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HBV Carrying Drug-Resistance Mutations in Chronically Infected Treatment-Naive Patients

2014; SAGE Publishing; Volume: 20; Issue: 4 Linguagem: Inglês

10.3851/imp2938

2040-2058

Michele Soares Gomes‐Gouvêa, Ariana Carolina Ferreira, Rosângela Teixeira, José Ricardo Almeida de Andrade, Adalgisa S.P. Ferreira, Lena MF Barros, Rosamar Eulira Fontes Rezende, Ana CS Santos Nastri, A.G. Leite, Leonora Z Piccoli, Josiane Galvan, Simone RSS Conde, Manoel C.P. Soares, Dimas Alexandre Kliemann, Dennis Armando Bertolini, Aline SO Kunyoshi, André Castro Lyra, Márcio K. Oikawa, Luciano Vieira de Araújo, Flair José Carrilho, Maria CJ Mendes-Corrêa, João Renato Rebello Pinho,

Hepatitis Viruses Studies and Epidemiology

Background Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date. Methods HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis. Results There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified sub-genotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients. Conclusions HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.