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Abstract Details
Efficacy of Entecavir plus Tenofovir Combination Therapy for Chronic Hepatitis B Patients with Multi-Drug Resistant Strains
Lee YB1, Lee JH2, Lee DH1, Cho H1, Ahn H1, Choi WM1, Cho YY1, Lee M1, Yoo JJ1, Cho Y1, Cho EJ1, Yu SJ1, Kim YJ1, Yoon JH1, Kim CY1, Lee HS1. Antimicrob Agents Chemother. 2014 Aug 25. pii: AAC.03845-14. [Epub ahead of print]
Author information
1Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea pindra@empal.com.
Abstract
The emergence of multi-drug resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) combination therapy against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7--31.7) months. Seventy-four out of 93 patients (79.6%) achieved complete virologic suppression, after a median 4.5 (95% confidence interval, 3.0--6.0) months. Cumulative probabilities of complete virologic suppression at month 6 were 63.6%: 55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively. During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P=0.072 and P=0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.