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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells
Viruses, Volume 14, No. 9, Article 2069, Year 2022
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Description
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.
Authors & Co-Authors
Huyveneers, Laura E.P.
Netherlands, Utrecht
University Medical Center Utrecht
de Jong, Dorien C.C.M.
Netherlands, Utrecht
University Medical Center Utrecht
Tesselaar, Kiki
Netherlands, Utrecht
University Medical Center Utrecht
Salgado, María
Spain, Badalona
Fundació Institut Dinvestigació en Ciències de la Salut Germans Trias I Pujol
Spain, Madrid
Instituto de Salud Carlos Iii
Brosens, Lodewijk Adriaan Anton
Netherlands, Utrecht
University Medical Center Utrecht
Díez-Martín, José Luís
Spain, Madrid
Hospital General Universitario Gregorio Marañón
van der Meer, Jan T.M.
Netherlands, Amsterdam
Amsterdam Umc
Sáez-Cirión, Asier
France, Paris
Institut Pasteur, Paris
Schulze-Zur-Wiesch, Julian
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Boelens, Jaap Jan
Netherlands, Utrecht
Princess Máxima Center for Pediatric Oncology
United States, New York
Memorial Sloan-kettering Cancer Center
Martínez-Picado, Javier
Spain, Badalona
Fundació Institut Dinvestigació en Ciències de la Salut Germans Trias I Pujol
Spain, Madrid
Instituto de Salud Carlos Iii
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Wensing, Annemarie Marie J.
Netherlands, Utrecht
University Medical Center Utrecht
Nijhuis, Monique M.
Netherlands, Utrecht
University Medical Center Utrecht
Statistics
Citations: 5
Authors: 13
Affiliations: 13
Identifiers
Doi:
10.3390/v14092069
ISSN:
19994915
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Design
Randomised Control Trial