4 months ago
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Doctors have apparently cured another person of HIV using a bone marrow transplant. Unlike previous cases, however, the patient was cured without needing donated stem cells from someone genetically immune to HIV. This development could change our understanding of how best to treat similar patients in the future, though these transplants still aren’t a practical solution for most people living with the virus.
The success story is a 60-year-old man from Germany who was diagnosed with HIV in 2009. In 2015, he also became diagnosed with acute myeloid leukemia (AML), a form of blood cancer. Doctors eventually advised that he undergo a bone marrow transplant for his AML, a radical treatment that functionally tries to replace a person’s immune system with one belonging to a healthy donor.
Doctors at Charité Universitatsmedizin Berlin performed the man’s transplant. Years earlier, in 2007, a team there performed the first bone marrow transplant for cancer that resulted in an HIV cure. At the time, the patient decided to stay anonymous and was nicknamed the Berlin Patient. He later revealed himself as Timothy Ray Brown and remained an HIV/AIDS advocate until his death in 2020 from a recurrence of his leukemia. This latest case has also chosen to go anonymous and has been dubbed the next Berlin Patient.
Brown and most others like him in the years since have received bone marrow from donors with two copies of a particular mutation in their CCR5 gene, which regulates the CCR5 receptor found on white blood cells. The mutation, called CCR5-delta 32, makes immune cells naturally resistant to infection from strains of HIV-1 (the more common type of HIV). By transplanting stem cells containing the mutation to HIV patients, the hope is that you can transfer over that resistance as well, allowing their bodies to permanently eliminate the virus.
Just a small percentage of people carry two copies of the CCR5-delta 32 mutation, however, and Charité doctors were only able to find a compatible donor for their patient who carried one copy. But to everyone’s surprise, the switch still worked. The patient chose to stop taking his HIV medication in 2018 and tests have continued to show no traces of the virus in his system (he also remains cancer-free). The man is now believed to be the seventh person cured of HIV using stem cells, but the first without needing both copies of the CCR5-delta 32 mutation.
The man’s case was presented this week at AIDS 2024, the 25th International AIDS Conference.
“A healthy person has many wishes, a sick person only one,” said the next Berlin Patient in a statement released by the International AIDS Society, which hosts the conference.
At this point, it’s not clear exactly how the next Berlin Patient was able to clear his HIV completely. People with only one copy of the CCR5-delta 32 mutation can still get infected by HIV, though it does seem to reduce the odds of catching it. So it’s possible that even one copy is enough to help eliminate its presence in someone already infected. But it’s also possible that simply flushing away an HIV-infected person’s immune system and replacing it with a new one, regardless of whether the CCR5-delta 32 mutation is around, can do the same. That said, other HIV patients who have received stem cell transplants from non-CCR5-delta 32 donors have seen their infections rebound within months, so other factors might be important to a cure, such as how quickly the donated immune system takes over.
Stem cell transplants are a last resort treatment for conditions like leukemia, due to their risky, even potentially life-threatening side effects. And these days most people with HIV can keep the virus in check with antiretrovirals, to the point of no longer being contagious to others. So these transplants will never become a widely used cure for HIV. But the lessons learned from these patients could help scientists develop more practical cures for HIV or help patients who need stem cell transplants for other reasons.
“The next Berlin Patient’s experience suggests that we can broaden the donor pool for these kinds of cases, although stem cell transplantation is only used in people who have another illness, such as leukemia,” said Sharon Lewin, president of the International AIDS Society, in a statement. “This is also promising for future HIV cure strategies based on gene therapy because it suggests that we don’t have to eliminate every single piece of CCR5 to achieve remission.”
