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

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.

[Stolen from Nature.com: https://www.nature.com/articles/s41586-019-1027-4]

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