‘Exceptional case’: A man referred to as a ‘Geneva patient’ is in long-term HIV recovery after receiving a bone marrow transplant that lacks a known mutation that blocks the virus, news that potentially opens avenues for research.
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His case was presented Thursday, ahead of the AIDS Society’s International Conference which opens Sunday in Brisbane, Australia.
Prior to him, five people had already been considered cured of HIV infection after undergoing a bone marrow transplant.
The recovered patients had leukemias and benefited from stem cell transplants that rejuvenated their immune systems.
Each time, their donors presented a rare mutation in the gene known as CCR5 delta 32, a genetic mutation known to prevent HIV from entering cells.
For a “patient from Geneva,” the situation is different: in 2018, to treat a particularly aggressive form of leukemia, he benefited from a stem cell transplant.
This time, however, the transplant came from a donor who did not carry the famous CCR5 mutation.
Thus, unlike the cells of other people who were considered cured, the donor’s cells theoretically allowed HIV to multiply.
However, the virus remains undetectable 20 months after cessation of antiretroviral therapy in this patient followed at the University Hospitals of Geneva, in collaboration with the Institut Pasteur, the Cochin Institute and the International IciStem Consortium.
His antiretroviral therapy was gradually reduced and permanently discontinued in November of 2021.
“undetectable”
Analyzes conducted during the 20 months following discontinuation of treatment did not reveal any viral particles, any activated viral reservoir, or an increase in immune responses against the virus in this person’s organism.
Scientific teams cannot rule out that the virus is still present, but they consider this to be a new remission of HIV infection.
Other HIV-positive patients before him had benefited from marrow transplants without the famous protective mutation.
“The virus reappeared after a few months,” the head of the viral reservoirs and immune control unit at the Pasteur Institute, Asyr Saez Sirion, told AFP.
“We consider that when we get past 12 months of undetectable virus, the likelihood that it will remain undetectable in the future increases exponentially,” he adds.
How do we explain such a phenomenon in this patient? Several hypotheses are on the table.
“In this particular case, the transplant may have made it possible to eliminate all affected cells without the need for the famous mutation,” suggests Mr. Saez-Sirion. “Or perhaps his immunosuppressive therapy, necessary after transplantation, may have played a role.”
“miracle”
This long remission is “encouraging,” but it is “one virion.” [une particule virale infectieuse] It could lead to a resurgence of the virus,” warned Sharon Lewin, president of the International AIDS Society Conference.
This patient “will need to be closely monitored over the next few months, if not years. It is impossible to predict the likelihood of a recovery,” he added.
If these lapses fuel the hope of one day beating HIV, bone marrow transplantation remains a heavy and risky operation: it is not adaptable to most HIV carriers.
According to the researchers, this “exceptional” case in any case opens up new horizons for research, such as the role that immunosuppressive therapies can play.
“This also encourages us to continue studying specific cells of innate immunity” (the first defensive barrier against various pathogens), which are likely to affect virus control, adds Asier Sáez-Cirión.
“We know that we will not transplant all patients with HIV, but this opens the doors to try to have permanent remission in the absence of a transplant with a mutation,” Professor Alexandra Calmy, Head of the HIV Unit at the University Hospitals of Geneva, confirmed on Thursday.
The patient, who has been living with HIV since the early 1990s, wishes to remain anonymous for the time being. Professor Calmy stressed that he considers this remission “a miracle that he dedicates to the future and to research”.
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