While oral oseltamivir decreased viral shedding in adults with influenza and without risk factors for complications of influenza compared with placebo, it did not significantly decrease the time to resolution of clinical symptoms, according to study results published in Clinical infectious Diseases.
In this double-blind, international, multicenter study (ClinicalTrials.gov identifier: NCT01314911), men and nonpregnant women who had influenza A or B without any underlying medical conditions that might increase the risk for complications from influenza were randomly assigned in a 1:1 ratio to receive either oseltamivir 75 mg or placebo orally twice a day for 5 days. The primary endpoint was the percentage of participants who had a day 2 nasopharyngeal swab sample that demonstrated viral shedding on polymerase chain reaction.
Of the 556 participants included in the study, 66% were from 4 sites in Thailand, 32% were from 27 sites in the United States, and 2% were from 3 sites in Argentina. The median age was 36 years, with a range of 18 to 64 years. Of the 501 participants with confirmed influenza infection by central laboratory testing, 46 were excluded from the primary endpoint analysis because they were part of the pilot study and 6 additional participants did not have a day 3 virologic endpoint sample available for testing (3 in each arm). Therefore, 449 participants remained; 220 were assigned to the oseltamivir group and 229 to the placebo group.
Results showed that 45.0% of participants in the oseltamivir group had virus detected at day 3 compared with 57.2% of participants in the placebo group (-12.2% difference; 95% CI, -21.4% to -3.0%; P =.0097). Among participants with influenza type A infection, a smaller number of participants in the oseltamivir group had detectable viral load vs placebo group: 38.6% vs 59.3%; difference, -20.7%. However, there was little difference in the proportion with detectable viral shedding between the 2 arms in participants with influenza B infection: 56.5% in the oseltamivir group and 52.9% in the placebo group (difference, 3.6%).
The median time to alleviation of symptoms was 79.0 hours for the oseltamivir group and 84.0 hours for the placebo group (P =.34). Subgroup analyses by influenza type, sex, and country/race did not reveal any significant interaction with treatment.
Researchers stressed that the findings from this study should not raise a question about the utility of oseltamivir in most populations, because this study enrolled a very specific low-risk population. While the use of neuraminidase inhibitors including oseltamivir is justified in treating those with influenza who require hospitalization, those who are very sick, and those who are at high risk for severe influenza complications, “the minimal virologic benefit and the nonsignificant clinical differences demonstrated in this study…should raise caution in automatically extending those recommendations to include treatment of a low-risk population,” concluded the researchers.
Beigel JH, Manosuthi W, Beeler J, et al. Effect of oral oseltamivir on virological outcomes in low-risk adults with influenza: a randomized clinical trial [published online July 27, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz634