Emergence of hepatitis B virus quasispecies with lower susceptibility to nucleos(t)ide analogues during lamivudine treatment

F. Moriconi; P. Colombatto; B. Coco; P. Ciccorossi; F. Oliveri; D. Flichman; A. M. Maina; R. Sacco; F. Bonino; M. R. Brunetto
August 2007
Journal of Antimicrobial Chemotherapy (JAC);Aug2007, Vol. 60 Issue 2, p341
Academic Journal
Objectives We studied the impact of hepatitis B virus (HBV) polymerase/reverse transcriptase (Pol/Rt) heterogeneity on adefovir rescue therapy in 34 consecutive chronic hepatitis B patients with viral breakthrough during lamivudine monotherapy. Methods The Pol/Rt A–F domains were directly sequenced in all patients at baseline, and 12 and 24 months. Response to therapy was evaluated at 3, 6, 12 and 24 months by quantitative HBV-DNA. Results Primary treatment failures did not occur. At 6 months 24/34 (70.6%) patients had viraemia P = 0.023). At least one of rtA181S and rtT184S substitutions correlated negatively with IVR and CVR (univariate analysis, P = 0.001) and was independently associated with absence of CVR (P = 0.016). Conclusions Lamivudine monotherapy favours the emergence of viral quasispecies that influence the response rate to adefovir rescue therapy independently from baseline viraemia and lower the susceptibility to other nucleos(t)ide analogues.


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