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

项目概要/摘要 联合国艾滋病规划署估计，全球15岁以下儿童暴露于艾滋病毒但未感染（CHEU） 2018年接近1500万，每年有100多万新生儿继续暴露于艾滋病毒 未受感染者，其中绝大多数居住在低收入和中等收入国家。发展中的公众 健康应对措施导致了子宫内接触CHEU的异质性。随着艾滋病的流行 艾滋病毒感染者（WLHIV）的孕妇正在获得更有效的抗逆转录病毒治疗， 在怀孕期间和怀孕期间虽然这大大减少了婴儿感染艾滋病毒的情况，但对婴儿的安全监测仍然存在问题。 怀孕期间的抗逆转录病毒治疗有限。即使暴露异质性，两个孩子 与未接触艾滋病毒的儿童相比， 未感染（CHU）。我们的工作和其他人的工作表明，传染病发病的风险增加， 死亡率、生长不良、代谢健康改变以及神经行为延迟和缺陷。当务之急是 可改变的生物，社会和结构机制驱动这些差异被确定，以告知 干预措施。博茨瓦纳是世界上艾滋病毒感染率第二高的国家。然而，这是第一个国家在次- 撒哈拉非洲向包括孕妇在内的公民提供免费抗逆转录病毒治疗， 艾滋病毒的流行和采用新的抗逆转录病毒药物，包括度鲁特韦。同时，博茨瓦纳- 哈佛艾滋病研究所伙伴关系（BHP）一直在进行涉及怀孕的WLHIV的尖端研究 自2001年Mashi研究（R 01 HD 37793）开始，我们已经抓获了制服和 统一的数据，包括产科和孕产妇抗逆转录病毒治疗信息、婴儿出生数据、婴儿抗逆转录病毒药物 预防类型和持续时间、母乳和/或配方奶喂养的婴儿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 CHEU的信息。利用我们强大的数据库， FLOURISH队列（跟踪纵向结果以了解、报告、干预和维持健康） 1，575对儿童/未受感染者-照顾者的婴儿、儿童和青少年中 (1100 CHEU，475 CHUU）. FLOURISH队列将使我们能够评估感染率的差异， CHEU和CHIU之间3岁以下的发病率和全因死亡率。学龄儿童 (6-10年龄），我们将评估CHEU中子宫内HIV/ARV暴露是否与 与CHU相比，神经行为功能的差异。最后，在10岁以上的儿童中，我们 将使用年龄、性别、 和体重指数（BMI）-频率匹配的CHIU作为对照。丰富的广度， 必和必拓的开创性研究将提供一个强大的平台， CHEU的结果可以得到回答，为干预性试验和机制研究的设计提供信息。

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.