The first HIV cure case in which the stem cell donor had a single — rather than double — gene mutation is opening the donor pool in renewed cure efforts to make stem cell transplants more widely available.
The anonymous patient is the first to achieve long-term HIV remission — in this case approaching 6 years — after receiving a single CCR5 delta 32 mutation. Specifically, the patient received a CCR5 wild-type, delta 32 transplant, known as a heterozygous transplant, for acute myeloid leukemia, investigators reported at the International AIDS Conference 2024 in Munich, Germany.
Other cures have involved donors with two copies of the CCR5 delta 32 mutation, known as homozygous.
Researchers are calling the anonymous patient “the next Berlin patient,” an homage to Timothy Ray Brown, the first, now renowned, American patient living at the time in Germany who was cured of HIV.
Brown — dubbed an ambassador of hope — would never test positive for HIV again, but at age 54, it would be the leukemia that led to his HIV cure that would take Brown’s life after spreading to his brain and spinal cord.
Expanding the Donor Pool
Since then, four others who received the dual-copy mutation in a homozygous stem cell transplant have experienced long-term HIV remission.
Another case, known as the “Geneva patient,” received a stem cell transplant from a wild-type CCR5 donor. Researchers from Geneva, Switzerland, reported that case last year at the conference.
Using donors with single mutations in addition to those with double mutations could meaningfully expand the pool of donors and the availability of allogeneic stem cell transplantation, said Christian Gaebler, MD, coleader of the personalized infectious medicine program at the Berlin Institute of Health and associate professor at Charité – Universitätsmedizin Berlin, who presented the case at the conference.
“When we don’t find a donor with these delta 32 mutations — and it’s hard to find them, especially in geographical regions outside western or northern countries where it’s almost impossible to find a homozygous delta 32 donor — it may be beneficial to take a heterozygous donor,” Gaebler said during an interview. “They’re easier to find.”
“This case is giving us hope that there is still a cure and underlying mechanisms that we’re currently not understanding,” said Christoph Spinner, MD, MBA, an infectious disease specialist at the University Hospital of the Technical University of Munich, and AIDS 2024 conference co-chair.
“Research is needed to understand and translate the findings of this case for the cure research around the globe,” he said.
Reducing the HIV Reservoir
The key mechanism in a cure is depletion of the HIV reservoir, Gaebler said, but more work is needed to better understand its role.
The most recent cured patient had the stem cell transplant to treat acute myeloid leukemia initially, Gaebler explained, and more than 5 years after the stem cell transplant and after discontinuing antiretroviral therapy, the patient has undetectable levels of HIV DNA and HIV RNA as well as higher levels of CD4+ and CD8+ T cells, he said.
“When we see this next Berlin patient and that we’re coming close to 6 years of HIV remission, I think we can quite confidently say we can have HIV reservoir reduction, HIV remission, and potentially HIV cure independent of the CCR5 status,” Gaebler said.
“These initial cases of HIV cure have triggered a lot of studies looking at CCR5 and basically modulating CCR5 expression, gene-edited cells, [and] CCR5 blockage,” he pointed out after his presentation. “This is all very valid and it will likely play a role, but it probably comes down to a combination of these things,” he said.
