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Tamiflu Resistant H1N1 Clusters Raise Concerns
Recombinomics Commentary 14:30
May 19, 2012

So far this season, 16 oseltamivir-resistant 2009 H1N1 viruses have been detected nationally. Three patients were using oseltamivir for 1 day or more at the time of specimen collection. Thirteen had no exposure to oseltamivir; out of those 13 patients, 2 had family members using oseltamivir. (Resistance of influenza A viruses to antiviral drugs can occur spontaneously or emerge during the course of antiviral treatment or antiviral exposure).

Eleven of the 16 oseltamivir-resistant viruses were collected from January to April 2012 and are from Texas

The above comments from the week 19 FluView support the sequence data which signals clonal expansion of oseltamivir (Tamiflu) resistant (H27Y) H1N1pdm09.  Transmitting H274Y would be detected in cases with no exposure to oseltamivir, as indicated for 13 of the 16 isolates described above.  Moreover, transmission would create clusters such as the H274Y in family members as described above. 

The detection of H274Y 1 day after the start of treatment would also signal transmission at sub-detection / reporting levels.  Isolates with H274Y levels below 50% are reported as wild-type, so it is unclear if the rapid appearance is due to levels below detection or simply below 50%, which quickly rise to more than 50% under oseltamivir selection pressure.

The sequences from the resistant cases are closely related to recent 2012 sequences than are more widespread than the cases with H274Y.  Similarly another recent case (53F) has D225G (A/North Carolina/09/2012).  Although no H274Y was listed in the NA sequence, the CDC released sequence data for all 8 gene segments, and this case was also closely related to the H274Y cases in Texas.

Thus, the clustering of H274Y in closely related sequences which represent a sub-clade that dominates recent 2012 sequences raises concerns that H274Y and D225G may be silently spreading in the United States.

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