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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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Gomes-Gouvea, Michele S. [1, 2] ; Ferreira, Ariana C. [1, 2] ; Teixeira, Rosangela [3] ; Andrade, Jose R. [3] ; Ferreira, Adalgisa S. P. [4] ; Barros, Lena M. F. [4] ; Rezende, Rosamar E. F. [5] ; Santos Nastri, Ana C. S. [6, 1, 2] ; Leite, Andrea G. B. ; Piccoli, Leonora Z. ; Galvan, Josiane ; Conde, Simone R. S. S. [7] ; Soares, Manoel C. P. [8] ; Kliemann, Dimas A. [9] ; Bertolini, Dennis A. [10] ; Kunyoshi, Aline S. O. [10] ; Lyra, Andre C. [11] ; Oikawa, Marcio K. [12] ; de Araujo, Luciano V. [13] ; Carrilho, Flair J. [1, 2] ; Mendes-Correa, Maria C. J. [6] ; Rebello Pinho, Joao R. [1, 2]
Número total de Autores: 22
Afiliação do(s) autor(es):
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[1] Univ Sao Paulo, Dept Gastroenterol, Sch Med, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sao Paulo Inst Trop Med, Lab Gastroenterol & Hepatol, Sao Paulo - Brazil
[3] Univ Fed Minas Gerais, Sch Med, Dept Internal Med, Belo Horizonte, MG - Brazil
[4] Univ Fed Maranhao, Clin Res Ctr, Sao Luis, Maranhao - Brazil
[5] Municipal Secretary Hlth, Sao Paulo - Brazil
[6] Univ Sao Paulo, Sch Med, Dept Infect Dis, Sao Paulo - Brazil
[7] Fundacao Santa Casa Misericordia Para, Belem, Para - Brazil
[8] Inst Evandro Chagas, Serv Hepatol, Ananindeua, Para - Brazil
[9] Hosp Nossa Senhora da Conceicao, Serv Infectol, Porto Alegre, RS - Brazil
[10] Univ Estadual Maringa, Lab Imunol Clin, Dept Anal Clin & Biomed, Maringa, Parana - Brazil
[11] Univ Fed Bahia, Dept Med, Div Gastroenterol & Hepatol, BR-41170290 Salvador, BA - Brazil
[12] Univ Fed ABC, Ctr Matemat Comp & Cognicao, Sao Paulo - Brazil
[13] Univ Sao Paulo, Escola Artes Ciencias & Humanidades, Sao Paulo - Brazil
Número total de Afiliações: 13
Tipo de documento: Artigo Científico
Fonte: ANTIVIRAL THERAPY; v. 20, n. 4, p. 387-395, 2015.
Citações Web of Science: 20
Resumo

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. (AU)

Processo FAPESP: 10/51208-2 - Prevalência de resistência primária aos antivirais utilizados no tratamento da hepatite B entre pacientes com infecção crônica pelo vírus da hepatite B não submetidos a tratamento
Beneficiário:Maria Cássia Jacintho Mendes Corrêa
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/50081-9 - Prevalência de resistência primária aos antivirais utilizados no tratamento da hepatite B entre pacientes com infecção crônica pelo vírus da hepatite B não submetidos a tratamento
Beneficiário:Michele Soares Gomes Gouvêa
Modalidade de apoio: Bolsas no Brasil - Doutorado