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: 8419654
• 负责人: Michael Joseph Boivin
• 金额: $ 50.93万
• 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/8419654
• 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. PUBLIC HEALTH RELEVANCE: Narrative This prospective 5 year study will assess developmental outcomes for uninfected infants exposed to ARVs who are participating in the PROMISE clinical trial where mothers receive antiretrovirals during pregnancy and then either mothers or infants receive antiretroviral drugs through out during breastfeeding. The study will be conducted at clinical research sites in Malawi and Uganda. It will compare these neurodevelopmental test results to findings among age and gender matched children from similar cultural backgrounds but who were not exposed to antiretrovirals.

描述(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/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发育期间接触长达24个月的抗逆转录病毒药物。尽管根据美国和欧洲的研究，较短期的产前和围产期接触被发现总体上是安全的，但也有人担心，长期接触可能会导致大脑或骨骼等末端器官的线粒体功能障碍。鉴于世界各地都有升级预防母婴传播的重大计划，认真评估这些抗逆转录病毒干预措施对儿童发育和成长的影响是重要的。我们建议进行一项纵向队列研究，以比较HIV和ARV感染的未感染婴儿的神经发育(ND)、神经认知(NC)、血液学和生长发育结果，以及他们60个月的生长发育和血液学参数；与具有相似社会经济和文化背景的非HIV非ARV暴露儿童的对照组进行比较。这项研究将联合招募在马拉维布兰太尔和乌干达坎帕拉进行的Promise母婴传播试验中接触艾滋病毒、ARV的未感染婴儿。对照年龄和性别匹配的健康儿童，将从Promise婴儿登记地点的健康儿童和急性护理诊所招募。在这些环境中验证的ND措施将在12个月和24个月时使用穆伦斯测试进行评估，并在60个月时使用考夫曼ABC进行NC测试；而神经学状况、血液学(CDC)和生长发育(身高、体重、头部和上中臂围)将每年收集。母亲教育和看护教育、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在子宫内和母乳喂养期间出生后接触ARV的时间。这项研究将为政策制定者和研究人员提供重要数据，以确定未感染HIV和ARV的婴儿在宫内和产后长期暴露于ARV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的政策提供信息。 公共卫生相关性：叙事这项为期5年的前瞻性研究将评估未感染抗逆转录病毒药物的婴儿的发育结果，这些婴儿参与了Promise临床试验，母亲在怀孕期间接受抗逆转录病毒药物治疗，然后母亲或婴儿在哺乳期间接受抗逆转录病毒药物治疗。这项研究将在马拉维和乌干达的临床研究地点进行。它将把这些神经发育测试结果与年龄和性别匹配、文化背景相似但没有接触抗逆转录病毒药物的儿童的研究结果进行比较。