final program.qxd - Parallels Plesk Panel

SS 4.1
Pharmacologic Prerequisites
No abstract available
SS 4.2
Resistance at Stake
No abstract available
SS 4.3
From Lipids to Cardiovascular Risk
No abstract available
SS 4.4
Future Trends
No abstract available
SS 5.1
HIV-associated lipodystrophy: pathophysiology
Jacqueline Capeau
Inserm U680 Faculté de Médecine Pierre et Marie Curie, 27 rue Chaligny 75012 Paris,
France
Hôpital Tenon, AP-HP, Paris
The lipodystrophy syndrome associates altered body fat repartition (peripheral lipoatrophy
and/or visceral fat hypertrophy) and metabolic alterations (dyslipidemia, insulin resistance
and altered glucose tolerance). The pathophysiology of these alterations is complex: in
addition to factors linked to the patient and to HIV infection, different studies argue for
adipose tissue being the target of some protease inhibitors (PIs) and of thymidine
analogues among the nucleoside analogues inhibitors of the viral reverse transcriptase
(NRTIs) acting through different mechanisms. Thymidine analogues are able to induce
mitochondrial dysfunction and to modify adipocyte phenotype, these alterations being
reverted in vitro by the addition of uridine. They also modify the adipose tissue pattern of
secretion of cytokines (TNF , IL-6) and other adipokines (adiponectin, leptin) probably
through the production of reactive oxygen species. Some PIs also act on adipocytes, alter
their differentiation and insulin sensitivity and also the pattern of secretion of adipokines
by adipose tissue. Lipodystrophic adipose tissue is markedly modified, with decreased
adipocyte and increased macrophage number resulting in a state of low grade
inflammation. These hypotheses could explain the loss of adipose tissue, while the
mechanisms of visceral fat hypertrophy remains speculative. Since some adipokines and
the free fatty acids released by insulin resistant adipocytes play a major role in the control
of liver and muscles insulin sensitivity, these alterations are probably involved in the
metabolic alterations seen in the patients with increased risks of cardiovascular disease
and of steatohepatitis. Besides strategies using plastic surgery, the treatment of
lipodystrophy remains difficult and, at present, privileges the switch of the more
deleterious drugs towards new molecules less aggressive for adipose tissue. Clinical trials
using uridine to reverse thymidine analogues toxicity or the thiazolidinedione pioglitazone
showed promising results on peripheral lipoatrophy but require further validation.
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