Neurocognitive development of HIV-exposed and uninfected infants in Malawi

项目摘要 在撒哈拉以南非洲，每年有100多万名儿童出生，他们可能感染艾滋病毒，但未受感染 随着抗逆转录病毒治疗（ART）的普及，这一人群将继续增加。在子宫内 艾滋病毒暴露具有广泛的健康影响，新的数据表明，CHEU有更高的风险， 与未暴露儿童相比，神经认知延迟。但生物因素，心理社会因素 环境和母婴互动对这一延迟的影响仍然不清楚。该提案将采取 评估宫内HIV暴露对神经认知功能影响的独特机会的优势 我们正在马拉维进行的一项临床研究的背景下，我们在筛选 孕妇，登记婴儿，并在三个新生儿适应性免疫进行免疫学分析， 类别：（1）CHEU出生的妇女诊断艾滋病毒在第一次产前检查，因此暴露于不受控制的 至少妊娠一半的病毒血症;（2）CHEU出生于妊娠前开始接受ART的女性， 检测不到的病毒载量;（3）未感染HIV的母亲所生的婴儿。我们采集脐带血单核细胞 细胞进行详细的免疫分析。在本提案中，我们将增加样本量， 脐带血标本单核细胞活化综合评估和这些婴儿的长期随访 到五岁。我们的目标是对神经认知功能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、艾滋病毒污名， 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一项关于 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 神经认知发展的影响我们假设在子宫内暴露于艾滋病毒会损害神经认知能力， 艾滋病毒感染母亲未经治疗而生下的儿童 在怀孕开始时，艾滋病毒携带者的孩子比艾滋病毒载量检测不到的母亲的孩子更晚。 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的社区卫生股的福祉。

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.