Ana Luiza Abdalla and Andrew Mouland in front of a flow cytometer at the Lady Davis Institute for Medical Research. The instrument was used to collect key data for the study
Photo Credit: Lucca Jones
Scientific Frontline: "At a Glance" Summary
- Main Discovery: Lithium treatment effectively prevents the reactivation of HIV in latent infected cells, keeping the virus dormant through a biological mechanism previously unidentified in this context.
- Methodology: Researchers utilized a novel fluorescence-based assay to distinguish between dormant and active virus in lab-grown human cells, testing lithium's efficacy while simultaneously disrupting the autophagy pathway to isolate the mechanism of action.
- Key Data: Experiments demonstrated that lithium's ability to suppress viral reactivation persisted even when the cell's autophagy (recycling) system was disabled, directly contradicting the prevailing hypothesis that autophagy was required for this effect.
- Significance: This finding supports the feasibility of a "functional cure"—strategies that keep the virus permanently dormant rather than eradicating it—and identifies a new biological target for maintaining HIV latency.
- Future Application: Development of new pharmaceutical agents that mimic lithium's viral suppression properties without causing the psychoactive side effects or toxicity associated with the drug's current clinical use.
- Branch of Science: Virology and Pharmacology
- Additional Detail: While lithium is an inexpensive and readily available drug, the authors explicitly warn against its current use by HIV patients due to significant side effects and the lack of human clinical trials for this specific indication.
Lithium, a widely used treatment for bipolar disorder and other mood disorders, has shown early promise in suppressing HIV, McGill University researchers report.
A new study published in iScience found that lithium can prevent infected cells from reactivating, and that it does so through an unexpected biological mechanism.
The findings point toward future treatments designed to mimic lithium’s beneficial effects while avoiding its broader impacts on the body.
“One major thrust in HIV cure research is asking whether existing drugs can be repurposed. Because lithium is inexpensive and already approved for other uses, it offers a faster starting point than developing a new drug from scratch,” said senior author Andrew Mouland, Professor in McGill’s Department of Medicine and Head of the HIV-1 RNA Trafficking Laboratory at the Lady Davis Institute for Medical Research.
The results do not mean people with HIV should take lithium, he said. The psychoactive drug can cause significant side effects and has not yet been tested in humans as an HIV treatment.
A step toward a ‘functional cure’
An estimated 40.8 million people around the world were living with HIV in 2024. Even with effective antiretroviral therapy, the virus can remain hidden in immune cells and rebound if daily treatment stops.
A “functional cure” aims to overcome this challenge. Rather than eliminating the virus entirely, the goal is to keep HIV dormant, so it cannot restart infection, potentially reducing the need for continuous daily medication.
“In our experiments, lithium directly suppressed HIV reactivation in lab-grown human cells, something that had not been clearly demonstrated before,” said first author Ana-Luiza Abdalla, who conducted the work as a PhD student at McGill and is now a postdoctoral fellow at the Montreal Neurological Institute.
Also, the team gained new insights into the mechanism involved.
Earlier research suggested lithium might work by activating autophagy, the cell’s recycling system. Because many drugs studied in HIV cure research affect this pathway, scientists assumed autophagy was responsible for keeping the virus dormant.
This study challenges that assumption, made possible by a fluorescence-based test developed by University of Manitoba researcher Thomas Murooka that allows scientists to distinguish between dormant and active virus in cells.
“What surprised us was that the effect persisted even when we disrupted autophagy,” Abdalla said. “That suggests other pathways are involved, possibly ones HIV relies on to restart.”
Funding: Funding was provided by the Canadian Institutes of Health Research
Published in journal: iScience
Title: Lithium attenuates HIV-1 latency reversal in an autophagy-independent way
Authors: Ana-Luiza Abdalla, Gabriel Guajardo-Contreras, Bao-An Chau, Meijuan Niu, Thomas Murooka, and Andrew J. Mouland
Source/Credit: McGill University
Reference Number: vi012126_01
.jpg)