Implications of HIV PrEP trials results

Abstract

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.

FIG. 1.

Morphology of (a) columnar epithelium and (b) squamous epithelium. (Reprinted with permission of Dr. Robin Shattock, Saint George's Hospital Medical School, London, England.)

FIG. 2.

Frequency of transmitted number of variants depending on route of transmission. HSX, heterosexual; MSM, men having sex with men; IDU, injection drug users. (Reprinted with permission of Keele et al.¹⁰)

FIG. 3.

Penetration of antiretroviral drugs in mucosal fluids and tissues. (Reprinted with permission of Dr. Angela Kashuba, University of North Carolina at Chapel Hill. Adapted from Taylor et al.)

FIG. 4.

Linkage of PK with protective outcome. Determining relationships among drug compartments may allow sampling in more accessible compartments (blood) to allow estimation of drug exposure in more distant compartments (tissue intracellular CD4 cells), which are expected to more closely correlate with seroconversion. (Reprinted with permission of Dr. Craig Hendrix, Johns Hopkins University.)