Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis.
Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis.
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DOI：
10.1097/qad.0000000000001922
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发表时间：
2018-08-24
期刊：
影响因子：
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通讯作者：
Partners Demonstration Study Team
中科院分区：
文献类型：
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作者：
Pyra M;Anderson PL;Hendrix CW;Heffron R;Mugwanya K;Haberer JE;Thomas KK;Celum C;Donnell D;Marzinke MA;Bukusi EA;Mugo NR;Asiimwe S;Katabira E;Baeten JM;Partners Demonstration Study Team
怀孕是艾滋病毒感染风险增加的时期，怀孕降低了用于治疗的抗逆转录病毒药物的浓度。我们使用口服暴露前预防(PrEP)评估了怀孕是否降低了未感染HIV的妇女中替诺福韦(TFV)和替诺福韦-二磷酸(TFV-DP)的浓度。我们分析了一项开放标签PrEP研究的数据，比较了37名孕妇和97名非孕妇血浆中TFV-DP和干血斑中TFV-DP的浓度。从日常电子监测中控制遵守情况的分析。孕妇TFV平均血药浓度为34.7 ng/m L，较上月平均记录剂量22.2次，而非孕妇平均血药浓度为86.5 ng/m L，平均23.1次。控制依从性后，孕妇的TFV浓度降低了58%，−为50.4 ng/mL(95%可信区间−为68.3，−为32.5)，差异有统计学意义。孕妇TFV-DP平均浓度为450.3 fmol/Pack，非孕妇为636.7 fmol/Pack。在调整依从性后，这种差异没有统计学意义；然而，在那些可量化的TFV-DP患者中，怀孕期间的浓度降低了27%(−202fmol/Pick[95%CI−384至−19])。在怀孕前和怀孕期间采集样本的参与者中，在妊娠期有显著下降，控制依从性：−28.1 ng/mLTFV(95%CI−52.3to−4.0)和−289.2 fmol/Pick TFV-DP(95%CI−439.0至−139.3)。与对艾滋病毒感染妇女进行抗逆转录病毒治疗的研究一致，我们发现TFV和TFV-DP浓度在怀孕期间较低。目前还没有确定的TFV浓度阈值来实现艾滋病毒预防。还需要进行更多的药代动力学研究和PrEP在妊娠期间的疗效研究。
Pregnancy is a time of increased HIV acquisition risk and pregnancy reduces concentrations of antiretrovirals used for treatment. We assessed whether pregnancy lowers concentrations of tenofovir (TFV) and tenofovir-diphosphate (TFV-DP) among HIV-uninfected women using oral pre-exposure prophylaxis (PrEP). We analyzed data from an open-label PrEP study, comparing concentrations of TFV in plasma and TFV-DP in dried blood spots (DBS) among 37 pregnant women and 97 non-pregnant women. Analyses controlled for adherence from daily electronic monitoring. The average plasma concentration of TFV among pregnant women was 34.7 ng/mL with 22.2 average recorded doses over the prior month versus 86.5 ng/mL with 23.1 doses among non-pregnant women. After controlling for adherence, TFV concentrations were 58% lower among pregnant women, a statistically significant difference of −50.4 ng/mL (95%CI −68.3 to −32.5). The average TFV-DP concentration was 450.3 fmol/punch among pregnant women and 636.7 fmol/punch among non-pregnant women. This difference was not statistically significant after adjusting for adherence; however, among those with quantifiable TFV-DP, concentrations were 27% lower during pregnancy (−202 fmol/punch [95%CI −384 to −19]). Among participants with samples before and during pregnancy, there were significant decreases during pregnancy, controlling for adherence: −28.1 ng/mL TFV (95%CI −52.3 to −4.0) and −289.2 fmol/punch TFV-DP (95%CI −439.0 to −139.3). Consistent with studies among HIV-infected women on ART, we found TFV and TFV-DP concentrations were lower during pregnancy. There is no established TFV concentration threshold to achieve HIV prevention. Additional pharmacokinetic studies and studies of PrEP efficacy in pregnancy are needed.