The New Anti-influenza Drug Baloxavir Marboxil: Can Influenza Viruses with Reduced Susceptibility to Baloxavir Maintain Viral Fitness?

Abstract

In 2018, baloxavir marboxil, which targets the polymerase acidic (PA) protein of influenza A and B viruses, was licensed in Japan and the United States. This anti-influenza drug is highly effective against these virus infections. During the 2018–2019 influenza season in Japan, however, influenza A viruses carrying an I38T mutation in PA that confers reduced susceptibility to baloxavir acid (the active form of baloxavir marboxil) were detected at a relatively high frequency in pediatric patients after treatment with this drug. In addition, influenza A virus PA-I38T variants were detected in patients before drug treatment. In animal models, the replicative abilities, pathogenicity, and transmissibility of influenza A virus PA-I38T variants isolated from patients have been shown to be comparable to those of wild-type isolates. In this chapter, we summarize recent findings regarding the fitness of influenza A viruses with reduced susceptibility to baloxavir acid isolated from patients.