Prevalence and Mutational Patterns of Lamivudine-resistant Hbv Strains in Chronically Infected Serbian Patients

This study aimed to determine the prevalence and mutational patterns of lamivudine-resistant hepatitis B virus (HBV) strains in chronically infected Serbian patients. The study included 154 patients on long-term lamivudine monotherapy. Resistance-associated mutations were identified by direct sequencing of the S/P gene. The genotypic resistance to lamivudine was confirmed in 54.5% of patients. Three primary resistance-associated mutations were found: rtM204V (55.9%), rtM204I (40.5%), rtA181T (3.6%) and two compensatory mutations rtV173L (17.8%) and rtL180M (67.8%). Seven mutational patterns were discovered with rtL180M+rtM204V being dominant (41.6%). The presence of resistanceassociated mutations was correlated to the older age of patients, the presence of clinically relevant HBsAg mutations and higher values of viral load. No correlation with HBV genotypes, subgenotypes or HBsAg subtypes was observed. High prevalence of resistance supports the use of genotypic testing in monitoring patients on lamivudine therapy and selecting those who would benefit from therapy with newly developed nucleos(t)ide analogs.