Background & Aims: Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug-resistant (MDR) CHB patients. Methods: In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks. Results: A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2–6) were included. At baseline, median age was 47.0 years, 89.1% were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11–6.73) log10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log10 IU/ml and 2.38 log10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients. Conclusions: In difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.
Bibliographical noteFunding Information:
Financial support: This investigator-initiated trial was supported by an unrestricted grant from Bristol-Myers Squibb, which also provided the study drug. Bristol-Myers Squibb had no role in the study design, data collection and analysis. The authors retained full responsibility for the collection and interpretation of data. Conflict of interest: SH Ahn has received unrestricted research grants from BMS, Gilead and Roche. SH Ahn has acted as advisor and lecturer for BMS, Gilead, Roche, MSD, Norvatis, Abbvie, GreenCross and ABIVAX. The other authors have declared that no competing interests exist.
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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