- Research Article
Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men
- Peter L. Anderson1,
- David V. Glidden2,
- Albert Liu3,
- Susan Buchbinder2,3,
- Javier R. Lama4,5,
- Juan Vicente Guanira5,
- Vanessa McMahan6,
- Lane R. Bushman1,
- Martín Casapía7,
- Orlando Montoya-Herrera8,
- Valdilea G. Veloso9,
- Kenneth H. Mayer10,11,
- Suwat Chariyalertsak12,
- Mauro Schechter13,
- Linda-Gail Bekker14,
- Esper Georges Kallás15,16,
- Robert M. Grant2,6,* and
- For the iPrEx Study Team
+ Author Affiliations
- 1University of Colorado Denver, Aurora, CO 80045, USA.
- 2University of California, San Francisco, San Francisco, CA 94143, USA.
- 3HIV Research Section, San Francisco Department of Public Health, San Francisco, CA 94102, USA.
- 4Investigaciones Medicas en Salud, Lima 14, Peru.
- 5Asociación Civil Impacta Salud y Educación, Lima, Peru.
- 6Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
- 7Asociación Civil Selva Amazónica, Iquitos, Maynas, Peru.
- 8Fundación Ecuatoriana Equidad, Guayaquil-Guayas, Ecuador.
- 9Instituto de Pesquisa Clinica Evandro Chagas, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro CEP 21040-900, Brazil.
- 10Brown University, Providence, RI 02912, USA.
- 11Fenway Institute, Fenway Health, Boston, MA 02215, USA.
- 12Research Institute for Health Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
- 13Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro CEP 20.210-030, Brazil.
- 14Desmond Tutu HIV Centre and Department of Medicine, University of Cape Town, Cape Town 7925, South Africa.
- 15Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, SP 05403-000, Brazil.
- 16Instituto de Investigação em Imunologia, Cerqueira Cesar, São Paulo, SP CEP 05403-900, Brazil.
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.
- Copyright © 2012, American Association for the Advancement of Science