Apoprotein c-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: association with the development of lipodystrophy.
Long-term therapy with protease inhibitors (PIs) can induce hypertriglyceridemia and development of a lipodystrophy. To better understand these metabolic alterations, the apoprotein and lipoparticle profile was investigated in male HIV patients under antiretroviral therapy: 49 received PIs, and 14 were given only two reverse transcriptase inhibitors. As controls, 63 male subjects were selected from a population study carried out in the Toulouse, France, area. Fasting glucose, insulin, and C-peptide were also determined. All patients under PIs displayed low levels of plasma glucose and increased insulin. PI administration was associated with moderate hypertriglyceridemia, low high-density cholesterol and apolipoprotein (apo) A-I levels. The most striking changes were a 2- to 3-fold increase in apo E and apo C-III, essentially recovered as associated to apo B-containing lipoparticles. Levels of those lipoparticles were two to eight times above control values. About 50% of PI-treated patients had developed a patent lipodystrophy. Multivariate analysis revealed that, among the investigated parameters, apo C-III was the only one found strongly associated with the occurrence of lipodystrophy (odds ratio, 5.5; P: < 0.015). Finally, 13 PI-receiving subjects with patent hypertriglyceridemia were given fenofibrate and were reevaluated 2 months later. Triglycerides, apo E, apo C-III, and the corresponding lipoparticles had returned to nearly normal levels. These results document the accumulation of potentially atherogenic lipoparticles under PIs. Apo C-III may play a pivotal role in the development of hypertriglyceridemia and lipodystrophy.
Laboratoire de Biochimie III and Institut National de la Santé et de la Recherche Médicale U326, Toulouse-Cédex, France.
E
E
Bonnet
J B
JB
Ruidavets
J
J
Tuech
J
J
Ferrières
X
X
Collet
J
J
Fauvel
P
P
Massip
B
B
Perret
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000097:blood; D001056:Apolipoproteins C / Q000097:blood*; D001057:Apolipoproteins E / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008060:Lipodystrophy / Q000097:blood / Q000139:chemically induced*; D008297:Male; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D008055:Lipids; D011480:Protease Inhibitors; D011345:Fenofibrate