ARIANA CAROLINA FERREIRA

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LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina

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  • article 33 Citação(ões) na Scopus
    HBV carrying drug-resistance mutations in chronically infected treatment-naive patients
    (2015) GOMES-GOUVEA, Michele S.; FERREIRA, Ariana C.; TEIXEIRA, Rosangela; ANDRADE, Jose R.; FERREIRA, Adalgisa S. P.; BARROS, Lena M. F.; REZENDE, Rosamar E. F.; NASTRI, Ana C. S. Santos; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; GALVAN, Josiane; CONDE, Simone R. S. S.; SOARES, Manoel C. P.; KLIEMANN, Dimas A.; BERTOLINI, Dennis A.; KUNYOSHI, Aline S. O.; LYRA, Andre C.; OIKAWA, Marcio K.; ARAUJO, Luciano V. de; CARRILHO, Flair J.; MENDES-CORREA, Maria C. J.; PINHO, Joao R. Rebello
    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.