Low Density Lipoprotein Apolipoprotein B Metabolism in Treatment-Naive HIV Patients and Patients on Antiretroviral Therapy

Abstract

Dyslipidaemia and lipodystrophy have been described in treated HIV patients and in a small percentage of untreated HIV patients. Lipodystrophy in these patients has been shown to be associated with a lower expression of low density lipoprotein (LDL) receptors. We have investigated the effect of antiretroviral treatment with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) on body fat distribution and LDL apolipoprotein B (apoB) kinetics in 12 HIV-negative controls and 52 HIV-infected patients, including antiretroviral treatment-naive (TN) patients (n=13) and patients taking two nucleoside analogues plus either a PI (n=15) or an NNRTI (n=24). LDL cholesterol was not different between groups. Compared with the controls, LDL apoB absolute synthetic rate (ASR) and fractional catabolic rate (FCR) were lower and residence time (RT) was higher in the PI and NNRTI groups (P<0.05). In the TN patients, LDL ASR was lower (P<0.05) and there was a trend for a lower FCR and higher RT compared with the controls (P=0.07). LDL apoB pool size was greater in the PI group compared with the controls (P<0.05). In the PI group, patients on ritonavir (RTV)-containing regimens had a lower LDL apoB ASR (P=0.009) and a trend to a lower LDL apoB FCR and increased RT compared with non-RTV-containing PI regimens (P=0.05). There was a positive correlation between LDL apoB FCR and limb fat/lean body mass (P=0.004) in all subjects. Decreased LDL FCR, despite unchanged LDL cholesterol, was demonstrated in both treated and untreated HIV patients. It was more marked with RTV-containing regimens and was associated with reduced limb fat. The increased LDL RT may lead to an increased risk of atherogenesis thus contributing to the risk for cardiovascular disease in these patients.