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Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: antiviral responses and evolution of mutations.

Abstract

OBJECTIVE

This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection.

METHODS

Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled.

RESULTS

Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%).

CONCLUSIONS

ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

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  • Authors+Show Affiliations

    ,

    Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.

    , , , , , , , , , , , , , , , ,

    Source

    Intervirology 57:5 2014 pg 239-47

    MeSH

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

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    24993731

    Citation

    TY - JOUR T1 - Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: antiviral responses and evolution of mutations. AU - Yim,Hyung Joon, AU - Lee,Hyun Jung, AU - Suh,Sang Jun, AU - Seo,Yeon Seok, AU - Kim,Chang Wook, AU - Lee,Chang Don, AU - Park,Sang Hoon, AU - Lee,Myung Seok, AU - Park,Choong Kee, AU - Chae,Hee Bok, AU - Kim,Moon Young, AU - Baik,Soon Koo, AU - Kim,Yun Soo, AU - Kim,Ju Hyun, AU - Lee,Jung Il, AU - Lee,Jin Woo, AU - Hong,Sun Pyo, AU - Um,Soon Ho, Y1 - 2014/06/28/ PY - 2013/07/15/received PY - 2014/02/06/accepted PY - 2014/7/5/entrez PY - 2014/7/6/pubmed PY - 2015/4/23/medline SP - 239 EP - 47 JF - Intervirology JO - Intervirology VL - 57 IS - 5 N2 - OBJECTIVE: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. METHODS: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. RESULTS: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). CONCLUSIONS: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients. SN - 1423-0100 UR - https://www.unboundmedicine.com/medline/citation/24993731/Adefovir_and_Lamivudine_Combination_Therapy_in_Patients_with_Entecavir_Resistant_Chronic_Hepatitis_B:_Antiviral_Responses_and_Evolution_of_Mutations_ L2 - https://www.karger.com?DOI=10.1159/000360399 ER -