Why is H5N1 influenza A that is circulating currently resistant to amantadine and rimantadine? 

Some strains of H5N1 are highly pathogenic to domestic birds and these have infected poultry in a number of countries, particularly is East Asia. The H5N1 influenza A that has been found in the Americas is more sensitive to amantadine and rimantadine than is the virus in Asia. These drugs interfere with the uncoating of the virus and resistant mutants map to a protein called M2. This is a transmembrane ion channel in the virus coat and is essential for infection. Amantadine and rimantadine inhibit M2 function and so they are sometimes referred to as M2 protein inhibitors. If mutations are currently arising in the M2 proteins of viruses in certain parts of the world that make them resistant to these drugs, there must be some selective pressure that leads to the selection of resistant mutants, i.e. they have a survival advantage. Normally, wild type drug-sensitive viruses kill their domestic host birds very rapidly and there is no time for M2 mutations to accumulate so what is this selective pressure?  It probably arises from the use of amantadine to treat birds on poultry farms in China. Thus, the birds do not die and there is time for resistant mutants to emerge. An American newspaper, The Washington Post, reported in 2005 that Chinese farms have been using amantadine for some time as a prophylactic against influenza in their chickens, which is obviously a very bad practice. According to the report, people in the Chinese pharmaceutical industry confirmed amantadine use. 

The neuraminidase inhibitors (oseltamivir (Tamiflu) and zanamivir (Relenza)) are likely to be effective against H5N1 but these drugs do not cure the patient. They must be given within 48 hours of the patient developing symptoms and can only lessen the severity of the disease.