Increased VLDL-apoB and IDL-apoB production rates in nonlipodystrophic HIV-infected patients on a protease inhibitor-containing regimen: a stable isotope kinetic study.
The aim of this study was to identify the first abnormalities of apolipoprotein B (apoB) metabolism in HIV-infected patients treated by antiretroviral therapy (ART) with protease inhibitors (PIs). The influence of ART on the metabolism of apoB in VLDL, IDL, and LDL was investigated in six patients receiving dual nucleoside reverse transcriptase inhibitors (NRTIs) and PI, and in five patients receiving NRTI and nevirapine. None of the patients had lipodystrophy. The study was performed in the fed state. Each subject received an intravenous injection of a 0.7 mg.kg-1 bolus of l-[1-13C]leucine, immediately followed by a 16 h constant infusion at 0.7 mg.kg-1.h-1. The VLDL- and IDL-apoB concentrations were significantly higher in PI-treated patients compared to non-PI-treated patients. The VLDL-apoB and IDL-apoB production rates were markedly higher in PI-treated patients compared to non-PI-treated patients (54.5 +/- 30.1 vs. 30.9 +/- 8.4 mg.kg-1.d-1, P = 0.04; and 43.5 +/- 20.0 vs. 18.7 +/- 7.8 mg.kg-1.d-1, P = 0.04, respectively). In conclusion, our study shows that patients receiving ART with PI present altered metabolism of the VLDL-IDL-LDL chain compared with patients treated without PI. These data confirm that PI therapy is associated with a physiopathological mechanism for dyslipidemia in addition to the effect of lipodystrophy on lipid metabolism.
Petit
Jean Michel
JM
Laboratoire de Biochimie and Institut National de la Santé et de la Recherche Médicale U498, Hôpital Universitaire du Bocage, 21000 Dijon, France. jean-michel.petit@chu-dijon.fr
Duong
Michel
M
Florentin
Emmanuel
E
Duvillard
Laurence
L
Chavanet
Pascal
P
Brun
Jean Marcel
JM
Portier
Henri
H
Gambert
Philippe
P
Verges
Bruno
B
D000328:Adult; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000097:blood; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D039682:HIV-Associated Lipodystrophy Syndrome; D006801:Humans; D007553:Isotope Labeling; D007700:Kinetics; D008074:Lipoproteins / Q000096:biosynthesis* / Q000097:blood; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000097:blood; D008297:Male
D001055:Apolipoproteins B; D017320:HIV Protease Inhibitors; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; C030104:lipoprotein cholesterol; D002784:Cholesterol