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

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

Data de publicació online: 05/03/2019 Revista: Nature

Abstract:

HIV-1 cure remains elusive with only one reported case a decade ago1,2. Termed the ‘Berlin patient’, the individual underwent two allogeneic haematopoietic stem-cell transplantation (allo-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. Critically, it is unclear which treatment or patient parameters contributed to this only documented case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An HIV-1-infected adult underwent allo-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 through a further 18 months. Plasma HIV-1 RNA has been undetectable at less than 1 copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assay from peripheral CD4 T lymphocytes shows 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 prior to transplant. CD4 T cells isolated from peripheral blood post-transplant did not express CCR5 and were only susceptible to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus (CMV)-specific responses were detectable. Likewise, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months post-treatment interruption it is premature to conclude that this patient has been cured, these data suggest that single allo-HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings further support the development of HIV remission strategies based on preventing CCR5 expression.

Autors: 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 Innes, Luke Muir, Laura Waters, John Frater, Andrew M. L. Lever, S. G. Edwards, Ian H. Gabriel & Eduardo Olavarria 

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