title: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study.
abstract: BACKGROUND
  Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved renal and bone safety compared with TDF-containing regimens. We report the 48 week safety and efficacy of a once-daily single tablet regimen of elvitegravir 150 mg (E), cobicistat 150 mg (C), emtricitabine 200 mg (F), and TAF 10 mg (E/C/F/TAF) in HIV-1-infected patients with mild to moderate renal impairment.
  
  
  METHODS
  We enrolled virologically suppressed HIV-1-infected subjects with estimated creatinine clearance (CrCl) 30-69 mL/min in a single-arm, open-label study to switch regimens to E/C/F/TAF. The primary endpoint was the change from baseline in glomerular filtration rate estimated using various formulae. This study is registered with ClinicalTrials.gov, number NCT01818596.
  
  
  RESULTS
  We enrolled and treated 242 patients with mean age 58 years, 18% Black, 39% hypertension, 14% diabetes. Through week 48, no significant change in estimated CrCl was observed. Two patients (0.8%) discontinued study drug for decreased creatinine clearance, neither had evidence of renal tubulopathy and both had uncontrolled hypertension. Subjects had significant improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001 for all). Hip and spine bone mineral density significantly increased from baseline to week 48 (mean percent change +1.47 and +2.29, respectively, P < 0.05). Ninety-two percent (222 patients) maintained HIV-1 RNA <50 copies per milliliter at week 48.
  
  
  CONCLUSIONS
  Switch to E/C/F/TAF was associated with minimal change in GFR. Proteinuria, albuminuria and bone mineral density significantly improved. These data support the efficacy and safety of once daily E/C/F/TAF in HIV+ patients with mild or moderate renal impairment without dose adjustment.
authors.affiliation: *Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom; †Department of Medicine, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain; ‡Therapeutic Concepts, Houston, TX; §Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; ‖King's College Hospital NHS Foundation Trust, London, United Kingdom; ¶Holdsworth House Medical Practice, Sydney, Australia; #HIV-NAT, Thai Red Cross AIDS Research Centre and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; **Gordon Crofoot Research, Houston, TX; ††Be Well Medical Center, Berkley, MI; ‡‡Department of Medicine, National Jewish Health, Denver, CO; §§Midway Research Center, Ft. Pierce, FL; ‖‖Department of Medicine, Khon Kaen University, Thailand; and ¶¶Gilead Sciences, Foster City, CA.
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
authors.forename: Jose R
authors.initials: JR
authors.lastname: Arribas
authors.forename: Joseph
authors.initials: J
authors.lastname: Gathe
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Gordon
authors.initials: G
authors.lastname: Crofoot
authors.forename: Paul
authors.initials: P
authors.lastname: Benson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lichtenstein
authors.forename: Moti
authors.initials: M
authors.lastname: Ramgopal
authors.forename: Ploenchan
authors.initials: P
authors.lastname: Chetchotisakd
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Custodio
authors.forename: Michael E
authors.initials: ME
authors.lastname: Abram
authors.forename: Xuelian
authors.initials: X
authors.lastname: Wei
authors.forename: Andrew
authors.initials: A
authors.lastname: Cheng
authors.forename: Scott
authors.initials: S
authors.lastname: McCallister
authors.forename: Devi
authors.initials: D
authors.lastname: SenGupta
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Fordyce
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000209:etiology; D015519:Bone Density / Q000187:drug effects; D000069547:Cobicistat / Q000627:therapeutic use*; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D000068679:Emtricitabine / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology; D015363:Quinolones / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000068698:Tenofovir / Q000627:therapeutic use*
chemical_list: D015363:Quinolones; C509700:elvitegravir; D000068698:Tenofovir; D000068679:Emtricitabine; D000069547:Cobicistat