1887

Abstract

Hepatitis C virus (HCV) is responsible for more than 180 million infections worldwide, and about 80 % of infections are reported in Low and Middle-income countries (LMICs). Therapy is based on the administration of interferon (INF), ribavirin (RBV) or more recently Direct-Acting Antivirals (DAAs). However, amino acid substitutions associated with resistance (RAS) have been extensively described and can contribute to treatment failure, and diagnosis of RAS requires considerable infrastructure, not always locally available. Dried serum spots (DSS) sampling is an alternative specimen collection method, which embeds drops of serum onto filter paper to be transported by posting to a centralized laboratory. Here, we assessed feasibility of genotypic analysis of HCV from DSS in a cohort of 80 patients from São Paulo state Brazil. HCV RNA was detected on DSS specimens in 83 % of samples of HCV infected patients. HCV genotypes 1a, 1b, 2a, 2c and 3a were determined using the sequence of the palm domain of NS5B region, and RAS C316N/Y, Q309R and V321I were identified in HCV 1b samples. Concerning therapy outcome, 75 % of the patients who used INF +RBV as a previous protocol of treatment did not respond to DAAs, and 25 % were end-of-treatment responders. It suggests that therapy with INF plus RBV may contribute for non-response to a second therapeutic protocol with DAAs. One patient that presented RAS (V321I) was classified as non-responder, and combination of RAS C316N and Q309R does not necessarily imply in resistance to treatment in this cohort of patients. Data presented herein highlights the relevance of studying circulating variants for a better understanding of HCV variability and resistance to the therapy. Furthermore, the feasibility of carrying out genotyping and RAS phenotyping analysis by using DSS card for the potential of informing future treatment interventions could be relevant to overcome the limitations of processing samples in several location worldwide, especially in LMICs.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.0.000326
2022-03-02
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/acmi/4/3/acmi000326.html?itemId=/content/journal/acmi/10.1099/acmi.0.000326&mimeType=html&fmt=ahah

References

  1. Lavanchy D. The global burden of hepatitis C. Liver Int 2009; 29 Suppl 1:74–81 [View Article] [PubMed]
    [Google Scholar]
  2. Paraskevis D, Stylianou DC, Hezka J, Stern Z, Oikonomopoulou M et al. HCV phylogeography of the general population and high-risk groups in cyprus identifies the island as a global sink for and source of infection. Sci Rep 2019; 9:10077 [View Article] [PubMed]
    [Google Scholar]
  3. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 2014; 59:318–327 [View Article] [PubMed]
    [Google Scholar]
  4. World Health Organization Progress report on access to hepatitisC treatment. Geneva, Switzerland: WHO; 2018 https://www.who.int/hepatitis/publications/hep-c-access-report-2018/en
  5. Graham CS, Swan T. A path to eradication of hepatitis C in low- and middle-income countries. Antiviral Res 2015; 119:89–96 [View Article] [PubMed]
    [Google Scholar]
  6. Petruzziello A, Marigliano S, Loquercio G, Cozzolino A, Cacciapuoti C. Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol 2016; 22:7824–7840 [View Article] [PubMed]
    [Google Scholar]
  7. Ishizaki A, Bouscaillou J, Luhmann N, Liu S, Chua R et al. Survey of programmatic experiences and challenges in delivery of hepatitis B and C testing in low- and middle-income countries. BMC Infect Dis 2017; 17:696 [View Article] [PubMed]
