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病的发生率， 围产期HIV感染儿童的发病率和死亡率，一些研究表明亚临床 超声心动图测量左心室结构和功能的异常。本研究的目的是 纵向评估围产期HIV感染青少年和年轻成人的心血管状况 并探索慢性炎症和/或线粒体异常是否与 超声心动图和生物标志物随时间的变化。本研究的具体目的是：1）确定 AMP中约6年前评估的心血管风险因素的纵向变化（青少年） 和AMP Up（年轻成人）围产期HIV感染（PHIV）和HIV暴露未感染（PHEU）队列， 儿科艾滋病毒/艾滋病队列研究（PHACS）;以及测量 艾滋病毒感染者的青年动脉粥样硬化或PDAY评分（心血管综合风险的衡量标准） 青少年纵向;和2）确定全身性线粒体功能障碍在 通过测定线粒体DNA（mtDNA）拷贝数/细胞、氧化 磷酸化（OXPHOS）酶活性、氧消耗（呼吸）和线粒体氧化磷酸化（OXPHOS）活性。 应力这项研究的结果可以确定是否有围产期艾滋病毒感染的青少年和年轻人， 长期暴露于HAART，这是在未来心血管疾病的风险增加。如果这是 在这种情况下，这项研究的结果可以为这种心血管风险增加的人群提供各种干预措施， 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.