Initially, a 13-year-old patient with avian influenza seemed fortunate as she only suffered from mild pneumonia on one lung and was promptly treated with Tamiflu. However, after a few days of stability, the patient began to experience difficulty breathing and quickly succumbed – a sign that the H5N1 virus had developed drug resistance.
“The patient was admitted to a hospital in Dong Thap Province, Vietnam on January 22 after experiencing a day of coughing and fever,” reports Dr. Menno de Jong from the Ho Chi Minh City Tropical Hospital and colleagues. After a few days, the medication seemed effective. However, the girl suddenly experienced breathing difficulties and required additional oxygen, with her pneumonia condition rapidly deteriorating. Ultimately, the patient died six days after being hospitalized.
Testing results from Hong Kong indicated that the virus attacking the girl had mutated in a way that rendered it “immune” to Tamiflu. The patient exhibited a “H274Y substitution factor in the neuraminidase enzyme – a sign of high oseltamivir (the brand name for Tamiflu) resistance,” the authors asserted in a report published in the New England Journal of Medicine.
A similar phenomenon has occurred with several patients treated with similar antiviral medications. At least 4 out of 8 individuals treated with Tamiflu have died.
For a long time, it has been understood that viruses often develop drug resistance, which is why AIDS treatment requires a combination of medications. “The best way to prevent drug resistance is to inhibit cell division as thoroughly and as early as possible. The ‘strike hard and strike early’ model applied in HIV/AIDS treatment is also effective for influenza and many other viral infections,” de Jong commented.
Tamiflu is one of two antiviral medications that belong to the neuraminidase inhibitor group. They target a protein on the surface of cells known as sialic acid, which is likened to an “entrance” into the cell. Influenza viruses often use an enzyme called neuraminidase (the ‘N’ in H5N1) to “open” this entrance and invade healthy cells.
Tamiflu is capable of inhibiting the neuraminidase enzyme, thus preventing the virus from attaching to the sialic acid “entrance.” However, influenza viruses tend to evolve and continuously change, leading to alterations in the structure of the neuraminidase enzyme. As a result, Tamiflu is unable to completely neutralize neuraminidase. “The structural limitations of Tamiflu make it susceptible to being weakened after a few viral mutations, allowing the neuraminidase molecule to remain intact and the virus to continue functioning,” said Dr. Anne Moscona, a pediatric viral disease expert at Cornell University.
Meanwhile, the structure of a similar medication, Relenza by GlaxoSmithKline, “is somewhat different, so it better restricts drug resistance in viruses.” However, Relenza (also known as zanamivir) has its own limitations: it is administered as an inhaler, making it unsuitable for some patients, and it is only effective in the lungs, while H5N1 attacks other organs as well.
Mỹ Linh (according to Reuters)
