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Antiviral efficacy of combination therapy with entecavir and adefovir for entecavir/lamivudine-resistant hepatitis B virus with or without adefovir resistance.

Abstract

There is little clinical information on the management of hepatitis B virus (HBV) that is resistant to multiple drugs including entecavir (ETV). The present retrospective cohort study assessed the antiviral efficacy of ETV/adefovir dipivoxil (ADV) combination therapy for ETV-resistant HBV with prior lamivudine (LAM) resistance, and either with or without previous ADV resistance. The cumulative probability of achieving a virological response (undetectable serum HBV DNA) was compared by Kaplan-Meier analysis and the Breslow method. Seventeen patients with ETV-resistant HBV who were treated with ETV/ADV combination therapy for at least 6 months at a tertiary care center, were included; seven had dual resistance to ETV and LAM [ADV-r(-) group] and 10 had triple resistance to ETV, LAM, and ADV [ADV-r(+) group]. The median follow-up period was 9 months (range, 6-23). A virological response was noted in seven patients after a median of 3 months (range, 3-12) of treatment; five in the ADV-r(-) group and two in the ADV-r(+) group. The cumulative probability of a virological response was significantly higher in the ADV-r(-) group than in the ADV-r(+) group (6 months cumulative probability, 57.1% vs. 11.1%). In conclusion, ETV/ADV combination therapy led to virological responses in five of seven patients with resistance to ETV and LAM, but a significantly poorer response in patients with prior ADV resistance than in those without prior ADV resistance. Therefore, ETV/ADV combination therapy could be a useful therapeutic option for ETV- and LAM-resistant HBV without prior ADV resistance.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

    , , ,

    Source

    Journal of medical virology 84:3 2012 Mar pg 424-30

    MeSH

    Adenine
    Adult
    Aged
    Antiviral Agents
    DNA, Viral
    Drug Resistance, Multiple, Viral
    Drug Therapy, Combination
    Female
    Guanine
    Hepatitis B virus
    Hepatitis B, Chronic
    Humans
    Lamivudine
    Male
    Middle Aged
    Mutation
    Organophosphonates
    Treatment Outcome
    Viral Load

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22246827