) encodes the subtype C Env gp120 from HIV-1 strain 96ZM651 in addition to 
the same Gag and parts of Pol used in RV144 (HIV-1 clade B LAI strain). The Bivalent 
Subtype C gp120 protein consists of two subtype C recombinant monomeric proteins, 
TV1.C gp120 and 1086.C gp120.  
4.8.4 
Choice of control 
The vaccine regimen with the unadjuvanted Bivalent subtype C gp120 protein will serve 
as an active control for the two regimens containing MF59® and alum adjuvants. 
4.8.5 
Rationale for the innate, early adaptive and mucosal sampling timepoints 
Examining the effects that the two adjuvants have on a variety of immune responses 
relative to each other and to the unadjuvanted protein is an important goal of this study.  
Systemic innate immune responses will be measured on Day 1 and Day 3 following the 
vaccination when participants are first exposed to protein ± adjuvants. For Groups 1, 2, 
and 4, this represents Day 1 and Day 3 following the third vaccination. For Group 3, this 
sampling will take place on Day 1 and Day 3 following the first vaccination. 
For Groups 1, 2, and 4, early systemic adaptive immune responses will be measured in 
samples collected at Day 0, Month 0.25, Month 3.25, Month 6.25, and Month 12.25. For 
Group 3, these samples will be collected at Day 0, Month 0.25, Month 6.25, and Month 
12.25. These samples will provide both baseline and postvaccine information.  
Systemic and mucosal samples collected at Day 0 provide the baseline values prior to 
vaccination while those collected at Month 6.5 provide data on peak vaccine-induced 
mucosal and systemic adaptive immune responses.   
Finally, collection at Month 18 will provide the opportunity to assess the durability of 
mucosal and systemic humoral immune responses 6 months after the last vaccination. 

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4.9 
Plans for future product development and testing 
The adjuvants used in this study (MF59® and aluminum hydroxide) have never been 
compared directly in a clinical trial. It is anticipated that the vaccine regimen given with 
MF59® will induce a systemic and mucosal Ab response of greater magnitude than the 
same vaccine regimen given with aluminum hydroxide and that both will surpass the 
magnitude of immune responses elicited by the unadjuvanted study products. Such a 
finding would strengthen the rationale for the planned efficacy trials in Southern Africa 
that will use MF59®. Moreover, the design of future vaccine studies could be adjusted if 
lower IgA responses are demonstrated in the vaccinees receiving the simulatenous 
administration of the ALVAC-HIV vector and protein combination at all timepoints 
compared to individuals receiving initial ALVAC-HIV prime followed by ALVAC-HIV 
plus protein boost, provided that coadministration at all timepoints is associated with 
other  potentially favorable immune responses, such as high V1V2 binding antibody 
titers. Future vaccine design could also be impacted if a longer dosing interval allows for 
improved antibody maturation. If we see that mucosal Ab responses are enhanced in the 
aluminum hydroxide group (similar to the results observed in the previously cited NHP 
studies), these data can be used in conjunction with data from other planned studies to 
better understand immune correlates of HIV risk and to inform improvements in future 
vaccines and vaccine trial designs. 
4.10 
Preclinical safety studies 
4.10.1 
IM local tolerability and systemic toxicity study in New Zealand White Rabbits 
(Study AB20670) 
An objective of the study was to determine the local tolerability and systemic toxicity of 
ALVAC-HIV (vCP2438)/ALVAC-HIV (vCP2438) with gp120+MF59 vaccines 
administered by the IM route to New Zealand White Rabbits 7 times at 2-week intervals, 
followed by a 2-week recovery period. 
There were no deaths during the study. No treatment-related clinical signs were reported 
during the study and treatment was locally well tolerated. Body temperature was slightly 
increased, mostly after the 1st injection, but returned to normal within 48 hours. There 
were no effects of treatment on body weight or food consumption. No treatment-related 
ophthalmological findings were observed at the end of the treatment period. 
When compared to the control group, a transient increase in C-reactive protein, globulin, 
fibrinogen, or neutrophil count was observed after one or more of the immunizations. 
These effects correlated with the inflammatory findings observed histopathologically at 
the injection sites. There were no other treatment-related differences from the controls 
amongst the biochemistry or hematological parameters. 
At necropsy, at the end of treatment, the only histologic changes due to the test items 
were in the injection sites and iliolumbar and sacral lymph nodes. In the sites injected 
with ALVAC or gp120s+MF59, the changes comprised inflammatory cell infiltrates, 
necrosis, fibrosis, hemorrhage, acellular material, and mineralization. These findings 
were often only minimal or slight. In the lymph nodes that drained the injected sites, 
there was minimal or slight increased lymphoid follicle development, increased 
paracortex, and granulocyte infiltrate. There was evidence of partial resolution of the 

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described changes at both injection site and lymph nodes, based on necropsy observations 
after the recovery period. 
In conclusion, under the defined study conditions, 7 intramuscular administrations of 
ALVAC-HIV (vCP2438) vaccine associated with gp120s/MF59 (last 4 injections) to the 
New Zealand White Rabbit at two-week intervals were clinically and locally well 
tolerated. The study supports the use of this vaccine regimen in human clinical trials. 
4.10.2 
ALVAC-HIV 
Nonclinical safety data from a variety of other ALVAC constructs inform the safety 
profile of ALVAC-HIV (vCP2438). These studies include the following: 
 
Platform biodistribution study of ALVAC-HIV in rats; 
 
ALVAC viral replication in different cell lines; 
 
Virulence of the ALVAC vector versus Vaccinia strains; 
 
Single dose toxicity studies by intravenous route with various ALVAC 
recombinants in mice and rats; 
 
Repeated dose toxicity studies using several routes of administration (including 
IM) with various ALVAC recombinants in cynomolgus and rhesus monkeys; 
 
Local tolerance and sensitization studies with various ALVAC recombinants in 
rabbits; and  
 
Hypersensitivity study with ALVAC-HIV (vCP125) in guinea pigs. 
The results of these studies show a satisfactory nonclinical safety profile and support the 
administration of the ALVAC-HIV (vCP2438) construct to humans. For additional 
information, see the ALVAC-HIV (vCP2438) IB. 
4.10.3 
Toxicity studies of HIV Env vaccines  
The nonclinical safety of 4 doses of the gp120 proteins when co-administered with 
ALVAC-HIV (vCP2438) as a boost after 3 doses of ALVAC-HIV (vCP2438) given 
alone (prime), was evaluated in study AB20670 in New Zealand White Rabbits, as 
mentioned in Section 4.10.1. Overall, the immunizations were clinically and locally well 
tolerated. 
The nonclinical safety of 6 doses of the gp120 proteins, when co-administered with 
DNA-HIV-PT123, was also evaluated in study AB20670 in New Zealand White Rabbits. 
There were no deaths during the study. No treatment-related clinical signs were reported 
during the study and treatment was locally well tolerated. There was no obvious effect on 
body temperature. A lower body weight gain was noted in males only over the study 
period. However this was not related with lower food consumption. No treatment-related 
ophthalmological findings were observed at the end of the treatment period. When 
compared to the control group, a slight transient increase in C-reactive protein 
concentration was noted mainly after the first administration. These effects correlated 
with the inflammatory findings observed histopathologically at the injection sites. An 
increase in creatine kinase was noted after the first administration only. At necropsy, at 
the end of treatment, the only histologic changes due to the test items were in the 
injection sites and iliolumbar lymph nodes. In the sites injected with DNA-HIV-PT123 or 

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gp120s+MF59, changes comprised fibrosis, hemorrhage, acellular material and 
inflammatory cell infiltrate usually minimal or slight, but occasionally more severe. In 
the lymph nodes which drained the injected sites, there was minimal to moderate 
increased paracortex and increased lymphoid follicle development and minimal 
granulocyte infiltration. There was evidence of partial resolution of the described changes 
at both injection site and lymph nodes, based on necropsy observations after the recovery 
period. In conclusion, under the defined study conditions, 6 intramuscular administrations 
of DNA-HIV-PT123 vaccine associated with gp120 proteins adjuvanted with MF59 to 
New Zealand White Rabbits at two-week intervals were clinically and locally well 
tolerated. 
In addition, nonclinical in vivo Good Laboratory Practice (GLP) toxicology studies were 
conducted with early candidate subtype B and E gp120 Env protein vaccine candidates 
that were subsequently advanced to phase 1-2 clinical trials. More recently, similar 
subtype B gp140 and subtype C gp140 vaccine candidates with MF59® have been tested 
in nonclinical safety studies. The subtype C gp140 previously tested was from the same 
strain (HIV-1 TV1) as 1 of the components (TV1.C gp120) in the proposed Bivalent 
Subtype C gp120/MF59® vaccine, and hence is very similar in sequence. Overall, 
toxicology studies revealed that both the subtype B gp140 and subtype C gp140 vaccines 
with MF59® were well tolerated and testing revealed no adverse local or systemic effects. 
Data from the following nonclinical studies are included in the IB:  
 
Subchronic IM toxicity study of Biocine® HIV Thai E gp120/SF 2 gp120 vaccine 
in rabbits; 
 
Repeat dose toxicity of IM HIV DNA/PLG prime followed by IM subtype B 
gp140/MF59® in rabbits; 
 
Repeat dose toxicity of intranasal (IN) subtype B gp140 with an LTK63 adjuvant 
followed by IM subtype B gp140 with MF59® in rabbits; and 
 
Repeat dose toxicity of IM SAAVI DNA-C2 followed by IM SAAVI MVA-C 
with subtype C gp140/ MF59® in rabbits. 
4.10.3.1 
Toxicity studies of MF59® 
MF59® is not associated with any potential for systemic toxicity and it has a low order of 
local reactogenicity. In repeat-dose rabbit studies, clinical pathology findings of increased 
fibrinogen and minor inflammatory and degenerative changes at the injection site are 
consistent with the effects of IM injections of an immunogenic adjuvant. These findings 
are readily reversible within days to 1 to 2 weeks. In repeat-dose toxicology studies in 
dogs, there were no effects on cardiovascular or central nervous system (safety 
pharmacology) parameters. MF59® is not genotoxic (Ames test) or clastogenic (mouse 
micronucleus), is not a dermal sensitizer (Guinea pig), and was not teratogenic (rat and 
rabbit) or a developmental toxicant (rat).  
Pivotal toxicology studies performed with MF59® include: 
 
single- and repeat-dose toxicity (including local tolerability),  
 
genotoxicity,  

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 
sensitization, and  
 
embryofetal and developmental toxicity.  
4.11 
Clinical studies 
4.11.1 
HVTN 100 
HVTN 100 protocol version 1.0 enrolled 252 participants between February and May 
2015. All Month 12 injections were completed by 2 June 2016. 
4.11.1.1 
Interim summary of blinded safety and tolerability data 
Blinded safety data reported as of November 2016 are summarized here. A total of 1198 
ALVAC or placebo injections were given to participants in the left deltoid and 703 
Bivalent Subtype C gp120/MF59 or placebo injections were given to participants in the 
right deltoid.  
The vaccine regimen is very well tolerated thus far with the vast majority experiencing no 
or mild local reactogenicity symptoms. Mild pain and/or tenderness was reported by 58% 
of participants for injections in the left deltoid and by 48% for injections in the right 
deltoid. Moderate pain and/or tenderness was reported by 18% of participants for 
injections in the left deltoid and by 11% for injections in the right deltoid. Severe pain 
and/or tenderness was reported from a left deltoid injection by 1 participant (following 
the 1st injection) and for a right deltoid injection by 2 participants (following the 3rd or 5th 
injection).  
For the left deltoid, grade 1 (mild) erythema and/or induration injection site reactions 
were reported by 6% of participants and grade 2 (moderate) reactions by 5% of 
participants. For the right deltoid, grade 1 erythema and/or induration injection site 
reactions were reported by 4% of participants and grade 2 reactions by 2% of 
participants. Three participants have reported erythema and/or induration reactions 
meeting grade 3 criteria (severe) based on size (≥ 10cm diameter or ≥ 100cm2 surface 
area) with no complications (such as ulceration, secondary infection, phlebitis, sterile 
abscess, or drainage). One person reported a grade 3 right deltoid erythema reaction 
(> 100 cm2) occurring on Day 2 following the 4th injection, which resolved within 4 days. 
This participant also self-reported severe induration on Day 3, which resolved within 1 
day. The participant returned to clinic on Day 4 for examination, and clinic staff observed 
severe erythema alone without induration or swelling. Antibiotics, analgesics, and 
antihistamines were prescribed and the participant was discontinued from further 
vaccinations but continued in follow-up. Another person reported grade 3 induration and 
erythema in the right deltoid on Day 3 after the 5th vaccination, resolving by Day 5. 
Antibiotics, anti-inflammatory, and analgesic medications were prescribed and were 
taken for 3 days. Another person reported severe erythema and induration reactions in the 
left deltoid occurring on Day 0 after the 5th vaccination and resolving by Day 3. 
Antihistamine, oral steroid, and analgesic/anti-inflammatory medications were taken. In 
all 3 participants, the needle used for injection was < 1.5” long, consistent with weight-
based guidance for needle length choice provided to sites in the SSPs [45,46].  
Systemic reactions have been reported in 69% of participants thus far, with the vast 
majority of those reactions being mild in intensity. Malaise and/or fatigue, headache, 
myalgia and arthralgia appear to be the most common reactions, occurring in 42%, 41%, 

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37%, and 30% of participants, respectively, thus far. Other systemic reactogenicity 
symptoms have included nausea (15%), chills (10%), fever (8%), and vomiting (4%). 
Maximum severity of systemic symptoms of moderate intensity has been reported in a 
total of 19% of participants; 7% reported systemic symptoms of moderate intensity after 
the 1st injection, 3% after the 2nd, 5% after the 3rd, 2% after the 4th, and 5% after the 5th. 
Severe systemic reactions have occurred in 2% of participants (4 participants): 2 
participants with severe arthralgia occurring after the 1st injection, 1 person with severe 
malaise and/or fatigue and 1 with severe headache, each after the 5th injection. 
4.11.1.2 
Interim summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) 
As of November 2016, 467 adverse events (AEs) have occurred in 181 participants (72% 
of participants), of which 282 AEs (60%) were mild, 165 were moderate, (35%), 13 (3%) 
were classified as severe, 3 (0.6%) were classified as potentially life-threatening, and 2 
(0.4%) were fatal. AEs were reported by participants most frequently in the Systems 
Organ Class (SOC) Infections and infestations (132 participants [52% of enrolled 
participants]), followed by the SOC Investigations (71 participants [28%]). Fourteen AEs 
occurring in 11 participants have been assessed by the site investigator as being related to 
study product; 11 were mild, 3 were moderate, and none were severe. These include 
injection site pruritus in 3 individuals (mild in 2, moderate in 1), lymphadenopathy in 2 
individuals (both mild), abdominal pain (moderate), generalized pruritus (moderate), and 
mild events of diarrhea, injection site nodule, gastritis, dizziness, headache, neutrophil 
count decreased, and oral paresthesia in 1 individual each.  
Eight SAEs, including 2 deaths, have occurred in 6 participants during the trial, all 
unrelated to study product. One participant experienced 3 separate SAE events resulting 
from 3 separate assault attacks: severe soft tissue injury due to assault, potentially life-
threatening subdural hematoma, and then multiple injuries to the head and chest that were 
fatal. SAEs in other participants were: gastrointestinal infection, bi-polar mood disorder, 
acute rheumatic fever, transient ischemic attack, and completed suicide. 
4.11.1.3 
Discontinued vaccinations and early terminations 
As of 21 November 2016, 232 participants have terminated the study: 207 at scheduled 
study exit (on-time) and 25 participants have terminated the study prematurely. Twenty-
two participants have discontinued vaccinations. Clinical events leading to early 
terminations and discontinuation of vaccinations (DOV) occurred in 6 participants: death 
from multiple injuries (unrelated to study product); death from completed suicide 
(unrelated to study product); severe local reactogenicity (DOV); hypertension (DOV for 
AE unrelated to study product); mild vomiting occurring on the day of 1st vaccination 
only (participant declined further study participation); psychiatric diagnosis (DOV and 
early termination for investigator discretion). Reasons for DOV or early termination in 
other participants included HIV infection, participant refusal, unable to contact, unable to 
schedule within visit windows, unable to adhere to study schedule, relocation, desiring to 
fall pregnant, desiring to donate eggs, unwilling to use contraception, and pregnancy. 
Two pregnancies have been reported to date, with one participant reporting a full term 
live birth and the other pregnant participant is continuing in follow-up.  
4.11.1.4 
Summary of Interim Immunogenicity data from HVTN 100 
Section [6.1.2] of version 1.0 of HVTN 100 (Part A) describes the immunological criteria 
guiding the decision whether to advance development of the ALVAC-HIV (vCP2438), 
Bivalent Subtype C gp120/MF59® regimen. Except for the increased stringency of the 

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V1V2 response rate criteria (LL of the 95% CI increased from ≥ 45% to ≥ 56%), these 
same criteria ultimately formed the basis of the decision to proceed forward with HVTN 
702, A pivotal phase 2b/3 multi-site, randomized, double-blind, placebo-controlled 
clinical trial to evaluate the safety and efficacy of ALVAC-HIV (vCP2438) and Bivalent 
Subtype C gp120/MF59 in preventing HIV-1 infection in adults in South Africa (Table 
4-7). Immunogenicity data from samples collected from HVTN 100 participants at the 
month 6.5 timepoint (2 weeks post 6 month vaccination) were compared to data from a 
new, randomly selected subset of stored samples from RV144 vaccine recipients who 
were HIV-1 uninfected upon completion of follow-up (the RV144 “comparator arm”). 
Samples from the RV144 comparator arm and HVTN 100 participants were analyzed 
contemporaneously using qualified assays in the same laboratories (along with placebo 
samples for blinding).  
All four immunogenicity Go criteria were met. 
Table 4-7 Go/No-Go criteria for advancement of the HVTN 100 vaccine regimen to efficacy 
testing 
Variable Measured at Month 6.5 
Rationale 
Go Criteria Threshold 
(LL of 95% CI) 
1. Env Ab Response Rate (≥ 2 of 3 
antigens) 
Adequate Ab take to vaccine Env 
≥75% 
2. Env Ab Magnitude(≥ 2 of 3 
antigens) 
Non-inferior Ab magnitude vs. RV144 
GM ratio 
(new/RV144) ≥50%* 
3. Env CD4 Response Rate (1 of 1 
antigen) 
Non-inferior CD4 T-cell take vs. RV144 
Difference within 
30%*  
4. Env V1V2 Response Rate (≥ 1 of 
3 antigens) 
Adequate to predict achieving estimated 
VE=50% for 2 years if V1V2 Ab is a 
predictive immune correlate  
≥ 56% 
*Non-inferior to RV144 response based on contemporaneous assessment of clade C vaccine samples vs. 
RV144 vaccinee samples by the same lab. 
Binding antibody responses to Env (criteria 1 and 2): 
At the month 6.5 timepoint, 100% of vaccinees in HVTN 100 part A developed binding 
antibodies to the gp120 Clade C strain Env antigens in the ALVAC vector, as well as the 
two Clade C strains in the bivalent gp120 protein boost (Figure 4-1). Antibody magnitude 
values measured by geometric mean titers were 3.6-8.8 fold greater than IgG binding 
antibody to vaccine-matched responses to Env antigens included in RV144 (Table 4-8), 
meeting criteria 1 and 2. 

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Figure 4-1  Box plots of the binding antibody titers to the vaccine antigens used in RV144 
and HVTN 100. The midline of the box plot indicates the median, the ends of the box indicate 
the 25th and 75th percentiles. Closed dots represent positive responses, open triangles 
represent negative responses. 
Table 4-8 HVTN 100 vs. RV144 Peak bAb magnitudes to gp120 among vaccinees 
Protocol 
Antigen 
n 
Geometric Mean Titer 
GMR 
(100/RV144) 
GMR  
95% CI 
100 
1086 
185 
26,257.5 
8.8 
(7.64, 10.2) 
RV144 
A244 
201 
2,968.9 
100 
TV1 
185 
10,726.7 
3.6 
(3.01, 4.34) 
RV144 
A244 
201 
2,968.9 
100 
ZM96 
185 
2,685.4 
3.6 
(2.95, 4.39) 
RV144 
92TH023 
201 
746.1 
CD4 responses (criterion 3) 
The CD4+ T cell response rate to vaccine-matched Env sequences in ALVAC 
(vCP2438), (Env peptide pool ZM96) in HVTN 100 participants was 58%. This was 
compared to the CD4+ T cell response rate to vaccine-matched Env sequences in 
ALVAC (vCP1521),( Env peptide pool 92TH023) in RV144 participants of 41%. The 
response rate difference (100-RV144) was 16% (95% CI: 6, 16%; p value 0.0019). This 
exceeded the LL response rate difference of -30%, meeting criterion #3. 
V1V2 antibody response rates (criterion 4) 
The binding antibody response rate to the vaccine-matched 1086.C V1V2 antigen was 
71% (95% CI 64% - 77%), thereby meeting criterion #4 that the prevalence of IgG 
antibodies to the Clade C V1V2 loop in at least one vaccine antigen must be at a lower 

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limit threshold of > 56% (which equates to a response rate of 63%) (Table 4-9). The 
cumulative V1V2 response is 80%; well above the 63% threshold that was established for 
modeling a 50% efficacy if V1V2 was the Sole Correlate of Protection. 
Table 4-9 HVTN 100 Binding Antibody Env V1V2 Response Rates, Per-Protocol Cohort 
(Go/No-Go Criterion 4) 
Antigen 
Treatment 
Response 
Rate 
95% CI 
LL of CI 
≥56% 
Criterion 4 
Passed? 
1086.C.V1V2 tags 
T1 (n=183) 
P2 (n=35) 
71% 
0% 
(64%, 77%) 
(0%, 10%) 
Yes 
Yes 
gp70-V1V2CladeB CaseA2 
T1 (n=183) 
P2 (n=35) 
50% 
0 % 
(43%, 57%) 
(0.0%, 9.9%) 
No 
 
gp70-V1V2.TV1 
T1 (n=183) 
P2 (n=35) 
62% 
0% 
(55%, 69%) 
(0%, 10%) 
No 
 
 
1086.C.V1V2 tags or gp70-V1V2.TV1 
T1 (n=183) 
80% 
(74%, 85%) 
N/A 
1086.C.V1V2 tags or 
 gp70-V1V2CladeB CaseA2 or gp70-
V1V2.TV1 
T1 (n=183) 
80% 
(74%, 85%) 
N/A 
 
Based on the immunogenicity results of the month 6.5 timepoint in HVTN 100, the 
decision was made to proceed with HVTN 702. 
4.11.2 
Other clinical studies with related ALVAC-HIV® vaccines 
The proposed ALVAC-HIV vaccine candidate specific for Southern Africa is ALVAC-
HIV (vCP2438). The vaccine is most similar to ALVAC-HIV (vCP1521) (the ALVAC-
HIV used in the RV144 trial) since it contains the same gag, pro and gp41env TM 
components. However, it has been adapted to include ZM96 gp120 env insert (subtype C) 
(rather than the TH023 gp120 env insert [subtype E] used for the RV144 study regimen 
in Thailand). 
There is extensive previous experience with other ALVAC-HIV vaccines informs the 
expected safety, tolerability, and immunogenicity profile of the new vaccine (see Table 
4-10). In all, more than 10,000 people have received ALVAC-HIV vaccines in clinical 
trials. The majority of these trials have been performed with ALVAC-HIV (vCP205), 
(vCP1452), or (vCP1521). These vaccines differ in the HIV gene inserts that have been 
introduced into the ALVAC vector.  

