Study: Blood Cancer Treatment Found to Kill Latent HIV-Infected Cells, Possible New Treatment

The blood cancer treatment venetoclax (Venclexta; Roche, Genentech, AbbVie) was found to kill latent HIV-infected cells, indicating a possible new treatment for the virus, according to the results of a preclinical study by the Walter and Eliza Hall Institute and The Peter Doherty Institute for Infection and Immunity.¹

When HIV-infected cells are latent, the virus remains in the body and is untreatable by therapies currently on the market, which is why patients with HIV must stay on treatment to suppress the virus. Currently, antiretroviral therapies (ART) are the standard of care treatment for patients with HIV, however, they cannot target latent infection.¹

“In attacking dormant HIV cells and delaying viral rebound, venetoclax has shown promise beyond that of currently approved treatments,” Philip Arandjelovic, PhD, a postdoctoral researcher at Walter and Eliza Hall Institute of Medical Research, said in a statement. “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.”¹

Investigators used a humanized mouse model of HIV infection and CD4⁺ T cells to determine whether venetoclax can help prime latent cells and clear HIV.²

In the preclinical analysis, the investigators found that venetoclax delayed HIV infection from rebounding by 2 weeks, even without ART, on an enhanced preclinical model of HIV. However, they also found that the drug can be combined with another drug, BH3-mimetic S63845, that acts on the same pathway and is currently in clinical trials.^1,2 They added that the combination can achieve a longer delay in viral rebound, indicating a shorter duration than venetoclax.¹

Additionally, they found that venetoclax could reduce the amount of HIV DNA in CD4⁺ T cells, which are a type of white blood cell that helps the immune system function.¹

“This indicates that venetoclax is selectively killing the infected cells, which rely on key proteins to survive. Venetoclax has the ability to antagonize one of the key survival proteins,” Youry Kim, PhD, a postdoctoral researcher at the Doherty Institute, said in the statement.¹

After the results of the preclinical trial, the investigators are adapting it into a clinical trial to assess whether venetoclax could be repurposed as a pathway for a cure to HIV. The phase 1/2b clinical trial will start by the end of 2023 in Denmark, with investigators planning to expand the study to Melbourne, Australia in 2024. The trial will be conducted with state-of-the-art technology and is aimed to replicate the preclinical trial from Walter and Eliza Hall Institute.¹

“The trial will assess the safety and tolerability of venetoclax in people living with HIV who are on suppressive antiretroviral therapy,” Marc Pellegrini, PhD, an infectious disease physician and executive director at the Centenary Institute, said in a statement.¹

The preclinical trial results were published in Cell Reports Medicine.² This study was the first to examine venetoclax to treat HIV persistence in preclinical models, according to the authors.¹

References

1. Could a cancer drug hold the key to a HIV cure?. News release. EurekAlert. August 30, 2023. Accessed September 5, 2023. https://www.eurekalert.org/news-releases/1000056
2. Arandjelovic P, Kim Y, Cooney JP, Preston SP, et al. Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice. Cell Rep Med. 2023;101178. doi:10.1016/j.xcrm.2023.101178