Aids Study Flushes Out Hidden Virus, Pointing to Possible Cure
Current anti-HIV drugs reduce the virus to undetectable levels without eradicating it. The virus survives by lying dormant in immune-system cells, where the medicines dont reach them. Scientists from Johns Hopkins University and the Howard Hughes Medical Institute reported yesterday that they developed a way of luring out these cells in laboratory experiments, an achievement they said may lead to a cure if repeated in humans.
In 2007, about 2.7 million people were newly infected with HIV, the virus that causes AIDS, and 2 million died of the disease, making it the worlds deadliest infectious malady, according to the Geneva-based World Health Organization, an arm of the United Nations. Scientists looking to stop HIV have turned to attacking so-called latent reservoirs of the virus after efforts to prevent infection, such as vaccines and gels, largely failed.
“This is a way in which you could envision finding a drug that would, in conjunction with existing treatment, allow us to cure patients,” said Robert Siliciano, the professor who led the study at Johns Hopkinss medical school in Baltimore. More research is needed, he said.
For about 12 years, doctors have known that HIV, or human immunodeficiency virus, can lie dormant in immune-system cells called resting CD4s found in the lymph nodes, spleen and blood. There the virus stops replicating, avoiding the drugs designed to kill it.
Roaring Back
Studies have shown latent HIV comes roaring back when treatment is interrupted, condemning patients to a lifetime on drugs such as Abbott Laboratories Kaletra that can cause side effects including nausea, liver damage and fat buildup. Eliminating the last vestiges of the virus could cure patients of the disease, allowing them to stop treatment.
Silicianos team mimicked HIV latency in a lab dish using a gene called Bcl-2 to turn normal CD4s into resting cells capable of hosting the dormant form of HIV.
The researchers used the model to test 2,400 chemicals, finding 17 that coaxed the virus out of hiding, kick-starting its normal process of replication. In a human, that would make the virus susceptible to drugs. The best performer was a compound called 5HN found in the leaves, bark and roots of the black walnut tree.
Key Thing
“Theyve found a way to find drugs — thats the key thing,” said Stephen Kent, a professor of immunology at the University of Melbourne, in a telephone interview yesterday. “Weve really just been guessing up to this point about ways to get at this. Having a system for screening drugs is a big advance over what weve had so far.”
The result was achieved without rousing non-infected CD4 cells, avoiding a potentially fatal scenario called a cytokine storm in which the bodys immune system overreacts.
“Its going to require additional research to find something that does the same thing but doesnt have lots of other effects,” Siliciano said. “Were pretty confident that well find lots of compounds that work, but whether any of those will be sufficiently free of other effects — thats not clear,” he said.
Second, recent studies have pointed to another reservoir of latent HIV that has yet to be identified, Siliciano said.
No Test
“We may have to find another drug to target that reservoir,” he said. “First we have to identify what it is.”
Theres no test for identifying whether a patient has latent HIV, meaning the only way to be sure a drug has polished off the virus is to cease treatment and see if it returns, the University of Melbournes Kent said.
The findings are an advance that may allow researchers to come up with a drug they could start testing in humans, Kent said.
“To get something like that into clinical trials is only a few short years — its not decades,” he said. “Then its got to work.”