Apoprotein C-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: Association with the development of lipodystrophy
E. Bonnet et al., Apoprotein C-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: Association with the development of lipodystrophy, J CLIN END, 86(1), 2001, pp. 296-302
Long-term therapy with protease inhibitors (PIs) can induce hypertriglyceri
demia and development of a lipodystrophy. To better understand these metabo
lic alterations, the apoprotein and lipoparticle profile was investigated i
n male HIV patients under antiretroviral therapy: 49 received PIs, and 14 w
ere given only two reverse transcriptase inhibitors. As controls, 63 male s
ubjects 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 increase
d insulin. PI administration was associated with moderate hypertriglyceride
mia, 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. Leve
ls of those lipoparticles were two to eight times above control values. Abo
ut 50% of PI-treated patients had developed a patent lipodystrophy. Multiva
riate analysis revealed that, among the investigated parameters, apo C-III
was the only one found strongly associated with the occurrence of lipodystr
ophy (odds ratio, 5.5; P < 0.015). Finally, 13 PI-receiving subjects with p
atent hypertriglyceridemia were given fenofibrate and were reevaluated 2 mo
nths later. Triglycerides, apo E, apo C-III, and the corresponding lipopart
icles had returned to nearly normal levels. These results document the accu
mulation of potentially atherogenic lipoparticles under PIs. Apo C-III may
play a pivotal role in the development of hypertriglyceridemia and lipodyst
rophy.