title: One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study.
abstract: Immune activation in HIV-1-infected individuals is reduced under antiretroviral therapies, but persists, resulting in various morbidities. To better characterize this phenomenon, using a panel of 68 soluble and cell surface markers, we measured the level of activation in circulating CD4+ and CD8+ T cells, B cells, monocytes, NK cells, polynuclear and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45years of age. As compared with age- and sex-matched uninfected individuals, we observed a persistence of activation in all the cell subpopulations analyzed, together with marks of inflammation and fibrinolysis. Two independent hierarchical clustering analyses allowed us to identify five clusters of markers that varied concurrently, and five patient groups, each with the same activation profile. The five groups of patients could be characterized by a marker of CD4+ T cell, CD8+ T cell, NK cell, monocyte activation or of inflammation, respectively. One of these profiles was strongly associated with marks of metabolic syndrome, particularly with hyperinsulinemia (OR 12.17 [95% CI 1.79-82.86], p=0.011). In conclusion, our study unveils biomarkers linked to metabolic syndrome that could be tested as predictive markers, and opens the way to new therapeutic approaches tailored to each patient group.
authors.affiliation: Institute for Human Genetics, CNRS UPR1142, 141 rue de la Cardonille, 34396, Montpellier cedex 5, France; Infectious Diseases Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Psomas
authors.affiliation: Institute for Human Genetics, CNRS UPR1142, 141 rue de la Cardonille, 34396, Montpellier cedex 5, France.
authors.forename: Mehwish
authors.initials: M
authors.lastname: Younas
authors.affiliation: Institute for Functional Genomics, Montpellier University, UMR5203, 141 rue de la Cardonille, 34396 Montpellier cedex 5, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Reynes
authors.affiliation: Immunology Department, University Hospital, Place du Pr Debré, 30029 Nîmes cedex, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Cezar
authors.affiliation: Immunology Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Portalès
authors.affiliation: Microbiology Department, University Hospital, 371 Av. du Doyen Gaston Giraud, 34295 Montpellier cedex 5, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Tuaillon
authors.affiliation: Institute for Human Genetics, CNRS UPR1142, 141 rue de la Cardonille, 34396, Montpellier cedex 5, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Guigues
authors.affiliation: Infectious Diseases Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Merle
authors.affiliation: Infectious Diseases Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Atoui
authors.affiliation: Infectious Diseases Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: Infectious Diseases Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France; IRD UMI 233, INSERM U1175, Montpellier University, 911 avenue Agropolis, 34294 Montpellier cedex 5, France; Montpellier University, 5 Boulevard Henri IV, 34967 Montpellier cedex 2, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Le Moing
authors.affiliation: Infectious Diseases Department, University Hospital, Place du Pr Debré, 30029 Nîmes cedex, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Barbuat
authors.affiliation: Medical Informatics Department, University Hospital, 39 Avenue Charles Flahault, 34090 Montpellier cedex 5, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Marin
authors.affiliation: Medical Informatics Department, University Hospital, 39 Avenue Charles Flahault, 34090 Montpellier cedex 5, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.affiliation: Montpellier University, 5 Boulevard Henri IV, 34967 Montpellier cedex 2, France; Infectious Diseases Department, University Hospital, Place du Pr Debré, 30029 Nîmes cedex, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Sotto
authors.affiliation: Immunology Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France; Montpellier University, 5 Boulevard Henri IV, 34967 Montpellier cedex 2, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eliaou
authors.affiliation: Institute for Functional Genomics, Montpellier University, UMR5203, 141 rue de la Cardonille, 34396 Montpellier cedex 5, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Sabatier
authors.affiliation: Infectious Diseases Department, University Hospital, 80 avenue A. Fliche, 34295 Montpellier cedex 5, France; IRD UMI 233, INSERM U1175, Montpellier University, 911 avenue Agropolis, 34294 Montpellier cedex 5, France; Montpellier University, 5 Boulevard Henri IV, 34967 Montpellier cedex 2, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.affiliation: Institute for Human Genetics, CNRS UPR1142, 141 rue de la Cardonille, 34396, Montpellier cedex 5, France; Immunology Department, University Hospital, Place du Pr Debré, 30029 Nîmes cedex, France; Montpellier University, 5 Boulevard Henri IV, 34967 Montpellier cedex 2, France. Electronic address: pcorbeau@igh.cnrs.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Corbeau
mesh_terms: D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D001777:Blood Coagulation; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060085:Coinfection; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism; D008875:Middle Aged; D019562:Viral Load; D014766:Viremia
chemical_list: D015415:Biomarkers
keywords: Cell activation; Coagulation; Endothelium; Hyperinsulinemia; Inflammation