H1N1 flu virus can mutate in immunosuppressed patients-study

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Patients with suppressed immune systems can quickly develop H1N1 flu infections that resist all known drugs, doctors in the Netherlands reported on Wednesday.

The case of a 5-year-old leukemia patient who died from swine flu after the virus mutated in his body showed that people with weakened immune systems may be at greater risk of developing dangerous drug-resistant infections, and illustrated the risks of using current drugs to treat these patients, the researchers said.

The H1N1 virus infecting the boy mutated to resist all three drugs approved to treat it, Dr. Charles Boucher of Erasmus University Medical Center in Rotterdam wrote in a letter to the New England Journal of Medicine.

"The current formulation of the two drugs that we have has an intrinsic problem with resistance. Single mutations are sufficient for the virus to become resistant,” Boucher said in a telephone interview.

It is a tricky issue for doctors, who have been advised to consider quickly using drugs for cancer patients who are considered especially vulnerable to flu in the first place.

The boy was being prepared for a bone marrow stem-cell transplant, a rigorous treatment that involves destroying the patient’s immune system first.

When he became ill with swine flu, he was given antibiotics and Tamiflu, known generically as oseltamivir. The drug is made and distributed by Roche and Gilead Sciences.

When Tamiflu seemed to wipe out the virus, the bone marrow transplant was done. Then the influenza resurfaced, Boucher and colleagues wrote.

Doctors then tried intravenous treatment with zanamivir, the generic name for GlaxoSmithKline’s and Biota’s Relenza. The boy recovered and, again, the virus seemed to disappear and he went home.

Nineteen days later, he was back in the hospital with flu symptoms. This time, Relenza failed to work. The child died three months later, in March.

Laboratory tests showed that the virus infecting the boy was also resistant to BioCryst’s peramivir, an experimental drug in the same class as Relenza and Tamiflu that was approved for emergency intravenous use during the pandemic.

This month, researchers reported that a woman in Singapore developed resistance to Tamiflu within 48 hours.

In March, U.S. doctors reported two other cases where resistance to Tamiflu developed. Both patients had weakened immune systems, like the boy in the Netherlands. One also became resistant to peramivir. In those cases, Relenza worked.

“In the normal setting, the immune system helps to prevent the growth of drug-resistant virus,” said Boucher. “In the absence of an immune system, there may be a slight enhancement in the risk.”

Most flu strains are already resistant to two older drugs, amantadine and rimantadine.

SOURCE: New England Journal of Medicine, September 30, 2010.

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