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A combination of two U.S. Food and Drug Administration (FDA)–approved cancer drugs effectively reduced HIV replication in the lab, according to a study published in the September issue of the Journal of Virology.Most of the approved antiretroviral (ARV) drugs are quite potent when used correctly, bringing down HIV by up to a million-fold. They all have a critical weakness, however, which is that over time HIV can mutate to the point where it becomes resistant to the drugs.
Several years ago, scientists began theorizing that it might be possible to use HIV’s ability to mutate against itself. What if, they wondered, HIV could be pushed to mutate so rapidly that mistakes cropped up in the genes of every new generation of virus. Would that defective virus accumulate in such numbers that the infection would burn itself out? This process, called lethal mutagenesis, has been tested with other viruses in small rodents, and it appears that it is at least theoretically possible.
“HIV’s ability to mutate makes it difficult to target and treat,” asserted Louis Mansky, PhD, from the University of Minnesota (UM), in an announcement about his study. “We wanted to take advantage of this behavior by stimulating HIV’s mutation rate, essentially using the virus as a weapon against itself.”
Mansky, and two other UM colleagues, Christine Clouser, PhD, and Steven Patterson, PhD, began looking for FDA-approved drugs with lethal mutagenesis potential. They figured that finding approved drugs with clear safety data would speed up the research process and allow scientists to more quickly begin human testing of any drugs proved effective in the lab. Two such drugs, Gemzar (gemcitabine) and Dacogen (decitabine), seemed particularly promising.
The team found that when the two drugs were used together, at concentrations so low that neither drug was effective when used alone, the combination shut down HIV reproduction by 73 percent. Both drugs, like all other cancer chemotherapies, can have serious side effects when used at typical doses. Researchers hope that they can use doses low enough to minimize such side effects.
“Our results suggest that HIV infectivity can be decreased by combining [drugs such as Gemzar and Dacogen],” the authors commented. “Our observations support a model in which increased mutation frequency decreases infectivity through lethal mutagenesis.”
“The findings provide hope that such an approach will someday help the 33 million people worldwide who currently live with HIV,” Mansky concluded.
The Friends of AIDS Foundation is dedicated to enhancing the quality of life for HIV positive individuals and empowering people to make healthy choices to prevent the spread of the HIV virus. To learn more about The Friends of AIDS Foundation, please visit: http://www.friendsofaids.org.
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