TENOFOVIR ALAFENAMIDE (TAF) FOR MULTIPLE DRUG-RESISTANT HEPATITIS B: A RANDOMIZED, MULTICENTER TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF SWITCHING FROM TDF TO TAF VS. CONTINUING TDF IN CHB PATIENTS WITH GENOTYPIC RESISTANCE TO ETV AND/OR ADV

Abstract

Background: Monotherapy with tenofovir disoproxil fumarate (TDF) showed a high rate of virologic response in patients with hepatitis B virus (HBV) resistant to entecavir and/or adefovir. Nonetheless, there is concern regarding renal and bone safety during long-term use of TDF, as previously shown by our 5-year TDF therapy trials. Tenofovir alafenamide (TAF) has shown similar antiviral efficacy with better renal and bone safety, compared with TDF in treatment-naïve chronic hepatitis B (CHB) patients.

Methods: This was a randomized trial to assess whether switching TDF to TAF shows non-inferior efficacy and better safety profile in patients with multidrug-resistant HBV compared to continuing TDF. Patients with HBV resistant to entecavir and/or adefovir under TDF monotherapy for at least 96 weeks were randomized 1:1 to switch to TAF (TAF group) or continue TDF (TDF group) for 48 weeks. The primary efficacy endpoint was the proportion of patients with HBV DNA <60 IU/mL in the full analysis set. Renal function and bone mineral density in the on-treatment analysis set were also assessed.

Results: Of 174 eligible patients under TDF monotherapy, 87 switched to TAF and 87 continued TDF. At baseline, 163 (93.7%) patients had HBV DNA less than 60 IU/mL (96.6% in TAF group vs. 90.8% in TDF group), and 149 (85.6%) patients had normal ALT (≤40 IU/L; 85.1% in TAF group vs. 86.2% in TDF group). At week 48, the proportion of patients with HBV DNA <60 IU/mL was 98.9% in TAF group, which was non-inferior to TDF group (97.8%; P=0.99). The proportion of patients with normal ALT at week 48 tended to be higher in TAF group compared with TDF group (92.0% vs. 79.3%; P=0.06). TAF group showed a significantly higher increase in bone mineral density (BMD) at spine compared with TDF group at week 48 (mean % change, +1.84% vs. 0.08%; P=0.01). TAF group, compared to TDF group, tended to show a larger increase in estimated glomerular filtration rate from baseline as measured by CKD-EPI (mean % change, +7.1% vs. +3.9%; P=0.07) and by Cockcroft-Gault formula (mean % change, +8.2% vs. +4.5%; P=0.06).

Conclusion: In CHB patients with multidrug-resistant HBV, switching TDF to TAF was as effective as TDF in virologic response with improved bone and renal safety.