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

CHERISH（儿童艾滋病毒暴露未感染研究，以告知生存和健康）

• 批准号: 10249343
• 负责人: Mary-Ann Davies
• 金额: $ 33.47万
• 依托单位: STELLENBOSCH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-29 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249343
• 关键词: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Africa South of the Sahara; Age; Anti-Retroviral Agents; Biostatistical Methods; Birth; Botswana; Breast Feeding; Cessation of life; Child; Child Health; Childhood; Cohort Studies; Collaborations; Communicable Diseases; Complex; Country; Drug Exposure; Ensure; Epidemic; Epidemiologic Methods; Epidemiology; Evaluation; Exposure to; Funding; Future; Government; Growth; HIV; HIV antiretroviral; Health; Health system; High Prevalence; Home; Hospitalization; Income; Individual; Infant; Infection; Intervention; Investments; Life; Light; Link; Longitudinal cohort; Malnutrition; Measurement; Measures; Mediating; Modality; Modeling; Modernization; Monitor; Morbidity - disease rate; Mothers; National Institute of Child Health and Human Development; Nutritional; Outcome; Pathway interactions; Patients; Pharmaceutical Preparations; Population; Pregnancy; Premature Birth; Prevalence; Prevention; Province; Public Health; Research; Resources; Risk; Rural; Scientific Advances and Accomplishments; Sentinel; Site; South Africa; Southern Africa; Statistical Methods; Subgroup; System; Touch sensation; United States; United States National Institutes of Health; Universities; Woman; adverse birth outcomes; antenatal; antiretroviral therapy; base; cohort; data centers; design; disparities in morbidity; early childhood; feeding; follow-up; health data; in utero; infancy; innovation; medication safety; multiple data sources; neurodevelopment; novel; pediatric human immunodeficiency virus; postnatal; prenatal exposure; socioeconomics; success; survival disparity; trend

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.

项目概要 尽管南非有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估暴露于环境中的儿童的结果 子宫内的艾滋病毒和抗逆转录病毒药物。通过严格的流行病学观察和现代生物统计学 方法，CHERISH 研究（儿童艾滋病毒暴露未感染研究以告知生存和健康） 提供了一个机会来确定是否在人口和个人层面上生存、住院、 HEU 儿童和 HIV 儿童的生长和神经发育结果相同 普遍孕产妇抗逆转录病毒治疗时代的未暴露未感染（HUU）。在西开普省 南非省的孕产妇产前艾滋病毒感染率为 19%，西开普省 健康数据中心根据独特的方式整理来自多个来源的与个人相关的电子健康数据 患者标识符与母婴唯一标识符的常规出生关联。我们将利用这一点 资源并以 NIH 在西开普省现有投资为基础，建立西开普省 - 2018-2024 年的广泛出生队列（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 & R33 ±450）和动态轻触队列（R61 ±450； R33 ±1,800)。具体来说，我们建议在 R61 期间建立和优化可持续衡量标准 西开普省 HEU 和 HUU 儿童的子宫内和产后暴露和结局的关键 4个层面：全省人口队列；城市和农村哨点（由 NIH 资助直至 2020 年，将通过 CHERISH 进行扩展）；静态详细城市队列（NICHD 资助的 B 阳性队列， 后续行动将通过 CHERISH 延长）；充满活力的轻触城市和乡村群体（即将成为新的 由 CHERISH 建立）。在 R33 期间，我们将利用这些群体来实现三个科学目标： 比较 1) 婴儿和 3 岁以下存活率，2) 婴儿和 3 岁以下全因和感染原因存活率 住院治疗以及 3) HEU 儿童 3-5 岁时的生长和神经发育结果 和HUU；此外，对于每个目标，我们将确定适合干预的因素来调节效果 HIV 和 ARV 暴露对生存、住院、生长和神经发育的影响。全省范围内 队列将告知艾滋病毒/抗逆转录病毒暴露对儿童生存和发病率的人群影响 与 HUU 相比，HEU 中的哪些人具有相似的社会经济、营养和环境健康限制 在艾滋病毒高流行环境中。哨点、静态和动态队列将应用先进的统计 确定 HEU 儿童存活率和发病率的因果路径和亚组的方法 差异，为艾滋病毒高流行地区卫生系统可行的有针对性的干预措施的设计提供信息 设置。这提供了一个可持续的、创新的和足够规模的队列模型，该模型具有适度的持续性 投资可以持续积累母子配对，终身跟进和评估机会 随着流行病的发展，子宫内艾滋病毒暴露及其预防和治疗方式的变化。