Cancer drug kills ‘silent’ HIV in cell and mice study
31 August 2023
Jacinta Bowler is a science journalist at Cosmos. They were published in the Best Australian Science Writing 2022.
A new mouse study has discovered that an existing cancer drug can kill some ‘silent’ HIV infected cells. The researchers are excited about their finding and are moving into clinical trials in humans.
However, questions remain about whether this could be a ‘cure’, or just a way to limit the number of these cells in the body. The research has been published in Cell Reports Medicine.
“Currently, for people living with HIV, they have to take antiretroviral medication their whole life. As soon as they’ve stopped taking antiretroviral medication, the virus rebounds,” one of the researchers, Dr Philip Arandjelovic told Cosmos.
The research was led by Arandjelovic at WEHI, the Walter and Eliza Hall Institute of Medical Research, in Melbourne and Youry Kim from the Doherty Institute.
“What we found was that using a preclinical mouse model of HIV infection, we could use a preexisting, repurposed anti-cancer drug called venetoclax to delay how long it takes the virus to reemerge in the body after we stop standard treatment,” Arandjelovic told Cosmos.
HIV (human immunodeficiency virus) is a virus which can infect humans, and over time causes the immune system to slowly fail.
Although current HIV medication – called antiretroviral therapy (ART) is effective at killing the HIV that is damaging the body and immune system, it can’t kill every single viral particle as some HIV hides or hibernates inside our cells. This is similar to malaria and chickenpox (or shingles as it’s known when it reappears). This “silent” HIV emerges from the cells when ART is stopped and begins to ‘repopulate’ the lost HIV in the body, again causing symptoms.
The team looked at the cancer drug venetoclax, as well as another potential cancer drug which is currently going through clinical trials called S63845, to see if they could attack the silent HIV while still in the cell. This could potentially remove the reservoir of virus.
Specifically, both the venetoclax and S63845 targets cells that are using more ‘pro-survival’ proteins. This means that some normal cells also die, but mostly it targets the HIV cells.
“Venetoclax specifically targets those pro-survival proteins and inhibits them,” says Arandjelovic. “It does that in cancer cells, but it can also do it in any other cell that’s addicted to these pro-survival proteins.”
The researchers at the Doherty Institute used cells from humans currently with HIV on ART, and the team at WEHI looked at mice which have been genetically engineered to be immunology similar humans. These are called “hu-mice” and were also infected with HIV and put on ART therapy.
In the cell part of the study, both venetoclax and S63845 were effective at killing the HIV virus and the cells that were harbouring them.
The WEHI team found that in the hu-mice, venetoclax delayed the time to viral rebound compared to a control by a week, while the 2-drug combination delayed the viral rebound an extra week on top of that.
Unfortunately, even when venetoclax and S63845 were used together, it couldn’t completely destroy all of the HIV cells in the hu-mice. The team could tell that it was working because it took those mice longer to ‘rebound’ back to higher HIV levels.
This is a good start, but it’s not a cure currently. Even if only a fraction of HIV cells remain, it could be enough to re-establish a population of HIV in the body. This was the case in the mice.
However, the team is moving towards clinical trials as they believe that humans might respond better than mice when it comes to ‘finishing off’ the last few cells.
“While our humanised mouse model is really sophisticated in a lot of ways … it doesn’t predict a full human response,” Arandjelovic told Cosmos.
The hu-mice “do have these immune cells, they don’t function exactly as a healthy humans’ immune system does. They don’t mount the strong anti-HIV response that typically we get in humans.”
Human trials with venetoclax should provide more information about whether a human immune response can limit the HIV that rebounds. The team are currently not pursuing a trial with both drugs simultaneously because S63845 is not available on the market.
Other researchers who weren’t involved in the research have also commented on the paper.
“The paper from Arandjelovic, Kim and co-authors shows that approaches previously used for the successful treatment of certain types of blood cancers increase the time to viral rebound in a humanised mouse model of HIV infection following anti-retroviral treatment interruption,” says Professor Anthony Kelleher, a Director of the Kirby Institute which investigates infectious diseases, including HIV.
“While the effect is present using one drug, currently in routine clinical use, the effect is best observed using the first drug in combination with a second drug, which is in early phase development.”
Originally published by Cosmos as Cancer drug kills ‘silent’ HIV in cell and mice study