Coordinating Center for the Pediatric HIV/AIDS Cohort Study II

描述（由申请人提供）：儿科HIV AIDS队列研究解决了两个关键的研究问题：（1）胎儿和婴儿暴露于抗逆转录病毒治疗（ART）用于预防HIV-1母婴传播时的后果，以及（2）儿童从青春期到成年的围产期HIV感染的临床过程。这些问题通过在美国和波多黎各的多个研究中心进行的两个单独的方案来解决。SMARTT研究的具体目的是在艾滋病毒暴露的婴儿中确定ART暴露的短期和长期安全性。为了实现这一目标，对受感染母亲所生的未感染艾滋病毒的儿童进行前瞻性的生长、神经发育、心脏和其他终末器官功能评估。将对异常儿童进行进一步评估，以确定其是否由ART毒性引起，特别强调线粒体功能障碍。AMP的具体目标是，在围产期HIV感染的青春期前和青少年队列中（1）确定HIV感染和ART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，包括物质使用。(2)确定艾滋病毒疾病和ART治疗的感染性和非感染性并发症，包括终末器官疾病（神经系统、肾脏、肺部、骨骼）以及营养和代谢异常。(3)研究影响艾滋病毒感染过程、并发症和治疗反应的遗传、表观遗传、病毒学（包括抗逆转录病毒耐药性）和免疫学因素。在这两种方案中，根据标准化方案对受试者及其主要照顾者进行前瞻性评价。两者均采用触发评价策略，特定异常结果导致额外评价以表征异常。收集储存库样本以作进一步生化及基因测试。 公共卫生相关性：确定怀孕期间预防性抗逆转录病毒疗法的安全性-包括个别药物的安全性-对于确定预防艾滋病毒母婴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，了解感染的长期后果及其治疗是为这些儿童提供护理所必需的。

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.