Kick and Kill

It's known as the “kick and kill” approach to combating HIV.

The idea is to “kick” quiet cells that aren't producing HIV, but are capable of doing so, into rearing their lethal heads. When they're not releasing the virus, there's no way to find and kill them. 

Standard HIV treatment, know as antiretroviral therapy (ART), keeps the dormant virus in these quiet cells from replicating. But once a patient stops taking ART, the virus comes roaring back.

Now, researchers at the University of North Carolina at Chapel Hill have made early steps toward a successful “kick and kill” treatment, using what's known as the “BLT mouse” modela way of using humanized mice to study potential HIV therapies.

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'An Incredible Model' for Studying HIV

Using BLT mice, J. Victor Garcia and colleagues at the University of North Carolina at Chapel Hill School of Medicine have found some success with the “kick and kill method.” The results of their work were published last week in the journal PLOS Pathogens.

“BLT” stands for stem cell "bone marrow, liver, and thymus," all of which come from humans. The mice had to be altered with human-like immune systems because the rodents could otherwise not be used effectively for HIV research, Garcia said. 

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“When we looked more carefully at different tissues in the mice, to our surprise, the liver and lungs had human cells in them very much like humans,” Garcia told Healthline. “What was really transforming was that when we looked at two important organs—the intestinal tracts and female reproductive tract—both were humanized and had human cells.” 

That meant that researchers could induce HIV infection rectally and vaginally in the mice, just like in humans, Garcia said. “These mice turned out to be an excellent model, an incredible model, for studying HIV transmission.

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A 'Guided Missile' 

Garcia and his colleagues, including Dr. David Margolis, teamed up with National Institutes of Health scientists Edward Berger and Ira Pastan. The NIH scientists created a genetically modified compound called 3B3-PE38. 

The 3B3 is an antibody that hones in on HIV-infected cells that are producing a specific protein on their surfaces. The antibody attaches to and then pierces the cells with PE38, a bacterial toxin.

Essentially, the antibody serves as a “guided missile” that carries the toxin “payload” on an HIV search and destroy mission, Berger told Healthline. 

For the study, the BLT mice were first treated with ART. Despite receiving high doses of medication, the virus remained present in all of the immune tissues the researchers analyzed. But when hammered with the 3B3-PE38 compound, evidence of the virus decreased six-fold.

Still, it did not completely wipe out the virus, meaning that it would eventually be able to multiply again. “It's not that we were able to offer a proof of principal that the kill step is viable, but a platform where we can test any strategy for HIV eradication,” Garcia said. “If a better 'kick' strategy comes around, we will be able to test it in this system.”

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How Can Scientists Keep Kicking?

“How do we keep the kick going? That's what we don't know,” Berger said. 

Still, he said that the study does offer promise for those treated immediately after infection, such as the Mississippi baby born to an HIV-positive mother. In a controversial move, the clinician in that case immediately began giving the child high doses of ART.

The baby made global headlines, because 21 months after discontinuing treatment, active levels of the HIV virus could not be found in the child's body. Researchers are now using the term “remission” to describe the baby's condition.

Berger said the French VISCONTI study, in which people treated early with ART continued to have low viral loads even after treatment ended, also offers hope for the “kick and kill” strategy.

Margolis said the two-part problem of eradicating HIV—that the virus doesn't always express itself, and that we can't kill it all even when it does appear—stubbornly remains.

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