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

被引：820

作者：

Anderson, Peter L. ^{[2
]}

Glidden, David V. ^{[1
]}

Liu, Albert ^{[3
]}

Buchbinder, Susan ^{[1
,3
]}

Lama, Javier R. ^{[4
,5
]}

Vicente Guanira, Juan ^{[5
]}

McMahan, Vanessa ^{[6
]}

Bushman, Lane R. ^{[2
]}

Casapia, Martin ^{[7
]}

Montoya-Herrera, Orlando ^{[8
]}

Veloso, Valdilea G. ^{[9
]}

Mayer, Kenneth H. ^{[10
,11
]}

Chariyalertsak, Suwat ^{[12
]}

Schechter, Mauro ^{[13
]}

Bekker, Linda-Gail ^{[14
,15
]}

Kallas, Esper Georges ^{[16
,17
]}

Grant, Robert M. ^{[1
,6
]}

机构：

[1] Univ Calif San Francisco, San Francisco, CA 94143 USA

[2] Univ Colorado Denver, Aurora, CO 80045 USA

[3] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA 94102 USA

[4] Invest Med Salud, Lima 14, Peru

[5] Asociac Civil Impacta Salud & Educ, Lima, Peru

[6] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA

[7] Asociac Civil Selva Amazon, Iquitos, Maynas, Peru

[8] Fdn Ecuatoriana Equidad, Guayaquil, Ecuador

[9] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas, BR-21040900 Rio De Janeiro, Brazil

[10] Brown Univ, Providence, RI 02912 USA

[11] Fenway Inst, Boston, MA 02215 USA

[12] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50200, Thailand

[13] Univ Fed Rio de Janeiro, Projeto Praca Onze, Hosp Escola Sao Francisco de Assis, BR-20210030 Rio De Janeiro, Brazil

[14] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa

[15] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa

[16] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, BR-05403000 Sao Paulo, Brazil

[17] Inst Invest Imunol, BR-05403900 Sao Paulo, Brazil

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2012年 / 4卷 / 151期

关键词：

HIV PREVENTION; PLASMA;

D O I：

10.1126/scitranslmed.3004006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：8