Boosting dose ritonavir does not alter peripheral insulin sensitivity in healthy HIV-seronegative volunteers

Abstract

Background: Some HIV protease inhibitors (PIs), including full-dose ritonavir (800 mg) and ritonavir-boosted lopinavir, acutely induce insulin resistance in the absence of HIV infection and changes in body composition. Boosting dose ritonavir (100-200 mg) is the most commonly prescribed PI, yet its effects on glucose metabolism have not been described in the absence of another PI.

Methods: In this randomized, double-blind, cross-over study, a single dose of ritonavir 200 mg or placebo was given to healthy HIV-seronegative volunteers before assessment of insulin sensitivity by euglycemic hyperinsulinemic clamp.

Results: Boosting dose ritonavir had no effect on insulin-mediated glucose disposal (M/I, placebo: 8.59 ± 0.83 vs. ritonavir: 8.51 ± 0.64 mg/kg per minute per μU/mL insulin, P = 0.89).

Conclusions: A single boosting dose of ritonavir does not alter insulin sensitivity, suggesting lopinavir is likely responsible for the induction of insulin resistance demonstrated in prior short-term studies of lopinavir/ritonavir. There is a dose-dependent effect of ritonavir on insulin sensitivity.

Trial registration: ClinicalTrials.gov NCT00525239.

Figures

Figure 1

(A) Plasma ritonavir levels during the euglycemic hyperinsulinemic clamp. Values presented are mean ± SEM. (B) Whole blood glucose levels (mg/dL) and rate of glucose infusion (mL/h) during the euglycemic hyperinsulinemic clamp after administration of placebo and boosting-dose ritonavir. Values presented are median ± IQR. (C) Insulin-mediated glucose disposal (mg/kg*min per μU/ml) with placebo and boosting-dose ritonavir administration. Values presented are mean ± SEM. A: Ritonavir Levels B: Whole blood glucose levels (mg/dL) and rate of glucose infusion (mL/h) C: Insulin-mediated Glucose Disposal