October 7, 2009
Current HIV/AIDS drugs work by reducing the virus to undetectable levels but cannot eradicate it. Instead, HIV lies dormant in immune-system cells unreachable by medicines. Now, researchers from Johns Hopkins University and Howard Hughes Medical Institute say they have developed a way to lure out these latent reservoirs in laboratory experiments, possibly paving the way to a cure if repeated in humans.
Scientists have known for about 12 years that HIV hides in resting CD4 cells found in the lymph nodes, spleen, and blood. Studies have shown latent HIV rebounds when treatment is interrupted. Led by Professor Robert Siciliano, the research team mimicked HIV latency in a lab dish, using the Bcl-2 gene to turn normal CD4s into resting cells capable of hosting the dormant form of HIV.
The model was then tested with 2,400 chemicals, 17 of which coaxed the virus out of hiding, starting up its normal process of replication. In humans, this would make HIV susceptible to drugs. The top performer was the compound 5HN, which is found in the leaves, bark, and roots of the black walnut tree.
Siciliano cautioned that the study has limitations, beginning with the possibility that 5HN may be too toxic for use in humans. "It's going to require additional research to find something that does the same thing but doesn't have lots of other effects," he said. "We're pretty confident that we'll find lots of compounds that work, but whether any of those will be sufficiently free of other effects - that's not clear."
In addition, recent research points to another reservoir of latent HIV that has yet to be identified, said Siciliano. "We may have to find another drug to target that reservoir. First we have to identify what it is."
Stephen Kent, a professor of immunology at the University of Melbourne who was not involved in the research, noted that there is no test to determine whether a patient has latent HIV, meaning the only way to know if a drug has killed off the virus is to cease treatment and see if it returns. But the new findings represent an advance, to be sure, he said.
The study, "Small-Molecule Screening Using a Human Primary Cell Model of HIV Latency Identifies Compounds that Reverse Latency Without Cellular Activation," was published online in the Journal of Clinical Investigation (2009;doi:10.1172/JCI39199).
10.02.2009; Simeon Bennett