In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation

Jensen BEO, Knops E, Cords L, Lübke N, Salgado M, Busman-Sahay K, Estes JD, Huyveneers LE, Perdomo-Celis F, Wittner M, Gálvez C, Mummert C, Passaes C, Eberhard JM, Münk C, Hauber I, Hauber J, Heger E, De Clercq J, Vandekerckhove L, Bergmann S, Dunay GA, Klein F, Häussinger D, Fischer JC, Nachtkamp K, Timm J, Kaiser R, Harrer T, Luedde T, Nijhuis M, Sáez-Cirión A, Schulze zur Wiesch J, Wensing AM, Martinez-Picado J, Kobbe G (2023)

Publication Type: Journal article, Original article

Publication year: 2023

Journal

Nature Medicine Nature Publishing Group

Book Volume: 29

Pages Range: 583-587

Journal Issue: 3

DOI: 10.1038/s41591-023-02213-x

Abstract

Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.

Authors with CRIS profile

Sabrina Seidel Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Thomas Harrer Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz

Involved external institutions

Institut Pasteur FR France (FR) Deutsches Zentrum für Infektionsforschung (DZIF) DE Germany (DE) University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL) Universitätsklinikum Köln DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) University Hospital Ghent BE Belgium (BE) IrsiCaixa Institute for AIDS Research ES Spain (ES) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Heinrich-Pette-Institut (HPI), Leibniz-Institut für Experimentelle Virologie / Heinrich Pette Institute – Leibniz Institute for Experimental Virology DE Germany (DE) Oregon Health and Science University (OSHU) US United States (USA) (US)

How to cite

APA:

Jensen, B.E.O., Knops, E., Cords, L., Lübke, N., Salgado, M., Busman-Sahay, K.,... Kobbe, G. (2023). In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation. Nature Medicine, 29(3), 583-587. https://doi.org/10.1038/s41591-023-02213-x

MLA:

Jensen, Björn Erik Ole, et al. "In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation." Nature Medicine 29.3 (2023): 583-587.

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