More evidence bird flu can evade drug – report

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) – Doctors in Vietnam reported on
Wednesday they had found more evidence that the H5N1 bird flu
virus can quickly mutate into a form that resists the effect of
Roche AG’s frontline drug Tamiflu.

Four of eight patients treated in Vietnam for bird flu
infections died despite the use of Tamiflu, Dr. Menno de Jong
of the Oxford University Clinical Research Unit at the Hospital
for Tropical Diseases in Ho Chi Minh City and colleagues wrote
in the New England Journal of Medicine.

Tests showed that in two of the patients, the virus had
become resistant to Tamiflu. And in one patient, the drug was
used very early on, as is recommended.

“It is becoming clear that to treat avian flu with
neuraminidase inhibitors (such as Tamiflu) we are going to need
higher doses and longer course of treatment for it to work,”
said Dr. Anne Moscona, an expert in pediatric viral diseases at
Weill Medical College of Cornell University, New York.

She and other experts said the findings showed that such
drugs must be preserved carefully and used properly.

The H5N1 influenza virus has killed 71 people in Indonesia,
Thailand, Vietnam, China and Cambodia since 2003.

The H5N1 strain is difficult for people to catch. However,
experts fear it could evolve into a form that could pass easily
from human to human, causing a pandemic that could kill
millions.

The researchers and outside experts said the report
concerned only a few people and stressed that more study is
needed. Of the 138 people known to have been infected with
H5N1, 31 have been treated with Tamiflu, Roche says.

“This currently is not a pandemic strain,” Dr. David Reddy,
Influenza Pandemic Taskforce Leader for Roche, told reporters
in a telephone briefing.

A MUTATING VIRUS

“As it becomes a human pandemic it must change. It must
shift. That may lead to a loss of virulence. However, we are
dealing with a worst-case scenario today and we have to learn
how to best manage it,” Reddy added.

The findings add to a report published in October about a
14-year-old Vietnamese girl who survived an H5N1 infection
after being treated with Tamiflu, but who had a drug-resistant
virus strain in her body.

Four drugs treat influenza, but H5N1 already resists two
older drugs, amantadine and rimantadine.

Countries have been stockpiling the newer drugs, known as
neuraminidase inhibitors — Roche and Gilead Science’s Tamiflu,
known generically as oseltamivir, and GlaxoSmithKline and
Biota’s Relenza, known generically as zanamivir.

De Jong and Moscona agreed that Relenza is a good
alternative to Tamiflu.

“Furthermore, Relenza is active against Tamiflu-resistant
virus,” De Jong said in an e-mail.

But Relenza currently must be inhaled and may not be useful
in patients with respiratory conditions such as asthma, and it
might not spread past the lungs to protect other organs.

There is not enough of either drug to treat more than a
fraction of patients should a bird flu pandemic erupt this
year. Roche is trying to license a generic process and step up
its own production to 600 million treatment courses by 2007.

There is an H5N1 vaccine but it is experimental and is
unlikely to work well against whatever pandemic strain may
eventually emerge.

De Jong said Tamiflu must be used early on in infection to
do any good against any type of influenza. As with AIDS, a
cocktail approach may be needed.

There are few options now. De Jong said one possibility to
add to a cocktail is an antiviral used against hepatitis called
ribavirin. BioCryst Pharmaceuticals, Inc. has a new
neuraminidase inhibitor in the works called peramivir, which
“may be an option in the future,” De Jong said.