Two new deaths, added to a similar case in October, showed the H5N1 virus was resistant to oseltamivir, sold under the name Tamiflu, according to an article released by the New England Journal of Medicine.
"Resistance can emerge during the currently recommended regimen of oseltamivir therapy," Menno de Jong and his team wrote in the article.
Treatment of the virus should include additional antiviral agents because Tamiflu may kill most, but not all, of the virus in a person's body, the study said.
The surviving virus is then resistant to the drug.
"Besides allowing the infection to proceed, such incomplete suppression provides opportunities for drug resistance to develop," the report said.
Up to 18 percent of children treated with the drug were found to carry
resistant variants of the virus, the authors said.
In an introduction to the article, Dr Anne Moscona wrote in the New England Journal of Medicine: "The recent emergence of oseltamivir resistant variants is therefore a matter of immediate concern."
The entire strategy of stockpiling the drug "is likely to lead to the use of insufficient doses or inadequate courses of therapy," she wrote.
"Shortages during a pandemic would inspire sharing of personal supplies, resulting in inadequate treatment”
"Such under-treatment is of particular concern in children, the main source for the dissemination of influenza within the community," she said.
One of the two patients who died was a 13-year-old Vietnamese girl who died eight days after becoming symptomatic with a fever and cough.