Differences in Cumulative Exposure and Adherence to Tenofovir in the VOICE, iPrEx OLE, and PrEP Demo Studies as Determined via Hair Concentrations
Differences in Cumulative Exposure and Adherence to Tenofovir in the VOICE, iPrEx OLE, and PrEP Demo Studies as Determined via Hair Concentrations
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DOI：
10.1089/aid.2016.0202
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发表时间：
2017-08-01
影响因子：
1.5
通讯作者：
Gandhi, Monica
中科院分区：
文献类型：
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作者：
Koss, Catherine A.;Bacchetti, Peter;Gandhi, Monica
在几项试验中，口服富马酸替诺福韦酯（TDF）/恩曲他滨（FTC）的暴露前预防（PrEP）可预防男性和女性感染艾滋病毒，并被广泛推荐。然而，在VOICE和FEM-PrEP试验中，基于TDF/FTC的PrEP并不能预防东部和南部非洲妇女感染艾滋病毒。在血浆中检测到替诺福韦，反映了最近几天的暴露和依从性，不到三分之一的参与者。头发中的药物浓度代表了数周至数月的累积暴露和依从性，以前从未在接受PrEP的女性中进行过检查。我们将VOICE试验中分配口服TDF/FTC的女性中的替诺福韦头发浓度与参加2项开放标签PrEP研究的男性和变性女性中的替诺福韦头发浓度进行了比较，这些研究包括iPrEx开放标签扩展（OLE）研究和美国PrEP示范项目（PrEP Demo）。替诺福韦头发浓度在VOICE中55%的人访问中可检测到，在iPrEx OLE中75%的人访问（p = .006），在PrEP Demo中98%的人访问（p < .001）。中位替诺福韦头发浓度分别对应于三项研究中每周服用的估计0.2、2.9和6.0 TDF/FTC剂量。在VOICE中，结合血浆和头发中的替诺福韦浓度数据表明不一致，低水平的产品使用。纳入短期和长期依从性措施可能有助于在全球PrEP推出期间更好地了解女性吸毒模式。
Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) prevented HIV acquisition among men and women in several trials and is broadly recommended. In the VOICE and FEM-PrEP trials, however, TDF/FTC-based PrEP did not prevent HIV acquisition among women in eastern and southern Africa. Tenofovir was detected in plasma, reflecting exposure and adherence in recent days, in fewer than one-third of participants. Drug concentrations in hair, which represent cumulative exposure and adherence over weeks to months, have never previously been examined among women on PrEP. We compared tenofovir hair concentrations among women assigned to oral TDF/FTC in the VOICE trial to those among men and transgender women enrolled in 2 open-label PrEP studies, the iPrEx open-label extension (OLE) study and the U.S. PrEP Demonstration Project (PrEP Demo). Tenofovir hair concentrations were detectable in 55% of person-visits in VOICE, 75% of personvisits in iPrEx OLE (p = .006), and 98% of person-visits in PrEP Demo (p < .001). Median tenofovir hair concentrations corresponded to an estimated 0.2, 2.9, and 6.0 TDF/FTC doses taken per week in the three studies, respectively. In VOICE, combining tenofovir concentration data from plasma and hair suggested inconsistent, low-level product use. Incorporation of both short-and long-term adherence measures may allow for an improved understanding of patterns of drug-taking among women during global PrEP roll-out.