Young-Suk Lim1, Byung Chul Yoo2, Kwan Soo Byun3, So Young Kwon2, Yoon Jun Kim4, Jihyun An1, Han Chu Lee1, Yung Sang Lee1. 1. Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 2. Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea. 3. Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. 4. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
RCT Entities:
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Entities:
Keywords:
ANTIVIRAL THERAPY; DRUG RESISTANCE; HEPATITIS B
Authors: Fabien Zoulim; Jolanta Białkowska-Warzecha; Mircea Mihai Diculescu; Adrian Eugen Goldis; Renate Heyne; Tomasz Mach; Patrick Marcellin; Jörg Petersen; Krzysztof Simon; Soumaya Bendahmane; Isabelle Klauck; Wojciech Wasiak; Harry L A Janssen Journal: Hepatol Int Date: 2016-05-20 Impact factor: 6.047
Authors: Norah A Terrault; Natalie H Bzowej; Kyong-Mi Chang; Jessica P Hwang; Maureen M Jonas; M Hassan Murad Journal: Hepatology Date: 2015-11-13 Impact factor: 17.425