ANTIRETROVIRAL DRUGS DURING PREGNANCY, HIV INFECTED WOMEN (SUB OF PACTG P1025)

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项前瞻性药代动力学(PK)研究，旨在评估目前处方的抗逆转录病毒(ARV)药物以及这些药物在感染艾滋病毒的怀孕妇女中的相互作用组合的药代动力学。受试者可以在怀孕26周或以上的时候报名。受试者必须参加PACTG方案P1025，并且目前在成人剂量时接受以下抗逆转录病毒药物或相互作用的组合之一：奈韦拉平200毫克，每天2次，氨丙那韦1200毫克，每日2次，阿巴卡韦300毫克，洛匹那韦/利托那韦400/100毫克，每日2次，或非标签剂量组合吲地那韦/利托那韦800/100毫克，每日2次。该研究的目标是：主要：描述目前用于怀孕艾滋病毒感染妇女的临床护理的选定抗逆转录病毒药物在怀孕期间的PK参数，并确定与a)来自非怀孕成年人的历史数据相比，这些抗逆转录病毒药物的治疗剂量方案在怀孕期间是否产生足够的药物暴露；以及b)研究队列中的相同妇女在产后期间。第二项：1.比较分娩时脐带血和母体血浆中抗逆转录病毒药物的浓度。2.通过测定尿液中6B-羟基皮质醇与皮质醇的比值，间接评价细胞色素P450 3A4的诱导作用。参与这项研究的孕妇将在怀孕第三个月和产后6至12周之间进行密集的PK采样。在每个PK采样日，通过测量尿中6B-羟基皮质醇和皮质醇的浓度来评估每个受试者的糖皮质激素代谢。受试者将在整个怀孕期间继续服用处方药物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a prospective pharmacokinetics (PK) study to evaluate the pharmacokinetics of currently prescribed antiretroviral (ARV) drugs and interacting combinations of these drugs in pregnant HIV-infected women. Subjects can enroll at > or equal to 26 weeks gestation. Subjects must be enrolled in PACTG protocol P1025 and currently receiving one of the following antiretroviral drugs or interacting combinations at adult dosing: nevirapine 200 mg b.i.d., amprenavir 1200 mg b.i.d., abacavir 300 mg b.i.d., lopinavir/ritonavir 400/100 mg b.i.d., or the off-label dosing combination of indinavir/ritonavir 800/100 mg b.i.d. The study objectives are: PRIMARY: To describe the PK parameters during pregnancy of selected antiretroviral drugs currently used in the clinical care of pregnant HIV-infected women, and to determine if therapeutic dosing regimens of these antiretroviral drugs produce adequate drug exposure during pregnancy compared to a) historical data from non-pregnant adults; and b) the same women in the study cohorts during the postpartum period. SECONDARY: 1. To compare antiretroviral drug concentrations in plasma from cord blood with those in maternal plasma at the time of delivery. 2. To indirectly assess the induction of cytochrome P450 3A4 by determining the ratio in urine of 6B-hydroxycortisol to cortisol. Pregnant women participating in the study will have intensive PK sampling performed during the third trimester of pregnancy and again between 6 and 12 weeks postpartum. Glucocorticoid metabolism will be evaluated in each subject on each PK sampling day by measurement of urine concentrations of 6B-hydroxycortisol and cortisol. Subjects will continue to take their prescribed medications throughout the course of their pregnancy.