title: 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.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Taylor
authors.forename: Grace A
authors.initials: GA
authors.lastname: Lee
authors.forename: Vivian Y
authors.initials: VY
authors.lastname: Pao
authors.forename: Jayaranjan
authors.initials: J
authors.lastname: Anthonypillai
authors.forename: Francesca T
authors.initials: FT
authors.lastname: Aweeka
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Schwarz
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D006805:Human Experimentation; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D007328:Insulin; D010919:Placebos; D005947:Glucose; D019438:Ritonavir