September 14, 2000
The best presentation of the afternoon, in my opinion, was from M. Noor from the University of California San Francisco (UCSF) group. They administered indinavir 800 mg q 8h (the usual dose we use in adults) to 10 non-HIV-infected individuals for four weeks and looked carefully at glucose metabolism, lipids and body shape (using fasting glucose, insulin, oral glucose tolerance test, an euglycemic clamp, fasting lipid, and body composition using DEXA and CT). An incredibly intensive study!
They look at the patients twice, both before receiving indinavir and then after four weeks of treatment. In only four weeks they presented evidence that these individuals became insulin resistant and one of them even became a diabetic. Because these patients were not receiving nucleoside analogs, we can be sure that this problem is definitely related to indinavir. There were no changes in lipid metabolism, and body composition remained stable in this short study. These results are in contrast with a previous study with ritonavir that showed severe alterations in lipid metabolism, but no effect in glucose metabolism when given to healthy subjects. So, it looks like not all protease inhibitors are created equal.