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Table 4-10 Recombinant ALVAC-HIV vaccine in human adult prevention trials 
Candidate vaccine 
# receiving 
ALVAC-HIV 
Protocol 
Status 
ALVAC-HIV (vCP125) 
20 
ANRS VAC01 
Completed 
ALVAC-HIV (vCP125) (low and high dose) 
92 
AVEG 012A/012B 
Completed 
ALVAC-HIV (vCP205) 
25 
ANRS VAC03 
Completed 
ALVAC-HIV (vCP205) (low and high dose) 
185 
AVEG 022/022A 
Completed 
ALVAC-HIV (vCP205) 
22 
AVEG 029 
Completed 
ALVAC-HIV (vCP205) 
56 
AVEG 027 
Completed 
ALVAC-HIV (vCP205) 
290 
HVTN 203 
Completed 
ALVAC-HIV (vCP205) 
56 
AVEG 032 
Completed 
ALVAC-HIV (vCP205) 
280 
AVEG 202/ HIVNET 014 
Completed 
ALVAC-HIV (vCP205) 
30 
AVEG 033 
Completed 
ALVAC-HIV (vCP205) 
20 
HIVNET 007 
Completed 
ALVAC-HIV (vCP300) 
20 
ANRS VAC07 
Completed 
ALVAC-HIV (vCP300) 
119 
AVEG 026 
Completed 
ALVAC-HIV vector (vCP205, 1433, 1452) 
20/35/35 
AVEG 034 
Completed 
ALVAC-HIV (vCP205/1452) 
15/40 
AVEG 034A 
Completed 
ALVAC-HIV (vCP1452) 
22 + 3 
ANRS 010 
Completed 
ALVAC-HIV (vCP1452) 
160 
HVTN 203 
Completed 
ALVAC-HIV (vCP1452) 
120 
HIVNET/HVTN 026 
Completed 
ALVAC-HIV (vCP1452) 
100 
HVTN 039 
Completed 
ALVAC-HIV (vCP1521) 
203 
RV 132/135 
Completed 
ALVAC-HIV (vCP1521) 
8202 
RV 144 
Completed 
ALVAC-HIV (vCP1521) 
135* 
RV 305 
Completed 
ALVAC-HIV (vCP1521) 
327 
RV 306 
Ongoing 
ALVAC-HIV (vCP1521) 
80 
HVTN 097 
Completed 
ALVAC-HIV (vCP2438) 
210 
HVTN 100 
Ongoing 
ALVAC-HIV (vCP2438) 
2700* 
HVTN 702 
Ongoing 
Total 
13,692** 
 
 
* Planned 
** Includes planned number of ALVAC recipients in HVTN 702. 
ALVAC-HIV® (vCP205) is an ALVAC vector vaccine with genetic inserts of the HIV-1 
gag gene (expressing the Gag p55-polyprotein of the HIV-1 LAI strain [clade B]), a 
fragment of the pol gene (that expresses the p15 Protease of the HIV-1 LAI strain), and a 
portion of the env gene (expressing the gp120 Env glycoprotein of the HIV-1 MN strain 
[clade B], and the anchoring TM region of gp41 of the HIV-1 LAI strain). The HIV genes 
are inserted in the C3 locus. 
ALVAC-HIV (vCP1452) vaccine is an ALVAC vector vaccine expressing the products 
of the HIV-1 env (Env gp160 protein of the HIV-1 MN Strain [clade B]) and gag (HIV-1 
LAI strain [clade B]) genes, the protease portion of the pol gene on a synthetic 
polynucleotide encompassing the known human CTL epitopes from the nef (BRU Strain) 
and the pol (LAI strain) gene products. The C3 locus was used for the insertion of the 
HIV-1 env and gag gene sequences and the C5 locus was used for the insertion of the 
sequences encoding the HIV-1 Nef and Pol CTL epitopes.  
ALVAC-HIV (vCP1521) vaccine was generated by co-insertion of genes encoding HIV-
1 gene products into the ALVAC genome in the C6 locus. The inserted HIV-1 gene 
sequences are: the region of the env gene encoding the extracellular Env gp120 moiety of 

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TH023 strain of HIV-1 (clade E) linked to the sequences encoding the HIV-1 TM anchor 
sequence of gp41 HIV-1 LAI strain (clade B); the gag gene encoding the entire Gag p55-
polyprotein of the HIV-1 LAI strain; and a portion of the pol sequences of the LAI strain 
of HIV-1 sufficient to encode the protease function. 
4.11.3 
Clinical safety experience with related ALVAC-HIV vaccines 
4.11.3.1 
Summary of safety, reactogenicity, and tolerability from related human experience 
The tolerability and safety of ALVAC-HIV (vCP1521) were evaluated initially in 2 phase 
1-2 studies in Thailand [24,27]. The most relevant data, however, come from the RV144 
efficacy study performed in Thailand [4,47], during which more than 8000 human 
subjects received the vaccine and ALVAC-HIV (vCP1521) was found to be safe and well 
tolerated. Vaccine recipients experienced local and/or systemic reactions significantly 
more frequently than placebo recipients; the frequencies of local reactions such as pain 
and tenderness were higher than those of systemic reactions such as headache, fatigue, 
arthralgia and myalgia; fever was rarely reported; ALVAC-HIV (vCP1521) was 
associated with a higher frequency of local reactions compared to the protein subunit 
used in the study (AIDSVAX® B/E); the frequency of both local and systemic reactions 
gradually declined with subsequent vaccine administrations; most local and systemic 
reactogenicity symptoms were mild to moderate, resolving rapidly and spontaneously in 
the vast majority of cases; and the frequencies of adverse events (AEs) and Serious 
Adverse Events (SAEs) were not different between vaccine and placebo groups. Overall, 
results with ALVAC-HIV (vCP1521) are consistent with other ALVAC-HIV constructs, 
supporting the conclusion that the safety, reactogenicity and tolerability profile of 
ALVAC-HIV is determined in greater measure by the vector than by the HIV genetic 
material inserted into it.  
Prior to the RV144 study, De Bruyn et al [48] characterized the tolerability and safety 
profile of ALVAC-HIV (vCP205) and ALVAC-HIV (vCP1452) (along with other 
ALVAC-vector vaccines) based on data from more than 1,000 clinical trial subjects. The 
authors concluded that:  
1.  ALVAC-HIV vaccines were safe and well tolerated, with a reactogenicity 
profile comparable to that of existing vaccines licensed for use in adults; and  
2. Reactogenicity was similar for different ALVAC-HIV constructs, suggesting that 
reactogenicity is determined in greater measure by the vector than by the 
additional genetic material inserted into the vector.  
Of interest as well was the observation that reactogenicity seemed to differ according to 
certain demographic variables: Black, non-Hispanic participants reported significantly 
less reactogenicity than did White, non-Hispanic participants; and males reported less 
pain than females. 
Additional information is available in the ALVAC-HIV (vCP2438) IB. 
4.11.3.2 
Summary of pregnancy occurrence and outcomes 
In study RV144 a total of 967 (30.6%) vaccine (vCP1521) and 955 (30.1%) placebo 
recipients reported a pregnancy during the study while 139 vaccine and 116 placebo 
recipients reported more than1 pregnancy. Birth was reported for 1843 infants, 14 of 
them representing 7 twin pairs. Of these, 277 births (137 vaccine and 140 placebo 

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recipients; 1 twin pair per treatment) occurred within 450 days of study entry. For these 
infants, birth weight, gestational age and Apgar scores were similar between the vaccine 
and placebo groups. Three congenital abnormalities (1 vaccine and 2 placebo recipients) 
were reported among these 277 births, the vaccine group abnormality being a respiratory 
distress syndrome with patent ductus arteriosus. Abnormal pregnancy outcomes were 
experienced in 165 out of 3165 (5.2%) vaccine female recipients and 139 out of 3169 
(4.4%) placebo female recipients (p = 0.13), and in 17.1% and 14.6% (p = 0.13) of 
vaccine and placebo pregnancies, respectively [47]. 
A total of 15 of the 245 female subjects became pregnant during the AVEG studies. 
Twelve subjects received ALVAC-HIV (vCP205) and 3 received placebo. Of these 15 
subjects aged 19 to 37 years, 9 subjects had live births, 3 subjects had elective abortions, 
1 subject had a spontaneous abortion, and the outcome of 2 pregnancies remains 
unknown. Of the 9 live births, 3 were by caesarean section. Overall, no complications 
during pregnancy or congenital abnormalities at the time of birth were reported. 
In study HVTN 203 [49] there were 2 participants with miscarriages among the total of 
80 female study participants who received ALVAC-HIV (vCP1452). These events were 
classified as unrelated to the study product by the investigators. 
4.11.3.3 
Summary of safety and tolerability data in African studies that have used ALVAC-HIV 
To date, 2 studies have been conducted and completed in Africa with ALVAC-HIV: 
HIVNET 007 and HIV Prevention Trials Network (HPTN) 027.  
HIVNET 007 [50] was a randomized, double-blind, placebo-controlled clinical trial 
conducted in Kampala, Uganda. In this study, 40 HIV-seronegative Ugandan volunteers 
were randomly assigned to receive ALVAC-HIV (vCP205) (n = 20), control ALVAC 
containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). 
Adverse reactions to immunizations were similar to those in previous trials with these 
vaccines in HIV-seronegative volunteers in the United States. No severe (grade 3 or 4) 
adverse reactions attributable to receipt of the vaccine were observed. 
HPTN 027 [51] was a phase 1 randomized, single-center, double-blind, placebo-
controlled trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP1521) 
in infants born to HIV-1 infected women in Uganda. 60 infants were enrolled with 48 in 
the active group and 12 in the placebo group. Forty-seven infants received all 4 
vaccinations and completed follow-up (38 in the vaccine arm and 9 in the placebo arm). 
There were 3 deaths in the HPTN 027 study (2 in the vaccine group and 1 in the placebo 
group); all were reported as unrelated to the vaccine. The deaths included pneumonia-like 
illness, cor pulmonale secondary to congenital heart disease complicated by pneumonia, 
and gastroenteritis complicated with electrolyte imbalance. The rate of SAEs was similar 
between groups (56% in the vaccine group and 50% in the placebo group). Thirteen 
infants in HPTN 027 experienced an AE that led to discontinuation of vaccinations: 10 
subjects in the vaccine group and 3 in the placebo group. There were no severe or life-
threatening reactogenicity events. Mild reactogenicity events were common in both study 
arms, with only 1 moderate event (irritability) in the placebo arm and 7 in the vaccine 
group (erythema, induration, pain, fever, and irritability). 
In addition, HVTN 097, which is administering the RV144 vaccine regimen but in a “low 
risk” South African population, is ongoing. As of 20 May 2014, no SAEs or severe AEs 
related to the study products have been reported in this study. 

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HVTN 097 was designed to evaluate whether the same vaccine regimen (with a higher 
dose of ALVAC-HIV) that was used in Thailand in Study RV144 would be comparably 
safe and immunogenic in a South African population. The study enrolled 100 healthy, 
HIV-1–uninfected participants aged 18 to 40 years, 51 male and 49 female. One hundred 
percent were black, non-Hispanic. Ninety-one participants completed vaccinations and 
follow-up. The study was completed in December 2013. There were 4 participants who 
discontinued vaccinations, 2 due to pregnancy and 2 due to “other” reason; there were no 
discontinuations due to AEs or reactogenicity. 
Local and systemic reactogenicity was assessed for the investigational ALVAC-HIV 
(vCP1521) and AIDSVAX vaccinations. Local injection site reactions of pain and/or 
tenderness were more common in participants receiving active HIV vaccinations versus 
placebo injections. Most pain and/or tenderness reactions to the HIV vaccinations were 
mild (48%), 28% were moderate (similar rates for ALVAC compared to the AIDSVAX 
vaccinations) and approximately 9% were severe (all but 1 severe pain/tenderness 
reactions were from ALVAC vaccination). In placebo recipients, the maximum pain 
and/or tenderness reactions were mild (52%). The majority of participants in both active 
(Group [G]1 and G2 combined) and placebo groups experienced no erythema and/or 
induration reactions (84% and 95%, respectively); with all but 1 reaction (> 9 cm 
erythema/induration from an ALVAC vaccination) being non-gradable by the Division of 
AIDS (DAIDS) AE Grading Table (0-25 cm2), occurring in G1. Moderate or severe 
systemic reactions associated with vaccine administration included malaise and/or fatigue 
(15% versus 5.3% in placebo), myalgia (12.5% versus 0% in placebo), headache (7.5% 
versus 21% in placebo), nausea (1.25% versus 0% in placebo), chills (3.75% versus. 
5.3% in placebo), and arthralgia (6.25% versus 0% in placebo). The maximum 
temperature elevations were Grade 2, which occurred in 2 vaccinees compared to 0 in 
placebo. Overall 88.75% of vaccine recipients experienced at least 1 adverse eventAE 
compared to 85% of placebo recipients. There were 2 SAEs and both were unrelated to 
treatment: thermal burn in a vaccinee and substance-induced psychotic disorder in a 
placebo recipient. There were no Grade 4 (life threatening) or 5 (death) AEs. There were 
5 Grade 3 AEs in vaccine recipients (6.25%) and 2 Grade 3 events in 1 placebo recipient 
(5.3%), all deemed unrelated to study treatment. These included alanine transaminase 
(ALT) increase, headache, hypertension, abnormal loss of weight, and thermal burn in 
vaccinees and substance-induced psychotic disorder and abnormal loss of weight in 1 
placebo recipient. Moderate AEs were experienced by 61.25% of vaccinees and 50% of 
placebo recipients. AEs considered related to the vaccine included itching at the injection 
site, lymph node swelling, faster heartbeat, abdominal pain, flu-like illness, diarrhea, 
injection site skin lump, and muscle spasms. Each of these reactions were mild or 
moderate, only occurred in 1 person (except for the skin lump which occurred in 3 
participants), and did not last long. All participants recovered without sequelae. A few 
participants had changes in their laboratory, blood, and urine test results that were 
considered related to the vaccinations and all returned to normal. Overall, the study 
indicated that the vaccine regimen used in RV144 appears safe and well-tolerated in 
South Africans. 
4.11.3.4 
Previous human experience with ALVAC-HIV used in combination with subunit protein 
boost adjuvanted with MF59® 
There has been meaningful previous human experience with the use of ALVAC-HIV 
vaccines in combination with recombinant gp120 proteins adjuvanted with MF59®. In all, 
more than 650 human subjects have received this combination across 9 clinical trials 
(Table 4-11). No safety signal of concern was identified in these studies.  

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Table 4-11 Clinical studies performed with ALVAC-HIV and gp120+MF59® 
Study 
(Country) 
ALVAC-HIV® 
Protein 
Subjectsa 
RV132 [27]  
(Thailand) 
vCP1521 
gp120 + MF59®  
clades B/E  
made in CHO cells 
n = 45 
AVEG 022A [52]  
(USA) 
vCP205 
gp120 + MF59®  
clade B 
made in CHO cells 
n = 47 
AVEG 029 [53]  
(USA) 
vCP205 
gp120 + MF59®  
clade B 
made in CHO cells 
n = 22 
AVEG 202/HIVNET 014 
[54] (USA) 
vCP205 
gp120 + MF59®  
clade B 
made in CHO cells 
n = 145 
AVEG 032 [55]  
(USA) 
vCP205 
gp120 +/- p24 + MF59®  
clade B  
gp120 made in CHO cells  
p24 made in S. cerevisiae 
n = 56 
AVEG 026 [56]  
(USA) 
vCP300b 
gp120 + MF59® 
clade B  
made in CHO cells 
n = 85 
AVEG 012A 012B [57]  
(USA) 
vCP125c 
gp120 + MF59® 
clade B  
made in CHO cells 
n = 40 
HVTN 100d  
(South Africa) 
vCP2438 
Bivalent Subtype C gp120 
+MF59 
Made in CHO cells 
n = 210 
HVTN 702 
(South Africa) 
vCP2438 
Bivalent Subtype C gp120 
+MF59 
Made in CHO cells 
n = 2700e 
Total 
 
 
N = 650f 
aNumber of subjects that received both the ALVAC-HIV prime and the gp120/MF59® boost. 
bALVAC-HIV (vCP300) is similar to vCP205 and contains additional sequences encoding Pol and Nef epitopes. 
cALVAC-HIV (vCP125) contains the gene for gp160 from clade B. 
d See Section 4.11.1. 
e Trial currently enrolling. Planned number of vaccinees. 
f Does not include planned vaccinees in HVTN 702. 
4.11.4 
Immunogenicity from related human experience 
Immunogenicity measures in ALVAC-HIV studies have evolved over a period of more 
than 2 decades, informed by evolution in knowledge about relevant immune responses. 
Initial studies focused on the measurement of CTL activity, CD4+ T-cell 
lymphoproliferation, and nAb activity. Subsequent studies have focused on Ab binding to 
the Env glycoproteins and on intracellular cytokine staining (ICS) as well. Most recently, 
a large collaborative consortium performed a case-control study to evaluate immune CoR 
based on the RV144 study that used the prime-boost regimen of ALVAC-HIV (vCP1521) 
and the gp120 protein AIDSVAX® B/E (see Section 4.1.2 above, [18]). 
As the development of assays for measuring immunogenicity has evolved during more 
than 20 years of testing in humans, immunogenicity data cannot be fully integrated. 
However, extensive data from previous studies with ALVAC-HIV can inform many 
relevant immunogenicity-related issues as described below.  

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4.11.4.1 
ALVAC-protein schedule and immunogenicity  
The selection of a vaccination schedule for the large efficacy trial in Thailand (RV144) 
was based on scientific knowledge at the time [58]. In addition to safety, the key 
parameters taken into consideration were the CTL immune responses and the nAb 
responses. The HIV vaccine field has evolved significantly since then and the relevance 
of these immune measures is currently debated. However, the demonstration of vaccine 
protection in RV144 mandates the conservation of vaccination regimen features that are 
believed to have contributed to vaccine protection, even when the mechanism of 
protection has not been definitely established. The following paragraphs summarize the 
considerations that were taken into account in the selection of a vaccine regimen and 
schedule for the RV144 study.  
Prior to RV144, several schedules of administration with ALVAC and protein boost were 
examined in multiple clinical trials [52,54,59-61]. While the studies were not designed or 
powered to discriminate statistically between the various vaccination schedules, an 
analysis of the data suggested that 4 doses of ALVAC induced better CTL responses than 
3 or 2 doses. Specifically, net point prevalence CTL response rates on Days 182 and 273 
using 4-dose immunization regimens (Months 0, 1, 3, and 6 or Months 0, 1, 6, and 9) 
produced higher response rates than the 3-dose regimen (Months 0, 1, and 6) on Days 
182 and 273. Regarding neutralization data, both ALVAC schedules (ALVAC alone and 
ALVAC plus subunit protein boost), showed significantly higher neutralization response 
rates compared to the control schedule.  
The addition of a subunit protein boost to ALVAC did not appear to alter the CTL 
response rates [60]. In contrast, the protein boost had a significant effect on Ab 
responses. The ALVAC plus subunit protein boost schedule had significantly higher nAb 
response rates when compared to the ALVAC alone schedule.  
On the basis of these observations, a 4-dose regimen (Months 0, 1, 3, and 6) of ALVAC 
was proposed in order to maximize CTL responses. In addition, two doses of the protein 
boost were proposed at months 3 and 6 to maximize Ab responses. The RV144 study 
implemented this vaccination schedule.  
This study replicates the RV144 vaccination schedule in Groups 1, 2, and 4. The schedule 
in Group 3 is based on the observation in HVTN 096 that concurrent administration of 
subunit protein during priming vaccinations appears to produce a favorable humoral 
response profile more rapidly. 
4.11.4.2 
Immunogenicity of ALVAC used in combination with protein boost plus MF59® 
The vaccine regimen proposed for development in South Africa combines ALVAC-HIV 
(vCP2438) with a bivalent recombinant gp120 protein (total of 200 mcg, 100 mcg of each 
protein) adjuvanted with MF59®. Both vaccine components have been adapted to target 
the predominant HIV clade circulating in South Africa (clade C). Interim 
immunogenicity data from HVTN 100 are summarized in Section 4.11.1.4. Studies prior 
to HVTN 100 with related vaccines provided useful preliminary information on whether 
peak immunogenicity is expected to be at least similar to that elicited by the RV144 
regimen and whether the use of MF59® could be dose sparing for the protein.  
Study RV132 [27] used ALVAC-HIV (vCP1521) in the same dose and schedule as in 
study RV144 but 45 subjects in1 of the study arms received a bivalent recombinant 

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gp120 protein manufactured in CHO cells by Novartis Vaccines and Diagnostics and 
adjuvanted with MF59® as a protein boost. The dose of the proteins was 150 mcg in total 
(100 mcg of the CM235 protein and 50 mcg of the SF2 protein). Study RV135 [24] used 
ALVAC-HIV (vCP1521) in the same dose and schedule as in study RV144, and 97 
subjects in two study arms received a bivalent recombinant gp120 protein manufactured 
in CHO cells by VaxGen/Global Solutions for Infectious Diseases (GSID) and 
adjuvanted with alum as a protein boost. The study explored two doses of the proteins: a 
total dose of 200 mcg (100 mcg for the A244 protein and 100 mcg for the MN protein) 
and a total dose of 600 mcg (300 mcg each of the same proteins used in the lower dose 
formulation). The vaccine regimen with ALVAC-HIV and 600 mcg of gp120 protein 
adjuvanted with alum was utilized in study RV144. Table 4-12 summarizes the nAb 
response rates for the pertinent study arms from these studies.  
Table 4-12 nAb response rates for selected regimens in RV132 and RV135 studies 
Study 
gp120 dose 
Adjuvant 
N 
NPO3 Strain 
SF2 Strain 
CM244 Strain 
MN Strain 
Any Clade E 
RV132 
[27] 
100 mcg 
CM235* 
50 mcg SF2** 
MF59® 
45 
89% 
61% 
95% 
19% 
100% 
RV135 
[24] 
100 mcg A244* 
100 mcg MN** 
alum 
50 
23% 
-- 
44% 
100% 
47% 
300 mcg A244* 
300 mcg MN** 
alum 
47 
31% 
-- 
64% 
98% 
71% 
* clade E Strain 
** clade B Strain 
The geometric mean (GM) nAb titers were also reported in these studies for 2 of the 
clade E strains. Data are summarized in Table 4-13. 
Table 4-13 nAb GM titers to clade E strains 
Study 
gp120 dose 
Adjuvant 
N 
NPO3 
Strain 
CM244 
Strain 
RV132 
[27] 
100 mcg CM235* 
50 mcg SF2** 
MF59® 
45 
45 
32.66 
RV135 
[24] 
100 mcg A244* 
100 mcg MN** 
alum 
50 
12.3 
7 
300 mcg A244* 
300 mcg MN** 
alum 
47 
14.8 
5.4 
* clade E Strain 
** clade B Strain 
Although these data should be interpreted with caution, they suggest that 100 mcg of 
gp120 protein adjuvanted with MF59® can induce Ab responses after ALVAC prime at 
least comparable to and possibly greater than 300 mcg of gp120 protein adjuvanted with 
alum after ALVAC prime. These data suggest that MF59® allows for protein dose sparing 
compared with the less potent alum adjuvant. 
4.11.5 
Clinical studies with Novartis HIV-1 subunit protein vaccines  
For description of interim safety/tolerability and immunogenicity results from Part A of 
HVTN 100, see Section 4.11.1. 
In addition, recombinant monomeric (gp120) subunit vaccine formulations closely related 
to Subtype C gp120/MF59® from Novartis Vaccines and Diagnostics (formerly Chiron) 

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have been tested in clinical trials. In addition, recombinant oligomeric (o-gp140) Env 
proteins for subtypes B and C from Novartis have been or are currently in clinical trials. 
Overall, in these studies, recombinant HIV-Env proteins manufactured by Novartis were 
well tolerated and immunogenic. In most cases, recombinant HIV-Env proteins (either 
gp120 or gp140) were CHO-based and administered with MF59®, Novartis’ proprietary 
oil-in-water emulsion adjuvant [62]. MF59® safety has been established in clinical studies 
as well as in commercial products. A seasonal influenza vaccine adjuvanted with MF59® 
(Fluad®) is licensed in EU and other countries for use in the elderly. MF59® is also used 
in a prepandemic H5N1 influenza vaccine (Aflunov®) licensed in EU for use in adults, 
and in two pandemic H1N1 influenza vaccines (Focetria® and Celtura®), licensed in EU 
and other countries for use in adults and children. More than 100 million doses of 
MF59®-adjuvanted influenza vaccines have been distributed in licensed products. 
Recombinant monomeric (gp120) vaccine candidates studied include Chiron’s early 
gp120-based candidates from subtypes B and E, most of which were CHO-based and 
administered with MF59®. More than 1200 subjects participated in the evaluation of the 
Chiron HIV SF2 gp120/MF59® vaccine and the Chiron HIV CM235 Thai E 
gp120/MF59® vaccine [27,40,56,63-65]. Two clinical trials were conducted using 
Novartis CHO-based subtype B gp140 recombinant Env protein with MF59®. There are 3 
ongoing phase 1 studies with Novartis CHO-based subtype C gp140/MF59® being 
conducted by the NIH-sponsored HVTN in the US and the Republic of South Africa 
(RSA). Table 4-14 summarizes clinical trial experience with Novartis gp120 and gp140 
recombinant vaccine candidates. 

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Table 4-14 Novartis recombinant gp120 and gp140 vaccines in human clinical trials [64] 
Candidate vaccine 
# receiving 
Novartis protein 
Protocol 
Status 
Yeast derived recombinant subtype B SF2 Env 2-3 
protein with MF59® and MTP-PE 
60 
AVEG 005 A/B/C 
Completed  
SF-2 gp120 (CHO) with MF59® and MTP-PE 
50 
AVEG 007 A/B/C 
Completed 
SF2 gp120 (CHO)/MF59® and ALVAC 
40 
AVEG 012A 012B 
Completed 
SF2 gp120 (CHO) with MF59®, SAF/2, SAF2 + 
MDP, aluminum hydroxide, MPL-A, liposome-
encapsulate MPL-A, MTP-PE/MF59® 
107 
AVEG 015 
Completed 
SF2 gp120 (CHO)/MF59® and ALVAC 
47 
AVEG 022A 
Completed 
SF2 gp120 (CHO) with MF59® 
24 
AVEG 024 
Completed 
SF2 gp120 (CHO)/MF59® and ALVAC 
85 
AVEG 026 
Completed 
SF2 gp120 (CHO)/MF59® and ALVAC 
22 
AVEG 029 
Completed 
SF2 gp120 (CHO) +/- yeast derived p24/MF59® and 
ALVAC 
56 
AVEG 032 
Completed 
SF2 gp120 (CHO) with MF59® 
126 
AVEG201 
Completed 
SF2 gp120 (CHO)/MF59® and ALVAC 
140 
AVEG 
202/HIVNET 014 
Completed 
SF2 gp120 & CM235 gp120 (CHO)/MF59® and 
ALVAC 
45 
RV132 
Completed 
Subtype B (SF162) gp140 (CHO) /MF59® and 
Subtype B DNA/PLG  
90 
HVTN 049 
Completed 
Subtype B (SF162) gp140 (CHO) /MF59® IN with 
LTK63 
20 
C86P1 
Completed 
Subtype C (TV1) gp140 (CHO)/MF59® and SAAVI 
DNA-C2 and SAAVI MVA-C 
24 
HVTN073E 
Completed 
Subtype C (TV1) gp140 (CHO) & ISS TAT 
11 
ISS P-002 
Terminated* 
Subtype C (TV1) gp140 (CHO)/MF59® 
36 
HVTN 088 
Completed 
Subtype C (TV1) gp140 (CHO)/MF59® and SAAVI 
DNA-C2 and SAAVI MVA-C 
110 
HVTN 086 
Completed 
Bivalent Subtype C gp120/MF59® and ALVAC-
HIV (vCP2438) 
210 
HVTN 100 
Ongoing 
Bivalent Subtype C gp120/MF59® and ALVAC-
HIV (vCP2438) 
2700 
HVTN 702 
Ongoing 
* Due to slow enrollment and expiration of the study product stability program. 
In general, these recombinant protein vaccines were immunogenic and well tolerated with 
no unusual or serious vaccine-associated AEs reported. Most of the reactions were mild 
to moderate in nature, and of short duration [4,27,40,56,63-67]. 
4.11.5.1 
Summary of safety, reactogenicity, and tolerability from recent human experience 
For description of interim safety/tolerability results from HVTN 100, see Section 
4.11.1.1. 

