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Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: results of a randomised trial
  1. Young-Suk Lim1,
  2. Byung Chul Yoo2,
  3. Kwan Soo Byun3,
  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, Korea
  2. 2Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
  3. 3Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
  4. 4Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
  5. 5Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 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, Korea; limys{at}amc.seoul.kr Professor Byung Chul Yoo, Department of Internal Medicine, Konkuk University School of Medicine, 120 Neugdong-ro, Gwangjin-gu, Seoul 143-701, Korea; 20150144{at}kuh.ac.kr

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.

  • ANTIVIRAL THERAPY
  • DRUG RESISTANCE
  • HEPATITIS B

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