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EMTRICITABINE-TENOFOVIR EXPOSURE AND PRE-EXPOSURE PROPHYLAXIS EFFICACY IN MEN WHO HAVE SEX WITH MEN
Author
Anderson, Peter L.
Glidden, David V.
Liu, Albert
Buchbinder, Susan
Lama, Javier R.
Guanira, Juan Vicente
McMahan, Vanessa
Bushman, Lane R.
Casapía, Martín
Montoya-Herrera, Orlando
Veloso, Valdiléa G.
Mayer, Kenneth H.
Chariyalertsak, Suwat
Schechter, Mauro
Bekker, Linda-Gail
Kallás, Esper Georges
Grant, Robert M.
Glidden, David V.
Liu, Albert
Buchbinder, Susan
Lama, Javier R.
Guanira, Juan Vicente
McMahan, Vanessa
Bushman, Lane R.
Casapía, Martín
Montoya-Herrera, Orlando
Veloso, Valdiléa G.
Mayer, Kenneth H.
Chariyalertsak, Suwat
Schechter, Mauro
Bekker, Linda-Gail
Kallás, Esper Georges
Grant, Robert M.
Affilliation
University of Colorado. Denver, Aurora, USA.
University of California. San Francisco, CA, USA.
San Francisco Department of Public Health. HIV Research Section. San Francisco, CA, USA.
University of California. San Francisco, CA, USA / San Francisco Department of Public Health. HIV Research Section. San Francisco, CA, USA.
Investigaciones Medicas en Salud. Lima, Peru / Asociación Civil Impacta Salud y Educación. Lima, Peru.
Asociación Civil Impacta Salud y Educación. Lima, Peru.
Gladstone Institute of Virology and Immunology. San Francisco, CA, USA.
University of Colorado. Denver, Aurora, USA.
Asociación Civil Selva Amazónica. Iquitos, Maynas, Peru.
Fundación Ecuatoriana Equidad. Guayaquil, Guayas, Ecuador.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.
Brown University. Providence, RI, USA / Fenway Health. Fenway Institute. Boston, MA, USA.
Chiang Mai University. Research Institute for Health Sciences. Chiang Mai, Thailand.
Universidade Federal do Rio de Janeiro. Hospital Escola São Francisco de Assis. Projeto Praça Onze. Rio de Janeiro, RJ, Brasil.
University of Cape Town. Desmond Tutu HIV Centre and Department of Medicine. Cape Town, South Africa.
Universidade de São Paulo. Faculdade de Medicina. Divisão de Imunologia Clínica e Alergia. São Paulo, SP, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brasil.
University of California. San Francisco, CA, USA / Gladstone Institute of Virology and Immunology. San Francisco, CA, USA.
University of California. San Francisco, CA, USA.
San Francisco Department of Public Health. HIV Research Section. San Francisco, CA, USA.
University of California. San Francisco, CA, USA / San Francisco Department of Public Health. HIV Research Section. San Francisco, CA, USA.
Investigaciones Medicas en Salud. Lima, Peru / Asociación Civil Impacta Salud y Educación. Lima, Peru.
Asociación Civil Impacta Salud y Educación. Lima, Peru.
Gladstone Institute of Virology and Immunology. San Francisco, CA, USA.
University of Colorado. Denver, Aurora, USA.
Asociación Civil Selva Amazónica. Iquitos, Maynas, Peru.
Fundación Ecuatoriana Equidad. Guayaquil, Guayas, Ecuador.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.
Brown University. Providence, RI, USA / Fenway Health. Fenway Institute. Boston, MA, USA.
Chiang Mai University. Research Institute for Health Sciences. Chiang Mai, Thailand.
Universidade Federal do Rio de Janeiro. Hospital Escola São Francisco de Assis. Projeto Praça Onze. Rio de Janeiro, RJ, Brasil.
University of Cape Town. Desmond Tutu HIV Centre and Department of Medicine. Cape Town, South Africa.
Universidade de São Paulo. Faculdade de Medicina. Divisão de Imunologia Clínica e Alergia. São Paulo, SP, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brasil.
University of California. San Francisco, CA, USA / Gladstone Institute of Virology and Immunology. San Francisco, CA, USA.
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.
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