Sequential therapy using lamivudine in entecavir-treated patients with undetectable HBV DNA–results at 48 weeks

Abstract

Background: The aim of this study was to determine the efficacyof entecavir-lamivudine sequential therapy in patients withundetectable viral load and normal ALT after initial entecavirtreatment. If effective, this may result in reducing the cost of ther-apy. Methods: This is a 2-year prospective trial of 50 patientstreated on entecavir 0.5 mg daily for over 6 months, and hadachieved normal ALT and undetectable HBV DNA (<12 IU/mL).Patients were randomly assigned to receive continued entecavirmonotherapy, or switched to lamivudine monotherapy, at aratio of 1:1. Liver biochemistry and HBV DNA were determinedat weeks 0, 4, 12, 24, 48, 72, and 96. Patients in the lamivu-dine arm with evidence of HBV DNA rebound, as defined byan increase to >20 IU/mL on 3 consecutive measurements,were switched back to entecavir. Mutational analysis using line-probe assay would be performed at weeks 0, 24, 48, and 96.Results: Of the 50 patients, 48 patients had follow-up to 48weeks. There were no significant differences at the time of treat-ment assignment between the entecavir-entecavir and the ente-cavir-lamivudine group with respect to age, gender, HBeAgstatus, and duration of prior entecavir treatment. There was noelevation of ALT observed in any patients during the 48 weekperiod. At 24 weeks, 22/25 (88%) patients in the lamivudinearm continued to have undetectable HBV DNA, compared to25/25 (100%) patients in the entecavir arm (p=NS). Threepatients (12%) in the lamivudine arm had HBV DNA>20IU/mL, 2 at week 12 (43 IU/mL and 93 IU/mL) and 1 at week24 (86 IU/mL). None of these patients developed lamivudineresistant mutations, and were switched back to entecavir. Nofurther virological rebound was seen after 24 weeks. In patientswith follow-up to 48 weeks, all patients remaining on lamivu-dine, and those in the entecavir arm had undetectable HBVDNA. There was no difference in cumulative HBV DNArebound between the 2 groups at 48 weeks (p=NS). Conclu-sion: Preliminary results suggest that sequential therapy usingentecavir followed by lamivudine was effective in suppressingHBV DNA after initial optimal viral suppression with entecavir.Further follow-up will determine the long-term efficacy andresistance development of entecavir-lamivudine sequential ther-apy.