Blood cancer drug attacks dormant HIV cells

An existing blood cancer drug has shown promise in killing ‘silent’ HIV cells and delaying reinfection, which could potentially lead to a future cure for the disease.

HIV primarily targets CD4⁺ T cells, a type of white blood cell crucial for the immune system to properly function. It is within these cells that HIV can lie dormant, ready to reactivate if the virus is not effectively suppressed.

These hibernating, infected cells are the reason why people living with HIV require lifelong treatment — antiretroviral therapy (ART) cannot target these cells, meaning it can only suppress the virus rather than cure it. If a person stops taking their medication, the hibernating cells will reactivate within a very short time frame, leading to a resurgence of the virus.

In a new study, published in the journal Cell Reports Medicine, researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) used the cancer drug venetoclax on enhanced preclinical models of HIV and found it delayed the virus from rebounding by two weeks, even without ART. As noted by co-first author Dr Philip Arandjelovic, “In attacking dormant HIV cells and delaying viral rebound, venetoclax has shown promise beyond that of currently approved treatments.”

He added, “Every achievement in delaying this virus from returning brings us closer to preventing the disease from re-emerging in people living with HIV. Our findings are hopefully a step towards this goal.”

The study marks the first time venetoclax has been used on its own to assess HIV persistence in preclinical models. However, the researchers also found the cancer treatment can be combined with another drug that acts on the same pathway and is currently in clinical trials, to achieve a longer delay in viral rebound, with a shorter duration of venetoclax treatment.

“It has long been understood that one drug may not be enough to completely eliminate HIV,” Arandjelovic said. “This finding has supported that theory, while uncovering venetoclax’s powerful potential as a weapon against HIV.”

As part of the same study, scientists at The Peter Doherty Institute for Infection and Immunity studied human CD4⁺ T cells donated by people living with HIV who are on suppressive ART, finding that venetoclax was also able to reduce the amount of HIV DNA in these white blood cells. Co-first author Dr Youry Kim, a postdoctoral researcher at the Doherty Institute, said venetoclax potently reduced the amount of intact viral DNA in patient cells when studied in the laboratory.

“This indicates that venetoclax is selectively killing the infected cells, which rely on key proteins to survive,” Kim said. “Venetoclax has the ability to antagonise one of the key survival proteins.”

A Phase I/IIb clinical trial using venetoclax to treat HIV will start at the end of the year in Denmark, with plans to expand the study to Melbourne in 2024. To be co-led by Doherty Institute Director Professor Sharon Lewin, the trial will replicate the preclinical study to assess safety and tolerability in people living with HIV who are on suppressive ART.

“It’s exciting to see venetoclax, which has already helped thousands of blood cancer patients, now being repurposed as a treatment that could also help change the lives of people living with HIV and put an end to the requirement for lifelong medication,” Lewin said.

Image credit: iStock.com/Artem_Egorov