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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 eGFR_CG < 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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