Oxidative stress predicts All-Cause mortality in HIV-Infected patients

Abstract

Objective We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients. Methods We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes F2-IsoPs and malondialdehyde MDA plasma levels in the first blood sample obtained after cohort engagement. Results 54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV- Transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein hsCRP, the association of F2-IsoPs with mortality remained significant adjusted OR per 1 log10 increase, 2.34 [1.23- 4.47], P = 0.009. The association of MDA with mortality was attenuated after adjustment: Adjusted OR 95% CI per 1 log10increase, 2.05 [0.91-4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR 95% CI per 1 log10 increase, 1.39 1.01-1.91, P = 0.043; and OR 95% CI per 1 log10 increase, 1.46 1.07-1.99, P = 0.014, respectively, when adjustment included F2-IsoPs and MDA. Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2- IsoPs, this association is independent of HIV-related factors and subclinical inflammation.