Neuraminidase Inhibitor Resistance Uncommon with Latest Pandemic Influenza A Strain

Although little NAI resistance was seen in the most-recent pandemic influenza A strain (H1N1pdm2009), it was detected in a few patients — mainly young children — after oseltamivir treatment.

Ever since influenza A viruses developed widespread resistance to adamantanes, the neuraminidase inhibitors (NAIs) osteltamivir and zanamivir have been the primary therapies. During the 2007–2008 influenza season, naturally occurring oseltamivir resistance associated with the H275Y neuraminidase mutation emerged among seasonal influenza A (H1N1) viruses. However, the affected strain was replaced in 2009 by H1N1pdm2009, which is typically oseltamivir susceptible.
Now, researchers have published the results of an industry-funded, prospective, multinational, observational study, conducted from December 2008 to March 2011, to detect and monitor the frequency of viral resistance to NAIs. A total of 1799 individuals with virologically confirmed influenza were enrolled. Among these participants, 1281 (71%) had influenza A and 1041 (58%) received antiviral therapy.

All 44 seasonal influenza A (H1N1) virus samples with detectable viral RNA that were obtained on day 1 had the H275Y mutation and demonstrated reduced susceptibility to oseltamivir. On the other hand, no genotypic resistance was seen in the H1N1pdm2009 isolates from day 1, and 99% were susceptible to oseltamivir. The H275Y mutation was detected in 17 H1N1pdm2009 uncultured swab samples collected after day 1; 13 of these samples were from children aged 5 years. Among patients with H1N1pdm2009 infections who were treated with oseltamivir monotherapy 48 hours after illness onset, 1 of 17 (6%) with the H275Y mutation showed viral clearance before day 6, compared to 165 of 410 (40%) patients without the mutation (P=0.004).

CITATION(S):

Whitley RJ et al. Global assessment of resistance to neuraminidase inhibitors, 2008–2011: The influenza resistance information study (IRIS). Clin Infect Dis 2013 May 1; 56:1197.