Oseltamivir for Treatment of Influenza Among Outpatient Veterans: Target Trial Emulation

The effectiveness of oseltamivir for the treatment of nonsevere influenza in preventing progression to severe illness is uncertain.

In a target trial emulation of veterans who presented to emergency departments in the Veterans Health Administration (VHA) and tested positive for influenza between 1 October 2022-31 January 2023, or 1 December 2023-31 March 2024, we compared treatment with oseltamivir versus no antiviral treatment within 6 hours of a positive influenza test. Following inverse probability of treatment weighting, we calculated cumulative incidence, risk differences (RDs), and risk ratios (RR) for hospitalization and intensive care unit (ICU) admission at 10 days and death at 30 days.

Among 28 920 veterans, 25 025 (87%) were male with median age 61 (45-72) years. Oseltamivir-treated patients had a lower risk of hospitalization (3.81% vs 6.96%; RD, -3.15% [95% confidence interval {CI}, -3.70% to -2.60%]; RR, 0.55 [CI, .49-.61]) and ICU admission (0.65% vs 1.38%; RD, -0.73% [CI, -.98% to -.48%]; RR, 0.47 [CI, .35-.62]) than untreated persons. The largest absolute risk reductions in hospitalization occurred in patients ≥65 years (RD, -5.21% [CI, -6.39% to -4.04%]) and among those prescribed treatment within 3 hours of testing positive (RD, -5.77% [CI, -6.54% to -5.00%]). Overall incidence of death was similar between groups (RD, 0.10% [CI -.07%-.27%]).

Oseltamivir reduced the risk of hospitalization and ICU admission but not death. Substantial reductions in hospitalization risk were observed in older adults and patients prescribed treatment within 3 hours of diagnosis.