Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C

ArticleAçık Erişim

Özet

Background Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. Materials and methods 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. Results In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. Conclusion We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment. © 2016 The Authors

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https://rdlopen.rawdatalibrary.net/r/ebyu/14815Resmi atıflarda kullanılan kalıcı adres
DOI
https://doi.org/10.1016/j.ijid.2016.07.003Yayıncı resmi DOI adresi
Tam Kayıt
AlanDeğerDil
dc.contributor.authorSargin Altunok, Elif
dc.contributor.authorSayan, Murat
dc.contributor.authorAkhan, Sila
dc.contributor.authorAygen, Bilgehan
dc.contributor.authorYildiz, Orhan
dc.contributor.authorTekin Koruk, Suda
dc.contributor.authorMistik, Resit
dc.contributor.authorDemirturk, Nese
dc.contributor.authorUral, Onur
dc.contributor.authorKose, Şükran
dc.contributor.authorAynioglu, Aynur
dc.contributor.authorKorkmaz, Fatime
dc.contributor.authorErsoz, Gülden
dc.contributor.authorTuna, Nazan
dc.contributor.authorAyaz, Celal
dc.contributor.authorKarakecili, Faruk
dc.contributor.authorKeten, Derya
dc.contributor.authorInan, Dilara
dc.contributor.authorYazici, Saadet
dc.contributor.authorKoculu, Safiye
dc.contributor.authorYildirmak, Taner
dc.date.accessioned2026-10-18T20:29:36.874487604Z
dc.date.available2026-10-18T20:29:36.874487604Z
dc.date.issued2016
dc.description.abstractBackground Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. Materials and methods 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. Results In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. Conclusion We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment. © 2016 The Authors
dc.description.sponsorshipFunding: This study was funded by Department of Scientific Research Project of Kocaeli University and Turkish Society of Clinic Microbiology and Infectious Diseases.
dc.identifier.doi10.1016/j.ijid.2016.07.003
dc.identifier.endpage5
dc.identifier.issn1201-9712
dc.identifier.pmid27401586
dc.identifier.scopus2-s2.0-84979254596
dc.identifier.startpage1
dc.identifier.urihttps://rdlopen.rawdatalibrary.net/r/ebyu/14815
dc.identifier.volume50
dc.language.isoen
dc.publisherElsevier B.V.
dc.relation.ispartofInternational Journal of Infectious Diseases
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBaseline resistance
dc.subjecthepatitis C virus
dc.subjectmutation
dc.subjectprotease inhibitors
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAntiviral Agents
dc.subjectDrug Resistance, Viral
dc.subjectFemale
dc.subjectGenotype
dc.subjectHepacivirus
dc.subjectHepatitis C, Chronic
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectOligopeptides
dc.subjectProline
dc.subjectSimeprevir
dc.subjectTurkey
dc.subjectViral Nonstructural Proteins
dc.subjectYoung Adult
dc.subjectamino acid
dc.subjectboceprevir
dc.subjectfaldaprevir
dc.subjectinterleukin 28B
dc.subjectproteinase inhibitor
dc.subjecttelaprevir
dc.subjectantivirus agent
dc.subjectN-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
dc.titleProtease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C
dc.typeArticle
dspace.entity.typePublication
rdl.citation.scopus11
rdl.departmentInfectious Diseases and Clinical Microbiology, Erzincan University Faculty of Medicine, Erzincan, Turkey.
rdl.oa.statusgold
rdl.source.indexSCOPUS
rdl.source.indexPUBMED