By Marie Rosenthal, MS
The seventh person with HIV who appears to be cured following a stem cell transplant (SCT) has an important distinction from the previous six people: The stem cell donor had a single instead of a double CCR5-Delta32 mutation, which is an important difference, explained Christian Gaebler, MD, MSc, an infectious disease specialist at Charité – Universitätsmedizin Berlin.
If providers can accept SCT donors with only a single mutation, HIV cure strategies could be more widely used.
Like Timothy Ray Brown, the first Berlin patient, who was also treated at Charité, this new patient developed acute myeloid leukemia (AML) after being diagnosed with HIV. The new patient, now 60 years of age, who wished to remain anonymous, tested positive for HIV in 2009 and was diagnosed with AML in 2015.
When it became clear that he would require an SCT, the team at Charité began looking for donors with the rare genetic mutation known as the “homozygous Delta32 CCR5 mutation because we know that this mutation provides natural resistant to HIV, and it has been crucial in the successful HIV cure cases,” Dr. Gaebler explained at AIDS 2024, held in Munich.
“However, in this instance our team of clinicians was unable to find a donor with the homozygous CCR5 mutation,” he said at a media briefing at AIDS 2024.
SCT is only an option for HIV patients who also develop certain cancers that do not respond to radiation or chemotherapy alone. The SCT from a healthy person in essence replaces the patient’s immune system.
To multiply, HIV enters various immune cells, which requires the CCR5 receptor. About 1% Europeans have a CCR5 receptor with a Delta32 mutation that prevents HIV from entering the cell, making people with this mutation naturally immune to HIV. If it is possible to find a stem cell donor whose tissue is a match for the recipient and that person carries this mutation, then SCT can cure the patient’s cancer and HIV.
Even though the donor was not herself immune, it became apparent that the SCT had been successful in curing HIV after the patient discontinued antiretroviral therapy (ART) on his own in 2018.
“It’s extremely surprising that the patient was cured even though the stem cell donor wasn’t immune to HIV,” said Dr. Gaebler, an expert on HIV and research group leader in the Department of Infectious Diseases and Critical Care Medicine at Charité and the Berlin Institute of Health at Charité. “In previous stem cell transplantation cases involving donors who were not immune, the virus resumed replicating after a few months.”
The second Berlin patient has had no detectable virus for more than five years even though he is not taking ART. This patient proves that it is possible to cure HIV even though a functional receptor for the virus to use remains, according to Dr. Gaebler.
“To our great surprise, it became clear that the stem cell transplantation had effectively depleted the HIV reservoir after the patient discontinued his recommended antiretroviral treatment on his own in 2018.
“We have performed comprehensive HIV reservoir testing, including in blood, but also various tissues, tissue reservoirs, and we have found no sign of HIV,” Dr. Gaebler said.
“The results of our studies suggest that it is possible to cure HIV, even when a functional receptor for the virus is present. And it shows that allogeneic immunity plays a fundamental role in HIV eradication beyond this rare Delta32 CCR5 mutation.”
Before undergoing SCT, the second Berlin patient was among the approximately 16% of people of European origin who, like the stem cell donor, carry both the healthy version and a mutated version of the CCR5 receptor in their cells (making them “heterozygous” for the Delta32 mutation). It is unclear whether this feature contributed to curing the patient.
Mr. Brown, an American living in Berlin, was diagnosed with HIV in 1995 and diagnosed with AML in 2006. By transplanting stem cells from a person with a homozygous (i.e., inherited from both parents) CCR5-Delta32 mutation, a team at Charité succeeded in treating his leukemia and eradicating HIV—the first such case worldwide. The case became public in 2008, but Mr. Brown was initially known as “the Berlin patient” to maintain his anonymity. He died in the United States in 2020 at the age of 54 after his leukemia returned.
