LAUSR

Background Presented herein are the post Week 48 through Week 96 resistance analyses for 2 Phase 3 studies evaluating tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate(TDF) for the treatment of chronic hepatitis B (CHB) in HBeAg +and HBeAg- adults. Methods HBV pol/RT population or deep sequencing was conducted for patients with ≥24 weeks of treatment with viremia (HBV DNA ≥69 IU/mL) at Week 96 or at early discontinuation post Week 48. Deep sequencing was conducted for patients with HBV DNA >159 IU/mL and sequence changes at the consensus sequence level (15%) are reported. Virologic breakthrough (VB) was defined as HBV DNA ≥69 IU/mL after achieving <69 IU/mL or a≥1.0-log10 increase from nadir. Phenotypic analysis using recombinant HBV in HepG2 cells was performed for VB patients who were adherent to study drug (plasma drug levels), patients with conserved site substitutions, or for polymorphic substitutions emergent in >1 patient. Results 1298 patients were randomised (TAF: n=866; TDF: n=432). A similar percentage of patients in the TAF or TDF arms qualified for sequence analysis post Week 48 through Week 96 of treatment (TAF: 10.5%, TDF: 10.9%). In the TAF arm, 87 patients qualified at Week 96: 32 had polymorphic site substitutions, and 9 had conserved site substitutions. In the TDF arm, 45 patients qualified at Week 96 11 had polymorphic site substitutions, and 2 had conserved site substitutions. At Week 96, a small percentage of patients experienced VB (TAF: 2.4%, TDF: 3.0%), and VB was often associated with documented study drug nonadherence (TAF: 22%, TDF: 46%). 27 patients qualified for phenotypic analysis post Week 48 through Week 96 (TAF: n=19, TDF: n=8) and no patient isolates tested showed a reduction in susceptibility to TAF or tenofovir, respectively. Conclusions The proportion of patients analysed and the HBV sequence changes observed were similar between patients in the TAF and TDF arms. Most substitutions occurred at polymorphic positions and no substitutions associated with resistance to TAF were detected through 96 weeks of treatment.