In contrast, zanamivir resistance has been rarely reported to date. Our results demonstrate that that a substantial number of patients may become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance may be significantly associated with pneumonia. Oseltamivir-resistance was not statistically significantly associated with other clinical complications and symptoms.

A meta-analysis of 4 studies reporting association between oseltamivir-resistance and pneumonia yielded a statistically significant risk ratio of 4.2 (95% CI 1.3 to 13.1, p = 0.02). Considerable heterogeneity between studies precluded definite inferences about subgroup results for immunocompromised patients, in-patients, and children. Subgroup analyses detected higher incidence rates among influenza A patients, especially for H1N1 subtype influenza. Only one study measured incidence of antiviral resistance among subjects given peramivir and was reported to be 0%. The incidence rate for all zanamivir resistance studies was 0%. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%). We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms. Subgroup analyses were done across a number of population groups. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review. To date, no studies have demonstrated widespread resistance to zanamivir. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. Until recently, the prevalence of antiviral resistance has been relatively low.

Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu В®) and zanamivir (Relenza В®) and two drugs which have received recent approval in Japan: peramivir and laninamivir. One class of antivirals, neuraminidase inhibitors (NAIs), is effective against all human influenza viruses.

Antivirals play a critical role in the prevention and the management of influenza.

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