6533b833fe1ef96bd129c197
RESEARCH PRODUCT
Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy
Ada BertoliMaria Chiara SorboMarianna AragriIlaria LenciElisabetta TetiEnnio PolilliVelia Chiara Di MaioLaura GianserraElisa BiliottiChiara MasettiCarlo F. MagniSergio BabudieriLaura A. NicoliniMartina MilanaPierluigi CacciatoreLoredana SarmatiAdriano M. PellicelliStefania PaolucciAntonio CraxìFilomena MoriscoValeria Pace PalittiMassimo SicilianoNicola CoppolaNerio IapadreMassimo PuotiGiuliano RizzardiniGloria TalianiCaterina PasquazziMassimo AndreoniGiustino ParrutiMario AngelicoCarlo Federico PernoValeria CentoFrancesca Ceccherini-silbersteinPietro AndreoneFausto BaldantiGiorgio BarbariniVincenzo BoccaccioLucio BoglioneMatteo BolisStefano BonoraVanni BorghiGiuseppina BrancaccioSavino BrunoBianca BruzzoneVincenza CalvarusoNicola CaporasoAntonio CiaccioAlessia CiancioPiero ColombattoRaffaele CozzolongoCecilia D'ambrosioGabriella D'ettorreFrancesco De LeonardisAndrea De LucaAntonio Di BiagioGiovanni Di PerriSimona FranciosoGiovanni Battista GaetaAntonio GasbarriniValeria GhisettiAlessia GiorginiAntonio GriecoGuido GubertiniRoberto GulminettiLara LambiaseSimona LandonioMiriam LichtnerIvana MaidaSimona MarencoLetizia MarinaroRenato MaseratiMichela MelisBarbara MenzaghiElisa MeregalliValeria MicheliFosca NieroMaurizio PaoloniAlessandro PieriMaria RendinaDante RomagnoliBarbara RossettiTina RuggieroVincenzo SangiovanniMario StaraceLaura SticchiPierluigi TarquiniPierluigi ToniuttoVincenzo VulloMaurizio Zazzi Hcv Virology Italian Resistance Networksubject
Male0301 basic medicineSofosbuvirHepacivirusDrug Resistancelcsh:MedicineHepacivirusViral Nonstructural Proteinsmedicine.disease_causeGastroenterologyHepatitis C Virus; HCV resistance-testchemistry.chemical_compound0302 clinical medicineGenotypePrevalenceVirallcsh:ScienceHCV resistance-testMultidisciplinarybiologyHepatitis CMiddle AgedSettore MED/07 - Microbiologia e Microbiologia ClinicaHepatitis CItalyCohortHCVFemale030211 gastroenterology & hepatologymedicine.drugAdultmedicine.medical_specialtyHepatitis C VirusGenotypeHCV RASHepatitis C virus03 medical and health sciencesInternal medicineDrug Resistance ViralmedicineHumansAdult; Aged; Drug Resistance Viral; Female; Hepacivirus; Hepatitis C; Humans; Italy; Male; Middle Aged; Prevalence; Viral Nonstructural Proteins; GenotypeNS5ANS5BAgedbusiness.industrylcsh:RHepatitis C Virus HCV resistance-testbiology.organism_classificationmedicine.disease030104 developmental biologychemistrylcsh:Qbusinessdescription
AbstractNatural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2–45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4–19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1–4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-06-12 |