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

Male Humans Animals Mice Middle Aged HIV-1 / genetics HIV Infections / genetics Hematopoietic Stem Cell Transplantation

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
03 2023
Historique:
received: 05 08 2022
accepted: 09 01 2023
pubmed: 23 2 2023
medline: 25 3 2023
entrez: 22 2 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41591-023-02213-x PMID: 36807684 PMC: PMC10033413
pubmed: 36807684
doi: 10.1038/s41591-023-02213-x
pii: 10.1038/s41591-023-02213-x
pmc: PMC10033413
doi:

Types de publication

Case Reports Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

583-587

Subventions

Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143411
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2023. The Author(s).

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Auteurs

Björn-Erik Ole 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.
ORCID: 0000-0003-1626-4855

Elena 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.
ORCID: 0000-0001-7398-3026

Leon Cords (L)

Infectious Diseases Unit, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0003-1340-8817

Nadine Lübke (N)

Institute of Virology, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Maria 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.
ORCID: 0000-0003-1551-7216

Kathleen Busman-Sahay (K)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
ORCID: 0000-0002-8549-0023

Jacob D Estes (JD)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.

Laura E P Huyveneers (LEP)

Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.

Federico Perdomo-Celis (F)

Institut Pasteur, Paris Cité University, HIV Inflammation and Persistence, Paris, France.

Melanie 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.

Cristina Gálvez (C)

IrsiCaixa AIDS Research Institute, Barcelona, Spain.

Christiane 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.

Caroline Passaes (C)

Institut Pasteur, Paris Cité University, HIV Inflammation and Persistence, Paris, France.
ORCID: 0000-0002-0813-2521

Johanna M 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.
ORCID: 0000-0002-8367-3870

Carsten Münk (C)

Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Ilona Hauber (I)

Leibniz Institute of Virology, Hamburg, Germany.

Joachim Hauber (J)

German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.
Leibniz Institute of Virology, Hamburg, Germany.

Eva 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.

Jozefien De Clercq (J)

HIV Cure Research Center and Department of General Internal Medicine and Infectious Diseases, Ghent University Hospital, Ghent, Belgium.

Linos Vandekerckhove (L)

HIV Cure Research Center and Department of General Internal Medicine and Infectious Diseases, Ghent University Hospital, Ghent, Belgium.
ORCID: 0000-0002-8600-1631

Silke Bergmann (S)

Infectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.

Gábor A 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.

Florian 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.
ORCID: 0000-0003-1376-1792

Dieter Häussinger (D)

Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
ORCID: 0000-0002-5936-682X

Johannes C Fischer (JC)

Institute for Transplant Diagnostics and Cell Therapeutics, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Kathrin Nachtkamp (K)

Department of Hematology, Oncology and Clinical Immunology, Medical Faculty, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, Germany.

Joerg Timm (J)

Institute of Virology, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
ORCID: 0000-0001-7799-3045

Rolf 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.

Thomas Harrer (T)

Infectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.

Tom Luedde (T)

Department of Gastroenterology, Hepatology and Infectious Diseases, Düsseldorf University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
ORCID: 0000-0002-6288-8821

Monique Nijhuis (M)

Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
ORCID: 0000-0001-6610-8282

Asier Sáez-Cirión (A)

Institut Pasteur, Paris Cité University, HIV Inflammation and Persistence, Paris, France.
ORCID: 0000-0003-2406-7536

Julian 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.
ORCID: 0000-0002-5033-1938

Annemarie M J Wensing (AMJ)

Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
Ezintsha, University of the Witwatersrand, Johannesburg, South Africa.

Javier 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.
ORCID: 0000-0002-4916-2129

Guido Kobbe (G)

Department of Hematology, Oncology and Clinical Immunology, Medical Faculty, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, Germany.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › In-depth virological and immunological...
questionsmedicales.fr › Eucaryotes › Animaux › In-depth virological and immunological...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › In-depth virological and immunological...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › In-depth virological and immunological...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › In-depth virological and immunological...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › In-depth virological and immunological...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › In-depth virological and immunological...