title: Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Infectious Diseases and Clinical Microbiology, Bitlis Public Hospital, Bitlis 13000, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Sargin Altunok
authors.affiliation: Clinical Laboratory, Kocaeli University Faculty of Medicine, Kocaeli 41380, Turkey; Near East University, Research Center of Experimental Health Sciences, Nicosia, Northern Cyprus.
authors.forename: Murat
authors.initials: M
authors.lastname: Sayan
authors.affiliation: Infectious Diseases And Clinical Microbiology, Kocaeli University Faculty of Medicine, Kocaeli 41380, Turkey.
authors.forename: Sila
authors.initials: S
authors.lastname: Akhan
authors.affiliation: Infectious Diseases And Clinical Microbiology, Erciyes University Faculty of Medicine, Kayseri 38030, Turkey.
authors.forename: Bilgehan
authors.initials: B
authors.lastname: Aygen
authors.affiliation: Infectious Diseases And Clinical Microbiology, Erciyes University Faculty of Medicine, Kayseri 38030, Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Yildiz
authors.affiliation: Infectious Diseases and Clinical Microbiology, Koc University Faculty of Medicine, İstanbul 34010, Turkey.
authors.forename: Suda
authors.initials: S
authors.lastname: Tekin Koruk
authors.affiliation: Infectious Diseases and Clinical Microbiology, Uludag University Faculty of Medicine, Bursa, Turkey.
authors.forename: Resit
authors.initials: R
authors.lastname: Mistik
authors.affiliation: Infectious Diseases and Clinical Microbiology, Afyon Kocatepe University Faculty of Medicine, Afyonkarahisar, Turkey.
authors.forename: Nese
authors.initials: N
authors.lastname: Demirturk
authors.affiliation: Infectious Diseases and Clinical Microbiology, Selçuk University Faculty of Medicine, Konya, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Ural
authors.affiliation: Infectious Diseases and Clinical Microbiology, Tepecik Training and Research Hospital, İzmir, Turkey.
authors.forename: Şükran
authors.initials: Ş
authors.lastname: Kose
authors.affiliation: Infectious Diseases and Clinical Microbiology, Zonguldak Ataturk Public Hospital, Zonguldak, Turkey.
authors.forename: Aynur
authors.initials: A
authors.lastname: Aynioglu
authors.affiliation: Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey.
authors.forename: Fatime
authors.initials: F
authors.lastname: Korkmaz
authors.affiliation: Infectious Diseases And Clinical Microbiology, Mersin University Faculty of Medicine, Mersin, Turkey.
authors.forename: Gülden
authors.initials: G
authors.lastname: Ersoz
authors.affiliation: Infectious Diseases and Clinical Microbiology, Sakarya University Faculty of Medicine, Sakarya, Turkey.
authors.forename: Nazan
authors.initials: N
authors.lastname: Tuna
authors.affiliation: Infectious Diseases and Clinical Microbiology, Dicle University Faculty of Medicine, Diyarbakir, Turkey.
authors.forename: Celal
authors.initials: C
authors.lastname: Ayaz
authors.affiliation: Infectious Diseases and Clinical Microbiology, Erzincan University Faculty of Medicine, Erzincan, Turkey.
authors.forename: Faruk
authors.initials: F
authors.lastname: Karakecili
authors.affiliation: Infectious Diseases and Clinical Microbiology, Necip Fazil City Hospital, Kahramanmaraş, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Keten
authors.affiliation: Infectious Diseases and Clinical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey.
authors.forename: Dilara
authors.initials: D
authors.lastname: Inan
authors.affiliation: Infectious Diseases and Clinical Microbiology, Göztepe Training and Research Hospital, İstanbul, Turkey.
authors.forename: Saadet
authors.initials: S
authors.lastname: Yazici
authors.affiliation: Infectious Diseases and Clinical Microbiology, Giresun Public Hospital, Giresun, Turkey.
authors.forename: Safiye
authors.initials: S
authors.lastname: Koculu
authors.affiliation: Infectious Diseases and Clinical Microbiology, Okmeydanı Training and Research Hospital, İstanbul, Turkey.
authors.forename: Taner
authors.initials: T
authors.lastname: Yildirmak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D000069616:Simeprevir / Q000627:therapeutic use; D014421:Turkey; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011392:Proline; D011480:Protease Inhibitors; D000069616:Simeprevir; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir; C512204:N-(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
keywords: Baseline resistance; hepatitis C virus; mutation; protease inhibitors