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

Abstract

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.