Sustained HIV remission after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells
Sáez-Cirión, Asier (Université Paris Cité (França))
Mamez, Anne-Claire (Geneva University Hospitals (Suïssa))
Avettand-Fenoel, Véronique (Virologie. CHU d'Orléans (França))
Nabergoj, Mitja (Institut Central des Hôpitaux (Suïssa))
Passaes, Caroline (Université Paris Cité (França))
Thoueille, Paul (Lausanne University Hospital (Suïssa))
Decosterd, Laurent (Lausanne University Hospital (Suïssa))
Hentzien, Maxime (Geneva University Hospitals (Suïssa))
Perdomo-Celis, Federico (Université Paris Cité (França))
Salgado, Maria (Instituto de Salud Carlos III)
Nijhuis, Monique (University of the Witwatersrand (Johannesburg, Sud-àfrica))
Mélard, Adeline (Institut Cochin-CNRS 8104/INSERM U1016/Université de Paris (França))
Gardiennet, Elise (Institut Cochin-CNRS 8104/INSERM U1016/Université de Paris (França))
Lorin, Valerie (Université Paris Cité (França))
Monceaux, Valérie (Université Paris Cité (França))
Chapel, Anaïs (Université Paris Cité (França))
Gourvès, Maël (Université Paris Cité (França))
Lechartier, Marine (Université Paris Cité (França))
Mouquet, Hugo (Université Paris Cité (França))
Wensing, Annemarie (University of the Witwatersrand (Johannesburg, Sud-àfrica))
Martínez Picado, Francisco Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Yerly, Sabine (Geneva University Hospitals (Suïssa))
Rougemont, Mathieu (Unaffiliated (Suïssa))
Calmy, Alexandra (Geneva University Hospitals (Suïssa))
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5Δ32 homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5 donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles) wild-type CCR5 donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4 T cells obtained after antiretroviral treatment interruption, while CD4 T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5.
Grants:	Agencia Estatal de Investigación PID2022-139271OB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Adult ; CD4-Positive T-Lymphocytes ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; HIV Infections ; HIV-1 ; Humans ; Male ; Middle Aged ; Receptors, CCR5 ; Remission Induction ; Tissue Donors ; Transplantation, Homologous ; Viral Load
Published in:	Nature Medicine, Vol. 30 Núm. 12 (december 2024) , p. 3544-3554, ISSN 1546-170X

DOI: 10.1038/s41591-024-03277-z
PMID: 39222660

19 p, 4.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles