Clinical usefulness of sequential hepatitis B virus DNA measurement (the roadmap concept) during adefovir treatment in lamivudine-resistant patients.

Background: Sequential on-treatment monitoring of hepatitis B virus (HBV) DNA levels, known as the roadmap concept, might predict the efficacy of oral therapy with nucleoside/nucleotide analogues among patients naive to this treatment. The goal of this study was to verify the usefulness of the roadmap concept to predict clinical outcomes of adefovir dipivoxil monotherapy in hepatitis B e antigen (HBeAg)-positive patients with lamivudine resistance.

Methods: In 231 patients, serum HBeAg, antibody against HBeAg and HBV DNA levels were measured at weeks 12, 24 and 48 of treatment and every 3 months thereafter.

Results: Complete (HBV DNA<60 IU/ml by PCR), partial (HBV DNA 60-<2,000 IU/ml) and inadequate (HBV DNA> or =2,000 IU/ml) virological responses at week 24 were observed in 49 (21.2%), 66 (28.6%) and 116 (50.2%) lamivudine-resistant patients, respectively, who were treated with adefovir dipivoxil monotherapy. At final assessment, rates of complete virological response in these groups were 100%, 71.2%, and 22.4%. Of the total 42 virological breakthroughs, 33 (78.6%) and 8 (19.1%) developed in the inadequate and partial response groups, respectively. Among the 91 patients who had HBV DNA<200 IU/ml at week 48, complete virological response and HBeAg seroconversion were finally achieved in 87 (95.6%) and 39 (42.9%) patients, respectively. Of these 91 patients, virological breakthrough and genotype mutations developed in only 4 (4.4%) and 3 (3.3%) patients. The roadmap concept predicted virological response, HBeAg seroconversion and breakthrough (odds ratios 3.68, 9.67 and 0.15, respectively).

Conclusions: The roadmap concept is useful for choosing between continuation of adefovir dipivoxil monotherapy or early switching to another therapy, or to suggest additional therapy in patients showing lamivudine resistance.