Abstract 18000: Mitochondrial Oxidative Stress and Function compared to Lipoprotein Level, Particle Number and Size in an HIV Positive Cohort

Abstract

Introduction: Dyslipidemia, arising from viral infection, antiretroviral treatment and changes in body composition, is a key metabolic abnormality believed to underlie increased CVD risk among HIV-infected subjects. Oxidative stress and mitochondrial function is linked to atherosclerosis and HIV treatment. We sought to determine the relationship between mitochondrial oxidative stress, function, and standard clinical lipid profile as well as lipoprotein subclass particle number and size among HIV-infected persons. Study Sample: HIV infected individuals, age > 40 years and on stable highly activite antiretroviral therapy for > 6 months. Methods: We considered the following measures: 1. mitochondrial-specific 8-oxo-deoxyguanine (8-oxo-dG) and 2. mitochondrial OXPHOS NADH dehydrogenase (Complex I) and cytochrome c oxidase (Complex IV) enzyme activity . Plasma total cholesterol, triglycerides, and HDL-C and LDL-C were directly measured. Lipoprotein subclass size and particle number were measured using proton NMR spectroscopy (LipoScience Assay). Unadjusted linear regression analysis was employed to study the association between mitochondrial and lipid parameters. A p-value of <0.05 was considered significant. Results: Among 109 HIV-infected persons (mean age 52 years, 14% women, 52% White, 14% Hispanic, 9% Asian), median CD4 count was 511 cell/mm 3 , median HIV RNA was 48 copies/mm 3 (majority with undetectable virus), BMI prevalence >= 25 kg/m 2 was 64%, diabetes 27%, HTN 34% and current cigarette smoking 28%. 8-oxo-deoxyguanine was associated with small HDL (umol/L) (p=0.03) and VLDL particle size (nm)(p=0.03). Complex I activity was inversely associated with VLDL & chylomicron particle number (nmol/L) (p=0.01), small VLDL particles (nmol/L) (p=0.005), LDL particle (total) (nmol/L) (p=0.02), and small LDL particle (total) (nmol/L) (p=0.02). Complex IV was not associated with any lipid parameters. None of the three mitochondrial parameters studied was associated with clinical lipid profile (total cholesterol, LDL, HDL, or triglycerides). Conclusions: Mitochondria oxidative stress and function is associated with lipoprotein subclass size and number but not with clinical lipid profile among treated HIV-infected individuals.