Secondary substitutions in the hemagglutinin and neuraminidase genes associated with neuraminidase inhibitor resistance are rare in the Influenza Resistance Information Study (IRIS)

Amino acid substitutions in influenza virus neuraminidase (NA) that cause resistance to inhibitors (NAI) generally result attenuation. However, viruses may acquire secondary the NA and hemagglutinin (HA) proteins can restore viral fitness. To assess which extent this happens, emergence of NAI – potentially compensatory was quantified immunocompetent individuals included Influenza Resistance Information Study (IRIS; NCT00884117). Known were detected by mutation specific RT-PCR 57 1803 (3.2%) oseltamivir-treated individuals, including 39 infected with A/H1N1pdm09 [H275Y] 18 A/H3N2 [R292K] virus. A total fifteen ten other amino acquired HA respectively, A/H1N1pdm09, B upon treatment oseltamivir but none these associated oseltamivir. All cultured known H275Y or R292K showed reduced susceptibility NA-star assay. Upon next-generation sequencing, vast majority resistant had no resistance-associated at high frequency. Only two viruses, HA-D52N NA-R152K detected. We conclude fitness a rare event population. • Individuals IRIS study queried for drug resistance- mutations. Emergence mutations 3.2% (57/1803) who received treatment. Newly identified genes did not resistance. The is event.