The new bird flu strain that has killed 36 people in China has proved resistant to Tamiflu for the first time, a development scientists said was "concerning".
The H7N9 virus was found to be resistant to Roche's widely used flu drug in three out of 14 patients who were studied in detail by doctors from Shanghai and Hong Kong.
Tamiflu, which is given as a pill, belongs to a group of medicines known as neuraminidase inhibitors that currently offer the only known treatment option for bird flu. GlaxoSmithKline's inhaled medicine Relenza has the same mode of action.
In one patient, the gene mutation responsible for resistance appears to have arisen after infection took hold, probably as a result of treatment with Tamiflu, leading to concerns that medication may be the trigger for resistance to develop.
"The apparent ease with which antiviral resistance emerges in A/H7N9 viruses is concerning; it needs to be closely monitored and considered in future pandemic response plans," the researchers wrote in an article published online by The Lancet medical journal on Tuesday.
Earlier genetic studies had raised worries about drug resistance but this is the first time that the problem has been documented in clinical cases.
For most of the 14 patients studied, Tamiflu successfully reduced the amount of virus found in throat swabs and helped speed clinical recovery. But it had no impact on the amount of virus found in swabs from three patients who became severely ill.
A spokeswoman for Swiss-based drugmaker Roche said rates of Tamiflu resistance remained low globally, but it took the issue of resistance "very seriously" and was collaborating with health authorities to monitor the situation.
The H7N9 virus is known to have infected 131 people in China since February, but no new cases have been detected since early May, according to the World Health Organization.
Experts from the United Nations agency said last week the bird flu outbreak in China had caused some $6.5 billion in losses to the economy.
Scientific studies of the virus have established it is being transmitted from birds - probably mostly chickens - to people. But experts have yet to identify the source of the circulating virus - the so-called "reservoir" - that is leading to chickens contracting it and sporadically passing it on to humans.