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

围产期 HIV 感染青少年和年轻人的心脏毒性纵向研究

• 批准号: 9977275
• 负责人: STEVEN EDWARD LIPSHULTZ
• 金额: $ 67.24万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977275
• 关键词: Adolescent; Adolescent and Young Adult; Anti-HIV Agents; Atherosclerosis; Biological Assay; Biological Markers; Blood Pressure; Cardiac; Cardiac Myocytes; Cardiotoxicity; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiovascular system; Cells; Characteristics; Child; Childhood; Chronic; Clinical; Echocardiography; Epidemic; Event; Exposure to; Future; Goals; HIV; HIV-infected adolescents; Heart; Heart Rate; Heart failure; Highly Active Antiretroviral Therapy; Individual; Inflammation; Inflammatory; Intervention; Lead; Left; Left Ventricular Function; Left ventricular structure; Longitudinal Studies; Lung; Measurement; Measures; Mitochondria; Mitochondrial DNA; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Oxidative Phosphorylation; Oxidative Stress; Oxygen Consumption; Pediatric HIV/AIDS Cohort Study; Pediatric cohort; Peripheral Blood Mononuclear Cell; Population; Protocols documentation; Reporting; Respiration; Risk; Risk Factors; Role; Severities; Severity of illness; Stress; Structure; Symptoms; Time; United States National Institutes of Health; Ventricular; Visit; Youth; antiretroviral therapy; cardioprotection; cardiovascular disorder risk; cardiovascular risk factor; cohort; enzyme activity; follow-up; heart damage; lifestyle intervention; mitochondrial dysfunction; mortality; perinatal HIV; premature; screening guidelines; young adult

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.

项目概要 虽然高效抗逆转录病毒疗法的广泛使用已显着降低了心脏功能 围产期 HIV 感染儿童的发病率和死亡率，多项研究表明亚临床 左心室结构和功能的超声心动图测量异常。本研究的目标是 纵向评估围产期艾滋病毒感染青少年和年轻人的心血管状况 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随时间变化。本研究的具体目的是 1) 确定 大约 6 年前在 AMP（青少年）中评估的心血管危险因素的纵向变化 AMP Up（年轻人）围产期 HIV 感染者 (PHIV) 和 HIV 暴露未感染者 (PHEU) 队列 儿科艾滋病毒/艾滋病队列研究 (PHACS)；并测量修改后的病理生物学决定因素 青年动脉粥样硬化或艾滋病毒感染者的 PDAY 评分（总体心血管风险的衡量标准） 青少年纵向； 2) 确定全身线粒体功能障碍在 通过测定线粒体 DNA (mtDNA) 拷贝/细胞、氧化来检测心血管异常和生物标志物 磷酸化 (OXPHOS) 酶活性、耗氧量（呼吸）和线粒体氧化 压力。这项研究的结果可以确定是否存在围产期感染艾滋病毒的青少年和年轻人， 长期接受高效抗逆转录病毒疗法（HAART），未来发生心血管疾病的风险会增加。如果这是 在这种情况下，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 降低他们未来发生不良心血管事件的风险。