Abstract 314: HIV infection iIduces Structural and Functional Changes in High Density Lipoproteins

Abstract

Coronary artery disease is a growing clinical problem in HIV-infected subjects. Increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function are poorly characterized. Here, we determined the composition and function of HDL particles isolated from plasma collected from ART-naive and ART-positive HIV-infected patients and compared them to HDL from a convenience control group. Proteomic profiling revealed decreased paraoxonase (PON) 1 and PON 3 in HDL from both treated and untreated HIV-positive patients, and PON activity of HDL from HIV-infected subjects was significantly lower than in control group. Lipidomic profiling found sphingomyelin and ether-linked glycerophospholipid species in the HDL particles correlated positively with viral load and negatively with CD4+ T cell counts in ART-naive subjects. Consistent with analysis of lipids, the level of PLTP showed a significant positive correlation with viral load and negative correlation with CD4+ T cell counts in ART-naïve HIV-positive samples. Given the low PON1 and 3 levels in HDL from HIV-infected subjects, we tested for the level of oxidized phospholipids in the HDL particles from a subset of HIV+ ART-naïve and treated subjects with completely suppressed viremia. No significant differences in oxidized lipids were found between HDL from control and untreated or PI-treated subjects, but a significant increase was detected in the NNRTI-treated samples. Similarly, the ratio of oxidized LDL to total LDL was significantly increased in the NNRTI-treated samples. These results suggest that reduced PON levels in HDL of HIV-infected subjects do not translate to increased levels of oxidized lipids, however, low PON may contribute to increased oxidation in NNRTI-treated patients. Finally, a negative correlation between cholesterol efflux capacity of HDL and viral load in ART-naive HIV-infected group was detected. Thus, HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, and this may increase risk of atherosclerosis in this patient population.