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

基本信息

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
项目类别：
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

项目摘要

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).

项目概要全球在子宫内接触艾滋病毒和抗逆转录病毒治疗后出生的未感染艾滋病毒的儿童数量增长到约 1500 万，每年有超过 100 万艾滋病毒暴露/未感染 (HEU) 婴儿出生。随着幼儿死亡率和一系列医疗疾病的增加，HEU 儿童包括弱势群体。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因素后的社会情绪结果数据母亲使用抗逆转录病毒疗法。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。许多艾滋病毒项目尽管最近有早期信号表明，目前正在推出多替拉韦 (DTG) 用于一线 ART 从受孕开始就出现 DTG 神经管缺陷。然而，尚无研究评估是否在子宫内接触基于 DTG 的 ART 对神经发育和/或社会发育构成独立威胁 HEU 儿童的情绪结果，EFV（或年龄较大儿童）的数据很少。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）2 岁时在子宫内接触基于 DTG 的 HEU 儿童 ARV 与基于 EFV 的 ART；并比较 HEU 儿童接受每种抗逆转录病毒疗法的结果暴露组与未暴露于艾滋病毒的幼儿。目标 2：对 ND 进行相同的比较和社会情感结果如目标 1，但在 5 岁时，并有额外的目标对这些学龄儿童进行更能预测未来功能的领域的评估（例如，执行功能）。目标 3：评估（随着时间的推移）并比较抑郁、焦虑和睡眠接受基于 DTG 的 ART 与基于 EFV 的 ART 的女性（以及感染艾滋病毒的女性）的问题评分与艾滋病毒阴性女性）。