The Acute Effects of HIV Protease Inhibitors on Insulin Suppression of Glucose Production in Healthy HIV-Negative Men

Background: The effects of different HIV protease inhibitors (PIs) on peripheral insulin resistance have been described, but less is known about their effects on insulin suppression of endogenous glucose production (EGP). Methods: We tested the acute effects of 3 PIs, indinavir, ritonavir, and amprenavir, on EGP quantified by stable isotope techniques during the hyperinsulinemic, euglycemic clamp in 3 similar placebo-controlled protocols. Results: EGP was higher with indinavir in the hyperinsulinemic state than with placebo (4.1 ± 1.3 vs. 2.2 ± 0.8 μLg·kg -1 ·min -1 , P = 0.04). A trend toward higher EGP was seen with ritonavir (3.6 ± 0.3 vs. 3.0 ± 0.5 μg·kg -1 ·min -1 , P = 0.08). There was no evidence that amprenavir blunted insulin suppression of EGP compared with placebo (2.9 ± 0.04 vs. 3.2 ± 0.7 μg·kg -1 ·min -1 , P = 0.63). Conclusions: Some PIs can acutely blunt the ability of insulin to suppress EGP, but, as with insulin resistance, the effects of PIs on EGP are drug-specific, not class-specific.