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A pilot study of urinary markers of endothelial function and oxidant stress for the prediction of cardiovascular disease (CVD) risk with antiretroviral therapy (ART)

Presented by Michael Boger, United States.

M. Boger1, G. Milne2, J. Morrow2, H. Erdem3, V. Mitchell3, D. Haas1, T. Hulgan1

1Vanderbilt University School of Medicine, Division of Infectious Diseases, Nashville, United States, 2Vanderbilt University School of Medicine, Clinical Pharmacology, Nashville, United States, 3Vanderbilt-Meharry Center for AIDS Research, Nashville, United States

Background: Traditional CVD risk predictors underestimate CVD outcomes in HIV-infected patients on ART. We hypothesize that ART-associated metabolic effects are mediated by oxidant stress and endothelial damage and may be better assessed by quantifying eicosanoids formed during atherosclerosis. Few of these markers have been evaluated for CVD risk prediction, particulary during HIV-infection. We studied selected eicosanoids, traditional CVD risk factors, and hsCRP, an established CVD risk marker, in HIV-infected patients on ART.
Methods: This pilot study is a cross-sectional analysis of a prospective clinic-based cohort of HIV-infected adults. Eligibility included receipt of stable ART (
³2 NRTIs), HIV-1 RNA <10,000 copies/mL, no known CVD or diabetes, and no current aspirin or tobacco use. Urine metabolites of F2-isoprostane (PGF2a), thromboxane (TxB2), prostacyclin (PGI-M), and prostaglandin-E (PGE-M) were measured by mass spectrometry/gas chromatography. Univariate analysis assessed correlations of eicosanoids with lipids, BMI, hsCRP, lactate, age, sex, race, protease inhibitor (PI) use, and clinical lipoatrophy.
Results: 33 subjects met inclusion criteria. Median age was 45 years, 24% were women, 55% non-white, and 45% were on a PI-containing regimen. Median CD4 and HIV-1 RNA were 515 cells/mm3 and <50 copies/mL, respectively. There were significant correlations between PGF2
a and hsCRP overall (r=0.357, p=0.04) and between PGI-M, TxB2, and hsCRP in women (r=0.899 and 0.843, respectively; p=0.01 for both). PGF2a was increased in women receiving PIs (p=0.04). There was a trend toward increased PGI-M in men with lipoatrophy (p=0.07). PGI-M and TxB2 correlated with increased non-HDL cholesterol (r=0.441 and 0.376, respectively; p=0.03 for both).
Conclusions: Urinary markers of oxidant stress and endothelial function correlated with established CVD risk factors (serum lipids and hsCRP) among HIV-infected patients on ART. Sex, PI use, and lipoatrophy may influence these measures. These data suggest that urinary eicosanoids may be promising markers of CVD risk in HIV-infected patients on ART and further study is warranted.

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