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Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial
  1. Young-Suk Lim1,
  2. Kwan Soo Byun2,
  3. Byung Chul Yoo3,
  4. So Young Kwon4,
  5. Yoon Jun Kim5,
  6. Jihyun An1,
  7. Han Chu Lee1,
  8. Yung Sang Lee1
  1. 1Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  2. 2Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
  3. 3Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  4. 4Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea
  5. 5Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
  1. Correspondence to Professor Young-Suk Lim, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea; limys{at}amc.seoul.kr and Professor Kwan Soo Byun, Department of Internal Medicine, Korea University Guro Hospital, 148, Gurodong-ro, Guro-gu, Seoul 152-703, Republic of Korea; [email protected]

Abstract

Objective Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV.

Design In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks.

Results Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71% vs 73%; p>0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (−3.66 vs −3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups.

Conclusions TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV.

Trial registration number ClinicalTrials.gov ID NCT01639092.

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