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Original article

HBV carrying drug-resistance mutations in chronically infected treatment-naive patients

Michele S Gomes-Gouvêa, Ariana C Ferreira, Rosangela Teixeira, José R Andrade, Adalgisa SP Ferreira, Lena MF Barros, Rosamar EF Rezende, Ana CS Santos Nastri, Andrea GB Leite, Leonora Z Piccoli, Josiane Galvan, Simone RSS Conde, Manoel CP Soares, Dimas A Kliemann, Dennis A Bertolini, Aline SO Kunyoshi, André C Lyra, Marcio K Oikawa, Luciano V de Araújo, Flair J Carrilho, Maria CJ Mendes-Corrêa, João R Rebello Pinho

Corresponding author name: Michele S Gomes-Gouvêa
Corresponding author e-mail: gomesmic@yahoo.com.br

Citation: Antiviral Therapy 2015; 20:387-395
doi: 10.3851/IMP2938

Date accepted: 02 October 2014
Date published online: 27 January 2015

Abstract

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 subgenotype (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.

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