Treatment of influenza with neuraminidase inhibitors: virological implications

N A Roberts1

  • 1Roche Products Ltd, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AY, UK. noel.roberts@roche.com

Insights

Emergence of influenza virus resistance to neuraminidase inhibitors (NAIs) is unlikely to occur rapidly in clinics. Studies show NAI-resistant influenza strains are slow to emerge and transient, even in vitro.

Area of Science:

  • Virology
  • Antimicrobial Resistance

Background:

  • Influenza virus resistance to antiviral drugs, like amantadine, necessitates evaluating resistance to neuraminidase inhibitors (NAIs).
  • Preliminary data suggest NAI-resistant influenza emergence is difficult both in vitro and clinically.

Purpose of the Study:

  • To assess the likelihood and characteristics of influenza virus resistance to neuraminidase inhibitors (NAIs).
  • To determine the predictive value of in vitro studies for clinical NAI resistance.
  • To identify optimal sampling times for detecting NAI-resistant influenza in patients.

Main Methods:

  • In vitro selection of resistant influenza virus strains.
  • Analysis of resistance mutations in neuraminidase and haemagglutinin genes.
  • Examination of clinical samples from NAI-treated patients.

Main Results:

  • NAI-resistant influenza virus is difficult to select in vitro.
  • Resistance mutations can arise in neuraminidase (subtype-specific) and haemagglutinin (potentially system-specific) genes.
  • Late-stage clinical samples (day 4+) are crucial for detecting slow-emerging, transient NAI resistance.

Conclusions:

  • Clinically relevant influenza subtypes are essential for predictive in vitro NAI resistance studies.
  • In vitro haemagglutinin mutations may not accurately predict clinical resistance.
  • Detecting NAI-resistant influenza requires analysis of late-treatment clinical samples due to slow and transient emergence.

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