    [Google Scholar]
  8. Kaito M, Watanabe S, Tsukiyama-Kohara K, Yamaguchi K, Kobayashi Y et al. Hepatitis C virus particle detected by immunoelectron microscopic study. J Gen Virol 1994; 75:1755–1760 [View Article] [PubMed]
    [Google Scholar]
  9. Pol S, Lagaye S. The remarkable history of the hepatitis C virus. Genes Immun 2019; 20:436–446 [View Article]
    [Google Scholar]
  10. Tsukiyama-Kohara K, Kohara M. Hepatitis C Virus: viral quasispecies and genotypesViral Quasispecies and Genotypes. Int J Mol Sci 2017; 19:1–8 [View Article] [PubMed]
    [Google Scholar]
  11. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989; 244:359–362 [View Article] [PubMed]
    [Google Scholar]
  12. Manns MP, Buti M, Gane E, Pawlotsky J-M, Razavi H et al. Hepatitis C virus infection. Nat Rev Dis Primers 2017; 3:17006 [View Article]
    [Google Scholar]
  13. Hedskog C, Parhy B, Chang S, Zeuzem S, Moreno C et al. Identification of 19 novel hepatitisnovel hepatitis c virus subtypes-further expandingvirus subtypes-further expanding HCV cclassification. Open Forum Infect Dis 2019; 6:fz076 [View Article]
    [Google Scholar]
  14. Borgia SM, Hedskog C, Parhy B, Hyland RH, Stamm LM et al. Identification of a novel hepatitis C virus genotype from Punjab, India: expanding classification of hepatitis C virus into 8 genotypes. J Infect Dis 2018; 218:1722–1729 [View Article]
    [Google Scholar]
  15. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM et al. International Committee on Taxonomy of Viruses (ICTV). HCV Classification; 2019
  16. Lontok E, Harrington P, Howe A, Kieffer T, Lennerstrand J et al. Resistance analysis in patients with genotype 1–6 HCV infection treated with sofosbuvir/velpatasvir in the phase iii studies. J Hepatol 2017; 89:6105–6116 [View Article]
    [Google Scholar]
  17. Perales C, Quer J, Gregori J, Esteban JI, Domingo E. Resistance of hepatitis C virus to inhibitors: complexity and clinical implications. Viruses 2015; 7:5746–5766 [View Article] [PubMed]
    [Google Scholar]
  18. Manns MP, von Hahn T. Novel therapies for hepatitis C - one pill fits all?. Nat Rev Drug Discov 2013; 12:595–610 [View Article] [PubMed]
    [Google Scholar]
  19. Dietz J, Susser S, Vermehren J, Peiffer K-H, Grammatikos G et al. Patterns of resistance-associated substitutions in patientswith chronic HCV infection following treatment with direct-actingantivirals. Gastroenterology 2018; 154:976–988 [View Article] [PubMed]
    [Google Scholar]
  20. Eltahla AA, Luciani F, White PA, Lloyd AR, Bull RA. Inhibitors ofthe hepatitis C virus polymerase; mode of action and resistance. Viruses 2015; 7:5206–5224 [View Article] [PubMed]
    [Google Scholar]
  21. Membreno FE, Lawitz EJ. The HCV NS5B nucleoside and non-nucleoside inhibitors. Clin Liver Dis 2011; 15:611–626 [View Article]
    [Google Scholar]
  22. Choi KH. Viral Polymerases. In Rossmann M, Rao V. eds Viral Molecular Machines. Advances in Experimental Medicine and Biology vol 726 pp 267–304
    [Google Scholar]
  23. Donaldson EF, Harrington PR, Rear JJO, Naeger LK. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology 2014; 61:56–65
    [Google Scholar]
  24. Castilho MCB, Martins AN, Horbach IS, Perez RM, Figueiredo FAF et al. Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients. Mem Inst Oswaldo Cruz 2011; 106:968–975
    [Google Scholar]
