title: Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial.
abstract: BACKGROUND
  The phase 4, METABOLIK trial demonstrated that changes in metabolic parameters with darunavir with low-dose ritonavir (DRV/r) were comparable to those observed with atazanavir with low-dose ritonavir (ATV/r). A comprehensive assessment of the effects of these agents on insulin sensitivity will provide additional, relevant clinical information.
  
  
  METHODS
  In this substudy of METABOLIK, HIV-1-infected, antiretroviral agent-naïve male subjects aged ≥18 years with a viral load of >1,000 copies/mL were randomized to receive DRV/r 800/100 mg once daily (qd) or ATV/r 300/100 mg qd, both with a fixed dose of tenofovir disoproxil fumarate/emtricitabine 300/200 mg qd. The effects of DRV/r versus ATV/r on insulin sensitivity over 48 weeks were compared using the euglycemic hyperinsulinemic clamp, the preferred method to assess insulin sensitivity; primary end point was the effect on insulin sensitivity during the first 12 weeks.
  
  
  RESULTS
  Twenty-seven subjects completed the study. In the DRV/r arm (n=14), median glucose disposal from baseline through weeks 12 and 48 was 9.3, 11.4, and 9.9 mg/kg*min, respectively; in the ATV/r arm (n=13), these values were 8.9, 8.6, and 9.1 mg/kg*min, respectively. Median insulin sensitivity in the DRV/r arm at baseline, week 12, and week 48 was 24.0, 25.0, and 21.5 mg/kg*min per μIU/mL×100, respectively; these values in the ATV/r arm were 20.7, 22.0, and 22.0 mg/kg*min per μIU/mL×100, respectively. Most subjects had ≥1 adverse event, including three serious adverse events (n=2 [DRV/r], n=1 [ATV/r]).
  
  
  CONCLUSIONS
  DRV/r and ATV/r displayed similar modest effects on insulin sensitivity using a euglycemic hyperinsulinemic clamp.
authors.affiliation: a Department of Medicine , University of Alabama School of Medicine , Birmingham , AL , USA.
authors.forename: Edgar Turner
authors.initials: ET
authors.lastname: Overton
authors.affiliation: b Department of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.affiliation: c Janssen Research & Development , Titusville , NJ , USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Coate
authors.affiliation: c Janssen Research & Development , Titusville , NJ , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.affiliation: d Janssen Scientific Affairs , LLC , Titusville , NJ , USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Perniciaro
authors.affiliation: d Janssen Scientific Affairs , LLC , Titusville , NJ , USA.
authors.forename: Yaswant K
authors.initials: YK
authors.lastname: Dayaram
authors.affiliation: e Janssen Global Services , LLC , Raritan , NJ , USA.
authors.forename: Guy
authors.initials: G
authors.lastname: De La Rosa
authors.affiliation: e Janssen Global Services , LLC , Raritan , NJ , USA.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Baugh
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000069446:Atazanavir Sulfate / Q000008:administration & dosage*; D000069454:Darunavir / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage*; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D007328:Insulin; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D000069454:Darunavir
keywords: Antiretroviral agents; Darunavir; Human immunodeficiency virus (HIV); Insulin sensitivity