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: 9927169
• 负责人: Adam Robert Cassidy
• 金额: $ 59.58万
• 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/9927169
• 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; combat; 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 在子宫内暴露于艾滋病毒和抗逆转录病毒疗法后出生的未感染艾滋病毒的儿童的全球人口 增长到约1 500万人，每年有100多万婴儿出生时接触/未感染艾滋病毒。 随着幼儿死亡率和一系列内科疾病的增加， 包括弱势群体。特别值得关注的是缺乏神经发育和 在子宫内暴露于一些最常见的- 使用母体抗逆转录病毒疗法。依法韦仑（EFV）是全球使用最广泛的抗逆转录病毒药物之一， 包括怀孕或可能怀孕的妇女。许多艾滋病毒项目 目前正在推出度鲁特韦（DTG）用于一线ART，尽管最近的早期信号， 从受孕开始就有DTG神经管缺陷。然而，没有研究评估是否在子宫内 暴露于基于DTG的ART对神经发育和/或社会- 高浓度铀儿童的情绪结果，EFV（或年龄较大的儿童）的数据很少。我们 目标1：评估和比较发展成果 在子宫内接触DTG的高浓缩铀儿童2岁时的神经发育、心理社会学 抗逆转录病毒药物与以EFV为基础的抗逆转录病毒药物;并比较每种抗逆转录病毒药物治疗高浓缩铀儿童的结果 暴露组与未暴露于艾滋病毒的幼儿。目的2：对ND进行相同的比较 目标1中的社会情感结果，但在5岁时，并有额外的针对性 在这些学龄儿童中评估更能预测未来功能的领域 (e.g.,执行功能）。目的3：评估（随着时间的推移）和比较抑郁，焦虑和睡眠 接受基于DTG的ART与基于EFV的ART的女性（以及艾滋病毒感染女性）的问题评分 vs.艾滋病毒阴性妇女）。