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.

• Authors: E Bonnet, J B Ruidavets, J Tuech, J Ferrières, X Collet, J Fauvel, P Massip, B Perret
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 86 Issue 1 Pg. 296-302 (Jan 2001) ISSN: 0021-972X [Print] United States
• PMID: 11232015 (Publication Type: Journal Article)

Chemical References

• Anti-HIV Agents
• Apolipoprotein C-III
• Apolipoproteins
• Apolipoproteins C
• Apolipoproteins E
• Blood Glucose
• Hypolipidemic Agents
• Lipids
• Protease Inhibitors
• Fenofibrate

Topics

• Adult
• Anti-HIV Agents (therapeutic use)
• Apolipoprotein C-III
• Apolipoproteins (blood)
• Apolipoproteins C (blood)
• Apolipoproteins E (blood)
• Blood Glucose (analysis)
• Female
• Fenofibrate (therapeutic use)
• HIV Infections (blood, drug therapy)
• Humans
• Hypolipidemic Agents (therapeutic use)
• Lipids (blood)
• Lipodystrophy (blood, chemically induced)
• Male
• Protease Inhibitors (adverse effects, therapeutic use)