A hypothesis has been proposedAlthough the precise mechanisms underlying the syndrome are not known a hypothesis has been proposed that may explain the pathogenesis of these changes.[14] The currently available protease inhibitors have a high affinity for the catalytic site of HIV-1 protease. This catalytic region has about 60% sequence homology with sequences on 2 proteins involved in the regulation of lipid metabolism: cytoplasmic retinoic acid-binding protein type 1 (CRABP-1) and low density lipoprotein-receptor- related protein (LRP).Moreover, CRABP-1 is involved in the production of cis-9-retinoic acid, and inhibition of this may result in impaired fat storage and release of lipids into the circulation. This hyperlipidaemia would be exacerbated by protease inhibitor binding to hepatic and endothelial LRP. Interestingly, several of the other features of the syndrome resemble the adverse effects of retinoic acid analogues such as isotretinoin. Although this hypothesis requires confirmation, if it is proved correct, future development plans for antiretroviral protease inhibitors should include evaluation of their effects against these important proteins. Protease inhibitors that do not interfere with these proteins should not cause the lipodystrophy syndrome. Not just men affected Most cases of lipodystrophy have occurred in men infected with HIV. However, this syndrome has also been reported in women.[15] In the first study documenting lipodystrophy syndrome in women, 19 of 118 (16%) protease inhibitor recipients complained of changes in body habitus between 2 to 22 months after starting therapy. The changes in women affected by the syndrome are similar to those seen in men. In addition to the increase in abdominal size reported by 90% of affected patients, 71% also reported an increase in breast size. Abnormalities in lipid profiles were also observed in most of these patients. A good response to therapy?Many patients who develop lipodystrophy have a good response to anti-HIV treatment and it has been suggested that the rapid bodyweight gain achieved by these patients, in combination with certain drugs, may be the cause of the abnormal fat distribution
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