Coordinating Center for the Pediatric HIV/AIDS Cohort Study II

描述(申请人提供)：儿科艾滋病毒艾滋病队列研究涉及两个关键研究问题：(1)胎儿和婴儿接受抗逆转录病毒治疗(ART)用于预防艾滋病毒-1母婴传播的后果，(2)儿童在青春期至成年期期间围产期艾滋病毒感染的临床过程。这些问题正通过在美国和波多黎各的多个地点实施的两个不同的方案得到解决。SMARTT研究的具体目标是，在感染艾滋病毒的婴儿中，确定ART暴露的短期和长期安全性。为了做到这一点，感染艾滋病毒的母亲所生的未感染艾滋病毒的孩子被前瞻性地评估了生长、神经发育、心脏和其他末端器官功能。将对有异常的儿童进行进一步评估，以确定他们是否由ART毒性所致，特别强调线粒体功能障碍。AMP的具体目标是，在一群患有围产期艾滋病毒的青少年中(1)确定艾滋病毒感染和抗逆转录病毒疗法对以下方面的影响：生长和发育；性成熟；青春期发育；心血管疾病风险因素的发展；认知、学术、职业、性和社会功能；心理健康；以及冒险行为，包括药物使用。(2)识别HIV疾病的感染性和非感染性并发症，ART治疗，包括终末器官疾病(神经、肾、肺、骨)和营养代谢异常。(3)研究影响HIV感染过程、并发症和治疗反应的遗传学、表观遗传学、病毒学(包括抗逆转录病毒耐药性)和免疫学因素。在这两个方案中，受试者和他们的主要照顾者根据标准化方案进行前瞻性评估。两者都采用了触发评价的策略，通过具体的异常发现导致额外的评价来表征异常。收集储存库标本，以进行进一步的生化和基因测试。 与公共卫生相关：确定孕期预防技术的安全性--包括个别药物的安全性--对于确定预防艾滋病毒经母亲传播的最安全战略是必要的。围产期艾滋病毒已成为一种慢性疾病，有必要了解感染的长期后果及其治疗，以便为这些儿童提供护理。

DESCRIPTION (provided by applicant): The Pediatric HIV AIDS Cohort Study addresses two critical research questions: (1) the consequences of fetal and infant exposure to antiretroviral therapy (ART) when used to prevent mother-to-child transmission of HIV-1, and (2) the clinical course of perinatal HIV infection among children as they proceed through adolescence towards adulthood. These questions are being addressed through two separate protocols being conducted at multiple sites in the US and Puerto Rico. The specific aim of the SMARTT Study is, among HIV-exposed infants, to define the short and long-term safety of ART exposure. To accomplish this, HIV-uninfected children born to infected mothers are evaluated prospectively for growth, neurodevelopment, cardiac and other end-organ function. Children with abnormalities will be further evaluated to determine if they result from ART toxicity, with particular emphasis on mitochondrial dysfunction. The specific aims of AMP are, among a cohort of pre-adolescents and adolescents with perinatal HIV (1) to define the impact of HIV infection and ART on: growth and development; sexual maturation; pubertal development; development of risk factors for cardiovascular disease; cognitive, academic, vocational, sexual, and social functioning; mental health; and risk taking behavior including substance use. (2) to identify infectious and non-infectious complication of HIV disease and ART therapy, including end organ disease (neurologic, renal, pulmonary, bone) and nutritional and metabolic abnormalities. (3) to study genetic, epigenetic, virologic (including antiretroviral resistance), and immunologic factors which impact the course of HIV infection, its complications and response to treatment. In both protocols, subjects and their primary caregivers are prospectively evaluated according to a standardized protocol. Both utilize a strategy of triggered evaluations, with specific abnormal findings leading to additional evaluations to characterize the abnormality. Repository specimens are collected for further biochemical and genetic testing. PUBLIC HEALTH RELEVANCE: Defining the safety of preventive ART during pregnancy - including the safety of individual drugs - is necessary to define the safest strategy to prevent mother-to-transmission of HIV. Perinatal HIV has become a chronic condition, and an understanding of the long-term outcomes of the infection and its treatment is necessary to provide care for these children.