This application proposes to continue as the Statistical and Data Management Center (SDMC) for the HIV Vaccine Trials Network (HVTN). To meet the statistical and data management goals described in RFA-AI-19- 002, and ultimately to achieve the scientific goal of the HVTN ? to develop a safe and globally effective HIV vaccine ? seven specific aims will be addressed:
Aim 1, to accomplish all specific aims using high-quality, timely, cost-efficient, and secure data management and safety monitoring by adhering to clinical data management standards and regulatory requirements and by using state-of-the-art, CDISC Standards compliant data systems that enable data exchange and provisioning;
Aim 2, to provide innovative statistical/computational biology study design and data analysis for standardized, phase 1-2a clinical trials that evaluate safety and immunogenicity of candidate HIV vaccines, including ?fast-track? iterative trials to screen vaccines for their ability to elicit broadly neutralizing antibodies, and that evaluate safety, pharmacokinetics, and immunological functions of directly administered broadly neutralizing monoclonal antibodies (mAbs);
Aim 3, to support the HVTN Laboratory Center with data management, statistical methods, and data analysis for developing immunological and virological assays and data analysis pipelines, toward vaccine immunogenicity characterization, systems vaccinology, and modeling of mAb concentrations and functions;
Aim 4, to provide robust and efficient design and analysis of phase 2b test-of-concept and phase 3 trials to assess vaccine efficacy or mAb efficacy to prevent HIV infection, including strategies for integrating other HIV prevention modalities into trial designs;
Aim 5, to employ novel quantitative methods for assessing within the phase 2b and 3 efficacy trials correlates of vaccine or mAb protection, where the correlates are based on markers measuring immune responses to vaccination or mAb concentration, human immune genetics, and genetic and immunological features of HIV viruses;
Aim 6, to adapt the functions of Aims 1?5 to vaccine or mAb clinical trials of HIV-exposed and HIV-unexposed infants;
and Aim 7, to adapt applicable functions of Aims 1?6 for tuberculosis vaccine clinical trials. Novel quantitative methodologies will be developed in support of the specific aims, to increase the efficiency, rigor, and scientific impact of the HVTN program. The research will be accomplished in harmonization with the HVTN Leadership and Operations Core and the HVTN Laboratory Center, and in collaboration with other HIV/AIDS research networks.
Aim 5 encapsulates the HVTN?s research approach to achieving a globally effective HIV vaccine, in that: (1) Iterative evaluation of refined versions of partially effective vaccine and mAb regimens will be required; (2) Correlates of vaccine protection are the key scientific tool for driving this iterative evaluation; (3) All Aim 1?4 research activities are ultimately directed toward achieving high-quality correlates of vaccine protection; and (4) Following licensure of an HIV vaccine, correlates of vaccine protection provide the basis for bridging efficacy to new populations, hence facilitating widespread vaccination that will be essential for ending the HIV pandemic.

Public Health Relevance

Despite recent advances in biomedical interventions that reduce the risk of HIV acquisition, worldwide an estimated 1.7 million people acquired HIV in 2018. Eliminating the pandemic will require a safe and effective HIV vaccine. Only through human clinical trials held to the highest scientific, ethical and regulatory standards will the goal of an HIV vaccine be realized.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
2UM1AI068635-15
Application #
9986473
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Renzullo, Philip O
Project Start
2006-06-29
Project End
2027-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
15
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Fong, Youyi; Huang, Ying; Lemos, Maria P et al. (2018) Rank-based two-sample tests for paired data with missing values. Biostatistics 19:281-294
Reeves, Daniel B; Duke, Elizabeth R; Wagner, Thor A et al. (2018) A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation. Nat Commun 9:4811
Thiam-Diouf, Arame; Metch, Barbara; Sharpe, Cameron et al. (2018) Substance use patterns of HVTN phase I clinical trial participants: Enrollment, risk reduction counseling and retention. Vaccine 36:1235-1242
Benkeser, David; Carone, Marco; Gilbert, Peter B (2018) Improved estimation of the cumulative incidence of rare outcomes. Stat Med 37:280-293
Lee, Unkyung; Sun, Yanqing; Scheike, Thomas H et al. (2018) Analysis of Generalized Semiparametric Regression Models for Cumulative Incidence Functions with Missing Covariates. Comput Stat Data Anal 122:59-79
Janes, Holly; Corey, Lawrence; Ramjee, Gita et al. (2018) Weighing the Evidence of Efficacy of Oral PrEP for HIV Prevention in Women in Southern Africa. AIDS Res Hum Retroviruses 34:645-656
Dietrich, Janan J; Lazarus, Erica; Andrasik, Michele et al. (2018) Mobile Phone Questionnaires for Sexual Risk Data Collection Among Young Women in Soweto, South Africa. AIDS Behav 22:2312-2321
Huang, Yunda; Karuna, Shelly; Carpp, Lindsay N et al. (2018) Modeling cumulative overall prevention efficacy for the VRC01 phase 2b efficacy trials. Hum Vaccin Immunother 14:2116-2127
Bekker, Linda-Gail; Moodie, Zoe; Grunenberg, Nicole et al. (2018) Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial. Lancet HIV 5:e366-e378

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