Neurodevelopment In HEU Children Exposed In Utero To Dolutegravir Or Efavirenz

子宫内暴露于多替拉韦或依非韦伦的 HEU 儿童的神经发育

• 批准号: 10192838
• 负责人: Adam Robert Cassidy
• 金额: $ 56.35万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10192838
• 关键词: 2 year old; 5 year old; AIDS/HIV problem; Achievement; Address; Affect; Africa South of the Sahara; Age; Anti-Retroviral Agents; Anxiety; Blood specimen; Botswana; Breast Feeding; Characteristics; Child; Child Development; Clinical; Cognitive; Communities; Conceptions; Country; Data; Deterioration; Development; Drops; Emotional; Epidemic; Evaluation; Exposure to; Fetus; Future; Goals; Guidelines; HIV; HIV Seronegativity; HIV antiretroviral; HIV-exposed uninfected infant; Health; Individual; Infant; Life; Longitudinal Studies; Medical; Mental Depression; Mental Health; Modernization; Morbidity - disease rate; Mother-to-child HIV transmission; Mothers; Neural Tube Defects; Neurodevelopmental Deficit; Neurologic Effect; Nursery Schools; Outcome; Pharmaceutical Preparations; Population; Positioning Attribute; Pregnancy; Prevention; Protocols documentation; Public Health; Recommendation; Regimen; Research; Resources; Risk; School-Age Population; Severities; Short-Term Memory; Sleep; Sleep Disorders; Tenofovir; Testing; Time; Toddler; Treatment Protocols; Visit; Vulnerable Populations; Woman; World Health Organization; aged; antiretroviral therapy; anxiety symptoms; base; depressive symptoms; early childhood; efavirenz; emtricitabine; executive function; experience; flexibility; in utero; infancy; instrument; mortality; neurodevelopment; neuropsychiatry; neurotransmission; pediatric human immunodeficiency virus infection; pregnant; prenatal exposure; programs; psychosocial; recruit; resilience; side effect; skills; social; sociodemographics; success

PROJECT SUMMARY The global population of HIV-uninfected children born following in utero exposure to HIV and ART has grown to ~15 million, with more than 1 million HIV-exposed/uninfected (HEU) babies born each year. With increased rates of early-childhood mortality and a range of medical morbidities, HEU children comprise a vulnerable population. Of particular concern is the lack of neurodevelopmental and social-emotional outcomes data following in utero exposure to some of the most commonly- used maternal ARV regimens. Efavirenz (EFV) is one of the most widely-used ARVs worldwide, including among women who are pregnant or may become pregnant. Many HIV programs are currently rolling out dolutegravir (DTG) for use in first-line ART, despite the recent early signal for neural tube defects with DTG from conception. However, no studies have evaluated whether in utero exposure to DTG-based ART poses an independent threat to neurodevelopmental and/or social- emotional outcomes in HEU children, and minimal data exist for EFV (or from older children). Our aims are thus as follows: Aim 1: To assess and compare developmental outcomes (neurodevelopment, psychosocial) at 2 years of age in HEU children exposed in utero to DTG-based ARV vs. EFV-based ART; and to compare outcomes between HEU children in each of these ARV exposure groups vs. HIV-unexposed toddlers. Aim 2: To undertake the same comparisons of ND and social-emotional outcomes as in Aim 1, but at 5 years of age, and with additional targeted assessment in these school-age children of domains that are more predictive of future functioning (e.g., executive function). Aim 3: To assess (over time) and compare depression, anxiety, and sleep problem scores in women taking DTG-based ART vs. EFV-based ART (and women living with HIV vs. HIV-negative women).

项目摘要 在子宫暴露于艾滋病毒和艺术的艾滋病毒未感染儿童的全球人口 每年出生的艾滋病毒暴露/未感染（HEU）的婴儿超过1500万。 随着早期死亡率和一系列医疗病毒的增加，HEU儿童 包括一个脆弱的人群。特别关心的是缺乏神经发育和 社会情感结果在子宫暴露于一些最常见的情况下的数据 - 使用的母体ARV方案。 Efavirenz（EFV）是全球最广泛使用的ARV之一， 包括怀孕或可能怀孕的妇女。许多艾滋病毒计划是 目前，尽管最近有早期信号 神经管缺陷与概念的DTG。但是，尚无研究评估子宫中是否 接触基于DTG的艺术对神经发育和/或社会构成独立威胁 - HEU儿童的情感结果，EFV（或来自大孩子）的数据最少。我们的 因此目的如下：目标1：评估和比较发展结果 （神经发育，社会心理）在2岁的HEU儿童中暴露于基于DTG的儿童 ARV与基于EFV的艺术；并比较在每个ARV中的HEU儿童之间的结果 暴露组与无暴露的幼儿。目标2：进行相同的ND比较 和AIM 1中的社会情感成果，但在5岁时，还有其他针对性的 在这些学龄儿童中评估领域，这些领域更可预测未来功能 （例如，执行功能）。目标3：评估（随着时间的时间）并比较抑郁，焦虑和睡眠 以DTG为基于DTG的艺术与EFV的艺术（以及艾滋病毒的妇女）的女性问题评分 与艾滋病毒阴性妇女）。