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A Bayesian averted infection framework for PrEP trials with low numbers of HIV infections: application to the results of the DISCOVER trial.

ABSTRACT: Trials of candidate agents for HIV pre-exposure prophylaxis (PrEP) might randomly assign participants to be given a new PrEP agent or oral coformulated tenofovir disoproxil fumarate plus emtricitabine. This design presents unique challenges in interpretation. First, with two active arms, HIV incidence might be low. Second, the effectiveness of tenofovir disoproxil fumarate plus emtricitabine varies across populations; thus, similar HIV incidence between groups could be consistent with a wide range of effectiveness for the new PrEP. We propose a two-part approach to trial results. First, we use Bayesian methods to incorporate assumptions about the background incidence of HIV in the trial in the absence of PrEP, possibly augmented by external data. On the basis of the estimated background incidence, we estimate and compare the number of averted (or prevented) HIV infections in each of the two trial groups, calculating the averted infections ratio. We apply these methods to a completed trial of tenofovir alafenamide plus emtricitabine for PrEP. Our framework shows that leveraging external information to estimate averted infections and the averted infections ratio enhances the efficiency and interpretation of active-controlled PrEP trials.

SUBMITTER: Glidden DV

PROVIDER: S-EPMC7664988 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Implications of HIV PrEP trials results.

Project description:Abstract Six randomized clinical trials have been implemented to examine the efficacy of tenofovir disoproxil fumarate (TDF) and/or TDF/emtricitabine (TDF/FTC) as preexposure prophylaxis for HIV-1 infection (PrEP). Although largely complementary, the six trials have many similar features. As the earliest results become available, an urgent question may arise regarding whether changes should be made in the conduct of the other trials. To consider this in advance, a Consultation on the Implications of HIV Pre-Exposure Prophylaxis (PrEP) Trials Results sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation (BMGF) was held on January 29, 2010, at the Natcher Conference Center, NIH, Bethesda, MD. Participants included basic scientists, clinical researchers (including investigators performing the current PrEP trials), and representatives from the U.S. Food and Drug Administration (FDA) and the agencies sponsoring the trials: the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Agency for International Development (USAID), the BMGF, and the U.S. NIH. We report here a summary of the presentations and highlights of salient discussion topics from this workshop.

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Confidence limits for the averted infections ratio estimated via the counterfactual placebo incidence rate.

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| S-EPMC10724312 | biostudies-literature

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