Purpose: Neuraminidase inhibitors (NAIs) are stockpiled internationally for an influenza pandemic, and can be used for extended-duration antiviral chemoprophylaxis of seasonal influenza among high-risk individuals with contraindications or inadequate immune response to influenza vaccination. Influenza A virus strains resistant to antiviral medications, including oseltamivir (the most commonly used and stockpiled NAI) are circulating worldwide. We sought to evaluate the safety and efficacy of NAIs for extended-duration influenza chemoprophylaxis.
Method: Using studies published in any language from 1966 to 2008 in multiple electronic databases and registries, we selected randomized, placebo-controlled, double-blinded human trials of extended duration (>4 weeks) NAI chemoprophylaxis reporting outcomes of laboratory-confirmed influenza or adverse events. Two reviewers independently assessed study quality and abstracted information from eligible studies. Data were pooled using random-effects models. Sensitivity analyses were performed by removing one study at a time.
Result: We identified 1,642 citations. Seven studies with a total of 7,021 unique participants met inclusion criteria. All studies were sponsored by pharmaceutical companies, and authors from every study but one reported conflicts of interest. The median age was 34.7 (range 28.8 to 81.2) years, and median female participants was 46.1% to 69.0% (median 62.5%). The majority of participants were Caucasian. The median intervention duration was 42 days (range 28 to 42 days). NAI chemoprophylaxis decreased the frequency of symptomatic influenza (relative risk [RR] 0.26, 95% confidence interval [CI] 0.18-0.37), but not asymptomatic influenza virus infection (RR 1.03, 95% CI 0.81-1.30). Recipients of NAIs did not experience an increase in adverse effects (RR 1.01, 95% CI 0.94-1.08) unless they received higher than standard prophylactic doses (P =0.00). There was no significant difference in the proportion of influenza illness (P=0.64) or adverse events (P=0.33) between zanamivir and oseltamivir, but the frequency of asymptomatic influenza virus infection was higher in zanamivir recipients (P=0.02).
Conclusion: Zanamivir and oseltamivir both appear to be highly efficacious for preventing symptomatic influenza among adults. Extended-duration chemoprophylaxis with NAIs does not decrease asymptomatic influenza virus infection. Additional research is needed to evaluate the safety and efficacy of NAIs in diverse racial groups, children, and immune compromised patients. 