Autopsy study defines composition and dynamics of the HIV-1 reservoir after allogeneic hematopoietic stem cell transplantation with CCR5Δ32/Δ32 donor cells Journal Article


Authors: Huyveneers, L. E. P.; Bruns, A.; Stam, A.; Ellerbroek, P.; de Jong, D.; Nagy, N. A.; Gumbs, S. B. H.; Tesselaar, K.; Bosman, K.; Salgado, M.; Hütter, G.; Brosens, L. A. A.; Kwon, M.; Diez Martin, J.; van der Meer, J. T. M.; de Kort, T. M.; Sáez-Cirión, A.; Schulze zur Wiesch, J.; Boelens, J. J.; Martinez-Picado, J.; Kuball, J. H. E.; Wensing, A. M. J.; Nijhuis, M.; on behalf of the IciStem Consortium
Article Title: Autopsy study defines composition and dynamics of the HIV-1 reservoir after allogeneic hematopoietic stem cell transplantation with CCR5Δ32/Δ32 donor cells
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. © 2022 by the authors.
Keywords: tissue; hiv-1; cure; allo-hsct; reservoir; ccr5δ32; hiv persistence
Journal Title: Viruses
Volume: 14
Issue: 9
ISSN: 1999-4915
Publisher: MDPI  
Date Published: 2022-09-01
Start Page: 2069
Language: English
DOI: 10.3390/v14092069
PUBMED: 36146874
PROVIDER: scopus
PMCID: PMC9503691
DOI/URL:
Notes: Article -- Export Date: 3 October 2022 -- Source: Scopus
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  1. Jaap Jan Boelens
    134 Boelens