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Widely Used Hepatitis B Drug Spurs HIV Drug Resistance

ing hepatitis B first,” she adds. Hepatitis B infection attacks the liver and can lead to cirrhosis, liver cancer or even death from liver failure.

Entecavir, first marketed in March 2005, has been a leading treatment for chronic forms of hepatitis B, which can be fatal to almost a quarter of those infected if it is left untreated. The drug’s label information currently states that is has no clinical effects on HIV.

According to Thio, some co-infected patients decide first to treat their hepatitis B infection if HIV has not yet weakened their immune system and to avoid the debilitating side effects of anti-HIV medications.

In the Hopkins study, researchers found in both laboratory and clinical tests that within six months of entecavir therapy, a so-called M184V mutation of HIV develops. Thio says viruses with this mutation are known to be resistant to lamivudine, better known as 3TC, a medication that prevents HIV replication and “is a cornerstone of most drug-combination therapies used to fight the immune system disease.” Because lamivudine is in the same category of HIV therapies as another widely used drug, emtricitabine, its effectiveness is also compromised by entecavir, she says.

Thio began to investigate entecavir’s effects on HIV in fall 2006 after noticing reports of anti-HIV activity in two co-infected patients, one at the Johns Hopkins Moore Clinic, which specializes in HIV/AIDS care, and another at a San Diego medical center. The patients (and there is now a third case) were taking only entecavir yet showed a tenfold decrease in the amount of HIV in their blood.

Previous studies had shown entecavir not to have any significant effects on HIV, but they were based on older tests that could not quantify the effects of HIV on individual immune cells or detect mutations. Thio believed that the recent patient cases called for a more thorough investigation with more advanced techniques.

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