  25. Noble CF, Malta F, Lisboa-Neto G, Gomes-Gouvêa MS, Leite AGB et al. Natural occurrence of NS5B inhibitor resistance-associated variants in Brazilian patients infected with HCV or HCV and HIV. Arch Virol 2017; 162:165–169 [View Article]
    [Google Scholar]
  26. Lange B, Roberts T, Cohn J, Greenman J, Camp J et al. Diagnostic accuracy of detection and quantification of HBV-DNA and HCV-RNA using dried blood spot (DBS) samples - a systematic review and meta-analysis. BMC Infect Dis 2017; 17:693 [View Article] [PubMed]
    [Google Scholar]
  27. Komas NP, Vickos U, Hübschen JM, Béré A, Manirakiza A et al. Cross-sectional study of hepatitis B virus infection in rural communities, Central African Republic. BMC Infect Dis 2013; 13:286 [View Article] [PubMed]
    [Google Scholar]
  28. Nobari RF, Meshkati M, Ataei B, Yazdani MR, Heidari K et al. Identification of patients with hepatitispatients with hepatitis C virus infection in persons with background of intravenous drug use: the first community announcement-based study fromvirus infection in persons with background of intravenous drug use: the first community announcement-based study from iran. Int J Prev Med 2012; 3:S170–5 [PubMed]
    [Google Scholar]
  29. Lopes CLR, Teles SA, Espírito-Santo MP, Lampe E, Rodrigues FP et al. Prevalence, risk factors and genotypes of hepatitis C virus infection among drug users, Central-Western Brazil. Rev Saude Publica 2009; 43 Suppl 1:43–50 [View Article] [PubMed]
    [Google Scholar]
  30. Saludes V, Folch C, Morales-Carmona A, Ferrer L, Fernàndez-López L et al. Community-based screening of hepatitis C with a one-step RNA detection algorithm from dried-blood spots: analysis of key populations in Barcelona, Spain. J Viral Hepat 2018; 25:236–244 [View Article] [PubMed]
    [Google Scholar]
  31. Tuaillon E, Mondain A-M, Meroueh F, Ottomani L, Picot M-C et al. Dried blood spot for hepatitis C virus serology and molecular testing. Hepatology 2010; 51:752–758 [View Article] [PubMed]
    [Google Scholar]
  32. Astbury S, Costa Nunes Soares MM, Peprah E, King B, Jardim ACG et al. Nanopore sequencing from extraction-free direct PCR of dried serum spots for portable hepatitis B virus drug-resistance typing. J Clin Virol 2020; 129:104483 [View Article] [PubMed]
    [Google Scholar]
  33. Ndiaye O, Gozlan J, Diop-Ndiaye H, Sall AS, Chapelain S et al. Usefulness of Dried Blood Spots (DBS) to perform hepatitis C virus genotyping in drug users in Senegal. J Med Virol 2017; 89:484–488 [View Article] [PubMed]
    [Google Scholar]
  34. Kania D, Bekalé AM, Nagot N, Mondain A-M, Ottomani L et al. Combining rapid diagnostic tests and dried blood spot assays for point-of-care testing of human immunodeficiency virus, hepatitis B and hepatitis C infections in Burkina Faso, West Africa. Clin Microbiol Infect 2013; 19:E533–41 [View Article] [PubMed]
    [Google Scholar]
  35. Dokubo EK, Evans J, Winkelman V, Cyrus S, Tobler LH et al. Comparison of Hepatitis C Virus RNA and antibody detection in dried blood spots and plasma specimens. J Clin Virol 2014; 59:223–227 [View Article] [PubMed]
    [Google Scholar]
  36. Marques BLC, do Espírito-Santo MP, Marques VA, Miguel JC, da Silva EF et al. Evaluation of dried blood spot samples for hepatitis C virus detection and quantification. J Clin Virol 2016; 82:139–144 [View Article] [PubMed]
    [Google Scholar]
  37. De Crignis E, Re MC, Cimatti L, Zecchi L, Gibellini D. HIV-1 and HCV detection in dried blood spots by SYBR Green multiplex real-time RT-PCR. J Virol Methods 2010; 165:51–56 [View Article] [PubMed]
