Clinical outcomes of HIV-exposed uninfected children during mid-childhood in rural Zimbabwe

项目总结 撒哈拉以南非洲感染艾滋病毒(HEU)的儿童在头两年的健康状况较差 比未接触艾滋病毒的未感染(HUU)儿童的寿命更长，死亡率更高，疾病发作更多，更贫穷 生长发育和认知发展受损。然而，目前仍不确定这些差距是否会像 儿童进入学校，以及早期生活中潜在的原因是什么。健康、成长和精神障碍 神经发育可能是多因素的，包括艾滋病毒特有的风险因素，如接触 孕产妇病毒血症和抗逆转录病毒药物，以及普遍的风险因素，如贫困、低出生体重和 母性抑郁症。这项提议充分利用了津巴布韦农村现有的HEU和HUU儿童群体， 他们从早孕到2岁都很有特点，现在7岁了。这个 这项提案的目标是，首先了解健康差异是否在学龄期持续存在， 对HEU和HUU的生长、身体和认知功能进行全面评估 第二，通过以下方式确定早期生活中的潜在原因网络 利用从怀孕早期到2岁之间的“暴露”测量的丰富数据集。 在这笔赠款的第一阶段(61 R61)，900名儿童参加了队列，之前纵向跟踪了 在津巴布韦农村进行的卫生卫生婴儿营养功效(SHEAR)试验，将由一个网络确定 村卫生工作者(VHW)，并在7岁时重新登记。所有参加SIRE的HEU儿童 将从整个农村地区确定(N=300)，并且对于每个登记的HEU儿童，匹配2个HUU儿童 将根据年龄、性别和分组进行选择(N=600)。艾滋病毒暴露和感染状况、社会环境、 将更新母婴配对的重大逆境和病史，并将每个孩子链接到 关于从怀孕到2岁的生物、社会和环境暴露的现有元数据。一个 整体基线评估将比较HEU和HUU的生长、身体和认知功能 儿童，队列将开始每月由vHW进行前瞻性健康监测，以确定急性疾病， 实时就诊和住院事件。在R61阶段结束时，学龄差距 将描述HEU和HUU儿童之间的生长、身体和认知功能，并 与这些差异相关的早期生活因素被识别出来。在第二阶段(R33)，每月展望 VHW将继续进行健康监测，并对生长发育、身体和认知功能进行年度评估 将进行(储存生物标本)，以查明高浓缩铀和高浓缩铀之间的纵向差距。 9岁、10岁和11岁的胡族儿童，以及与这些结果相关的早期暴露。一个 由300名儿童组成的小组(150名HEU和150名HUU)将接受认知功能、心理和心理的深入表型 健康，身体成分，新陈代谢健康，炎症和慢性并存，使用一系列切割- EDGE技术，提供对HEU儿童在儿童期中期的功能能力的详细见解。

Project summary HIV-exposed uninfected (HEU) children in sub-Saharan Africa have poorer health outcomes in the first 2 years of life than HIV-unexposed uninfected (HUU) children, with higher mortality, more illness episodes, poorer growth and impaired cognitive development. However, it remains uncertain whether these disparities persist as children enter school, and what the underlying causes are in early life. Impairments in health, growth and neurodevelopment are likely multifactorial, including both HIV-specific risk factors such as exposure to maternal viremia and antiretroviral drugs, and universal risk factors such as poverty, low birth weight and maternal depression. This proposal leverages an existing cohort of HEU and HUU children in rural Zimbabwe, who were well characterized from early pregnancy to 2 years of age, and are now turning 7 years old. The goal of this proposal is, first, to understand whether health differences persist at school-age, by undertaking holistic assessments of the growth, physical and cognitive function of HEU and HUU children in mid-childhood and, second, to identify the network of underlying causes in early life, by leveraging the rich dataset of `exposome' measurements between early pregnancy and 2 years of age. In the first phase of this grant (R61), a cohort of 900 children, previously followed longitudinally in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe, will be identified by a network of Village Health Workers (VHW) and re-enrolled at 7 years of age. All HEU children who participated in SHINE from an entire rural district will be identified (N=300), and for each enrolled HEU child, 2 HUU children matched on age, sex and cluster will be selected (N=600). HIV exposure and infection status, social circumstances, major adversities and medical history of mother-child pairs will be updated, and each child will be linked to existing meta-data on biological, social and environmental exposures from pregnancy to 2 years of age. A holistic baseline assessment will compare growth, physical and cognitive function between HEU and HUU children, and the cohort will begin monthly prospective health surveillance by VHW to identify acute illness, clinic visits and hospitalization episodes in real-time. At the end of the R61 phase, disparities in school-age growth, physical and cognitive function between HEU and HUU children will have been characterized, and the early-life factors associated with these differences identified. In the second phase (R33), monthly prospective health surveillance by VHW will continue, and an annual assessment of growth, physical and cognitive function (with storage of biological specimens) will be undertaken, to identify longitudinal disparities between HEU and HUU children at ages 9, 10 and 11 years, and the early-life exposures associated with these outcomes. A subgroup of 300 children (150 HEU and 150 HUU) will undergo deep phenotyping of cognitive function, mental health, body composition, metabolic health, inflammation and chronic comorbidities using a range of cutting- edge techniques, to provide detailed insights into the functional capacity of HEU children in mid-childhood.