Long-term study supports tenofovir alafenamide for chronic hepatitis B

Background and aims

Tenofovir alafenamide (TAF) has demonstrated comparable efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety, in Chinese participants with chronic hepatitis B enrolled in two Phase 3 trials. This study aimed to evaluate the long-term virologic efficacy, serological and biochemical responses, resistance, and renal and bone safety of TAF over eight years in this population.

Methods

Participants completing the three-year double-blind phase were eligible to receive open-label TAF 25 mg/day for up to an additional five years (totaling eight years). Analyses of viral suppression (HBV DNA < 29 IU/mL), alanine aminotransferase normalization, serological responses, resistance surveillance, and safety outcomes were conducted.

Results

Among 334 enrolled participants, 212 of 227 participants randomized to TAF continued open-label TAF (TAF-TAF), and 99 of 107 participants on TDF switched to open-label TAF (TDF-TAF). At Year 8, 79.3% (180/227) and 78.5% (84/107) of participants in the TAF-TAF and TDF-TAF groups, respectively, achieved viral suppression (missing = failure); rates increased to 95.2% (180/189) and 95.5% (84/88) when excluding missing data. Alanine aminotransferase normalization rates remained high and comparable between groups. Serologic response rates continued to increase over time, with higher rates observed in the TAF-TAF group. Estimated glomerular filtration rate (by Cockcroft-Gault) and hip/spine bone mineral density remained stable in the TAF-TAF group through eight years; the small declines in these renal and bone parameters observed during double-blind TDF treatment improved after switching to open-label TAF. No resistance to TAF was detected.

Conclusions

This eight-year analysis provides robust evidence supporting the long-term efficacy and safety of TAF in Chinese patients with CHB. As the longest investigation of TAF in this population, our study not only supports the favorable long-term renal and bone safety of TAF but also demonstrates that declines in renal and bone parameters associated with TDF may be reversible after switching to TAF. These findings are particularly relevant for the aging CHB population in China and reinforce the role of TAF as the preferred long-term treatment option.