    [Google Scholar]
  38. Naidoo A, Parboosing R, Moodley P. Real-time polymerase chain reaction optimised for hepatitis C virus detection in dried blood spots from HIV-exposed infants, KwaZulu-Natal, South Africa. Afr J Lab Med 2016; 5:269 [View Article] [PubMed]
    [Google Scholar]
  39. Greenman J, Roberts T, Cohn J, Messac L. Dried blood spot in the genotyping, quantification and storage of HCV RNA: a systematic literature review. J Viral Hepat 2015; 22:353–361 [View Article]
    [Google Scholar]
  40. Abe K, Konomi N. Hepatitis C virus RNA in dried serum spotted onto filter paper is stable at room temperature. J Clin Microbiol 1998; 36:3070–3072 [View Article] [PubMed]
    [Google Scholar]
  41. Mahajan S, Choudhary MC, Kumar G, Gupta E. Evaluation of dried blood spot as an alternative sample collection method for hepatitis C virus RNA quantitation and genotyping using a commercial system. Virusdisease 2018; 29:141–146 [View Article] [PubMed]
    [Google Scholar]
  42. WDI Classifying countries by income [Internet]; 2019 https://datatopics.worldbank.org/world-development-indicators/stories/the-classification-of-countries-by-income.html accessed 19 November 2020
  43. Vercauteren K, Brown RJP, Mesalam AA, Doerrbecker J, Bhuju S et al. Targeting a host-cell entry factor barricades antiviral-resistant HCV variants from on-therapy breakthrough in human-liver mice. Gut 2016; 65:2029–2034 [View Article] [PubMed]
    [Google Scholar]
  44. Morice Y, Roulot D, Grando V, Stirnemann J, Gault E et al. Phylogenetic analyses confirm the high prevalence of hepatitis C virus (HCV) type 4 in the Seine-Saint-Denis district (France) and indicate seven different HCV-4 subtypes linked to two different epidemiological patterns. J Gen Virol 2001; 82:1001–1012 [View Article] [PubMed]
    [Google Scholar]
  45. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013; 30:2725–2729 [View Article] [PubMed]
    [Google Scholar]
  46. Kuiken C, Thurmond J, Dimitrijevic M, Yoon H. The LANL hemorrhagic fever virus database, a new platform for analyzing biothreat viruses. Nucleic Acids Res 2012; 40:D587–92 [View Article] [PubMed]
    [Google Scholar]
  47. Pickett BE, Sadat EL, Zhang Y, Noronha JM, Squires RB et al. ViPR: an open bioinformatics database and analysis resource for virology research. Nucleic Acids Res 2012; 40:D593–8 [View Article] [PubMed]
    [Google Scholar]
  48. de Oliveira T, Deforche K, Cassol S, Salminen M, Paraskevis D et al. An automated genotyping system for analysis of HIV-1 and other microbial sequences. Bioinformatics 2005; 21:3797–3800 [View Article] [PubMed]
    [Google Scholar]
  49. Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S et al. NCBI BLAST: a better web interface. Nucleic Acids Res 2008; 36:W5–9 [View Article] [PubMed]
    [Google Scholar]
  50. Döring M, Büch J, Friedrich G, Pironti A, Kalaghatgi P et al. geno2pheno[ngs-freq]: a genotypic interpretation system for identifying viral drug resistance using next-generation sequencing data. Nucleic Acids Res 2018; 46:W271–W277 [View Article] [PubMed]
    [Google Scholar]
  51. Struck D, Lawyer G, Ternes A-M, Schmit J-C, Bercoff DP. COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification. Nucleic Acids Res 2014; 42:e144 [View Article] [PubMed]
    [Google Scholar]
  52. Singer JB, Thomson EC, McLauchlan J, Hughes J, Gifford RJ. GLUE: a flexible software system for virus sequence data. BMC Bioinformatics 2018; 19:532 [View Article] [PubMed]
    [Google Scholar]
