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

Created on 26 Sep 2026

Authors

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

Published in

Vaccines. Volume 14. Issue 9. Sep 09, 2026. Epub Sep 09, 2026.

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.

PMID:
42797615
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.

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