Cardiovascular Status of HAART-Exposed Infants/Children

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。这导致血清转复者（感染艾滋病毒的妇女所生的未感染艾滋病毒的婴儿）人数迅速增加。这代表了美国暴露于HAART的大多数婴儿。与这种接触相关的长期后果和毒性尚不清楚，但在动物模型中表明存在严重的心脏毒性。本研究将利用NIH申办的WITS和p2C2 HIV血清转化队列，以确定HAART暴露如何影响左心室（LV）结构和功能、血清心肌肌钙蛋白T（cTnT）、血清脑钠肽前体（proBNP）和血清高敏C反应蛋白（hsCRP）。p2C2血清转化者队列未接受抗逆转录病毒治疗或单用齐多夫定（无HAART），与正常人相比，LV收缩力持续显著降低，随访时间长达5年。WITS血清逆转者队列主要暴露于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转化者队列中急性心肌损伤的生物标志物cTnT进行系列评估来检验。HAART导致心肌细胞线粒体功能受损导致LV功能障碍的假设将通过对proBNP（一种与LV功能障碍、LV容量和压力增加导致LV牵拉以及神经激素激活相关的生物标志物）的系列评估进行检验。HAART导致加速动脉粥样硬化的假设将通过hsCRP的系列评估来检验，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在血清逆转者中的心血管作用，以及在这一迅速扩大的人群中进行未来心血管随访和心血管预防和治疗试验的必要性。

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.