Entecavir (ETV) therapy in chronic hepatitis B patients previously treated with adefovir (ADV) with incomplete response on-treatment or relapse off-treatment

Background: The primary aims of antiviral therapy for the treatment of chronic hepatitis B (CHB) are the suppression of viral replication and remission of liver disease. However, a significant proportion of CHB patients treated with adefovir (ADV) have a suboptimal response to treatment, increasing the risks of disease progression and development of resistance. Due to the absence of cross-resistance in vitro, entecavir (ETV) therapy is recommended in patients not responding to ADV. Methods: Study ETV-079 was a randomized, open-label study comparing the viral kinetics, efficacy and safety of ETV (0.5 mg/day) with ADV (10 mg/day) in nucleoside-naive HBeAg(+) patients. After 48 weeks of treatment, patients from both arms of this study were eligible to enroll in the rollover study ETV-901 and receive treatment with ETV (1.0 mg/day). Results: Eighteen of the 24 ADV-treated patients who enrolled in ETV-901 from ETV-079 either failed to achieve undetectable HBV DNA (PCR<300 copies/mL) or relapsed following ADV therapy and were subsequently switched to ETV. Among the patients who relapsed off-treatment between ETV-079 and -901, the treatment gap ranged from 1–128 days. At entry into ETV-901, the median HBV DNA for the whole group was 6.31 log10 copies/mL. Median exposure to ETV (1.0 mg) in ETV-901 was 46 weeks, and all 18 patients currently remain on study therapy. At Week 24, the mean reduction in HBV DNA was −4.54 log10 copies/mL and 8/16 (50%) achieved HBV DNA <300 copies/mL. Nine patients had reached Week 48 in ETV-901; all had reductions in HBV DNA to <104 copies/mL and 8/9 (89%) had HBV DNA <300 copies/mL. Genotypic resistance testing was not performed. The safety profile of ETV in these ADV-experienced patients remained consistent with the previously reported experience. Conclusions: The majority of patients who had incomplete virological response or experienced virological relapse following ADV treatment in study ETV-079 had rapid reductions in HBV DNA when switched to ETV in study ETV-901. HBV DNA levels continued to decline to