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Another cure of HIV by allogeneic stem cell transplantation

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Research

After ten years and multiple unsuccessful attempts, the only known case of cure from HIV infection – the “Berlin patient” – has apparently been reproduced. As a multidisciplinary team led by Ian H. Gabriel and Eduardo Olavarria from UCLH reported in Nature March 2019, an HIV-1-infected adult allo-transplanted for Hodgkin’s lymphoma from a CCR5Δ32/Δ32 donor has been HIV free after removal of antiretroviral therapy (ART) for more than 18 months. The rigorous study underlines several important notions that need to be repeated, given some of the public responses following the publication: (i) Allo-SCT is NOT a treatment option for HIV. This should already be obvious, since the CCR5Δ32 allele is only present in a small proportion of humankind (app. 1% of Caucasians are homozygous). Moreover, modern ART allows HIV-infected individuals an essentially normal life, whereas allo-SCT is only acceptable as treatment of life-threatening diseases. (ii) Even if an HIV-infected patient requires allo-SCT for a malignant neoplasia, the safety and efficacy with regard to treating the latter remain the primary objectives, i.e. neither selection of the treatment regimen nor the (CCR5Δ32/Δ32) donor choice should increase the risk for the patient. This is nicely illustrated by the current report. The unrelated (9/10) donor was only accepted since no fully matched donors were identified in the registry. And the London group applied a reduced-intensity conditioning regimen to ensure reduced toxicity, even though this might have impaired anti-HIV activity. Also, ART was withdrawn 16 months after SCT, only. Given these premises it can be anticipated that allo-SCT from CCR5Δ32/Δ32 donors will be remaining anecdotal. However, novel strategies of genome editing of autologous HSC and T cells with designer nucleases (e.g., CCR5-specific ZFN, TALEN, CRISPR/Cas) and HIV-targeting recombinases and nucleases (e.g., Brec1) might help overcoming the limitations associated with allo-SCT.

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