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。在资源有限的环境中，母乳喂养对婴儿的生存至关重要，干预措施的目的是在怀孕、分娩和整个母乳喂养期间提供抗逆转录病毒预防。这可能会使胎儿和婴儿在大脑和身体快速发育期间暴露于长达24个月的抗逆转录病毒药物。尽管根据美国和欧洲的研究，发现产前和围产期短期接触通常是安全的，但人们担心长期接触可能导致终末器官（如大脑或骨骼）的线粒体功能障碍。鉴于有在全世界推广预防母婴传播的重大计划，必须认真评估这些抗逆转录病毒药物干预措施对儿童发育和成长的影响。 我们建议进行一项纵向队列研究，以比较暴露于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60个月以上的生长和血液学参数;来自相似社会经济和文化背景的非HIV非ARV暴露儿童的对照组。该研究将共同招募来自布兰太尔马拉维和坎帕拉乌干达的PROMISE PMTCT试验的暴露于HIV ARV的未感染婴儿。将从PROMISE婴儿入组地点的健康儿童和急性护理诊所招募年龄和性别匹配的对照健康儿童。将在12个月和24个月时使用Mullens检验评估在这些环境中已验证的ND指标，并在60个月时使用考夫曼ABC进行NC检验;而每年将收集神经系统状态、血液学（CDC）和生长（身高、体重、头和上臂中围）。分析中还将调整产妇和看护人的教育、家庭环境评估。主要的独立变量是宫内和产后母乳喂养期间抗逆转录病毒药物暴露的持续时间。 这项研究将为政策制定者和研究人员提供重要的数据，以确定暴露于艾滋病毒和抗逆转录病毒药物的未感染婴儿在子宫内和产后长期暴露于抗逆转录病毒药物是否与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防止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.