Mechanism of lipid disorder in HIV infection: apolipoprotein-B kinetics, fat distribution, insulin resistance and adipocytokines in patients taking protease inhibitors or non-nucleoside reverse transcriptase inhibitors

Abstract

The relationship between antiretroviral treatment of HIV infection, body fat distribution, insulin resistance (HOMA), adipocytokine and apolipoprotein-B (apoB) kinetics was investigated in 12 HIV negative controls and 55 HIV-infected patients including antiretroviral treatment-naïve patients (n=15) and patients taking two nucleoside analogues plus either a protease inhibitor (PI, n=15) or non-nucleoside reverse transcriptase inhibitor (NNRTI, n = 25). The HIV positive treatment groups had mild dyslipidaemia. The apo-B fractional clearance rate (FCR) was reduced in the HIV positive groups. Peripheral fat was lower in treated patients and correlated with duration of therapy. There was a positive correlation between peripheral fat and apo-B clearance rate and a negative correlation with apo-B pool size. Adiponectin was reduced in all HIV positive groups and correlated positively with HDL-cholesterol, apo-B FCR and limb fat and correlated negatively with plasma triglycerides and HOMA. In a linear regression model which included HOMA, adiponectin level but not HOMA was predictive of apo-B FCR and HDL cholesterol. These results suggest that mild dyslipidaemia resulting from antiretroviral therapy is due to a decrease in apo-B FCR which is strongly related to loss of peripheral fat. Adiponectin may have a direct effect on lipoprotein metabolism which may be independent of insulin