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David Margolis, UNC researchers find cancer drug that may help fight HIV
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UNC researchers find lymphoma treatment exposes dormant cells, clues to cure.
charlotteobserver.com, By Jay Price
CHAPEL HILL Researchers at UNC-Chapel Hill have discovered what could be a vital step toward a cure for HIV.
By giving patients a drug normally used for treating some kinds of lymphoma, they have managed to make dormant, hidden HIV viruses reveal their presence.
That's crucial if scientists want to find a way to target the viruses and completely eliminate them from the body, said Dr. David Margolis, a professor of medicine, microbiology and immunology, and epidemiology who lead the study.
Margolis was speaking by telephone Thursday afternoon from Seattle, just before presenting the findings at a major conference on retroviruses and opportunistic infections.
HIV is the virus that causes AIDS. In recent years, patients have been able to hold it at bay with elaborate cocktails of antiretroviral drugs.
Even though these drug regimens can halt the progress of the disease, they can be costly, and they cause side effects.
Also, the virus remains, hiding in certain cells, and can turn active again if patients stop taking the drugs.
Researchers believed that a crucial step toward purging the body of HIV was finding a trigger to luring the virus from its hiding place. That's what the UNC team did, for the first time.
The study worked like this: Six HIV-infected men whose conditions were stable and who were on antiretrovirals were given a single dose of a drug called vorinostat.
Earlier studies by Margolis and others had found that the drug attacks the enzymes that keep HIV hiding in specialized immune system cells that the virus uses to replicate itself.
Within hours, all six patients had a significant increase in detectable forms of HIV in these cells. That showed that the "on-off" switch for the virus had, at least mildly, been flicked on, forcing the virus to show itself.
"This proves for the first time that there are ways to specifically treat viral latency, the first step towards curing HIV infection," said Margolis. "It shows that this class of drugs, HDAC inhibitors, can attack persistent virus. Vorinostat may not be the magic bullet, but this success shows us a new way to test drugs to target latency, and suggests that we can build a path that may lead to a cure."
What's next?
The next steps in the research include a fuller exploration of that HDAC inhibitors' effects on the virus, Margolis said, including such things as examining how HIV might respond to multiple doses and other variables.
The findings from that research will determine the next directions for scientists working toward a cure, he said.
The research was done as part of a UNC-led national consortium called the Collaboratory of AIDS Researchers for Eradication, which is funded by the National Institute of Allergy and Infectious Diseases.
Margolis is the principal investigator for the consortium, which won a $32 million federal grant last year to search for ways to cure HIV patients by eliminating those hidden remnants of the virus. These reservoirs are bits of HIV genetic material that languish in certain cells within the immune system.
The latest finding burnishes UNC-CH's growing reputation in HIV research. Last year another UNC-CH-led group announced that the antiretroviral drugs used to treat the virus can be a strong barrier to spreading of the disease. That finding was named the biggest scientific breakthrough of 2011 by the journal Science.
The prevention method and the new discovery by Margolis' team could work together. If a way to purge patients of the virus can be found, that and prevention methods could be used to put HIV in a kind of squeeze play that could sharply reduce the massive cost in dollars and misery that HIV/AIDS exacts on society, Margolis said in an interview last year. The prevention efforts could stop new infections, and a cure could end existing ones. "We need to work from both ends," he said. "Prevention, and then in cases where we aren't able to prevent it, we need tools to eradicate the disease."
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