CHERISH (Children HIV Exposed Uninfected Research to Inform Survival and Health)

项目摘要 尽管南非超过五分之一的儿童未感染艾滋病毒(HEU)，但没有 南非的系统，以可持续的长期方式评价儿童受感染的后果 子宫内的艾滋病毒和抗逆转录病毒药物。通过严格的观察流行病学和现代生物统计学 方法，珍爱研究(儿童艾滋病毒暴露于未感染的研究，告知生存和健康) 提供了一个机会来确定在人群和个人层面上生存、住院、 HEU儿童和HIV儿童的生长和神经发育结果是相同的 未暴露的未感染(HUU)在普遍的孕产妇抗逆转录病毒治疗时代。在西开普省 南非的西开普省，产妇产前艾滋病毒感染率为19% 健康数据中心根据独特的数据管理来自多个来源的电子个人链接健康数据 患者识别符与母婴常规出生关联的唯一识别符。我们将利用这一点 利用NIH在西开普省的现有投资资源，建立一个西开普省- 2018-2024年出生的广泛队列(R61±360,000；R33±585,000)，与两个哨点同步(R61 ±36,000；R33±58,500)，静态详细队列(R61和R33±450)和动态轻触队列(R61±450； R33±1800)。具体地说，我们建议在R61期间建立和优化可持续衡量 西开普省HEU和HUU儿童宫内和产后暴露和结局的关键因素 在4个级别：全省人口队列；城市和农村哨所(由国立卫生研究院资助，直至 2020年，将通过HERISE扩大)；静态详细的城市队列(NICHD资助的B-阳性队列， 后续行动通过珍视延伸)；动态轻触城乡队列(新 由珍爱建立)。在R33期间，我们将利用这些群体来追求三个科学目标： 比较1)婴儿和3岁以下的存活率，2)婴儿和3岁以下的全因和感染性原因 住院和3)3-5岁HEU儿童的生长和神经发育结果 和HUU；此外，对于每个目标，我们将确定适合于干预的因素，以调节效果 艾滋病毒和抗逆转录病毒暴露对生存、住院、生长和神经发育的影响。全省范围内 队列将通报艾滋病毒/抗逆转录病毒感染对儿童存活率和儿童发病率的人群影响 与具有相似的社会经济、营养和环境对健康的限制的HUU相比，谁是HEU 在艾滋病毒高流行的环境中。哨点现场、静态和动态队列将应用高级统计 方法确定HEU儿童存活率和发病率的原因路径和亚组 差异，以便为艾滋病毒高发区卫生系统可行的针对性干预措施的设计提供信息 设置。这提供了一个可持续、创新且规模足够大的队列模式，该模式正在适度进行 投资可以继续积累母婴配对，终身跟踪并有机会进行评估 随着疫情的演变，宫内暴露于艾滋病毒及其预防和治疗方式的变化。

Project Summary Despite more than one in five children in South Africa being HIV exposed uninfected (HEU), there are no systems in South Africa to evaluate in a sustainable long-term manner the outcomes of children exposed to HIV and antiretroviral drugs in utero. Through rigorous observational epidemiologic and modern biostatistical methods, the CHERISH study (Children HIV Exposed Uninfected Research to Inform Survival and Health) presents an opportunity to determine whether at a population and individual level survival, hospitalization, growth and neurodevelopmental outcomes are equivalent in children who are HEU and children who are HIV unexposed uninfected (HUU) in the era of universal maternal antiretroviral therapy. In the Western Cape Province of South Africa, where maternal antenatal HIV prevalence is 19%, the Western Cape Provincial Health Data Center curates electronic individual-linked health data from multiple sources according to unique patient identifiers with routine birth linkage of maternal and infant unique identifiers. We will leverage this resource and build on existing NIH investments in the Western Cape to establish a Western Cape province- wide cohort of births from 2018-2024 (R61 ±360,000; R33 ±585,000), in synchrony with two sentinel-sites (R61 ±36,000; R33 ±58,500), a static detailed cohort (R61 & R33 ±450) and dynamic light-touch cohort (R61 ±450; R33 ±1,800). Specifically we propose during the R61 to establish and optimize sustainable measurement of key in utero and postnatal exposures and outcomes in children who are HEU and HUU in the Western Cape at 4 levels: province-wide population cohort; urban and rural sentinel sites (supported by NIH funding until 2020, to be expanded through CHERISH); static detailed urban cohort (NICHD-funded B-Positive cohort, follow-up to be extended through CHERISH); dynamic light-touch urban and rural cohorts (to be newly established by CHERISH). During the R33 we will harness these cohorts to pursue three scientific aims: to compare 1) infant and under 3-year survival, 2) infant and under 3-year all-cause and infectious-cause hospitalization and 3) growth and neurodevelopmental outcomes at age 3-5 years in children who are HEU and HUU; Furthermore, for each aim we will identify factors amenable to intervention that mediate the effects of HIV and ARV exposure on survival, hospitalization, growth and neurodevelopment. The province-wide cohort will inform the population-level impact of HIV/ARV-exposure on child survival and morbidity in children who are HEU compared to HUU with similar socioeconomic, nutritional and environmental constraints to health in an HIV high-prevalence setting. The sentinel-site, static and dynamic cohorts will apply advanced statistical methods to identify causal pathways and sub-groups of children who are HEU with survival and morbidity disparities to inform design of targeted interventions feasible for health systems in HIV high prevalence settings. This presents a sustainable, innovative and adequately sized cohort model that with modest ongoing investment can continue to accumulate mother-child pairs with lifelong follow-up and opportunities to evaluate changes in in utero exposure to HIV and its prevention and treatment modalities as the epidemic evolves.