Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.
Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.
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DOI：
10.1126/scitranslmed.3004006
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发表时间：
2012-09-12
影响因子：
17.1
通讯作者：
iPrEx Study Team
中科院分区：
文献类型：
--
作者：
Anderson PL;Glidden DV;Liu A;Buchbinder S;Lama JR;Guanira JV;McMahan V;Bushman LR;Casapía M;Montoya-Herrera O;Veloso VG;Mayer KH;Chariyalertsak S;Schechter M;Bekker LG;Kallás EG;Grant RM;iPrEx Study Team
尚未确定与预防HIV-1感染相关的药物浓度。本研究在iPrEx试验的一项子研究中评估了男男性行为者的药物浓度，iPrEx试验是一项每日口服恩曲他滨/富马酸替诺福韦酯暴露前预防（PrEP）的随机安慰剂对照试验。HIV感染者在首次发现HIV时的血浆和冻存的外周血单个核细胞（vPBMC）中任何可检测到的药物的频率低于对照组在研究的匹配时间点（8% vs 44%，P<0.001）和该访视前90天（11% vs 51%，P<0.001）。与安慰剂组相比，细胞内替诺福韦二磷酸盐（TFV-DP）浓度为16 fmol/百万vPBMC时，HIV感染率降低90%。在另一项研究STRAND中直接观察到的剂量产生了TFV-DP浓度，当使用该iPrEx模型进行分析时，每周2次剂量对应的HIV-1风险降低76%，每周4次剂量对应的HIV-1风险降低96%，每周7剂，99%。在一系列剂量和药物浓度下观察到预防益处，这表明了优化该人群PrEP方案的方法。
Drug concentrations associated with protection from HIV-1 acquisition have not been determined. This study evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial, a randomized placebo controlled trial of daily oral emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis (PrEP). Any detectable drug in blood plasma and viably cryopreserved peripheral blood mononuclear cells (vPBMCs) was less frequent in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% vs 44%, P<0.001) and in the 90 days prior to that visit (11% vs 51%, P<0.001). An intracellular tenofovir-diphosphate (TFV-DP) concentration of 16 fmol per million vPBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, STRAND, yielded TFV-DP concentrations that, when analyzed with this iPrEx model, corresponded with HIV-1 risk reduction of 76% for 2 doses per week, 96% for 4 doses per week, 99% for 7 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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影响因子：
2
作者：
Glidden, DV;Vittinghoff, E
通讯作者：
Vittinghoff, E
影响因子：
3.7
作者：
Keller MJ;Madan RP;Torres NM;Fazzari MJ;Cho S;Kalyoussef S;Shust G;Mesquita PM;Louissaint N;Chen J;Cohen HW;Diament EC;Lee AC;Soto-Torres L;Hendrix CW;Herold BC
通讯作者：
Herold BC
影响因子：
4.9
作者：
Baheti, Gautam;Kiser, Jennifer J.;Fletcher, Courtney V.
通讯作者：
Fletcher, Courtney V.
影响因子：
168.9
作者：
Kashuba, Angela D. M.;Patterson, Kristine B.;Dumond, Julie B.;Cohen, Myron S.
通讯作者：
Cohen, Myron S.
影响因子：
4.9
作者：
Kiser, Jennifer J.;Fletcher, Courtney V.;Havens, Peter L.
通讯作者：
Havens, Peter L.