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).

项目总结 在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1500万，每年有100多万艾滋病毒感染/未感染(HEU)婴儿出生。 随着儿童早期死亡率和一系列医学疾病的增加，HEU儿童 包括一个脆弱的群体。特别令人担忧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。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。许多艾滋病毒项目都是 目前正在推出多洛替格雷(DTG)用于一线抗逆转录病毒治疗，尽管最近有早期信号表明 DTG从受孕开始出现神经管缺陷。然而，还没有研究评估是否在子宫内。 接触基于DTG的抗逆转录病毒药物对神经发育和/或社会- HEU儿童的情绪结果，以及EFV(或来自年龄较大的儿童)的最低数据。我们的 因此，目标如下：目标1：评估和比较发展成果 (神经发育、心理社会)宫内暴露于DTG的HEU儿童2岁时 抗逆转录病毒疗法与基于EFV的抗逆转录病毒疗法的比较；并比较HEU儿童在每种抗逆转录病毒疗法中的结局 暴露组与未接触艾滋病毒的学步儿童。目标2：对ND进行同样的比较 和目标1相同的社交-情绪结果，但在5岁时，并有额外的目标 在这些学龄儿童中评估对未来功能更具预测性的领域 (例如，执行职能)。目标3：(随着时间的推移)评估和比较抑郁、焦虑和睡眠 接受基于DTG的抗逆转录病毒疗法的妇女与基于EFV的抗逆转录病毒疗法的妇女(以及感染艾滋病毒的妇女)之间的问题分数 与艾滋病毒阴性妇女的对比)。