It’s a an unprecedented success and one revolutionary advance in the world of medical and scientific research: A patient, whose identity has not been revealed, has cured of AIDS with a stem cell treatment no protective mutation.
He “Geneva patient“-as he is called, joins the group of people who have successfully cured HIV after a stem cell transplant, becoming the first person in the world to achieve this without their donor carrying the CCR5Δ32 mutation, known to confer protection against HIV infection.
This unprecedented success, published in the journal Nature Medicine, was achieved within the framework of the IciStem consortium, co-coordinated by IrsiCaixa – center jointly promoted by the “La Caixa” Foundation and the Department of Health of the Generalitat of Catalonia – and the University of Utrecht, and was led by the University Hospital of Geneva and the Pasteur Institute.
Today, thirty-two months after stopping antiretroviral treatment (ART), The presence of the virus in the blood remains undetectable. “This case is particularly interesting because it shows us that HIV remission is possible even without the CCR5Δ32 mutation. In addition, we have identified what the possible mechanisms that allowed the cure in this case would be, opening new avenues of research that bring us ever closer to the eradication of HIV”, explains Javier Martínez-Picado, ICREA research professor at IrsiCaixa and coordinator by IciStem.
The individual, who has not made his identity public, was diagnosed HIV positive in May 1990 and immediately started antiretroviral treatment. In January 2018, he was diagnosed with myeloid sarcoma and in July of the same year he suffered a tstem cell transplant from a compatible donor. A month after the transplant, tests already showed that The patient’s blood cells had been completely replaced by those of the donor, and this was accompanied by a decrease HIV-carrying cells in your body.
Before the transplant, despite the optimization of antiretroviral treatment, the “Geneva patient” still had viruses capable of replicating. However, after the transplant, the medical and scientific team observed a drastic reduction in HIV-related parameters: no viral particles, an undetectable reservoir and no immune response indicating that the body recognized the presence of the virus. “Previously, transplants without the CCR5Δ32 mutation had already been performed in other HIV-positive patients. However, if treatment was stopped, a viral resurgence occurred, but slower than that which would be observed in a non-transplanted HIV-positive person.
The “Geneva patient” was the first to achieve long-term remission“, comments Maria Salgado, principal researcher at IrsiCaixa and coordinator of IciStem.
Coinciding with the publication of the case of the “Geneva patient”, it was announced last July, in the 25th edition of the International AIDS Conference (Munich, Germany), the second case of cure after a transplant of stem cells susceptible to HIV infection. Specifically, this patient’s compatible donor had only one copy of the gene containing the CCR5Δ32 mutation, meaning that his cells have very little protection against HIV.
This new case reinforces the conclusions of the “Geneva patient” and provides more evidence on the possibility of achieving remission HIV without the protective mutation.
The role of immunosuppression and the interaction between donor and recipient immunity The research team proposes several hypotheses to explain why the “Geneva patient” reached keep HIV under control without treatment. A key factor is alloimmunity, that is, the interaction between the donor’s immune system and that of the recipient.
This hypothesis coincides with a previous study, led by IrsiCaixa, which links this mechanism to the reduction of the viral reservoir during a stem cell transplant. “After a transplant, the recipient’s immune cells perceive those of the donor as a threat, and vice versa, which triggers a ‘battle’ between the two immune systems,” explains Salgado. During this confrontation, many of the recipient’s immune cells, including those infected with HIV, die and They are eventually replaced by those of the donor. Although this process is very aggressive for the body, it is crucial to eliminate latent HIV in cells that could reactivate the infection.
In the case of the “Geneva patient”, the team chose to administer ruxolitinib, an immunosuppressive drug which aims to reduce the collateral damage caused for this immune battle, but which has also demonstrated in laboratory studies the ability to block the replication of HIV and prevent its reactivation. This drug has been identified as another factor contributing to HIV remission.
Finally, the team highlights the Crucial role of Natural Killer cells (NK) cells in this patient. These cells patrol the body to find and eliminate dangerous cells, such as those infected with HIV, and keep the immune system on alert.
Although stem cell transplantation is not a viable therapeutic option for all people living with HIV, the exceptional nature of the case of the “Geneva patient” opens new perspectives for research of therapies that can take advantage of alloimmunity and immunosuppressive drugs to cure HIV.
“We are faced a discovery that could change the course of HIV cure research“, concludes Martínez-Picado. “The next step will be to delve deeper into the mechanisms that enabled this remission and explore how we can reproduce these results in a larger population of HIV-positive people,” he adds.
