Viral shedding and susceptibility to oseltamivir in hospitalized immunocompromised patients with influenza in the Influenza Resistance Information Study (IRIS)

Background: Immunocompromised patients are at greater risk of complicated influenza and may be more likely to develop antiviral resistance. This observational sub-study of the Influenza Resistance Information Study (NCT00884117) aimed to study antiviral resistance in immunocompromised patients with influenza and characterize its effect on clinical and virological outcomes. Methods: Eligible immunocompromised patients were aged >= 1 year with a local rapid diagnostic or PCR test positive for influenza <= 96 h after diagnosis and with influenza symptoms. Nasal and throat swabs were taken for RT-PCR analysis on day 1 and then every 3 days until patients were virus-free. Resistance was assessed by mutation-specific RT-PCR, phenotypic susceptibility analysis and Sanger sequencing. Results: Of 42 patients enrolled, 29 (69%) were influenza-positive (RT-PCR) on day 1: 18 adults and 11 children aged 1-12 years. Six patients were severely immunocompromised. On days 3, 6 and 9, most patients tested (18/24, 9/15 and 6/9, respectively) had not cleared the virus. Two of five patients assessed after day 9 continued shedding virus until day 15. H1N1pdm09 viruses harbouring H275Y mutations were detected in post-baseline samples from four patients (aged 52-61 years), one of whom had prolonged viral shedding. No genotypic antiviral resistance was detected in the other 20 treated patients (prevalence of resistance, 17%). Correlation between level of immune compromise and resistance or outcomes could not be assessed. Ten patients (seven influenza-positive) were admitted to intensive care and three died. Conclusions: In these patients with mild/moderate immunocompromise, emergence of oseltamivir-resistant viruses was not common. Severity of influenza symptoms ranged from mild to moderate, but correlation with level of compromise could not be determined.