Developmental and Growth Outcomes for ARV Exposed HIV Uninfected African Children

描述（由申请人提供）：预防艾滋病毒母婴传播（PMTCT）在资源丰富的环境中取得了重大进展，通过在怀孕期间使用抗逆转录病毒药物和避免母乳喂养，传播率已降至2%以下。在母乳喂养对婴儿生存至关重要的资源有限的环境中，干预措施旨在在怀孕、分娩/分娩期间以及整个母乳喂养期间提供抗逆转录病毒（ARV）预防。这可能会使胎儿和婴儿在大脑和身体快速生长的时期接触长达24个月的抗逆转录病毒药物。尽管根据美国和欧洲的研究，短期的产前和围产期暴露通常是安全的，但人们担心，长期暴露可能导致脑或骨等终端器官的线粒体功能障碍。鉴于在全世界范围内都有提高预防母婴传播的主要计划，认真评估这些抗逆转录病毒药物干预措施对儿童发育和生长的影响是很重要的。我们建议进行一项纵向队列研究，比较暴露于HIV和ARV的未感染婴儿的神经发育（ND）、神经认知（NC）、血液学和生长结果，以及他们在60个月以上的生长和血液学参数；另一组是来自相似社会经济和文化背景的非艾滋病毒和非抗逆转录病毒感染儿童。这项研究将在马拉维布兰太尔和乌干达坎帕拉的PROMISE PMTCT试验中共同招募暴露于艾滋病毒抗逆转录病毒的未感染婴儿。对照健康儿童的年龄和性别相匹配，将从允诺婴儿入组地点的健康儿童和急症护理诊所招募。在这些环境中验证的ND措施将在12个月和24个月时使用Mullens Test进行评估，在60个月时使用Kaufman ABC进行NC测试；而神经系统状态、血液学（CDC）和生长（身高、体重、头部和上臂中围）将每年收集一次。产妇和看护教育、家庭环境评估也将在分析中加以调整。主要的自变量是子宫内和产后母乳喂养期间抗逆转录病毒暴露的持续时间。这项研究将为政策制定者和研究人员提供重要数据，以了解艾滋病毒和抗逆转录病毒暴露的未感染婴儿在子宫内和产后延长抗逆转录病毒暴露是否与ND、骨髓抑制或身体发育方面的长期后遗症有关。这反过来将有助于为预防母婴传播政策提供信息。

DESCRIPTION (provided by applicant): The Prevention of Mother to Child Transmission (PMTCT) of HIV has made major progress in resource rich settings where transmission has been reduce to less than 2% with use of antiretroviral drugs during pregnancy and avoidance of breastfeeding. In resource limited settings where breastfeeding is crucial for infant survival, interventions are aimed at providing antiretroviral (ARV) prophylaxis during pregnancy, labor/delivery and then throughout breastfeeding. This will potentially expose the fetus and infant to as long as 24 months of antiretroviral drugs during a period of rapid brain and physical growth. Although shorter term prenatal and peripartum exposure has been found to generally safe based on studies in the US and Europe, there are concerns that longer term exposures may lead to mitochondrial dysfunction in end organs such as the brain or bone. Given that there are major plans to upscale PMTCT worldwide, it is important to carefully assess the impact of these ARV interventions on child development and growth. We propose to conduct a longitudinal cohort study to compare neurodevelopmental (ND), neurocognitive (NC), hematologic and growth outcomes of HIV and ARV exposed uninfected infants as well as their growth over 60 months and hematologic parameters; to a control group of non HIV non ARV exposed children from similar socioeconomic and cultural backgrounds. The study will co-enroll HIV ARV exposed uninfected infants from the PROMISE PMTCT trial in Blantyre Malawi and Kampala Uganda. Control healthy children matched for age, and gender will be recruited from well child and acute care clinics at the sites where the PROMISE infants have been enrolled. ND measures that have validated in these settings will be assessed at 12 and 24 months using the Mullens Test, and NC testing using the Kaufman ABC at 60 months; while neurologic status, hematologic (CDC) and growth (height, weight, head and upper mid arm circumference will be gathered annually. Maternal and caretaker education, home environment assessments will also be adjusted for in the analyses. The main independent variable of interest is duration of ARV exposure both in utero and postnatally during breastfeeding. This study will provide important data to policy makers and researchers on whether extended in utero and post partum ARV exposure among HIV and ARV exposed uninfected infants is associated with long term sequelae in terms of ND, bone marrow suppression or physical growth. This in turn will help inform PMTCT policies.