Chronic immune activation, oxidation and antioxidant/cytoprotective responses in the natural and treated course of HIV infection and structural markers of arteriopathy.

摘要

This was a longitudinal study nested in the Multicenter AIDS Cohort Study (MACS). The overall aims were: (i) to characterize immune activation, oxidative stress and Nrf2-regulated cytoprotective gene expression during the natural and treated course of HIV infection, and (ii) to evaluate their association with subclinical atherosclerosis (coronary artery calcification, carotid intima-media thickness (IMT) and lesions).The study population were seroconverters enrolled in the MACS cardiovascular sub-study who had initiated highly active antiretroviral therapy (HAART) and had available repository specimens (n=85). Assessment of neopterin (immune activation), F2-isoprostanes (oxidative stress), and the gene expression of nuclear factor erythroid 2 related factor 2 (Nrf2), here oxygenase 1 (HO-1), NADPH-quinone oxido-reductase 1 (NQO-1), glutamate cysteine ligase (GCLm), and glutathione peroxidase 1 (GPx-1) in peripheral blood mononuclear cells was performed at four times: before HIV infection, early HIV infection, advanced HIV infection before HAART, and during HAART prior to the arterial assessment. Data were analyzed using non-parametric methods and multivariable regression (logistic for presence of coronary calcification and carotid lesions, and quantile for IMT).This study found (i) evidence of incomplete restoration of immune markers to their pre-seroconversion levels and persistent immune activation during HAART (ii) a significant association of persistent HIV viremia and immune activation with low levels of HDL-cholesterol during HAART (iii) no definitive evidence of increased oxidative stress associated with progression of HIV infection and antiretroviral treatment (iv) a tendency toward higher levels of immune activation during HAART among those with coronary calcification in comparison with those without calcification, but no consistent evidence of association between immunological or virological markers of HIV infection and markers of subclinical atherosclerosis (v) evidence of association between Frisoprostanes during advanced HIV infection and presence of coronary calcification (Adjusted OR per 10 pg/ml of F2-isoprostanes change from pre-seroconversion: 1.21 (95% CI 1.00, 1.47), p=0.04) and carotid lesions (Adjusted OR per 10 pg/ml of F2-isoprostanes: 1.39 (95% CI 1.14, 1.70), p 0.001) and (vi) evidence of association between GPx-1 gene expression during advanced HIV infection and presence of coronary calcification (Adjusted OR per one unit difference in expression: 0.27 (95% CI 0.1, 1.0)).