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Cancer Drug Unmasks HIV in Immune Cells


A member of the audience looks at slides during a speech given by leading AIDS vaccine official in Washington, July 25, 2012.
A member of the audience looks at slides during a speech given by leading AIDS vaccine official in Washington, July 25, 2012.
WASHINGTON — People infected with HIV, the virus that causes AIDS, must take anti-retroviral drugs for the rest of their lives in order to control their disease.

Otherwise, reservoirs of dormant virus hiding within the immune system can become active, and the infection can reemerge. Now, researchers have discovered that a cancer drug can dislodge these latent copies of the AIDS virus. They view the development as a critical step toward curing HIV-infected people.

HIV has evolved a way to survive inside the human body by integrating itself into the genetic architecture of immune-system T-cells, the specialized white blood cells targeted by the AIDS virus. Anti-retroviral drugs can suppress HIV to near undetectable levels, giving the immune system a chance to repair itself. But the AIDS virus is always lurking in miniscule numbers - roughly one in every million T cells - and threatening to come back to life should an individual ever stop taking the anti-retroviral cocktail.

Now, researchers have succeeded in flushing this latent virus out of its hiding place, with a drug used to treat lymphoma, a rare and potentially deadly cancer of the lymphatic system.

David Margolis, a professor of microbiology and immunology at the University of North Carolina Chapel Hill has been studying how HIV hides, dormant, within immune-system cells, says that in some lymphomas, the drug, vorinostat, makes cancer cells die. But Margolis adds that in HIV-infected cells, the cancer drug causes the latent virus to show itself.

“Theoretically, doing this clinically would be a way to sort of unmask the hidden virus; flush the virus out of hiding," he says. "And that might then allow us to develop ways to get rid of the leftover virus in people that are on treatment so they could stop treatment and there would be nowhere for the virus to come back from.”

Margolis and his colleagues studied eight HIV-infected patients who were medically stable on anti-retroviral therapy. Their levels of HIV CD4 T cells, which the virus uses to reproduce itself, were measured both before and after the men were given vorinostat.

“What we saw in every single person was a tiny amount of virus detectable before the dose of the drug," he says. "And the amount of virus that was detectable went up on average about five-fold, five times, after a single exposure to the drug.”

Margolis says his so-called “proof of concept” experiment demonstrates that HIV can be flushed out of hiding with vorinostat and then targeted for destruction by anti-AIDS drugs.

But none of the participants was cured, he adds.

Margolis was joined in the work by researchers at the U.S. National Cancer Institute, Harvard University School of Public Health in Massachusetts, the University of California San Diego and Merck and Company, the maker of vorinostat.

Their article on the use of the cancer drug vorinostat in the treatment of HIV was published in the journal Nature.
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