Could an Existing Cancer Drug Hold the Key to an HIV Cure?

Hidden HIV cells, known as latent infection, are responsible for the virus permanently remaining in the body and cannot be treated by current therapy options. These hibernating, infected cells are the reason why people living with HIV require life-long treatment to suppress the virus.

Led by WEHI and The Peter Doherty Institute for Infection and Immunity the landmark study is being translated into a new clinical trial to assess whether the blood cancer treatment can be repurposed to offer a pathway towards an HIV cure.

An estimated 39 million people worldwide are living with HIV, including more than 29,400 Australians.

Antiretroviral therapy (ART) is the standard of care treatment given to people living with HIV and is highly effective. But the medication cannot target hibernating HIV-infected cells, meaning it can only suppress the virus — not cure it.

ART for people living with HIV is life-long: if a person stops taking this medication, hibernating HIV-infected cells will reactivate within a very short timeframe, leading to a resurgence of the virus.

In the new study, WEHI researchers used the cancer drug venetoclax on enhanced pre-clinical models of HIV and found it delayed the virus from rebounding by two weeks, even without ART.

Co-first author, Dr Philip Arandjelovic from WEHI, said the discovery is an exciting step towards developing treatment options for the tens of millions of people currently living with HIV globally.

“In attacking dormant HIV cells and delaying viral rebound, venetoclax has shown promise beyond that of currently approved treatments,” he said. “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.”

However, 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.

The 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. 

“The trial will assess the safety and tolerability of venetoclax in people living with HIV who are on suppressive antiretroviral therapy,” said Prof Pellegrini.

Melbourne Laureate Professor Sharon Lewin, a joint corresponding author, concluded: “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 life-long medication.”

Sources: 

Philip Arandjelovic, Youry Kim, James P. Cooney, Simon P. Preston, Marcel Doerflinger, James H. McMahon, Sarah E. Garner, Jennifer M. Zerbato, Michael Roche, Carolin Tumpach, Jesslyn Ong, Dylan Sheerin, Gordon K. Smyth, Jenny L. Anderson, Cody C. Allison, Sharon R. Lewin, Marc Pellegrini. Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice. Cell Reports Medicine, 2023; 101178 DOI: 10.1016/j.xcrm.2023.101178

Walter and Eliza Hall Institute. “Could a cancer drug hold the key to an HIV cure?.” ScienceDaily. ScienceDaily, 30 August 2023. <www.sciencedaily.com/releases/2023/08/230830131950.htm>.

Images from:

Photo by National Cancer Institute

https://unsplash.com/photos/KMvoHcB-w5g