HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation

Ravindra K. Gupta (), Sultan Abdul-Jawad, Laura E. McCoy, Hoi Ping Mok, Dimitra Peppa, Maria Salgado, Javier Martinez-Picado, Monique Nijhuis, Annemarie M. J. Wensing, Helen Lee, Paul Grant, Eleni Nastouli, Jonathan Lambert, Matthew Pace, Fanny Salasc, Christopher Monit, Andrew J. Innes, Luke Muir, Laura Waters, John Frater, Andrew M. L. Lever, Simon G. Edwards, Ian H. Gabriel and Eduardo Olavarria
Additional contact information
Ravindra K. Gupta: Division of Infection and Immunity, UCL
Sultan Abdul-Jawad: Division of Infection and Immunity, UCL
Laura E. McCoy: Division of Infection and Immunity, UCL
Hoi Ping Mok: University of Cambridge
Dimitra Peppa: CNWL NHS Trust
Maria Salgado: IrsiCaixa AIDS Research Institute
Javier Martinez-Picado: IrsiCaixa AIDS Research Institute
Monique Nijhuis: University Medical Center
Annemarie M. J. Wensing: University Medical Center
Helen Lee: University of Cambridge
Paul Grant: UCLH
Eleni Nastouli: UCLH
Jonathan Lambert: UCLH
Matthew Pace: University of Oxford
Fanny Salasc: University of Cambridge
Christopher Monit: Division of Infection and Immunity, UCL
Andrew J. Innes: Imperial College Healthcare NHS Trust, Hammersmith Hospital
Luke Muir: Division of Infection and Immunity, UCL
Laura Waters: CNWL NHS Trust
John Frater: University of Oxford
Andrew M. L. Lever: University of Cambridge
Simon G. Edwards: CNWL NHS Trust
Ian H. Gabriel: Imperial College Healthcare NHS Trust, Hammersmith Hospital
Eduardo Olavarria: Imperial College Healthcare NHS Trust, Hammersmith Hospital

Nature, 2019, vol. 568, issue 7751, 244-248

Abstract: Abstract A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago1,2. The individual—who is known as the ‘Berlin patient’—underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin’s lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression.

Date: 2019
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DOI: 10.1038/s41586-019-1027-4

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