Factors influencing inadequate or suboptimal response to adefovir with or without genotypic resistance



The aim of the study was to explore the factors in inadequate-responders to treatment with adefovir (ADV) with or without genotypic resistance. The reverse-transcriptase (RT) gene of hepatitis B virus (HBV) was sequenced in 161 patients with inadequate-response to ADV and analyzed for HBV genotypes using a phylogenetic approach. Seventy-six patients (47.2%) were found to carry the rtA181V/T/S or rtN236T residue substitution, and most of them had viral rebound. In the patients with viral rebound and ADV genotypic resistance, 19 (25.7%) showed rtA181V/T/S + rtN236T substitutions. In the other patients, it was found that HBV genotypes and cirrhosis influenced the selection of ADV-resistant positions by univariate analysis and multiple logistic regression analysis. The rtN236T was more frequent in patients with genotype B, and the rtA181V/T/S was more common in patients with genotype C (χ2 = 11.543, P = 0.001). Multiple logistic regression analysis showed that the rtN236T and time resistant strains occurred during ADV-treatment were statistically significant for influencing rtA181 variation types (P = 0.007 and P = 0.024, respectively), and the occurrence of rtA181T was found to be significantly earlier than rtA181V. In conclusion, genotypic resistance was not detected in the majority of primary nonresponders to ADV when compared to the patients with viral rebound. The different HBV genotypes influence the selection of ADV-resistant mutation positions. The rtA181T occurs more frequently in patients with the rtN236T and it occurs earlier when compared to the rtA181V. These findings suggest that early judgment of adequate response and making a decision for interference in patients treated with ADV are of importance in clinical practice. J. Med. Virol. 84: 1030–1036, 2012. © 2012 Wiley Periodicals, Inc.