  53. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: molecular evolutionary genetics analysis across computing platformsMolecular Evolutionary Genetics Analysis across Computing Platforms. Mol Biol Evol 2018; 35:1547–1549 [View Article] [PubMed]
    [Google Scholar]
  54. Hillis DM, Bull JJ. An empirical test of bootstrapping as a method for assessing confidence in phylogenetic analysis. Syst Biol 1993; 42:182 [View Article]
    [Google Scholar]
  55. Di Maio VC, Cento V, Mirabelli C, Artese A, Costa G et al. Hepatitis C virus genetic variability and the presence of NS5B resistance-associated mutations as natural polymorphisms in selected genotypes could affect the response to NS5B inhibitors. Antimicrob Agents Chemother 2014; 58:2781–2797 [View Article] [PubMed]
    [Google Scholar]
  56. Soulier A, Poiteau L, Rosa I, Hézode C, Roudot-Thoraval F et al. Dried blood spotsBlood Spots: a tool to ensure broad access to hepatitisA Tool to Ensure Broad Access to Hepatitis C screening, diagnosis, and treatment monitoringScreening, Diagnosis, and Treatment Monitoring. J Infect Dis 2016; 213:1087–1095 [View Article] [PubMed]
    [Google Scholar]
  57. Shepherd SJ, Baxter RE, Gunson RN. Evaluation of the Abbott m2000 system for dried blood spot detection of hepatitis C virus RNA. J Clin Virol 2019; 110:7–10 [View Article] [PubMed]
    [Google Scholar]
  58. Hezode C, Reau N, Svarovskaia ES, Doehle BP, Shanmugam R et al. Resistance analysis in patients with genotype 1-6 HCV infection treated with sofosbuvir/velpatasvir in the phase III studies. J Hepatol 2018; 68:895–903 [View Article] [PubMed]
    [Google Scholar]
  59. Llibre A, Shimakawa Y, Mottez E, Ainsworth S, Buivan T-P et al. Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus. Gut 2018; 67:2017–2024 [View Article] [PubMed]
    [Google Scholar]
  60. Krajden M, Ziermann R, Khan A, Mak A, Leung K et al. Qualitative detection of hepatitis C virus RNA: comparison of analytical sensitivity, clinical performance, and workflow of the Cobas Amplicor HCV test version 2.0 and the HCV RNA transcription-mediated amplification qualitative assay. J Clin Microbiol 2002; 40:2903–2907 [View Article] [PubMed]
    [Google Scholar]
  61. Brandão CPU, Marques BLC, Marques VA, Villela-Nogueira CA, Do Ó KMR et al. Simultaneous detection of hepatitis C virus antigen and antibodies in dried blood spots. J Clin Virol 2013; 57:98–102 [View Article] [PubMed]
    [Google Scholar]
  62. Vázquez-Morón S, Ardizone Jiménez B, Jiménez-Sousa MA, Bellón JM, Ryan P et al. Evaluation of the diagnostic accuracy of laboratory-based screening for hepatitis C in dried blood spot samples: a systematic review and meta-analysis. Sci Rep 2019; 9:7316 [View Article] [PubMed]
    [Google Scholar]
  63. Alidjinou EK, Deldalle J, Hallaert C, Robineau O, Ajana F et al. RNA and DNA Sanger sequencing versus next-generation sequencing for HIV-1 drug resistance testing in treatment-naive patients. J Antimicrob Chemother 2017; 72:2823–2830 [View Article] [PubMed]
    [Google Scholar]
  64. Blach S, Zeuzem S, Manns M, Altraif I, Duberg A-S et al. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol 2017; 2:161–176 [View Article] [PubMed]
    [Google Scholar]
  65. Campiotto S, Pinho JRR, Carrilho FJ, Da Silva LC, Souto FJD et al. Geographic distribution of hepatitis C virus genotypes in Brazil. Braz J Med Biol Res 2005; 38:41–49 [View Article] [PubMed]
    [Google Scholar]
