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

J Acquir Immune Defic Syndr. 2016 Apr 15;71(5):530-7. doi: 10.1097/QAI.0000000000000908.

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.

Findings: 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.

Interpretation: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / etiology
  • Bone Density / drug effects
  • Cobicistat / therapeutic use*
  • Drug Substitution*
  • Drug Therapy, Combination
  • Emtricitabine / therapeutic use*
  • Female
  • Glomerular Filtration Rate / drug effects
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Proteinuria / etiology
  • Quinolones / therapeutic use*
  • Renal Insufficiency / etiology
  • Renal Insufficiency / physiopathology
  • Renal Insufficiency / prevention & control*
  • Tenofovir / therapeutic use*

Substances

  • JTK 303
  • Quinolones
  • Tenofovir
  • Emtricitabine
  • Cobicistat

Associated data

  • ClinicalTrials.gov/NCT01818596