Cancer drugs to defeat HIV?

University of Minnesota researchers say they have found a potential new treatment for HIV, using a mixture of two anti-cancer drugs that are already on the market.

In lab experiments, the two drugs -- gemcitabine and decitabine -- were able to stop the AIDS virus by causing it to "mutate itself to death," the researchers said.

The discovery, announced by the university Monday, has not been tried in people yet. But the researchers say the study is encouraging because it's a new way of attacking the virus and because the drugs are not experimental -- they've already been approved by the Food and Drug Administration (FDA) for treating other diseases.

"Our goal was to actually look at the already approved FDA drugs to see if we could find any that had anti-HIV activity," said researcher Louis Mansky, who has been studying HIV for 20 years. If the researchers succeed, he said, they would be able to cut through some of the regulatory hurdles and "speed this entire drug discovery process up."

In this case, the scientists found that the two drugs, which are normally used for cancer or precancerous conditions, could render HIV harmless in a plastic dish of infected cells.

In effect, they exploited one of the traits that makes HIV so hard to cure -- its ability to mutate quickly -- by speeding up the rate of mutations until the virus could no longer function and died off.

Mansky said the two-drug combination killed off the HIV cells quickly, sometimes in a matter of hours, in the lab experiments.

He added, however, that they won't be ready to study the treatment in people for some time; the researchers are still testing it in animals and have yet to develop a pill form of the medications, which are normally given by injection.

Still, some AIDS experts were clearly encouraged.

"Any time Lou Mansky comes up with a novel approach, that's news and that's a good thing," said Dr. Frank Rhame, a specialist in HIV/AIDS at Abbott Northwestern's Clinic 42 in Minneapolis. "There's a long way to go before you can ever use it to help people, but that's a very good start."

Most AIDS drugs work by interfering with the virus' ability to reproduce and infect other cells. But sometimes the virus mutates and becomes resistant to those drugs, leaving patients with few good options.

"There still hasn't been anything that can fully wipe out the disease when someone has it," said David Folkens, communications director for the Minnesota AIDS Project. He said the group is cautious about new research, especially when it has yet to be proven in patients. "It's an interesting concept, and would be really exciting if it continues to bear out," he said. "We're certainly hoping that one of these discoveries comes along and really improves care."

The idea of trying to get HIV to self-destruct this way -- known as "lethal mutagenesis" -- isn't new, said Mansky. It first surfaced in scientific circles a number of years ago. The problem, he said, was that the early drugs that spurred the virus to mutate quickly were "too toxic" for patients. At that point, as he put it, "the applause died down" and scientists moved on. "This happens a lot in biomedical research, and certainly AIDS," he said. "Somebody comes up with a great idea, the concept sounds exciting, but when the scientists are working out the details, it's clearly more complicated."

Scientists have known for some time that HIV can became weaker the more it mutates, said Dr. Homayoon Khanlou, chief of medicine at the AIDS Healthcare Foundation in Los Angeles. He said one such experimental drug showed some promise a few years ago, but faltered in follow-up tests. "Basically, it was stopped, which was very disappointing," he said.

At the University of Minnesota, Mansky and his collaborators started looking at seven cancer drugs to see if they might also have an effect on HIV. They note that developing a drug from scratch can cost $600 million and take more than 12 years.

"We were trying to purposely short-circuit that long, tedious process," said Mansky, by "drug repositioning," or finding a fresh use for an existing drug.

The same idea has breathed new life into a number of medications, the researchers pointed out. Zyban, the smoking cessation drug, started out as an antidepressant; and Viagra evolved from a heart-disease medication.

The researchers found that at least two of the cancer drugs could reduce HIV's ability to infect new cells, but that the combination of the two was more effective than either one alone.

They've begun a study in mice, he said, and so far the results are similar.

One big question, he said, is the long-term effect on HIV patients, who might have to take the drugs for years. "It's not clear what the side effects would be," he said. That's one reason doctors would be cautious about trying the drugs without more research.

The study, recently published online, appears in the September issue of the Journal of Virology.

Maura Lerner • 612-673-7384