title: Effect of ritonavir-boosted tipranavir or darunavir on the steady-state pharmacokinetics of elvitegravir.
abstract: OBJECTIVE
  Elvitegravir (EVG) is in phase 3 development in combination with ritonavir (RTV)-boosted protease inhibitors in treatment-experienced, HIV-infected patients. Two studies evaluated pharmacokinetic (PK) interactions among EVG and RTV-boosted tipranavir (TPV/r) or darunavir (DRV/r).
  
  
  METHODS
  Healthy volunteers received EVG/r alone (study 1: 200/100 mg once daily; study 2: 125/100 mg once daily), TPV/r (500/200 mg twice daily) or DRV/r (600/100 mg twice daily) alone, and EVG (200 or 125 mg as applicable) added to TPV/r (500/200 mg twice daily) or DRV/r (600/100 mg twice daily) in a randomized crossover design, with assessment of steady-state PK for EVG, TPV, DRV, and RTV. Safety was assessed by clinical monitoring. Studies were powered to conclude lack of an interaction if the 90% confidence interval for the geometric mean ratios of the AUCtau and Cmax for EVG, TPV, and DRV were within predefined no-effect boundaries. Trough concentrations were also assessed.
  
  
  RESULTS
  No subjects discontinued for adverse events during treatment with EVG/r alone. On coadministration, AUCtau and Cmax of EVG and TPV and EVG and DRV were within prespecified no-effect boundaries versus treatment alone; trough concentrations were also not substantially altered.
  
  
  CONCLUSIONS
  The PK of EVG and TPV or DRV were not altered after coadministration of EVG with TPV/r or DRV/r. EVG PK was similar with varied RTV doses of 100 mg once daily, 100 mg twice daily, or 200 mg twice daily. EVG can be added to TPV/r or DRV/r regimens without dose adjustment.
authors.affiliation: Clinical Research, Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. anita.mathias@gilead.com
authors.forename: Anita A
authors.initials: AA
authors.lastname: Mathias
authors.forename: John
authors.initials: J
authors.lastname: Hinkle
authors.forename: Gong
authors.initials: G
authors.lastname: Shen
authors.forename: Jeff
authors.initials: J
authors.lastname: Enejosa
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Piliero
authors.forename: Vanitha
authors.initials: V
authors.lastname: Sekar
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mack
authors.forename: Frank
authors.initials: F
authors.lastname: Tomaka
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kearney