Switch studies in virologically suppressed patients

Switch to E/C/F/TAF
GS-US-292-0112 Study
Original article : Pozniak A. JAIDS 2016;71:530-7
Dernière mise à jour : 17/03/2016

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • In virologically suppressed HIV-infected subjects with renal impairment, switch to E/C/F/TAF was associated with minimal change in eGFR
  • Proteinuria and albuminuria significantly improved
  • Bone mineral density significantly improved in patients receiving TDF-containing regimens prior to switching to E/C/F/TA
  • Virologic success was maintained in 92% of patients
  • These data support the efficacy and safety of once daily E/C/F/TAF in HIV-1 infected patients with mild (eGFR 50-69 mL/min) or moderate (eGFR 30-49 mL/min) renal impairment without dose adjustment

Design


Co-formulated EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg (E/C/F/TAF) qd with food

Endpoints

  • Primary: change from baseline at W24 in estimated glomerular filtration rate by various formulas: Cockroft-Gault, CKD-EPI-cystatin C, CKD-EPI-creatinine
  • Secondary: eGFR at W48 and W96, measured GFR, renal and bone biomarkers, hip and spine BMD (DXA), adverse events, virologic control

Baseline characteristics

Estimated GFR (mL/min): Median change from Baseline to Week 24

  • No clinically appreciable change in estimated creatinine clearance
  • In 32 patients, GFR was measured by iohexol clearance: actual GFR was not affected over 24 weeks of treatment for the whole group, subgroups with baseline eGFRCG < 50 vs ≥ 50, or with or without TDF prior to switch

Proteinuria: median value (mg/g) at baseline and W48


*All Total and TDF changes statistically significant; †all non-TDF changes not statistically significant.

Clinically significant proteinuria and albuminuria: baseline and W48

BMD: mean change (%, SD) from baseline to W48

Adverse events

  • Most common adverse events
    • Diarrhea 11%
    • Upper respiratory tract infection 9%
    • Arthralgia 9%
    • Bronchitis 8%
    • Osteopenia 8%
    • Nausea 8%
    • Headache 7%
    • Pain in extremity 7%
    • Back pain 7%
    • Dizziness 6%
    • Fatigue 6%
    • Renal cyst 6%
    • Cough 6%
  • Adverse events leading to study drug discontinuation, N = 8 (3%), 2/8 for decreased GFR (both patients with hypertension)
  • Fractures, N = 6, all related to mechanical trauma

Fasting lipid changes

  • Decrease in patients who used non-TDF-containing regimens prior to switching to E/C/F/TAF
  • Increase in those using TDF-containing regimens prior to E/C/F/TAF

Pharmacokinetics

  • EVG and COBI: in the range of historical data in patients without renal impairment
  • FTC: higher than historical data in patients without renal impairment, higher in patients with eGFR < 50 mL/min vs ≥ 50 mL/min
  • TAF: consistent with historical data in patients without renal impairment
    • TFV: higher than historical data in patients without renal impairment, but well below the TFV exposures from TDF-containing regimens

Efficacy at W48

  • HIV-1 RNA < 50 c/mL: 92%
  • Virologic failure: 1% (N = 3)

 

   

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