Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates

Abstract

Aim: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.

Methods: Between June 2008 and August 2010, a cross-sectional control study was conducted comprising 79 patients with chronic HBV infection-related liver disease who had been administered ADV monotherapy. Patients underwent liver imaging. Serum DNA extracts were analyzed for HBV DNA levels, genotypes, and serology markers, and deep sequencing of the HBV P gene was performed.

Results: ADV-resistant patients were found either with a single mutated locus, or with coexisting mutated loci. The most prevalent mutations were rtA181T, rtV214A, and rtN236T. Twenty-six patients had more than two mutated loci. The mutants were distributed among the patients without any significant affinity for gender, age, end-stage of liver disease, complications of non-alcoholic fatty liver disease, or HBV DNA levels. Patients with the rtA181T mutant were primarily infected with genotype C and e-antigen negative HBV, while patients with the rtN236T mutant were primarily infected by genotype B HBV (χ(2) = 6.004, 7.159; P = 0.023, 0.007). The duration of treatment with ADV was shorter in the single mutant group compared with the multi-mutant group (t = 2.426, P = 0.018).

Conclusion: Drug-resistant HBV mutants are complex and diverse. Patients should receive the standard and first-line antiviral treatment, strictly comply with medication dosage, and avoid short-term withdrawal.

Keywords: Adefovir dipivoxil; Drug-resistant mutant; Gene sequencing; Hepatitis B virus.