2023-07-20 12:35:39
“What is happening to me is magnificent, magical”. A man, who prefers to remain anonymous, is officially in long remission from HIV after a bone marrow transplant that did not show a mutation known to block the virus. Nicknamed the “Geneva patient”, he had been living with the virus since the early 1990s. His case was presented this Thursday in Brisbane, ahead of the Conference of the International AIDS Society which will open on Sunday in Australia.
A sixth patient in remission not quite like the others
Before him, five people have already been considered probably cured of HIV infection after receiving a bone marrow transplant. The cured patients all had a very particular situation in common. They were suffering from blood cancers and benefited from a stem cell transplant which deeply renewed their immune system. But each time, their donor presented a rare mutation of a gene known as CCR5 delta 32, a genetic mutation known to prevent the entry of HIV into cells.
For the “patient from Geneva”, a 49-year-old man, the situation is different: in 2018, to treat a particularly aggressive form of leukemia, he benefited from a stem cell transplant. But this time, the transplant came from a donor who did not carry the famous CCR5 mutation. Thus, unlike the cells of other people considered cured, those of the donor person theoretically allowed HIV to reproduce. And yet, the virus remains undetectable 20 months after the interruption of antiretroviral treatment in this patient followed at the University Hospitals of Geneva, in collaboration with the Institut Pasteur, the Institut Cochin and the international consortium IciStem.
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No virus particles detected
His antiretroviral treatment was gradually reduced and definitively stopped in November of 2021. And the analyzes carried out during the 20 months which followed the cessation of treatment detected neither viral particles, nor an activatable viral reservoir, nor an increase in immune responses against the virus in the organism of this person. The scientific teams cannot exclude that the virus still persists, but they consider that this is a new remission of the HIV infection.
Other patients with HIV had benefited before him from marrow transplants without the famous protective mutation. But “the virus reappeared after a few months,” says Asier Sáez-Cirión, head of the Viral Reservoirs and Immune Control Unit at the Institut Pasteur. “We consider that when we exceed 12 months of undetectable virus, the probability that it will remain undetectable in the future increases significantly,” he adds.
Why did it work?
How to explain such a phenomenon in this patient? Several hypotheses are on the table. “In this specific case, perhaps the transplant made it possible to eliminate all the infected cells without the need for the famous mutation”, suggests Asier Sáez-Cirión. “Or maybe his immunosuppressive treatment, required after the transplant, played a role.”
This long remission is “encouraging” but “a single virion (an infectious viral particle, editor’s note) can cause the virus to rebound”, warned Sharon Lewin, president of the Conference of the International AIDS Society. This patient “will need to be monitored closely over the next few months, if not years. The likelihood of a rebound is impossible to predict,” he added.
Hope but…
If these remissions nourish the hope of one day overcoming HIV, a bone marrow transplant remains a very heavy and risky operation: it is not adaptable to most carriers of the virus.
These cases nevertheless open up new avenues of research, such as the possible role that immunosuppressive treatments could play. “This also encourages us to continue to study certain cells of innate immunity” (the first defense barrier against various pathogens, Ed), likely to influence the control of the virus, adds Asier Sáez-Cirión.
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