Long-Term HIV Remission Breakthrough Shifts Cure Research Focus
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A German man, often referred to as Berlin 2 (B2) and reported to be 60 years old, has become the seventh known patient worldwide to achieve long-term remission from HIV. This extraordinary development occurred six years after he received a stem cell transplant to treat an aggressive form of acute myeloid leukemia (cancer).
The patient was first diagnosed with HIV in 2009 and developed leukemia in 2015. Following chemotherapy to wipe out most of his immune system, he received a full stem cell transplant later that year. In 2018, against medical advice, he stopped taking antiretroviral therapy (ART). Since that time, virus levels in his body have remained undetectable and may be nonexistent.
While ART is the cornerstone of treatment for HIV, making life manageable and suppressing the virus’s progression, it does not eliminate the virus. HIV is a tenacious virus that attacks immune cells and can remain dormant within long-lived immune cells, forming latent reservoirs that are essentially invisible to the immune system and untouched by ART. If ART is stopped, the virus can re-emerge. Full stem cell transplants, however, have a proven record in depleting these reservoirs.
In five of the seven documented cases of long-term HIV remission (including the original Berlin patient, London, Duesseldorf, New York, and City of Hope patients), the stem cell donors possessed two copies (homozygous) of a rare mutation called CCR5 Δ32. This mutation breaks the CCR5 "keyhole" that HIV exploits to attach to and enter host cells, essentially preventing the virus from unlocking the door and depriving it of new places to hide.
What makes B2's case a significant breakthrough is the characteristic of his donor. Unlike the majority of successful previous cases, B2 received donor stem cells containing only one copy (heterozygous) of the CCR5 Δ32 mutation. B2 himself already had one inherited copy of the mutation. Previously, experts had assumed that homozygous donor cells (two copies) were essential for curing HIV.
The success achieved with B2—who remains HIV-free three years after stopping ART—suggests that double copies of CCR5 Δ32 are not a requirement for durable HIV remission after stem cell treatment. This shifts the focus away from relying on rare "unicorn donors" who carry two copies of the mutation.
Researchers led by immunologist Christian Gaebler believe this result offers a tantalizing new path toward understanding other potential ways of curing HIV. The key may be mechanisms like the graft-versus-reservoir response—where the new donor cells recognize and wipe out remaining HIV hideouts—and sustained reduction of persistent reservoirs.
This case, along with the sixth patient from Geneva whose donor completely lacked the CCR5 Δ32 allele, supports the idea that significant reductions of persistent reservoirs can lead to HIV cure independent of homozygous CCR5 Δ32-mediated viral resistance. These mechanisms may be achievable through pharmaceutical treatments and gene editing, and research is already underway to that effect.
The success of the stem cell procedure underscores the critical importance of modulating and potentially eliminating the HIV reservoir in strategies aimed at long-term remission and cure. The findings for the Berlin patient (B2) were published in the journal Nature.
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Keywords: Long-Term HIV Remission Breakthrough
Long-Term HIV Remission Breakthrough