  66. Alvarado-Mora MV, Moura IM, Botelho-Lima LS, Azevedo RS, Lopes E et al. Distribution and molecular characterization of hepatitis C virus (HCV) genotypes in patients with chronic infection from Pernambuco State, Brazil. Virus Res 2012; 169:8–12 [View Article] [PubMed]
    [Google Scholar]
  67. Vieira DS, Alvarado-Mora MV, Botelho L, Carrilho FJ, Pinho JR et al. Distribution of hepatitis c virus (HCV) genotypes in patients with chronic infection from Rondônia, Brazil. Virol J 2011; 8:165 [View Article] [PubMed]
    [Google Scholar]
  68. Nishiya AS, de Almeida-Neto C, Ferreira SC, Alencar CS, Di-Lorenzo-Oliveira C et al. HCV genotypes, characterization of mutations conferring drug resistance to protease inhibitors, and risk factors among blood donors in São Paulo, Brazil. PLoS One 2014; 9:e86413 [View Article] [PubMed]
    [Google Scholar]
  69. Romano CM, de Carvalho-Mello IMVG, Jamal LF, de Melo FL, Iamarino A et al. Social networks shape the transmission dynamics of hepatitis C virus. PLoS One 2010; 5:e11170 [View Article] [PubMed]
    [Google Scholar]
  70. Zarife MAS, Silva LK, Silva MBS, Lopes GB, Barreto ML et al. Prevalence of hepatitis C virus infection in north-eastern Brazil: a population-based study. Trans R Soc Trop Med Hyg 2006; 100:663–668 [View Article] [PubMed]
    [Google Scholar]
  71. Pacheco SDB, Silva-Oliveira GC, Maradei-Pereira LMC, Crescente JÂB, Lemos JAR de et al. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil. Rev Soc Bras Med Trop 2014; 47:367–370 [View Article] [PubMed]
    [Google Scholar]
  72. Silva MBS, Andrade TM, Silva LK, Rodart IF, Lopes GB et al. Prevalence and genotypes of hepatitis C virus among injecting drug users from Salvador-BA, Brazil. Mem Inst Oswaldo Cruz 2010; 105:299–303 [View Article] [PubMed]
    [Google Scholar]
  73. Coutinho C, Bastos LS, da Mota JC, Toledo L, Costa K et al. The risks of HCV infection among Brazilian crack cocaine users: incorporating diagnostic test uncertainty. Sci Rep 2019; 9:443 [View Article] [PubMed]
    [Google Scholar]
  74. Magiorkinis G, Magiorkinis E, Paraskevis D, Ho SYW, Shapiro B et al. The global spread of hepatitis C virus 1a and 1b: a phylodynamic and phylogeographic analysis. PLoS Med 2009; 6:e1000198 [View Article] [PubMed]
    [Google Scholar]
  75. Nakano T, Lu L, Liu P, Pybus OG. Viral gene sequences reveal the variable history of hepatitis C virus infection among countries. J Infect Dis 2004; 190:1098–1108 [View Article] [PubMed]
    [Google Scholar]
  76. Morice Y, Cantaloube J-F, Beaucourt S, Barbotte L, De Gendt S et al. Molecular epidemiology of hepatitis C virus subtype 3a in injecting drug users. J Med Virol 2006; 78:1296–1303 [View Article] [PubMed]
    [Google Scholar]
  77. Pereira LMMB, Martelli CMT, Moreira RC, Merchan-Hamman E, Stein AT et al. Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study. BMC Infect Dis 2013; 13:60 [View Article] [PubMed]
    [Google Scholar]
  78. Guimarães V de S, Melo T de, Ferreira R de C, Almeida S de, Martins LC. Prevalence of hepatitis C virus genotypes in the State of Pará, Brazil. Rev Soc Bras Med Trop 2018; 51:508–512 [View Article] [PubMed]
    [Google Scholar]
  79. Bassit L, Da Silva LC, Ribeiro-Dos-Santos G, Maertens G, Carrilho FJ et al. Chronic hepatitis C virus infections in brazilian patients: association with genotypes, clinical parameters and response to long term alpha interferon therapy. Rev Inst Med Trop Sao Paulo 1999; 41:183–189 [View Article] [PubMed]
    [Google Scholar]
