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Publications

Journal Article Review Epublish

PubMed: 42797615 DOI: 10.3390/vaccines14090794

A Population-Based HIV Vaccine Efficacy Trial Design: Statistical Framework and Design Considerations.

Vaccines (Basel) 14(9)

Authors: Holly Janes, Fei Gao, Susan Buchbinder, Charles S Wiysonge, Kimberly Louis, Blossom Napoleon, Amelia Mfiki, Derrick Mapp, Glenda Gray

Affiliations

  • Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N M2-C200, Seattle, WA 98109, USA.
  • Bridge HIV, San Francisco Department of Public Health, University of California, San Francisco, 25 Van Ness Avenue, Suite 100, San Francisco, CA 94114, USA.
  • Cochrane South Africa, South African Medical Research Council, Francie van Zijl Drive, Parow Valley, Cape Town 7500, South Africa.
  • Vaccine Trials Unit, Fred Hutchinson Cancer Center, 901 Boren Ave, #1320, Seattle, WA 98104, USA.
  • Aurum Klerksdorp Clinical Research Site, Jade Square, OR Tambo Street, Klerksdorp 2570, South Africa.
  • Groote Schuur Clinical Research Site, South African National Aids Council (SANAC)-Civil Society, J52 Old Main Building Groote Schuur Hospital, Cape Town 8001, South Africa.
  • Shanti Project, 27 Maiden Lane, Suite 400, San Francisco, CA 94108, USA.
  • Infectious Disease and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, South African Medical Research Council, Tygerberg, P.O. Box 19070, Cape Town 7505, South Africa.

Abstract

An HIV vaccine will be a critical tool for ending the epidemic, yet the next vaccine efficacy trial is likely five or more years away as the field focuses on the early-phase evaluation and optimization of vaccines that induce broadly neutralizing antibodies. At the same time, the HIV prevention landscape has evolved substantially, with the discovery of highly effective means of preventing HIV, challenging the identification of HIV prevention trial designs that are ethically sound and scientifically robust. We explore a population-based, individually randomized, proof-of-concept trial design for evaluating the efficacy of a future candidate vaccine to prevent HIV acquisition and to validate the neutralizing antibody marker as an immune correlate. The design is intended to lay the foundation for a subsequent licensure trial and the development and refinement of future HIV vaccine regimens. Key design features include broad, population-based eligibility criteria; the incorporation of external data; decentralized approaches to recruitment, specimen, and data collection; and strong community partnerships. We compare the approach with alternative trial designs and outline their limitations. The population-based design represents a compelling option for generating credible and generalizable evidence, while enabling future HIV vaccine licensure and development.

MeSH

Vaccines, Antibodies, Neutralizing, Vaccine Efficacy