Cardiovascular Status of HAART-Exposed Infants/Children

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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.