  80. Stramer SL, Glynn SA, Kleinman SH, Strong DM, Caglioti S et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid–amplification testing. N Engl J Med 2004; 351:760–768 [View Article] [PubMed]
    [Google Scholar]
  81. Tobler LH, Stramer SL, Lee SR, Masecar BL, Peterson JE et al. Impact of HCV 3.0 EIA relative to HCV 2.0 EIA on blood-donor screening. Transfusion 2003; 43:1452–1459 [View Article] [PubMed]
    [Google Scholar]
  82. Jaques B, Saldanha PC de A, Moraes ACR de. Profile of blood donations with a positive serology in Southern Brazil. Hematol Transfus Cell Ther 2020; 42:129–133 [View Article] [PubMed]
    [Google Scholar]
  83. Kretzer IF, do Livramento A, da Cunha J, Gonçalves S, Tosin I et al. Hepatitis C worldwide and in Brazil: silent epidemic--data on disease including incidence, transmission, prevention, and treatment. Sci World J 2014; 2014:1–10 [View Article] [PubMed]
    [Google Scholar]
  84. Terrault NA, Dodge JL, Murphy EL, Tavis JE, Kiss A et al. Sexual transmission of hepatitis C virus among monogamous heterosexual couples: the HCV partners study. Hepatology 2013; 57:881–889 [View Article] [PubMed]
    [Google Scholar]
  85. Neumayr G, Propst A, Schwaighofer H, Judmaier G, Vogel W. Lack of evidence for the heterosexual transmission of hepatitis C. QJM 1999; 92:505–508 [View Article] [PubMed]
    [Google Scholar]
  86. Danta M, Brown D, Bhagani S, Pybus OG, Sabin CA et al. Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours. AIDS 2007; 21:983–991 [View Article] [PubMed]
    [Google Scholar]
  87. de Bruijne J, Schinkel J, Prins M, Koekkoek SM, Aronson SJ et al. Emergence of hepatitis C virus genotype 4: phylogenetic analysis reveals three distinct epidemiological profiles. J Clin Microbiol 2009; 47:3832–3838 [View Article] [PubMed]
    [Google Scholar]
  88. Kuehlkamp VM, Schuelter-Trevisol F. Prevalence of human immunodeficiency virus/hepatitis C virus co-infection in Brazil and associated factors: a review. Braz J Infect Dis 2013; 17:455–463 [View Article] [PubMed]
    [Google Scholar]
  89. Cheinquer H, Sette H, Wolff FH, de Araujo A, Coelho-Borges S et al. Treatment of cChronic HCV infection with the new direct acting antiviralsInfection with the New Direct Acting Antivirals (DAA): first report of a real world experienceFirst Report of a Real World Experience in Southern Brazil. Ann Hepatol 2017; 16:727–733 [View Article] [PubMed]
    [Google Scholar]
  90. Costa VD, Brandão-Mello CE, Nunes EP, Dos Santos Silva PGC, de Souza Rodrigues L et al. Treatment of chronic HCV infection with DAAs in Rio de Janeiro/Brazil: SVR rates and baseline resistance analyses in NS5A and NS5B genes. PLoS One 2019; 14:e0216327 [View Article] [PubMed]
    [Google Scholar]
  91. Ministério da Saúde Boletim Epidemiológico Hepatites Virais 2020; 2020 http://www.aids.gov.br/pt-br/pub/2020/boletim-epidemiologico-hepatites-virais-2020
  92. Portari-Filho LH, Álvares-da-Silva MR, Gonzalez A, Ferreira AP, Villela-Nogueira CA et al. How are HCV-infected patients being identified in Brazil: a multicenter study. Braz J Infect Dis 2019; 23:34–39 [View Article]
    [Google Scholar]
  93. Puchades Renau L, Berenguer M. Introduction to hepatitis C virus infection: overview and history of hepatitis C virus therapies. Hemodial Int 2018; 22 Suppl 1:S8–S21 [View Article] [PubMed]
    [Google Scholar]
  94. Te HS, Randall G, Jensen DM. Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol 2007; 3:218–225 [PubMed]
    [Google Scholar]
  95. Asahina Y, Izumi N, Enomoto N, Uchihara M, Kurosaki M et al. Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C. J Hepatol 2005; 43:623–629 [View Article] [PubMed]
