Health of HIV-Infected Mothers after pMTCT, Botswana

描述(由申请人提供)：产妇健康问题是旨在预防发展中世界艾滋病毒-1母婴传播(MTCT)方案的一个重要但未得到充分研究的方面。在这方面，关于产妇健康的两个最重要和最紧迫的问题是：1)感染艾滋病毒的妇女进行母乳喂养是否与过高的产妇发病率和死亡率有关；2)考虑到在单剂NVP后经常出现耐药的艾滋病毒-1病毒感染病例，曾服用单剂NVP预防母婴传播的妇女对含有奈韦拉平的联合抗逆转录病毒疗法的反应。感染艾滋病毒的母亲目前正在博茨瓦纳参加由NICHD资助的一项随机临床试验，该试验正在研究母婴传播预防战略。妇女被随机分成两组，一组是单次短程服用齐多夫定的围产期预防，另一组是在给婴儿预防性注射齐多夫定的同时母乳喂养，或者是配方奶喂养。在这项研究中，艾滋病妇女将接受政府ART计划一线含有NVP的ART方案。这项建议的主要目标是：1.检查随机婴儿喂养策略(母乳喂养与配方奶喂养)与产妇艾滋病或死亡时间之间的关系；2.评估在分娩期间接受单剂量NVP或安慰剂治疗的妇女中，在开始接受含有NVP的抗逆转录病毒药物治疗52周后出现病毒学应答(血浆HIV-1 RNA和400拷贝/毫升)的妇女的比例。次要目标包括阐明感染艾滋病毒的母亲母乳喂养可能导致产妇发病率和死亡率过高的原因，包括微量营养素缺乏；在分娩期间曾接受单剂NVP和安慰剂的妇女出现基因耐药和病毒学失败；以及博茨瓦纳孕妇和产后妇女对抗逆转录病毒疗法的耐受性、安全性和坚守。这一已经存在的可获得抗逆转录病毒治疗的队列提供了一个独特的机会，可以用相对较少的额外资源投资来回答对公共卫生有重大影响的问题。

DESCRIPTION (provided by applicant): Maternal health concerns are an important but understudied aspect of programs designed to prevent mother-to-child HIV-1 transmission (MTCT) in the developing world. Two of the most important and urgent questions regarding maternal health in this context are 1) whether breastfeeding by HIV-infected women is associated with excess maternal morbidity and mortality, and 2) the response to nevirapine (NVP)-containing combination antiretroviral therapy (ART) among women who have previously taken single-dose NVP for the prevention of MTCT, given the frequent emergence of drug resistant HIV-1 after single-dose NVP. HIV-infected mothers are currently being enrolled in a NICHD-funded randomized clinical trial in Botswana that is studying strategies for MTCT prevention. Women are randomized to either perinatal prophylaxis with short course zidovudine + single-dose NVP or to zidovudine alone, and to either breastfeed while giving their infant prophylactic zidovudine or to formula-feed. Women with AIDS in this study will be offered the Government ART program first-line NVP-containing ART regimen. The primary objectives of this proposal are: 1.To examine the association between randomized infant feeding strategy (breast- versus formula feeding) and time to maternal AIDS or death, and 2. To assess the proportion of women with virologic response (plasma HIV-1 RNA < 400 copies / mL) at 52 weeks after initiating NVP-containing ART among women who previously received single-dose NVP versus placebo during labor. Secondary objectives include elucidation of the etiology of possible excess maternal morbidity and mortality associated with breastfeeding by HIV-infected mothers, including micronutrient deficiency; the emergence of genotypic resistance and virologic failure in women who previously received single-dose NVP versus placebo during labor; and the tolerability and safety of and adherence to ART among pregnant and postpartum women in Botswana. This already-existing cohort with access to ART provides a unique opportunity to answer questions that have significant public health implications with a relatively small investment of additional resources.