Four patients at Duke University Medical Center contracted a mutated strain of the H1N1 virus that is resistant to the anti-viral drug Tamiflu, which helps ease the duration and severity of illness.

It's not clear how or where the patients, three of whom died, acquired the resistant strain. All three patients had severe underlying illnesses before they contracted influenza.

Two earlier cases of Tamiflu-resistant infections were reported last summer in North Carolina, but Dr. Cameron Wolfe, an infectious disease specialist at Duke, said there is no evidence the cases are linked.

Resistance to Tamiflu, which has also occurred in seasonal flu, removes one of the weapons against the illness, although only the vaccine can protect patients from getting the infection. Another anti-viral drug, Relenza, has shown no weakness against the H1N1 virus.

Wolfe said the Centers for Disease Control and Prevention confirmed the mutant strain in the four Duke patients after doctors became concerned the patients were not responding well to treatment.

"It was pretty astute in hindsight," he said.

Wolfe said Tamiflu resistance may actually be more widespread than doctors realize, because most people who are infected with the H1N1 virus do not get sick enough to get tested at their doctors' office, or need the anti-viral drug.

State health officials are planning a press conference this afternoon to provide more information.