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| Credit NIAID |
While spontaneous `resistance' to oseltamivir (aka `Tamiflu') develops in roughly 1%-2% of treated patients, for the past 18 months we've been watching a slow increase in the number of antiviral resistant H1N1 viruses around the world.
These resistant viruses, however, are generally thought to be less biologically `fit' than their susceptible counterparts, and are only rarely transmitted to others.
Of course, that can always change - as we saw in 2008 - when in the course of a less than a year the (pre-pandemic) H1N1 virus defied all expectations and went from being 99% susceptible to oseltamivir to 99% resistant (see CIDRAP article With H1N1 resistance, CDC changes advice on flu drugs).
While an influenza antiviral crisis seemed unavoidable, in an unlikely Deus Ex Machina moment a new swine-origin H1N1 virus - one that happened to retain its sensitivity to Tamiflu - swooped in as a pandemic strain in the spring of 2009, supplanting the older resistant H1N1 virus.
Since 2009 we've been closely watching for signs of increased antiviral resistance in seasonal flu - and while a few isolated pockets have occurred - none have established a foothold.
- Four years ago, in EID Journal: Cluster of Oseltamivir-Resistant & Antigenically Drifted Influenza A(H1N1)pdm09 Viruses, Texas, USA, January 2020, we looked at a cluster of resistant seasonal flu viruses which emerged just before COVID shut down influenza around the globe.
- In 2016, in Eurosurveilance: A(H1N1)pdm09 Virus With Cross-Resistance To Oseltamivir & Peramivir - Japan, March 2016 we looked at an elevated number of NAI resistant viruses with `permissive mutations' circulating in Japan.
- In 2014's Eurosurveillance: Community Cluster Of Antiviral Resistant pH1N1 in Japan, we looked at a cluster of six genetically similar resistant viruses in Sapporo, Japan - but without epidemiological links.
But in March of 2024 we saw a worrisome report in The Lancet - Global Emergence of Neuraminidase Inhibitor-Resistant Influenza A(H1N1)pdm09 Viruses with I223V and S247N Mutations - which reported a much higher incidence of oseltamivir resistance among samples tested in Hong Kong in 2023.
Unlike the near total collapse of oseltamivir effectivess in 2008 - which was due to a an H275Y mutation in the NA - this was due to I223V and S247N, and was not as profound of a loss in effectiveness.
Four months later (see Viruses: Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases) researchers at the Robert Koch-Institute that reported seeing an uptick in permissive secondary mutations (NA-V241I and NA-N369K) in the NA or circulating H1N1 viruses that they believe may enable resistant strains to transmit more efficiently.
Earlier this summer we looked at a report from Spain which reported an increase in the number of the NA-S247N mutation in seasonal flu viruses collected in Spain over the 2023-2024 flu season (see Virus Research: A 15-year Study of Neuraminidase Mutations and the Increasing of S247N Mutation in Spain).
Today, Taiwan's CDC is responding to reports of a substantial increase in H1N1 resistant viruses in 2025. While it doesn't report causitive genetic changes (e.g. H275Y or I223V S247N) - or the degree of resistance - it does report an incidence of 6.5% in 2025.
Whether this is a localized fluke - or an early indication of a trend - is to early to say. Obviously we'll be watching for any similar reports as this year's flu season progresses.
I've posted a translation below.
The CDC responded to media reports about the emergence of resistance to influenza antiviral drugs, stating that the resistance rate is still low and limited to influenza A (H1N1). The current epidemic has shifted to influenza A (H3N2), and the impact is assessed to be limited.
Release Date：2025-09-29 Regarding today's (29th) media report that a frontline physician group reported that "the incidence of resistance to oral and injectable influenza antiviral drugs has increased, resulting in a decrease in efficacy", the Centers for Disease Control (CDC) explained as follows:
1. According to CDC monitoring data, approximately 6.5% of the A H1N1 virus strains tested this year (2025) have resistance-related mutations to the oral antiviral drug Tamiflu or oseltamivir and the injectable antiviral drug Peramivir, which is slightly higher than last year (the statistics at the end of last year were 3.2%). No resistance to the above-mentioned drugs was detected in A H3N2 and B influenza virus strains this year. In addition, no resistance-related mutations were detected for the oral self-paid antiviral drug Baloxavir this year, regardless of A H1N1, A H3N2 or B influenza.
Second, the CDC assesses that the aforementioned drug resistance rate remains low and is limited to influenza A (H1N1). Furthermore, since entering the influenza season in Taiwan in September, the prevalence of community-circulating influenza viruses has recently shifted to influenza A (H3N2), which has not detected drug resistance (51.3% in the past four weeks, higher than influenza A (H1N1) at 43.4%), with the prevalence of influenza A (H1N1) continuing to decline.
Third, starting October 1st of this year, publicly funded influenza antiviral medication will be expanded to cover high-risk groups, in addition to the original year-round use. Anyone experiencing flu-like symptoms, after evaluation by a physician, can receive medication without rapid testing. Publicly funded influenza vaccination will also be available on the same day. The prevalent viruses have also shifted to influenza A (H3N2). The aforementioned drug resistance in some influenza A (H1N1) strains has limited impact on clinical treatment and epidemic control. The CDC will continue to closely monitor the prevalence of influenza strains and drug resistance, and will adjust relevant prevention and control strategies on a rolling basis.
The CDC once again reminds the public not to underestimate the severity of influenza. It is essential to maintain good respiratory hygiene and cough etiquette, including frequent hand washing. If you experience flu-like symptoms such as fever and cough, wear a mask and seek medical attention promptly. If you are sick, rest at home. For information on the use of publicly funded pharmacies, a list of contracted medical institutions, and influenza prevention and control information, please visit the CDC's global information website (https://www.cdc.gov.tw) or call the toll-free epidemic prevention hotline 1922 (or 0800-001922).
