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"HIV cure will be possible with a combination of strategies"

Updated

Javier Martínez-Picado is one of the leading researchers in the fight against AIDS and coordinates the international consortium IciStem from Barcelona

The researcher Javier Martínez-Picado.
The researcher Javier Martínez-Picado.IRSICAIXA

Behind some of the most important recent developments in the fight against HIV is the name of Javier Martínez-Picado.

Researcher at IrsiCaixa, ICREA professor, and member of the Royal Academy of Sciences and Arts of Barcelona, the scientist recently published his most recent 'paper', demonstrating how therapeutic innovations against HIV have affected the pathogen's ability to hide in the body.

But his name is also associated with recent significant advances such as the cure of several patients through hematopoietic transplantation - both with the CCR5Delta32 mutation and without it - or the description of five cases of complete remission of infection in children who acquired the virus from their mothers.

All these findings pave the way for the idea that finding a cure for HIV is possible.

"Virus cure is possible, but it must be scalable," emphasized Martínez-Picado this week at the opening conference of the GeSIDA Congress held in Zaragoza. He reiterated this a few days later at the CIBER network meeting in Valencia to celebrate its first 10 years, where he spoke with EL MUNDO.

"So far, virus elimination has been achieved in people with a severe hematologic disease needing a transplant. It is not applicable to every person with HIV, but everything we have learned from this and other approaches is being used to develop scalable therapies. I am optimistic. I started at a time when curing HIV was said to be impossible. And we have shown that it is not, although for now they are only proof of concept," he points out.

He is convinced that, as it happened with antiretroviral therapy, virus cure will also come from a "combination of strategies."

"Curing HIV will require at least two conceptual convergences," the researcher notes. The first involves reducing the viral reservoir, the 'hiding places' the virus uses to hide, a characteristic that currently requires people with HIV to take antiretroviral therapy for life. The other involves increasing people's immunity. "HIV precisely attacks people's immune system. It damages their system. Therefore, we need to find ways to boost the immune system as effectively as possible."

This is how advanced therapies against HIV dismantle the 'hiding places' the virus uses to hide

Strategies in this direction are being explored, the researcher reveals. For example, through CAR-T cells or through immune checkpoint inhibitors, among others.

One clue that the researcher has been following for years through the international program IciStem, which he co-leads from Barcelona, is the CCR5Delta32 mutation, a kind of shield against the virus that prevents it from infecting cells.

The international consortium IciStem, co-led from Barcelona, has completely eliminated the virus in five people who, due to a severe hematologic disease, needed to undergo hematopoietic transplantation. In these cases, donors with the CCR5Delta32 mutation were chosen. However, researchers have found that this 'shield' is not an essential requirement. In September of this year, they published details of the so-called 'Geneva patient', the first case of HIV cure after a stem cell transplant without the mentioned protective mutation.

"We are seeing other cases starting to interrupt treatment after a transplant. We knew since 1996 that this mutation prevented the virus from entering the body, but it wasn't until 2009 that the first case of cure, Timothy Brown, was confirmed. It took 13 years from the discovery that this mutation inactivates this receptor until we applied it in Medicine. The second case, done by us, happened 10 years later. But since 2019, we have achieved six more cases. It's slow progress, but it's happening. I am optimistic about scientific advances," he says.

"We are using everything we have learned from transplants to try to find a scalable therapy. Like the CAR-T cell project being developed by IrsiCaixa researcher María Salgado or a gene therapy project we are developing with the NIH that is showing promising results," the researcher continues.

"We advance and learn from successes and mistakes," he maintains. And any new advance can be useful both now and in the future, he warns: "I always tell my students that they have to look beyond the experiment they are doing because behind HIV, any other retrovirus could come in the future, and everything we know about this virus can be applied to others."