HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention.
HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention.
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DOI：
10.1097/qai.0000000000000172
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Celum C
中科院分区：
文献类型：
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作者：
Donnell D;Baeten JM;Bumpus NN;Brantley J;Bangsberg DR;Haberer JE;Mujugira A;Mugo N;Ndase P;Hendrix C;Celum C
补充数字内容在文本中可用。抗逆转录病毒暴露前预防（PrEP）是一种新的艾滋病毒预防策略，其依从性是已知的疗效决定因素。PrEP药物的血液浓度是依从性的一个客观标志。在安慰剂对照的PrEP疗效试验中，富马酸替诺福韦酯（TDF）和TDF与恩曲他滨（FTC/TDF）在4747名有HIV感染伴侣的非洲女性和男性中进行，我们测量了活跃PrEP组参与者的血浆替诺福韦浓度：29名HIV血清转化者（病例）和196名随机选择的未感染对照。在对照组中，71%的就诊者的替诺福韦浓度>40 ng/mL，与稳态每日剂量一致，而在就诊时首次检测到HIV的病例为21%。药丸计数数据表明，96%的对照组和66%的病例在这些相同的访视中具有>80%的依从性。基于浓度>40 ng/mL，PrEP对HIV的估计保护作用对于接受TDF的个体为88%（95%置信区间：60至96，P < 0.001），对于接受FTC/TDF的个体为91%（95%置信区间：47至98，P = 0.008）。在随访期间，对照组的PrEP浓度模式一致;在第1个月浓度>40 ng/mL的81%中，75%在第12个月保持该浓度。29名血清转换者中只有5名似乎始终坚持PrEP。替诺福韦浓度>40 ng/mL与年龄较大和研究时间较短相关;浓度≤40 ng/mL更常见于参与者报告与HIV感染伴侣没有性行为时。与每日剂量一致的替诺福韦血浆浓度高度预测了对HIV获得的保护。大多数服用PrEP的人似乎都有很高的坚持性。
Supplemental Digital Content is Available in the Text. Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P < 0.001) for individuals receiving TDF and 91% (95% confidence interval: 47 to 98, P = 0.008) for individuals receiving FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; among the 81% with concentrations >40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations ≤40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.