title: Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.
abstract: 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.
authors.affiliation: University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.forename: Albert
authors.initials: A
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: Javier R
authors.initials: JR
authors.lastname: Lama
authors.forename: Juan Vicente
authors.initials: JV
authors.lastname: Guanira
authors.forename: Vanessa
authors.initials: V
authors.lastname: McMahan
authors.forename: Lane R
authors.initials: LR
authors.lastname: Bushman
authors.forename: Martín
authors.initials: M
authors.lastname: Casapía
authors.forename: Orlando
authors.initials: O
authors.lastname: Montoya-Herrera
authors.forename: Valdilea G
authors.initials: VG
authors.lastname: Veloso
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.forename: Suwat
authors.initials: S
authors.lastname: Chariyalertsak
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Esper Georges
authors.initials: EG
authors.lastname: Kallás
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068679:Emtricitabine; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine