They achieve unprecedented remission of HIV

BARCELONA (EFE).— The international IciStem consortium confirmed the first case of a patient in whom remission of the human immunodeficiency virus (HIV) was achieved after a stem cell transplant without the mutation that confers protection against the pathogen.

The individual, known as the “Geneva patient” and whose identity has not been made public, is the sixth person to achieve HIV remission after a stem cell transplant.

It differs from the previous five by having received stem cells from a donor who did not have the CCR5-delta 32 mutation, known to confer protection against HIV, IrsiCaixa reported yesterday.

The study, published in the journal “Nature Medicine”, suggests that the CCR5-delta 32 mutation “facilitates healing, but is not essential to achieve it.”

“This case is especially interesting because it shows us that HIV remission is possible even without the CCR5-delta 32 mutation. In addition, we have identified what would be the possible mechanisms that have allowed cure in this case, opening new avenues of research that allow us are getting closer and closer to the eradication of HIV,” said Javier Martínez-Picado, Icrea research professor at IrsiCaixa and also coordinator of IciStem.

The “Geneva patient” was diagnosed with HIV in May 1990 and immediately began antiretroviral treatment.

In January 2018 he was diagnosed with myeloid sarcoma and in July of the same year he underwent a stem cell transplant from a donor who was compatible.

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 in HIV-carrying cells throughout the body.

Before the transplant, despite the optimization of antiretroviral treatment, the patient still had viruses with the capacity to replicate.

Instead, after the transplant the medical and scientific team observed a drastic reduction in parameters related to HIV: no virus particles, an undetectable reservoir and no immune response that indicated that the body recognized the presence of the pathogen.

The “Geneva patient” is the first to achieve prolonged remission over time, said María Salgado, researcher at IrsiCaixa and coordinator of IciStem.

Transplants without the CCR5-delta 32 mutation had previously been performed in other patients with HIV, but if treatment was stopped, viral regrowth occurred, although slower than that which would be observed in a non-transplanted person with HIV, the researchers have indicated.

The research team has proposed several hypotheses to explain why this patient has managed to keep HIV under control without treatment and they point out that “alloimmunity is key, that is, the interaction between the immune system of the donor and that of the recipient.”

“After a transplant, the recipient’s immune cells perceive the donor’s immune cells as a threat, and vice versa, triggering a battle between the two immune systems,” Salgado said.

During this confrontation, many immune cells of the recipient, including those infected with HIV, die and 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 the cells that could reactivate the infection,” added IrsiCaixa.

In the case of the “Geneva patient”, the team chose to administer ruxolitinib, an immunosuppressive drug that aims to reduce the collateral damage caused in the immune battle, but which has also demonstrated in laboratory studies the ability to block the replication of the HIV and avoiding its reactivation.

This drug has been identified as another factor that has contributed to HIV remission.

Finally, the team highlighted the “crucial role of Natural Killer (NK) cells in this patient.”

These are cells that “patrol the body with the aim of finding dangerous cells, such as those infected by HIV, and eliminating them, as well as keeping the immune system alert.”

The case has been carried out within the framework of the IciStem consortium, co-coordinated by IrsiCaixa, which is a center promoted jointly by the “la Caixa” Foundation and the Department of Health of the Generalitat of Catalonia, together with the University of Utrecht. and it has been led by the Geneva University Hospital and the Pasteur Institute.