Single doses of indinavir (Crixivan) or ritonavir (Norvir) have been shown to decrease insulin-mediated glucose disposal in healthy, HIV negative subjects, thus demonstrating that some HIV protease inhibitors can cause insulin resistance in those without HIV infection, hyperlipidemia or HIV-associated lipodystrophy.

In the current study, investigators evaluated the effect of a single dose of amprenavir (Agenerase), and HIV PI that reportedly does not affect insulin-mediated glucose disposal.

This was a randomized, double-blind, cross-over study, a single dose of amprenavir 1200 mg or placebo was given to six healthy HIV-negative men 1 h before assessment of insulin sensitivity by euglycaemic hyperinsulinaemic clamp.

Results

• There were no significant differences in body weight, fasting plasma glucose, serum insulin or lipid levels before each clamp experiment.
• Free fatty acid levels were not significantly different at baseline and were suppressed similarly with insulin administration during both experiments.
• The non-oxidative component of total glucose disposal also did not change with either placebo or amprenavir administration.

Based on these results, the authors write, “A single dose of amprenavir in HIV-negative men did not decrease insulin-mediated glucose disposal as assessed by the euglycaemic hyperinsulinaemic clamp.”

“Relatively lower therapeutic levels of amprenavir may explain why amprenavir inhibits GLUT4 in vitro, but does not inhibit insulin-mediated glucose disposal.”

12/09/05

Reference
G A Lee and others. A single dose of amprenavir does not induce insulin resistance in healthy normal volunteers. Abstract 15. 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. November 13-16, 2005, Dublin, Ireland. Antiviral Therapy 2005; 10:L11.