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

Young Suk Lim, Byung Chul Yoo, Kwan Soo Byun, So Young Kwon, Yoon Jun Kim, Jihyun An, Han Chu Lee, Yung Sang Lee

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    64 Citations (Scopus)

    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 log10 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 log10 IU/mL vs -3.31 log10 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. Trial registration number: NCT01639066.

    Original languageEnglish
    Pages (from-to)1042-1051
    Number of pages10
    JournalGut
    Volume65
    Issue number6
    DOIs
    Publication statusPublished - 2016 Jun 1

    Bibliographical note

    Funding Information:
    This work was supported by Gilead Sciences, which also provided the study drug (tenofovir disoproxil fumarate). Gilead Sciences was permitted to review the manuscript and suggest changes, but had no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript. The final decision on content was exclusively retained by the authors. This study was also supported by a grant from the Korean Health Technology Rand D Project, Ministry of Health and Welfare, Republic of Korea (HI14C1731). YSL is an advisory board member of Bayer Healthcare, Bristol-Myers Squibb and Gilead Sciences, and receives research funding from Bayer Healthcare, Bristol-Myers Squibb, Gilead Sciences and Novartis. The remaining authors have nothing to disclose that would be relevant for the publication of this manuscript.

    Publisher Copyright:
    © 2016, BMJ Publishing Group. All rights reserved.

    Copyright:
    Copyright 2017 Elsevier B.V., All rights reserved.

    ASJC Scopus subject areas

    • Gastroenterology

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