• Genes, Diet, and Atherogenic Dyslipidemia
  Ronald Krauss
• HIV Protease Inhibitors Increase Secretion of Apolipoprotein B-lipoproteins from Hepatoma Cells by Preventing Proteasomal Degradation
  Henry Ginsberg
• Differences in Postprandial Lipid Metabolism in Patients with PI-Associated and NRTI-Associated Lipodystrophy
  Lisa Ware
• Increased tPA Antigen Levels in the HIV Lipodystrophy Syndrome are Reduced in Response to Metformin
  Colleen Hadigan

These four sessions were devoted to dyslipidemia, endothelial dysfunction and bones. The first session on dyslipidemia started with a review from Ronald Krauss about genes, diet, and lipids and their contribution to atherogenesis. Dr. Ginsberg from Columbia University then presented data showing that, at very high doses, protease inhibitors inhibit the proteasome. This would inhibit the degradation of some lipoproteins, like apoB, and lead to an increased secretion of lipoproteins into the circulation. This explains the hypertriglyceridemia associated with protease inhibitor treatment. I have difficulty, as some other people in the audience pointed out, believing that inhibition of the proteasome of the cell (critical for many cell functions) would not lead to more generalized problems in the body then just increased lipids. As usual, further studies are needed.

Lisa Ware from the Chelsea and Westminster hospital in London looked at the rate of clearance of labeled triacylglycerol (TAG) and non-esterified fatty acids (NEFA) in a cohort of patients on protease inhibitor-based therapy who were experiencing lipodystrophy. She compared these patients to patients in double nucleoside regimens who also had lipodystrophy. Patients on protease inhibitors with lipodystrophy had an increased retention time of lipids as TAG vs. the other group that tended to retain as NEFA. This suggests that things are never simple and that these differences may influence the evolution of body composition in different antiretroviral regimens.

Colleen Hadigan from the Harvard group presented data demonstrating that the levels of tissue plasminogen activator (tPA) -- a marker of increased cardiovascular risk -- were increased in patients with lipodystrophy, when compared to the Framingham cohort. These levels decreased after treatment with metformin, which could improve the cardiovascular risk of these patients.