Naturally occurring hepatitis C virus (HCV) NS3/4A protease inhibitor resistance-related mutations in HCV genotype 1-infected subjects in Italy

• Published in: Journal of antimicrobial chemotherapy Vol. 67; no. 4; pp. 984 - 987
• Main Authors: Vicenti, Ilaria, Rosi, Andrea, Saladini, Francesco, Meini, Genny, Pippi, Francesco, Rossetti, Barbara, Sidella, Letizia, Di Giambenedetto, Simona, Almi, Paolo, De Luca, Andrea, Caudai, Cinzia, Zazzi, Maurizio
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2012; Oxford Publishing Limited (England)
• Subjects: 5' Untranslated Regions; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral Agents - pharmacology; Biological and medical sciences; Carrier Proteins - genetics; Disease resistance; Drug Resistance, Viral; Genotype; Genotype & phenotype; Genotypes; Hepacivirus - drug effects; Hepacivirus - genetics; Hepacivirus - isolation & purification; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - epidemiology; Hepatitis C, Chronic - virology; HIV; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Italy - epidemiology; Medical sciences; Molecular Sequence Data; Mutation; Mutation, Missense; Pharmacology. Drug treatments; Prevalence; Protease inhibitors; Protease Inhibitors - pharmacology; Proteinase inhibitors; RNA, Viral - genetics; Sequence Analysis, DNA; Viral diseases; Viral hepatitis; Viral Nonstructural Proteins - genetics; Italy; Europe; genotyping; PIs; drug resistance; Human; Treatment resistance; Typing; Hepatic disease; Genotype; Infection; Virus; Viral disease; Digestive diseases; Antiviral; Genetics; Mutation; Flaviviridae; Hepatitis C virus; Hepacivirus; Protease inhibitor; Viral hepatitis C
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkr581

Objectives To assess the prevalence of hepatitis C virus (HCV) NS3/4A protease inhibitor (PI) resistance mutations in HCV genotype 1-infected PI-naive individuals in Italy. Patients and methods One hundred and twelve patients infected with HCV genotype 1a or 1b (based on Versant HCV Genotype 2.0 or 5′UTR/core sequencing) and never treated with any HCV PI were evaluated. The whole NS3 region was analysed by population sequencing and mutations related to resistance to linear and macrocyclic PIs were recorded. Results Forty-six HCV-monoinfected and 66 HCV/HIV-coinfected subjects were studied. Complete NS3 sequence information was obtained for 109 (97.3%) samples: 67 subtype 1a and 42 subtype 1b. Subtype assignment by NS3 sequencing was concordant in 100.0% and 83.9% of cases with the original 5′UTR sequencing and Versant result, respectively. At least one mutation related to PI resistance was detected in 21 (19.3%) isolates. However, 11 of these had only Q80K, expected to confer resistance to one investigational macrocyclic compound, and were detected only in subtype 1a. Boceprevir and telaprevir resistance-related mutations were detected in 10 (9.2%) isolates and included V36L, T54S and V55A. Only one isolate harboured two mutations (V36L and T54S). There was no association between HCV PI resistance and HIV coinfection or exposure to HIV PIs. Conclusions A minority of untreated HCV genotype 1 patients in Italy harbour a virus population carrying HCV PI resistance-related mutations. The clinical implications of this finding warrant further analysis.