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

Author(s):Show less -

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]}

Affiliation:Show less -

^[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

• Document type: Journal article
• Source: ANTIVIRAL THERAPY; v. 20, n. 4, p. 387-395, 2015.
• Web of Science Citations: 20

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. (AU)

• FAPESP's process: 10/51208-2 - Prevalence of primary resistance to antiviral therapy against hepatitis B in patients with chronic hepatitis B virus infection and not submitted to treatment
• Grantee: Maria Cássia Jacintho Mendes Corrêa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/50081-9 - Prevalence of primary resistance to antiviral therapy against hepatitis B in patients with chronic hepatitis B virus infection and not submitted to treatment
• Grantee: Michele Soares Gomes Gouvêa
• Support Opportunities: Scholarships in Brazil - Doctorate