In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation.
- Resource Type
- Academic Journal
- Authors
- Jensen BO; Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. bjoern-erikole.jensen@med.uni-duesseldorf.de.; Knops E; Institute of Virology, University and University Hospital Cologne, University of Cologne, Cologne, Germany.; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.; Cords L; Infectious Diseases Unit, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Lübke N; Institute of Virology, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.; Salgado M; IrsiCaixa AIDS Research Institute, Barcelona, Spain.; Center for Biomedical Research in Infectious Diseases (CIBERINFEC), Carlos III Health Institute, Madrid, Spain.; Germans Trias i Pujol Research Institute, Barcelona, Spain.; Busman-Sahay K; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.; Estes JD; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.; Huyveneers LEP; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.; Perdomo-Celis F; Institut Pasteur, Paris Cité University, HIV Inflammation and Persistence, Paris, France.; Wittner M; Infectious Diseases Unit, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.; Gálvez C; IrsiCaixa AIDS Research Institute, Barcelona, Spain.; Mummert C; Infectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.; Bavarian Nordic, Martinsried, Germany.; Passaes C; Institut Pasteur, Paris Cité University, HIV Inflammation and Persistence, Paris, France.; Eberhard JM; Infectious Diseases Unit, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.; Helmholtz Center for Infection Research, Helmholtz Institute for One Health, Greifswald, Germany.; Münk C; Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.; Hauber I; Leibniz Institute of Virology, Hamburg, Germany.; Hauber J; German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.; Leibniz Institute of Virology, Hamburg, Germany.; Heger E; Institute of Virology, University and University Hospital Cologne, University of Cologne, Cologne, Germany.; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.; De Clercq J; HIV Cure Research Center and Department of General Internal Medicine and Infectious Diseases, Ghent University Hospital, Ghent, Belgium.; Vandekerckhove L; HIV Cure Research Center and Department of General Internal Medicine and Infectious Diseases, Ghent University Hospital, Ghent, Belgium.; Bergmann S; Infectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.; Dunay GA; German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.; Leibniz Institute of Virology, Hamburg, Germany.; University Children's Research, UCR@Kinder-UKE, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Klein F; Institute of Virology, University and University Hospital Cologne, University of Cologne, Cologne, Germany.; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.; Häussinger D; Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.; Fischer JC; Institute for Transplant Diagnostics and Cell Therapeutics, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.; Nachtkamp K; Department of Hematology, Oncology and Clinical Immunology, Medical Faculty, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, Germany.; Timm J; Institute of Virology, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.; Kaiser R; Institute of Virology, University and University Hospital Cologne, University of Cologne, Cologne, Germany.; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.; Harrer T; Infectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.; Luedde T; Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.; Nijhuis M; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.; Sáez-Cirión A; Institut Pasteur, Paris Cité University, HIV Inflammation and Persistence, Paris, France.; Schulze Zur Wiesch J; Infectious Diseases Unit, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. j.schulze-zur-wiesch@uke.de.; German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany. j.schulze-zur-wiesch@uke.de.; Wensing AMJ; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.; Ezintsha, University of the Witwatersrand, Johannesburg, South Africa.; Martinez-Picado J; IrsiCaixa AIDS Research Institute, Barcelona, Spain.; Center for Biomedical Research in Infectious Diseases (CIBERINFEC), Carlos III Health Institute, Madrid, Spain.; University of Vic-Central University of Catalonia, Barcelona, Spain.; Catalan Institution for Research and Advanced Studies, Barcelona, Spain.; Kobbe G; Department of Hematology, Oncology and Clinical Immunology, Medical Faculty, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, Germany.
- Source
- Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
- Subject
- Language
- English
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.
(© 2023. The Author(s).)