FLOURISH - Following Longitudinal Outcomes to Understand, Report, Intervene and Sustain Health for Infants, Children, Adolescent who are HIV Exposed Uninfected

FLOURISH - 遵循纵向结果来了解、报告、干预和维持未感染艾滋病毒的婴儿、儿童、青少年的健康

• 批准号: 10064161
• 负责人: Jennifer Jao
• 金额: $ 43.12万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-17 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10064161
• 关键词: 10 year old; 15 year old; 17 year old; 3 year old; Acquired Immunodeficiency Syndrome; Adolescent; Adoption; Adverse effects; Africa South of the Sahara; Age; Anti-Retroviral Agents; Automobile Driving; Biological; Birth; Blood Pressure; Body mass index; Botswana; Breast; Caregivers; Central obesity; Cessation of life; Child; Complex; Country; Data; Databases; Discipline of obstetrics; Dyslipidemias; Enrollment; Epidemic; Epidemiologic Methods; Exposure to; Frequencies; Future; Growth; HIV; HIV antiretroviral; Health; Health Policy; Heterogeneity; High Prevalence; Home environment; Impaired fasting glycaemia; Individual; Infant; Infant Health; Institutes; Insulin Resistance; Intervention; Intervention Trial; Life Cycle Stages; Link; Maternal Health; Metabolic; Monitor; Morbidity - disease rate; Newborn Infant; Outcome; Participant; Passive Immunity; Pharmaceutical Preparations; Population; Pregnancy; Pregnant Women; Prophylactic treatment; Protease Inhibitor; Public Health; Regimen; Reporting; Research; Research Infrastructure; Risk; Risk Factors; Safety; School-Age Population; Seminal; Structure; Treatment Protocols; Woman; Work; antiretroviral therapy; cardiometabolic risk; cardiometabolism; cohort; comparison group; data harmonization; efavirenz; experience; feeding; health disparity; high risk; immune activation; improved; in utero; innovation; low and middle-income countries; mortality; neurobehavioral; prenatal exposure; recruit; response; sex; social; social structure; socioeconomics; therapy design

Project Summary/Abstract UNAIDS estimates the global population of children under 15 years of age HIV-exposed yet uninfected (CHEU) approached 15 million in 2018, and each year more than 1 million newborns continue to be HIV-exposed uninfected, the overwhelming majority of whom reside in low- and middle-income countries. Evolving public health responses have contributed to the heterogeneity of in utero exposures for CHEU. As the HIV epidemic has matured, pregnant women living with HIV (WLHIV) are accessing more potent antiretroviral regimens prior to and during pregnancy. While this has dramatically reduced infant HIV acquisition, safety monitoring of antiretroviral treatment (ART) in pregnancy has been limited. Even with exposure heterogeneity, both children and youth HEU continue to experience higher risk for poorer outcomes compared with children HIV-unexposed and uninfected (CHUU). Our work and the work of others has shown increased risk of infectious morbidity, mortality, poorer growth, altered metabolic health, and neurobehavioral delays and deficits. It is imperative that modifiable biological, social, and structural mechanisms driving these disparities be identified to inform interventions. Botswana has the 2nd highest prevalence of HIV worldwide. Yet, it was the first country in sub- Saharan Africa to provide free ART to its citizens including pregnant women, leading the continent in the response to the HIV epidemic and in adoption of new ARVs, including dolutegravir. Concurrently, Botswana – Harvard AIDS Institute Partnership (BHP) has been conducting cutting-edge research involving pregnant WLHIV and their children since 2001 when the Mashi study (R01HD37793) opened. We have captured uniform and harmonized data, including obstetric and maternal ART information, infant birth data, infant antiretroviral (ARV) prophylaxis type and duration, infant duration of breast and/or formula feeding and other socioeconomic data. Our curated database contains information on >5,000 CHEU. Leveraging our robust database, we will establish the FLOURISH cohort (Following Longitudinal Outcomes to Understand, Report, Intervene, and Sustain Health of Infants, Children and Adolescents who are HIV-Exposed Uninfected) of 1,575 child/adolescent-caregiver pairs (1100 CHEU, 475 CHUU). The FLOURISH cohort will enable us to evaluate differences in rates of infectious morbidity and all-cause mortality between CHEU and CHUU up to 3 years of age. Among school-aged children (6-10 years of age), we will assess whether in utero HIV/ARV exposure among CHEU is associated with differences in neurobehavioral functioning compared with CHUU. Lastly, among children ≥ 10 years of age, we will assess associations between in utero HIV/ARV exposure and cardiometabolic risk factors using age, sex, and body mass index (BMI)-frequency matched CHUU as a comparator. The rich breadth of well-characterized seminal BHP studies will provide a robust platform from which key scientific questions regarding life course outcomes of CHEU can be answered, informing the design of interventional trials and mechanistic studies.

