Neurocognitive development of HIV-exposed and uninfected infants in Malawi

马拉维暴露于艾滋病毒和未感染艾滋病毒的婴儿的神经认知发育

• 批准号: 10424474
• 负责人: Melissa Gladstone
• 金额: $ 59.66万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10424474
• 关键词: 2 year old; 5 year old; Address; Africa South of the Sahara; Age-Months; Biological Factors; Birth; Blood specimen; Caring; Categories; Cells; Child; Child Development; Child Health; Child Welfare; Childhood; Clinical Research; Communicable Diseases; Conceptions; Data; Development; Diagnosis; Domestic Violence; Enrollment; Environment; Environmental Risk Factor; Evaluation; Exposure to; Family; Flow Cytometry; Future; Goals; HIV; HIV Antigens; HIV Infections; HIV-exposed uninfected infant; Health; Home environment; Immunologics; Immunologist; Impairment; Improve Access; Infant; Infection; Inflammation; Interdisciplinary Study; Intervention; Lead; Life; Link; Long-Term Effects; Malawi; Measures; Mental Depression; Mental Health; Methods; Mononuclear; Mother-Child Relations; Mothers; Neonatal; Neurocognitive; Neurocognitive Deficit; Neurological outcome; Outcome Assessment; Personal Satisfaction; Population; Pregnancy; Pregnant Women; Prior Therapy; Psychosocial Assessment and Care; Psychosocial Factor; Resource-limited setting; Risk; Sample Size; Scientist; Social support; Socioeconomic Factors; Socioeconomic Status; Specialist; Standardization; T-Lymphocyte; Treatment/Psychosocial Effects; Umbilical Cord Blood; Vertical Disease Transmission; Viral Load result; Viremia; Visit; Vulnerable Populations; Woman; adaptive immunity; antenatal; antiretroviral therapy; cohort; effective intervention; experience; experimental study; follow-up; high risk; immune activation; immunological status; improved; in utero; maternal depression; maternal stress; monocyte; pediatrician; postnatal; prenatal exposure; psychosocial; psychosocial stressors; screening; social; social stigma; therapy development

PROJECT SUMMARY Every year, over a million children who are HIV-exposed but uninfected (CHEU) are born in sub-Saharan Africa and this population will continue to increase with improving availability of antiretroviral therapy (ART). In utero HIV exposure has broad ranging health impacts and emerging data suggest that CHEU have higher risk of neurocognitive delay compared to unexposed children. But the contribution of biological factors, the psychosocial environment and maternal-child interactions to this delay remains poorly characterized. This proposal will take advantage of the unique opportunity to evaluate the impact of in utero HIV exposure on neurocognitive development in children in the context of an ongoing clinical study we are conducting in Malawi. We are screening pregnant women, enrolling infants and conducting immunological analysis of neonatal adaptive immunity in three categories: (1) CHEU born to women diagnosed with HIV at the first antenatal visit, thus exposed to uncontrolled viremia for at least half of gestation; (2) CHEU born to women initiated on ART prior to conception with undetectable viral loads; and (3) infants born to HIV uninfected mothers. We collect cord blood mononuclear cells at birth to conduct a detailed immunological analysis. In this proposal, we will increase our sample size, incorporate assessment of monocyte activation from cord blood specimens and extend follow up of these infants to five years of age. Our goal is to conduct rigorously validated longitudinal assessments of neurocognitive development and psychosocial factors including maternal mental health, socioeconomic status, HIV stigma, home environment and mother-child interactions. Our interdisciplinary study team of infectious disease specialists, developmental pediatricians, social scientists and immunologists will lead one of the first studies of CHEU in resource-limited settings to simultaneously address the impact of biological and psychosocial factors on neurocognitive development. We hypothesize that in utero exposure to HIV will impair neurocognitive development in the first five years of life and children born to HIV-infected mothers with untreated HIV infection at the start of pregnancy will demonstrate more delay than children of mothers with undetectable HIV viral load throughout pregnancy. We further hypothesize that both immunological status at birth and psychosocial factors will contribute to impaired neurocognitive development in CHEU. This study will provide detailed evidence to develop interventions to improve the well-being of CHEU in resource-limited settings.

项目概要 每年，撒哈拉以南非洲地区出生的儿童有超过一百万暴露于艾滋病毒但未感染的儿童 (CHEU) 随着抗逆转录病毒治疗（ART）的可用性的提高，这一人群将继续增加。在子宫内 接触 HIV 会对健康产生广泛的影响，新出现的数据表明 CHEU 的感染风险较高 与未暴露的儿童相比，神经认知延迟。但生物因素、社会心理因素的贡献 环境和母婴互动对这种延迟的影响仍然不明确。该提案将采取 利用独特的机会来评估子宫内艾滋病毒暴露对神经认知的影响 我们正在马拉维进行一项正在进行的临床研究，以了解儿童的发育情况。我们正在筛选 孕妇、婴儿入组并对三组新生儿进行新生儿适应性免疫的免疫学分析 类别： (1) CHEU 是在第一次产前检查时被诊断出感染艾滋病毒的妇女所生的，因此暴露在不受控制的环境中 至少一半妊娠期存在病毒血症； (2) 受孕前接受 ART 治疗的妇女所生的 CHEU 无法检测到的病毒载量； (3) 未感染艾滋病毒的母亲所生的婴儿。我们采集脐带血单核 细胞在出生时进行详细的免疫学分析。在这个提案中，我们将增加样本量， 纳入脐带血样本中单核细胞活化的评估并延长对这些婴儿的随访 至五岁。我们的目标是对神经认知进行严格验证的纵向评估 发展和心理社会因素，包括孕产妇心理健康、社会经济地位、艾滋病毒耻辱、 家庭环境和母子互动。我们的传染病跨学科研究团队 专家、发育儿科医生、社会科学家和免疫学家将领导首批研究之一 CHEU 在资源有限的环境中同时解决生物和心理社会因素的影响 关于神经认知发展。我们假设在子宫内接触艾滋病毒会损害神经认知 生命头五年的发育以及未经治疗的艾滋病毒感染母亲所生的孩子 与艾滋病病毒载量无法检测到的母亲的孩子相比，在怀孕初期的孩子会表现出更多的延迟 整个怀孕期间。我们进一步假设出生时的免疫状态和心理社会因素 将导致 CHEU 神经认知发育受损。这项研究将提供详细的证据 制定干预措施以改善资源有限环境中 CHEU 的福祉。