Effect of Pregnancy and Concomitant Antiretrovirals on the Pharmacokinetics of Tenofovir in Women With HIV Receiving Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Versus Women With HBV Receiving Tenofovir Disoproxil Fumarate Monotherapy.
Effect of Pregnancy and Concomitant Antiretrovirals on the Pharmacokinetics of Tenofovir in Women With HIV Receiving Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Versus Women With HBV Receiving Tenofovir Disoproxil Fumarate Monotherapy.
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DOI：
10.1002/jcph.1746
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发表时间：
2021-03
影响因子：
2.9
通讯作者：
PANNA Network and iTAP Study Group
中科院分区：
文献类型：
--
作者：
Bukkems VE;Smolders EJ;Jourdain G;Burger DM;Colbers AP;Cressey TR;PANNA Network and iTAP Study Group
推荐替诺福韦二异丙酯富马酸盐（TDF）作为HIV感染孕妇抗逆转录病毒治疗（ART）的一部分，并作为单药治疗B型肝炎病毒（HBV）单一感染的孕妇，将感染传播给婴儿的风险很高。替诺福韦（TFV）血浆暴露量在妊娠期间降低;然而，伴随抗逆转录病毒药物和病毒感染本身也会影响TFV的药代动力学。我们的目的是比较接受基于TDF的ART（联合或不联合利托那韦增强的蛋白酶抑制剂（r/PI））的孕妇与接受TDF单药治疗的HBV孕妇的TFV药代动力学。非r/PI方案主要是整合酶链转移抑制剂或基于非核苷逆转录酶的方案。合并来自ART（潘纳）的HIV孕妇药代动力学研究和评估HBV孕妇TFV药代动力学的研究（iTAP）的数据。共纳入196名孕妇，其中59名HIV感染者（32名接受r/PI）和137名HBV单一感染者。与产后1个月相比，使用TDF和r/PI或TDF和非r/PI的HIV感染女性和接受TDF单药治疗的HBV感染女性在妊娠晚期从时间0至24小时的个体内TFV血药浓度-时间曲线下面积分别降低了25%、26%和21%。接受非r/PI的孕妇与接受TDF单药治疗的HBV孕妇的TFV血浆浓度-时间曲线下面积从0至24小时相似（1.84 vs 1.86 µg · h/mL）;然而，接受TDF + r/PI的孕妇的暴露量较高（2.41 µg · h/mL; P < .01）。妊娠减少了TFV暴露，并且相对大小不受伴随抗逆转录病毒药物或病毒感染的影响，但TDF和r/PI之间的药物相互作用在妊娠期间仍然存在，导致暴露量高于TDF和非r/PI或TDF单药治疗。
Tenofovir disoproxil fumarate (TDF) is recommended as part of antiretroviral therapy (ART) for pregnant women with HIV and as monotherapy for pregnant women with hepatitis B virus (HBV) monoinfection at high risk of transmitting infection to their infants. Tenofovir (TFV) plasma exposures are reduced during pregnancy; however, concomitant antiretrovirals and the viral infection itself can also influence TFV pharmacokinetics. Our aim was to compare TFV pharmacokinetics in pregnant women receiving TDF‐based ART, with or without a ritonavir‐boosted protease inhibitor (r/PI), to pregnant women with HBV receiving TDF monotherapy. Non‐r/PI regimens were primarily integrase strand transfer inhibitors or nonnucleoside reverse transcriptase inhibitor–based regimens. Data were combined from a pharmacokinetic study of pregnant women with HIV on ART (PANNA), and a study assessing TFV pharmacokinetics in pregnant women with HBV (iTAP). A total of 196 pregnant women, 59 with HIV (32 receiving r/PIs) and 137 with HBV monoinfection were included. Intraindividual TFV area under the plasma concentration–time curve from time 0 to 24 hours was 25%, 26%, and 21% lower during the third trimester compared to 1 month postpartum in women with HIV using TDF and an r/PI or TDF and non‐r/PI and women with HBV receiving TDF monotherapy, respectively. TFV area under the plasma concentration–time curve from time 0 to 24 hours was similar in pregnant women receiving non‐r/PI to pregnant women with HBV receiving TDF monotherapy (1.84 vs 1.86 µg • h/mL); however, pregnant women receiving TDF with an r/PI had higher exposures (2.41 µg • h/mL; P < .01). Pregnancy reduces TFV exposure and the relative size was not impacted by concomitant antiretroviral drugs or viral infection, but a drug‐drug interaction between TDF and r/PI remains during pregnancy, leading to higher exposures than those on TDF and non‐r/PI or TDF monotherapy.