'Kick and Kill' Technique Targets Dormant HIV Cells

A synthetic particle awakens dormant HIV cells then knocks them out.

Scientists have developed a molecule that could “kick and kill” HIV, according to a press release.

The development of antiretroviral therapy (ART) have transformed HIV from what was once a death sentence to what is now a chronic disease; however, there is still no cure.

To evade ART and the immune system response, the virus hides in reservoir pools. Scientists have long been searching for ways to eliminate these reservoirs, however, a research team from UCLA, Stanford University, and the National Institutes of Health may have developed a strategy.

The approach involves the use of an agent that wakes up the dormant virus, causing it to start replicating so the immune system or the virus itself kills the cells holding HIV. This technique is referred to as “kick and kill.”

In a study published in PLOS Pathogens, investigators successfully used this approach with a synthetic molecule in lab animals, effectively kicking and killing HIV. The method has not yet been tested in humans.

“The latent HIV reservoir is very stable and can reactivate virus replication if a patient stops taking antiretroviral drugs for any reason,” said lead author Matthew Marsden in the release. “Our study suggests that there may be means of activating latent virus in the body while the patient is on antiretroviral drugs to prevent the virus from spreading, and that this may eliminate at least some of the latent reservoir.”

For the study, investigators administered antiretroviral drugs to mice infected with HIV, followed by the administration of a synthetic compound called SUW133 to activate the dormant HIV in the mice.

The findings showed up to 25% of previously dormant cells that began expressing HIV died within 24 hours of activation, according to the release.

SUW133 is based on a natural compound extracted from Bugula neritina called bryostatin 1. The findings showed the new compound is less toxic than the naturally occurring version.

“The findings are significant because several previous attempts to activate latent virus have had only limited success,” senior author Jerome Zack, said in the release. “Most studies showed weak activation of the virus, or severe toxicity, with little effect on the reservoir.”

Marsden noted that the findings in mice will not necessarily translate to humans, but with further development, this approach could lower the viral reservoir enough for HIV-positive patients to be able to discontinue ART.

The investigators plan to learn how to make SUV133 less toxic and to evaluate its efficacy in larger animals before testing in humans, according to the release.