Adefovir-based combination therapy with entecavir or lamivudine for patients with entecavir-refractory chronic hepatitis B

• Published in: Journal of medical virology 2012-01, Vol.84 (1), p.18-25
• Main Authors: Kim, Soon Sun, Cheong, Jae Youn, Lee, Dami, Lee, Myoung Hee, Hong, Sun Pyo, Kim, Soo-Ok, Cho, Sung Won
• Format: Article
• Language: English
• Subjects: adefovir; Adenine - administration & dosage; Adenine - analogs & derivatives; Adult; Antiviral Agents - administration & dosage; Biological and medical sciences; chronic hepatitis B; DNA, Viral - blood; Drug Resistance, Viral; Drug Therapy, Combination - methods; entecavir resistance; Fundamental and applied biological sciences. Psychology; Guanine - administration & dosage; Guanine - analogs & derivatives; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; Human viral diseases; Humans; Infectious diseases; lamivudine; Lamivudine - administration & dosage; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Organophosphonates - administration & dosage; Treatment Outcome; Viral diseases; Viral Load; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.22227

This study evaluated the efficacy of adefovir (ADV) plus lamivudine (LAM) or ADV add‐on therapy for patients with entecavir (ETV)‐refractory hepatitis B infection. Twenty‐nine ETV‐resistant and 8 patients with suboptimal response to ETV were enrolled. Twenty‐seven patients received ADV + LAM therapy and 10 patients received ADV + ETV therapy for >24 weeks. In 29 patients who were ETV‐resistant, the mean reduction in HBV DNA levels at 24 weeks was not different between the ADV + LAM and ADV + ETV groups (−1.98 log10 IU/ml vs. −2.16 log10 IU/ml; P = 0.792). Primary non‐response was observed in 52.2% (12/23) of ADV + LAM group and 33.3% (2/6) of ADV + ETV group (P = 0.651). Initial virologic response (IVR) was observed in 17.4% (4/23) of ADV + LAM group and 33.3% (2/6) of ETV + ADV group (P = 0.362). In eight patients with suboptimal response to ETV, the ADV + ETV group had a greater reduction in HBV DNA at 24 and 48 weeks than the ADV + LAM group (−2.29 log10 IU/ml vs. −0.09 log10 IU/ml and −2.04 log10 IU/ml vs. −0.72 log10 IU/ml; P = 0.020 and P = 0.012, respectively). Primary non‐response and IVR did not significantly differ between the two groups [100% (4/4) vs. 50% (2/4) and 0% (0/4) vs. 50% (2/4); P = 0.429 and P = 0.429, respectively]. The antiviral efficacies of ADV‐based therapy with ETV or LAM for patients with ETV‐resistant hepatitis B were limited and did not differ between the two groups. However, adding ADV to ETV may be more effective than ADV + LAM therapy in patients with suboptimal virologic response to ETV. J. Med. Virol. 84:18–25, 2011. © 2011 Wiley Periodicals, Inc.