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Scientists Hone in on the Best Way to Expose HIV Hidden in the Viral Reservoir, a Crucial Step Toward an Eventual Cure

July 25, 2017

Researchers at the University of North Carolina are one step closer in the quest to find a cure for HIV, announcing earlier this month that they have identified a better dosing strategy for a drug that exposes HIV hiding inside the body's viral reservoir.

HIV is difficult to completely eradicate because it buries itself within the genetic material of certain cells, meaning that people with HIV have to take medication indefinitely to keep the virus at bay. For years, researchers have known that a certain class of drugs called "histone deacetylase" (HDAC) inhibitors" can unlock the so-called viral reservoir, prompting the hidden HIV virus to expose itself. Exposing the viral reservoir is considered the first step in current cure research strategies; the second step is to eradicate the exposed virus from the body.

Although David Margolis, M.D., director of the HIV Cure Center at the University of North Carolina and co-author of a recent paper in the Journal of Clinical Investigation, doesn't like to use the phrase 'kick and kill' ("it makes it sound too dangerous," he told TheBodyPRO.com), it's a common way people describe this approach to cure.

In the recently published paper, Margolis and his colleagues tested several different dosing strategies of an HDAC inhibitor called vorinostat on 16 volunteers and identified an ideal dosing strategy: one that seemed to have the most dramatic impact on the viral reservoir and the most tolerable side-effect profile for patients.

Vorinostat was initially registered as an oncology drug by the pharmaceutical company Merck, but it proved interesting to HIV cure researchers because of its apparent effect on the viral reservoir.

"Prior research [of vorinostat] was generally measuring at a single time point," Margolis told TheBodyPRO.com. "We really didn't know for sure how much of the drug should be given, how often and how long it would work."

Although only three out of the initial 16 patients completed the trial, the researchers felt they collected enough information to offer an informed suggestion on an ideal dosing regimen given the current evidence on vorinostat.

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"We thought it was better to share that now rather than wait three to four years," said Margolis. "This is the first study to carefully measure that effect over time," he said, noting: "We don't have perfect information, but at least we're showing the beginning of a roadmap."

Based on the efficacy and toxicity profile of vorinostat, Margolis and his colleagues suggest a regimen of 400 mg every three days, and patients should not be treated for more than a month at a time because of toxicity. Drugs like vorinostat wear off over time, but dosing continuously is too hard on patients, he said.

In the future, as researchers continue to investigate a cure, they will continue to optimize the dosing schedule of vorinostat and other drugs like it. It's important to note, however, that this recent study of vorinostat only contributes to the first half of the "kick and kill" cure efforts.

"The virus was kicked," Margolis said. "There was some real exposure of the latent reservoir, but at the level we could measure, we didn't see any clearance of the infection with just the kick."

To fully eradicate HIV from the body, researchers must administer a drug, such as vorinostat, that can expose the virus and then administer another drug that can stimulate the immune system to "kill" the exposed virus.

"We already have kill strategies, or immunotherapy strategies, lined up," said Margolis, who, alongside his colleagues at the HIV Cure Research Center, has initiated studies with dendritic cell vaccines and ex-vivo T cells: Two immunotherapies seen as promising options for the final eradication of HIV.

It's important for people to remember that scientists are inching closer to a cure, although "it's one step at a time, and it's a slow process," he said. Overall, he said, progress toward a cure would not happen without the dedicated volunteers who choose to contribute to science.

"In the short term, there's no benefit for them, but without their contribution, we won't go anywhere," he said.

The reason this study is so important is because, when it comes to cure research, even something as simple as a dosing regimen must be clearly documented, measured and quantified.

"We can't make assumptions about anything. We have to actually measure and know what we're doing," Margolis said.

Sony Salzman is a freelance journalist reporting on health care and medicine, who has won awards in both narrative writing and radio journalism. Follow Salzman on Twitter: @sonysalz.


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