Virus Load Kinetics and Resistance Development during Oseltamivir Treatment in Infants and Children Infected with Influenza A(H1N1)2009 and Influenza B Viruses

Abstract

Infants and children are the most effective transmitters of influenza, while bearing a high risk of hospitalization and adverse disease outcomes. This study aims to investigate virus load kinetics and resistance development during oseltamivir therapy in infants and children infected with influenza A(H1N1)2009 and influenza B viruses. Virus load and phenotypic/genotypic neuraminidase inhibitor resistance were determined at baseline, at day 5 and in additional follow-up samples, if available. Patient-specific viral clearance parameters were determined along with virologic and clinical predictors in patients responding to therapy. No evidence of baseline oseltamivir resistance was detected in 36 patients infected with influenza A(H1N1)2009 (n= 27) or influenza B (Victoria, Yamagata; n= 9) prior to oseltamivir therapy. On average, viral loads were lower for influenza type B Victoria (median = /ml) than in drug resistant (median = /ml), and sensitive A(H1N1)2009 (median = /ml), p = 0.04 and p = 0.09 respectively. Times required to achieve non-detectable virus load were significantly longer in drug resistant A(H1N1)2009 compared to drug sensitive A(H1N1)2009 (p = 0.003) and drug sensitive influenza B Victoria (p = 0.001; median time required 8 days). No evidence of viral rebound was observed once viral clearance was achieved. Our data indicate that influenza subtyping in combination with baseline viral load measurements may help to determine minimum time of antiviral therapy in the individual child patient. Lower than expected virologic response rates in patients without malabsorption or compliance issues, may hint towards rare instances of resistance development.