Pregnancy Outcomes and Infant Survival in the Era of Universal HAART in Africa

 描述(申请人提供)：在全球范围内，再次承诺消除艾滋病毒的母婴传播(MTCT)。在马拉维，建议对所有怀孕、哺乳或怀孕期间感染艾滋病毒的妇女进行普遍的终身联合抗逆转录病毒治疗(ART)。在这种称为备选方案B+的方法中，无论妇女的免疫状况或艾滋病毒临床疾病的阶段如何，都会开出联合抗逆转录病毒疗法。最近一项名为Promise的大型多点随机临床试验的结果表明，联合ART可以将HIV的MTCT率降低到非常低的水平(~0.5%)。Promise试验的疗效结果支持2013年世卫组织推荐使用联合抗逆转录病毒治疗的指南。Promise研究还表明，一些抗逆转录病毒药物可能与不良妊娠结局有关，如低出生体重(LBW)和早产(PT)，并可能增加早期新生儿死亡。虽然Promise没有随机选择马拉维的B+方案，但一些药物在两种方案中都是通用的。我们提出了一项观察性研究，有两个特定的目标，与Promise的安全发现有关。在目标1中，我们将比较感染HIV和未感染HIV的妇女的妊娠结局(LBW、PT和宫内生长受限)。目标2将比较感染艾滋病毒的婴儿(感染艾滋病毒的母亲所生的婴儿)和未接触艾滋病毒的婴儿(未感染艾滋病毒的母亲所生的婴儿)的存活率。早在非洲使用抗逆转录病毒药物的早期研究表明，与未感染艾滋病毒的妇女及其子女相比，感染艾滋病毒的未经治疗的妇女及其子女在怀孕结局和婴儿存活率方面存在显著差异。这些差异被归因于艾滋病毒。这项拟议研究的目标是评估通用抗逆转录病毒疗法是否如备选方案B+那样消除了这些差异。这是一个紧迫而重要的问题。如果与艾滋病毒相关的妊娠结局和存活率方面的巨大差异仍然存在，那么这些结果背后的其他因素将需要进一步检查。拟议的研究是探索性的，将提供初步数据，以概念化更大的研究，以检查这些结果的复杂原因--包括抗逆转录病毒疗法的安全性--并确定是否需要进一步的干预。这项研究将在马拉维的布兰太尔的主要医院和几个健康中心进行。总共将有1350名妇女参加；675名感染艾滋病毒的健康妇女在怀孕前或怀孕期间接受备选B+ART治疗，675名未感染艾滋病毒的妇女。这些妇女和她们的孩子将在产后接受长达一年的前瞻性跟踪。出生体重和胎龄将在出生时进行评估，病例报告表格将在登记和每次后续访问时填写。

 DESCRIPTION (provided by applicant): Globally, there is a renewed commitment to eliminate mother-to-child transmission (MTCT) of HIV. In Malawi, universal, lifelong combination antiretroviral treatment (ART) is recommended for all HIV-infected women who are pregnant, breastfeeding, or between pregnancies. In this approach, known as Option B+, combination ART is prescribed irrespective of a woman's immune status or stage of HIV clinical disease. Findings from a recent, large multisite randomized clinical trial known as PROMISE showed that combination ART can reduce rates of MTCT of HIV to very low levels (~0.5%). The efficacy results of the PROMISE trial support the 2013 WHO guidelines where use of combination ART was recommended. The PROMISE study also showed that some ART drugs may be associated with adverse pregnancy outcomes such as low birth weight (LBW) and preterm (PT) birth and may increase early neonatal death. While PROMISE did not randomize women to Malawi's specific Option B+ regimen, some drugs are common to both regimens. We propose an observational study with two specific aims that relate to safety findings from PROMISE. In Aim 1, we will compare pregnancy outcomes (LBW, PT and intrauterine growth restriction) between HIV-infected and HIV-uninfected women. Aim 2 will compare survival between HIV-exposed infants (born to HIV-infected mothers) and HIV-unexposed infants (born to HIV-uninfected mothers). Earlier studies that predated ART use in Africa showed substantial differences in pregnancy outcomes and infant survival among HIV-infected untreated women and their children compared to HIV-uninfected women and their children. These differences were attributed to HIV. The goal of the proposed study is to assess if universal ART, as in Option B+, has eliminated these differences. This is an urgent and important question. If substantial differences in pregnancy outcomes and survival associated with HIV still remain, other factors underlying these outcomes will need further examination. The proposed study is exploratory and will provide preliminary data to conceptualize larger studies to examine the complex causes of these outcomes - including safety of ARTs - and to determine if further interventions are needed. The study will be conducted in Blantyre, Malawi in the main hospital and several health centers. A total sample of 1350 women will be enrolled; 675 HIV-infected healthy women on Option B+ ART prior to or during pregnancy and 675 HIV-uninfected women. These women and their children will be prospectively followed postnatally for up to one year. Birth weight and gestational age will be assessed at birth and case reports forms will be completed at enrollment and each follow-up visit.