Media release

From: Springer Nature

Virology: HIV-1 remission after heterozygous CCR5 Δ32 stem cell transplant

Details of a 60-year-old male individual from Germany who achieved sustained HIV remission after a stem cell transplant, the seventh-known case reported to date, are published in Nature this week. This individual received cells with just one copy of a mutated gene for a protein required in HIV-1 infection (unlike earlier remissions that used cells with two copies), which suggests that the pool of stem cell donors with the potential to eliminate HIV could be larger than previously thought.

Most of the six previously reported patients who experienced clearance of HIV following stem cell transplants for cancer had received cells that were homozygous (contained two copies) for a mutation in a gene that encodes the protein CCR5. The normal (wild-type) version of this protein forms a receptor that is essential for HIV infection; cells with the mutant version (CCR5 Δ32) are therefore resistant to HIV. It had been assumed that these homozygous donor cells were needed, but recent studies have indicated HIV remission is possible with donor cells that express wild-type CCR5, suggesting that other factors may contribute to the clearance of the virus.

Christian Gaebler and colleagues report a case of HIV-1 remission achieved after a stem cell transplant in which the donor cells carried only one copy of the mutated receptor gene (CCR5 Δ32 heterozygous). The patient, a 60-year-old male individual from Berlin, was diagnosed with HIV in 2009 and developed acute myeloid leukaemia in 2015. The patient underwent an allogeneic stem cell transplant to treat the cancer, although a homozygous CCR5 Δ32 donor could not be found. Three years after the transplant, the patient stopped antiretroviral therapy and no evidence of HIV-1 replicating in the patient was found six years after the transplant.

These findings provide further evidence that the presence of cells that lack CCR5 expression is not a prerequisite to achieve HIV-1 remission after stem cell transplantation. Although the precise mechanisms that underlie HIV-1 clearance are uncertain, the latest case indicates that the pool of potential donor cells can be expanded to include heterozygous CCR5 Δ32 cells.

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Two additional papers by independent groups will also publish at the same time.

Steven Deeks and colleagues identify immune features associated with control of HIV-1 in individuals who exhibited HIV-1 replication control after receiving combination immunotherapy. Although the trial did not have a control arm and therefore firm conclusions cannot be made about the efficacy of the combination immunotherapy, the group identified features of T cells that were associated with virus control in those individuals who showed slower rebound after therapy. David Collins and colleagues identified similar T cell features in individuals who exhibited virus control in previously reported clinical trials of interventions to induce HIV-1 remission.