Effectiveness of tenofovir alafenamide for chronic hepatitis B patients with a poor response to the previously used nucleos(t)ide analogs.

Background: Few studies have demonstrated the potency of tenofovir alafenamide (TAF) in patients with poor response to other nucleos(t)ide analogs (NAs).

Methods: We conducted a retrospective study comprising consecutive 40 patients exhibiting a poor response to other NAs, who subsequently received TAF-containing regimens. The primary outcome was the prevalence of virological response (VR) at each time and maintained virological response (MVR) under TAF-containing regimens until week 96.

Results: In the entire cohort, the prevalence of MVR was 71.1% (27/38). Further, poor tenofovir disoproxil fumarate (TDF) response was significantly associated with a lower prevalence of MVR (p = 0.014). In TDF-naïve patients, the prevalence of MVR was 92.3% (12/13) and 62.5% (5/8) in patients with lamivudine resistance (LAM-r) and entecavir resistance (ETV-r), respectively. Further, viral load and HBeAg status at baseline were associated with a lower prevalence of MVR (p = 0.013). Among the seven patients with prior TDF exposure, 2 patients achieved MVR. Among them, one patient with development of viral breakthrough during TDF/LAM achieved MVR after switching to TAF/ETV. In contrast, one of the five patients with non-MVR had three substitutions (rtS106C, rtD134N/S, and rtL269I) of quadruple mutations in addition to ETV-r. Other patients with rtA181T + rtN236T also could not achieve MVR.

Conclusion: TAF exhibited high antiviral potency in patients with LAM-r and ETV-r. However, TAF potency was associated with previous TDF response, viral load, and HBeAg status at baseline. Additionally, a quadruple mutation may impact tenofovir resistance; however, further studies are needed to verify this.