SWITCHING TO ADEFOVIR PLUS ENTECAVIR IS EFFECTIVE AND LEADS TO STRONG VIRAL SUPPRESSION IN HBV MONO-INFECTED PATIENTS FAILING SEQUENTIAL OR COMBINATION THERAPY WITH LAMIVUDINE AND ADEFOVIR

Aims: In patients failing lamivudine or adefovir monotherapy due to suboptimal viral response or development of viral resistance switching or add-on therapy has been the common therapeutical approach used in clinical practice over the last years. Although both approaches often lead to suppression of viral replication, a subset of mainly HBeAg positive patients with highly replicative active HBV remains viremic. These patients have an increased risk of selection of multi-drug resistance viral strains. The aim of this observational cohort study was to investigate the efficacy and safety of the combination of adefovir (10mg) and entecavir (1mg) in compliant chronic HBV patients failing combination (n=10) of lamivudin (100mg) and adefovir (10mg) or sequential mono therapy (n=5). Methods: open label, retro- and prospective cohort study. Quantitative HBV-DNA measurement with a LLoD of 400 copies/ml detection was used. Resistance testing was done at baseline in all patients using Innolipa line-probe assay DR V.2 and direct sequence analysis. Results: 15 Patients (m/f: 8/7; 9/15 HBeAg positive) with a median age of 41 years were included in this cohort study. At baseline median ALT and HBV-DNA were 0.66 ULN and 2×105 copies/ml. The median treatment duration of the combination therapy Adefovir plus Entecavir was 14 months and there were no significant side effects associated with the therapy. Of note a highly significant drop of HBV-DNA levels (median 3.7 log; p<0.0001) was observed in all patients and 11/15 patients became HBV-DNA undetectable. Discussion: Switching therapy to entecavir and adefovir in adherent HBV mono-infected patients failing sequential or combination therapy with lamivudine and adefovir was highly efficient and well tolerated. More data are needed to determine the optimal antiviral strategy in nucleos(t)ide experienced patients