Researchers find new way to expose hidden HIV, raising hopes for a cure

Researchers at the Peter Doherty Institute for Infection and Immunity in Melbourne created special fat-based carriers, known as lipid nanoparticles (LNPs), that can deliver mRNA into the specific white blood cells where HIV lies dormant. Once inside, the mRNA instructs the cells to reveal the hidden virus.

HIV’s ability to form hidden reservoirs—dormant pockets of virus in certain immune cells—has been one of the biggest obstacles to finding a cure. These reservoirs are the reason nearly 40 million people worldwide must stay on lifelong treatment to suppress the virus and prevent symptoms or transmission.

Dr Paula Cevaal, a research fellow at the Doherty Institute and co-first author of the study, said delivering mRNA to these white blood cells was once thought to be impossible because they would not take up the lipid nanoparticles used to carry it.

The researchers developed a new type of LNP, known as LNP X, that these cells will accept. “Our hope is that this new nanoparticle design could be a new pathway to an HIV cure,” Cevaal said.

When a colleague first presented test results at the lab’s weekly meeting, the team could hardly believe them, Cevaal recalled.

“We sent her back into the lab to repeat it, and she came back the next week with results that were equally good. So we had to believe it. And of course, since then, we’ve repeated it many, many, many more times.

“We were overwhelmed by how [much of a] night and day difference it was – from not working before, and then all of a sudden it was working. And all of us were just sitting gasping like, ‘wow’.”

The study was laboratory based and carried out using cells donated by people living with HIV.

Turning it into a treatment will still require successful tests in animals, followed by safety trials in humans, likely to take years, before efficacy trials can begin.

Further research will be needed to determine whether revealing the virus is enough for the immune system to eliminate it naturally, or whether additional therapies will be needed to fully clear HIV from the body.

“In the field of biomedicine, many things eventually don’t make it into the clinic – that is the unfortunate truth; I don’t want to paint a prettier picture than what is the reality,” Cevaal said.

“But in terms of specifically the field of HIV cure, we have never seen anything close to as good as what we are seeing, in terms of how well we are able to reveal this virus.

“So from that point of view, we’re very hopeful that we are also able to see this type of response in an animal, and that we could eventually do this in humans.”

Dr Michael Roche, co-senior author of the research from the University of Melbourne, said the discovery could have broader implications beyond HIV, with the targeted white blood cells also involved in other diseases, including cancers.

Dr Jonathan Stoye, a retrovirologist and emeritus scientist at the Francis Crick Institute, who was not involved in the study, said the approach taken by the Melbourne team appeared to be a major advance on existing strategies to force the virus out of hiding.

However, he said further studies would be needed to determine how best to kill the virus once exposed.

“Ultimately, one big unknown remains. Do you need to eliminate the entire reservoir for success or just the major part?

“If just 10 per cent of the latent reservoir survives, will that be sufficient to seed new infection? Only time will tell.

“However, that does not detract from the significance of the current study, which represents a major potential advance in delivery of mRNA for therapeutic purposes to blood cells.”