Radboud University Medical Center, Nijmegen, The Netherlands.
Hospital Universitario Virgen de las Nieves, Granada, Spain.
Clin Infect Dis. 2015 Sep 1;61(5):809-16. doi: 10.1093/cid/civ366. Epub 2015 May 5.
The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women.
An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated.
Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9).
Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women.
NCT00825929.
在人类免疫缺陷病毒（HIV）感染的孕妇中使用拉替拉韦对于预防母婴 HIV 传播非常重要，尤其是在需要快速降低 HIV RNA 载量或无法使用首选抗逆转录病毒药物的情况下。怀孕期间的生理变化会降低抗逆转录病毒药物的暴露。我们研究了怀孕对拉替拉韦药代动力学的影响以及其在 HIV 感染孕妇中的安全性和疗效。
在接受拉替拉韦 400mg 每日两次治疗的 HIV 感染孕妇中进行了一项开放标签、多中心、4 期研究（HIV 感染孕妇中新开发的抗逆转录病毒药物的药代动力学网络）。在妊娠晚期和产后获得稳态药代动力学特征，以及脐带和产妇分娩时的浓度。评估了安全性和病毒学疗效。
共纳入 22 例患者，其中 68%的患者在妊娠期间开始使用拉替拉韦。接近分娩时，86%的患者病毒载量无法检测到（<50 拷贝/ml）。没有儿童感染 HIV。拉替拉韦的暴露量高度可变。与产后相比，第三孕期的平均总血浆浓度-时间曲线下面积（AUC）和 12 小时后血浆浓度（C12h）分别降低了 29%和 36%：几何均数比值（90%置信区间）分别为 AUC0-12h 的 0.71（0.53-0.96）和 C12h 的 0.64（0.34-1.22）。中位数脐带与母体血药浓度比值为 1.21（四分位间距，1.02-2.17；n=9）。
拉替拉韦在怀孕期间耐受良好。拉替拉韦的药代动力学显示出广泛的变异性。与产后相比，第三孕期观察到的拉替拉韦暴露量平均下降，认为没有临床意义。拉替拉韦可在 HIV 感染孕妇中按标准剂量使用。
NCT00825929。
