Selected Brief Highlights from the Lipodystrophy Conference

Selected Brief Highlights from the Lipodystrophy Conference
San Diego, June 27

I'm at the 1st Intl Workshop on Adverse Reactions and Lipodystrophy in HIV in San Diego, which immediately followed the Resistance Meeting. Several interesting points were suggested by a number of studies. The information is preliminary and I believe needs to be further explored but each bullet point described below is interesting and comes from at least one study. When I return to NYC a more comprehensive report will be forthcoming.

1. D4T may be associated with lipodystrophy. Several studies showed data associating the use of d4T with the development of lipodystrophy. Kees Brinkman of Amsterdam said d4T appears to cause mitochondrial toxicity moreso than AZT. He said in a personal conversation with me that ddI and 3TC do not cause mitochondrial toxicity. He said to me that studies with abacavir are in progress. He suggests that mitochondrial toxicity may be associated with the development of lipodystrophy. Several studies at this meeting showed data associating d4T with lipodystrophy. But Doug Ward from the CDC cautioned that although his study suggests that as well he suggested a correlation of the development of lipodystrohy with time on successful therapy. In other words, the lipodystrophy may not be developing due to d4T use but because therapy was successful over a period of time. Other researchers, particularly Don Kotler, suggest that lipodystrophy may be the result of raised CD4s and viral load reduced to low levels due to therapy after a prolonged period of HIV infection. Kotler has also suggested that it may also be an HIV infection itself that is associated with lipodystrophy. One abstract here and at Retrovirus in February suggested 3TC may be associated with lipodystrophy but
this appears a little more speculative.

2. NRTI therapy appears associated with lipodystrophy. Several studies here as well as several studies reported at Retrovirus, which were discussed in the April NATAP Reports newsletter, show data that lipodystrophy developed in people who have taken NRTIs and have not taken protease inhibitors. But the incidence of lipodystrophy increases after switching to a PI regimen.

3. One study presented here by Julian Falutz of Montreal showed that therapy with a saquinavir HAART regimen cause less incidence of lipodystrophy (24%) than an indinavir regimen (61%). The people on saquinavir were taking either Invirase or Fortovase but generally the effect on viral load was the same (undetectable). Data from his study and a second study reported a higher incidence of HIV/HAART associated lipodystrophy or alterations of fat tissue distribution for females than for men. One study reported an incidence of 26% vs 6.5% for women. Falutz also reported that women had more cases of elevated triglycerides (84% vs 14%), more cases of elevated cholesterol (53% vs 15%), and hypertension. 98% of individuals in this study were receiving combination therapy with a PI, and 51/210 had <500 copies/ml viral load.

4. Duration of therapy may correlate with lipodystrophy development It appears as though as time goes on the number of people with lipodystrophy may be increasing.. Individuals on double NRTI therapy for a few years who then switch to a PI regimen may be more likely to develop lipodystrophy.

5. At Retrovirus a Spanish study group reported on 12 weeks of data for individuals with lipodystrophy and undetectable viral load who switched to nevirapine in place of the PI. They reported improved lipids and some perception of improved body appearance. At this meeting they told me that after 1 year only 1 person's viral load rebounded but that fat redistribution did not improve.