PACTG 1039 (VERSION 10) A PHASE III RANDOMIZED TRIAL OF THE SAFETY AND ANTIR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要 I. 假设 在为打算在产后停止治疗的孕妇提供治疗时，必须考虑重要问题。本试验的目的是检查三种NRTI与两种NRTI和一种PI治疗的安全性和有效性。该假设是治疗不符合现行PHS指南的孕妇开始治疗（如果未怀孕，则不会开始治疗）（阿巴卡韦/拉米夫定/齐多夫定）将1）将母婴传播艾滋病毒的风险降低到可达到的最低水平，2）将胎儿毒性和母体药物副作用的风险降至最低，3）为母亲保留未来的治疗选择，4）最大限度地减少对怀孕期间和未来使用的抗逆转录病毒药物产生耐药性的可能性。 二. 具体目标 初级 通过比较A组和B组中妊娠34周（或分娩前末次病毒载量，如果发生在34周内）时病毒学抑制< 400拷贝/mL的女性比例，同时继续接受指定治疗，检查3种NRTI与2种NRTI和1种PI治疗的安全性和有效性。 二次 1. 比较孕妇分娩时CD 4+淋巴细胞计数和血浆HIV-1病毒载量与HIV相关健康状况的关系。 2. 描述A组和B组女性的治疗依从性。 3. 通过产后3、6和12个月以及开始任何新的抗逆转录病毒治疗前的CD 4+淋巴细胞计数和血浆HIV-1病毒载量，评估产后妇女的HIV相关健康状况。 4. 比较A组和B组妇女在分娩时、产后3、6和12个月以及所有治疗失败病例和开始任何新的抗逆转录病毒治疗前的HIV-1基因型耐药性的发展。 5. 比较A、B组妊娠期糖耐量异常、妊娠期糖尿病及乳酸异常的发生率。 6. 比较A组和B组妇女所生婴儿的不良结局发生率，包括：贫血、低血糖和肝功能异常、早产和低出生体重、围产期HIV传播。 7. 回顾性评价HLA-B57、HLA-DR 7和HLA-DQ 3基因多态性在识别孕妇发生阿巴卡韦超敏反应风险中的预测价值、敏感性和特异性。 8. 确定B组入组的前12名女性在妊娠晚期稳态时洛匹那韦/利托那韦（533/133 mg，PO Q12 H）的峰浓度和曲线下面积（AUC）（见第9.0节）。 9. 比较A组和B组在入院、分娩和产后6周时T细胞受体重排切除DNA环（TREC）的浓度。

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. ABSTRACT I. HYPOTHESIS Important issues must be considered when providing treatment to pregnant women who intend to discontinue treatment postpartum. The aim of this trial is to examine the safety and efficacy of treatment with three NRTIs versus two NRTIs and one PI. The hypothesis is treating pregnant women who do not meet the current PHS guidelines for initiation of therapy (and would not start treatment if they were not pregnant) with an all NRTI regimen (abacavir/lamivudine/zidovudine) will 1) reduce the risk of maternal to child transmission of HIV to the lowest attainable level, 2) minimize the risk of fetal toxicity and maternal drug side effects, 3) preserve therapeutic options for the mother for the future and 4) minimize the likelihood of developing resistance to antiretrovirals used during pregnancy and in the future. II. SPECIFIC AIMS Primary To examine the safety and efficacy of treatment with three NRTIs versus two NRTIs and one PI, by comparing the proportion of women in group A and B with virologic suppression to < 400 copies per mL at 34 weeks gestation (or the last viral load prior to delivery if this occurs < 34 weeks), while continuing on assigned therapy. Secondary 1. To compare HIV-related health status of women at delivery by CD4+ lymphocyte counts and plasma HIV-1 viral load. 2. To describe adherence to therapy among women in Groups A and B. 3. To assess the HIV- related health status of women postpartum as determined by CD4+lymphocyte counts and plasma HIV-1 viral load at 3, 6, and 12 months postpartum, and prior to the initiation of any new antiretroviral therapy. 4. To compare the development of HIV-1 genotypic resistance among women in Group A and Group B at the time of delivery, and at 3, 6, and 12 months postpartum and in all cases of treatment failure and prior to the initiation of any new antiretroviral therapy. 5. To compare the incidence of abnormal glucose tolerance, gestational diabetes and abnormal lactate levels during pregnancy between Group A and B. 6. To compare the incidence of adverse outcomes among infants born to women in Group A and B, including: anemia, hypoglycemia and abnormal liver function studies, prematurity, and low birth weight, perinatal HIV transmission. 7. To evaluate retrospectively the predictive value, sensitivity and specificity of polymorphisms in HLA-B57, HLA-DR7 and HLA-DQ3 in identifying pregnant women at risk for development of abacavir hypersensitivity. 8. To determine the peak concentration and area under the curve (AUC) of lopinavir/ritonavir (533/133 mg taken PO Q12H) in the first 12 women enrolled in Group B at steady-state in the third trimester of pregnancy (see section 9.0). 9. To compare the concentration of T-cell receptor-rearrangement excision DNA circles (TREC) in Group A and B at entry, delivery, and at 6 weeks postpartum.