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 围产期感染艾滋病毒儿童的发病率和死亡率，几项研究表明，亚临床 超声心动图测量左心室结构和功能的异常。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记物随时间变化。这项研究的具体目的是：1)确定 青少年AMP患者心血管危险因素6年前的纵向变化 和AMP UP(青壮年)围产期感染艾滋病毒(PHIV)和暴露于HIV的未感染(PHEU)队列 儿科HIV/AIDS队列研究(PHACS)；并测量改良的病理生物学决定因素 青年中的动脉粥样硬化或HIV感染者的PDAY评分(衡量总体心血管风险) 2)确定系统性线粒体功能障碍在青春期的作用 通过测定线粒体DNA(MtDNA)拷贝数/细胞，氧化性心血管异常和生物标记物 磷酸化(OXPHOS)酶活性、氧耗(呼吸)和线粒体氧化 压力。这项研究的结果可以确定是否有围产期感染艾滋病毒的青少年和年轻人， 长期暴露于HAART，未来患心血管疾病的风险增加。如果这是 本研究的结果可以为这一心血管高危人群的各种干预提供参考 降低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 (PHEU) 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 determine the role of systemic mitochondrial dysfunction in cardiovascular abnormalities and biomarkers by assaying mitochondrial DNA (mtDNA) copies/cell, oxidative phosphorylation (OXPHOS) enzyme activities, oxygen consumption (respiration), and mitochondrial 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.