title: A randomized study of pharmacokinetics, efficacy, and safety of 2 raltegravir plus atazanavir strategies in ART-treated adults.
abstract: BACKGROUND
  New antiretroviral drug classes provide opportunities to explore novel regimens.
  
  
  METHODS
  HIV+ adults (<50 copies/mL) receiving atazanavir (ATV) were randomized to raltegravir (RAL) 400 mg + ATV 300 mg twice daily (q12h) for 4 weeks followed by RAL 800 mg + ATV/ritonavir 300/100 mg once daily (q24h) for 4 weeks or vice versa. Validated assays quantitated RAL and ATV plasma concentrations. Primary endpoint was geometric mean ratio (GMR) of ATV minimum concentration (Cmin) for q24h/q12h. Equivalence was 90% confidence interval (CI) of GMR lying between 0.80 and 1.25. Participants could consent to a total 48-week follow-up.
  
  
  RESULTS
  Twenty-five men, mean age 45 (range, 35-57) years, were evaluated. ATV and RAL demonstrated considerable pharmacokinetic variability. There was no period or sequence effect for pharmacokinetic parameters (P > 0.1 all measures). Ninety percent CIs of ATV GMR C(min) [1.30 (90% CI: 1.08 to 1.58)] and RAL GMR C(min) [0.48 (90% CI: 0.31 to 0.75)] demonstrated nonequivalence. Seventy-six percent consented to follow-up. There were no serious adverse events and no discontinuations due to adverse events over 48 weeks; HIV RNA remained undetectable.
  
  
  CONCLUSIONS
  In virologically suppressed adults, regimens comprising ATV plus RAL were efficacious and safe. ATV q12h troughs were lower than ritonavir-boosted atazanavir q24h; RAL q24h troughs were lower than q12h.
authors.affiliation: Kirby Institute/University of New South Wales, Sydney, Australia. dcarey@kirby.unsw.edu.au
authors.forename: Dianne
authors.initials: D
authors.lastname: Carey
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Pett
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.forename: Handan
authors.initials: H
authors.lastname: Wand
authors.forename: Karen
authors.initials: K
authors.lastname: MacRae
authors.forename: Kate
authors.initials: K
authors.lastname: Beileiter
authors.forename: John E
authors.initials: JE
authors.lastname: Ray
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boyd
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D000069446:Atazanavir Sulfate; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010949:Plasma / Q000737:chemistry; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000068898:Raltegravir Potassium; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate