Commonly used in the treatment of bipolar disorder and other mood disorders, lithium could prove promising for inhibiting HIV, a research team from McGill University has found.
A study published in
iScience reveals that lithium can indeed prevent infected cells from reactivating and that the biological mechanism behind this action is not what was expected.
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This finding paves the way for the development of treatments that would act like lithium, but without producing its undesirable effects on the body.
"The quest for other indications for existing drugs holds an important place in HIV research. Since it is inexpensive and already approved for other uses, lithium could allow us to avoid the long process of development from scratch," explains Andrew Mouland, a professor in the Department of Medicine at McGill University, director of the HIV-1 RNA Diversion Laboratory at the Lady Davis Institute for Medical Research and senior author of the study.
HIV-positive individuals should not start taking lithium for this purpose right away, he clarifies. This psychoactive drug can have significant side effects and has not yet been tested in humans as a treatment against HIV.
A step toward a "functional cure"
In 2024, the estimated number of people living with HIV worldwide was 40.8 million. Even when effective antiretroviral treatment is administered, the virus can remain hidden in immune cells and reactivate if the carrier interrupts their daily treatment.
The goal of a "functional cure" is to address this problem. Rather than completely eliminating HIV, the aim is to keep it dormant so that it cannot reactivate and, perhaps, so that carriers no longer have to take medication every day.
"In our experiments, lithium directly inhibited the reactivation of HIV in human cells cultured in the laboratory, an effect that had never been clearly demonstrated before," states Ana-Luiza Abdalla, lead author of the study, who conducted her work as a PhD student at McGill University. She is now a postdoctoral researcher at the Montreal Neurological Institute-Hospital.
Furthermore, the research team gained new insights into the mechanism at play.
Previous research suggested that lithium's action relied on its ability to activate autophagy, a cellular recycling mechanism. Since many drugs studied in HIV treatment research act on this mechanism, scientists assumed it was autophagy that kept the virus dormant.
However, the research team is questioning this hypothesis based on the results of a fluorescence test developed by Thomas Murooka, a researcher at the University of Manitoba, which allows distinguishing dormant viruses from active viruses in cells.
"What surprised us is that the effect persisted even when we disrupted autophagy," specifies Ana-Luiza Abdalla. "This finding seems to indicate that other pathways are involved, perhaps pathways that allow HIV to reactivate."