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: 10876119
• 负责人: Mary-Ann Davies
• 金额: $ 51.95万
• 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 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10876119
• 关键词: 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; Disparity; Drug Exposure; Electronics; Ensure; Epidemic; Epidemiologic Methods; Epidemiology; Evaluation; Exposure to; Funding; Future; Government; Growth; HIV; HIV/AIDS; 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; Observational epidemiology; 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; 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; syndemic; 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.

项目摘要 尽管南非有五分之一以上的儿童暴露于艾滋病毒而未感染（HEU）， 在南非建立系统，以可持续的长期方式评估儿童接触 艾滋病毒和抗逆转录病毒药物在子宫内。通过严格的观察流行病学和现代生物统计学 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，以确定是否在人口和个人水平的生存，住院， 高浓缩铀儿童和艾滋病毒儿童的生长和神经发育结果相当 在普及孕产妇抗逆转录病毒治疗的时代，未受感染的未暴露者（HUU）。在西开普 南非西开普省孕产妇产前艾滋病毒感染率为19% 健康数据中心根据独特的 患者标识符与产妇和婴儿唯一标识符的常规出生联系。我们会利用这个 资源和建立在现有的NIH投资在西开普省建立西开普省- 2018-2024年出生的广泛队列（R61 ± 360，000; R33 ± 585，000），与两个哨兵站点（R61）同步 ± 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 ± 1，800）。具体而言，我们建议在R61期间建立和优化可持续的测量 西开普省使用高浓缩铀和高浓缩铀的儿童在子宫内和产后的主要接触情况和结果 在4个级别：全省范围的人口队列;城市和农村哨点（由NIH资助， 2020年，将通过CHERISH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扩展）;动态的轻度接触城市和农村队列（将通过CHERISH扩展）; 由CHERISH建立）。在R33期间，我们将利用这些群体追求三个科学目标： 比较1）婴儿和3年以下生存率，2）婴儿和3年以下全因和感染性疾病 住院治疗和3）高浓缩铀儿童3-5岁时的生长和神经发育结果 此外，对于每个目标，我们将确定易于干预的因素，这些因素介导了这些影响 艾滋病毒和抗逆转录病毒药物暴露对生存、住院、生长和神经发育的影响。全省范围 队列将告知艾滋病毒/抗逆转录病毒药物暴露对儿童存活率和儿童发病率的人口影响 高浓缩铀与高浓缩铀相比，具有类似的社会经济、营养和环境健康制约因素 在艾滋病高流行率的环境中。哨兵网站，静态和动态队列将应用先进的统计 确定高浓缩铀儿童存活率和发病率的因果途径和亚组的方法 在艾滋病毒高流行率地区，为卫生系统设计可行的有针对性的干预措施提供信息的差距 设置.这提出了一个可持续的，创新的和适当规模的队列模型， 投资可以继续积累母子配对，并提供终身跟踪和评估机会， 随着艾滋病的发展，子宫内感染艾滋病毒及其预防和治疗方式的变化。