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

• Research Article

HIV

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

1. Peter L. Anderson¹,
2. David V. Glidden²,
3. Albert Liu³,
4. Susan Buchbinder²,³,
5. Javier R. Lama⁴,⁵,
6. Juan Vicente Guanira⁵,
7. Vanessa McMahan⁶,
8. Lane R. Bushman¹,
9. Martín Casapía⁷,
10. Orlando Montoya-Herrera⁸,
11. Valdilea G. Veloso⁹,
12. Kenneth H. Mayer¹⁰,¹¹,
13. Suwat Chariyalertsak¹²,
14. Mauro Schechter¹³,
15. Linda-Gail Bekker¹⁴,
16. Esper Georges Kallás¹⁵,¹⁶,
17. Robert M. Grant²,⁶,* and
18. For the iPrEx Study Team

+ Author Affiliations

1. ¹University of Colorado Denver, Aurora, CO 80045, USA.
2. ²University of California, San Francisco, San Francisco, CA 94143, USA.
3. ³HIV Research Section, San Francisco Department of Public Health, San Francisco, CA 94102, USA.
4. ⁴Investigaciones Medicas en Salud, Lima 14, Peru.
5. ⁵Asociación Civil Impacta Salud y Educación, Lima, Peru.
6. ⁶Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
7. ⁷Asociación Civil Selva Amazónica, Iquitos, Maynas, Peru.
8. ⁸Fundación Ecuatoriana Equidad, Guayaquil-Guayas, Ecuador.
9. ⁹Instituto de Pesquisa Clinica Evandro Chagas, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro CEP 21040-900, Brazil.
10. ¹⁰Brown University, Providence, RI 02912, USA.
11. ¹¹Fenway Institute, Fenway Health, Boston, MA 02215, USA.
12. ¹²Research Institute for Health Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
13. ¹³Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro CEP 20.210-030, Brazil.
14. ¹⁴Desmond Tutu HIV Centre and Department of Medicine, University of Cape Town, Cape Town 7925, South Africa.
15. ¹⁵Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, SP 05403-000, Brazil.
16. ¹⁶Instituto de Investigação em Imunologia, Cerqueira Cesar, São Paulo, SP CEP 05403-900, Brazil.

1. ↵*To whom correspondence should be addressed. E-mail: robert.grant@ucsf.edu

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.

• Copyright © 2012, American Association for the Advancement of Science

Citation: P. L. Anderson, D. V. Glidden, A. Liu, S. Buchbinder, J. R. Lama, J. V. Guanira, V. McMahan, L. R. Bushman, M. Casapía, O. Montoya-Herrera, V. G. Veloso, K. H. Mayer, S. Chariyalertsak, M. Schechter, L.-G. Bekker, E. G. Kallás, R. M. Grant, F. t. Team, Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men. Sci. Transl. Med. 4, 151ra125 (2012).

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