# 2250
Oseltamivir (Tamiflu) is one of our front line antivirals against the influenza virus, and up until very early this year very few instances of resistance to this drug had been encountered.
On January 25th, 2008 Norwegian authorities notified the WHO (World Health Organization) of a sudden high rate of resistance to Tamiflu among 12 of 16 samples (75%) collected in late 2007.
This resistance is caused by a mutation, known as H274Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 274.
Over the past 6 months, more reports of Oseltamivir resistance have been received by the WHO, and in some regions, the incidence has been as high as 100%.
This (reparagraphed for readability) from the latest WHO surveillance report :
(Hat Tip Ironorehopper for posting this on Flutrackers)
WHO has received several reports from National Influenza Centres in the southern hemisphere regarding influenza A(H1N1) virus resistance to oseltamivir.
In South Africa, a total of 139 A(H1N1) viruses have been isolated during the 2008 influenza season to date. Of those, 107 isolates have been tested for oseltamivir resistance by the National Institute of Communicable Diseases (NICD) and 100% were found to be resistant to oseltamivir by genotypic analysis.
Only one of these 107 patients was receiving oseltamivir at the time of sampling, and no unusual clinical features or underlying conditions were found.
From Australia, 10 of 10 A(H1N1) viruses tested, and from Chile, 4 of 32 A(H1N1) viruses tested showed the specific neuraminidase mutation (H274Y) associated with oseltamivir resistance.
The WHO maintains a Q&A page on this growing problem here, although it doesn't appear to have been updated since Feb 15th of this year.
A portion of this FAQ, reproduced below, shows that they have few clues as to what is driving this mutation.
Q6. Is there an explanation for the high frequency of oseltamivir resistance?
The frequency of oseltamivir resistance in H1N1 viruses in the current influenza season is unexpected and the reason why a high percentage of these viruses are resistant is currently unknown.
Available information does not indicate selective drug pressure is driving the development of resistance since few of the patients are known to have taken oseltamivir. Influenza viruses are continuously changing and it is possible that a resistant strain has emerged spontaneously or has continued to spread in the community after being selected initially in someone treated with oseltamivir.
Further detailed laboratory characterization of circulating H1N1 viruses and epidemiological information on patients will be needed to help answer this question.
With only GSK's Relenza, and potentially older antivirals such as Amantadine (which we essentially stopped using 3 years ago due to growing resistance problems with the H3N2 virus), as alternatives - the expanding incidence of Tamiflu resistance among seasonal H1N1 influenza viruses is worrisome.
Thus far, we've only seen a handful of resistant cases among H5N1 (bird flu) cases, and Tamiflu continues to remain reasonably effective.
