PT  - JOURNAL ARTICLE
AU  - Young-Suk Lim
AU  - Kwan Soo Byun
AU  - Byung Chul Yoo
AU  - So Young Kwon
AU  - Yoon Jun Kim
AU  - Jihyun An
AU  - Han Chu Lee
AU  - Yung Sang Lee
TI  - 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
AID  - 10.1136/gutjnl-2014-308353
DP  - 2016 May 01
TA  - Gut
PG  - 852--860
VI  - 65
IP  - 5
4099  - http://gut.bmj.com/content/65/5/852.short
4100  - http://gut.bmj.com/content/65/5/852.full
SO  - Gut2016 May 01; 65
AB  - 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.