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Treatment response and evolution of HBV resistance during lamivudine plus adefovir or entecavir therapy in patients with adefovir-resistant mutants.

Abstract

BACKGROUND

Here, we investigated the treatment response and evolution of HBV resistance during lamivudine (LAM) plus adefovir (ADV) and entecavir (ETV) monotherapy in patients with ADV-resistant mutants.

METHODS

Of the 53 patients with ADV-resistant mutants, 25 received combined LAM plus ADV therapy (LAM+ADV group) and 28 received ETV monotherapy (ETV group) for at least 12 months (median 24 months and range 12-67 months).

RESULTS

During 24 months therapy, no significant difference was noted in HBV DNA reduction from baseline, HBV DNA<200 copies/ml, hepatitis B e antigen loss and ALT normalization between the two groups. In the LAM+ADV group, patients with single rtN236T resistant mutation had higher rates of undetectable HBV DNA than those with the double mutant rtA181T/V+rtN236T at months 3-18 of therapy. No virological breakthrough occurred except for one patient with rtN236T resistant mutation who experienced virological and biochemical breakthrough after the emergence of an additional rtA181T mutant under LAM+ADV therapy. Of the 28 patients receiving ETV monotherapy, ETV-resistant mutants developed in 8. The cumulative rates of ETV-resistant mutations and virological breakthrough at months 12, 24 and 36 were 3.6%, 25.7% and 46.8%, respectively. ADV-resistant mutations were rapidly replaced by LAM-resistant mutations (median 12 months) followed by ETV-resistant mutations.

CONCLUSIONS

There was no significant difference in virological response between the LAM+ADV and ETV groups in patients with ADV-resistant mutants. LAM+ADV were less effective in patients with the double mutant rtA181T/V+rtN236T than the single rtN236T mutation. The incidence of ETV-resistant mutation was high in patients with LAM/ADV-resistant mutants treated with ETV monotherapy.

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  • Authors+Show Affiliations

    ,

    Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

    , , , , , ,

    Source

    Antiviral therapy 17:4 2012 pg 701-9

    MeSH

    Adenine
    Adult
    Aged
    Antiviral Agents
    Base Sequence
    Cloning, Molecular
    DNA, Viral
    Drug Administration Schedule
    Drug Resistance, Viral
    Drug Therapy, Combination
    Female
    Genotype
    Guanine
    Hepatitis B
    Hepatitis B virus
    Humans
    Lamivudine
    Male
    Middle Aged
    Mutation
    Organophosphonates

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    22358132

    Citation

    TY - JOUR T1 - Treatment response and evolution of HBV resistance during lamivudine plus adefovir or entecavir therapy in patients with adefovir-resistant mutants. AU - Chen,Chien-Hung, AU - Wang,Jing-Houng, AU - Lu,Sheng-Nan, AU - Hu,Tsung-Hui, AU - Hung,Chao-Hung, AU - Chang,Min-Hui, AU - Changchien,Chi-Sin, AU - Lee,Chuan-Mo, Y1 - 2012/02/23/ PY - 2011/9/01/accepted PY - 2012/2/23/aheadofprint PY - 2012/2/24/entrez PY - 2012/2/24/pubmed PY - 2012/9/6/medline SP - 701 EP - 9 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 17 IS - 4 N2 - BACKGROUND: Here, we investigated the treatment response and evolution of HBV resistance during lamivudine (LAM) plus adefovir (ADV) and entecavir (ETV) monotherapy in patients with ADV-resistant mutants. METHODS: Of the 53 patients with ADV-resistant mutants, 25 received combined LAM plus ADV therapy (LAM+ADV group) and 28 received ETV monotherapy (ETV group) for at least 12 months (median 24 months and range 12-67 months). RESULTS: During 24 months therapy, no significant difference was noted in HBV DNA reduction from baseline, HBV DNA<200 copies/ml, hepatitis B e antigen loss and ALT normalization between the two groups. In the LAM+ADV group, patients with single rtN236T resistant mutation had higher rates of undetectable HBV DNA than those with the double mutant rtA181T/V+rtN236T at months 3-18 of therapy. No virological breakthrough occurred except for one patient with rtN236T resistant mutation who experienced virological and biochemical breakthrough after the emergence of an additional rtA181T mutant under LAM+ADV therapy. Of the 28 patients receiving ETV monotherapy, ETV-resistant mutants developed in 8. The cumulative rates of ETV-resistant mutations and virological breakthrough at months 12, 24 and 36 were 3.6%, 25.7% and 46.8%, respectively. ADV-resistant mutations were rapidly replaced by LAM-resistant mutations (median 12 months) followed by ETV-resistant mutations. CONCLUSIONS: There was no significant difference in virological response between the LAM+ADV and ETV groups in patients with ADV-resistant mutants. LAM+ADV were less effective in patients with the double mutant rtA181T/V+rtN236T than the single rtN236T mutation. The incidence of ETV-resistant mutation was high in patients with LAM/ADV-resistant mutants treated with ETV monotherapy. SN - 2040-2058 UR - https://www.unboundmedicine.com/medline/citation/22358132/Treatment_response_and_evolution_of_HBV_resistance_during_lamivudine_plus_adefovir_or_entecavir_therapy_in_patients_with_adefovir_resistant_mutants_ L2 - http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+73-40-5 ER -