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: 10657825
• 负责人: Jennifer Jao
• 金额: $ 61.28万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657825
• 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; Body mass index; Botswana; Breast; Caregivers; Central obesity; Cessation of life; Child; Child Care; Complex; Country; Data; Databases; Discipline of obstetrics; Disparity; Dyslipidemias; Enrollment; Epidemic; Epidemiologic Methods; Exposure to; Frequencies; Future; Growth; HIV; Health; Health Policy; Heterogeneity; High Prevalence; Home; Impaired fasting glycaemia; Individual; Infant; Infant Health; 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; Youth; antiretroviral therapy; blood pressure elevation; 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; 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.

项目摘要/摘要 联合国艾滋病规划署估计全球15岁以下儿童感染艾滋病毒但未感染的人口(CHEU) 2018年接近1500万，每年有100多万新生儿继续感染艾滋病毒 他们中的绝大多数人居住在低收入和中等收入国家。不断发展的公众 健康反应导致CHU宫内暴露的异质性。随着艾滋病毒的流行 已经成熟，孕妇携带艾滋病毒(WLHIV)正在获得更有效的抗逆转录病毒方案 怀孕前和怀孕期间。虽然这大大减少了婴儿感染艾滋病毒的机会，但安全监测 妊娠期间的抗逆转录病毒治疗(ART)一直受到限制。即使有暴露的异质性，两个孩子 与未接触艾滋病毒的儿童相比，青年HEU继续经历较差结局的更高风险 和未感染(CHUU)。我们的工作和其他人的工作表明，感染发病率的风险增加了， 死亡率、生长不良、新陈代谢健康改变、神经行为延迟和缺陷。当务之急是 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 干预措施。博茨瓦纳的艾滋病毒流行率在世界上排名第二。然而，它是世界上第一个 撒哈拉非洲向包括孕妇在内的公民提供免费艺术，引领非洲大陆 应对艾滋病毒流行和采用新的抗逆转录病毒药物，包括多洛替格列韦。同时，博茨瓦纳- 哈佛大学艾滋病研究所伙伴关系(BHP)一直在进行涉及怀孕WLHIV的尖端研究 和他们的孩子，自2001年马什书房(R01HD37793)开学以来。我们已经捕获了制服和 统一数据，包括产科和产妇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、婴儿哺乳和/或配方奶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有关&gt；5,000 Cheu的信息。利用我们强大的数据库，我们将建立 蓬勃发展的队列(跟踪纵向结果以了解、报告、干预和维持健康 未感染艾滋病毒的婴儿、儿童和青少年)1,575对儿童/青少年-照料者 (1100 CHU，475 CHU)。活跃的队列将使我们能够评估感染率的差异 CHU和CHU在3岁以下的发病率和全因死亡率。在学龄儿童中 (6-10岁)，我们将评估宫内暴露在CHU中的艾滋病毒/ARV是否与 神经行为功能与CHU相比有差异。最后，在≥10岁的儿童中，我们 将评估子宫内HIV/ARV暴露与心脏代谢危险因素之间的关系，使用年龄，性别， 并以体重指数(BMI)-频率匹配的CHUU为比较对象。丰富多彩的人物形象 开创性的必和必拓研究将提供一个强大的平台，从这个平台上可以解决关于生命过程的关键科学问题 CHEU的结果是可以回答的，为介入试验和机制研究的设计提供了信息。