Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells

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 quanti...

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Detalles Bibliográficos
Autores: Huyveneers, Laura E. P., Bruns, Anke, Stam, Arjen, Ellerbroek, Pauline, de Jong, Dorien, Nagy, Noémi A., Gumbs, Stephanie B. H.|||0000-0003-0797-437X, Tesselaar, Kiki|||0000-0002-9847-0814, Bosman, Kobus, Salgado, Maria|||0000-0003-1551-7216, Hütter, Gero, Brosens, Lodewijk A. A., Kwon, Mi|||0000-0002-3855-7774, Diez Martin, Jose, van der Meer, Jan T. M., de Kort, Theun M., Sáez-Cirión, Asier|||0000-0003-2406-7536, Schulze zur Wiesch, Julian|||0000-0002-5033-1938, Boelens, Jaap Jan|||0000-0003-2232-6952, Martínez Picado, Francisco Javier|||0000-0002-4916-2129, Kuball, Jurgen|||0000-0002-3914-7806, Wensing, Annemarie M. J., Nijhuis, Monique|||0000-0001-6610-8282
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:281808
Acceso en línea:https://ddd.uab.cat/record/281808
https://dx.doi.org/urn:doi:10.3390/v14092069
Access Level:acceso abierto
Palabra clave:Allo-HSCT
CCR5Δ32
Cure
HIV-1
HIV persistence
Reservoir
Tissue
Descripción
Sumario: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.

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