Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men

Peter L. Anderson, David V. Glidden, Albert Liu, Susan Buchbinder, Javier R. Lama, Juan Vicente Guanira, Vanessa McMahan, Lane R. Bushman, Martín Casapía, Orlando Montoya-Herrera, Valdilea G. Veloso, Kenneth H. Mayer, Suwat Chariyalertsak, Mauro Schechter, Linda Gail Bekker, Esper Georges Kallás, Robert M. Grant

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760 Scopus citations


Drug concentrations associated with protection from HIV-1 acquisition have not been determined. We evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial (1). In this randomized placebo-controlled trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was detected less frequently in blood plasma and in viable cryopreserved peripheral blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%; P < 0.001). An intracellular concentration of the active form of tenofovir, tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that, when analyzed according to the iPrEx model, corresponded to an HIV-1 risk reduction of 76% for two doses per week, 96% for four doses per week, and 99% for seven doses per week. Prophylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.

Original languageEnglish
Article number151ra125
JournalScience Translational Medicine
Issue number151
StatePublished - 12 Sep 2012
Externally publishedYes


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