Cancer Drugs Force HIV to Mutate to Death


24 August 2010


HIV, the AIDS virus, has the ability to change quickly, frustrating efforts to find a vaccine.  However, the apparent advantage of mutation may also be a weakness.

Since HIV was discovered in 1981, scientists have been trying to kill it or render it harmless. They haven't been able to kill it so far, and the best drugs available keep the virus at low levels by hindering its replication. But it's still in the body and can hide in the brain and bone marrow.

Change for change sake

HIV mutates regularly, blocking efforts by the human immune system to stop it. Professor Louis Mansky is director of the Institute for Molecular Virology at the University of Minnesota.

University of Minnesota
Professor Louis Mansky


"HIV has this propensity for rapidly mutating and evolving. And is really in a lot of ways the main reason why there hasn't been an effective vaccine developed and why there's continual problems with drug resistance," he says.

But new findings suggest that rather than trying to prevent those mutations, they should be sped up. Researchers used two cancer drugs approved by the government - decitabine and gemcitabine – on HIV in tissue samples in the lab.

"Well, we were specifically looking for drugs that had already been approved by the FDA (Food and Drug Administration) for other purposes. And we were screening to look for ones that may have been overlooked in the past for anti-HIV activity," says Mansky.

The need for speed

The cancer drugs had a profound effect on HIV in the tissue samples.

"The drugs do not directly inhibit the virus from replicating. What they do is to basically cause the virus to elevate its mutation rate. And through that process, allow it to continue to replicate and basically kill off its infectivity by this process of lethal mutagenesis, which is elevating the mutation rate to the point to where the virus is no longer infectious," he says.

Simply put, HIV mutates itself to death. And it happens fairly quickly.

Mansky says the next step is animal studies. But before that can be done, the cancer drugs, which are administered intravenously, must be converted to pill form. That's how most antiretroviral drugs are now taken. And they must also be shown to not only be effective against HIV, but safe.