HIV Cure? An Existing Cancer Drug Shows Promise in Killing “Silent” HIV Cells and Delaying Reinfections

Potential HIV Cure? Blood Cancer Drug Demonstrates Promise in Eliminating Dormant HIV Cells and Postponing Reinfections

In a groundbreaking development, the blood cancer medication venetoclax is displaying significant potential in targeting dormant HIV cells, potentially paving the way for a future HIV cure.

Promising strides have been made by utilizing an existing blood cancer drug to eliminate ‘silent’ HIV cells and prolong the time before reinfections occur. This pre-clinical breakthrough holds the potential to revolutionize HIV treatment strategies and eventually lead to a cure for the disease.

Hidden within the body, latent HIV cells contribute to the virus’s enduring presence and are impervious to current therapeutic interventions. These dormant, infected cells are the cause behind the lifelong treatment regimen required to suppress the virus in individuals living with HIV.

Pioneered by the esteemed WEHI and The Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, this monumental study is in the process of being translated into a new clinical trial. This trial aims to assess the possibility of repurposing the blood cancer treatment to provide a viable pathway toward achieving an HIV cure.

Key Findings at a Glance:

In a collaborative effort between WEHI and the Doherty Institute, the cancer drug venetoclax, built upon a revolutionary research discovery at WEHI, has proven effective in eradicating dormant HIV-infected cells and crucially, delaying the virus’s resurgence.
While current treatments are adept at suppressing the virus, they fall short in targeting the dormant HIV-infected cells that perpetuate the virus’s reappearance.
A forthcoming clinical trial set to take place in Denmark and Australia will investigate the viability of using venetoclax as a potential avenue to develop an HIV cure.

Global HIV Landscape and Existing Treatments:

An estimated 39 million people worldwide are afflicted by HIV, with over 29,400 of them residing in Australia.
Antiretroviral therapy (ART) serves as the standard treatment for individuals with HIV, exhibiting high efficacy. However, this medication falls short in addressing dormant HIV-infected cells, limiting its capacity to effectuate a cure.
ART necessitates lifelong adherence; cessation of the medication prompts dormant HIV-infected cells to reactivate within an exceedingly brief period, leading to a resurgence of the virus.
An estimated 98% of Australians living with HIV maintain undetectable viral levels, achieved through consistent ART administration.

Significant Study Discoveries:

In this novel study, researchers at WEHI employed the cancer drug venetoclax on enhanced pre-clinical HIV models, demonstrating its ability to delay viral rebound by up to two weeks, even in the absence of ART.
Dr. Philip Arandjelovic of WEHI, a co-first author, lauds this discovery as an exciting stride toward expanding treatment options for the millions living with HIV globally.
He emphasizes that venetoclax’s potential in attacking dormant HIV cells and delaying viral resurgence offers a new avenue for exploration beyond currently approved treatments.

Venetoclax in Focus:

This study marks the first instance of venetoclax being utilized independently to assess HIV persistence in pre-clinical models.
Researchers also uncovered the potential for combining venetoclax with another drug that targets the same pathway, a drug presently undergoing clinical trials. This combination exhibits potential for extended delays in viral rebound, with a shorter duration of venetoclax treatment.
The finding underscores the notion that a singular drug might not suffice for complete HIV elimination, while also revealing venetoclax’s potent capacity to combat the virus.

The Hidden Battlefield of HIV:

HIV predominantly targets CD4+ T cells, a subset of white blood cells pivotal for immune system functionality.
Within these cells lies dormant HIV, poised to reactivate in the absence of effective viral elimination.
Human CD4+ T cells, donated by individuals on suppressive ART, were employed by scientists at the Doherty Institute. Venetoclax showcased its ability to reduce HIV DNA levels within these white blood cells.
Dr. Youry Kim, a co-first author and a Postdoctoral researcher at the Doherty Institute, notes venetoclax’s efficacy in selectively eliminating infected cells that rely on specific proteins to survive.

Upcoming Clinical Endeavors:

VENCLEXTA, marketed commercially as venetoclax, emerges from a groundbreaking discovery by Professor David Vaux AO in 1988. This drug is the result of a collaborative effort between WEHI and companies Roche, Genentech, and AbbVie. Its development occurred through collaboration and trials in Australia.
Phase I/IIb clinical trials, employing venetoclax to treat HIV, are scheduled to commence in Denmark by year-end, with Melbourne becoming part of the study in 2024. Esteemed figures like Professor Sharon Lewin, Professor Marc Pellegrini, and Dr. Thomas Rasmussen will spearhead the trial.
The trial aims to assess the safety and tolerability of venetoclax in individuals with HIV who are on suppressive antiretroviral therapy.
Professor Sharon Lewin, a joint corresponding author, envisions venetoclax, with its history of aiding blood cancer patients, as a potential treatment to transform the lives of those living with HIV, ultimately eliminating the need for lifelong medication.

Reference: “Venetoclax, alone and in combination with the BH3-mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice” by 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, and Marc Pellegrin, 30 August 2023, Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2023.101178

This research received support from the National Health and Medical Research Council (NHMRC), The Sylvia & Charles Viertel Senior Medical Research Fellowship, Australian Centre for HIV and Hepatitis Virology Research, the Victorian Government, and Australian Government.

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More about HIV Cure

• Study: “Venetoclax, alone and in combination with the BH3-mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice”
• WEHI – Walter and Eliza Hall Institute
• The Peter Doherty Institute for Infection and Immunity
• VENCLEXTA (venetoclax) by Roche
• Antiretroviral therapy (ART) for HIV
• HIV/AIDS Statistics Overview
• Sharon R. Lewin – Doherty Institute Profile
• Marc Pellegrini – WEHI Research Profile
• Thomas Rasmussen – Aarhus University Profile