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

Clin Microbiol Infect. 2016 Apr;22(4):386.e1-386.e3. doi: 10.1016/j.cmi.2015.12.007. Epub 2015 Dec 17.

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.

Keywords: Clades 1 and 2; HCV-PI; HIV; Q80K polymorphism; genotype 1a; natural RAV.

MeSH terms

  • Adult
  • Antiviral Agents / pharmacology*
  • Cyclopropanes
  • Drug Resistance, Viral*
  • Female
  • Genotype*
  • HIV Infections / complications*
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / virology*
  • Humans
  • Lactams, Macrocyclic
  • Macrocyclic Compounds / pharmacology
  • Male
  • Mutation, Missense
  • Proline / analogs & derivatives
  • Protease Inhibitors / pharmacology*
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Simeprevir / pharmacology
  • Sulfonamides
  • Viral Nonstructural Proteins / genetics

Substances

  • Antiviral Agents
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • RNA, Viral
  • Sulfonamides
  • Viral Nonstructural Proteins
  • Proline
  • Simeprevir
  • paritaprevir