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Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men

Anderson, Peter L.; Glidden, David V.; Liu, Albert; Buchbinder, Susan; Lama, Javier R.; Vicente Guanira, Juan; Mcmahan, Vanessa; Bushman, Lane R.; Casapia, Martin; Montoya-Herrera, Orlando; Veloso, Valdilea G.; Mayer, Kenneth H.; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallas, Esper Georges; Grant, Robert M. Universidade De São Paulo

SCIENCE TRANSLATIONAL MEDICINE, WASHINGTON, v. 4, n. 151, supl. 1, Part 2, pp. 912-916, SEP 12, 2012

AMER ASSOC ADVANCEMENT SCIENCE; WASHINGTON 2012

Acesso online

  • Título:
    Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men
  • Autor: Anderson, Peter L.; Glidden, David V.; Liu, Albert; Buchbinder, Susan; Lama, Javier R.; Vicente Guanira, Juan; Mcmahan, Vanessa; Bushman, Lane R.; Casapia, Martin; Montoya-Herrera, Orlando; Veloso, Valdilea G.; Mayer, Kenneth H.; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallas, Esper Georges; Grant, Robert M.
  • Universidade De São Paulo
  • Assuntos: Infection; Plasma; Cell Biology; Medicine; Research & Experimental
  • É parte de: SCIENCE TRANSLATIONAL MEDICINE, WASHINGTON, v. 4, n. 151, supl. 1, Part 2, pp. 912-916, SEP 12, 2012
  • Descrição: 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. Pro-phylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.
    NIH
    NIH [R21MH085598, UO1 AI084735, RO1 AI062333, UO1 AI064002, UL1 RR024131]
  • DOI: 10.1126/scitranslmed.3004006
  • Títulos relacionados: SCIENCE TRANSLATIONAL MEDICINE
  • Editor: AMER ASSOC ADVANCEMENT SCIENCE; WASHINGTON
  • Data de publicação: 2012
  • Idioma: Inglês

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