Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis

Background: To support an update of WHO influenza guidelines, we performed a systematic review and network meta-analysis of the evidence on antiviral drugs for prophylaxis of influenza. Methods: We analyzed randomized controlled trials published as of September 2023 on the efficacy and safety of antivirals compared to another antiviral or placebo, standard care, or no prophylaxis for prevention of symptomatic influenza. Paired reviewers independently screened studies, extracted data and assessed the risk of bias. We used frequentist random effects to perform network meta-analyses and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation (GRADE) methodology. Findings: We included thirty-three trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19096 individuals. Zanamivir, oseltamivir, laninamivir and baloxavir probably achieve important reductions in symptomatic influenza in persons at high risk of severe disease (moderate certainty) when given promptly after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in persons at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir and baloxavir might achieve important reductions in symptomatic zoonotic influenza in persons exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). These antivirals do not result in an important incidence of adverse events related to drugs or serious adverse events, with varying certainty of evidence. Interpretation: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir or baloxavir probably decreases the risk of symptomatic seasonal influenza in persons at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols <https://www.crd.york.ac.uk/prospero/> ### Funding Statement WHO ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: EMBASE, MEDLINE, the Cochrane Central Registry of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health, Epistemonikos and ClincalTrials.gov databases I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data included were derived from publicly available documents cited in the references. Extracted data are available upon request to the corresponding author.