A double-blind randomized trial of adefovir dipivoxil in Chinese subjects with HBeAg-positive chronic hepatitis B

Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were enrolled in a multicenter, double-blind, randomized, placebo-controlled study of adefovir dipivoxil (ADV) 10 mg once daily. There was a significant difference in reduction of serum hepatitis B virus (HBV) DNA after 12 weeks between subjects who received ADV and those who received the placebo (3.4 and 0. 1 log(10) copies/mL, respectively, P <.001). Further reductions in serum HBV DNA and increases in the proportion of subjects with an HBV DNA level of at most 10(5) copies/mL, with HBV DNA undetectable, and with ALT normalization were observed in ADV-treated subjects at week 52 (median HBV DNA reduction of 4.5 log(10) copies/mL, 67% with HBV DNA <= 10(5) copies/mL, 28% with HBV DNA undetectable, and 79% with ALT normalization). Subjects who initially received ADV lost some treatment benefit after being rerandomized to the placebo in week 40. Subjects with YMDD mutant HBV at baseline had virological, biochemical, and serological responses to treatment that were similar to those of subjects with wild-type HBV. The incidence of clinically adverse events was similar in nature and severity between the treatment groups, and there was no evidence of renal toxicity. No adefov-irrelated HBV mutations were identified. In conclusion, treatment with ADV 10 mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg-positive CHB, and did not lead to the emergence of drug resistance. The study is continuing for an additional 4 years with all subjects on open-label ADV 10 mg daily.