title: A Mature NK Profile at the Time of HIV Primary Infection Is Associated with an Early Response to cART.
abstract: Natural killer (NK) cells are major effectors of the innate immune response. Despite an overall defect in their function associated with chronic human immunodeficiency virus (HIV) infection, their role in primary HIV infection is poorly understood. We investigated the modifications of the NK cell compartment in patients from the ANRS-147-Optiprim trial, a study designed to examine the benefits of intensive combination antiretroviral therapy (cART) in patients with acute or early primary HIV infection. Multiparametric flow cytometry combined with bioinformatics analyses identified the NK phenotypes in blood samples from 30 primary HIV-infected patients collected at inclusion and after 3 months of cART. NK phenotypes were revealed by co-expression of CD56/CD16/NKG2A/NKG2C and CD57, five markers known to delineate stages of NK maturation. Three groups of patients were formed according to their distributions of the 12 NK cell phenotypes identified. Their virological and immunological characteristics were compared along with the early outcome of cART. At inclusion, HIV-infected individuals could be grouped into those with predominantly immature/early differentiated NK cells and those with predominantly mature NK cells. Several virological and immunological markers were improved in patients with mature NK profiles, including lower HIV viral loads, lower immune activation markers on NK and dendritic cell (DC), lower levels of plasma IL-6 and IP-10, and a trend to normal DC counts. Whereas all patients showed a decrease of viremia higher than 3 log10copies/ml after 3 months of treatment, patients with a mature NK profile at inclusion reached this threshold more rapidly than patients with an immature NK profile (70 vs. 38%). In conclusion, a better early response to cART is observed in patients whose NK profile is skewed to maturation at inclusion. Whether the mature NK cells contributed directly or indirectly to HIV control through a better immune environment under cART is unknown. The NK maturation status of primary infected patients should be considered as a relevant marker of an immune process contributing to the early outcome of cART that could help in the management of HIV-infected patients.
authors.affiliation: CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Immunity and Cancer Team, Aix Marseille Univ , Marseille , France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gondois-Rey
authors.affiliation: APHP, Hôpital Bicêtre, Internal Medecin Unit, Le Kremlin-Bicêtre, France; U1184, Paris-Sud Univ, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM U1184, ImVA "Immunology of Chronic Viral Infections and Autoimmune Diseases", Le Kremlin-Bicêtre, France; Institut Pasteur, HIV, Inflammation and Persistance Unit, Paris, France; Virology Laboratory, APHP CHU Necker-Enfants Malades, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Chéret
authors.affiliation: CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Immunity and Cancer Team, Aix Marseille Univ , Marseille , France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Mallet
authors.affiliation: CNRS, INSERM, Institut Paoli-Calmettes, CRCM, CiBi Platform, Aix Marseille Univ , Marseille , France.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Bidaut
authors.affiliation: CNRS, INSERM, Institut Paoli-Calmettes, CRCM, CiBi Platform, Aix Marseille Univ , Marseille , France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Granjeaud
authors.affiliation: U1184, Paris-Sud Univ, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM U1184, ImVA "Immunology of Chronic Viral Infections and Autoimmune Diseases", Le Kremlin-Bicêtre, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Lécuroux
authors.affiliation: Institut Pasteur, HIV, Inflammation and Persistance Unit , Paris , France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Ploquin
authors.affiliation: Institut Pasteur, HIV, Inflammation and Persistance Unit , Paris , France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Müller-Trutwin
authors.affiliation: Virology Laboratory, APHP CHU Necker-Enfants Malades, Paris, France; EA 7327 Paris Descartes University, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.affiliation: Virology Laboratory, APHP CHU Necker-Enfants Malades, Paris, France; EA 7327 Paris Descartes University, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoël
authors.affiliation: Dipartimento di Scienze della Salute and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Genova, Italy; Clinica Malattie Infettive, IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
authors.affiliation: APHP, Hôpital Tenon, Infectious Diseases Unit , Paris , France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.affiliation: APHP, Hôpital Bicêtre, Internal Medecin Unit , Le Kremlin-Bicêtre , France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.affiliation: INSERM, CESP U1018, Epidemiology and population health, APHP, Hôpital Bicêtre, Paris 11 Univ , Le Kremlin-Bicêtre , France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Immunity and Cancer Team, Aix Marseille Univ , Marseille , France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
keywords: HIV; NK cells maturation; cART; memory-like NK; primary infection