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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要尽管高度活性抗逆转录病毒疗法的广泛使用显着降低了心脏几项研究表明亚临床的发病率和死亡率左心室结构和功能的超声心动图测量值异常。这项研究的目的是纵向评估受HIV感染的青少年和年轻人的心血管状态并探索慢性炎症和/或线粒体异常是否与超声心动图和生物标志物会随着时间而变化。这项研究的具体目的是1）确定大约6年前在AMP（青少年）评估的心血管危险因素的纵向变化和AMP UP（年轻人）受HIV感染（pHIV）和艾滋病毒暴露，未感染的（PHEU）队列小儿艾滋病毒/艾滋病队列研究（PHACS）；并测量修改的病理生物学决定因素 HIV感染的青年或PDAY评分的动脉粥样硬化（一种量度的心血管风险）青少年纵向； 2）确定系统性线粒体功能障碍在通过测定线粒体DNA（mtDNA）副本/细胞，氧化，心血管异常和生物标志物磷酸化（OXPHOS）酶活性，氧气消耗（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HIV感染的青少年和年轻人，长期暴露于HAART，后者的风险增加了未来的心血管病。如果是案例，这项研究的结果可以告知这种增加的心血管风险群体的各种干预措施减少他们未来不良心血管事件的风险。