Safety and efficacy of switching to tenofovir alafenamide (TAF) in virally suppressed chronic hepatitis b (CHB) patients with renal impairment: Week 48 results from a phase 2 open- label study

Document Type

Conference Proceeding

Publication Date


Publication Title

Am J Gastroenterol


Introduction: Switching to TAF, a novel tenofovir prodrug, has shown maintenance of viral suppression with stable or improved bone and renal safety at Week 24 in CHB patients with moderate to severe renal impairment (eGFR by Cockcroft-Gault [eGFRCG] , 60 mL/min) and ESRD patients on HD. We evaluated the safety and efficacy in these virally suppressed patients with renal impairment 1 year after switching to TAF in a Phase 2 study. Methods: CHB patients with renal impairment receiving TDF and/or other OAVs for ≥48 weeks and virally suppressed for ≥6 months with HBV DNA < 20 IU/mL at screening were enrolled into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG 15 to , 60 mL/min) and 2) ESRD (eGFRCG < 15 mL/min) on chronic HD. All patients were switched to TAF 25 mg QD for 96 weeks (given post-HD on days of dialysis for ESRD patients). Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters, viral suppression, and biochemical responses were assessed in all patients at Week 48. Results: 93 patients (moderate-severe impairment 78; ESRD 15) were enrolled from 26 sites in 8 countries; 89% of patients remained on study at Week 48. At baseline, 74% were male, 77% Asian, 68% ≥60 y, 83% HBeAg-negative and median ALT was 17 U/L. Up to 25% overall (both cohorts) had osteoporosis at hip and/or spine, and a high proportion had comorbidities (60% HTN> 24% DM). Key efficacy/safety results at Week 48 are summarized in the Table. Efficacy (HBV DNA, 20 IU/mL) was maintained in nearly all patients on treatment at Week 48 and a high proportion had normal ALT levels. Five patients discontinued study drug early (withdrew consent) with last available HBV DNA < 20 U/mL; 1 patient had HBV DNA ≥20 IU/mL and 1 patient died. Relative to baseline levels, switching to TAF resulted in stable hip/spine BMD in moderate to severe renal impairment patients, with a slight decrease in hip BMD in ESRD patients. Slight improvements were observed in renal parameters including eGFRCG and markers of renal tubular function in moderate to severely impaired patients. TAF was well tolerated, with no Grade 3/4 or serious adverse events related to study drug. Conclusion: In renally-impaired CHB patients, including ESRD patients on HD, viral suppression was well maintained, and the bone and renal safety were stable or improved 48 weeks after switching to TAF.

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Not assigned.





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