Australian researchers have found that a medicine used to treat blood cancer can kill ‘silent’ HIV cells and delay reoccurrence in a milestone pre-clinical discovery that could lead to a future cure for the disease.
Antiretroviral therapy, the standard management for HIV, can remove traces of the virus from the blood, but a hidden reservoir of HIV persists in the cells of patients on treatment. This means patients are never completely cured and need to be on HIV drugs for the rest of their lives.
“Most HIV patients on antiretroviral drug treatments have little to zero chances of passing it on and can lead normal and healthy lives, but the virus is never eliminated from their cells fully,” explained Dr Oliver Mito, who offers HIV care and treatment, and who was not part of the research. “This is because some of the virus “sleeps” dormantly in the immune system cells, ready to replicate when ARV use is withdrawn, and therefore cannot be eliminated,” he says.
“You cannot attack an enemy you cannot see or detect unless they get out of their hiding place.” These dormant infected cells are why people with HIV require life-long treatment to suppress the virus. “Being able to stop HIV from hiding would be an important part of finding an HIV cure,” Dr Mito says.
And now, the cancer drug Venetoclax has been shown to kill hibernating HIV-infected cells. Led by the Walter and Eliza Hall Institute of Medical Research (WEHI) and The Peter Doherty Institute for Infection and Immunity, leading medical research institutes in Melbourne, Australia, a clinical trial on people is underway to assess whether the blood cancer drug can be repurposed towards finding an HIV cure.
At the pre-clinical level, the researchers used venetoclax on human CD4+ T cells donated by people living with HIV who are on suppressive ARVs. The scientists found venetoclax was also able to reduce the amount of HIV DNA in these white blood cells. They also found that the drug delayed the virus from rebounding by two weeks, even without ARVs.
Dr Philip Arandjelovic, co-author in the study, said the discovery is an exciting step towards developing treatment options for the tens of millions of people currently living with HIV globally.
“In attacking dormant HIV cells and delaying viral rebound, venetoclax has shown promise beyond currently approved treatments,” he said. “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.”
“This indicates venetoclax is selectively killing the infected cells, which rely on key proteins to survive. Venetoclax can antagonise one of the key survival proteins,” said Dr Kim.
The clinical trial on humans using venetoclax to treat HIV will start at the end of this year in Denmark, with plans to expand the study to Melbourne in 2024.