HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2019
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| _version_ | 1826300004972625920 |
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| author | Gupta, R Abdul-Jawad, S McCoy, L Mok, H Peppa, D Salgado, M Martinez-Picado, J Nijhuis, M Wensing, A Lee, H Grant, P Nastouli, E Lambert, J Pace, M Salasc, F Monit, C Innes, A Muir, L Waters, L Frater, J Lever, A Edwards, S Gabriel, I Olavarria, E |
| author_facet | Gupta, R Abdul-Jawad, S McCoy, L Mok, H Peppa, D Salgado, M Martinez-Picado, J Nijhuis, M Wensing, A Lee, H Grant, P Nastouli, E Lambert, J Pace, M Salasc, F Monit, C Innes, A Muir, L Waters, L Frater, J Lever, A Edwards, S Gabriel, I Olavarria, E |
| author_sort | Gupta, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:10:33Z |
| format | Journal article |
| id | oxford-uuid:db671f89-7911-4194-bbdc-941bb004d176 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:10:33Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:db671f89-7911-4194-bbdc-941bb004d1762022-03-27T09:10:22ZHIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:db671f89-7911-4194-bbdc-941bb004d176EnglishSymplectic Elements at OxfordSpringer Nature2019Gupta, RAbdul-Jawad, SMcCoy, LMok, HPeppa, DSalgado, MMartinez-Picado, JNijhuis, MWensing, ALee, HGrant, PNastouli, ELambert, JPace, MSalasc, FMonit, CInnes, AMuir, LWaters, LFrater, JLever, AEdwards, SGabriel, IOlavarria, EHIV-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. |
| spellingShingle | Gupta, R Abdul-Jawad, S McCoy, L Mok, H Peppa, D Salgado, M Martinez-Picado, J Nijhuis, M Wensing, A Lee, H Grant, P Nastouli, E Lambert, J Pace, M Salasc, F Monit, C Innes, A Muir, L Waters, L Frater, J Lever, A Edwards, S Gabriel, I Olavarria, E HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation |
| title | HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation |
| title_full | HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation |
| title_fullStr | HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation |
| title_full_unstemmed | HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation |
| title_short | HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation |
| title_sort | hiv 1 remission following ccr5δ32 δ32 haematopoietic stem cell transplantation |
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