Cardiac Toxicity in Perinatally HIV-infected Adolescents and Young Adults, a Longitudinal Study

项目摘要 虽然高效抗逆转录病毒疗法的广泛使用显著降低了心脏发病率和 围产期感染艾滋病毒儿童的死亡率，几项研究表明 超声心动图测量左心室结构和功能。这项研究的目标是纵向 评估围产期HIV感染青少年和青壮年的心血管状况并探讨 慢性炎症和/或线粒体异常是否与超声心动图和 生物标志物会随着时间的推移而变化。这项研究的具体目的是：1)确定纵向变化 大约6年前在AMP(青少年)和AMP UP(青年)中评估的心血管危险因素 成人)儿童艾滋病毒/艾滋病围产期感染艾滋病毒(PHIV)和暴露于艾滋病毒的未感染(HEU)队列 队列研究(PHACS)和测量青年或青少年动脉粥样硬化的改良病理生物学决定因素 纵向的HIV感染青少年的PDAY评分(衡量总体心血管风险)；以及2) 评价全身线粒体功能在心血管指标异常中的作用 通过分析线粒体耗氧量(呼吸作用)和氧化应激来确定生物标记物。结果是 这项研究可以识别是否有围产期感染艾滋病毒的青少年和青壮年，长期 暴露于HAART，这将增加未来患心血管疾病的风险。如果是这样的话， 这项研究的结果可以为这一心血管风险增加的人群提供各种干预措施以减少 他们未来发生不良心血管事件的风险。

Project Summary While the widespread use of highly active antiretroviral therapy has markedly decreased cardiac morbidity and mortality in perinatally HIV-infected children, several studies have suggested subclinical abnormalities in echocardiographic measures of left ventricular structure and function. The goal of this study is to longitudinally evaluate the cardiovascular status of perinatally HIV-infected adolescents and young adults and to explore whether chronic inflammation and/or mitochondrial abnormalities are associated with echocardiographic and biomarker changes over time. The specific aims of this study are to 1) to determine longitudinal changes of cardiovascular risk factors that were assessed ~6 years ago in the AMP (adolescents) and AMP Up (young adults) perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (HEU) cohorts of the Pediatric HIV/AIDS Cohort Study (PHACS) and to measure modified Pathobiological Determinants of Atherosclerosis in Youth or PDAY scores (a measure of aggregate cardiovascular risk) in HIV-infected adolescents longitudinally; and 2) to evaluate the role of systemic mitochondrial function in abnormalities of cardiovascular measures and biomarkers by assaying for mitochondrial oxygen consumption (respiration) and oxidative stress. The results of this study can identify if there are perinatally HIV-infected adolescents and young adults, with long term exposure to HAART, which are at increased risk of future cardiovascular morbidities. If this is the case, the results of this study can inform various interventions in this increased cardiovascular risk group to decrease their future risk of adverse cardiovascular events.