Detection of Variants With Reduced Baloxavir Marboxil Susceptibility After Treatment of Children With Influenza A During the 2018-2019 Influenza Season

J Infect Dis. 2020 Jun 16;222(1):121-125. doi: 10.1093/infdis/jiaa061.

Abstract

During the 2018-2019 influenza seasons, we detected reduced baloxavir marboxil (baloxavir) susceptible variants with I38S or I38T amino acid substitutions on the PA subunit of influenza virus ribonucleic acid polymerase in 7 of 18 baloxavi-treated children and found that virus titer rebounded in some of these children with variants. We also found fever durations to be similar between patients with or without the variants, but the patients with variants shed the virus 3 days longer and took longer to improve clinical symptoms than those without variants. The emergence of these variants should be monitored during future influenza seasons.

Keywords: antiviral therapy; baloxavir; influenza; oseltamivir; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Dibenzothiepins / therapeutic use*
  • Drug Resistance, Viral / drug effects*
  • Drug Resistance, Viral / genetics*
  • Female
  • Genetic Variation
  • Humans
  • Infant
  • Infant, Newborn
  • Influenza A Virus, H3N2 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza, Human / drug therapy*
  • Japan / epidemiology
  • Male
  • Morpholines / therapeutic use*
  • Pyridones / therapeutic use*
  • Triazines / therapeutic use*

Substances

  • Antiviral Agents
  • Dibenzothiepins
  • Morpholines
  • Pyridones
  • Triazines
  • baloxavir