Developmental and Growth Outcomes for ARV Exposed HIV Uninfected African Children

暴露于抗逆转录病毒药物（ARV）、未感染艾滋病毒的非洲儿童的发育和生长结果

• 批准号: 8705555
• 负责人: Michael Joseph Boivin
• 金额: $ 45.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705555
• 关键词: 5 year old; Acute; African; Age; Age-Months; Anti-Retroviral Agents; Behavior; Birth; Bone Marrow Suppression; Brain; Breast Feeding; Caregivers; Caring; Centers for Disease Control and Prevention (U.S.); Child; Child Behavior Checklist; Child Development; Clinic; Clinical Trials; Cohort Studies; Control Groups; Cultural Backgrounds; Data; Development; Education; Enrollment; Equipment and supply inventories; Europe; Exposure to; Fetus; Gender; Growth; HIV; Head; Height; Home environment; Infant; Intervention; Lead; Learning; Malawi; Measures; Modeling; Mothers; Neurocognitive; Neurologic; Neurological observations; Neurological status; Nevirapine; Nursery Schools; Organ; Outcome; Perinatal Exposure; Pharmaceutical Preparations; Policies; Policy Maker; Pregnancy; Prevention; Process; Prophylactic treatment; Randomized; Randomized Controlled Trials; Recruitment Activity; Regimen; Research Design; Research Personnel; Resources; Site; Symptoms; Test Result; Testing; Uganda; Vertical Disease Transmission; Visuospatial; Weaning; Weight; Zidovudine; arm; base; bone; child battery; clinical research site; early childhood; executive function; in utero; interest; intrapartum; memory process; mitochondrial dysfunction; neurocognitive test; neuropsychological; prenatal; prospective; socioeconomics; therapy design; transmission process

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.

描述（由申请人提供）：在资源丰富的地区，预防艾滋病毒母婴传播 (PMTCT) 已取得重大进展，通过在怀孕期间使用抗逆转录病毒药物和避免母乳喂养，艾滋病毒传播率已降至 2% 以下。在资源有限的环境中，母乳喂养对于婴儿的生存至关重要，干预措施的目的是在怀孕、临产/分娩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期间接触长达 24 个月的抗逆转录病毒药物。尽管根据美国和欧洲的研究发现，短期产前和围产期暴露通常是安全的，但有人担心，长期暴露可能会导致大脑或骨骼等终末器官的线粒体功能障碍。鉴于全球范围内有扩大预防母婴传播的重大计划，仔细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非常重要。 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，以及他们在 60 个月内的生长情况和血液学参数；对照组由来自相似社会经济和文化背景的非艾滋病毒非抗逆转录病毒暴露儿童组成。该研究将共同​​招募来自马拉维布兰太尔和乌干达坎帕拉的 PROMISE PMTCT 试验中暴露于 HIV 抗逆转录病毒药物的未感染婴儿。控制与年龄和性别相匹配的健康儿童将从 PROMISE 婴儿招募地点的儿童健康和急症护理诊所招募。在这些环境中已验证的 ND 测量将在 12 个月和 24 个月时使用 Mullens 测试进行评估，并在 60 个月时使用 Kaufman ABC 进行 NC 测试；每年都会收集神经系统状态、血液学 (CDC) 和生长（身高、体重、头部和上臂围）。母亲和看护者教育、家庭环境评估也将在分析中进行调整。感兴趣的主要自变量是这项研究将为政策制定者和研究人员提供重要数据，以了解未感染 HIV 和 ARV 的婴儿在子宫内和产后是否会延长 ARV 暴露时间。与 ND、骨髓抑制或身体生长方面的长期后遗症相关，这反过来将有助于为 PMTCT 政策提供信息。