Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: results of a randomised trial

Abstract

Objective Little clinical data are available regarding the optimal treatment of patients who harbour adefovir-resistant HBV. Design In this multicentre trial, patients who had adefovir-resistant HBV with serum HBV DNA levels > 60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n= 50) or TDF and entecavir (ETV, 1 mg/day) combination therapy (TDF/ETV, n= 52) for 48 weeks. All who completed 48 weeks in either group received TDF monotherapy for 48 additional weeks. Results Baseline characteristics were comparable between groups, including HBV DNA levels (median, 3.38 log(10) IU/mL). All patients had adefovir-resistant HBV mutations; rtA181V/T and/or rtN236T. The proportion of patients with HBV DNA < 15 IU/mL was not significantly different between the TDF-TDF and TDF/ETV-TDF groups at weeks 48 (62% vs 63.5%; p= 0.88) and 96 (64% vs 63.5%; p= 0.96). The mean change in HBV DNA levels from baseline was not significantly different between groups at week 48 (-3.03 log(10) IU/mL vs -3.31 log(10) IU/mL; p= 0.38). Virological breakthrough occurred in one patient on TDF-TDF and two patients on TDF/ETV-TDF over 96 weeks; all were attributed to poor drug adherence. At week 96, five and two patients in the TDF-TDF and TDF/ETV-TDF groups, respectively, retained some of their baseline resistance mutations (p= 0.44). None developed additional resistance mutations. Safety profiles were comparable in the two groups. Conclusions In patients with adefovir-resistant HBV and multiple-drug failure, TDF monotherapy provided a virological response comparable to that of TDF and ETV combination therapy, and was safe up to 96 weeks.