HBV Carrying Drug-Resistance Mutations in Chronically Infected Treatment-Naive Patients. Issue 4 (May 2015)

• Record Type: Journal Article
• Authors: Gomes-Gouvêa, Michele S; Ferreira, Ariana C; Teixeira, Rosangela; Andrade, José R; Ferreira, Adalgisa SP; Barros, Lena MF; Rezende, Rosamar EF; Nastri, Ana CS Santos; Leite, Andrea GB; Piccoli, Leonora Z; Galvan, Josiane; Conde, Simone RSS; Soares, Manoel CP; Kliemann, Dimas A; Bertolini, Dennis A; Kunyoshi, Aline SO; Lyra, André C; Oikawa, Marcio K; De Araújo, Luciano V; Carrilho, Flair J; Mendes-Corrêa, Maria CJ; Pinho, João R Rebello
• Is Part Of: Antiviral therapy. Volume 20:Issue 4(2015)
• Page Start: 387
• Page End: 395
• Publication Date: 2015-05
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP2938
• Languages: English
• ISSNs: 1359-6535

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 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.