title: Distribution of natural resistance to NS3 protease inhibitors in hepatitis C genotype 1a separated into clades 1 and 2 and in genotype 1b of HIV-infected patients.
abstract: Naturally occurring resistance-associated variants (RAVs) within the protease domain of hepatitis C virus (HCV) genotype (G) 1a separated into clades 1 and 2, and G1b were investigated in 59 HIV/HCV coinfected patients. RAVs were detected in 10/23 G1a/clade 1 and 1/19 G1b (p 0.0059). A similar frequency of RAVs was found when comparing G1a/clade 2 and G1b (p 0.1672). A cross-resistance to the macrocyclic compounds simeprevir and paritaprevir was detected in two G1a/clade 2 and 1 G1b sequences and none of G1a/clade 1 sequences. The simultaneous characterization of subtype and natural RAVs by population analysis of the NS3 domain by may add important information for anti-HCV treatment strategies including protease inhibitors.
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy; Vita-Salute University, Milan, Italy. Electronic address: bagaglio.sabrina@hsr.it.
authors.forename: S
authors.initials: S
authors.lastname: Bagaglio
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Uberti-Foppa
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Messina
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Merli
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy.
authors.forename: H
authors.initials: H
authors.lastname: Hasson
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Andolina
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Galli
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy; Vita-Salute University, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: Department of Infectious Diseases, Scientific Institute Ospedale San Raffaele, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Morsica
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D020125:Mutation, Missense; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D000069616:Simeprevir / Q000494:pharmacology; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D011392:Proline; D011480:Protease Inhibitors; D012367:RNA, Viral; D000069616:Simeprevir; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C585405:paritaprevir
keywords: Clades 1 and 2; HCV-PI; HIV; Q80K polymorphism; genotype 1a; natural RAV