The latest HIV treatment case shows unexpected developments

first HIV Curative cases in which stem cell donors had a single gene mutation rather than a double one have opened up the donor pool in new curative efforts to make stem cell transplants more widely available.

This anonymous patient is the first to achieve long-term HIV remission (in this case, nearly six years) after receiving a single CCR5 delta 32 mutation. Specifically, the patient received a CCR5 wild-type delta 32 transplant (heterozygous transplant), Acute myeloid leukemiaThe researchers reported their findings at the International AIDS Conference 2024 in Munich, Germany.

Other treatments involve donors who have two copies of the CCR5 delta 32 mutation, known as homozygotes.

The researchers are calling the anonymous patient “the next Berlin patient,” a nod to the now-famous American patient, Timothy Ray Brown, who was living in Germany at the time and was the first to be cured of HIV.

Brown, who was called an ambassador of hope, never tested positive for HIV again, but at the age of 54, the leukemia that had led to his HIV treatment spread to his brain and spinal cord and took his life.

Expanding the donor pool

Since then, four other people who received homozygous stem cell transplants with the double-copy mutation have experienced long-term HIV remission.

Another case, known as the “Geneva patient,” received a stem cell transplant from a wild-type CCR5 donor, and was reported by researchers in Geneva, Switzerland, at a conference last year.

“The use of donors with single mutations, in addition to donors with double mutations, could significantly expand the donor pool and the availability of allogeneic stem cell transplantation,” said Christian Gaebler, MD, co-leader of the Programme for Personalised Infectious Disease Medicine at the Berlin Institutes of Health and associate professor at Charité University Medicine Berlin, who presented the case at the meeting.

“If we can't find a donor with the delta 32 mutation, it may be beneficial to accept a heterozygous donor, because they are hard to find, especially outside of Western and Nordic countries, where finding a homozygous delta 32 donor is nearly impossible,” Gaebler said in an interview. “Heterozygous donors are easier to find.”

“This case gives us hope that there may still be treatments and underlying mechanisms that we currently lack,” said Christoph Spinner, MD, MBA, infectious diseases specialist at the Technical University Hospital Munich and co-chair of the AIDS 2024 conference.

“Research is needed to understand the findings from this case and apply them to treatment research around the world,” he said.

Reducing the HIV reservoir

A key mechanism for treatment is HIV reservoir depletion, Gaebler says, but more research is needed to better understand its role.

Dr. Gaebler explained that the recently cured patient originally underwent a stem cell transplant to treat his acute myeloid leukemia, and more than five years after stem cell transplant and after discontinuing antiretroviral therapy, the patient's HIV DNA and HIV RNA are undetectable, and his CD4+ and CD8+ T-cell counts have increased.

“When we look at the next patient in Berlin and see that he is approaching six years of HIV remission, we can say with confidence that he will achieve HIV reservoir reduction, HIV remission and possibly an HIV cure, regardless of CCR5 status,” Gaebler said.

“These early cases of HIV cure sparked a lot of research looking at CCR5, particularly the regulation of CCR5 expression, and gene-edited cells. [and] “Inhibition of CCR5,” he noted after the presentation, “is all very plausible and probably plays some role, but it probably comes down to a combination of these factors.”