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The ‘Geneva patient’ was diagnosed with HIV in May 1990 and immediately began antiretroviral treatment.
The international consortium IciStem, co-coordinated by the Spanish Institute for AIDS Research, IrsiCaixa, has confirmed the first case of a patient who has achieved remission of the Human Immunodeficiency Virus (HIV) after a stem cell transplant who did not have the mutation that confers protection against the virus.
The individual, known as the ‘Geneva patient’ and whose identity has not been made public, is the sixth person to achieve HIV remission following a stem cell transplant.
He differs from the previous five in that he received stem cells from a donor who did not have the CCR5Δ32 mutation, known to confer protection against HIV, IrsiCaixa reported on Tuesday.
The study, published in the journal Nature Medicine , suggests that the CCR5Δ32 mutation “facilitates healing, but is not essential for it.”
“This case is particularly interesting because it shows us that HIV remission is possible even without the CCR5Δ32 mutation. In addition, we have identified the possible mechanisms that have allowed the cure in this case, opening up new avenues of research that bring us ever closer to the eradication of HIV,” said ICREA research professor at IrsiCaixa and IciStem coordinator Javier Martínez-Picado.
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 compatible donor.
One 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 the number of HIV-carrying cells in his body.
Before the transplant, despite optimization of antiretroviral treatment, the patient still had virus capable of replicating.
However, after the transplant, the medical and scientific team observed a dramatic reduction in HIV-related parameters: no virus particles, an undetectable reservoir, and no immune response indicating that the body was recognizing the presence of the virus.
“The Geneva patient was the first to achieve long-term remission,” said senior researcher at IrsiCaixa and coordinator of IciStem, Maria Salgado.
Transplants without the CCR5Δ32 mutation have been performed in other HIV patients before, but if treatment was stopped, viral regrowth occurred, albeit at a slower rate than would be seen in a non-transplanted HIV patient, the researchers said.
Hypothesis of success
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 donor’s immune system and that of the recipient.”
“After a transplant, the recipient’s immune cells perceive the donor’s as a threat, and vice versa, triggering a battle between the two immune systems,” Salgado said.
During this confrontation, many of the recipient’s immune cells, including those infected with HIV, die and are eventually replaced by those from 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,” added IrsiCaixa.
In the case of the ‘Geneva patient’, the team opted 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 HIV replication and prevent 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,” according to the entity.
The case has been carried out within the framework of the IciStem consortium, co-coordinated by IrsiCaixa, which is a centre jointly promoted by the ‘la Caixa’ Foundation and the Department of Health of the Generalitat de Catalunya, together with the University of Utrecht and led by the University Hospital of Geneva and the Pasteur Institute .
