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August 14, 2014

Drug Combination Controls HIV in Mice by Targeting Hidden Virus

by Jessica Berman

Antiretroviral therapies work well to keep HIV infection at bay. As soon as the drugs are discontinued, though, the AIDS virus comes roaring back in a matter of weeks. Now, researchers have developed a treatment that attacks hidden HIV so there is no rebound when antiviral drugs are stopped.

Using mice that were genetically bred to become infected with the AIDS virus, researchers have managed to access and unmask latent reservoirs of HIV and destroy them. In more than half of the rodents, the infection did not recur after antiretroviral therapy was stopped.

Because antiretroviral drugs and the human immune system can’t reach these hidden pockets of infected cells, taking anti-AIDS drugs is a lifelong commitment. If patients discontinue the HIV therapy for one reason or another, the virus rebounds within about two months after the drugs to suppress it are stopped.

The experimental treatment regimen -- developed by researchers at Rockefeller University in New York -- takes a two-pronged approach. It combines so-called broadly neutralizing antibodies against HIV with existing anti-cancer drugs that researchers use as viral “inducers,” to stimulate and unmask the latent infection.

Eliminating infection

The antibodies -- produced by only a very small subset of people infected with HIV -- recognize and destroy a broad range of microbial invaders. By themselves, however, they are not enough to vanquish the infection.  

But they can kill the infection when combined with three viral inducers. Rockefeller's Ari Halper-Stromberg helped develop the strategy, which they call “shock and kill.”

“I think it’s just a layman’s term or a way of clearly explaining the idea, which is to shock the virus -- to wake it up from its latent state -- and then obviously you need to kill it in order to have an effect because it is risky. If you just shock it and you don’t kill then it you could have a lot of problems,” he said.

Halper-Stromberg said a number of labs have tried unsuccessfully to use viral inducers and antiretroviral drugs to attack HIV reservoirs, but his lab is the first to succeed by using broadly neutralizing antibodies.

Researchers isolated these antibodies from the subset of infected individuals who produced them, and they also engineered the special immune fighter cells in the lab.

Remaining obstacles

Scientists say there are many obstacles to making the therapy available to people infected with HIV, including the cost of the scarce and extremely expensive antibodies. At this point, that would put the treatment out of reach for most individuals.

“I think that would have to be worked out on another level, and maybe with scale it becomes a little more accessible," said Halper-Stromberg. "But a major benefit for patients is that potentially you could take the therapy much less frequently.”

So rather than every day, patients would need a treatment every month or two.

Researchers are poised to begin human trials, adding viral inducers to the regimen of patients who currently take infusions of the antibodies to manage their infection.

An article describing “shock and kill” therapy for HIV is published in the journal Cell.