Lamivudine-resistance mutations can be selected even at very low levels of hepatitis B viraemia

Objective: To investigate lamivudine (LAM)-resistance profiles of hepatitis B virus (HBV) at the early stages of virological breakthrough (serum HBV-DNA 12-345 IU/ml) or when HBV-DNA is undetectable. Methods: Sixty-four HBV-mono-infected patients were enrolled: 25 had virological breakthrough with serum HBV-DNA ranging from 12 to 345 IU/ml during first-line LAM-monotherapy; 24 were on LAM-monotherapy, and 15 were on LAM + adefovir dipivoxil (ADV) with undetectable serum HBV-DNA (<12 IU/ml). Results: HBV-reverse transcriptase was successfully sequenced in 22 (88.0%) LAM-treated patients with HBV-DNA between 12 and 345 IU/ml, and in 12 (30.8%) patients receiving LAM (+/- ADV) with HBV-DNA < 12 IU/ml. Drug-resistance mutations were observed in 17(77.2%) LAM-treated patients with virological breakthrough: 8 M204V, 7 M2041, 1 M204I/V, and 1 A181T. One or >= 2 compensatory mutations were found in 10(58.8%) and in 4(23.5%) patients. Drug-resistance mutations were present also in patients with undetectable serum HBV-DNA: M2041 was detected in 2 patients receiving LAM-monotherapy, and V84M in 1 patient receiving LAM + ADV. Conclusion: Overall findings support the existence of drug-resistance mutations even at very low levels of viral replication. The persistence of low-level HBV replication and consequent drug-resistance emergence should be considered when choosing therapeutic strategies. (C) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.