The purpose of this research is to analyze retrospective and prospective myocardial tissue samples for HIV viral genome and other viral genomes, inflammatory mediators, and other potential causes of cardiac dysfunction (such as apoptosis) in children with HIV who have been and who will be closely followed with serial cardiologic, immunologic, and virologic measurements and with pathologic post-mortem examinations as part of the Pediatric Pulmonary and Cardiovascular Complications of Vertically Acquired HIV infection (P2C2 HIV) Study at BCM and Boston Children's Hospital (BCH). In addition, the researchers will add HIV- infected children closely followed on other NIH protocols at the BCM Pediatric HIV Research Center for a projected total of 55 study/220 control patients who come to cardiac autopsy. Using molecular techniques such as the polymerase chain reaction (PCR) and in situ hybridization, the researchers will correlate virus DNA localization with pathological changes, characterize defects in adenoviral or other viral gene expression, resulting in viral persistence, and determine the role of adenoviral- or other viral-induced apoptosis in idiopathic dilated cardiomyopathy. Preliminary data have shown clearly the presence of common viral (especially adenoviral) DNA sequences in heart muscle of HIV-infected children. The researchers will correlate these findings with premortem measurements obtained on the P2C2 HIV Study, such as lymphocyte phenotyping, serum HIV RNA copy number and cardiac troponin level, and echocardiography. The hypothesis for this project is that HIV viral burden, immunosuppression, and HIV disease progression will lead to secondary viral infections, abnormal cytokine gene activations, upregulation of intercellular adhesive molecules, apoptosis, and viral gene mutations in cardiac tissue. Because chronic cardiac disease is a major health problem in children with HIV infection, particularly those living past five years of age, clinicians must understand the pathophysiology leading up to the heart failure. Possibly, the results of this research will achieve that goal and, even, lead to improved methods of early diagnosis and more sophisticated treatment regimens of pediatric HIV cardiac disease based upon a better definition of involved molecular mechanisms.
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