Re: Flu Found Resistant to Main Antiviral Drug
Blaming influenza for being resistant to Tamiflu is like blaming the water for running out a hole in a bucket.
One of the many holes in Tamiflu is H274Y, Roche discovered it while developing Tamiflu,
"Volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) virus and treated with the neuraminidase (NA) inhibitor oseltamivir were monitored for the emergence of drug-resistant variants. Two (4%) of 54 resistant viruses were detected by NA inhibition assay among last-day isolates recovered from 54 drug recipients. They bore a substitution His274Tyr in the NA."
Selection of Influenza Virus Mutants in Experimentally Infected Volunteers Treated with Oseltamivir
The Journal of Infectious Diseases <b>2001</b>;183:523?531
http://www.journals.uchicago.edu/doi...086/318537#tb4
but explained it away as irrelevant.
Roche's research published in <b>2002</b>, "The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo". (Antiviral Res. 2002 Aug;55(2):307-17 ) which assured us "Virus carrying a H274Y mutation is unlikely to be of clinical consequence in man".
http://www.ncbi.nlm.nih.gov/pubmed/12103431
Tamiflu was designed to make money, not to be resistance proof, it suceeded.
In contrast Relenza was designed to be resistance proof, it suceeded, but it was less popular than Tamiflu because it uses an inhaler.
"There is no evidence of zanamivir resistance in viruses isolated from normal healthy patients after treatment with the drug. The only case of in vivo zanamivir resistance is that of an 18-month-old immunocompromised child, who acquired an influenza B virus infection and failed to respond to ribavirin treatment. The child was subsequently treated with zanamivir and after 12 days of treatment a virus containing an R152K NA mutation was isolated. This virus also contained a mutation in the HA protein, T198I, which had appeared prior to the NA mutation. In contrast, resistance to oseltamivir occurs in 1%-4% of adults and 4%-8% of the paediatric population."
http://jac.oxfordjournals.org/cgi/co...39886104f542f3
The problem is that when the importance of superior design and resistance is finally acknowledged it will be too late to do anything about it. Relenza manufacture is woefully limited and development of iv zanamivir, which could have been used systemically for all ages, and in hospitals was abandoned through lack of interest.
Blaming influenza for being resistant to Tamiflu is like blaming the water for running out a hole in a bucket.
One of the many holes in Tamiflu is H274Y, Roche discovered it while developing Tamiflu,
"Volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) virus and treated with the neuraminidase (NA) inhibitor oseltamivir were monitored for the emergence of drug-resistant variants. Two (4%) of 54 resistant viruses were detected by NA inhibition assay among last-day isolates recovered from 54 drug recipients. They bore a substitution His274Tyr in the NA."
Selection of Influenza Virus Mutants in Experimentally Infected Volunteers Treated with Oseltamivir
The Journal of Infectious Diseases <b>2001</b>;183:523?531
http://www.journals.uchicago.edu/doi...086/318537#tb4
but explained it away as irrelevant.
Roche's research published in <b>2002</b>, "The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo". (Antiviral Res. 2002 Aug;55(2):307-17 ) which assured us "Virus carrying a H274Y mutation is unlikely to be of clinical consequence in man".
http://www.ncbi.nlm.nih.gov/pubmed/12103431
Tamiflu was designed to make money, not to be resistance proof, it suceeded.
In contrast Relenza was designed to be resistance proof, it suceeded, but it was less popular than Tamiflu because it uses an inhaler.
"There is no evidence of zanamivir resistance in viruses isolated from normal healthy patients after treatment with the drug. The only case of in vivo zanamivir resistance is that of an 18-month-old immunocompromised child, who acquired an influenza B virus infection and failed to respond to ribavirin treatment. The child was subsequently treated with zanamivir and after 12 days of treatment a virus containing an R152K NA mutation was isolated. This virus also contained a mutation in the HA protein, T198I, which had appeared prior to the NA mutation. In contrast, resistance to oseltamivir occurs in 1%-4% of adults and 4%-8% of the paediatric population."
http://jac.oxfordjournals.org/cgi/co...39886104f542f3
The problem is that when the importance of superior design and resistance is finally acknowledged it will be too late to do anything about it. Relenza manufacture is woefully limited and development of iv zanamivir, which could have been used systemically for all ages, and in hospitals was abandoned through lack of interest.
ossible causes of antiviral treatment failure