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J Viral Hepat ; 16(4): 279-85, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19222742

RESUMO

The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/40, mean age: 42.9+/-13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (<10(7) copies/mL) was a significant predictor of response to ADV treatment (P<0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Farmacorresistência Viral , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Substituição de Aminoácidos/genética , Antivirais/farmacologia , DNA Viral/sangue , DNA Viral/genética , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Organofosfonatos/farmacologia , Terapia de Salvação/métodos , Análise de Sequência de DNA , Resultado do Tratamento , Carga Viral
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