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In addition, 2 other clinical trials have been conducted recently using Novartis CHO-
based subtype B gp140 with MF59®. In addition there have been 4 recent clinical trials 
using Novartis CHO-based subtype C gp140.  
A phase 1 single-center trial (C86P1) was conducted using Novartis CHO-based subtype 
B gp140 recombinant Env protein in Great Britain by the Mucosal Vaccines for Poverty 
Related Diseases (MUVAPRED) Consortium to assess safety, tolerability, and 
immunogenicity of IN administration of subtype B gp140 with and without the mucosal 
adjuvant LTK63 (detoxified mutant heat labile protein) followed by IM boosting with 
subtype B gp140/MF59®. This study enrolled 30 healthy volunteers aged 18-45, with 20 
to receive gp140. The protocol was amended to halt further IN administration of LTK63 
following a report of an AE (ie, facial nerve paralysis) with a possible association with 
the LTK63 adjuvant in another study [68]. During the study, there was 1 SAE reported of 
Bell’s Palsy (facial nerve paralysis) considered possibly related to the study vaccine 
LTK63 in a subject who never received any subtype B gp140 protein or any protein with 
MF59® adjuvant. IN vaccination was reactogenic resulting in upper respiratory tract 
symptoms including nasal congestion, nasal discomfort, pharyngolaryngeal pain and 
rhinorrhea. The subtype B gp140 MF59® was well tolerated following IM boost.  
Another completed study with Novartis subtype B gp140 MF59® was a multicenter, 
placebo-controlled trial (HVTN 049) conducted by the HVTN in the United States [69]. 
Subjects received1 of three doses of a DNA/PLG vaccine (subtype B gag DNA/PLG and 
subtype B env DNA/PLG microparticles, at doses of 250/250, 500/500, or 1000/1000 
mcg) or placebo (5 to 1 ratio) as a single IM injection at 0, 1 and 2 months, followed by a 
boost of subtype B gp140 with MF59® (or placebo) at 6 and 9 months. An additional 
group of subjects received subtype B gp140 with MF59® without DNA prime, 
administered at 0, 3, and 9 months. Overall 96 healthy, HIV-1-uninfected adult subjects 
were enrolled and 86 subjects completed all planned vaccinations. There were no SAEs 
reported as related to study vaccine. There were four events reported as SAEs that were 
not considered related to the study vaccine. A death attributed to cocaine overdose 
occurred in1 subject, 10 days after receipt of the second dose of the placebo. One subject 
had a Grade 3 increase in creatine phosphokinase (CPK) to 2311 U/L 14 days after the 
first DNA prime vaccination, which resolved within a week. Another subject had a Grade 
4 increase in CPK to 4806 U/L 15 days after the first DNA prime vaccination, which 
resolved within two weeks. Both subjects reported having initiated new exercise 
programs. One subject experienced severe fatigue 20 days after the fourth immunization 
(including1 dose of subtype B gp140/MF59®), attributed to working two jobs and long 
hours. Overall, the regimens were generally well tolerated.  
A third study, HVTN 073E, was conducted in the US and the RSA as an extension to the 
previous HVTN 073/SAAVI03 study. This extension study examined the safety and 
immunogenicity of two boosting doses of Novartis subtype C gp140/MF59® or placebo 
in subjects who previously received 3 vaccinations of SAAVI DNA-C2 and two 
vaccinations of SAAVI MVA-C. This study enrolled 27 subjects. There was 1 report of 
endometrial intra-epithelial neoplasia resulting in hospitalization for hysterectomy, which 
was assessed as unrelated to study agents. 
Two other recent phase 1 studies with Novartis subtype C gp140/MF59® have been 
conducted by the HVTN in the US and RSA. In addition, a phase 1 trial was conducted 
by the Istituto Superiore di Sanità (ISS) in Italy. One of these trials, HVTN 088, was 
conducted in the United States in order to evaluate the safety and immunogenicity of a 
long-interval, cross-clade subtype C gp140/MF59® boost in subjects previously 

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administered subtype B gp120/MF59® or subtype B gp140/MF59® in previous trials. This 
includes subjects from the HVTN049 DNA/PLG prime, gp140/MF59® boost study 
described above. The study enrolled 16 previously vaccinated subjects and 20 naive 
controls. Individuals were identified who had received a clade B Env protein with MF59® 
4-17 years earlier, most in combination with a DNA or ALVAC prime. These individuals 
were enrolled in HVTN 088 to receive a clade C protein boost in an open label phase 1 
trial. There have been 3 SAEs reported in this trial, 1 involving traumatic injury, 1 
instance of gastroenteritis, and 1 of appendicitis. All of these were assessed as unrelated 
to study agents.  
The second HVTN study, HVTN 086, was conducted in the RSA. It evaluated the safety 
and immunogenicity of various combinations of SAAVI DNA-C2, SAAVI MVA-C, and 
Novartis subtype C gp140/MF59®. All scheduled clinic visits have been completed, 
though study participants remain subject to annual contacts to assess their health status. 
This study enrolled 184 subjects.To date, 6 SAEs have been reported in this study, 1 case 
of acute tonsillitis that required hospitalization, 1 of schizophrenia requiring 
hospitalization (later determined to be a pre-existing condition),1 of pelvic inflammatory 
disease, 1 soft-tissue injury,1 instance of anemia, and 1 instance of alcohol-related 
cardiomyopathy. All were assessed as not related to the study products. 
The ISS study (ISS P-002) conducted in Italy examined the safety and immunogenicity of 
subtype C gp140 co-administered with ISS TAT compared to subtype C gp140 alone or 
TAT alone. The study includes intradermal and IM injections (100 mcg for subtype C 
gp140 and 7.5 mcg for ISS TAT). This study did not include MF59®. While this study 
was stopped early due to slow enrollment and subsequent expiration of the study product 
stability program, no SAEs were reported in this study. 
4.11.5.2 
Summary of immunogenicity from recent human experience 
The immunogenicity of Novartis recombinant proteins has been demonstrated 
consistently in all clinical trials and in both of the recently completed studies using 
Novartis CHO-based subtype B gp140 MF59®. In the HVTN 049 DNA/PLG prime 
protein boost study, the primary cellular immunogenicity endpoints included interferon 
gamma (IFN-γ) enzyme-linked immunospot (ELISpot) and ICS responses. 
Immunogenicity was assessed 14 days after each vaccination. Env-specific IFN-γ 
ELISpot response rates did not increase substantially compared to baseline after the three 
DNA/PLG prime vaccinations, but did rise after the first protein/MF59® boost. nAb titers 
against the homologous SF162 isolate were detectable in two subjects after the third 
DNA/PLG priming vaccination and in 13 subjects after the first protein boost. 
Neutralization was boosted to high titer in all but 1 subject following the second protein 
boost. Similarly in the group of subjects who received subtype B gp140/MF59® without a 
DNA/PLG prime, a nearly complete response to the SF162 isolate was observed at the 
second vaccination (all but1 subject) which lasted through the third vaccination. Binding 
Ab titers against Env, measured by enzyme-linked immunosorbent assay (ELISA), were 
detected following the first subtype B gp140/MF59® boost and were very high following 
the second boost administration.  
The C86P2 MUVAPRED IN study, demonstrated immunogenicity with considerable IgG 
and IgA Ab responses to subtype B gp140 in serum, cervical, and vaginal secretions of 
subjects following IN administration of subtype B gp140 with the adjuvant LTK63 and 
an IM boost with subtype B gp140 and M59 adjuvant. nAb responses against the 

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homologous SF162 were also detected in all groups following IM boost with subtype B 
gp140 and MF59® adjuvant. 
In addition, in the HVTN 088 long-interval boost study, 16 previously primed volunteers 
and 20 naïve volunteers each received 2 doses of the subtype C gp140/MF59® given 6 
months apart. HIV-1 specific CD4+ and CD8+ T-cell responses were measured by an 
ICS assay. Ab responses were measured with a Luminex binding Ab assay and a nAb 
assay in TZM-bl cells. Despite the long interval (4-17 years from prior protein/MF59® 
administration), 5 of 16 (31%) primed participants demonstrated CD4+ T-cell responses 
to Env at baseline, which increased to 12 of 16 (75%) after a single protein boost. IgG 
and IgA responses to Con S gp140 were present in 64% (IgG) and 7% (IgA) of primed 
participants at baseline, and rose to 93% and 85%, respectively, after 1 dose of protein. 
71% of primed participants demonstrated nAb against Tier 1 clade B isolate MN at 
baseline. After a single booster dose of protein, 100% of the primed participants 
neutralized MN and 93% showed neutralizing activity against a clade C isolate, 
MW965.26. Unprimed participants did not demonstrate CD4+ responses or Ab responses 
to Env until after the second dose, which elicited IgG and IgA responses to vaccine-
matched oligomeric TV1 Env in 88% and 50%, respectively. nAb developed to MN in 
38% and to MW965.26 in 88% of the unprimed participants. 
Three of the 4 vaccine regimens in HVTN 086 contained Novartis subtype C 
gp140/MF59®, either as a boost following pox-vector (MVA) primes, administered 
concurrently with a pox-vector (MVA) vaccine, or in a concurrent pox-vector/protein 
boost and second protein boost following DNA plasmid primes. Ab responses were 
measured with a Luminex binding Ab assay and a nAb assay in TZM-bl cells. All three 
vaccine regimens containing subtype C gp140/MF59® elicited high rates (82–100%) and 
magnitudes of IgG binding Ab against a range of gp120 and gp140 antigens. All vaccine 
regimens had evidence of nAb to (Tier 1) HIV strains MN.3, MW965.26, and SF162.LS, 
with the MVA- and DNA-primed regimens showing the highest titers to MW965.26, a 
clade C strain. HIV-1 specific CD4+ and CD8+ T-cell responses to global potential T-
cell epitopes (PTEg) were measured by an ICS assay. The MVA- and DNA-primed 
vaccine regimens  elicited the highest rates of CD4+ T cells producing IFN-γ and/or IL-2 
(77% and 45%, respectively), while the regimen with concurrent MVA/protein 
administration elicited the lowest rate (13%). 
See also Section 4.11.1.4. 
4.12 
Potential risks of study products and administration 
Table 4-15 includes general risks of vaccine administration along with risks known from 
prior clinical studies of ALVAC-HIV products and of envelope protein vaccines 
adjuvanted with MF59® and with aluminum hydroxide.  

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Table 4-15 Summary of potential risks of study products and administration 
Common 
 
Mild to moderate injection site pain, tenderness, erythema, or 
swelling/induration/edema 
 
Malaise/fatigue, myalgia, arthralgia, nausea/vomiting, lymphadenopathy, 
asthenia, fever, or headache in the first few days following injection 
 
Arm movement limitation 
 
A vaccine-induced positive HIV Ab test result 
Less common 
 
Severe injection site pain or tenderness 
 
Chills, flu-like syndrome, diarrhea, rash, 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, bruising/ecchymosis, laceration, other transient 
lesions, itching, or bleeding related to the injection procedure 
Uncommon or rare 
 
Severe localized injection site reaction, such as > 10 cm diameter erythema 
or induration, sterile abscess or secondary bacterial infection  
 
Allergic reaction, including rash, urticaria, angioedema, eyelid swelling, 
bronchospasm, or anaphylaxis 
 
Injection site pruritus, warmth or other non-specific injection site reaction 
 
Generalized pruritus 
 
Oral paresthesia 
 
Syncope, insomnia 
 
Abdominal pain, anorexia, gastritis, dysgeusia 
 
Skin disorder, acne 
 
Muscle damage at the injection site 
Theoretical risks 
 
Autoimmune disease  
 
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 compare the humoral immune responses induced by ALVAC-HIV (vCP2438) prime 
with 2 ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59® boosts or 2 
ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120 admixed with Aluminum 
Hydroxide Suspension boosts in HIV-uninfected participants 
Primary endpoint 1:  
Occurrence and level of vaccine-induced systemic IgG Ab binding to the 3 gp120 Env 
proteins contained in the vaccine regimen (ZM96, TV1.C, and 1086.C) at the Month 6.5 
timepoint 
Primary objective 2:  
To compare the humoral immune responses induced by ALVAC-HIV (vCP2438) prime 
with 2 ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59® boosts to the 
regimen with 3 ALVAC-HIV (vCP2438) + Bivalent Subtype C /MF59® vaccinations in 
HIV-uninfected participants 
Primary endpoint 2:  
Occurrence and level of vaccine-induced serum IgA Ab binding to the 3 gp120 Env 
proteins contained in the vaccine regimen (ZM96, TV1.C, and 1086.C) at the Month 6.5 
timepoint 
Primary objective 3:  
To evaluate the safety and tolerability of each vaccine regimen through the Month 6.5 
timepoint 
Primary endpoint 3:  
Severe local and systemic reactogenicity signs and symptoms (pain, tenderness, 
erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, 
arthralgia) within 3 days after each vaccine dose 
AEs by body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred 
term, severity, and assessed relationship to study products within 30 days after each 
vaccine dose 
SAEs, AEs of special interest (AESIs), and new chronic conditions requiring medical 
intervention for ≥ 30 days, throughout the study 

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Laboratory measures: white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, 
platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphate (ALP), and creatinine at baseline and following vaccinations 
AEs leading to early participant withdrawal or early discontinuation of study product(s) 
administration throughout the study 
5.2 
Secondary objectives and endpoints 
Secondary objective 1: 
To further evaluate the humoral and cellular systemic immune responses to the different 
vaccine regimens 
Secondary endpoint 1: 
Occurrence and level of vaccine-induced serum IgG Ab binding to the 3 gp120 Env 
proteins contained in the vaccine regimen (ZM96, TV1.C, and 1086.C) at the Month 12, 
12.5, and 18 timepoints 
Vaccine-induced serum IgG Ab binding to V2 Env proteins at 6.5, 12, 12.5, and 18 
months 
Vaccine-induced CD4+ T-cell responses to the HIV proteins included in the vaccine at 
6.5, 12, 12.5, and 18 months 
Vaccine-induced serum IgG3 Ab binding to Env proteins at 6.5, 12, 12.5, and 18 months 
HIV-specific CD4+ T cell polyfunctionality by ICS  
Secondary objective 2: 
To evaluate the safety and tolerability of each vaccine regimen through Month 18 
Secondary endpoint 2:  
Endpoints as indicated in primary endpoints 2 
5.3 
Exploratory objectives 
Exploratory objective 1 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, and clinical trial conduct 
Exploratory endpoint 1 
Additional immunogenicity assays may be performed on blood and mucosal samples, 
including samples at innate and adaptive immunity timepoints, based on the HVTN 

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Laboratory Assay Algorithm. These assays are outlined in the Laboratory Accessory 
document. 
Exploratory objective 2 
To assess whether the gut microbiome correlates with vaccine responses 
Exploratory endpoint 2 
Gut microbiome characterization via rRNA sequencing using optionally provided stool 
specimens 
 

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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling 132 healthy, HIV-uninfected adult participants aged 18 
to 40 years. 
During the consent process, participants will be given the choice whether or not to 
participate in the innate/mucosal subset until it is fully accrued. Participants who are not 
in this subset, will be randomized in a 3:3:3:1 ratio to: (1) ALVAC primes at months 0 
and 1 followed by ALVAC + Bivalent Subtype C gp120 adjuvanted with MF59® at 
Months 3, 6, and 12; (2) ALVAC + ALVAC primes at months 0 and 1 followed by 
Bivalent Subtype C gp120 adjuvanted with alum at Months 3, 6, and 12; (3) ALVAC + 
Bivalent Subtype C gp120 adjuvanted with MF59® at all vaccination timepoints (Months 
0, 1, 6, and 12); or (4) ALVAC primes at months 0 and 1 followed by ALVAC + 
Bivalent Subtype C gp120 with no adjuvant at Months 3, 6, and 12. Eligible participants 
who enroll in the innate/mucosal subset will be randomized to these 4 groups in a 1:1:1:1 
ratio. A 3 month accrual period is anticipated. To ensure a relative balance of participants 
of each sex at birth in the subset and the non-subset portions of the trial, no more than 
approximately 60% of participants of either sex will be enrolled into the subset or non-
subset portions of the trial. Hence, when approximately 43 participants of either sex have 
been enrolled in the innate/mucosal subset, recruitment for that sex will stop. Similarly, 
when approximately 36 participants of either sex have been enrolled in the non-subset 
portion, recruitment for 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 nine phase 1 
and1 phase 2a HVTN vaccine trials, which began enrolling after June 2005 (data as of 
June 2011), indicate that 15% is a reasonable estimate for the rate of missing data at 
Month 6.5. For this reason, the sample size calculations in Section 6.1.2 account for 15% 
enrolled participants having missing data for 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. The ability of the study to detect serious adverse events 
(SAEs) (see Section 11.2.3) 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 adjuvanted vaccine arm of the study (n = 36), 
there is a 90% chance of observing at least 1 event if the true rate of such an event is 
6.2% or more; and there is a 90% chance of observing no events if the true rate is 0.3% or 
less. For the unadjuvanted vaccine arm (n = 24), there is a 90% chance of observing at 
least 1 event if the true rate of such an event is 9.1% or more; and there is a 90% chance 
of observing no events if the true rate is 0.4% or less. For the vaccine arms combined (n = 
132), there is a 90% chance of observing at least 1 event if the true rate of such an event 
is 1.7% or more; and there is a 90% chance of observing no events if the true rate is 

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0.08% or less. As a reference, in HVTN vaccine trials from December 2000 through 
April 2014, about 6.5% of South African participants who received placebos experienced 
an SAE.  
Probabilities of observing 0, 1 or more, and 2 or more events among arms of size 24 and 
36 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. 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
vaccine arms of size 24 and 36, for different true event rates 
True event rate (%) 
Pr(0/24) 
Pr(1+/24) 
Pr(2+/24) 
Pr(0/36) 
Pr(1+/36) 
Pr(2+/36) 
0.1 
0.976 
0.024 
<0.001 
0.965 
0.035 
0.001 
0.5 
0.887 
0.113 
0.006 
0.835 
0.165 
0.014 
1 
0.786 
0.214 
0.024 
0.696 
0.304 
0.050 
4 
0.375 
0.625 
0.110 
0.230 
0.770 
0.425 
10 
0.080 
0.920 
0.708 
0.023 
0.977 
0.887 
An alternative way of describing the statistical properties of the study design is in terms 
of the 95% CI for the true rate of an adverse event based on the observed data. Table 6-2 
shows the 2-sided 95% CIs for the probability of an event based on a particular observed 
rate. Calculations are done using the score test method [70]. If none of the 132 
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 adjuvant-vaccinated 
population is 2.8. For each individual adjuvanted vaccine arm (n = 36), the 2-sided upper 
confidence bound for this rate is 9.6%. For the vaccine arm with no adjuvant (n = 24), the 
2-sided upper confidence bound for this rate is 13.8%. 
Table 6-2 Two-sided 95% CIs based on observing a particular rate of safety endpoints for 
vaccine arms of size 24, 36, and 132 (pooled) 
Observed event rate 
CI (%) 
0/24 
(0.0, 13.8) 
1/24 
(0.2, 20.2) 
2/24 
(2.3, 25.8) 
 
 
0/36 
(0.0, 9.6) 
1/36 
(0.5, 14.2) 
2/36 
(1.5, 18.1) 
 
 
0/132 
(0.0, 2.8) 
1/132 
(0.0, 4.2) 
2/132 
(0.4, 5.4) 
6.1.2 
Sample size calculations for immunogenicity 
The primary immunogenicity objective of this trial is to characterize the vaccine-induced 
humoral immune responses of the 4 vaccine regimens at Month 6.5. The precision with 
which the true response rate can be estimated from the observed data depends on the true 
underlying response rate and the sample size. Two-sided 95% CIs for the response rate 
based on observing a particular rate of responses in the vaccinees is shown in Table 6-3. 

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Calculations are done using the score test method [70]. The sample size n = 20 and n = 30 
assume a 15% missing data rate. 
Another primary question of interest regarding immunogenicity is the comparison of the 
Month 6.5 response rates of insert-directed serum IgG from the binding Ab assay to 
detect moderate differences in response rates between the 2 arms primed with ALVAC 
followed by ALVAC + Bivalent Subtype C gp120 adjuvanted either with MF59® or with 
alum. A separate primary objective is to compare the Month 6.5 response rates of insert-
directed serum IgA from the binding Ab assay for the arm primed with ALVAC followed 
by ALVAC + Bivalent Subtype C gp120 adjuvanted with MF59® to the arm with 
concurrent administration of ALVAC and  Bivalent Subtype C gp120 adjuvanted with 
MF59® at all vaccination timepoints. Within each of these group comparisons, no 
adjustment will be made for the use of multiple inserts.  
Table 6-3 Two-sided 95% CIs for the true response rate based on observing a particular rate 
of responses in the vaccinees (n = 20, 30) 
n 
No. of 
responses 
Observed response 
rate (%) 
CI (%) 
20 
6 
30.0 
(14.5, 51.9) 
20 
10 
50.0 
(29.9, 70.1) 
20 
12 
60.0 
(38.7, 78.1) 
20 
14 
70.0 
(48.1, 85.5) 
20 
16 
80.0 
(58.4, 91.9) 
30 
9 
30.0 
(16.7, 47.9) 
30 
15 
50.0 
(33.2, 66.8) 
30 
18 
60.0 
(42.3, 75.4)  
30 
21 
70.0 
(52.1, 83.3) 
30 
24 
80.0 
(62.7, 90.5) 
As shown in Table 6-4, there is adequate power for a formal comparison of 
immunogenicity response rates between adjuvanted vaccine arms of size n = 30 to detect 
moderate differences in response rates of ~35%. These calculations use a Fisher’s exact 
2-sided test with a Type I error rate of 0.05.  
Table 6-4 Power for comparison of response rates between 2 arms (n1 = 30, n2 = 30) 
True response rate 
Arm 1 (%) 
Maximum true response rate in Arm 2 in 
order to detect a difference 
80% power 
90% power 
40 
8 
5 
50 
14 
10 
60 
22 
18 
70 
32 
27 
80 
42 
37 
90 
56 
51 
95 
64 
59 
In addition to comparing insert-directed serum IgG response rates at Month 6.5 between 
the aluminum hydroxide and MF59® adjuvanted arms, it is also of interest to compare 

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differences in the magnitudes of the responses. Power calculations use Lachenbruch’s 2-
part test to compare the response rates and the continuous insert-directed IgG responses 
at Month 6.5. Given that power is sufficient to compare the response rates, the study will 
also be well powered for this comparison involving magnitudes. For example, with n = 
30 per arm there is 80% power to detect a difference with a true response rate of 92% in 1 
arm with GM = 6.31 and variance of 2.06 in responders and a response rate of 80% in the 
other arm with GM = 5.18 and variance of 2.06 in responders. Response rates of 92% and 
94% with GMs of 6.31 and 6.42 (variance 2.06, 1.89 respectively) correspond to the 
responses observed at Month 6.5 in RV144 with the A244 and 92TH023 inserts. See 
Table 6-5 for power with other response rates and magnitudes (variance = 2.06 for each 
arm for true response rate = 92% and variance = 1.89 for true response rate = 94%) 
Many other immunogenicity endpoints will also be analyzed to characterize the innate 
and adaptive immune profiles of the vaccine arms. These include vaccine-induced IgG 
Ab binding to V2 Env proteins, vaccine-induced CD4+ T-cell responses to the HIV 
proteins included in the vaccine and vaccine-induced IgG3 Ab binding to Env proteins. 
Table 6-5 Power for comparison of response rates and levels between 2 vaccine arms (n1 = 
30, n2 = 30) 
True response rate (%) 
and GM Arm 1 
Maximum true response rate and GM in Arm 
2 in order to detect a difference 
80% power 
90% power 
94 
6.42 
85 
5.25 
85 
5.05 
94 
6.42 
80 
5.37 
80 
5.15 
94 
6.42 
75 
5.51 
75 
5.18 
92 
6.31 
85 
5.15 
85 
5.00 
92 
6.31 
80 
 5.18 
80 
5.07 
92 
6.31 
75 
 5.22     
75 
5.14 
6.2 
Randomization  
The randomization sequence will be obtained by computer-generated random numbers 
and provided to each HVTN CRS through the SDMC’s Web-based randomization 
system. The randomization for the subset and non-subset portion of the trial will each be 
done in blocks to ensure balance across arms and stratified by country. At each 
institution, the pharmacist with primary responsibility for dispensing study products is 
charged with maintaining security of the treatment assignments. 
6.3 
Blinding 
Participants and site staff (except for site pharmacists) will be blinded as to participant 
treatment group assignments for the 3 heterologous prime boost arms of the study 
(Groups 1, 2, 4); the ALVAC +  Bivalent Subtype C gp120 adjuvanted with MF59 at all 
vaccination time points will not be blinded (Group 3). Study product assignments are 
accessible to those HVTN CRS pharmacists, DAIDS protocol 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.  

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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 (if he or she is in a blinded arm of the study).  
Emergency unblinding decisions will be made by the site investigator. If time permits, 
the HVTN 107 PSRT should be consulted before emergency unblinding occurs. 
6.4 
Statistical analysis 
This section describes the final study analysis, 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. The analysis is a 
modified intent-to-treat analysis 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. 
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 (malaise and/or fatigue, 

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myalgia, headache, nausea, vomiting, chills, arthralgia) 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.  
6.4.3.3 
Local laboratory values  
Boxplots of local laboratory values will be generated for baseline values and for values 
measured during the course of the study by treatment arm and visit. Each boxplot will 
show the first quartile, the median, and the third quartile. Outliers (values outside the 
boxplot) will also be plotted. If appropriate, horizontal lines representing boundaries for 
abnormal values will be plotted. 
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 DAIDS AE Grading Table (see Section 
9.10) 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. 
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.  

