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Apoprotein C-III and E-Containing Lipoparticles Are Markedly Increased in HIV-Infected Patients Treated with Protease Inhibitors: Association with the Development of Lipodystrophy

Laboratoire de Biochimie III and Institut National de la Santé et de la Recherche Médicale U326 (J.T., X.C., J.Fa., B.P.), Service des Maladies Infectieuses (E.B., P.M.), and Institut National de la Santé et de la Recherche Médicale U518 (J.-B.R., J.Fe.), Toulouse University Hospital, 31059 Toulouse-Cédex, France

Address correspondence and requests for reprints to: Bertrand Perret, Institut National de la Santé et de la Recherche Médicale U326, Hôpital Purpan, 31059 Toulouse-Cédex, France. E-mail: perret{at}purpan.inserm.fr

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.

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