项目概要/摘要 联合国艾滋病规划署估计全球 15 岁以下暴露于艾滋病毒但未感染的儿童人数 (CHEU) 2018 年接近 1500 万，每年有超过 100 万新生儿继续感染艾滋病毒 未感染者，其中绝大多数居住在低收入和中等收入国家。 随着艾滋病毒的流行，健康应对措施导致了 CHEU 子宫内暴露的异质性。 已经成熟，感染艾滋病毒（WLHIV）的孕妇正在接受更有效的抗逆转录病毒疗法 虽然这大大减少了婴儿感染艾滋病毒的机会，但安全监测 即使存在暴露异质性，两个孩子的妊娠期抗逆转录病毒治疗（ART）也很有限。 与未接触艾滋病毒的儿童相比，HEU 青年继续面临更高的结局较差风险 我们的工作和其他人的工作表明感染发病的风险增加， 死亡率、生长不良、代谢健康改变以及神经行为迟缓和缺陷。 确定导致这些差异的可改变的生物、社会和结构机制，以告知 博茨瓦纳的艾滋病毒感染率位居世界第二，但它是第一个艾滋病毒感染率较低的国家。 撒哈拉非洲地区将向包括孕妇在内的公民提供免费的抗逆转录病毒治疗，在该大陆处于领先地位 应对艾滋病毒流行并采用新的抗逆转录病毒药物，包括多替拉韦，同时，博茨瓦纳 – 哈佛艾滋病研究所合作伙伴 (BHP) 一直在开展涉及怀孕 WLHIV 的尖端研究 自 2001 年马士研究室 (R01HD37793) 开业以来，我们就捕获了制服和孩子。 统一数据，包括产科和孕产妇 ART 信息、婴儿出生数据、婴儿抗逆转录病毒 (ARV) 预防类型和持续时间、婴儿母乳和/或配方奶喂养持续时间以及其他社会经济数据。 我们精心策划的数据库包含超过 5,000 个 CHEU 的信息。利用我们强大的数据库，我们将建立。 FLOURISH 队列（根据纵向结果来理解、报告、干预和维持健康 1,575 对儿童/青少年看护者中未感染 HIV 的婴儿、儿童和青少年） (1100 CHEU, 475 CHUU) FLOURISH 队列将使我们能够评估传染率的差异。 CHEU 和 CHUU 之间 3 岁以下学龄儿童的发病率和全因死亡率。 （6-10 岁），我们将评估 CHEU 中子宫内 HIV/ARV 暴露是否与 最后，在 10 岁以上的儿童中，我们与 CHUU 相比在神经行为功能方面存在差异。 将使用年龄、性别、 和体重指数 (BMI) 频率匹配 CHUU 作为比较器的丰富广度。 必和必拓的开创性研究将提供一个强大的平台，通过该平台可以解决有关生命历程的关键科学问题 CHEU 的结果可以得到解答，为介入试验和机制研究的设计提供信息。