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UCLA study improves method to eradicate HIV-infected cells

(Maleeha Zaman/Daily Bruin)

By Parsa Mokhtar

Feb. 22, 2022 12:04 a.m.

UCLA researchers recently refined a new method to target and eliminate HIV-infected cells.

The study, published Jan. 10, showed how the treatment, known as the kick and kill method, successfully destroyed human immune cells infected with a dormant form of HIV in mice.

HIV infects a subset of immune cells in humans and, if left untreated, can develop into AIDS, a condition in which patients have extremely low counts of immune cells. Individuals with AIDS have a weakened immune system, and the syndrome typically results in death within 10 years of diagnosis, according to a 2016 article published in the journal Public Health.

Jerome Zack, a senior author of the study and chair of the Department of Microbiology, Immunology and Molecular Genetics, said when an individual is first infected with HIV, some of the virus infects cells and remains dormant. These dormant infected cells evade current HIV therapies and enable the virus to multiply once the individual stops treatment.

The method consists of two steps. In the first part of the method – the kick portion – Zack said researchers activate the cells infected with the dormant HIV, allowing the previously undetected cell to now be recognized. UCLA collaborated with Paul Wender, a professor of chemistry at Stanford University, who synthesizes chemical products used for researching different potential treatments.

Since these dormant infected cells can now be recognized, researchers inject immune cells in mice to initiate the kill step.

The kick and kill method significantly depleted the population of infected cells, appearing to have completely purged them in 40% of the mice, who showed no proof of infection after treatment, according to the study. These results were exciting because when current HIV patients halt their treatment after the viral genome seems to be depleted, latent infected cells rebound infection, Zack said.

“This study provides compelling evidence that a kick and kill approach might lead to treatment interruption – if not eradication,” said Wender, who has been studying molecules of this type for decades, in an emailed statement.

Dr. Jocelyn Kim, an assistant professor of medicine and lead author of the study, said previous papers mainly focused on the kick component of the kick and kill method.

One of this study’s distinguishing factors is that researchers developed a method that can be used to tag each individual virus infecting a mouse, almost like a barcode, Zack said. This enabled researchers to monitor the infected reservoir and see that it was, in fact, being depleted.

The mice they used were also central to being able to test the drugs’ effectiveness, Wender said, adding that the mouse model – developed by Zack – was an important tool for HIV research. While mice cannot be infected with HIV, researchers transplant human immune cells into the mice that are then infected, Zack said.

“By collaborating, we don’t have to reinvent the wheel – it already exists,” Wender said.

Before the possibility of clinical trials, the researchers will need to first show their method works on larger animal models, like monkeys.

Looking ahead, Zack, Wender and Kim said they believe the kick and kill approach may be effective as a supplement to HIV medication or even a full replacement of it.

“We’ve been working on this approach for 25 years now,” Zack said. “It was rewarding to see that it has potential.”

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Parsa Mokhtar
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