title: The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults.
abstract: BACKGROUND
  Therapy with some HIV protease inhibitors (PI) contributes to insulin resistance and type 2 diabetes mellitus, by inhibition of insulin-sensitive glucose transporters. Atazanavir (ATV) is a new PI with substantially less in vitro effect on glucose transport than observed with other PI, including lopinavir (LPV) or ritonavir (RTV).
  
  
  METHODS
  Randomized, double-blind, crossover study of the effect of 5 days of administering ATV, lopinavir/ritonavir (LPV/r) or placebo on insulin-stimulated glucose disposal in 30 healthy HIV-negative subjects. Each subject was studied on two of three possible treatments with a wash-out period between treatments.
  
  
  RESULTS
  The mean insulin-stimulated glucose disposal (mg/min per kg body weight) per unit insulin (microU/ml) (M/I) was 9.88, 9.80 and 7.52 for placebo, ATV and LPV/r, respectively (SEM, 0.84 for all). There was no significant difference between ATV and placebo. The M/I for LPV/r was 23% lower than that for ATV (P = 0.010) and 24% lower than that for placebo (P = 0.008). The mean glycogen storage rates were 3.85, 4.00 and 2.54 mg/min per kg for placebo, ATV and LPV/r, respectively (SEM, 0.39 for all). There was no significant difference between ATV and placebo. The glycogen storage rate for LPV/r was 36% lower than ATV (P = 0.003) and 34% lower than placebo (P = 0.006).
  
  
  CONCLUSIONS
  ATV given to healthy subjects for 5 days did not affect insulin sensitivity, while LPV/r induced insulin resistance. This observation is consistent with differential in vitro effects of these PI on glucose transport. Further data are needed to assess clinical implications for body composition.
authors.affiliation: Clinical Pharmacology Unit, Bristol-Myers Squibb, Princeton, New Jersey 08543, USA. mustafa.noor@bms.com
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Noor
authors.forename: Rex A
authors.initials: RA
authors.lastname: Parker
authors.forename: Edward
authors.initials: E
authors.lastname: O'Mara
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Grasela
authors.forename: Alexander
authors.initials: A
authors.lastname: Currie
authors.forename: Sally L
authors.initials: SL
authors.lastname: Hodder
authors.forename: Fred T
authors.initials: FT
authors.lastname: Fiedorek
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000069446:Atazanavir Sulfate; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D018023:HIV Seronegativity; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008060:Lipodystrophy / Q000378:metabolism; D061466:Lopinavir; D009842:Oligopeptides / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D017320:HIV Protease Inhibitors; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D006003:Glycogen