Virological and clinical outcomes in outpatients treated with baloxavir or oseltamivir: A Japanese multicenter study in the 2019-2020 influenza season

Although the virological and clinical efficacies of baloxavir for influenza and the post-treatment emergence of variant viruses have been reported in clinical trials, its efficacies have not been fully investigated in clinical settings. This prospective, observational investigator-initiated study was conducted during the 2019-2020 Japanese influenza season. In outpatients receiving baloxavir or oseltamivir, nasopharyngeal samples were obtained on day 1 before treatment and on the scheduled days 5 and 10 after treatment. RT-PCR and sequencing were performed to detect polymerase acidic protein (PA) E23X/I38X and neuraminidase (NA) H275Y variants in clinical and cultivated samples. Fever and illness-related symptoms were recorded using self-reporting diaries. Overall, 116 outpatients, 76 treated with baloxavir (34 under 12 years) and 40 with oseltamivir (32 under 12 years), were eligible. Of these, 91 were infected with A (H1N1)pdm09 (78.4%), of which 58 received baloxavir and 33 received oseltamivir. PA variants were detected in clinical (1.7%, 1/58; 3.8%, 1/26 for children under 12 years) and isolated (3.4%, 2/58; 3.8%, 1/26 for children under 12 years) samples obtained on day 5 after baloxavir treatment, but not on day 10. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after baloxavir treatment were 5.2% (3/58) and 0.0% (0/58), respectively. Of the three viruses isolated on day 5, two (66.7%, 2/3) were PA I38 T/F variants with reduced baloxavir susceptibility. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after oseltamivir treatment were 30.3% (10/33) and 6.1% (2/33), respectively. Only the two viruses isolated on day 10 were NA H275Y variants. The median duration of fever in baloxavir and oseltamivir recipients was 22.3 and 27.5 h, respectively. No patients with PA or NA variants showed prolonged durations of fever. Baloxavir was virologically effective for influenza in the clinical setting of the 2019-2020 Japanese season. Variant emergence after baloxavir treatment was limited to the early post-treatment stage.