Key result
Treatment-emergent non-I38 polymerase acidic substitutions in influenza viruses conferred reduced susceptibility to baloxavir and were associated with virus rebound.
Why the study?
Do non-I38 PA substitutions emerge during baloxavir treatment and confer reduced susceptibility and virus rebound?
Do non-I38 PA substitutions emerge during baloxavir treatment and confer reduced susceptibility and virus rebound?
Non-I38 substitutions in the PA endonuclease represent alternate pathways to baloxavir resistance and should be monitored.
Answers are grounded in this paper and cite their sources.
Non-I38 PA substitutions may reduce baloxavir susceptibility with rebound; leaves open need for expanded resistance surveillance.
Influenza viruses harboring treatment-emergent I38F/M/N/T substitutions in the polymerase acidic (PA) endonuclease exhibited reduced susceptibility to baloxavir and were associated with virus rebound and variable clinical response in clinical trials. US regulatory review of registrational trial data also identified treatment-emergent PA substitutions E23K in A/H1N1 viruses and E23G/K, A37T, and E199G in A/H3N2 viruses, which conferred reduced susceptibility to baloxavir, although to a lesser degree than I38F/M/N/T substitutions, and were associated with virus rebound. Although these non-I38 substitutions emerged less frequently than substitutions at I38, they represent alternate pathways to baloxavir virologic resistance and should be monitored accordingly.
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Ince et al. (2020) conducted a review in Influenza. Baloxavir marboxil was evaluated on Reduced susceptibility to baloxavir and virus rebound. Treatment-emergent non-I38 polymerase acidic substitutions in influenza viruses conferred reduced susceptibility to baloxavir and were associated with virus rebound.
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