In the lipodystrophy syndrome, strange changes in the distribution of fat occur. For instance, it is not uncommon for fat in the face, arms and legs to disappear while fat in the breast and stomach increase. As well, levels of fatty substances — cholesterol and triglycerides — tend to increase, particularly in PHAs who use HAART. It is becoming increasingly clear that both protease inhibitors (PIs) and nukes play a role in the lipodystrophy syndrome. Nukes can affect the ability of fat cells to produce energy. These drugs can also cause fat cells to waste away. As previously mentioned, PIs can affect the ability of fat cells to absorb and burn glucose (sugar) to release energy. They also appear to affect the growth and development of fat cells. PIs can block the production of new fat cells and, over the long term, can cause mature fat cells to commit suicide, or apoptosis. The net effect of this is to cause fat, at least in some places, to disappear. Thus it is possible that nukes and PIs taken together have an even greater effect on the loss of fat than either group of drugs alone.

In laboratory experiments with fat cells, French researchers have found that the anti-diabetic drugs known as the glitazones are able to reverse the negative effects that PIs can have on fat cells. Therefore, glitazones have the potential to stop or even reverse some of the signs/symptoms of lipodystrophy — at least those signs/symptoms related to fat redistribution. This potential beneficial effect of glitazones needs to be tested in controlled clinical trials.

REFERENCES

1. Shiramizu B, Westgard E, Cossarizza A, et al. Competitive PCR-analysis of subcutaneous adipose tissue mitochondrial DNA from individuals with highly active antiretroviral therapy-associated lipodystrophy. Abstract 20 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.

2. Caron M, Auclair M, Kornprobst M and Capeau J. Differential in vitro effects of indinavir, nelfinavir and amprenavir on cell differentiation, insulin sensitivity and apoptosis in an adapted adipose cell model: preventive impact of rosiglitazone. Abstract 24 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.

3. Agrawal KC, LaRussa VF and Mondal D. Synergestic anti-adipogenic effects of HIV-1 protease inhibitors and TNF-alpha in dTC-l1 cells: role of ECM degrading proteases. Abstract 25 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.

4. Antella A, Moreno S, Rubí J, et al. Significant correlation between fat distribution abnormalities, elevatedplasma lipid levels and asymptomatic hyperlactatemia: a possible connection between lipodystrophy and mitochondrial toxicity. Abstract 33 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.

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