Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) have investigated the potential of the blood cancer drug venetoclax in addressing the persistence of HIV in the body.
HIV, which primarily targets CD4+ T cells, can hide within these cells in a dormant state, eluding antiretroviral therapy (ART) and necessitating lifelong treatment. If medication is discontinued, these dormant cells can quickly reactivate, causing a resurgence of the virus.
In their groundbreaking study published in the journal Cell Reports Medicine, scientists employed venetoclax in enhanced preclinical HIV models. Surprisingly, the drug delayed viral rebound by two weeks, even without ART. Dr. Philip Arandjelovic, co-first author, noted, “Venetoclax’s ability to target dormant HIV cells and delay viral rebound presents promising prospects beyond current treatments.”
Arandjelovic emphasized, “Each stride in delaying the virus’s return takes us nearer to preventing its resurgence in individuals living with HIV. Our discoveries mark a significant step in that direction.”
This study is the first to evaluate venetoclax independently for its impact on HIV persistence in preclinical models. The research also revealed that combining venetoclax with another drug targeting the same pathway, currently in clinical trials, could extend the delay in viral rebound while reducing the duration of venetoclax treatment.
Dr. Youry Kim, co-first author from The Peter Doherty Institute for Infection and Immunity, conducted research on CD4+ T cells from individuals living with HIV on suppressive ART. The study found that venetoclax effectively reduced HIV DNA levels in these white blood cells.
Kim explained, “Venetoclax selectively eliminates infected cells that rely on specific proteins for survival, offering a promising strategy against HIV.”
The next step involves a Phase I/IIb clinical trial set to commence in Denmark by the year-end, with plans to expand to Melbourne in 2024. Co-led by Professor Sharon Lewin, Director of the Doherty Institute, the trial aims to assess the safety and tolerability of venetoclax in people living with HIV on suppressive ART.
Professor Lewin commented, “Repurposing venetoclax as a treatment for HIV is a remarkable development that could transform the lives of those living with the virus, potentially eliminating the need for lifelong medication.”
Source: Labonline