Influence of antiretroviral therapy on oxidative stress and cardiovascular risk:: A prospective cross-sectional study in HIV-Infected patients

Background: Oxidative stress (OS) results from excessive free radical production, exceeding endogenous antioxidant defense mechanisms, which can damage a wide variety of cellular components. One of the main consequences is the attack of free radicals on polyunsaturated fatty acids contained in low-density lipoprotein (LDL) lipids, causing lipid peroxidation and subsequent elevated concentrations of lipid peroxides and their metabolites, which are strongly suggestive of oxidative damage. OS is increased among HIV-infected patients, but whether it implicates a higher risk for cardiovascular disease or the influence of antiretroviral therapy (ART) on OS remains unknown. Objective: The aim of this study was to assess the relationship of OS with established cardiovascular risk factors and with ART as measured by total peroxide concentration. Methods: A prospective cross-sectional study was conducted in 245 consecutive HIV-infected patients during a 2-month period (September 15, 2003-November 15, 2003) at the HIV clinic of the Infectious Disease Unit, Hospital General Universitario de Elche, Universidad Miguel Hernandez, Elche, Spain. Laboratory measurements included total peroxide concentrations, C-reactive protein (CRP) levels, fasting lipid levels, white blood cell type CD4+ T-lymphocyte counts, plasma HIV RNA, and routine blood tests. To measure OS, total peroxide concentration was determined quantitatively with a colorimetric assay. The association of peroxide concentrations with HIV-related variables and cardiovascular risk factors was examined using univariate and multivariate analyses. Results: Two hundred forty-five patients were screened and enrolled in the study; no patients refused enrollment. Median (interquartile range [IQR]) age of the patients was 40.2 (35.4-46.2) years; 194 (79.2%) were male, and 238 (97.1%) white. Median (IQR) weight was 67.5 (60.4-76.0). Ninety-five (38.8%) patients were receiving a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen at the time of enrollment; 52 (21.2%) were on a protease inhibitor (PI)-based regimen. Peroxide concentrations were above reference values (<400 mu mol/L) in 121 (49.4%) patients. Peroxide levels correlated positively with CRP (P < 0.001) and LDL-cholesterol (LDL-C) (P = 0.003), and negatively with age (P = 0.002) and body mass index (P < 0.001). Among patients on ART, peroxide concentrations were significantly lower in those treated with NNRTI-based regimens than in those receiving PIs (median [IQR], 331.2 [196.2-495.7] vs 472.8 [302.5-586.5] mu mol/L; P = 0.003). In multivariate analysis, when peroxide concentration was dichotomized according to reference values (<400 mu mol/L), age (odds ratio [OR], 0.96; 95% Cl, 0.93-0.99; P = 0.007) and ART including NNRTI (OR, 0.52; 95% CI, 0.28-0.95; P = 0.03) were associated with low peroxide concentrations, while LDL-C (OR, 1.01; 95% CI, 1.00-1.02; P = 0.03) predicted the highest values. Conclusions: The results from this study suggest that, among this cohort of HIV-infected patients, peroxide concentration used as a marker of OS was associated with other established cardiovascular risk factors. Antiretroviral regimens based on NNRTIs were associated with low peroxide concentrations. In contrast, high peroxide levels were found in patients receiving PI-based regimens.