    [Google Scholar]
  96. Jardim ACG, Yamasaki LHT, de Queiróz ATL, Bittar C, Pinho JRR et al. Quasispecies of hepatitis C virus genotype 1 and treatment outcome with peginterferon and ribavirin. Infect Genet Evol 2009; 9:689–698 [View Article] [PubMed]
    [Google Scholar]
  97. Hedegaard DL, Tully DC, Rowe IA, Reynolds GM, Bean DJ et al. High resolution sequencing of hepatitis C virus reveals limited intra-hepatic compartmentalization in end-stage liver disease. J Hepatol 2017; 66:28–38 [View Article] [PubMed]
    [Google Scholar]
  98. Vercauteren K, Brown RJP, Mesalam AA, Doerrbecker J, Bhuju S et al. Targeting a host-cell entry factor barricades antiviral-resistant HCV variants from on-therapy breakthrough in human-liver mice. Gut 2016; 65:2029–2034 [View Article]
    [Google Scholar]
  99. Hang JQ, Yang Y, Harris SF, Leveque V, Whittington HJ et al. Slow binding inhibition and mechanism of resistance of non-nucleoside polymerase inhibitors of hepatitis C virus. J Biol Chem 2009; 284:15517–15529 [View Article] [PubMed]
    [Google Scholar]
  100. Uchida Y, Nakamura S, Kouyama J-I, Naiki K, Motoya D et al. Significance of NS5B substitutions in genotypeSubstitutions in Genotype 1b hHepatitis C virus evaluated by bioinformatics analysisVirus Evaluated by Bioinformatics Analysis. Sci Rep 2018; 8:8818 [View Article] [PubMed]
    [Google Scholar]
  101. Peres-da-Silva A, Brandão-Mello CE, Lampe E. Prevalence of sofosbuvir resistance-associated variants in Brazilian and worldwide NS5B sequences of genotype-1 HCV. Antivir Ther 2017; 22:447–451 [View Article] [PubMed]
    [Google Scholar]
  102. Svarovskaia ES, Dvory-Sobol H, Parkin N, Hebner C, Gontcharova V et al. Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials. Clin Infect Dis 2014; 59:1666–1674 [View Article] [PubMed]
    [Google Scholar]
  103. Tong X, Le Pogam S, Li L, Haines K, Piso K et al. In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir. J Infect Dis 2014; 209:668–675 [View Article] [PubMed]
    [Google Scholar]
  104. Lontok E, Harrington P, Howe A, Kieffer T, Lennerstrand J et al. Hepatitis C virus drug resistance-associated substitutions: State of the art summary. Hepatology 2015; 62:1623–1632 [View Article] [PubMed]
    [Google Scholar]
  105. Svarovskaia ES, Gane E, Dvory-Sobol H, Martin R, Doehle B et al. L159F and V321A sofosbuvir-associated hepatitis C virus NS5B substitutions. J Infect Dis 2016; 213:1240–1247 [View Article] [PubMed]
    [Google Scholar]
  106. Hamano K, Sakamoto N, Enomoto N, Izumi N, Asahina Y et al. Mutations in the NS5B region of the hepatitis C virus genome correlate with clinical outcomes of interferon-alpha plus ribavirin combination therapy. J Gastroenterol Hepatol 2005; 20:1401–1409 [View Article] [PubMed]
    [Google Scholar]
  107. Shi ST, Herlihy KJ, Graham JP, Fuhrman SA, Doan C et al. In vitro resistance study of AG-021541, a novel nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Antimicrob Agents Chemother 2008; 52:675–683 [View Article] [PubMed]
    [Google Scholar]
  108. McCown MF, Rajyaguru S, Kular S, Cammack N, Nájera I. GT-1a or GT-1b subtype-specific resistance profiles for hepatitis C virus inhibitors telaprevir and HCV-796. Antimicrob Agents Chemother 2009; 53:2129–2132 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.0.000326
Loading
/content/journal/acmi/10.1099/acmi.0.000326
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error