Longer-term follow-up of patients with body fat changes who have switched from a protease inhibitor to a PI-sparing combination shows that body fat maldistribution does not improve after six to twelve months in the vast majority of cases, according to presentations today at the Seventh Retroviruses Conference in San Francisco.
Studies reporting on switches from PIs to efavirenz or nevirapine all showed that by and large, fat distribution was not significantly affected by the therapy switch, even though all studies showed improvements in cholesterol and triglyceride levels, and little evidence of viral rebound after the switch.
However, switching to abacavir did result in significant improvement in one study, and one Spanish study showed some improvement in central obesity after a switch to efavirenz.
A 48 week randomised study of Spanish patients with lipodystrophy who switched from a PI-containing regimen to d4T/ddI/nevirapine did not show significant improvements in body fat distribution in the switch group(Ruiz), and there was no significant differences in levels of cholesterol and triglycerides between those who switched and those who stayed on a PI-containing regimen. Levels of lipids declined in both groups of patients.
An Australian study of switching from PI containing therapy to abacavir/nevirapine/adefovir/hydroxyurea also found no significant improvement amongst the switch group. The study was designed to identify an option for PI recipients who had taken several nucleoside combinations and therefore had probably developed some resistance to nucleoside analogues.
Body fat continued to decline, and did so more significantly, in those who switched to the PI-sparing regimen, probably due to the frequency of nausea and vomiting that interfered with food intake. However, central fat accumulation (hard fat in the abdomen) did decrease after 24 weeks, and so did cholesterol and triglyceride levels. Interestingly, patients believed that their fat maldistribution had improved, even though DEXA measurements showed no significant change (Carr).
A 24 week US study of 40 individuals with lipodystrophy who substituted nevirapine for a protease inhibitor found that fat maldistribution actually worsened, despite improvements in cholesterol and triglyceride levels, leading the investigators to conclude that the syndrome may be irreversible (Tebas).
More optimistically, French investigators reported that 50% of those with central obesity who switched from a PI to abacavir experienced significant improvement in central obesity after 24 weeks (Rozenbaum). Other measures of fat maldistribution did not show significant improvement. The study looked at 34 patients in the CNA30017 study, so the numbers in this study are fairly small.
Barcelona researchers reported significant improvement in central fat accumulation in eleven out of twenty patients who switched from a PI-containing regimen to efavirenz, but no improvement in peripheral fat wasting after 24 weeks (Martinez).
However, a French group reported no improvement after six months in either lipid levels or body fat in 43 patients switched from a protease inhibitor to efavirenz (Bonnet).
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References
Bonnet E et al. Evaluation of lipodystrophy syndrome and lipidic profile in HIV patients after switching from protease inhibitors to efavirenz. Abstract 49, Seventh Conference on Retroviruses, San Francisco 2000.
Carr A et al. A randomised multicenter study of protesae inhibitor substitution in aviremic patients with antiretroviral lipodystrophy syndrome. Abstract 204, Seventh Conference on Retroviruses, San Francisco 2000.
Martinez E et al. Impact of switching from HIV-1 protease inhibitors to efavirenz in patients with lipodystrophy. Abstract 50, Seventh Conference on Retroviruses, San Francisco 2000.
Ruiz L et al. Clinical, virological and immunological benefit of switching from a protease inhibitor by nevirapine in HAART-experienced patients suffering lipodystrophy: 36 week follow-up. Abstract 206, Seventh Conference on Retroviruses, San Francisco 2000.
Tebas P et al. A prospective open label pilot trial of a maintenance nevirapine containing regimen in patients with undetectable viral loads on protease inhibitor regimens for at least six months. Abstract 45, Seventh Conference on Retroviruses, San Francisco 2000.