HIV-1 remission following CCR5 Delta 32/Delta 32 haematopoietic stem-cell transplantation
Por:
Gupta, RK, Abdul-Jawad, S, Mccoy, LE, Mok, HP, Peppa, D, Salgado, M, Martinez-Picado, J, Nijhuis, M, Wensing, AMJ, Lee, H, Grant, P, Nastouli, E, Lambert, J, Pace, M, Salasc, F, Monit, C, Innes, AJ, Muir, L, Waters, L, Frater, J, Lever, AML, Edwards, SG, Gabriel, IH and Olavarria, E
Publicada:
11 abr 2019
Categoría:
Multidisciplinary
Resumen:
A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago(1,2). 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 (CCR5 Delta 32/Delta 32) 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 CCR5 Delta 32/Delta 32 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 CCR5 Delta 32 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.
Filiaciones:
Gupta, RK:
UCL, Div Infect & Immun, London, England
UCLH, Dept Infect, London, England
CNWL NHS Trust, Dept HIV, Mortimer Market Ctr, London, England
Univ Cambridge, Dept Med, Cambridge, England
Africa Hlth Res Inst, Durban, South Africa
Abdul-Jawad, S:
UCL, Div Infect & Immun, London, England
Mccoy, LE:
UCL, Div Infect & Immun, London, England
Mok, HP:
Univ Cambridge, Dept Med, Cambridge, England
Peppa, D:
CNWL NHS Trust, Dept HIV, Mortimer Market Ctr, London, England
Univ Oxford, Nuffield Dept Med, Oxford, England
:
irsiCaixa AIDS Res Inst, Badalona, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Vic, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
Nijhuis, M:
Univ Med Ctr, Dept Med Microbiol, Translat Virol, Utrecht, Netherlands
Wensing, AMJ:
Univ Med Ctr, Dept Med Microbiol, Translat Virol, Utrecht, Netherlands
Lee, H:
Univ Cambridge, Dept Haematol, Cambridge, England
Grant, P:
UCLH, Dept Virol, London, England
Nastouli, E:
UCLH, Dept Virol, London, England
Lambert, J:
UCLH, Dept Haematol, London, England
Pace, M:
Univ Oxford, Nuffield Dept Med, Oxford, England
Salasc, F:
Univ Cambridge, Dept Med, Cambridge, England
Monit, C:
UCL, Div Infect & Immun, London, England
Innes, AJ:
Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Dept Clin Haematol, London, England
Imperial Coll London, London, England
Muir, L:
UCL, Div Infect & Immun, London, England
Waters, L:
CNWL NHS Trust, Dept HIV, Mortimer Market Ctr, London, England
Frater, J:
Univ Oxford, Nuffield Dept Med, Oxford, England
NIHR Oxford Biomed Res Ctr, Oxford, England
Lever, AML:
Univ Cambridge, Dept Med, Cambridge, England
Natl Univ Singapore, Dept Med, Singapore, Singapore
Edwards, SG:
CNWL NHS Trust, Dept HIV, Mortimer Market Ctr, London, England
Gabriel, IH:
Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Dept Clin Haematol, London, England
Imperial Coll London, London, England
Chelsea & Westminster Hosp Fdn NHS Trust, Dept Haematol, London, England
Olavarria, E:
Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Dept Clin Haematol, London, England
Imperial Coll London, London, England
Green Submitted, Green Accepted
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