Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells
Huyveneers, Laura E. P. (University Medical Center Utrecht)
Bruns, Anke (University Medical Center Utrecht)
Stam, Arjen (University Medical Center Utrecht)
Ellerbroek, Pauline (University Medical Center Utrecht)
de Jong, Dorien (University Medical Center Utrecht)
Nagy, Noémi A. (University Medical Center Utrecht)
Gumbs, Stephanie B. H. (University Medical Center Utrecht)
Tesselaar, Kiki (University Medical Center Utrecht)
Bosman, Kobus (University Medical Center Utrecht)
Salgado, Maria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Hütter, Gero (DKMS CC)
Brosens, Lodewijk A. A. (University Medical Center Utrecht)
Kwon, Mi (Hospital General Universitario Gregorio Marañón)
Diez Martin, Jose (Hospital General Universitario Gregorio Marañón)
van der Meer, Jan T. M. (Amsterdam UMC)
de Kort, Theun M. (Leiden University Medical Center)
Sáez-Cirión, Asier (Université Paris Cité)
Schulze zur Wiesch, Julian (UMC Hamburg-Eppendorf)
Boelens, Jaap Jan (Memorial Sloan Kettering Cancer Center)
Martínez Picado, Francisco Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Kuball, Jurgen (University Medical Center Utrecht)
Wensing, Annemarie M. J. (University Medical Center Utrecht)
Nijhuis, Monique (University Medical Center Utrecht)

Date:	2022
Abstract:	Allo-HSCT with CCR5Δ32/Δ32 donor cells is the only curative HIV-1 intervention. We investigated the impact of allo-HSCT on the viral reservoir in PBMCs and post-mortem tissue in two patients. IciS-05 and IciS-11 both received a CCR5Δ32/Δ32 allo-HSCT. Before allo-HSCT, ultrasensitive HIV-1 RNA quantification; HIV-1-DNA quantification; co-receptor tropism analysis; deep-sequencing and viral characterization in PBMCs and bone marrow; and post-allo-HSCT, ultrasensitive RNA and HIV-1-DNA quantification were performed. Proviral quantification, deep sequencing, and viral characterization were done in post-mortem tissue samples. Both patients harbored subtype B CCR5-tropic HIV-1 as determined genotypically and functionally by virus culture. Pre-allo-HSCT, HIV-1-DNA could be detected in both patients in bone marrow, PBMCs, and T-cell subsets. Chimerism correlated with detectable HIV-1-DNA LTR copies in cells and tissues. Post-mortem analysis of IciS-05 revealed proviral DNA in all tissue biopsies, but not in PBMCs. In patient IciS-11, who was transplanted twice, no HIV-1-DNA could be detected in PBMCs at the time of death, whereas HIV-1-DNA was detectable in the lymph node. In conclusion, shortly after CCR5Δ32/Δ32, allo-HSCT HIV-1-DNA became undetectable in PBMCs. However, HIV-1-DNA variants identical to those present before transplantation persisted in post-mortem-obtained tissues, indicating that these tissues play an important role as viral reservoirs.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Allo-HSCT ; CCR5Δ32 ; Cure ; HIV-1 ; HIV persistence ; Reservoir ; Tissue
Published in:	Viruses, Vol. 14 (september 2022) , ISSN 1999-4915

DOI: 10.3390/v14092069
PMID: 36146874

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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)
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