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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% CI estimates calculated using the score test method [70]. 
Fisher’s exact tests will be used for the primary analysis comparing the IgG response 
rates of the arm with ALVAC primes followed by ALVAC +  Bivalent Subtype C gp120 
adjuvanted with MF59® boosts(Group 1) vs the aluminum hydroxide adjuvanted arm 
(Group 2) at Month 6.5 with a significant difference declared if the 2-sided p-value is 
≤ 0.05. Fisher’s exact tests will also be used to compare IgA response rates between the 
arm with ALVAC primes and Bivalent Subtype C gp120 adjuvanted with MF59® boosts 
(Group 1) and the arm with ALVAC +  Bivalent Subtype C gp120 adjuvanted with 
MF59® coadministered at all vaccination timepoints (Group 3) at Month 6.5; this is 
considered a separate primary objective and thus no multiplicity adjustment will be made. 
Fisher’s exact tests will also be used to compare response rates between the unadjuvanted 
and adjuvanted arms at Month 6.5 and other time points; these analyses are viewed as 
secondary and therefore no multiplicity adjustment will be made. 
For quantitative assay data (eg, level of vaccine-induced IgG Ab binding to the 2 gp120 
Env proteins contained in the vaccine regimen), graphical and tabular summaries of the 
distributions by antigen, treatment arm, and timepoint will be made. The difference 
between arms at a specific timepoint 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. To test for differences among the 4 vaccine arms, first 
a Kruskal-Wallis rank test or an F-test (depending on the normality assumption) will be 
used to test for overall differences. Secondly, if the overall test is significant at the 2-
sided 0.05 level, then individual tests comparing the 3 pairs of vaccine arms will be done 
unless pre-specified. If rank-based tests are used then the tests will be inverted to 
construct Hodges-Lehmann point-estimates and 2-sided (1 - 0.05/3) × 100% CIs about 
the differences in location centers of the 3 pair-wise comparisons of vaccine arms. An 
appropriate data transformation (eg, log10 transformation) may be applied to better satisfy 
assumptions of symmetry and homoscedasticity (constant variance). 
Some immunologic assays have underlying continuous or count-type readout that are 
dichotomized into responder/nonresponder categories (eg, binding antibody multiplex 
assay [BAMA]). If treatment arm differences for these assays are best summarized by a 
mixture model, then Lachenbruch’s test statistic [71] will be used to evaluate the 
composite null hypothesis of equal response rates in the MF59® vs aluminum hydroxide 
adjuvanted arms and equal response distributions among responders in the 2 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.  
This approach will also be used to compare the arm with ALVAC primes followed by 
ALVAC +  Bivalent Subtype C gp120 adjuvanted with MF59® boosts at Month 3, 6, 12 
(Group 1) to the arm with ALVAC +  Bivalent Subtype C gp120 adjuvanted with MF59® 
coadministered at all vaccination timepoints (Group 3). 
Based upon previous AIDS Vaccine Evaluation Group (AVEG) and HVTN trials, 
missing 15% of immunogenicity results for a specific assay is common due to study 

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participants terminating from the study early, problems in shipping specimens, or low cell 
viability of processed PBMCs. To achieve unbiased statistical estimation and inferences 
with nonparametric tests and generalized linear models fit by generalized estimating 
equation (GEE) methods, missing data need to be missing completely at random 
(MCAR). MCAR assumes that the probability of an observation being missing does not 
depend upon the observed responses or upon any unobserved covariates but may depend 
upon covariates included in the model (eg, missing more among whites than nonwhites). 
When missing data are minimal (specifically if no more than 20% of participants are 
missing any values), then nonparametric tests and GEE methods will be used, because 
violations of the MCAR assumption will have little impact on the estimates and 
hypothesis tests. These models will include as covariates all available baseline predictors 
of the missing outcomes.  
If a substantial amount of immunogenicity data are missing (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 [72] will be used, because they accommodate 
the censoring. In addition, secondary analyses of repeated immunogenicity measurements 
may be done using weighted GEE [73] methods, which are valid under MAR. All of the 
models described above will include as covariates all available baseline predictors of the 
missing outcomes.  
6.4.4.2 
Analysis of CD4+ T-cell response as measured by the ICS assay  
The analysis of the CD4+ T-cell response rate as measured by the ICS assay will be 
evaluated and compared as described under the general approach. The positivity call for 
each peptide pool will include a multiple comparison adjustment for the number of 
peptide pools used in the assay using the discrete Bonferroni adjustment. The magnitude 
of response will be analyzed as described for quantitative data in the general approach 
section. Graphs will be used to display the background-subtracted magnitudes for each 
participant by protein, treatment arm and timepoint, with a box plot of data from positive 
responders superimposed on the individual data values. Statistical testing comparing the 
magnitudes will be based on positive responders only. The same approach will be used to 
analyze other T cell subsets of interest. 
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. 

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6.4.5.1 
Safety 
During the course of the trial, unblinded analyses of safety data will be prepared 
approximately every 4 months for review by the SMB. Ad hoc safety reports may also be 
prepared for SMB review at the request of the HVTN 107 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 
A limited unblinded statistical analysis by treatment assignment of a primary 
immunogenicity endpoint may be performed when all participants have completed the 
Month 6.5 visit and data are available for analysis from at least 80% of these participants. 
The Laboratory Program will review the analysis report prior to distribution to the 
protocol chairs, DAIDS, vaccine developer, and other key HVTN members and 
investigators. Distribution of reports will be limited to those with a need to know for the 
purpose of informing future trial-related decisions. 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. 
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 40 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 
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 
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. 

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Laboratory Inclusion Values 
Hemogram/Complete blood count (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 ALP < 1.25 times the institutional upper limit of 
normal; creatinine ≤ institutional upper limit of normal. 
Virology 
16. Negative HIV-1 and -2 blood test: Sites may use locally available assays that have been 
approved by HVTN Laboratory Operations. 
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). 
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: 

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 
Agree to consistently use effective contraception (Appendix C) for sexual activity 
that could lead to pregnancy from at least 21 days prior to enrollment through the last 
required protocol clinic visit. Effective contraception is defined as using: 
 
Condoms (male or female), or 
 
Diaphragm or cervical cap, 
PLUS 1 of the following methods: 
 
Intrauterine device (IUD), 
 
Hormonal contraception (in accordance with Republic of South Africa: National 
Contraception Clinical Guidelines),  
 
Successful vasectomy in the male partner (considered successful if a volunteer 
reports that a male partner has [1] documentation of azoospermia by microscopy, 
or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite 
sexual activity postvasectomy); or 
 
Any other contraceptive method approved by the HVTN 107 PSRT 
 
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 
Other 
23. Volunteers who were born female consenting to provide cervical samples:  pap smear 
within the 3 years prior to enrollment, with the latest result reported as normal or ASCUS 
(atypical squamous cells of undetermined significance); for those 21 years and older that 
have not had a pap smear within the last 3 years prior to enrollment, must be willing to 
undergo a pap smear with the result reported as normal or ASCUS prior to sample 
collection. 
7.2 
Exclusion criteria 
General 
1. Blood products received within 120 days before first vaccination  
2. Investigational research agents received within 30 days before first vaccination 
3. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic 
blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, 
known hyperlipidemia  

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4. Intent to participate in another study of an investigational research agent or any other 
study that requires non-HVTN HIV antibody testing during the planned duration of the 
HVTN 107 study  
5. Pregnant or breastfeeding 
Vaccines and other Injections 
6. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received 
control/placebo in an HIV vaccine trial, the HVTN 107 PSRT will determine eligibility 
on a case-by-case basis. 
7. 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 in 
a volunteer’s country of residence. For volunteers who have received control/placebo in 
an experimental vaccine trial, the HVTN 107 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 107 PSRT on a 
case-by-case basis. 
8. 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) 
9. 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) 
10. Allergy treatment with antigen injections within 30 days before first vaccination or 
that are scheduled within 14 days after first vaccination  
Immune System  
11. 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.) 
12. Serious adverse reactions to vaccines or to vaccine components such as eggs, egg 
products, or neomycin, 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.)  
13. Immunoglobulin received within 60 days before first vaccination 
14. Autoimmune disease  
15. Immunodeficiency 
Clinically significant medical conditions  

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16. Untreated or incompletely treated syphilis infection 
17. 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. 
18. 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 
19. 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. 
20. Current anti-tuberculosis (TB) prophylaxis or therapy 
21. 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; 
 
 Needed emergency care, urgent care, hospitalization, or intubation for asthma. 
22. Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not 
excluded: history of isolated gestational diabetes.) 
23. Thyroidectomy, or thyroid disease requiring medication during the last 12 months 

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24. 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. 
25. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) 
26. 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) 
27. 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. 
28. Asplenia: any condition resulting in the absence of a functional spleen 
29. History of hereditary angioedema, acquired angioedema, or idiopathic angioedema. 
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 11.3. 
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 

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 
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. 
 
Pregnancy: for participants who become pregnant, no study vaccinations will be 
given; except for participants who may have been pregnant during the study but are 
no longer pregnant as shown by two negative urine pregnancy tests taken from two 
different urine samples that may be collected on the same day; in this circumstance, 
the HVTN 107 PSRT should be consulted to determine if the participant may resume 
vaccinations. 
Vaccinations should not be administered outside the visit window period specified in the 
HVTN 107 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 interval between a study vaccination and completion of the 2 week 
postvaccination 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).  
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 107 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 (Vaccinations will be stopped while a participant is pregnant. If the 
participant is no longer pregnant and can be vaccinated within an appropriate 
visit window, vaccinations may resume, see Section 7.3.1); 
 
Any grade 4 local or systemic reactogenicity symptom, lab abnormality, or AE 
that is subsequently considered to be related to vaccination; 

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 
Any grade 3 lab abnormality or other clinical AE (exception: fever or vomiting 
and subjective local and systemic symptoms) that is subsequently considered to 
be related to vaccination; upon review, the PSRT may allow continuation of 
vaccination if the participant has grade 3 erythema and/or induration;  
 
SAE that is subsequently considered to be related to vaccination;  
 
Clinically significant type 1 hypersensitivity reaction associated with study 
vaccination. Consultation with the HVTN 107 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). 
 
A study participant who misses a study injection is permitted to continue with 
subsequent study injections that can still be scheduled within the time interval 
specified in the HVTN 107 Study Specified Procedures (SSP) unless there is a 
protocol-mandated reason for discontinuation.  
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 Sections 7.3.4 and 9.7.1). 
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,  
 
Investigator decides, in consultation with Protocol Team leadership, to terminate 
participation (eg, if participant exhibits inappropriate behavior toward clinic staff), or 
 
Any condition where termination from the study is required by applicable 
regulations. 
 

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8 
Study product preparation and administration 
CRS pharmacists should consult the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks for standard pharmacy operations. The protocol schema is 
shown in Table 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 
Treatment 1 (T1): ALVAC-HIV (vCP2438) to be administered as 1 mL IM in LEFT 
deltoid (unless medically contraindicated) at months 0, 1, 3, 6, and 12 
AND 
Bivalent Subtype C gp120/MF59® (an admixture of 100 mcg of TV1.C gp120, 100 mcg 
of 1086.C gp120, and MF59C.1) to be administered as 0.5mL IM in RIGHT deltoid 
(unless medically contraindicated) at Months 3, 6, and 12 
Group 2 
Treatment 2 (T2): ALVAC-HIV (vCP2438) to be administered as 1 mL IM in LEFT 
deltoid (unless medically contraindicated) at months 0, 1, 3, 6, and 12 
AND 
Bivalent Subtype C gp120 (an admixture of 100 mcg of TV1.C gp120 and 100 mcg of 
1806.C gp120) admixed with Aluminum Hydroxide Suspension to be administered as 
0.5mL IM in RIGHT deltoid (unless medically contraindicated) at Months 3, 6, and 12 
Group 3 
Treatment 3 (T3): ALVAC-HIV (vCP2438) to be administered as 1 mL IM in LEFT 
deltoid (unless medically contraindicated) at months 0, 1, 6, and 12 
AND 
Bivalent Subtype C gp120/MF59® (an admixture of 100 mcg of TV1.C gp120, 100 mcg 
of 1086.C gp120, and MF59C.1) to be administered as 0.5mL IM in RIGHT deltoid 
(unless medically contraindicated) at Months 0, 1, 6, and 12 
Group 4 
Treatment 4 (T4): ALVAC-HIV (vCP2438) to be administered as 1 mL IM in LEFT 
deltoid (unless medically contraindicated) at months 0, 1, 3, 6, and 12 

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AND 
Bivalent Subtype C gp120 (an admixture of 100 mcg of TV1.C gp120 and 100 mcg of 
1806.C gp120) admixed with Sodium Chloride for Injection, 0.9% to be administered as 
0.5mL IM in RIGHT deltoid (unless medically contraindicated) at Months 3, 6, and 12 
8.2 
Study product formulation  
ALVAC-HIV (vCP2438) [Labeled as ALVAC-HIV (vCP2438)] 
ALVAC-HIV (vCP2438) is provided as a lyophilized, white to beige product. It must be 
stored refrigerated (2-8°C). Once reconstituted with 1 mL of Diluent 0.4% NaCl, it 
appears as a clear to slightly opalescent solution, colorless with possible presence of 
particles or filaments.  
The study product is described in further detail in the IB. 
Diluent for ALVAC-HIV (vCP2438) [Labeled as Diluent 0.4% NaCl] 
The diluent is provided in a vial filled with a volume to deliver 0.5 mL of sterile sodium 
chloride solution (NaCl 0.4%). Two vials of diluent are required to prepare one dose. It 
must be stored refrigerated (2-8°C). DO NOT FREEZE. 
Bivalent Subtype C gp120 composed of two different proteins: 
TV1.C gp120 protein [labeled as TV1.C gp120]: The TV1.C gp120 protein will be 
provided in a 2 mL glass vial containing approximately 0.58 mL (462 mcg protein) of a 
clear colorless to slightly yellow liquid. The product must be stored frozen at -61°C or 
colder. 
1086.C gp120 protein [labeled as 1086.C gp120]: The 1086.C gp120 protein will be 
provided in a 2 mL glass vial containing approximately 0.58 mL (462 mcg protein) of a 
clear colorless to slightly yellow liquid. The product must be stored frozen at -61°C or 
colder. 
MF59® [labeled as MF59C.1] is supplied as an oil-in-water emulsion. The MF59 
adjuvant has a milky white opaque appearance and is provided in a glass vial containing a 
total volume of 0.7 mL. The product must be stored refrigerated at 2 - 8°C. Do not freeze. 
The Bivalent Subtype C gp120 and the MF59® are described in further detail in the 
Bivalent Subtype C gp120/MF59® IB. 
Aluminum Hydroxide Suspension appears as an opaque,  white gelatinous precipitate in 
aqueous suspension.  It is provided in 3 mL glass vials each containing 0.7 mL of 
aluminum hydroxide (5 mg/mL as aluminum). The product should be stored refrigerated 
at 2 - 8° C. Do not freeze. 
The study product is described in further detail in the Bivalent Subtype C gp120 admixed 
with Aluminum Hydroxide Suspension IB supplement. 

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Sodium Chloride for Injection, 0.9% (normal saline, Sodium Chloride for Injection, 
0,9%) 
Sodium Chloride for Injection, 0.9% will be used for the Bivalent Subtype C gp120 alone 
group to maintain blinding between the groups. It must be stored as directed by the 
manufacturer. 
8.3 
Preparation of study products 
Pharmacists should refer to USP 38 General Chapter Physical Tests / <797> 
Pharmaceutical Compounding - Sterile, and should follow the requirements of their 
country, their institution, and their pharmacy regulatory authority regarding these 
procedures. At a minimum, study products must be prepared in a biological safety 
cabinet/isolator by appropriately trained/qualified pharmacy personnel using aseptic 
technique. 
8.3.1 
ALVAC-HIV (vCP2438) (All Groups) 
One vial of ALVAC-HIV (vCP2438) and 2 vials of diluent (NaCl 0.4%) are needed to 
prepare this dose.  
Before reconstitution, the pharmacist will allow the vials to equilibrate to room 
temperature. The pharmacist, using aseptic technique, will withdraw a total of 1 mL from 
the 2 vials containing diluent (NaCl 0.4%) and slowly inject (the 1 mL of diluent) into the 
vial containing the lyophilized ALVAC-HIV. The pharmacist will then set the vial aside 
and allow the vial to sit for up to 3 minutes to allow for dissolution of the vaccine. The 
pharmacist will gently swirl the vial to assure the contents are well dissolved. DO NOT 
SHAKE THE VIAL. (Note: Presence of particles or filaments in the dissolved solution is 
possible). Using aseptic technique, the pharmacist will then withdraw the total contents of 
the ALVAC-HIV vial into a 2, 3 or 5 mL syringe.  
The syringe should be labeled as “ALVAC-HIV 1 mL” as well as “Administer in Left 
Deltoid”. Once the dose is drawn up in a syringe, the study product should be 
administered as soon as possible within 30 minutes (per Immunization Action Coalition 
[IAC] and US Centers for Disease Control and Prevention [CDC] recommendations).  
Any unused portion of reconstituted vials or expired syringes are disposed of in 
accordance with institutional or pharmacy policy for a biological safety level 1 product. 
8.3.2 
Bivalent Subtype C gp120/MF59® (Groups 1 and 3) 
One vial of TV1.C gp120 protein,1 vial of 1086.C gp120 protein, and 1 vial of MF59C.1 
will be needed to prepare the dose. Prior to dispensing, the pharmacist will remove the 
TV1.C gp120 and 1086.C gp120 from the freezer and allow to thaw at room temperature. 
(Note: Once thawed the 1086.C gp120 and/or TV1.C gp120 vials should be used 
immediately for preparation or stored in a refrigerator at 2-8°C for no longer than 24 
hours. Unused 1086.C gp120 and/or TV1.C gp120 protein vials should be quarantined for 
destruction after this time.) The pharmacist will also remove the MF59C.1 vial from the 
refrigerator and mix by repeated gentle swirling and inversion (do not shake vigorously). 

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Using aseptic technique, the pharmacist will gently swirl the contents of the vial 
containing TV1.C gp120 and then withdraw 0.35 mL of TV1.C gp120 from the correct 
vial and inject it into the vial containing MF59C.1. The pharmacist will then gently swirl 
the vial containing 1086.C gp120 after which, using aseptic technique, the pharmacist 
will withdraw 0.35 mL of 1086.C gp120 from the correct vial and inject it into the 
MF59C.1 vial (which contains TV1.C gp120 and MF59C.1). After gentle swirling and 
inversion (do not shake vigorously) the pharmacist, using aseptic technique, will 
withdraw 0.5 mL of the mixed preparation for dosing into a 1 or 2 mL syringe. 
The syringe should be labeled as “HVTN 107 study product” and have an overlay applied 
to the syringe. Although Group 3 is not blinded, this will maintain consistency with the 
other groups. The syringe must also be labeled for administration in RIGHT deltoid and 
“Gently roll the syringe prior to administration”. The syringe containing study product 
should be bagged for transport to the clinic where it will be administered. This study 
product should be administered immediately, defined as within 30 minutes as per IAC 
recommendations. If this is not possible, the vaccine should be stored at 2°C-8°C until 
administration and if not used within 2 hours, it should be discarded. 
8.3.3 
Bivalent Subtype C gp120 admixed with Aluminum Hydroxide Suspension (Group 
2) 
One vial of TV1.C gp120 protein,1 vial of 1086.C gp120 protein, 1 vial of Aluminum 
Hydroxide Suspension, 1 vial/ampule of Sterile Water for Injection, and 1 empty 
sterilized vial will be needed to prepare the dose. Prior to dispensing, the pharmacist will 
remove the TV1.C gp120 and 1086.C gp120 from the freezer and allow to thaw at room 
temperature. (Note: Once thawed the 1086.C gp120 and/or TV1.C gp120 vials should be 
used immediately for preparation or stored in a refrigerator at 2-8°C for no longer than 24 
hours. Unused 1086.C gp120 and/or TV1.C gp120 protein vials should be quarantined for 
destruction after this time.) The pharmacist will also remove the Aluminum Hydroxide 
Suspension vial from the refrigerator and the Sterile Water for Injection from storage.  
Using aseptic technique, the pharmacist will gently swirl the contents of the vial 
containing aluminum hydroxide, withdraw 0.35 mL of the aluminum hydroxide and 
inject it into the empty sterilized vial.  The pharmacist will then add 0.35 mL of Sterile 
Water for Injection to the mixing vial which contains the 0.35 mL of aluminum 
hydroxide.  The mixing vial should be gently swirled and inverted (do not shake). Next, 
the pharmacist will take the vial containing TV1.C gp120 and withdraw 0.35 mL of 
TV1.C gp120 from the vial and inject it into the mixing vial (which contains aluminum 
hydroxide mixed with Sterile Water for Injection). The pharmacist will then gently swirl 
the vial containing 1086.C gp120 after which, using aseptic technique, the pharmacist 
will withdraw 0.35 mL of 1086.C gp120 from the correct vial and inject it into the mixing 
vial (which contains TV1.C gp120 and aluminum hydroxide mixed with Sterile Water for 
Injection).  After gentle swirling and inversion (do not shake vigorously) the pharmacist, 
using aseptic technique, will withdraw 0.5 mL of the mixed preparation for dosing into a 
1 or 2 mL syringe. 
The syringe should be labeled as “HVTN 107 study product” and have an overlay applied 
to the syringe. The syringe must also be labeled for administration in RIGHT deltoid and 
“Gently roll the syringe prior to administration”. The syringe containing study product 
should be bagged for transport to the clinic where it will be administered. This study 
product should be administered immediately, defined as within 30 minutes as per IAC 

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recommendations. If this is not possible, the vaccine should be stored at 2°C-8°C until 
administration and if not used within 2 hours, it should be discarded.  
8.3.4 
Bivalent Subtype C gp120 (Group 4) 
One vial of TV1.C gp120 protein,1 vial of 1086.C gp120 protein, Sodium Chloride for 
Injection, 0.9%, and 1 empty sterilized vial will be needed to prepare the dose. Prior to 
dispensing, the pharmacist will remove the TV1.C gp120 and 1086.C gp120 from the 
freezer and allow to thaw at room temperature. (Note: Once thawed the 1086.C gp120 
and/or TV1.C gp120 vials should be used immediately for preparation or stored in a 
refrigerator at 2-8°C for no longer than 24 hours. Unused 1086.C gp120 and/or TV1.C 
gp120 protein vials should be quarantined for destruction after this time.) 
The pharmacist will also obtain the sodium chloride for injection and 1 empty sterilized 
vial from storage.  
Using aseptic technique, the pharmacist will transfer 0.7 mL of Sodium Chloride for 
Injection in to the empty sterilized vial. The pharmacist will then gently swirl the 
contents of the vial containing TV1.C gp120 and withdraw 0.35 mL of TV1.C gp120 
from the correct vial and inject it into the mixing vial containing the sodium chloride for 
injection. The pharmacist will then gently swirl the vial containing 1086.C gp120 after 
which, using aseptic technique, the pharmacist will withdraw 0.35 mL of 1086.C gp120 
from the correct vial and inject it into the mixing vial (which contains TV1.C gp120 and 
sodium chloride for injection). After gentle swirling and inversion (do not shake 
vigorously) the pharmacist, using aseptic technique, will withdraw 0.5 mL of the mixed 
preparation for dosing into a 1 or 2 mL syringe. 
The syringe should be labeled as “HVTN 107 study product” and have an overlay applied 
to the syringe. The syringe must also be labeled for administration in RIGHT deltoid and 
“Gently roll the syringe prior to administration”. The syringe containing study product 
should be bagged for transport to the clinic where it will be administered. This study 
product should be administered immediately, defined as within 30 minutes as per IAC 
recommendations. If this is not possible, the vaccine should be stored at 2°C-8°C until 
administration and if not used within 2 hours, it should be discarded.  
8.4 
Administration 
All injections are to be given IM in the deltoid indicated. At sites where registered 
pharmacists are legally authorized to administer injections, the HVTN CRS may choose 
to have the pharmacist administer vaccinations. 
When preparing a dose in a syringe and administering the dose, consideration should be 
given to the volume of solution in the needle before and after the dose is administered. 
Particularly, if the needle used to withdraw the product is replaced prior to vaccine 
administration, consideration should be given to conserving the full dose of product. The 
pharmacy and clinic staff members are encouraged to work together to administer the 
dose specified in the protocol.  
All injections are to be given using standard IM injection technique. 

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For all syringes containing Bivalent Subtype C gp120 with or without adjuvant, the 
person administering the injection should gently roll the syringe prior to administration of 
the study product. These syringes will be labeled as “HVTN 107 study product”. 
If an injection is administered in the contralateral deltoid due to a medical 
contraindication, the appropriate study staff should document this clearly. Under this 
circumstance, this is NOT a protocol violation. Two injections administered into the same 
deltoid should be at least 2.4 cm apart and should be documented in the participant’s 
study record. 
8.5 
Acquisition of study products 
The ALVAC-HIV (vCP2438) and diluent (0.4% NaCl) will be supplied by Sanofi 
Pasteur and will be available through the NIAID Clinical Research Products Management 
Center (CRPMC). 
Bivalent Subtype C gp120 and the MF59® adjuvant will be supplied by GlaxoSmithKline 
Biologicals, S.A. and will be available through the CRPMC. 
Aluminum Hydroxide Suspension will be provided by the NIH, NIAID, Vaccine 
Research Center and will be available through the CRPMC. 
Once an HVTN CRS is protocol registered, the pharmacist can obtain study products 
from the CRPMC by following the ordering procedures given in Pharmacy Guidelines 
and Instructions for DAIDS Clinical Trials Networks. 
Sterile Water for Injection (used for preparation of Bivalent Subtype C gp120 admixed 
with Aluminum Hydroxide Suspension) will not be provided through the protocol and 
must be obtained by the site. 
Sodium Chloride for Injection, 0,9% will not be provided through the protocol and must 
be obtained by the site. 
Empty sterilized vials for study product mixing will be provided through the protocol and 
may be obtained from the CRPMC. 
8.6 
Pharmacy records 
The HVTN CRS pharmacist is required to maintain complete records of all study 
products. The pharmacist of record is responsible for maintaining randomization codes 
and randomization confirmation notices for each participant in a secure manner. 
8.7 
Final disposition of study products 
All unused study products must be returned to the CRPMC after the study is completed 
or terminated unless otherwise instructed by the CRPMC. The procedures and relevant 
form are included in the Pharmacy Guidelines and Instructions for DAIDS Clinical Trials 
Networks.  

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9 
Clinical procedures 
The schedules of clinical procedures are shown in Appendix J, Appendix K, Appendix L, 
and Appendix M. 
9.1 
Informed consent 
Informed consent is the process of working with participants so that they fully understand 
what will and may happen to them while participating in a research study. The HVTN 
informed consent form documents that a participant (1) has been informed about the 
potential risks, benefits, and alternatives to participation, and (2) is willing to participate 
in an HVTN study. Informed consent encompasses all written or verbal study information 
HVTN CRS staff provide to the participant, before and during the trial. HVTN CRS staff 
will obtain informed consent of participants according to HVTN policies and procedures. 
The informed consent process continues throughout the study. Key study concepts should 
be reviewed periodically with the participant and the review should be documented. At 
each study visit, HVTN CRS staff should consider reviewing the procedures and 
requirements for that visit and for the remaining visits. Additionally, if any new 
information is learned that might affect the participants’ decisions to stay in the trial, this 
information will be shared with trial participants. If necessary, participants will be asked 
to sign revised informed consent forms. 
An HVTN CRS may employ recruitment efforts prior to the participant consenting. For 
example, some HVTN CRSs use a telephone script to prescreen people before they come 
to the clinic for a full screening visit. Participants must sign a screening or protocol-
specific consent before any procedures are performed to determine eligibility. HVTN 
CRSs must submit recruitment and prescreening materials to IRB/EC and any applicable 
Regulatory Entity (RE) for human subjects protection review and approval. 
Note: As defined in the DAIDS Protocol Registration Manual, an RE is “Any group other 
than the local IRB/EC responsible for reviewing and/or approving a clinical research 
protocol and site-specific informed consent forms (ICFs) prior to implementation at a 
site.” CRSs are responsible for knowing the requirements of their applicable REs. 
9.1.1 
Screening consent form 
Without a general screening consent, screening for a specific study cannot take place 
until the site receives protocol registration from the DAIDS RSC Protocol Registration 
Office. 
Some 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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9.1.2 
Protocol-specific consent forms 
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. A 
sample protocol-specific consent form for the main study is located in Appendix A. A 
separate sample consent form for other uses of specimens is located in Appendix E. 
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 E. The consent form(s) must be developed in accordance with requirements of 
the following: 
 
CRS’s IRB/EC, 
 
CRS’s institution and any applicable REs, and 
 
Elements of informed consent as described in Title 45 CFR Part 46 and Title 21 
CFR, Part 50, and in the International Conference on Harmonisation (ICH) E6, 
Good Clinical Practice: Consolidated Guidance 4.8.  
Study sites are strongly encouraged to have their local CABs review their 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. 
9.1.3 
Assessment of Understanding 
Study staff are responsible for ensuring that participants fully understand the study before 
enrolling them. This process involves reviewing the informed 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 Understanding (see Section 9.1.3); 
 
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; 
 
Assessment of concomitant medications the volunteer is taking, including 
prescription and nonprescription drugs, vitamins, topical products, 
alternative/complementary medicines (eg, herbal and health food supplements), 
recreational drugs, vaccinations, and allergy shots (record the complete generic name 
for all medications); 
 
Laboratory tests as defined in the inclusion and exclusion criteria, including: 
 
Screening HIV test,  
 
CBC with differential and platelet count,  
 
Chemistry panel (ALT, AST, ALP, and creatinine), 
 
Urine dipstick (urinalysis if indicated, see Section 9.9), 
 
HBsAg,  
 
Anti-HCV Ab, 
 
Syphilis test, 
 
Urine or serum pregnancy test (volunteers who were born female); 
 
Pap smear  (Only for volunteers who were born female and who agree to provide 
cervical samples; not required if volunteer has had Pap smear within previous 3 
years with most recent result normal or ASCUS; 
 
Administration of behavioral risk assessment questionnaire; 

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 
Obtaining of volunteer demographics in compliance with the NIH Policy on 
Reporting Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 2001 
(available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-053.html); 
 
Counseling on HIV testing and risk reduction, performed in compliance with the US 
Centers for Disease Control and Prevention (CDC)’s current guidelines or other local 
guidelines for HIV counseling, testing, and referral as described in Section 9.7; and 
 
Discussion of pregnancy prevention. A pregnant or breastfeeding person may not be 
enrolled in this trial. Specific criteria and assessment of contraception and pregnancy 
status are described in study inclusion criteria. Discussion of pregnancy prevention 
includes advising a participant who was born female and who reports no current 
sexual activity that could lead to that participant becoming pregnant to have a plan to 
begin adequate birth control. This plan would be put to use if, during the study, the 
participant becomes sexually active in a way that could lead to that participant 
becoming pregnant.  
9.2.1 
Use of screening results from another HVTN study 
If a participant screens for an HVTN study at the same HVTN CRS but then does not join 
that study, screening results from that effort may be applied to the screening for this 
protocol, as long as the screening was done under participant consent, the participant has 
signed a consent form to begin screening for this study, and the tests were conducted 
within the time periods specified in the eligibility criteria (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. 

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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). 
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. 
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 may be 
given the postvaccination memory tool and instructed on how to complete it. The site will 
make arrangements to obtain daily reports of reactogenicity events from the participant 
during the reactogenicity period (as described in Section 9.10). 
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 9.7);  
 
Pregnancy prevention assessment (as described in Section 9.2 and 9.8); and 
 
Assessment of new or unresolved social impacts (site staff will ask participant about 
the status of any unresolved social impacts and if s/he has experienced any new 
social impacts as a result of the trial participation). 
Additional procedures will be performed at scheduled visits as specified in Appendix J, 
Appendix K, Appendix L, and Appendix M:  
 
HIV infection assessment including pretest 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 
 
Administration of the social impact assessment questionnaire (types of impacts 
assessed involve personal relationships, health insurance, life insurance, educational 
or employment opportunities, housing, immigration, or travel); 
 
Administration of behavioral risk assessment questionnaire; 
 
Specimen collection (blood/mucosal/stool) should be completed prior to vaccination 
(see Appendix F, Appendix G, Appendix H, and Appendix I); 
 
For participants who agree to join and who have been randomized to the 
innate/mucosal subset (see Section 9.5): 
 
Urine test for gonorrhea and chlamydia; 
 
Vaginal swab for Trichomonas and bacterial vaginosis (for participants providing 
cervical samples); 

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 
Vaginal swab (if indicated) for  hyphae/budding yeast (for participants providing 
cervical samples); 
 
Mucosal specimen collection; 
 
Syphilis serology. 
9.4 
Follow-up visits 
The following procedures are performed at all scheduled follow-up visits: 
 
Risk reduction counseling (as described in Section 9.7);  
 
Pregnancy prevention assessment (as described in Section 9.2 and 9.8); and 
 
Assessment of new or unresolved social impacts (site staff will ask participant about 
the status of any unresolved social impacts and if s/he has experienced any new 
social impacts as a result of the trial participation); 
 
Assessment of new or continuing concomitant medications (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 J, Appendix K, Appendix L, and Appendix M:  
 
Administration of behavioral risk assessment questionnaire; 
 
Administration of the social impact assessment questionnaire (types of impacts 
assessed involve personal relationships, health insurance, life insurance, educational 
or employment opportunities, housing, immigration, or travel); 
 
HIV infection assessment including 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 (blood/mucosal/stool) should be completed prior to vaccination 
(see Appendix F, Appendix G, Appendix H, and Appendix I); 

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 
Clinical laboratory tests including: 
 
CBC with differential and platelet count, 
 
Chemistry panel (see Section 9.2), and 
 
Urine dipstick (urinalysis if appropriate; see Section 9.9); 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. 
 
For participants who have been enrolled to the innate/mucosal subset to provide 
mucosal samples (see Section 9.5): 
 
Urine test for gonorrhea and chlamydia; 
 
Vaginal swab for Trichomonas and bacterial vaginosis (for participants providing 
cervical samples); 
 
Vaginal swab (if indicated) for hyphae/budding yeast (for participants providing 
cervical samples); 
 
Syphilis serology; 
 
Pregnancy test (see Section 9.5); 
 
Mucosal specimen collection. 
9.5 
Innate immunity and mucosal sampling 
Innate immunity samples and mucosal samples will be collected at the timepoints 
indicated in Appendix G, Appendix I, Appendix K, and Appendix M from the subset of 
study participants who agree to these procedures. 
Participants who consent to provide cervical, rectal, or semen samples will be tested for 
the following infections at the mucosal sampling visits: gonorrhea, chlamydia, and 
syphilis. Participants who consent to provide cervical fluid samples will be tested for 
trichomoniasis and for bacterial vaginosis and (if clinically indicated) for hyphae/budding 
yeast. Test results will be provided to participants and all participants who test positive 
for 1 or more of these infections will receive counseling as well as treatment or referral 
for treatment as appropriate. Sample collection may not be performed or may be deferred 
to a later date within the visit window if a contraindication to sampling (eg, active GTI) is 
present (as indicated below). 
Rectal fluid sampling (both sexes): For participants born female, a pregnancy test must 
be performed and be negative prior to any rectal mucosal sampling. 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. Rectal secretion sampling should be deferred if a participant is menstruating, but 
should be performed as soon as possible, if still within the visit window. In addition, 
rectal sampling will not be performed (or may be deferred to a later date if still within the 

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visit window) if there is a contraindication to rectal secretion sampling, such as an active 
infection or inflammation of the colorectal area (such as an herpes simplex virus (HSV)-2 
outbreak or inflamed hemorrhoids or colitis/diarrhea) or if the participant has any active 
genital tract infection (GTI). 
For 48 hours prior to sample collection, participants should abstain from: 
 
Receptive anal sex,  
 
Insertion of any foreign object or substance into the anus (including but not limited to 
cleaning products [creams, gels, lotions, pads, etc.], lubricant, enemas, and douching 
even with water), and  
 
Using perianal or intra-anal steroid or other anti-inflammatory cream in or around the 
anus.  
Cervical sampling (only for participants who were born female): Participants must 
report having had a pap smear within the 3 years prior to enrollment, with the latest result 
reported as normal or ASCUS. A pregnancy test must be performed on the day of 
cervical sampling. The pregnancy test can be performed after collection has taken place. 
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. Cervical sampling should be deferred if a participant is 
menstruating, but should be performed as soon as possible, if still within the visit 
window. In addition, cervical sampling will not be performed (or may be deferred to a 
later date if still within the visit window) if a participant has an active ulcerative genital 
lesion or is known to have an active GTI at the scheduled timepoint. Participants 
providing cervical secretion samples should be advised as follows: 
 
Do not use anything with spermicide, lubricants, or topical/intravaginal medications 
(eg, topical yeast infection treatments) for 48 hours before the samples are collected;  
 
Do not douche for 48 hours before the samples are collected;  
 
Do not have vaginal sex and/or insert any foreign object or substance into the vagina 
for 48 hours before the samples are collected;  
Semen sampling (only for participants who were born male): Participants providing 
semen samples are asked to refrain from ejaculation for at least 48 hours prior to 
specimen collection. In addition, mucosal sampling will not be performed (or may be 
deferred to a later date within the visit window) if a participant is known to have an 
active GTI at the scheduled timepoint. 
9.6 
Stool sampling 
Stool samples will be collected at 2 timepoints from study participants who agree to this 
procedure: prior to enrollment (before the injection of the vaccine) and at the Month 6.5 
timepoint. These samples will be collected using swabs, either via rectal swabs or by 
taking swabs from stool. 

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If participants opt to collect stool samples at home, they should be instructed to deliver 
the sample to the clinic within 24 hours after they are collected. 
9.7 
HIV counseling and testing 
HIV counseling will be performed in compliance with the CDC’s guidelines or other 
local guidelines for HIV counseling and referral. HIV testing will be performed in 
accordance with the current HVTN HIV testing algorithm following enrollment. 
Participants will be counseled routinely during the trial on the avoidance of HIV infection 
and on the potential negative social impacts of testing Ab positive due to the vaccine. 
They will also be counseled on the risks of HIV Ab 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 
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. 
9.7.1 
Distinguishing intercurrent HIV infection from vaccine-induced positive serology 
The study product may elicit an Ab 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 J, 
Appendix K, Appendix L, and Appendix M. 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. 

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 
HIV testing will be performed at multiple timepoints throughout the study (see 
Appendix F, Appendix G, Appendix H, and Appendix I). The Laboratory Program 
(or approved diagnostic laboratory) will follow the HVTN HIV testing algorithm (see 
Study Specific Procedures [SSP]), which is able to distinguish vaccine-induced Ab 
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 (VISP). 
 
All participants who received vaccine product and who have vaccine-induced 
positive or indeterminate HIV-1 serology (as measured by the standard anti-HIV Ab 
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).  
9.7.2 
VISP registry  
Experimental HIV vaccines may induce Ab production to HIV antigens, producing 
reactive results on commercially available HIV test kits. This is called “vaccine-induced 
seropositivity” (VISP) (see Section 9.7.1). 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 
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. 
9.8 
Contraception status 
Contraception status is assessed and documented at every scheduled clinic visit for a 
participant who was born female and who is sexually active in a way that could cause that 
participant to become pregnant. Prior to enrollment and throughout the study, staff will 
ask participants to verbally confirm their use of adequate contraceptive methods. A 
participant who was born female and is sexually active in a way that could cause that 
participant to become pregnant should be reminded at all scheduled clinic visits of the 
importance of using contraception and should be referred to specific counseling, 
information, and advice as needed. (Specific contraception requirements are listed in 
Section 7.1). This reminder should be documented in the participant’s study record. 
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. 

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9.9 
Urinalysis 
Dipstick testing may be performed in the clinic or the lab, as long as the required 
elements (glucose, protein, and hemoglobin) are tested. The examination is performed on 
urine obtained by clean catch. 
If the screening dipstick is transiently abnormal due to 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. 
9.10 
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 (DAIDS) Table 
for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 
2017], except as noted in Section 11.2.2. 
The reactogenicity assessment period is 3 full days following each vaccination per the 
assessment schedule shown in Table 9-1 Participants may be given a postvaccination 
memory tool on which to record symptoms and instructed in how to use it. Participants 
are also instructed to be in contact with the site daily to report symptoms during the 
assessment period. Clinic staff will follow new or unresolved reactogenicity symptoms 
present at day 3 to resolution. Participants are instructed to contact the clinic for events 
that arise during the period between 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.  
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 3 full days 
after), or those meeting criteria for SAE/adverse events requiring expedited reporting to 
regulatory authorities, are recorded on an adverse experience log form.  

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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 
Between 12:00am and 11:59pm day 
1 
HVTN CRS staff or 
participant 
2 
Between 12:00am and 11:59pm day 
2 
HVTN CRS staff or 
participant 
3b 
Between 12:00am and 11:59pm day 
3 
HVTN CRS staff or 
participant 
a Day of vaccination 
b New or unresolved reactogenicity symptoms present on day 3 are followed until resolution 
9.10.1 
Assessment of systemic and local symptoms 
Systemic symptoms include increased body temperature, malaise and/or fatigue, myalgia, 
headache, chills, arthralgia, nausea, 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. 
9.10.2 
Assessment of injection site 
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. 
9.10.3 
Assessment of lymph nodes 
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). 
9.11 
Visit windows and missed visits 
Visit windows are defined in HVTN 107 Study Specific Procedures. For a visit not 
performed within the window period, a Missed Visit form is completed. If the missed 

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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. 
9.12 
Early termination visit 
In the event of early participant termination, site staff should consider if the following 
assessments are appropriate: a final physical examination, clinical laboratory tests 
(including urine dipstick, CBC with differential, platelet count, and chemistry panel), 
pregnancy testing, social impact assessment, and HIV test. 
9.13 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more injections of 
study product will be given during the pregnancy, but remaining visits and study 
procedures should be completed unless medically contraindicated. For participants who 
are no longer pregnant, see Section 7.3.1. If the participant terminates from the study 
prior to the pregnancy outcome, the site should make every effort to keep in touch with 
the participant in order to ascertain the pregnancy outcome. Pregnancies and pregnancy 
outcomes will be reported. 

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10 
Laboratory 
10.1 
HVTN CRS laboratory procedures 
The HVTN 107 Site Lab Instructions and SSP provide further guidelines for operational 
issues concerning the clinical and processing laboratories. These documents include 
guidelines for general specimen collection, special considerations for phlebotomy, 
specimen labeling, whole blood processing, HIV screening/diagnostic testing, and 
general screening and safety testing. 
Tube types for blood collection are specified in Appendix F, Appendix G, Appendix H, 
and Appendix I. For tests performed locally, the local lab may assign appropriate tube 
types. 
In specific situations, the samples 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 F, Appendix G, Appendix H, 
and Appendix I. 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 timepoint 
The primary immunogenicity timepoint in this study is month 6.5 (ie, 2 weeks after the 
4th vaccination visit). Endpoint assays for humoral and cellular responses are performed 
on participants at the primary immunogenicity timepoint 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 F, Appendix G, Appendix H, and Appendix I. 
10.4 
Endpoint assays: humoral 
10.4.1 
HIV-1 multiplex Ab assay 
Total binding IgG antibodies to HIV-1 Env proteins (including V2 regions of interest) 
will be assessed on plasma/serum and mucosal secretion samples from study participants 
taken at the primary immunogenicity timepoints and baseline. Specimens from other 
timepoints as well as other HIV antigens and Ab isotypes may also be assayed based on 
the results of the initial assay.  

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10.4.2 
Neutralizing Ab (nAb) assay 
HIV-1–specific nAb assays may be performed on serum samples from study participants 
taken at the primary immunogenicity timepoint. Specimens from the baseline and other 
timepoints may also be analyzed at the discretion of the HVTN Laboratory Program, 
which may be contingent on the results of the primary immunogenicity timepoint. Tier 1 
assays will test neutralization of HIV-1 strains represented in the highly neutralization-
sensitive tier 1 viruses. The tier 2 assays will test neutralization of a panel of heterologous 
primary isolates [74]. 
10.5 
Endpoint assays: cellular 
10.5.1 
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. ICS parameters will include cytokines such as 
IFN-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)-α, and may include other 
cytokines (such as cytokines relevant to Th2 and Th17 responses) to identify T cells of 
specific functionality. Markers of cytotoxic potential (Granzyme B, perforin, and CD57) 
may also be included. Data will be reported as percentages of CD4+ or CD8+ T cells 
responding to a specific peptide pool. Additional cell surface markers, cytokines, or 
functional markers may also be analyzed. 
Phenotyping of T cells (eg, T follicular helper [Tfh]), B cells (eg, plasmablasts), dendritic 
cells, monocytes, natural killer (NK) cells, or other leukocytes may be performed for 
lineage, maturation, homing, and activation markers using PBMC samples. 
10.6 
Innate immunity assays 
10.6.1 
Soluble factors in serum or plasma 
Multiplex cytokine array and/or ELISA may be used to measure soluble cytokines, 
chemokines, and other immunomodulatory factors in the serum or plasma. Analytes may 
include factors such as IFN-γ, IL-6, TNF-α, IL-10, IP (IFN-γ–induced protein)-10, and/or 
monocyte chemotactic protein (MCP)-1. 
10.6.2 
Gene expression 
Whole blood will be cryopreserved in a ribonucleic acid (RNA) protection reagent. RNA 
may be isolated and used for transcriptome analyses. Signatures of gene expression 
changes will be analyzed over time after vaccination.  
10.7 
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 postvaccination 
timepoints. Other participants (including control recipients) may be HLA-typed to 

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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-1 disease progression may also be assessed.  
10.8 
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. 
10.9 
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.  
10.9.1 
Microbiome analysis 
Swabs of stool will be shipped to a central laboratory. Specimens are processed to enable 
nucleic acid sequencing. 16s rRNA sequences will then be determined using pyro-
sequencing approaches or other methods. 
10.10 
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 covered by the protocol Appendix F, 
Appendix G, Appendix H, or Appendix I, or the informed consent form (Appendix A, 
Appendix E). 
This research may relate to HIV, vaccines, the immune system, and other diseases. This 
could include genetic testing and, potentially, genome-wide studies. This research is done 
only to the extent authorized in each study site’s informed consent form, or as otherwise 
authorized under applicable law. Other 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 

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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. 
10.11 
Biohazard containment 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, and blood products, appropriate precautions will be 
employed by all personnel in the drawing of blood and shipping and handling of all 
specimens for this study, as currently recommended by the CDC and the NIH or other 
applicable agencies. 
All dangerous goods materials, including Biological Substances, Category A or Category 
B, must be transported according to instructions detailed in the International Air 
Transport Association Dangerous Goods Regulations. 

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11 
Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
11.1.1 
HVTN 107 PSRT 
The HVTN 107 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 (CSS). 
The clinician members of HVTN 107 PSRT are responsible for decisions related to 
participant safety. 
A medical officer from an organization in Southern Africa designated by the study 
sponsor will also participate in the PSRT.  
The Protocol Team clinic coordinator, project manager, vaccine developer representative, 
clinical trial manager, and others may also be included in HVTN 107 PSRT meetings. 
11.1.2 
HVTN SMB 
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 evaluations of cumulative reactogenicity events, AEs, 
laboratory safety data, and individual reports of adverse events requiring expedited 
reporting to DAIDS and pertinent national regulatory authorities. 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 107 PSRT.  
Study sites will receive SMB summary minutes and are responsible for forwarding them 
to their IRB/EC and any applicable RE. 
11.1.3 
SDMC roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring include: 

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 
Maintaining a central database management system for HVTN clinical data; 
 
Providing reports of clinical data to appropriate groups such as the HVTN 107 PSRT 
and HVTN SMB (see Section 11.1.2); 
11.1.4 
HVTN Core roles and responsibilities in safety monitoring 
 
Daily monitoring of clinical data for events that meet the safety pause and HVTN 
107 PSRT AE review criteria (see Section 11.3); 
 
Notifying HVTN CRSs and other groups when safety pauses or planned holds are 
instituted and lifted (see Section 11.3); 
 
Querying HVTN CRSs for additional information regarding reported clinical data; 
and 
 
Providing support to the HVTN 107 PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
Sites must submit all safety forms (eg, reactogenicity, adverse experience, urinalysis, 
local lab results, concomitant medications) before the end of the next business day after 
receiving the information. The forms should not be held in anticipation of additional 
information at a later date. If additional information is received at a later date, the forms 
should be updated and resubmitted before the end of the next business day after receiving 
the new information. 
11.2.2 
AE reporting 
An AE is any untoward medical occurrence in a clinical investigation participant 
administered a study product/procedure(s) and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an investigational study product/procedure(s), whether or not 
related to the investigational study product/procedure(s). All AEs are graded according to 
the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events, Version 2.1 [March 2017], available on the RSC website at 
http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx, except that: 
 
Unintentional weight loss is required to be reported as an adverse event only if it 
is considered to be deleterious to the participant’s health (see HVTN 107 SSP). 
 
Injection Site Erythema or Redness and Injection Site Induration or Swelling will 
not consider interference with usual social and functional activities such that: 
o Grade 1 is: 2.5 to < 5 cm in diameter OR 6.25 to < 25 cm2 surface area; 

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o Grade 2 is: ≥ 5 to < 10 cm in diameter OR ≥ 25 to < 100 cm2 surface 
area; 
o Grade 3 is: ≥ 10 cm in diameter OR ≥ 100 cm2 surface area OR 
Ulceration OR Secondary infection OR Phlebitis OR Sterile abscess OR 
Drainage;  
o Grade 4 is: Potentially life-threatening consequences (e.g., abscess, 
exfoliative dermatitis, necrosis involving dermis or deeper tissue). 
In general, unsolicited AEs will be collected over 30 days post-each vaccination visit. All 
collected 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 pertinent national regulatory authorities (Section 11.2.3); (2) if the AE meets 
the criteria for a safety pause/prompt AE review (Section 11.3); and (3) if the AE is a 
potential immune-mediated disease that may be listed as an AE of special interest 
(AESI). A sample list of AESIs is provided in Appendix N. 
The following AEs will be collected and reported throughout the entire study: 
 
SAEs and AEs requiring expedited reporting to DAIDS (EAEs); 
 
AESIs; 
 
New chronic conditions requiring medical intervention for ≥ 30 days; 
 
New diagnosed or treated STIs; and 
 
AEs leading to early participant withdrawal or early discontinuation of study 
product(s) administration. 
CRSs are expected to notify HVTN clinical safety staff of any serious safety concern 
requiring their attention (see Table 11-1). Telephone numbers and email addresses are 
found on the HVTN 107 home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn107/SitePages/Home.aspx). 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 of Record (IoRs) or their designees are required to submit 
AE information in accordance with IRB/EC and any applicable RE requirements. 
11.2.3 
Expedited reporting of AEs to DAIDS 
Requirements, definitions, and methods for expedited reporting of AEs to DAIDS 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/safetyandpharmacovigilance/. The SAE Reporting Category will 
be used. 

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The internet-based DAIDS Adverse Experience Reporting System (DAERS) must be 
used for expedited AE (EAE) reporting to DAIDS. In the event of system outages or 
technical difficulties, expedited AE reports may be submitted via the DAIDS EAE Form. 
This form is available on the DAIDS RSC website at http://rsc.tech-res.com/clinical-
research-sites/safety-reporting/daids/paper-eae-reporting. 
For questions about DAERS, please contact CRMSsupport@niaid.nih.gov or from within 
the DAERS application itself. For questions about expedited reporting, please contact the 
DAIDS RSC Safety Office at DAIDSRSCSafetyOffice@tech-res.com.  
Under ICH E2A (Clinical Safety Data Management: Definitions and Standards for 
Expedited Reporting), an SAE is defined as any untoward medical occurrence that at any 
dose:  
 
results in death, 
 
is life-threatening (Note: The term “life-threatening” in the definition of “serious” 
refers to an event in which the patient was at risk of death at the time of the event; it 
does not refer to an event, which hypothetically might have caused death, if it were 
more severe), 
 
requires patient hospitalisation or prolongation of existing hospitalisation,  
 
results in persistent or significant disability/incapacity,  
 
is a congenital anomaly/birth defect, or 
 
is a medically important event or reaction  
Medical and scientific judgment should be exercised when deciding if other situations are 
serious. Such instances could include medical events that may not be immediately life-
threatening or result in death or hospitalization, but which may jeopardize the patient or 
may require intervention to prevent one of the outcomes listed in the definition above. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias or convulsions not resulting in hospitalization, 
or development of drug dependency or drug abuse. 
The expedited reporting period for this study comprises the entire study period for each 
individual participant (from study enrolment until study completion or discontinuation 
from the study).  
The study products that must be considered in determining relationships of AEs requiring 
expedited reporting to DAIDS and pertinent national regulatory authorities are: 
 
ALVAC-HIV (vCP2438) 
 
Bivalent Subtype C gp120/MF59® 
 
Bivalent Subtype C gp120 admixed with Aluminum Hydroxide  
 
Bivalent Subtype C gp120 
Clinic staff will report SAEs as indicated in Section 11.3, Safety pause and prompt PSRT 
AE review to HVTN Core or within 3 working days for SAEs not described in Table 
11-1, AE notification and safety pause/AE review rules, in addition to completing the 
standard AE form.  

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11.2.4 
Expedited reporting of AEs to regulatory authorities  
The study sponsor or designee(s) prepares and files expedited reports to appropriate 
regulatory authorities within the timelines required by pertinent national regulatory 
authorities. SAEs will be reported to the South Africa Medicines Control Council (MCC) 
within 24 hours of the sponsor becoming aware of each event followed, as needed, with 
full safety reports deemed reasonably related to study product within the time frame 
specified in the MCC guidelines.  
Site IoRs/designees will submit EAE information and any other relevant safety 
information to their ECs/IRBs in accordance with EC/IRB requirements. 
11.3 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and vaccination with the product 
related to the event that triggered the pause will be held until further notice. The AEs that 
will lead to a safety pause or prompt HVTN 107 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 107 
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 action 
HVTN Core action 
SAE, related 
Grade 5 or 
Grade 4 
Phone immediately, email 
and submit forms 
immediatelya 
Immediate pause 
SAE, not related 
Grade 5 
Phone immediately, email 
and submit forms 
immediatelya 
Immediate HVTN 107 
PSRT notification 
SAE, related 
Grade 3 
Email and submit forms 
immediately 
Prompt HVTN 107 PSRT 
AE review to consider 
pause 
AEb, related 
Grade 4 or 
Grade 3 
Email and submit forms 
immediately 
Prompt HVTN 107 PSRT 
AE review to consider 
pause 
 
a Phone numbers and email addresses are found in the Key Contacts under Safety Reporting and Clinical Monitoring on the HVTN 107 
home page. 
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 107 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 107 PSRT reviews safety data and decides whether the 
pause can be lifted or permanent discontinuation of vaccination is appropriate, consulting 

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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 107 
PSRT assessment, the trial sponsor or designee(s) notifies pertinent national regulatory 
authorities as needed. 
If an immediate HVTN 107 PSRT notification or prompt HVTN 107 PSRT AE review is 
triggered, HVTN Core notifies the HVTN 107 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 107 PSRT AE review cannot be 
completed within 72 hours of notification (excluding weekends and US federal holidays), 
an automatic safety pause occurs. 
The HVTN requires that each CRS submit to its IRB/EC protocol-related safety 
information (such as 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 107 PSRT (see Section 
11.4.2). 
11.4 
Review of cumulative safety data 
Routine safety review occurs at the start of enrollment and then throughout the study. 
Reviews proceed from a standardized set of protocol-specific safety data reports. These 
reports are produced by the SDMC and include queries to the HVTN CRSs. Events are 
tracked by internal reports until resolution.  
11.4.1 
Daily review 
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 107 PSRT AE review criteria. 
11.4.2 
Weekly review 
During the injection phase of the trial, the HVTN 107 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 107 PSRT. HVTN Core 
reviews reports of clinical and laboratory AEs. Events identified during the review that 
are considered questionable, inconsistent, or unexplained are referred to the HVTN CRS 
clinic coordinator for verification. 
11.5 
Study termination 
This study may be terminated early by the determination of the HVTN 107 PSRT, the 
MCC or other pertinent national regulatory authority, NIH, Office for Human Research 
Protections (OHRP), or vaccine developer(s). In addition, the conduct of this study at an 

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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 107 Study Specific Procedures.  
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.  

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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 DNA 
Because this study is evaluating products containing recombinant DNA, it must comply 
with regulations set forth in the NIH’s Guidelines for Research Involving Recombinant or 
Synthetic Nucleic Acid Molecules. Information about the study must be submitted to site 
Institutional Biosafety Committees (IBC) and must be approved before participants are 
enrolled at the site. Investigators at each site are responsible for obtaining IBC approval 
per NIH guidelines section IV-B07-a-(1). IBC review and approval must be documented 
by the investigator and submitted as part of initial protocol registration for this trial. If 
this protocol is amended, investigators should follow the requirements of their IBC. 
12.3 
Specific regulatory considerations for Republic of South Africa and 
other Southern African countries 
The Republic of South Africa has laws regarding the use, manufacture, importation, and 
experimentation of products which are genetically modified. These are contained in the 
Genetically Modified Organism (GMO) Act 15 of 1997, administered by the South 
African National Department of Agriculture, Pretoria. The Registrar of GMO shall be 
consulted on all formal developments relating to this protocol and clinical trial, and as 
required, a formal application will be made to the Registrar of GMO to review the HVTN 
107 clinical trial, to obtain approval for the proposed clinical trial and for the importation 
of the study products.  
Any regulations specific to other countries containing CRSs at which HVTN 107 will be 
implemented will also be observed. 
12.4 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants quickly to 
avoid imminent harm, or to report study findings that may otherwise concern their health 
or welfare.  
When such communication is needed, the CRS will request that its IRB/EC and any 
applicable RE expedite review of the message. If this review cannot be completed in a 
timeframe consistent with the urgency of the required communication, the site should 
contact the participant first, and then notify the IRB/EC and any applicable RE of the 
matter as soon as possible. 

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13 
Version history 
The Protocol Team may modify the original version of the protocol. Modifications are 
made to HVTN protocols via clarification memos, letters of amendment, or full protocol 
amendments.  
The version history of, and modifications to, Protocol HVTN 107 are described below. 
Protocol history and modifications 
Date: May 4, 2017 
Protocol version: Version 3.0 
Protocol modification: Full Protocol Amendment 2 
Item 1 
Added: Optional stool sampling 
Item 2 
Updated in Section 3, Overview and Section 8.5, Acquisition of study products: 
Bivalent Subtype C gp120 and MF59 supplier 
Item 3 
Updated in Section 3.1, Protocol Team 
Item 4 
Reference updated in Section 4.1.3, Rationale for the proposed study 
Item 5 
Revised in Sections 4.8.1: ALVAC-HIV (vCP2438) dose description 
Item 6 
Added in Section 4.10, Preclinical safety studies and Section 4.10.3, Toxicity studies 
of HIV Env vaccines: Study AB20670 
Item 7 
Added as new Section 4.11.1, HVTN 100: Summary of interim HVTN 100 safety 
and immunogenicity results 
Item 8 
Updated in Sections 4.11.2 through 4.11.5: Clinical experience 
Item 9 
Updated in Section 4.12, Potential risks of study products and administration: Table 
4-15 
Item 10 Revised in Section 7.3.3, Discontinuing vaccination for a participant: Criteria for 
discontinuation 
Item 11 Added in Sections 8.3.2 through 8.3.4: Study product storage post-thawing 
Item 12 Clarified in Section 8.5, Acquisition of study products: Provision of empty sterilized 
vials and site acquisition of Aluminum Hydroxide Suspension and Sterile Water for 
Injection 
Item 13 Clarified in Section 9.5: Mucosal sampling 
Item 14 Clarified in Section 9.13, Pregnancy: Pregnancy reporting 
Item 15 Updated in Sections 9.7.1, 10.1, and 14: Site lab instructions source 
Item 16 Clarified in Section 9.10.2, Assessment of injection site: Erythema and induration 
Item 17 Corrected in Sections 10.1 through 10.3: Cross-references to Laboratory procedure 
appendices 
Item 18 Updated in Section 10.10, Other use of stored specimens: “Other use” definition 

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Item 19 Updated in Section 9.10, Assessments of reactogenicity, 11.2.2, AE reporting and 
Section 14, Document references (other than literature citations): AE grading table 
version 
Item 20 Updated in Section 11.2.2, AE reporting: Safety reporting and contact information 
Item 21 Updated in Section 11.2.3, Expedited reporting of AEs to DAIDS: DAIDS template 
text 
Item 22 Added in Section 11.5, Study termination: MCC 
Item 23 Updated in Section 14, Document references (other than literature citations): 
Document URLs 
Item 24 Updated: Section 15, Acronyms and abbreviations 
Item 25 Revised in Appendix A, Sample informed consent form: Maximum blood draw 
volume 
Item 26 Updated in Appendix A, Sample informed consent form: HVTN protocol template 
text 
Item 27 Updated in Appendix C: Language concerning approved birth control methods 
Item 28 Updated in Appendices A and E: Consent language regarding “other uses” of stored 
samples 
Item 29 Updated in Appendix A, Item 26: Study-related injury language 
Item 30 Added to “Questions” section in Appendices A and E: Contact titles, IRB/EC name, 
document references, and MCC contact information 
Item 31 Adjusted in Appendices F through I: Blood draw volumes for laboratory assays 
Item 32 Revised in Appendices F through I: Endpoint laboratory designations 
Item 33 Clarified in footnotes to Appendices J through M: Window for blood and specimen 
collection prior to vaccination at Visits 2 and 17 
Item 34 Added as Appendix O: Protocol signature page 
Item 35 Corrected in Clarification Memo 1 to protocol Version 2.0 
Item 36 Clarified in Clarification Memo 2 to protocol Version 2.0 
Item 37 Minor typographical, formatting, and cross-reference errors have been corrected 
throughout the protocol document 
Date: September 23, 2016 
Protocol version: Version 2.0 
Protocol modification: Clarification Memo 2 
Item 1 
Updated in Section 4.2, ALVAC-HIV (vCP2438): Formulation and manufacturing 
information 
Item 2 
Updated in Section 4.5, Aluminum Hydroxide Suspension: Alum source 
Item 3 
Updated in Section 8, Study product preparation and administration: Formulation 
information, preparation instructions, and product acquisition 
Item 4 
Clarified in Section 9.5, Innate immunity and mucosal sampling: Pregnancy testing 
for cervical sampling 

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Item 5 
Clarified in Section 9.9, Assessments of reactogenicity: Postvaccination memory 
tool 
Date: September 3, 2015 
Protocol version: Version 2.0 
Protocol modification: Clarification Memo 1 
Item 1 
Corrected in Section 9.4, Follow-up visits: Outside testing and belief questionnaire 
removed 
Item 2 
Corrected in Appendix A, Sample informed consent form: Typographical errors 
Item 3 
Corrected in Appendices F and H: Blood draw for syphilis testing 
Item 4 
Corrected in Appendices J, K, L, and M: Timepoints for vaccinations (and 
associated reactogenicity assessments), pregnancy test, CBC, chemistry panel, 
syphilis testing 
Item 5 
Corrected in Appendices L and M: Footnoted cross-references to Laboratory 
Procedures tables 
Date: June 23, 2015 
Protocol version: Version 2.0 
Protocol modification: Full Protocol Amendment  1 
 
Item 1 
Study design revised: New Group 3 added with concurrent ALVAC-protein administration 
at Months 0, 1, 6, and 12 
Item 2 
Updated on cover page, in Sections 3 and 8.5, and in Appendix A: Protein vaccine and 
MF59 study product provider 
Item 3 
Updated in Sections 4.3.1, 4.3.2, 4.4, and 4.6: Novartis product descriptions 
Item 4 
Updated in Section 4.11.4, Clinical studies with Novartis HIV-1 subunit protein vaccines: 
Safety and immunogenicity information 
Item 5 
Updated: Table 4-12, Summary of potential risks of study products and administration 
Item 6 
Added in Section 5.2, Secondary objectives: CD4+ T cell polyfunctionality endpoint 
Item 7 
Revised: Section 6, Statistical considerations 
Item 8 
HVTN protocol template updates incorporated into Section 7, Selection and withdrawal of 
participants 
Item 9 
HVTN protocol template update incorporated into Section 9.1, Informed consent 
Item 10 Section 9.3, Enrollment and vaccination visits: Provision of postvaccination symptom log to 
study participants made optional 
Item 11 HVTN protocol template updates incorporated into Section 11, Safety reporting 
Item 12 Document references (other than literature citations) updated 
Item 13 Aluminum hydroxide adjuvant information updated 
Item 14 Updated: Appendix A, Sample informed consent form 
Item 15 Revised: Appendix B, Injection schedule for sample informed consent form 
Item 16 Revised: Appendix D, Tables of procedures (for sample informed consent form) 

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Item 17 Revised for consistency with Appendix A: Appendix E, Sample consent form for use of 
samples and information in other studies 
Item 18 Revised in Appendices F through M: Procedure tables 
Item 19 Updated in Section 3.1: Other contributors to the original protocol 
Item 20 Updated in Sections 9.9, 11.2.2, and 14: DAIDS AE Grading Table 
Item 21 Revised in Section 11.2.2, AE reporting: Exceptions to AE reporting requirements 
Item 22 Minor corrections of typographical and formatting errors have been corrected throughout the 
protocol 
Date: August 27, 2014 
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. 
 
ABPI. Guidelines for Phase 1 Clinical Trials 2012 Edition. Available at 
http://www.abpi.org.uk/our-work/library/guidelines/Pages/phase-1-trials-2012.aspx 
 
Current CDC Guidelines. Revised Recommendations for HIV Testing of Adults, 
Adolescents, and Pregnant Women in Health-Care Settings. Available at 
http://www.cdc.gov/mmwr/PDF/rr/rr5514.pdf  
 
Division of AIDS (DAIDS) Clinical Research Policies and Standard Procedures 
Documents. Available at https://www.niaid.nih.gov/research/daids-clinical-research-
policies-standard-procedures 
 
Division of AIDS Protocol Registration Manual. Available at 
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf 
 
U.S. Department of Health and Human Services, National Institutes of Health, 
National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of 
AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events, Version 2.1 [March 2017]. Available from: http://rsc.tech-res.com/clinical-
research-sites/safety-reporting/daids-grading-tables   
 
The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 2.0, 
January 2010. Available at http://rsc.tech-res.com/clinical-research-sites/safety-
reporting/manual 
 
Reporting Adverse Drug Reactions in South Africa. Available at 
http://www.mccza.com/documents/ae9635a42.11_ADR_reporting_May03_v1_2.pdf  
 
Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants 
in South Africa. Available at 
http://www.mccza.com/documents/7c21ba77SA_GCP_guidelines_second_edition_2
006.pdf 
 
Republic of South Africa: National Contraception Clinical Guidelines. December 
2012. Available at 
http://www.gov.za/sites/www.gov.za/files/Contraception_Clinical_Guidelines_28jan
2013-2.pdf 
 
Ethics in Health Research: Principles, Processes and Structures (Second edition, 
2015), Department of Health, Republic of South Africa. Available at 
http://www.nhrec.org.za/docs/Documents/EthicsHealthResearchFinalAused.pdf  

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 
Declaration of Helsinki (last updated October 2013), World Medical Association. 
Available at http://www.wma.net/en/30publications/10policies/b3/ 
 
Guidelines on Ethics for Medical Research: HIV Preventive Vaccine Research. 
Available at http://www.mrc.ac.za//ethics/ethicsbook5.pdf 
 
South Africa Genetically Modified Organism (GMO) Act 15 of 1997. Available at 
http://www.saflii.org/za/legis/num_act/gmoa1997286/ 
 
HVTN 107 Special Instructions. Accessible through the HVTN protocol-specific 
website. 
 
HVTN 107 Study Specific Procedures. Accessible through the HVTN protocol-
specific website. 
 
HVTN 107 Site Lab Instructions. Accessible through the HVTN protocol-specific 
website. 
 
HVTN Manual of Operations. Accessible through the HVTN website. 
 
Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
http://www.iata.org/publications/dgr/Pages/index.aspx 
 
Lab assay algorithm. Accessible upon request. 
 
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 
 
International Conference on Harmonisation (ICH) E2A, Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting. Available at 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E
2A/Step4/E2A_Guideline.pdf  
 
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/office-biotechnology-
activities/biosafety/nih-guidelines  
 
NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical Research. 
Available at http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-01-053.html  
 
Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks, July 
2008.  
 
Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials. Available at https://www.niaid.nih.gov/sites/default/files/daids-
sourcedocpolicy.pdf 

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 
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 
 
Immunization Action Coalition, Vaccines with Diluents: How to Use Them. 
Available at http://www.immunize.org/catg.d/p3040.pdf 
 
US Centers for Disease Control and Prevention. Vaccine Storage & Handling 
Toolkit, June 2016. Available at 
http://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/storage-handling-toolkit.pdf  
See Section 16 for literature cited in the background and statistics sections of this 
protocol. 

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15 
Acronyms and abbreviations 
 
Ab 
antibody 
Ad26 
adenovirus serotype 26 
AE 
adverse event 
ALP 
alkaline phosphate 
ALT 
alanine aminotransferase 
ART 
antiretroviral therapy 
ASCUS 
atypical squamous cells of undetermined significance 
AST 
aspartate aminotransferase 
AVEG 
AIDS Vaccine Evaluation Group 
BAMA 
binding antibody multiplex assay 
β-HCG 
beta human chorionic gonadotropin 
BMI 
body mass index 
CAB 
Community Advisory Board 
CAPRISA Centre for the AIDS Programme of Research in South Africa 
CBC 
complete blood count 
CCID 
cell cultural infectious dose 
CDC 
US Centers for Disease Control and Prevention 
CEF 
chick embryo fibroblast 
CFR 
Code of Federal Regulations 
CHIL 
Cape Town HVTN Immunology Laboratory 
CHO 
Chinese hamster ovary 
CI 
confidence interval 
CoR 
correlate of risk 
CRF 
case report form 
CPK 
creatine phosphokinase 
CRPMC 
NIAID Clinical Research Products Management Center 
CRS* 
clinical research site 
CSS 
Clinical Safety Specialist 
CTL 
cytotoxic T lymphocyte 
DAERS 
DAIDS Adverse Experience Reporting System 
DAIDS 
Division of AIDS (US NIH) 
DHHS 
US Department of Health and Human Services 
DHVI 
Duke Human Vaccine Institute 
DOV 
discontinuation of vaccinations 
EAE 
adverse events requiring expedited reporting to DAIDS 
EC 
Ethics Committee 
ELISA 
enzyme-linked immunosorbent assay 
ELISpot 
enzyme-linked immunospot 

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EMA 
European Medicines Agency 
FDA 
US Food and Drug Administration 
FHCRC 
Fred Hutchinson Cancer Research Center 
GCP 
Good Clinical Practice 
GEE 
generalized estimating equation 
GLP 
Good Laboratory Practice 
GM 
geometric mean 
GMO 
genetically modified organism 
GMP 
Good Manufacturing Practice 
GPP 
Good Participatory Practice 
GSID 
Global Solutions for Infectious Diseases 
GSK 
GlaxoSmithKline 
GTI 
genital tract infection 
HBsAG 
hepatitis B surface antigen 
HCRISA 
Hutchinson Centre Research Institute - South Africa 
HCV 
hepatitis C virus 
HLA 
human leukocyte antigen 
HPTN 
HIV Prevention Trials Network 
HSML 
HIV Sero-Molecular Laboratory 
HSV 
herpes simplex virus 
HVTN 
HIV Vaccine Trials Network 
IAC 
Immunization Action Coalition 
IB 
Investigator’s Brochure 
IBC 
Institutional Biosafety Committee 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
ICS 
intracellular cytokine staining 
IFN-γ 
interferon gamma 
IgA 
immunoglobulin (isotype) A 
IgG 
immunoglobulin (isotype) G 
IL 
interleukin 
IM 
intramuscular 
IN 
intranasal 
IP  
IFN-γ–induced protein 
IRB 
Institutional Review Board 
ISS 
Istituto Superiore di Sanità 
IUD 
intrauterine device 
MAR 
missing at random 
MCAR 
missing completely at random 
MCC 
(South Africa) Medicines Control Council 
MCP  
monocyte chemotactic protein  
MedDRA Medical Dictionary for Regulatory Activities 

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MMR 
measles, mumps, and rubella 
MUVAPRED 
Mucosal Vaccines for Poverty Related Diseases 
nAb 
neutralizing antibody 
NAEPP 
National Asthma Education and Prevention Program 
NHP 
nonhuman primate 
NIAID 
National Institute of Allergy and Infectious Diseases (US NIH) 
NICD 
National Institute for Communicable Diseases (Johannesburg, South Africa) 
NIH 
US National Institutes of Health 
NK 
natural killer (cells) 
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 
PHRU 
Perinatal HIV Research Unit 
PI 
Principal Investigator 
PSRT 
Protocol Safety Review Team 
RAB 
DAIDS Regulatory Affairs Branch 
RE 
regulatory entity 
RNA 
ribonucleic acid 
RSA 
Republic of South Africa 
RSC 
DAIDS Regulatory Support Center 
SAE 
serious adverse event 
SAIL 
South African Immunology Laboratory 
SCHARP Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
statistical and data management center 
SIV 
simian immunodeficiency virus 
SMB 
Safety Monitoring Board 
SPF 
specific pathogen free 
SPT 
DAIDS Safety and Pharmacovigilance Team 
SSP 
Study Specific Procedures 
TB 
tuberculosis 
Tfh 
T follicular helper (CD4+) 
TM 
transmembrane 
TNF 
tumor necrosis factor 
VISP 
Vaccine induced seropositivity 
VRC 
Vaccine Research Center 
WBC 
white blood cell 
* CRSs were formerly referred to as HIV Vaccine Trial Units (HVTUs). Conversion to 
use of the term CRS is in process, and some HVTN documents may still refer to HVTUs. 

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16 
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  69.   Spearman P, Lally MA, Elizaga M, Montefiori D, Tomaras GD, McElrath MJ, Hural J, De 
Rosa SC, Sato A, Huang Y, Frey SE, Sato P, Donnelly J, Barnett S, Corey LJ. A 
trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing 
antibodies but limited breadth of neutralization in human volunteers. J Infect Dis 
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  71.   Lachenbruch PA. Comparisons of two-part models with competitors. Stat Med 
2001;20:1215-34. 
 
  72.   Hughes JP. Mixed effects models with censored data with application to HIV RNA levels. 
Biometrics 1999;55:625-9. 
 
  73.   Rotnitzky A, Robins J. Analysis of semi-parametric regression models with non-ignorable 
non-response. Stat Med 1997;16:81-102. 
 
  74.   Seaman M, Janes H, Hawkins N, randpre L, Devoy C, Giri A, Coffey R, Harris L, Wood B, 
Daniels M, Bhattacharya T, Lapedes A, Polonis V, McCutchan F, Gilbert P, Self S, 
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Appendix A 
Sample informed consent form 
Title: A Phase 1/2a partially double-blinded, randomized clinical trial to characterize the 
safety and immunogenicity of clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C 
gp120 alone, with MF59® adjuvant, and with alum adjuvant in healthy, HIV uninfected 
adult participants 
HVTN protocol number: HVTN 107 
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 study vaccines. HIV is the virus that causes AIDS. 
About 132 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) and the Bill & Melinda Gates Foundation are paying for the study.  
1. We are doing this study to answer several questions. 
 
Are the study vaccines safe to give to people? 
 
Are people able to take the study vaccines without becoming too uncomfortable? 
 
How do people’s immune systems respond to the study vaccines? (Your immune 
system protects you from disease.) 
2. The study vaccines cannot give you HIV. 
The study vaccines are not made from actual HIV. It is impossible for the study vaccines 
to give you HIV. Also, they cannot cause you to give HIV to someone else. 
3. We do not know if the study vaccines 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 

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the vaccine. In other 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 vaccines are experimental. 
The study vaccines are called ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 
(gp120 is a protein). From here on, we will call them ALVAC and Protein, or the study 
vaccines. They are experimental HIV vaccines. That means we do not know whether the 
study vaccines will be safe to use in people, or whether they will work to prevent HIV 
infection. These study vaccines are used only in research studies. 
The study vaccines were developed by Sanofi Pasteur and Novartis Vaccines and 
Diagnostics (now GSK Vaccines).  
The ALVAC vaccine is made out of canarypox virus. Canarypox virus infects birds but 
cannot infect humans. This virus has small bits of man-made DNA inserted into it. DNA 
is a natural substance found in all living things, including people and some viruses. The 
canarypox virus helps get the DNA into the body’s cells. The DNA then tells those cells 
to make small amounts of proteins that look like some of the ones found in HIV.  
The Protein vaccine has man-made pieces of a protein found on the outside of HIV. This 
vaccine will be given in this study either on its own or mixed with one of two adjuvants. 
An adjuvant is something added to the vaccine to help the immune system respond better. 
In this study the adjuvants used are called Aluminum hydroxide (alum) or MF59. Alum 
adjuvants are used in many licensed vaccines that have been given to millions of people. 
MF59 has been included in flu vaccines licensed in many countries. It has also been 
included in other vaccines that have been given to over 50,000 people in clinical trials 
without causing any serious health problems. MF59 is made by Novartis Vaccines and 
Diagnostics. The alum adjuvant in this study is provided by the US NIH Vaccine 
Research Center. 
These HIV study vaccines have not been given to people before. However, similar 
ALVAC and Protein vaccines have been given to more than 10,000 people in clinical 
trials without causing any serious health problems. Most of these people received study 
vaccines with an alum adjuvant. This includes a study in South Africa, HVTN 097, in 
which 80 participants received similar ALVAC and protein vaccines with alum adjuvant. 
Also, more than 300 people have received a similar combination of these vaccines with 
the MF59 adjuvant in clinical trials without having any serious health problems. The 
ALVAC and Protein vaccines with MF59 are now being given to 210 participants in 
another study in South Africa, HVTN 100. 
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 at the 
injection site. Most people can still do their planned activities after getting a vaccine. 

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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 vaccines: 
This section lists the side effects 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.  
In earlier studies with similar ALVAC and Protein vaccines, some people found it 
difficult or painful to move their arm for a short while after the injection(s). Some people 
felt tired or weakened, and some people had swollen lymph nodes. A small number of 
people had diarrhea, flu-like symptoms, or severe pain or swelling at the place on their 
arm where they got the injection(s). An even smaller number had trouble sleeping, 
stomach pain, loss of appetite, an odd taste in their mouths, fainting, acne, eyelid swelling 
or felt itching at the place on their arm where they got the injection. These problems 
usually happened within a couple of days of injection(s) and usually went away on their 
own within a few days. Not everyone had these problems. 
Joining the study 
5. It is completely up to you whether or not to join the study.  
Take your time in deciding. If it helps, talk to people you trust, such as your doctor, 
friends or family. If you decide not to join this study, or if you leave it after you have 
joined, your other care at this clinic and the benefits or rights you would normally have 
will not be affected. 
If you join this study, you may not be allowed to join other HIV vaccine or HIV 
prevention studies now or in the future. You cannot be in this study while you are in 
another study where you receive 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 6 if you use a separate screening consent that covers these procedures. 
6. If you decide 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 

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 
Listening to your heart and lungs 
 
Feeling your abdomen (stomach and liver) 
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 B, Hepatitis C, and syphilis. We will ask you about medications you 
are taking. South African sites should maintain the following sentence. All other sites 
should delete: Only medicines that have been registered in South Africa, or approved for 
study use, may be used in this study. 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 
also ask if you have ever been allergic to eggs, egg products, or the antibiotic Neomycin. 
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) 
7. If we find that you have a health problem unrelated to the study vaccines 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, but we will not pay for it. 
8. If you were born female and could become pregnant, you must agree to use birth 
control to join this study. 
Site: List approved birth control methods here if you do not want to hand out the separate 
Approved Birth Control Methods sheet. 
You should not become pregnant during the study because we do not know how the study 
vaccines could affect the developing baby. You must agree to use effective birth control 
from 3 weeks 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. Site: Delete the preceding sentence if you include the birth control sheet 
in this consent form. If you join the study, we will test you for pregnancy at some visits, 
including before each study injection.  
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
9. You will come to the clinic for scheduled visits about 14 times over 18 months. 
Site: Insert range of visit lengths. 
Visits can last from [#] to [#] hours. 
You may have to come for more visits if you have a lab or health issue.  
If you agree to give extra samples, we may ask you to come in for 3 extra visits (we will 
describe this more in section 13).  

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We may contact you after the main study ends (for example, to tell you about the study 
results). 
10. 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). 
You do not have to pay anything to be in this study. 
11. We will give you the study products on a schedule. 
There are 4 groups in this study. Overall, you will get 8 injections during the study with a 
needle into your upper arms. The ALVAC vaccine will go into the left arm. The Protein 
vaccine will go into the right arm. 
Site: A picture version of the injection schedule has been provided in Appendix B. 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 
give this picture to volunteers. 
 
Group 
Injection schedule 
First injection 
1 month later 
3 months later 
6 months later 
12 months later 
GROUP 1 
(about 36 
people) 
ALVAC 
ALVAC 
ALVAC + 
Protein/MF59® 
ALVAC + 
Protein/MF59® 
ALVAC + 
Protein/MF59® 
GROUP 2 
(about 36 
people) 
ALVAC 
ALVAC 
ALVAC + 
Protein/Alum 
ALVAC + 
Protein/Alum 
ALVAC + 
Protein/Alum 
GROUP 3 
(about 36 
people) 
ALVAC + 
Protein/MF59® 
ALVAC + 
Protein/MF59® 
 
ALVAC + 
Protein/MF59® 
ALVAC + 
Protein/MF59® 
GROUP 4 
(about 24 
people) 
ALVAC 
ALVAC 
ALVAC + 
Protein 
ALVAC + 
Protein 
ALVAC + 
Protein 
You will have to wait in the clinic for about a half hour after each injection to see if there 
are any problems. Then for that night and for three more days, you will need to tell the 
clinic staff how you feel. To help you do this, we can give you tools and show you how 
to use them. We will ask you the ways we can contact you. If you do not contact us on 
each of the three days after your injections, we will contact you by the ways you wish to 
be contacted. If you have a problem, we will continue to check on you until it goes away.  
You may have to wait until everyone completes their final study visits to find out which 
study group you were in. 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. 
Also, please contact clinic staff 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.  

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12. In addition to giving you the study products, we will:  
 
Do regular HIV testing, as well as counseling on your results and on how to avoid 
getting HIV; 
 
Perform 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, 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 225 mL (2 teaspoons to a little less than 1 cup). Your 
body will make new blood to replace the blood we take out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate blood 
in the US can give a total of about 500 mL in an 8-week period.”). Modify the example 
for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix D, Table of procedures (for informed consent form) in this section 
or distribute it as a separate sheet if it is helpful to your study participants. You are not 
required to do either.. 
We will be looking for side effects. We will review the results of these procedures and 
tests with you at your next visit, or sooner if necessary. If any of the results are important 
to your health, we will tell you.  
13. We would like to learn more about how your immune system responds to the 
vaccine by collecting extra samples. We would like to collect blood samples, rectal 
fluid, cervical fluid, and semen. 
Some spots in this study are only open to participants who agree to give these extra 
samples. Because of this, you may have to agree to give the extra samples in order to join 
the study. However, if enough people have agreed to give extra samples, we may not 
need yours, even if you are willing to give them. 
Most people are exposed to HIV on their rectum, vagina/cervix, or penis, so it is 
important to learn if the study vaccines affect those areas. We also want to see if the 
study vaccines affect your blood the same way as in those areas.  
Participants born female who are over 21 years of age need to have had a Pap smear with 
normal results within the past 3 years in order to give cervical samples. We can tell you 
where to get a Pap smear if you have not had one within that time. 
When we take rectal, cervical, and semen samples, we will also do tests for the following 
infections: syphilis, gonorrhea, chlamydia, trichomoniasis, and bacterial vaginosis. We 
may also test you for yeast infection. We will explain what each of these infections is. If 

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the tests say you have an infection, we will provide counseling and will help you get 
treatment. This study cannot pay for that treatment. [Site: Revise preceding sentence if 
you provide or pay for STI treatment.] 
Blood samples: We will ask you to come in 2 or 3 extra times for blood draws, depending 
on which group you are in. These extra visits will be 1 day and 3 days after your first 
vaccination, or 1 day, 3 days, and 7 days after your third vaccination. The amount of 
blood we would collect at each of these study visits is about 40 to 50 mL (a little less than 
¼ cup). 
Fluid samples: We will collect fluids from your rectum and from your cervix (if you 
have one). If you were born male and can provide a sample, we will collect semen at 
these visits.  
We want to collect fluids from these areas 5 times:  
 
before your first study injection,  
 
2 weeks after your second to last study injections, 
 
at the time of your last study injections, 
 
2 weeks after your last study injections, and also 
 
6 months after your last study injections.  
For all participants who agree to provide extra samples, we will collect rectal fluids 
by wiping the lining of your rectum with a cotton swab, sponge, or brush, or we may 
place a special strip of absorbing paper inside the rectum for about 5 minutes. An 
anoscope, a plastic viewing tube 5-8 centimeters long and 1¼ centimeters wide, may be 
inserted into the rectum so that the clinician can see better when doing this procedure. 
For the 2 days before we collect your rectal fluid, we will ask you to:  
 
not have receptive anal intercourse (have someone else’s penis inside your rectum);  
 
not put anything into your anus, including cleaning products (creams, gels, lotions, 
pads, etc.), lubricant, or enemas;  
 
not douche (even with water); and 
 
not use any anti-inflammatory creams in or around your anus.  
We will not collect rectal fluid if you are pregnant, or if we think you may have an anal 
or rectal infection. You should tell us if your rectal area is sore. 
For participants who were born female, to collect cervical fluids we will give you a 
menstrual cup (a small flexible plastic cup, shaped like a bell) to insert into your vagina. 
The study staff will explain how to insert and remove the cup, or they can do it for you 
here. We will explain how many cups we will collect and how long you should wear 
them. 
For the 2 days before we collect cervical samples, we ask you:  

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 
not to use any spermicide, lubricants, douche (even with water), or medication in 
or around your vagina; and 
 
not to have vaginal intercourse or insert anything into your vagina.  
Do not insert the menstrual cup:  
 
if you think you may be pregnant. 
 
if you think you may have a cervical or vaginal infection.  
We may ask you to collect this sample at a later date. 
For participants who were born male, you may provide the semen at home or here. We 
will give you a plastic cup and ask you to ejaculate into it. We must receive the semen 
sample within 2 hours or less after it is collected. For at least 2 days before providing the 
semen, we ask you: 
 
not to have sex, including oral sex 
 
not to ejaculate 
 
not to use anything with lubricants 
 
not to put saliva on the penis 
You should tell us if you think you have an infection on your penis. If you have an 
infection, we may not use your sample.  
At the end of this consent form, we will ask you if you allow us to collect these samples. 
If you agree to provide these samples, you can change your mind at any time during the 
study. 
14. We would also like to collect stool samples. 
We would like to collect two small samples of your stool to look at the bacteria living in 
your stomach. We want to learn if your immune response to the study vaccines is 
influenced by these bacteria. We will do this once at the day of enrollment (month 0) and 
again at your 6.5 month visit. If you agree, we will give you more information about how 
we will collect these samples. 
You can give stool samples without having any extra clinic visits. You can give stool 
samples and not give rectal fluid, cervical fluid, or semen. 
At the end of this consent form, we will ask if you allow us to collect stool samples.  
15. We will test your samples for this study. 
We will send your samples (without your name) to labs approved by the HVTN to test 
how your immune system responds to the study products.  

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Most of these labs will be in South Africa, but some will be in the United States. In rare 
cases, some of your samples may be sent to labs approved by the HVTN in other 
countries for research related to this study. 
Researchers may also do genetic testing related to this study on your samples. Your genes 
are passed to you from your birth parents. They affect how you look and how your body 
works. The differences in people’s genes can help explain why some people get a disease 
while others do not. These types of genetic tests involve some of your genes, not all of 
your genes (your genome). The researchers will study the genes related to the immune 
system and HIV and those that affect how people get HIV.  
If you become HIV infected, the researchers may look at all of the genes of the virus 
found in your samples. If you give stool samples, the researchers may look at all of the 
genes of the bacteria found in your samples. In both cases, the researchers will use this 
information to learn more about HIV and the study products. The researchers may put 
this information about the virus and/or bacteria into a protected database so that other 
researchers can access it. They would not be able to link the information from your 
samples to you.  
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. 
16. 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.  
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. [Site: insert specific information if your regulatory authority requires it.] 
Your samples will be stored in the HVTN repository in South Africa.  
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.] 

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Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, there is 
no plan to share any money with you. The researcher is not likely to ever know who you 
are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. They are 
not part of your medical record. The studies are only being done for research purposes. 
Will the HVTN sell my samples and information? No, but the HVTN may share your 
samples with other researchers. Once we share your samples and information, we will not 
be able to get them back. 
How do other researchers get my samples and information? When a researcher wants to 
use your samples and/or information, their research plan must be approved by the HVTN. 
Also, the researcher’s institutional review board (IRB) or ethics committee (EC) will 
review their plan. [Site: If review by your institution’s IRB/EC/RE is also required, insert 
a sentence stating this.] IRBs/ECs protect the rights and well-being of people in research. 
If the research plan 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 

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 
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. 
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, 
 
[Insert name of local IBC], 
 
[Insert name of local IRB/EC] , 
 
[Insert name of local and/or national regulatory authority as appropriate], 
 
Sanofi Pasteur and GSK Vaccines and people who work for them, 

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 
The HVTN and people who work for them,  
 
The HVTN Safety Monitoring Board; and 
 
The US Office for Human Research Protections. 
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. At this clinic, we have to report the following 
information:  
Site: Include any public health or legal reporting requirements. Bulleted examples should 
include all appropriate cases (reportable communicable disease, risk of harm to self or 
others, etc.). 
 
[Item 1] 
 
[Item 2] 
 
[Item 3] 
The results of this study may be published. No publication will use your name or identify 
you personally. 
We may share information from the study with other researchers. We will not share your 
name or information that can identify you. 
When the study is done, we may share the information from the study with others so they 
can see it and use it. We will not share any information that will let someone identify 
you. 
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 
additional injections.  
This may happen if: 
 
you do not follow instructions, 
 
the researcher thinks that staying in the study might harm you, 
 
you get HIV, 
 
you enroll in a different research study where you receive 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.  
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. 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 at the 
injection site. 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 is likely to 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 receive a positive test result caused by the study vaccines at any time, we can 
provide you with free HIV testing for as long as you need it. If this happens, we do not 
know how long you will test positive due to the study vaccines. If you receive a positive 

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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 continues 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 
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.   
Unknown risks:  

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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 vaccines 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 
vaccines 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.  
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 
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. 

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If you get sick or injured in this study, there is a process to decide if it is related to the 
study vaccines 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 funds may 
come from different groups, as described below. 
(Sites: Adjust the language in this paragraph (or remove altogether) so it is applicable to 
your site.) In this study, our clinic has insurance to cover your medical treatment in case 
of a study-related injury, following the Association of the British Pharmaceutical Industry 
guidelines for payment of study-related injury. We can give you a copy of these 
guidelines. In rare cases, insurance funds may not be enough. In this situation, the 
vaccine developers have agreed to pay the reasonable cost of medical expenses that arise 
from injuries caused by the study products.  
For study-related injuries that cannot be funded as described above, the HVTN has 
limited funds to pay medical costs that it determines are reasonable. (Sites: insert locale- 
appropriate medical insurance language in the following sentence) If the injury is not 
study related, then you and 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. 
Questions  
27. If you have questions or problems at any time during your participation in this 
study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, or become sick or 
injured during the study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research participant, 
or problems or concerns about how you are being treated in this study, contact 
[name or title and telephone number of person on IRB or other appropriate organization]. 
The study has been structured in accordance with the Declaration of Helsinki (last 
updated October 2013) which deals with the recommendations guiding doctors in 
biomedical research involving human participants, the Ethics in Health Research: 
Principles, Structures and Processes Second Edition 2015, and Guidelines for Good 
Practice in the Conduct of Clinical Trials in Human Participants in South Africa. We can 
provide you with copies of these guidelines if you wish to review them. 
If you want to leave this study, contact 
[name and telephone number of the investigator or other study staff]. 

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You can reach a study staff member 24-hours a day at [telephone number]. 
South African sites: Include the following: 
If you have questions about this trial you should first discuss them with your doctor or the 
ethics committee (contact details as provided on this form). After you have consulted 
your doctor or the ethics committee and if they have not provided you with answers to 
your satisfaction, you should write to the South African Medicines Control Council 
(MCC) at: 
The Registrar of Medicines 
Medicines Control Council 
Department of Health 
Private Bag X828 
PRETORIA 
0001 
 
Fax: (012) 395 9201 
 
e-mail: gouwsj@health.gov.za 
 Your permissions and signature  
28. In section 13 of this form, we told you about optional additional sampling. This 
includes blood draws at extra visits and also collection of rectal and cervical or 
semen samples. Please write your initials or make your mark in the boxes next to the 
options you choose. 
 
I agree to blood draws at extra clinic visits and to provide rectal and cervical or 
semen samples. 
OR 
 
I do not agree to this extra sampling. 
29. In section 14 of this form, we told you about collecting stool samples. Please write 
your initials or make your mark in the box next to the option you choose. 
 
I agree to provide stool samples. 
I do not agree to provide stool samples. 
Site: Delete the following section if using a separate consent for use of samples and 
information in other studies. 
30. 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 choice about how your 
samples and information can be used 
 

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I allow my extra samples combined with limited information to be used for 
other studies related to HIV, vaccines, 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. 
31. 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 
Injection schedule for sample informed 
consent form 
This table shows the injections you will get while you are in the study. This table does 
not show all of your study visits. 
 
 

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Appendix C 
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 
vaccines could affect the developing baby.  
You must agree to use effective birth control, from 3 weeks before your first study 
injection until 6 months after your last study injection.  
Effective birth control means using any of the following methods every time you have 
sex: 
 
Male or female condoms; or, 
 
Diaphragm or cervical cap; 
PLUS 1 of the following methods: 
 
Birth control drugs that prevent pregnancy—given by pills, patches, vaginal 
rings, or inserts under the skin;  
 
Intrauterine device (IUD); or 
 
You are only having sex with a partner who has had a vasectomy. (We will ask 
you some questions to confirm that the vasectomy was successful.).  
You do not have to use birth control if: 
 
You have 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 D 
Tables of procedures (for sample informed consent form) 
Main study (Groups 1, 2, and 4) 
 
 
Time after 1st injection visit (in months) 
Procedure 
Screening 
visit(s) 
First injection 
visit 
¼  
1 
1½  
3 
3½  6 
6¼  6½ 
9 
12 
12¼ 
12½ 
15 
18 
Injection 
 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born 
female)* 
√ 
√ 
 
√ 
 
√ 
 
√ 
 
 
 
√ 
 
 
√ 
 
HIV testing & pretest counseling 
√ 
 
 
 
 
√ 
 
√ 
 
 
√ 
√ 
 
 
√ 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Stool sample collection (optional) 
 
√ 
 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
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.  
* Persons who had a complete hysterectomy (removal of the uterus) or had their ovaries removed (verified by medical records), are not required to have a pregnancy test. 
 
Main study (Group 3) 
 
 
Time after 1st injection visit (in months) 
Procedure 
Screening 
visit(s) 
First 
injection 
visit 
¼  1 
1½  
3 
6 
6¼  6½ 
9 
12 
12¼ 
12½ 
15 
18 
Injection 
 
√ 
 
√ 
 
 
√ 
 
 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
√ 
 
 
 
 
 
 
 
 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born female)* 
√ 
√ 
 
√ 
 
 
√ 
 
 
 
√ 
 
 
√ 
 
HIV testing & pretest counseling 
√ 
 
 
 
 
√ 
√ 
 
 
√ 
√ 
 
 
√ 
√ 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Stool sample collection (optional) 
 
√ 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
* Persons who had a complete hysterectomy (removal of the uterus) or had their ovaries removed (verified by medical records), are not required to have a pregnancy test. 

Version 3.0 / May 4, 2017 
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Extra visits and sampling (Groups 1, 2, and 4) 
 
 
 
Time after 1st injection visit (in months) 
Procedure 
Screening visit(s) 
First injection visit 
¼  1 
1½  3 
3 +  
1 day 
3 + 
3 days 
3¼  3½  6 
6¼  6½ 
9 
12 
12¼ 
12½ 
15 
18 
Injection 
 
√ 
 
√ 
 
√ 
 
 
 
 
√ 
 
 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born female)* 
√ 
√ 
 
√ 
 
√ 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
HIV testing & pretest counseling 
√ 
 
 
 
 
√ 
 
 
 
 
√ 
 
 
√ 
√ 
 
 
 
 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pap smear† 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rectal/cervical fluids/semen samples 
 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
Stool sample collection (optional) 
 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
GTI testing (urine and/or swab or blood) 
 
√ 
 
 
 
 
 
 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
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.  
* Persons who had a complete hysterectomy (removal of the uterus) or had their ovaries removed (verified by medical records), are not required to have a pregnancy test. 
† For participants who were born female and who agree to provide cervical fluid samples.  
Extra visits and sampling (Group 3) 
 
 
 
 
 
Time after 1st injection visit (in months) 
Procedure 
Screening visit(s) 
First injection visit 
+ 1 day 
+ 3 days 
¼  1 
1½  3 
6 
6¼  6½ 
9 
12 
12¼ 
12½ 
15 
18 
Injection 
 
√ 
 
 
 
√ 
 
 
√ 
 
 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
 
 
√ 
 
 
 
 
 
 
 
 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test (participants born female)* 
√ 
√ 
 
 
 
√ 
 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
HIV testing & pretest counseling 
√ 
 
 
 
 
 
 
√ 
√ 
 
 
√ 
√ 
 
 
 
 
Risk reduction counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pap smear† 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rectal/cervical fluids/semen samples 
 
√ 
 
 
 
 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
Stool sample collection (optional) 
 
√ 
 
 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
GTI testing (urine and/or swab or blood) 
 
√ 
 
 
 
 
 
 
 
 
√ 
 
√ 
 
√ 
 
√ 
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.  
* Persons who had a complete hysterectomy (removal of the uterus) or had their ovaries removed (verified by medical records), are not required to have a pregnancy test. 
† For participants who were born female and who agree to provide cervical fluid samples.  

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Appendix E 
Sample consent form for use of samples and 
information in other studies 
Title: A Phase 1/2a partially double-blinded, randomized clinical trial to characterize the 
safety and immunogenicity of clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C 
gp120 alone, with MF59® adjuvant, and with alum adjuvant in healthy, HIV uninfected 
adult participants 
HVTN protocol number: HVTN 107 
Site: [Insert site name] 
When samples are no longer needed for this study, the HVTN wants to keep them for use 
in other studies. We will call these “extra samples.” 
This form gives you information so you can decide if you want your extra samples and 
information used in other studies. You will mark your decision at the end of the form. If 
you have any questions, please ask.  
1. Do I have to agree?  
No. You are free to say yes or no, or to change your mind after you sign this form. At 
your request, we will destroy all extra samples that we have. Your decision will not affect 
your being in this study or have any negative consequences here.  
2. Where are the samples stored?  
Extra samples are stored in a secure central place called a repository. [Site: insert specific 
information if your regulatory authority requires it.] Your samples will be stored in the 
HVTN repository in South Africa.  
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. 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 141 of 155 
6. Will the HVTN sell my samples and information?  
No, but the HVTN may share your samples with other researchers. Once we share your 
samples and information, we will not be able to get them back. 
7. How do other researchers get my samples and information?  
When a researcher wants to use your samples and/or information, their research plan 
must be approved by the HVTN. Also, the researcher’s institutional review board (IRB) 
or ethics committee (EC) will review their plan. [Site: insert review by your institution’s 
IRB/EC, if applicable.] 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 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 products.  
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 his 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.   

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 142 of 155 
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 this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, or become sick or 
injured during the study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research participant, 
or problems or concerns about how you are being treated in this study, contact 
[name or title and telephone number of person on IRB or other appropriate organization]. 
The study has been structured in accordance with the Declaration of Helsinki (last 
updated October 2013) which deals with the recommendations guiding doctors in 
biomedical research involving human participants, the Ethics in Health Research: 
Principles, Structures and Processes Second Edition 2015, and Guidelines for Good 
Practice in the Conduct of Clinical Trials in Human Participants in South Africa. We can 
provide you with copies of these guidelines if you wish to review them. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
You can reach a study staff member 24-hours a day at [telephone number]. 
South African sites: Include the following: 
If you have questions about this trial you should first discuss them with your doctor or the ethics 
committee (contact details as provided on this form). After you have consulted your doctor or the 
ethics committee and if they have not provided you with answers to your satisfaction, you should 
write to the South African Medicines Control Council (MCC) at: 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 143 of 155 
The Registrar of Medicines 
Medicines Control Council 
Department of Health 
Private Bag X828 
PRETORIA 
0001 
 
Fax: (012) 395 9201 
 
e-mail: mogobm@health.gov.za 
13. Please choose only one of the options below and write your initials or make your 
mark in the box next to it. Whatever you choose, the HVTN keeps track of your 
choice about how your samples and information can be used. 
 
 
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 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 144 of 155 
Appendix F 
Laboratory procedures (Groups 1, 2, and 4) 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Day:
D0
D1
D3
D7
D28
D42
D84
D85
D87
D91
D98
D168
D175
D182
D273
D364
D371
D378
D455
D546
Weeks
W0
W1
W4
W6
W12
W13
W14
W24
W25
W26
W39
W52
W53
W54
W60
W72
Month
M0
M0.25
M1
M1.5
M3
M3.25
M3.5
M6
M6.25
M6.5
M9
M12
M12.25
M12.5
M15
M18
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. capacity)4
ALVAC
ALVAC
ALVAC+prot+MF59 OR 
Alum OR No Adj
ALVAC+prot+MF59 OR 
Alum OR No Adj
ALVAC+prot+MF59 OR 
Alum OR No Adj
Total
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
2mL
4
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
4
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics9
HSML-NICD
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
10
—
—
—
—
10
—
—
10
10
—
—
10
209
70
STI Serology
Syphilis
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
Safety labs
CBC/ Diff/ platelets
Local lab
Local lab
EDTA
5mL
5
—
—
—
5
—
5
—
—
—
—
5
—
—
5
—
—
—
5
5
—
35
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
5
—
5
—
—
—
—
5
—
—
5
—
—
—
5
5
—
35
Immunogenicity & Virologic assays 6
HLA host genetics7
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
17
Cellular assays
ICS
BARC
HVTN Labs
ACD
8.5mL
—
85
—
—
—
—
85
—
—
—
—
85
—
—
85
—
85
—
85
—
85
595
Phenotyping (pTfh and plasmablasts)
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
17
—
—
—
—
—
—
—
—
17
—
—
17
17
—
—
—
85
Humoral assays
Binding Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
8.5
—
—
8.5
8.5
8.5
—
8.5
—
8.5
68
Neutralizing Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
8.5
—
—
8.5
—
8.5
—
8.5
—
8.5
60
Storage
PBMC
BARC
ACD
8.5mL
—
42.5
—
—
34
—
59.5
—
—
—
—
59.5
—
59.5
59.5
—
59.5
51
59.5
—
59.5
544
Serum
BARC
SST
8.5mL
—
17
—
—
—
—
17
—
—
—
—
17
—
—
17
17
17
—
17
—
17
136
Visit total
24
196
0
0
61
0
189
10
0
0
0
189
10
77
189
36
206
68
189
20
199
1659
56-Day total
24
220
220
220
281
281
469
199
199
199
199
387
10
87
275
36
206
274
462
20
199
URINE COLLECTION
Urinalysis
Local lab
Local lab
X
—
—
—
X
—
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
Pregnancy Test8
Local lab
Local lab
X
X
—
—
—
X
—
X
—
—
—
—
X
—
—
—
X
—
—
X
—
STOOL COLLECTION (OPTIONAL)
Stool
BARC
HVTN Labs
—
X10
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
—
—
—
—
Screening 
visit3
 
Shaded visits not required. 
1 BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd. (Johannesburg, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory–National Institute for Communicable Diseases (Johannesburg, South Africa) 
2 HVTN Laboratories include: Cape Town HVTN Immunology Laboratory (CHIL, Cape Town, South Africa); South African Immunology Laboratory–National Institute for Communicable Diseases (SAIL-NICD, Johannesburg, South Africa); Fred Hutchinson 
Cancer Research Center (Seattle, Washington, USA); Duke Human Vaccine Institute, Duke University Medical Center (Durham, North Carolina, USA) 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination.  
4 Local 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). 
 
6 Immunogenicity assays will be performed at M0 (for binding Ab assay) and M6.5 and 12. Based on the number of responders observed at these timepoints, lab assays may be performed on participants for humoral and cellular responses at other timepoints. 
7 Genotyping 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. 
8 Pregnancy tests may be performed on blood specimens. 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 At an early termination visit for a withdrawn or terminated participant (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 21 above.  
10 Optional stool specimen must be collected prior to first vaccination. 
 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 145 of 155 
Appendix G 
Laboratory procedures (Groups 1, 2, and 4 – innate and mucosal subset) 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Day:
D0
D1
D3
D7
D28
D42
D84
D85
D87
D91
D98
D168
D175
D182
D273
D364
D371
D378
D455
D546
Weeks
W0
W1
W4
W6
W12
W13
W14
W24
W25
W26
W39
W52
W53
W54
W60
W72
Month
M0
M0.25
M1
M1.5
M3
M3.25
M3.5
M6
M6.25
M6.5
M9
M12
M12.25
M12.5
M15
M18
Ship to1
Assay location2
Tube 
Type4
Tube size (vol. 
capacity)4
ALVAC
ALVAC
ALVAC+prot+MF59 OR 
Alum OR No Adj
ALVAC+prot+MF59 OR 
Alum OR No Adj
ALVAC+prot+MF59 OR 
Alum OR No Adj
Total
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
2mL
4
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
4
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 9
HSML-NICD
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
10
—
—
—
—
10
—
—
10
10
—
—
10
209
70
STI Serology
Syphilis
Local lab
Local lab
SST
5mL
5
5
—
—
—
—
—
—
—
—
—
—
—
—
5
—
5
—
5
—
5
30
Safety labs
CBC/ Diff/ platelets
Local lab
Local lab
EDTA
5mL
5
—
—
—
5
—
5
5
5
5
5
5
—
—
5
—
—
—
5
5
—
55
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
5
—
5
—
—
—
—
5
—
—
5
—
—
—
5
5
—
35
Immunogenicity & Virologic assays 6
HLA host genetics 7
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
17
Cellular assays
ICS
BARC
HVTN Labs
ACD
8.5mL
—
42.5
—
—
—
—
42.5
—
—
—
—
42.5
—
—
85
—
42.5
—
42.5
—
42.5
340
Phenotyping (pTfh and plasmablasts)
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
17
—
—
17
—
—
17
—
—
17
—
—
17
17
—
—
—
119
Humoral assays
Binding Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
8.5
—
—
8.5
8.5
8.5
—
8.5
—
8.5
68
Neutralizing Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
8.5
—
—
8.5
—
8.5
—
8.5
—
8.5
60
Innate Immunity
Serum cytokines
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
—
8.5
8.5
8.5
8.5
—
—
—
—
—
—
—
—
—
—
43
RNA Gene Expression
BARC
HVTN Labs
Tempus
3mL
—
3
—
—
—
—
—
3
3
3
3
—
—
—
—
—
—
—
—
—
—
15
Phenotyping
BARC
HVTN Labs
ACD
8.5mL
—
8.5
—
—
—
—
—
8.5
17
17
8.5
—
—
—
—
—
—
—
—
—
—
60
Storage
PBMC
BARC
ACD
8.5mL
—
68
—
—
59.5
—
51
—
8.5
8.5
8.5
59.5
—
59.5
59.5
—
59.5
59.5
59.5
—
85
646
Serum
BARC
SST
8.5mL
—
17
—
—
—
—
17
—
—
—
—
17
—
—
17
17
17
—
17
—
17
136
Visit total
24
204
0
0
87
0
138
52
42
42
51
146
10
77
194
36
168
77
151
20
187
1702
56-Day total
24
228
228
228
314
314
452
190
232
274
324
470
10
87
280
36
168
245
396
20
187
URINE COLLECTION
Urinalysis
Local lab
Local lab
X
—
—
—
X
—
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
Pregnancy Test8
Local lab
Local lab
X
X
—
—
—
X
—
X
—
—
—
—
X
—
X11
—
X
—
X11
X
X11
Chlamydia/Gonorrhea
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
CERVICAL/VAGINAL SWAB COLLECTION
Trichomonas vaginalis
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Bacterial vaginosis
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Yeast10
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
MUCOSAL COLLECTION
Semen
BARC
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Cervical secretion
BARC
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Rectal secretion
BARC
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
STOOL COLLECTION (OPTIONAL)
Stool
BARC
HVTN Labs
—
X12
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
—
—
—
—
Screening 
visit3
 
Shaded visits not required. 
1 BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory–National Institute for Communicable Diseases (Johannesburg, South Africa) 
2 HVTN Laboratories include: Cape Town HVTN Immunology Laboratory (CHIL, Cape Town, South Africa); South African Immunology Laboratory–National Institute for Communicable Diseases (SAIL-NICD, Johannesburg, South Africa); Fred Hutchinson 
Cancer Research Center (Seattle, Washington, USA); Duke Human Vaccine Institute, Duke University Medical Center (Durham, North Carolina, USA) 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination.  
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment) and Section 9.4 (postenrollment). 
 
6 Immunogenicity assays will be performed at M0 (for binding Ab assay) and M6.5 and 12. 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 
7 Genotyping 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. 
8 Pregnancy tests may be performed on blood specimens. 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 At an early termination visit for a withdrawn or terminated participant (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 21 above.  
10 Cervical/vaginal swab collection for participants providing cervical mucosal samples–only if clinically indicated. 
11 Pregnancy testing at the indicated visit is only required of participants who are born female and are providing a cervical and/or rectal secretion sample. 
12 Optional stool specimen must be collected prior to first vaccination. 
 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 146 of 155 
Appendix H 
Laboratory procedures (Group 3) 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Day:
D0
D1
D3
D7
D28
D42
D84
D85
D87
D91
D98
D168
D175
D182
D273
D364
D371
D378
D455
D546
Weeks
W0
W1
W4
W6
W12
W13
W14
W24
W25
W26
W39
W52
W53
W54
W60
W72
Month
M0
M0.25
M1
M1.5
M3
M3.25
M3.5
M6
M6.25
M6.5
M9
M12
M12.25
M12.5
M15
M18
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. capacity)4
ALVAC+prot+MF59
ALVAC+prot+MF59
ALVAC+prot+MF59
ALVAC+prot+MF59
Total
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
2mL
4
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
4
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics9
HSML-NICD
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
10
—
—
—
—
10
—
—
10
10
—
—
10
209
70
STI Serology
Syphilis
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
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 & Virologic assays 6
HLA host genetics7
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
17
Cellular assays
ICS
BARC
HVTN Labs
ACD
8.5mL
—
85
—
—
—
—
85
—
—
—
—
—
—
—
85
—
85
—
85
—
85
510
Phenotyping (pTfh and plasmablasts)
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
17
—
—
—
—
—
—
—
—
17
—
—
17
17
—
—
—
85
Humoral assays
Binding Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
—
—
—
8.5
8.5
8.5
—
8.5
—
8.5
60
Neutralizing Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
—
—
—
8.5
—
8.5
—
8.5
—
8.5
51
Storage
PBMC
BARC
ACD
8.5mL
—
42.5
—
—
34
—
59.5
—
—
—
—
—
—
59.5
59.5
—
59.5
51
59.5
—
59.5
485
Serum
BARC
SST
8.5mL
—
17
—
—
—
—
17
—
—
—
—
—
—
—
17
17
17
—
17
—
17
119
Visit total
24
196
0
0
61
0
189
10
0
0
0
0
10
77
189
36
206
68
189
20
199
1470
56-Day total
24
220
220
220
281
281
469
199
199
199
199
199
10
87
275
36
206
274
462
20
199
URINE COLLECTION
Urinalysis
Local lab
Local lab
X
—
—
—
X
—
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
Pregnancy Test8
Local lab
Local lab
X
X
—
—
—
X
—
—
—
—
—
—
X
—
—
—
X
—
—
X
—
STOOL COLLECTION (OPTIONAL)
Stool
BARC
HVTN Labs
—
X10
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
—
—
—
—
Screening 
visit3
 
Shaded visits not required. 
1 BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory–National Institute for Communicable Diseases (Johannesburg, South Africa) 
2 HVTN Laboratories include: Cape Town HVTN Immunology Laboratory (CHIL, Cape Town, South Africa); South African Immunology Laboratory–National Institute for Communicable Diseases (SAIL-NICD, Johannesburg, South Africa); Fred Hutchinson 
Cancer Research Center (Seattle, Washington, USA); Duke Human Vaccine Institute, Duke University Medical Center (Durham, North Carolina, USA) 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination.  
4 Local 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). 
 
6 Immunogenicity assays will be performed at M0 (for binding Ab assay) and M6.5 and 12. Based on the number of responders observed at these timepoints, lab assays may be performed on participants for humoral and cellular responses at other timepoints. 
7 Genotyping 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. 
8 Pregnancy tests may be performed on blood specimens. 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 At an early termination visit for a withdrawn or terminated participant (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 21 above.  
10 Optional stool specimen must be collected prior to first vaccination. 
 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 147 of 155 
Appendix I 
Laboratory procedures (Group 3 – innate and mucosal subset) 
Visit:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Day:
D0
D1
D3
D7
D28
D42
D84
D85
D87
D91
D98
D168
D175
D182
D273
D364
D371
D378
D455
D546
Weeks
W0
W1
W4
W6
W12
W13
W14
W24
W25
W26
W39
W52
W53
W54
W60
W72
Month
M0
M0.25
M1
M1.5
M3
M3.25
M3.5
M6
M6.25
M6.5
M9
M12
M12.25
M12.5
M15
M18
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. capacity)4
ALVAC+prot+MF59
ALVAC+prot+MF59
ALVAC+prot+MF59
ALVAC+prot+MF59
Total
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
2mL
4
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
4
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 9
HSML-NICD
HSML-NICD
EDTA
10mL
—
—
—
—
—
—
—
10
—
—
—
—
10
—
—
10
10
—
—
10
209
70
STI Serology
Syphilis
Local lab
Local lab
SST
5mL
5
5
—
—
—
—
—
—
—
—
—
—
—
—
5
—
5
—
5
—
5
30
Safety labs
CBC/ Diff/ platelets
Local lab
Local lab
EDTA
5mL
5
5
5
5
5
—
5
—
—
—
—
—
—
—
5
—
—
—
5
5
—
45
Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
—
—
5
—
5
—
—
—
—
—
—
—
5
—
—
—
5
5
—
30
Immunogenicity & Virologic assays 6
HLA host genetics 7
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
17
Cellular assays
ICS
BARC
HVTN Labs
ACD
8.5mL
—
42.5
—
—
—
—
42.5
—
—
—
—
—
—
—
85
—
42.5
—
42.5
—
42.5
298
Phenotyping (pTfh and plasmablasts)
BARC
HVTN Labs
ACD
8.5mL
—
17
—
—
17
—
—
—
—
—
—
—
—
17
—
—
17
17
—
—
—
85
Humoral assays
Binding Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
—
—
—
8.5
8.5
8.5
—
8.5
—
8.5
60
Neutralizing Ab Assay
BARC
HVTN Labs
SST
8.5mL
—
8.5
—
—
—
—
8.5
—
—
—
—
—
—
—
8.5
—
8.5
—
8.5
—
8.5
51
Innate Immunity
Serum cytokines
BARC
HVTN Labs
SST
8.5mL
—
8.5
8.5
8.5
8.5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
34
RNA Gene Expression
BARC
HVTN Labs
Tempus
3mL
—
3
3
3
3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
12
Phenotyping
BARC
HVTN Labs
ACD
8.5mL
—
8.5
17
17
8.5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
51
Storage
PBMC
BARC
ACD
8.5mL
—
34
8.5
8.5
17
—
42.5
—
—
—
—
—
—
59.5
59.5
—
59.5
59.5
59.5
—
85
493
Serum
BARC
SST
8.5mL
—
8.5
—
—
—
—
17
—
—
—
—
—
—
—
17
17
17
—
17
—
17
111
Visit total
24
166
42
42
64
0
129
10
0
0
0
0
10
77
194
36
168
77
151
20
187
1395
56-Day total
24
190
232
274
338
338
467
139
139
139
139
139
10
87
280
36
168
245
396
20
187
URINE COLLECTION
Urinalysis
Local lab
Local lab
X
—
—
—
X
—
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
Pregnancy Test8
Local lab
Local lab
X
X
—
—
—
X
—
—
—
—
—
—
X
—
X11
—
X
—
X11
X
X11
Chlamydia/Gonorrhea
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
CERVICAL/VAGINAL SWAB COLLECTION
Trichomonas vaginalis
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Bacterial vaginosis
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Yeast10
Local lab
Local lab
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
MUCOSAL COLLECTION
Semen
BARC
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Cervical secretion
BARC
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
Rectal secretion
BARC
HVTN Labs
—
X
—
—
—
—
—
—
—
—
—
—
—
—
X
—
X
—
X
—
X
STOOL COLLECTION (OPTIONAL)
Stool
BARC
HVTN Labs
—
X12
—
—
—
—
—
—
—
—
—
—
—
—
X
—
—
—
—
—
—
Screening 
visit3
 
Shaded visits not required. 
1 BARC = Bio Analytical Research Corporation South Africa (Pty) Ltd (Johannesburg, South Africa); HSML-NICD = HIV Sero-Molecular Laboratory–National Institute for Communicable Diseases (Johannesburg, South Africa) 
2 HVTN Laboratories include: Cape Town HVTN Immunology Laboratory (CHIL, Cape Town, South Africa); South African Immunology Laboratory–National Institute for Communicable Diseases (SAIL-NICD, Johannesburg, South Africa); Fred Hutchinson 
Cancer Research Center (Seattle, Washington, USA); Duke Human Vaccine Institute, Duke University Medical Center (Durham, North Carolina, USA) 
3 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination.  
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment) and Section 9.4 (postenrollment). 
 
6 Immunogenicity assays will be performed at M0 (for binding Ab assay) and M6.5 and 12. Based on the number of responders observed at these timepoints, lab assays may be performed on participants for humoral and cellular responses at other timepoints. 
7 Genotyping 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. 
8 Pregnancy tests may be performed on blood specimens. 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 At an early termination visit for a withdrawn or terminated participant (see Section 9.12), blood should be drawn for HIV diagnostic testing, as shown for visit 21 above.  
10 Cervical/vaginal swab collection for participants providing cervical mucosal samples–only if clinically indicated. 
11 Pregnancy testing at the indicated visit is only required of participants who are born female and are providing a cervical and/or rectal secretion sample. 
12 Optional stool specimen must be collected prior to first vaccination. 
 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 148 of 155 
Appendix J 
Procedures at HVTN CRS (Groups 1, 2, and 4) 
Visit: 
01a 
02g 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17g 
18 
19 
20 
21 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D28 
D42 
D84 
D85 
D87 
D91 
D98 
D168 
D175 
D182 
D273 
D364 
D371 
D378 
D455 
D546 
 
Month: 
 
M0 
 
 
M0.25 
M1 
M1.5 
M3 
 
 
M3.25 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M12.25 
M12.5 
M15 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
VAC2 
 
VAC3 
 
 
 
 
VAC4 
 
 
 
VAC5 
 
 
 
 
 
Study proceduresb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Abbreviated physical exam 
— 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Risk reduction counseling 
X 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Pregnancy prevention assessmentc 
X 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Behavioral risk assessment 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm eligibility, obtain demographics, 
randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
X 
— 
Concomitant medications 
X 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/adverse experienced 
— 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
HIV infection assessmente 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm HIV test results provided to 
participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
Stool sample collection (optional)i 
— 
(X)j 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
(X) 
— 
— 
— 
— 
— 
— 
— 
Local lab assessment 
 
 
— 
— 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
Pregnancy (urine or serum HCG)f  
X 
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
X 
— 
— 
CBC, differential, platelet 
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
Chemistry panel (see Section 9.2)  
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
Syphilis, Hepatitis B, Hepatitis C 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Vaccination procedures 
 
 
 
 
 
 
 
 
— 
— 
— 
— 
 
 
 
 
 
 
 
 
 
 
Vaccination 
— 
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Reactogenicity assessmentsh 
— 
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant  
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
Shaded visits not required. 
a Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
b For specimen collection requirements, see Appendix F. 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d AEs to be collected and reported through 30 days after each vaccination, except as noted in Section 11.2.2. 
e Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
f For a participant who was born female, pregnancy test must be performed within 24 hours of vaccination with negative results received 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 tests may be used to 
confirm the results of, or substitute for, a urine pregnancy test. 
g 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 urine or serum pregnancy test, if indicated (see footnote “f”). Lab tests 
may be drawn within the 14 days prior to vaccination. 
h Reactogenicity assessments performed daily for at least 3 days postvaccination (see Section 9.10). 
i Collect dietary, antibiotic use, and gastrointestinal symptom information from participants providing stool specimen. 
j Optional stool specimen must be collected prior to first vaccination. 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 149 of 155 
Appendix K 
Procedures at HVTN CRS (Groups 1, 2, and 4 – innate and mucosal subset)  
Visit: 
01a  
02 k 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 k 
18 
19 
20 
21 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D28 
D42 
D84 
D85 
D87 
D91 
D98 
D168 
D175 
D182 
D273 
D364 
D371 
D378 
D455 
D546 
 
Month: 
 
M0 
 
 
M0.25 
M1 
M1.5 
M3 
 
 
M3.25 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M12.25 
M12.5 
M15 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
VAC2 
 
VAC3 
 
 
 
 
VAC4 
 
 
 
VAC5 
 
 
 
 
 
Study proceduresb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Abbreviated physical exam 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Risk reduction counseling 
X 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Pregnancy prevention assessmentc 
X 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Behavioral risk assessment 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm eligibility, obtain demographics, 
randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
X 
— 
Concomitant medications 
X 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/adverse experienced 
— 
X 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
HIV infection assessmente 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm HIV test results provided to 
participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
Local lab assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
Pregnancy (urine or serum HCG)f 
X 
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
X 
X 
— 
CBC, differential, platelet 
X 
— 
— 
— 
X 
— 
X 
X 
X 
X 
X 
X 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
Chemistry panel (see Section 9.2  
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
Hepatitis B, Hepatitis C 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Syphilis 
X 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Pap smearg 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Chlamydia/gonorrhea (urine)h 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Trichomonas vaginalisi 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Bacterial vaginosisi 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Yeastj 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
 
 
 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 150 of 155 
Visit: 
01a  
02k 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 k 
18 
19 
20 
21 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D28 
D42 
D84 
D85 
D87 
D91 
D98 
D168 
D175 
D182 
D273 
D364 
D371 
D378 
D455 
D546 
 
Month: 
 
M0 
 
 
M0.25 
M1 
M1.5 
M3 
 
 
M3.25 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M12.25 
M12.5 
M15 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
VAC2 
 
VAC3 
 
 
 
 
VAC4 
 
 
 
VAC5 
 
 
 
 
 
Mucosal sample collection 
(optional) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rectal secretions, cervical 
secretions, semen 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Stool sample collection 
(optional)m 
— 
(X)n 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
(X) 
— 
— 
— 
— 
— 
— 
— 
Vaccination procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
— 
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Reactogenicity assessmentsl 
— 
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant  
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
 
Shaded visits not required. 
a Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
b For specimen collection requirements, see Appendix G 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d AEs to be collected and reported through 30 days after each vaccination, except as noted in Section 11.2.2.. 
e Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
f For a participant who was born female, pregnancy test must be performed within 24 hours of vaccination with negative results received 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 tests may be used to 
confirm the results of, or substitute for, a urine pregnancy test. 
g Only for volunteers born female providing  cervical samples. Per Section 9.2, women with a most recent normal (or ASCUS) Pap result within 3 years prior to enrollment do not need to have a Pap smear. 
h Urine testing for Chlamydia and gonorrhea will be done only if the participant consents to provide mucosal samples. Specimen collection for this testing will take place at the time of mucosal sampling, prior to vaccination (if scheduled). 
i This testing will be done for participants providing cervical mucosal samples. Specimen collection for this testing will take place at the time of mucosal sampling, prior to vaccination (if scheduled). 
j This testing will be done for participants providing cervical mucosal samples only if clinically indicated. Specimen collection for this testing will take place at the time of mucosal sampling, prior to vaccination (if scheduled). 
k Blood draws and other sample collection 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 urine or serum pregnancy test, if indicated 
(see footnote “f”). Blood  draws and other samples may be collected within the 14 days prior to vaccination. 
l Reactogenicity assessments performed daily for at least 3 days postvaccination (see Section 9.10). 
m Collect dietary, antibiotic use, and gastrointestinal symptom information from participants providing stool specimen.  
n Optional stool specimen must be collected prior to first vaccination. 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 151 of 155 
Appendix L 
Procedures at HVTN CRS (Group 3) 
Visit: 
01a 
02g 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17g 
18 
19 
20 
21 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D28 
D42 
D84 
D85 
D87 
D91 
D98 
D168 
D175 
D182 
D273 
D364 
D371 
D378 
D455 
D546 
 
Month: 
 
M0 
 
 
M0.25 
M1 
M1.5 
M3 
 
 
M3.25 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M12.25 
M12.5 
M15 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
VAC2 
 
 
 
 
 
 
VAC3 
 
 
 
VAC4 
 
 
 
 
 
Study proceduresb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Abbreviated physical exam 
— 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Risk reduction counseling 
X 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Pregnancy prevention assessmentc 
X 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Behavioral risk assessment 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm eligibility, obtain 
demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Social impact assessment 
questionnaire 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
X 
— 
Concomitant medications 
X 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/adverse 
experienced 
— 
X 
— 
— 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
HIV infection assessmente 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm HIV test results provided 
to participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
— 
— 
X 
X 
— 
— 
X 
X 
Stool sample collection (optional)i 
— 
(X)j 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
(X) 
— 
— 
— 
— 
— 
— 
— 
Local lab assessment 
 
 
— 
— 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
Pregnancy (urine or serum HCG)f  
X 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
X 
— 
— 
CBC, differential, platelet 
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 
 
 
 
 
 
 
 
 
— 
— 
— 
— 
 
 
 
 
 
 
 
 
 
 
Vaccinationg 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Reactogenicity assessmentsh 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant  
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
Shaded visits not required. 
a Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
b For specimen collection requirements, see Appendix H. 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d AEs to be collected and reported through 30 days after each vaccination, except as noted in Section 11.2.2. 
e Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
f For a participant who was born female, pregnancy test must be performed within 24 hours of vaccination with negative results received 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 tests may be used to 
confirm the results of, or substitute for, a urine pregnancy test. 
g 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 (see footnote “f”). Lab tests may be 
drawn within the 14 days prior to vaccination. 
h Reactogenicity assessments performed daily for at least 3 days postvaccination (see Section 9.10). 
i Collect dietary, antibiotic use, and gastrointestinal symptom information from participants providing stool specimen. 
j Optional stool specimen must be collected prior to first vaccination. 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 152 of 155 
Appendix M 
Procedures at HVTN CRS (Group 3 – innate and mucosal subset) 
Visit: 
01a  
02k 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17k 
18 
19 
20 
21 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D28 
D42 
D84 
D85 
D87 
D91 
D98 
D168 
D175 
D182 
D273 
D364 
D371 
D378 
D455 
D546 
 
Month: 
 
M0 
 
 
M0.25 
M1 
M1.5 
M3 
 
 
M3.25 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M12.25 
M12.5 
M15 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
VAC2 
 
 
 
 
 
 
VAC3 
 
 
 
VAC4 
 
 
 
 
 
Study proceduresb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Risk reduction counseling 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Pregnancy prevention assessmentc 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Behavioral risk assessment 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm eligibility, obtain demographics, 
randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
X 
— 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/adverse experienced 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
— 
— 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
HIV infection assessmente 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
— 
X 
— 
— 
X 
X 
— 
— 
X 
X 
— 
Confirm HIV test results provided to 
participant 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
X 
— 
— 
X 
X 
— 
— 
X 
X 
Local lab assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
Pregnancy (urine or serum HCG)f 
X 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
X 
X 
— 
CBC, differential, platelet 
X 
X 
X 
X 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
Chemistry panel (see Section 9.2)  
X 
— 
— 
— 
X 
— 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
X 
— 
— 
Hepatitis B, Hepatitis C 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Syphilis 
X 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Pap smearg 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Chlamydia/gonorrhea (urine)h 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Trichomonas vaginalisi 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Bacterial vaginosisi 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Yeastj 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
 
 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 153 of 155 
Visit: 
01a  
02k 
03 
04 
05 
06 
07 
08 
09 
10 
11 
12 
13 
14 
15 
16 
17 k 
18 
19 
20 
21 
Post 
Day: 
 
D0 
D1 
D3 
D7 
D28 
D42 
D84 
D85 
D87 
D91 
D98 
D168 
D175 
D182 
D273 
D364 
D371 
D378 
D455 
D546 
 
Month: 
 
M0 
 
 
M0.25 
M1 
M1.5 
M3 
 
 
M3.25 
M3.5 
M6 
M6.25 
M6.5 
M9 
M12 
M12.25 
M12.5 
M15 
M18 
 
Procedure 
Scr. 
VAC1 
 
 
 
VAC2 
 
 
 
 
 
 
VAC3 
 
 
 
VAC4 
 
 
 
 
 
Mucosal sample collection (optional) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rectal secretions, cervical secretions, 
semen 
— 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
— 
X 
— 
X 
— 
X 
— 
Stool sample collection (optional)m 
 
(X)n 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
 
 
 
 
 
 
Vaccination procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Reactogenicity assessmentsl 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
— 
X 
— 
— 
— 
X 
— 
— 
— 
— 
— 
Poststudy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unblind participant  
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
 
Shaded visits not required. 
a Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
b For specimen collection requirements, see Appendix I. 
c Pregnancy prevention assessment is required only for participants who were born female and are capable of becoming pregnant. 
d AEs to be collected and reported through 30 days after each vaccination, except as noted in Section 11.2.2.. 
e Includes pre-test counseling. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
f For a participant who was born female, pregnancy test must be performed within 24 hours of vaccination with negative results received 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 tests may be used to 
confirm the results of, or substitute for, a urine pregnancy test. 
g Only for volunteers born female providing  cervical samples. Per Section 9.2, women with a most recent normal (or ASCUS) Pap result within 3 years prior to enrollment do not need to have a Pap smear. 
h Urine testing for Chlamydia and gonorrhea will be done only if the participant consents to provide mucosal samples. Specimen collection for this testing will take place at the time of mucosal sampling, prior to vaccination (if scheduled). 
i This testing will be done for participants providing cervical mucosal samples. Specimen collection for this testing will take place at the time of mucosal sampling, prior to vaccination (if scheduled). 
j This testing will be done for participants providing cervical mucosal samples only if clinically indicated. Specimen collection for this testing will take place at the time of mucosal sampling, prior to vaccination (if scheduled). 
k Blood draws and other sample collection 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 ruine or serum pregnancy test, if indicated 
(see footnote “f”). Blood  draws and other samples may be collected within the 14 days prior to vaccination. 
l Reactogenicity assessments performed daily for at least 3 days postvaccination (see Section 9.10). 
m Collect dietary, antibiotic use, and gastrointestinal symptom information from participants providing stool specimen.   
n Optional stool specimen must be collected prior to first vaccination. 
 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 154 of 155 
Appendix N 
Adverse events of special interest 
AEs of special interest (AESI) for this protocol include but are not limited to potential 
immune-mediated diseases; representative examples of AESI are listed below. Updates to 
AESI will be provided as an appendix to the HVTN 107 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) 
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 
 
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 

HVTN 107 Version 3.0 / May 4, 2017 
HVTN107_v3.0_FINAL.docx / Page 155 of 155 
Appendix O 
Protocol Signature Page 
 
A Phase 1/2a partially double-blinded, randomized clinical trial to characterize the safety 
and immunogenicity of clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 
alone, with MF59® adjuvant, and with alum adjuvant in healthy, HIV-uninfected adult 
participants 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in compliance with 
United States (US) Health and Human Service regulations (45 CFR 46); applicable U.S. 
Food and Drug Administration regulations; standards of the International Conference on 
Harmonization Guideline for Good Clinical Practice (E6); Institutional Review 
Board/Ethics Committee determinations; all applicable in-country, state, and local laws 
and regulations; and other applicable requirements (e.g., US National Institutes of Health, 
Division of AIDS) and institutional policies 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
DAIDS Protocol Number: HVTN 107 
DAIDS Protocol Version: Version 3.0 
Protocol Date: May 4, 2017