Virological response and incidence of adefovir resistance in lamivudine-resistant patients treated with adefovir dipivoxil

• Published in: Antiviral therapy Vol. 11; no. 6; pp. 771 - 778
• Main Authors: CHEN, Chien-Hung, WANG, Jing-Houng, LEE, Chuan-Mo, HUNG, Chao-Hung, HU, Tsung-Hui, WANG, Jyh-Chwan, LU, Sheng-Nan, CHANGCHIEN, Chi-Sin
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2006
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adenine - therapeutic use; Adult; Aged; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; DNA-Directed DNA Polymerase - drug effects; DNA-Directed DNA Polymerase - genetics; DNA-Directed DNA Polymerase - metabolism; Drug Resistance, Viral - genetics; Drug Therapy, Combination; Female; Hepatitis B virus - drug effects; Hepatitis B virus - enzymology; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; Humans; Lamivudine - pharmacology; Lamivudine - therapeutic use; Male; Medical sciences; Middle Aged; Mutation; Organophosphonates - pharmacology; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Treatment Outcome; Human; Purine nucleotide; Antiretroviral agent; Acyclic nucleotide; RNA-directed DNA polymerase; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; Organic phosphonate; Epidemiology; Incidence; Resistance; Nucleotidyltransferases; Adefovir; Dideoxynucleoside; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Pyrimidine nucleoside
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350601100604

The incidence of adefovir dipivoxil (ADV) resistance in patients with lamivudine (3TC)-resistant mutants who received ADV therapy remains unclear. The aims of this study were to determine the virological response to ADV, the incidence and the risk factors of ADV resistance, and the associated factors of initial virological response (IVR) in lamivudine-resistant patients. Forty-six consecutive lamivudine-resistant chronic hepatitis B patients treated with ADV for more than 12 months with or without 3TC overlapping were prospectively examined for virological response and adefovir resistance. IVR was documented in 24 (52.2%) of patients. Of the 46 patients, 11 had ADV resistance (5 rtN236T, 5 rtA181T, 1 rtA181T and rtN236T). The cumulative incidence of ADV resistance at month 6, 12, 18 and 24 was 0%, 6.5%, 24.6% and 38.3% respectively. Compared with those without ADV resistance, patients with ADV resistance had a significantly higher rate of liver cirrhosis. Based on Cox regression analysis, the significant risk factor of ADV resistance was younger age (OR=0.92, 95% CI=0.86-0.99, P=0.023) and liver cirrhosis (OR=5.3, 95% CI=1.12-25.09, P=0.036). In addition, patients with ADV resistance were associated with higher HBV DNA levels and lower HBV DNA reduction in first 6 months of ADV treatment than those without ADV resistance. Only half of our patients achieved IVR on ADV treatment. The incidence of ADV resistance was high in 3TC-resistant patients treated with ADV.