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

PACTG 1039（版本 10）安全性和抗病毒性的 III 期随机试验

• 批准号: 7605889
• 负责人: William Thomas Shearer
• 金额: $ 1.19万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605889
• 关键词: Adherence; Adverse drug effect; Anemia; Area Under Curve; CD4 Lymphocyte Count; Child; Computer Retrieval of Information on Scientific Projects Database; Development; Enrollment; Funding; Future; Genetic Polymorphism; Gestational Diabetes; Grant; Guidelines; HIV; HIV-1; HLA-B57; HLA-DQ3; HLA-DR7 Antigen; Health Status; Hypersensitivity; Hypoglycemia; Incidence; Infant; Institution; Lamivudine/Zidovudine; Lopinavir/Ritonavir; Low Birth Weight Infant; Mothers; Outcome; Patient currently pregnant; Perinatal; Phase; Plasma; Postpartum Period; Postpartum Women; Predictive Value; Pregnancy; Pregnant Women; Prematurity of fetus; Randomized Controlled Clinical Trials; Research; Research Personnel; Resistance; Resistance development; Resources; Risk; Safety; Sensitivity and Specificity; Source; T-Cell Receptor-Rearrangement Excision DNA Circles; Therapeutic; Third Pregnancy Trimester; Time; Toxic effect; Treatment Efficacy; Treatment Failure; Treatment Protocols; United States National Institutes of Health; Viral Load result; Week; Woman; abacavir; abstracting; antiretroviral therapy; fetal; glucose tolerance; liver function; transmission process

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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要 一、假说 在为打算产后停止治疗的孕妇提供治疗时，必须考虑重要的问题。这项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。该假说用于治疗不符合当前PHS开始治疗指南的孕妇(如果她们未怀孕，将不会开始治疗)，使用All NRTI方案(阿巴卡韦/拉米夫定/齐多夫定)将1)将艾滋病毒通过母婴传播的风险降低到可获得的最低水平，2)将胎儿毒性和母亲药物副作用降至最低，3)为母亲保留未来的治疗选择，4)尽量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 主要 通过比较A组和B组孕妇在妊娠34周(或分娩前的最后一次病毒载量，如果发生在34周)时每毫升400拷贝病毒抑制的比例，同时继续指定的治疗，来检验三种NRTI与两种NRTI和一种PI治疗的安全性和有效性。 次要的 1.通过检测孕妇外周血中CD4+淋巴细胞计数和血浆HIV-1病毒载量，比较产妇分娩时HIV相关健康状况。 2.描述A组和B组妇女坚持治疗的情况。 3.在产后3个月、6个月和12个月，在开始任何新的抗逆转录病毒治疗之前，通过CD4+淋巴细胞计数和血浆艾滋病毒-1病毒载量来评估妇女产后与艾滋病毒有关的健康状况。 4.比较A组和B组妇女在分娩时、产后3、6和12个月以及在所有治疗失败和开始任何新的抗逆转录病毒治疗之前的艾滋病毒-1基因耐药性的发展情况。 5.比较A、B两组孕妇糖耐量异常、妊娠期糖尿病、孕期乳酸水平异常的发生率。 6.比较A组和B组产妇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、低出生体重、围产期艾滋病毒传播。 7.回顾性评价人类白细胞抗原-B57、人类白细胞抗原-DR7和人类白细胞抗原-DQ3基因多态性在诊断孕妇阿巴卡韦过敏风险中的预测价值、敏感性和特异性。 8.测定B组妊娠晚期稳定期前12名妇女的洛比那韦/利托那韦(533/133 mg，口服Q12H)的峰值浓度和曲线下面积(AUC)(见第9.0节)。 9.比较A、B两组入院时、分娩时及产后6周T细胞受体重排切除DNA环(TREC)的浓度。