Decrease in LDL size in HIV-positive adults before and after lopinavir/ritonavir-containing regimen: an index of atherogenicity?

Background: Hypertriglyceridemia (HTG) is frequently observed during highly active antiretroviral therapy (HAART) including protease inhibitor. Apolipoprotein (apo) CIII could be involved in this HTG by inhibition of triglyceride (TG) hydrolysis, which leads to the occurrence of small dense low density lipoprotein (sdLDL), a recognized cardiovascular risk factor. Objective: To characterize the influence of lopinavir/ritonavir-containing regimen on lipoprotein profile. Design and methods: 24 antiretrovira-experienced HIV infected adults (including 14 patients in therapeutic interruption of at least 2 months) and 14 HIV uninfected healthy controls were enrolled. Serum lipid parameters (total cholesterol (TC), HDL-C, LDL-C, TG, apoA1, apoB, apoCIII), lipoprotein composition and LDL size were determined before initiation of lopinavir/ritonavir-containing regimen, and at 1 and 3 months thereafter. Results: At baseline an atherogenic lipid profile was evidenced, characterized by a moderate HTG associated to a smaller mean LDL size (25.16 vs 25.93 nm, P < 0.001), an enrichment in TG of LDL (11.4 vs 6.0%, P < 0.01) and a high prevalence of sdLDL (75 vs 7%, P < 0.01) when compared to controls. After 1 month of lopinavir/ritonavir-containing regimen, a significant reduction of LDL size (24.81 vs 25.16 run, P < 0.05) and a significant increase in cholesterol total (5.53 vs 4.49 mmol/l, P < 0.001), in TG (4.20 vs 2.01 mmol/l, P < 0.001), in apoAl (1.28 vs 1.11 g/l, P < 0.001), in apoB (1.08 vs 0.94 g/l, P < 0.01), in apoCIII (0.16 vs 0.10 g/l, P < 0.001), in TG percentage in LDL (14.4 vs 11.4, P < 0.05) and in TG percentage in HDL (10.2 vs 8.3, P < 0.05) were observed. Conclusions: Advanced stage of HIV infection is associated with an atherogenic lipid profile including a high prevalence of sdLDL. Lopinavir/ritonavir-containing regimen accentuates the reduction of LDL size. Since fibrates decrease TG and increase LDL size, they appear as a logical option to manage HAART-induced HTG. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.