@article{e32ff86ffaee4a2694882346d2ae20f5,
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.",
keywords = "Autopsy, HIV Infections, HIV Seropositivity, HIV-1/genetics, Hematopoietic Stem Cell Transplantation, Humans, RNA, HIV-1, HIV persistence, tissue, cure, allo-HSCT, CCR5Δ32, reservoir",
author = "Huyveneers, {Laura E.P.} and Anke Bruns and Arjen Stam and Pauline Ellerbroek and {de Jong}, Dorien and Nagy, {No{\'e}mi A.} and Gumbs, {Stephanie B.H.} and Kiki Tesselaar and Kobus Bosman and Maria Salgado and Gero H{\"u}tter and Brosens, {Lodewijk A.A.} and Mi Kwon and {Diez Martin}, Jose and {van der Meer}, {Jan T.M.} and {de Kort}, {Theun M.} and Asier S{\'a}ez-Ciri{\'o}n and {Schulze zur Wiesch}, Julian and Boelens, {Jaap Jan} and Javier Martinez-Picado and Kuball, {J{\"u}rgen H.E.} and Wensing, {Annemarie M.J.} and Monique Nijhuis",
note = "Funding Information: This work was supported by amfAR, the Foundation for AIDS Research through the ARCHE program [108930-56-RGRL, 109293-59-RGRL, 109552-61-RGRL], and by the Dutch Aidsfonds [P-2013034, P-60802, P-13204]. Funding Information: All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. AJS resports a grant form Dutch Government (ZonMw) and is a committee member for revision Dutch guideline on Sexually Transmitted Diseases in primary care. JJB reports consultancy fees for the following companies: Avrobio, Omeros, Advanced Clinical, Bluebird Bio, Equillium, Sobi, and SmartImmune. MS reports grants or contracts from Spanisch Ministry of research and private TV fundraising funding (Marat{\'o} TV3) and payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Autonomous University of Barcelona and GESIDA Spain. ASC report grants or contracts from ANRS, NIH, and MSDAVENIR; payments from MSD, ViiV healthcare, and Gilead, and a patent for a method for reprogramming CD8+ T-cells to enhance their therapeutic potential and applications thereof; U.S. Patent application # 63/301, 532 and chair of the Sidaction Scientific and Medical Committee. JHEK reports grants or contracts from Novartis, Miltenyi, and Gadeta. MN reports grants from Gilead: Rosetta (Global INI resistance); Dutch Government (ZonMw/NWO): VIMP2, Bridge project; COVIDex-vivo models, Health Holland: Clear COVID organoids2cureHIV, amfAR: Epigenetic engineering of HIV, NSF: SARS-CoV-2 mutation frequency and evolution and honoraria for lectures from Virology Education. AW reports grants from Gilead, Aidfsonds, Dutch Government (ZonMw/NOW), and Health Holland/NLF4 cure, as well as consulting fees from Gilead, Janssen, Viiv/GSK, and honoraria for lectures from Virology Education and Southern African HIV Clinicians Society. Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = sep,
day = "17",
doi = "10.3390/v14092069",
language = "English",
volume = "14",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",
}