ousia's update: half year results, page-9

ousia, tamiflu has only been used in H5N1 infection in maybe a few dozen patients, yet resistance has emerged quite rapidly, with a couple of patients dying despite being given large doses within a short time frame of infection. AFAIK the rapidity of resistance emergence with tamiflu is unparaleled in antibiotic or antiviral use. Tamiflu resistant H5N1 has retained its lethality and in ferret studies it has retained it's transmissability.

As Moscona says:
http://content.nejm.org/cgi/content/full/353/25/2633
"Why is resistance developing to oseltamivir? Several years ago,structural analysis3 predicted that aspects of the chemical structure of oseltamivir (not present in zanamivir) could facilitate the development of resistance mutations that would permit neuraminidase to function, allowing drug-resistant virus to survive and propagate. This prediction is now being validated by clinical data. "

It may be with the aggressiveness of infection that waiting for symptoms with ANY neuraminidase inhibitor will be too late. Consider the implications of a major pandemic. Everyone will stay home, stay away from work, thus leading to complete economic collapse. It is increasingly being recognised that prophylaxis for essential workers is the only way to avoid this catastrophe, potentially far worse than the pandemic itself. Use of medications in prophylaxis is well known to be an effective way to cause resistance. I believe it is only a matter of time before the scientific advice will be to use inhaled relenza as the mainstay of prophylaxis, as it is much more "resistance proof" than tamiflu. Also this then reduces the amount of tamiflu resistance developing so that it might still be useful in treatment of systemic infections.

It is true that tamiflu is better at systemic penetration but I think we will find that treatment of H5N1 is going to end up as a minor role of these antivirals. Also conceptually a combination treatment with relenza and tamiflu is likely to be more effective than either alone. There is a weight of scientific research gradually backing up relenza more and more.