Antiviral Resistance in Influenza: Clinical and Public Health Implications

Timely antiviral treatment and prevention can diminish the morbidity and mortality caused by influenza seasonal, zoonotic, and pandemic infections. However, the emergence of antiviral resistance threatens the utility of available agents and sometimes contributes to poor clinical outcomes. Adamantanes, once effective, are now obsolete for seasonal influenza use due to widespread resistance. Neuraminidase inhibitors remain the mainstay of therapy, but oseltamivir-resistant A(H1N1) virus spread globally in 2007-2009, and treatment-emergent oseltamivir resistance arises more commonly in some influenza A subtypes and hosts, as does baloxavir resistance. Resistant influenza variants sometimes occur in birds and pigs, highlighting the importance of surveillance in animal reservoirs. Genotypic and phenotypic methods are complementary in detecting and characterizing viral resistance. Combination antiviral therapy reduces the risk of treatment-emergent resistance in some studies, but further clinical trials are needed. Future priorities include developing antivirals and combinations with higher barriers to resistance, improving real-time detection of resistant variants, and strengthening surveillance in both humans and animals to inform clinical management and public health responses.