OBJECTIVETo explore a new strategy for effective and economical anti-virus therapy for HBV infection, we conducted a sequence administration of lamivudine and interferon alpha 1b to evaluate its effects on HBV replication and rebound as well as YMDD mutation induced by lamivudine.

METHODS150 HBV patients having at least 6 months history of infection were assigned randomly into 5 groups. Each group of these patients was either treated with lamivudine, interferon alpha 1b, lamivudine combined with interferon, sequence administration of lamivudine and interferon (sequence group) or no anti-virus therapy (control group) for 12 months. The serum samples were collected at 0, 3, 6, 9, 12 and 18th months and were assayed for ALT, AST, HBeAg, HBV DNA (quantitive PCR) as well as YMDD mutation types by microarray.

RESULTSThe anti-virus replication effects were shown as early as the 3rd month in the sequence group but not in the IFN and control groups. The significant and persistent inhibition effect of it on HBV replication and improvement of liver function was shown. It was more effective than lamivudine or IFN treatments at the end of the drug administration and 6 months later after the drug was withdrawn. We also found that this sequence administration pattern can significantly shorten the period of treatment of lamivudine as well as reduce the rate of YMDD mutation and rebound of HBV replication after lamivudine withdrawal. It is also more economical than a combined therapy of lamivudine with IFN.

CONCLUSIONThis sequence administration of lamivudine and IFN pattern can significantly improve the anti-virus effect on HBV replication, shorten the period of treatment with lamivudine, reduce the mutation rate of YMDD and prevent the rebound of HBV after drug withdrawal.