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Widely Used Hepatitis B Drug Spurs HIV Drug Resistance

e and her team combined various concentrations of entecavir with 100,000 human immune cells from a healthy blood donor, then infected them with an HIV test virus and measured the number of cells infected over time.

The lab test, developed at Hopkins by study co-author Robert Siliciano, M.D., Ph.D., a professor at Hopkins and a Howard Hughes Medical Institute investigator, specifically tests what drugs affect HIV and can be tailored to probe effects on any particular mutant of HIV.

Lab results showed that entecavir, in concentrations less than a tenth of what is used in humans, cut the number of newly infected cells in half. However, at increasing concentrations, the drug had no greater impact on suppressing HIV replication. HIV is a virus renowned for its ability to change form and thus evade or develop resistance to therapies designed to stop its action.

Similar testing with entecavir, immune cells and the M184V form of HIV showed that the drug did not stop the virus from infecting the cells. This provided evidence, scientists say, that the drug specifically fostered development of this mutation in HIV, later confirmed by clinical testing.

When researchers tested the blood of one of the co-infected patients for the M184V mutation, they found none in samples taken at the start of entecavir thereapy. But they did find it in 61 percent of viral samples tested after four months of therapy, and 96 percent at six months.

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