Department of Pharmacy, Radboud Institute for Health Sciences (RIHS), Radboud university medical center, Nijmegen, The Netherlands.
Saint-Pierre University Hospital, Brussels, Belgium.
Clin Infect Dis. 2022 Sep 10;75(4):623-629. doi: 10.1093/cid/ciab1010.
Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is included in the majority of the recommended first-line antiretroviral regimens for patients living with human immunodeficiency virus (HIV), but there are limited data on TAF use in pregnant women. We aimed to examine the plasma pharmacokinetics of TAF and TFV in pregnant women from Europe.
Pregnant women living with HIV were included from treatment centers across Europe, and intensive pharmacokinetic sampling in the third trimester and postpartum was performed. Pharmacokinetic parameters of TAF and TFV were determined with noncompartmental analysis. The proportion of women with a TAF area under the curve (AUClast) below the target of 53.1 ng∗h/mL was determined. Clinical efficacy and safety outcome parameters were reported.
In total, 20 pregnant women living with HIV were included. At the third trimester, geometric mean TAF AUClast and Cmax were decreased by 46% and 52%, respectively, compared with postpartum. TFV AUC0-24h, Cmax, and Ctrough decreased by 33%, 30%, and 34%, respectively. The proportion of women with a TAF AUClast < 53.1 ng∗h/mL was 6% at third trimester and 0% postpartum. One out of 20 women had a viral load > 50 copies/mL at third trimester and no mother-to-child transmission occurred.
TAF plasma concentrations were reduced by about half in women living with HIV during third trimester of pregnancy but remained above the predefined efficacy target in the majority of the pregnant women. TFV concentrations were reduced by approximately 30% during third trimester. Despite the observed exposure decrease, high virologic efficacy was observed in this study.
替诺福韦艾拉酚胺（TAF）是替诺福韦（TFV）的前体药物，被纳入了大多数推荐的一线抗逆转录病毒治疗方案中，用于治疗人类免疫缺陷病毒（HIV）感染者，但关于 TAF 在孕妇中的应用数据有限。本研究旨在研究欧洲孕妇中 TAF 和 TFV 的血浆药代动力学。
本研究纳入了来自欧洲各地治疗中心的 HIV 感染孕妇，并在妊娠晚期和产后进行了强化药代动力学采样。采用非房室分析方法测定 TAF 和 TFV 的药代动力学参数。确定 TAF 曲线下面积（AUClast）低于 53.1ng·h/mL 目标的女性比例。报告了临床疗效和安全性结局参数。
共纳入 20 例 HIV 感染孕妇。与产后相比，妊娠晚期 TAF AUClast 和 Cmax 分别下降了 46%和 52%。TFV AUC0-24h、Cmax 和 Ctrough 分别下降了 33%、30%和 34%。妊娠晚期 TAF AUClast<53.1ng·h/mL 的女性比例为 6%，产后为 0%。20 例女性中有 1 例在妊娠晚期病毒载量>50 拷贝/ml，但未发生母婴传播。
在 HIV 感染孕妇妊娠晚期，TAF 血浆浓度下降约一半，但在大多数孕妇中仍高于预先设定的疗效目标。妊娠晚期 TFV 浓度下降约 30%。尽管观察到暴露减少，但本研究中观察到了较高的病毒学疗效。
