title: Cobicistat-boosted protease inhibitors in HIV-infected patients with mild to moderate renal impairment.
abstract: BACKGROUND
  Cobicistat (COBI) is a pharmacoenhancer that optimizes systemic exposures of protease inhibitors (PIs) such as atazanavir (ATV) and darunavir (DRV).
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of switching ritonavir (RTV) to COBI in patients with creatinine clearance (CrCl) 50 to 89 mL/min who are virologically suppressed on a stable regimen containing ritonavir (RTV)-boosted ATV or DRV. Other components of the regimen remained unchanged.
  
  
  METHODS
  A phase 3, non-comparative, open-label clinical trial.
  
  
  RESULTS
  Seventy-three patients were enrolled. At week 48, 82% maintained virologic suppression. No emergent resistance developed. Serious adverse events (AEs) occurred in 7%, and study drug discontinuation due to AEs occurred in 10% (7 patients). There were 2 renal discontinuations and no cases of proximal renal tubulopathy. Small reductions in CrCl (median [IQR]) were observed as early as week 2, after which they were nonprogressive through week 48 (-3.8 [-9 to 0.8]). Changes in CrCl by baseline CrCl (< 70 vs ≥ 70) were -1.1 [-6.5 to 6.3] versus -6.6 [-12.4 to -0.7], respectively.
  
  
  CONCLUSIONS
  In HIV-1-infected patients with CrCl 50 to 89 mL/min switching from RTV to COBI, COBI-boosted PIs in combination with 2 nucleos(t)ide reverse transcriptase inhibitors were well-tolerated and effective in maintaining virologic suppression. The renal safety profile of COBI in this study was consistent with the long-term data in patients without renal impairment from the phase 3 studies of COBI-containing regimens.
authors.affiliation: Tarrant County Infectious Disease, Fort Worth, Texas.
authors.forename: Cheryl K
authors.initials: CK
authors.lastname: McDonald
authors.affiliation: The Research Institute, Springfield, Massachusetts.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martorell
authors.affiliation: Midway Immunology and Research Center, Fort Pierce, Florida.
authors.forename: Moti
authors.initials: M
authors.lastname: Ramgopal
authors.affiliation: Clinique Medicale du Quartier Latin, Montreal, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Laplante
authors.affiliation: Brighton and Sussex Medical School, Brighton, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.affiliation: Kings College Hospital, London, UK.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Yapei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Joanne
authors.initials: J
authors.lastname: Curley
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Abram
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Joseph
authors.initials: J
authors.lastname: Custodio
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Hiba
authors.initials: H
authors.lastname: Graham
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Rhee
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Javier
authors.initials: J
authors.lastname: Szwarcberg
mesh_terms: D000328:Adult; D000368:Aged; D002219:Carbamates / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000069547:Cobicistat; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*; D013844:Thiazoles / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D002219:Carbamates; D017320:HIV Protease Inhibitors; D013844:Thiazoles; D000069547:Cobicistat
keywords: HIV clinical trials; cobicistat; renal impairment