Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells
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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; Bruns, Anke; Stam, Arjen; Ellerbroek, Pauline; de Jong, Dorien; Nagy, Noémi A; Gumbs, Stephanie B H; Tesselaar, Kiki; Bosman, Kobus; Salgado, Maria; Hütter, Gero; Brosens, Lodewijk A A; Kwon, Mi; Diez Martin, Jose; van der Meer, Jan T M; de Kort, Theun M; Sáez-Cirión, Asier; Schulze Zur Wiesch, Julian; Boelens, Jaap Jan; Martinez-Picado, Javier; Kuball, Jürgen H E; Wensing, Annemarie M J; Nijhuis, Monique; IciStem Consortium.
In: VIRUSES-BASEL, Vol. 14, No. 9, 2069, 17.09.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells
AU - Huyveneers, Laura E P
AU - Bruns, Anke
AU - Stam, Arjen
AU - Ellerbroek, Pauline
AU - de Jong, Dorien
AU - Nagy, Noémi A
AU - Gumbs, Stephanie B H
AU - Tesselaar, Kiki
AU - Bosman, Kobus
AU - Salgado, Maria
AU - Hütter, Gero
AU - Brosens, Lodewijk A A
AU - Kwon, Mi
AU - Diez Martin, Jose
AU - van der Meer, Jan T M
AU - de Kort, Theun M
AU - Sáez-Cirión, Asier
AU - Schulze Zur Wiesch, Julian
AU - Boelens, Jaap Jan
AU - Martinez-Picado, Javier
AU - Kuball, Jürgen H E
AU - Wensing, Annemarie M J
AU - Nijhuis, Monique
AU - IciStem Consortium
PY - 2022/9/17
Y1 - 2022/9/17
N2 - 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.
AB - 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.
KW - Autopsy
KW - HIV Infections
KW - HIV Seropositivity
KW - HIV-1/genetics
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - RNA
U2 - 10.3390/v14092069
DO - 10.3390/v14092069
M3 - SCORING: Journal article
C2 - 36146874
VL - 14
JO - VIRUSES-BASEL
JF - VIRUSES-BASEL
SN - 1999-4915
IS - 9
M1 - 2069
ER -
