Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5 Delta 32/Delta 32 Donor Cells
Por:
Huyveneers, LEP, Bruns, A, Stam, A, Ellerbroek, P, de Jong, D, Nagy, NA, Gumbs, SBH, Tesselaar, K, Bosman, K, Salgado, M, Hutter, G, Brosens, LAA, Kwon, M, Martin, JD, van der Meer, JTM, de Kort, TM, Saez-Cirion, A, zur Wiesch, JS, Boelens, JJ, Martinez-Picado, J, Kuball, JHE, Wensing, AMJ and Nijhuis, M
Publicada:
1 sep 2022
Resumen:
Allo-HSCT with CCR5 Delta 32/Delta 32 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 CCR5 Delta 32/Delta 32 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 CCR5 Delta 32/Delta 32, 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.
Filiaciones:
Huyveneers, LEP:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
Bruns, A:
Univ Med Ctr Utrecht UMCU, Dept Internal Med & Infect Dis, NL-3584 CX Utrecht, Netherlands
Univ Med Ctr Utrecht UMCU, Dept Hematol, NL-3584 CX Utrecht, Netherlands
Stam, A:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
Ellerbroek, P:
Univ Med Ctr Utrecht UMCU, Dept Internal Med & Infect Dis, NL-3584 CX Utrecht, Netherlands
de Jong, D:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
Nagy, NA:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
Gumbs, SBH:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
Tesselaar, K:
Univ Med Ctr Utrecht UMCU, Cent Lab Translat Immunol, NL-3584 CX Utrecht, Netherlands
Bosman, K:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
:
IrsiCaixa AIDS Res Inst, Badalona 08916, Spain
Inst Hlth Sci Res Germans Trias & Pujol IGTP, Badalona 08916, Spain
Inst Salud Carlos III, Consorcio Ctr Invest Biomed Red Enfermedades Infe, Madrid 28029, Spain
Hutter, G:
DKMS CC, D-72072 Tubingen, Germany
Brosens, LAA:
Univ Med Ctr Utrecht UMCU, Dept Pathol, NL-3584 CX Utrecht, Netherlands
Kwon, M:
Hosp Gen Univ Gregorio Maranon, Dept Hematol, Madrid 28007, Spain
Martin, JD:
Hosp Gen Univ Gregorio Maranon, Dept Hematol, Madrid 28007, Spain
van der Meer, JTM:
Amsterdam UMC, Dept Internal Med, NL-1105 AZ Amsterdam, Netherlands
de Kort, TM:
Leiden Univ, Dept Anat & Embryol, Med Ctr, NL-2333 ZA Leiden, Netherlands
Saez-Cirion, A:
Univ Paris Cite, Inst Pasteur, HIV Inflammat & Persistence, F-75015 Paris, France
zur Wiesch, JS:
UMC Hamburg Eppendorf, Dept Internal Med, D-20251 Hamburg, Germany
Boelens, JJ:
Princess Maxima Ctr, Dept Hematol & Oncol, NL-3584 CS Utrecht, Netherlands
Mem Sloan Kettering Canc Ctr, Stem Cell Transplant & Cellular Therapies, Pediat, New York, NY 10065 USA
:
IrsiCaixa AIDS Res Inst, Badalona 08916, Spain
Inst Hlth Sci Res Germans Trias & Pujol IGTP, Badalona 08916, Spain
Inst Salud Carlos III, Consorcio Ctr Invest Biomed Red Enfermedades Infe, Madrid 28029, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain
Univ Vic, Cent Univ Catalonia UVic UCC, Vic 08500, Spain
Kuball, JHE:
Univ Med Ctr Utrecht UMCU, Dept Hematol, NL-3584 CX Utrecht, Netherlands
Univ Med Ctr Utrecht UMCU, Cent Lab Translat Immunol, NL-3584 CX Utrecht, Netherlands
Wensing, AMJ:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
Nijhuis, M:
Univ Med Ctr Utrecht UMCU, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
gold, Green Published
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