Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients

Abstract

ObjectiveWe aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients.MethodsWe 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.Results54 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 log10 increase, 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.ConclusionOxidative 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.

Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg

“…This index is often used to assess the impact of HAART or HIV-1 virus in patients [23,24]. Figure 1A shows the plasma levels of isoprostane in rats after 6 weeks of treatment: cART treatment alone led to a modest 41% increase in isoprostane in normal Mg control rats; HIV-Tg alone exhibited a 92% higher isoprostane level; and cART treatment of Tg rats further elevated isoprostane levels 2.8-fold compared to normal Mg controls.…”

Polymorphism rs1385129 Within Glut1 Gene SLC2A1 Is Linked to Poor CD4+ T Cell Recovery in Antiretroviral-Treated HIV+ Individuals

“…Thus, these observations support the model that elevated glycolysis facilitates metabolic exhaustion that drives CD4+ T cell loss ( 5 , 6 ). Indeed, Glut1 expression on CD4+ T cells is associated with increased metabolic activity, including upregulated glucose influx, increased ROS production, and cell stress ( 1 , 59 – 62 ).…”

Reaction Kinetics Direct a Rational Synthesis of an HIV‐1 Inactivator of Nucleocapsid Protein 7 and Provide Mechanistic Insight into Cellular Metabolism and Antiviral Activity

“…Lastly, we examined the susceptibility of the thiol in 2 to oxidation (which could inform how this molecule is metabolized under oxidative stress in cells). The rate of 2 oxidation upon exposure to 30 % hydrogen peroxide (2.3 equiv) in a solution (70:25:5) of PBS 10X buffer/[D 6 ]DMSO/D 2 O (25 °C) is displayed in Figure E. Qualitatively, the thiol 2 is rapidly consumed to produce the disulfide 5 (half‐life ≈1 min), followed by a more gradual disproportionation to the benzisothiazolinone 6 (half‐life ≈45 min).…”