Generic Drugs May Stop Common Infection in AIDS Patients

Generic medications that treat other disorders also may be able to stop a fatal viral infection that has become increasingly common among AIDS patients.

Researchers at Brown University found that some antipsychotic medications and possibly even antihistamine drugs-can block the virus from entering the central nervous system, where it can trigger a serious condition that causes dementia, vision loss, movement and speech impairment and even death.

Called the JC virus, using a patient's initials, it is very common—up to 80% of American adults carry it. But its devastating results, a condition called progressive multifocal leukoencephalopathy (PML), affects only approximately one in 200,000 healthy people.

PML is much more prevalent in patients who have AIDS-approximately 4% develop it. The overall incidence of PML in AIDS patients has increased 50-fold since 1979, largely because of the rise in the number of people who are infected with HIV. People who have had organ transplants, cancer treatment or who have a compromised immune system are also susceptible to PML.

The Study

In their study, researchers first discovered that chlorpromazine, a drug normally used to control psychotic symptoms, was able to stop JCV from entering cells.

However, since chlorpromazine produces troubling side effects, such as low blood pressure and tremors, they wanted to see if other medications might also block JCV from entering cells, without causing those side effects. They tested seven other drugs, and found three-serotonin, ketanserin and ritanserin effectively prevented infection by blocking the same entry point, a receptor called 5HT2A.

"These results open up the possibility that drugs that target the 5HT2A receptor might be useful in preventing the development of PML in AIDS patients...or they may prevent disease progression in patients already diagnosed with the disease," says study author Walter Atwood, an associate professor of medical science at Brown University in Rhode Island.

Reaction

Because so many people carry the JC virus, yet few develop PML, researchers wanted to determine how the virus was entering the cells in the central nervous systems of the people who do get PML.

"We wanted to know how the virus gets in, and they've found the door," says Dr. Charles Gonzalez, an infectious disease and immunology specialist at New York University Medical Center. "Not only did they find the door, but they figured out how to stop the virus from using the key to open the lock."

What's most exciting, he says, is that the drugs that block the receptor have already been approved for use in other disorders by the US Food and Drug Administration (FDA).

"For patients and doctors, this is a home run," says Gonzalez. Atwood cautions that his research was only done on cells in the lab; the drugs haven't yet been tested on patients who have PML.

However, he notes that the antihistamine cyproheptadine, which doctors sometimes prescribe as an appetite stimulant for people who have AIDS, also blocks 5HT2A. Since this drug is relatively benign, he says doctors may start using it "off-label" to treat or attempt to prevent PML. Atwood is currently working with neurology centers to set up small-scale clinical trials to see if cyproheptadine can, in fact, prevent PML.

"Basic research sometimes unexpectedly gives you quick and simple results," says Gonzalez. "The fact that this won't take much is great in terms of prevention."