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.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Gomes-Gouvêa MS,Ferreira AC,Teixeira R,Andrade JR,Ferreira AS,Barros LM,Rezende RE,Nastri AC,Leite AG,Piccoli LZ,Galvan J,Conde SR,Soares MC,Kliemann DA,Bertolini DA,Kunyoshi AS,Lyra AC,Oikawa MK,de Araújo LV,Carrildoi
10.3851/IMP2938subject
Has Abstractpub_date
2015-01-01 00:00:00pages
387-95issue
4eissn
1359-6535issn
2040-2058journal_volume
20pub_type
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