Cancer drug shows promise in HIV cure research

Unconventional approaches: Investigating a cancer drug's role in HIV eradication.

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A medicine used for blood cancer has shown promise in killing hidden HIV cells that stay in the body and cause the virus to return. These invisible HIV cells are why the virus stays in the body and can’t be treated with current methods. People with HIV need lifelong treatment to control the virus because of these hidden cells.

Researchers from WEHI and The Peter Doherty Institute for Infection and Immunity did a significant study. They’re now starting a new test to see if the blood cancer medicine could be used to cure HIV.

Around the world, about 39 million people have HIV, and in Australia, there are more than 29,400 people with it. People with HIV get antiretroviral therapy (ART), which works well. But this treatment can’t stop hidden HIV cells from returning, so it can’t cure the virus.

People with HIV need to take ART for their whole lives. If they stop taking it, the hidden HIV cells wake up quickly, and the virus returns. About 98% of people in Australia with HIV have so little virus that it can’t be detected, thanks to their ongoing ART treatment.

Researchers at WEHI did a new study. They used a cancer drug called venetoclax on unique models of HIV. They found that it delayed the virus from coming back 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 millions of people living with HIV globally. “In attacking dormant HIV cells and delaying viral rebound, venetoclax has shown promise beyond currently approved treatments.”

“We’re getting closer to stopping this virus from returning, which means we’re closer to preventing HIV from returning in people who have it. Our results are a step in that direction.”

This is the first time they tried using venetoclax by itself to see how it affects HIV in tests before clinical trials.

Researchers also discovered that when they used the cancer medicine with another drug that works the same way and is being tested in people, the delay in the virus coming back was even longer. This means they could use less venetoclax medicine but still get good results.

“It’s been known for a while that one drug might not be enough to get rid of HIV completely. This discovery supports that idea and shows that venetoclax could be a powerful tool against HIV,” explained Dr. Arandjelovic.

HIV mainly attacks a type of white blood cell called CD4+ T cells. These cells are significant for the immune system to work well. HIV can stay quiet inside these cells. It’s like sleeping but can wake up and cause trouble if not dealt with.

Researchers used CD4+ T cells from people with HIV who are taking strong medicine. They found that venetoclax could lower the amount of HIV DNA in these cells. Dr. Youry Kim, one of the authors, said that venetoclax could enormously decrease the amount of working viral DNA in the cells when tested in the lab.

This means venetoclax might kill the infected cells, which need particular proteins to survive. Venetoclax can stop one of these essential proteins from working, so the infected cells could die.

A drug called Venetoclax, also known as VENCLEXTA, results from necessary research from 1988 by Professor David Vaux AO. This drug came from a collaboration between WEHI and companies like Roche, Genentech, and AbbVie. It was created by Roche, Genentech, and AbbVie, and its testing and development happened in Australia.

A clinical trial, called Phase I/IIb, will start at the end of the year in Denmark. They’ll be using venetoclax to treat HIV. They plan to expand the study to Melbourne in 2024. This trial will be led by Professor Sharon Lewin, Professor Marc Pellegrini, and Dr. Thomas Rasmussen.

Professor Marc Pellegrini, who helped with the study, said the trial will be like the lab study they did at WEHI. They will test if venetoclax is safe and okay for people with HIV who are already taking antiretroviral therapy.

Professor Sharon Lewin, another person who worked on the study, said, “It’s exciting to see that venetoclax, which has already helped many blood cancer patients, is now being tested to help people with HIV. This could change their lives and maybe even stop the need for lifelong medication.”

Journal Reference:

  1. Philip Arandjelovic, Youry Kim, 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 Reports Medicines. DOI: 10.1016/j.xcrm.2023.101178.
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