Challenges in Entecavir Drug Treatment

According to a new report in the New England Journal of Medicine,treating hepatitis B patients with the drug entecavir can cause those who are also infected with HIV to become resistant to two of the most important drugs in the anti-HIV arsenal.

the researchers reported that a patient infected with both hepatitis B and HIV who was treated with entecavir developed a mutant strain of HIV that is resistant to the antiviral drugs lamivudine and emtricitabine. Entecavir is manufactured by Bristol-Myers Squibb and is marketed under the trade name Baraclude.

The research team was led by Chloe Thio and Howard Hughes Medical Institute investigator Robert Siliciano, both at The Johns Hopkins University School of Medicine. The analyses reported in the paper were performed by lead authors Moira McMahon, Benjamin Jilek, and Timothy Brennan in the Siliciano laboratory.

The group’s initial report of the findings in February, 2007, at the Conference on Retroviruses and Opportunistic Infections led the drug’s manufacturer, Bristol-Myers Squibb, to change its product labeling to warn of the potential for HIV drug resistance, notify prescribing physicians, and inform the Food and Drug Administration.

The United States Department of Health and Human Services now recommends against using entecavir as the first option in treating hepatitis B in co-infected patients who are not already using drugs to suppress HIV. More than 4 million people worldwide are believed to be infected with both viruses.

The scientists emphasized that finding drug resistance in this setting underscores the need to test all antiviral drugs for anti-HIV activity before they are approved for use.

Entecavir is a chemically altered version of a chemical called a nucleoside. The drug blocks viral replication by plugging itself into a polymerase enzyme in the hepatitis B virus that helps produce new viral DNA.

However, the hepatitis B polymerase closely resembles the reverse transcriptase enzyme that HIV uses to copy its genome inside an infected cell. Thus, there was a possibility that treating co-infected patients for hepatitis B with entecavir might also have an effect on HIV. But earlier tests by Bristol-Myers Squibb using techniques available at the time did not detect such an effect on HIV, said Siliciano.

However, Thio, study co-author Robert Hegarty, and Braden Hale of the Naval Medical Center in San Diego recently identified three co-infected patients in whom entecavir treatment did inhibit HIV replication.

Source-Eurekalert
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