Cardiovascular Status of HAART-Exposed Infants/Children

暴露于HAART的婴儿/儿童的心血管状况

• 批准号: 6788823
• 负责人: STEVEN EDWARD LIPSHULTZ
• 金额: $ 124.72万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6788823
• 关键词: AIDS therapy; HIV infections; acute phase protein; adult human (21+); atrial natriuretic peptide; biomarker; cardiotoxin; child (0-11); clinical research; combination chemotherapy; echocardiography; heart ventricle; human subject; medical complication; myocardium disorder; placental transfer; troponin; vertical transmission; women' s health

DESCRIPTION (provided by applicant): HIV-infected pregnant women frequently receive HAART therapy that is associated with reduced maternal-fetal transmission of HIV infection. This has resulted in a rapidly increasing number of seroreverters (HIV-uninfected infants born to HIV-infected women). This represents the majority of infants in the United States exposed to HAART. The long-term consequences and toxicities associated with this exposure are not known but severe cardiotoxicity is suggested in animal models. This study will utilize the NIH-sponsored WITS and p2C2 HIV seroreverter cohorts to determine how left ventricular (LV) structure and function, serum cardiac troponin T (cTnT), serum pro brain natriuretic peptide (proBNP), and serum high sensitivity C reactive protein (hsCRP) are affected by HAART exposure. The p2C2 seroreverter cohort has been exposed to no antiretroviral therapy or zidovudine alone (no HAART) and has persistent significantly depressed LV contractility compared to normal with up to 5 years of follow-up. The WITS seroreverter cohort has been exposed mostly to HAART and, by following the P2C2 protocol for assessment of LV structure and function, will determine the incremental effect of HAART on LV structure and function. The hypothesis that HAAT results in fetal and neonatal myocardiocyte injury and death will be tested by serial assessment of cTnT, a biomarker of acute myocardial injury, in both seroreverter cohorts. The hypothesis that HAART results in impaired myocardiocyte mitochondrial function resulting in LV dysfunction will be tested by serial assessment of proBNP, a biomarker related to LV dysfunction, LV volume and pressure increases resulting LV stretch, and to neurohormonal activation. The hypothesis that HAART results in accelerated atherosclerosis will be tested by serial assessment of hsCRP, a biomarker of generalized inflammation predictive of increased subsequent coronary artery disease. This study will determine the cardiovascular effects of HAART in seroreverters and the need for future cardiovascular follow-up and cardiovascular preventive and therapeutic trials in this rapidly expanding population.

描述（由申请人提供）： 感染 HIV 的孕妇经常接受 HAART 治疗，这与减少 HIV 感染的母婴传播有关。这导致血清回复者（感染艾滋病毒的妇女所生的未感染艾滋病毒的婴儿）数量迅速增加。这代表了美国接受 HAART 治疗的大多数婴儿。与这种暴露相关的长期后果和毒性尚不清楚，但动物模型表明存在严重的心脏毒性。本研究将利用 NIH 赞助的 WITS 和 p2C2 HIV 血清转复者队列来确定左心室 (LV) 结构和功能、血清心肌肌钙蛋白 T (cTnT)、血清前脑钠肽 (proBNP) 和血清高敏 C 反应蛋白 (hsCRP) 如何受到 HAART 暴露的影响。 p2C2 血清逆转者队列未接受抗逆转录病毒治疗或单独使用齐多夫定（无 HAART），并且在长达 5 年的随访中，与正常人相比，左心室收缩力持续显着降低。 WITS 血清恢复者队列主要接受 HAART，通过遵循 P2C2 方案评估 LV 结构和功能，将确定 HAART 对 LV 结构和功能的增量影响。 HAAT 导致胎儿和新生儿心肌细胞损伤和死亡的假设将通过对两个血清逆转者队列中急性心肌损伤的生物标志物 cTnT 的连续评估进行检验。 HAART 导致心肌细胞线粒体功能受损，从而导致左室功能障碍的假设将通过对 proBNP 的系列评估进行检验，proBNP 是与左室功能障碍、左室容量和压力增加导致左室伸展以及神经激素激活相关的生物标志物。 HAART 导致动脉粥样硬化加速的假设将通过 hsCRP 的连续评估进行检验，hsCRP 是预测随后冠状动脉疾病增加的全身炎症的生物标志物。这项研究将确定HAART对血清恢复者的心血管影响，以及未来在这个快速扩大的人群中进行心血管随访和心血管预防和治疗试验的必要性。