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dc.contributor.authorGupta, Ravindraen
dc.contributor.authorSultan, Abdul-jawaden
dc.contributor.authorMcCoy, Lauraen
dc.contributor.authorMok, Hoien
dc.contributor.authorPeppa, Dimitrien
dc.contributor.authorSalgado, Mariaen
dc.contributor.authorMartinez-Picado, Javieren
dc.contributor.authorNijhuis, Moniqueen
dc.contributor.authorWensing, Annemarieen
dc.contributor.authorLee, Helenen
dc.contributor.authorGrant, Paulen
dc.contributor.authorNastouli, Elenien
dc.contributor.authorLambert, Jonathanen
dc.contributor.authorPace, Matthewen
dc.contributor.authorSalasc, Fannyen
dc.contributor.authorMonit, Christopheren
dc.contributor.authorInnes, Andrewen
dc.contributor.authorMuir, Lukeen
dc.contributor.authorWaters, Lauraen
dc.contributor.authorFrater, Johnen
dc.contributor.authorLever, Andrewen
dc.contributor.authorEdwards, SGen
dc.contributor.authorGabriel, Ianen
dc.contributor.authorOlavarria, Eduardoen
dc.date.accessioned2019-02-28T00:30:56Z
dc.date.available2019-02-28T00:30:56Z
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/290071
dc.description.abstractHIV-1 cure remains elusive with only one reported case a decade ago. Termed the “Berlin Patient”, the individual underwent 2 allogeneic Hematopoietic 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 leukemia. 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 <1 copy/ml 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 whilst 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.
dc.description.sponsorshipNIHR AmFAR
dc.publisherNature Publishing Group
dc.titleHIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem cell transplantationen
dc.typeArticle
prism.publicationNameNatureen
dc.identifier.doi10.17863/CAM.37294
dcterms.dateAccepted2019-02-26en
rioxxterms.versionofrecord10.1038/s41586-019-1027-4en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-02-26en
dc.contributor.orcidGupta, Ravindra [0000-0001-9751-1808]
dc.contributor.orcidMok, Hoi [0000-0003-1402-7194]
dc.contributor.orcidSalasc, Fanny [0000-0002-6574-1358]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/N02043X/1)
cam.issuedOnline2019-03-05en
dc.identifier.urlhttps://rdcu.be/bpBaBen
cam.relation.webpagehttps://rdcu.be/bpBaB
rioxxterms.freetoread.startdate2019-09-05


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