HIV-Related Proteinuria and Endothelial Dysfunction

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DESCRIPTION (provided by applicant): Renal and cardiovascular diseases in HIV-infected patients are increasingly reported and may be interrelated. Total proteinuria, a widely used initial screening marker for renal disease, is extremely common in HIV-infected patients. In the general population, proteinuria is also associated with systemic endothelial dysfunction, a predictor of future cardiovascular events. Therefore, we hypothesize that endothelial dysfunction may be associated with the high prevalence of proteinuria in the HIV-infected population. Furthermore, because protease inhibitors are associated with endothelial dysfunction, we hypothesize that this class of antiretrovirals may specifically result in glomerular endothelial disease, manifested initially as microalbuminuria. The specific aims of this study are to (1) determine the relationships between proteinuria and systemic endothelial dysfunction in HIV-infected patients and (2) determine the effects of protease inhibitor-based HAART on microalbuminuria in HIV-infected patients. To address Aim #1, we propose to perform a prospective, cohort study of HIV-infected subjects cared for at the Indiana University Medical Center. Specifically, ultrasound-measured flow mediated dilation of the brachial artery (a physiologic measurement of endothelial function), lipids, insulin and glucose levels, anthropometrics, lifestyle factors, and blood pressures of two HIV-infected groups (those with persistent proteinuria vs. those without proteinuria) will be compared at baseline and again in two years. Aim #2 will be addressed by performing a secondary analysis of a metabolic substudy (chaired by the principal investigator's primary mentor) of AIDS Clinical Trials Group study 384, which compared the use of protease inhibitor-based regimens with nonnucleoside reverse transcriptase-based regimens for the initial antiretroviral treatment of HIV-infected patients. Archived urine samples obtained at regular intervals through the duration of this substudy will be used to measure microalbuminuria levels. Taken together, the results of these studies will form the basis for future prevention and therapeutic trials targeted at both renal and cardiovascular diseases in HIV-infected patients. The proposed research will foster the principal investigator's clinical research career development, as supervised by established independent investigators (primary mentor: Michael P. Dub6) in the fields of HIV metabolic and renal complications, renal vascular and glomerular pathology, and clinical trials design and implementation.