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.


METHODS
24 antiretroviral-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 nm, 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 apoA1 (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.
Department of Biochemistry, University Hospital, 191 av du doyen Gaston Giraud, Montpellier 34295, France.
S
S
Badiou
C
C
Merle De Boever
A M
AM
Dupuy
V
V
Baillat
J P
JP
Cristol
J
J
Reynes
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016632:Apolipoprotein A-I / Q000378:metabolism; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000378:metabolism; D001056:Apolipoproteins C / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D061466:Lopinavir; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011744:Pyrimidinones / Q000276:immunology / Q000627:therapeutic use*; D019438:Ritonavir / Q000276:immunology / Q000627:therapeutic use*; D013223:Statistics as Topic; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism; D019562:Viral Load
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D015415:Biomarkers; D008076:Cholesterol, HDL; D017320:HIV Protease Inhibitors; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D011744:Pyrimidinones; D014280:Triglycerides; D061466:Lopinavir; D019438:Ritonavir