Determinants of Low-Density Lipoprotein Particle Diameter during Antiretroviral Therapy Including Protease Inhibitors in HIV-1-Infected Patients

Abstract

Lipid disorders are frequent in HIV-1-infected patients taking combination antiretroviral therapy (cART) that includes protease inhibitors (PIs). The presence of small dense low-density lipoprotein particles might be an important predictive marker of cardiovascular disease in this setting. This cross-sectional substudy of the ANRS 126 trial was designed to identify variables influencing LDL diameter. We studied 81 stable HIV-1-infected patients with dyslipidaemia (LDL-cholesterol >4.1 mmol/l, triglycerides <8.8 mmol/l) receiving PI-including cART regimens and no lipid-lowering drugs. LDL diameter was assessed by gradient gel electrophoresis. Relationships between LDL diameter and demographic, metabolic and HIV-related variables were identified by using non-parametric univariate tests and multiple linear regression models. In univariate analysis, LDL diameter was related to demographic variables, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-c) levels, and the numbers and duration of exposure to nucleoside reverse transcriptase inhibitors and PIs. In multivariable linear regression analysis, LDL diameter was negatively associated with the TG level (P<0.0001) and positively associated with the HDL-c level (P<0.0001). For each 1-mmol/l increase in TG, LDL diameter fell by 0.281 nm. Conversely, for each 1-mmol/l increase in HDL-c, LDL diameter rose by 1.175 nm. Higher TG and lower HDL-c levels are associated with smaller LDL particle diameter. Small-diameter LDL particles could contribute to early atherogenic processes in HIV-1-infected patients on cART.