Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil
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Citações na Scopus
18
Tipo de produção
article
Data de publicação
2017
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOMED CENTRAL LTD
Citação
BMC INFECTIOUS DISEASES, v.17, article ID 716, 6p, 2017
Resumo
Background: Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). Methods: Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naive patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). Results: The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. Conclusions: Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naive patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.
Palavras-chave
HIV/HCV coinfection, NS5A, DAA therapy, Resistance-associated substitutions
Referências
- Asselah T, 2016, LIVER INT, V36, P47, DOI 10.1111/liv.13027
- Bagaglio S, 2016, VIRUSES-BASEL, V8, DOI 10.3390/v8040091
- Bartels DJ, 2013, J VIROL, V87, P1544, DOI 10.1128/JVI.02294-12
- Boesecke C, 2016, INFECTION, V44, P93, DOI 10.1007/s15010-015-0856-9
- Dietz J, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0134395
- Feld JJ, 2015, NEW ENGL J MED, V373, P2599, DOI 10.1056/NEJMoa1512610
- Feld JJ., 2017, CLINI LIVER DIS, V9, P115
- Foster GR, 2015, NEW ENGL J MED, V373, P2608, DOI 10.1056/NEJMoa1512612
- Fridell RA, 2011, HEPATOLOGY, V54, P1924, DOI 10.1002/hep.24594
- Hall T.A., 1999, NUCL ACIDS S SER, V41, P95, DOI 10.1021/BK-1999-0734.CH008
- Hepatitis C, 2015, HEPATOLOGY, V62, P932, DOI [DOI 10.1002/HEP.27950, 10.1002/hep.27950]
- Hernandez D, 2013, J CLIN VIROL, V57, P13, DOI 10.1016/j.jcv.2012.12.020
- Kalaghatgi P, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0155869
- Karageorgopoulos Drosos E, 2015, World J Hepatol, V7, P1936, DOI 10.4254/wjh.v7.i15.1936
- Krishnan P, 2016, ANTIMICROB AGENTS CH, V60, P1106, DOI 10.1128/AAC.02606-15
- Krishnan P, 2015, ANTIMICROB AGENTS CH, V59, P979, DOI 10.1128/AAC.04226-14
- Larousse JA, 2015, VIROL J, V12, DOI 10.1186/s12985-015-0318-0
- Lawitz E, 2015, LANCET, V385, P1075, DOI 10.1016/S0140-6736(14)61795-5
- Lawitz EJ, 2012, J HEPATOL, V57, P24, DOI 10.1016/j.jhep.2011.12.029
- Nguyen LT, 2016, ANTIVIR THER, V21, P447, DOI 10.3851/IMP3025
- Liu R, 2015, ANTIMICROB AGENTS CH, V59, P6922, DOI 10.1128/AAC.01390-15
- Lontok E, 2015, HEPATOLOGY, V62, P1623, DOI 10.1002/hep.27934
- Malta FD, 2010, MEM I OSWALDO CRUZ, V105, P92, DOI 10.1590/S0074-02762010000100014
- Mesquita F, 2016, BMC PUBLIC HEALTH, V16, DOI 10.1186/s12889-016-3784-4
- Nakamoto S, 2014, WORLD J GASTROENTERO, V20, P2902, DOI 10.3748/wjg.v20.i11.2902
- Nettles RE, 2011, HEPATOLOGY, V54, P1956, DOI 10.1002/hep.24609
- Paolucci S, 2013, VIROL J, V10, DOI 10.1186/1743-422X-10-355
- Pawlotsky JM, 2016, GASTROENTEROLOGY, V151, P70, DOI 10.1053/j.gastro.2016.04.003
- Peres-da-Silva A, 2015, J ANTIMICROB CHEMOTH, V70, P726, DOI 10.1093/jac/dku462
- Platt L, 2016, LANCET INFECT DIS, V16, P797, DOI 10.1016/S1473-3099(15)00485-5
- Plaza Z, 2012, ANTIVIR THER, V17, P921, DOI 10.3851/IMP2091
- Rockstroh JK, 2015, LANCET HIV, V2, pE319, DOI 10.1016/S2352-3018(15)00114-9
- Ross-Thriepland D, 2015, J GEN VIROL, V96, P727, DOI 10.1099/jgv.0.000009
- Sarrazin C, 2016, GASTROENTEROLOGY, V151, P501, DOI 10.1053/j.gastro.2016.06.002
- Sarrazin C, 2016, J HEPATOL, V64, P486, DOI 10.1016/j.jhep.2015.09.011
- Uchida Y, 2016, HEPATOL RES, V46, P1234, DOI 10.1111/hepr.12673
- Wang CF, 2013, ANTIMICROB AGENTS CH, V57, P2054, DOI 10.1128/AAC.02494-12
- Welzel TM, 2017, J HEPATOL, V67, P224, DOI 10.1016/j.jhep.2017.03.014
- Wyles D, 2017, ANTIVIR THER, DOI [10.3851/IMP3181, DOI 10.3851/IMP3181]
- Wyles DL, 2015, NEW ENGL J MED, V373, P714, DOI 10.1056/NEJMoa1503153
- Yoshimi S, 2015, J MED VIROL, V87, P1913, DOI 10.1002/jmv.24255
- Zeuzem S, 2015, ANN INTERN MED, V163, P1, DOI 10.7326/M15-0785
Coleções
Artigos e Materiais de Revistas Científicas - FM/MGT
Artigos e Materiais de Revistas Científicas - FM/MIP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/07
Artigos e Materiais de Revistas Científicas - LIM/52
Artigos e Materiais de Revistas Científicas - ODS/03
Artigos e Materiais de Revistas Científicas - FM/MIP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/07
Artigos e Materiais de Revistas Científicas - LIM/52
Artigos e Materiais de Revistas Científicas - ODS/03