title: Elevated IP10 levels are associated with immune activation and low CD4⁺ T-cell counts in HIV controller patients.
abstract: BACKGROUND
  Although HIV controllers (HICs) achieve long-term control of viremia in the absence of antiretroviral therapy (ART), they display marked immune activation. The levels of inflammatory biomarkers in HICs and the biomarkers' relationships with immunologic and virologic status have yet to be fully characterized.
  
  
  METHODS
  A cohort study.
  
  
  METHODS
  Plasma levels of seven biomarkers [tumor necrosis factor (TNF)α, interleukin (IL)6, IL10, interferon gamma-induced protein 10 (IP10), monocyte chemoattractant protein-1 (MCP1), soluble CD14 (sCD14), soluble CD163 (sCD163)] were compared in 70 HICs, 33 HIV-1-infected, treatment-naive noncontrollers (viremic patients), 30 ART-treated patients and 40 healthy donors. In HICs, we investigated the interplay between biomarkers, cell activation and the CD4⁺ T-cell count.
  
  
  RESULTS
  HICs had higher levels of IP10, TNFα and sCD14 than healthy donors did (P < 0.01 for each). Also, TNFα and sCD14 levels of the HICs were similar to those measured in viremic and ART-treated patients. However, the levels of IL6 and IL10 were significantly lower in HICs than in viremic or ART-treated patients. In HICs, only IP10 levels differed significantly from those in both healthy donors and viremic patients, and were positively correlated with the expression of CD8⁺ and CD4⁺ T-cell activation markers. The IP10 levels of HICs were still elevated 12 and 24 months after the initial assay. Lastly, IP10 levels at enrollment were negatively correlated with the CD4⁺ T-cell count at enrollment and 12 months later.
  
  
  CONCLUSIONS
  HICs display a number of inflammatory features associated with persistent T-cell immune activation.
authors.affiliation: aINSERM U1012, Régulation de la réponse immune, infection VIH1 et autoimmunité, Université Paris Sud bAPHP, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud cINSERM U1018, Centre de recherche en Epidémiologie et Santé des Populations, Université Paris Sud, Le Kremlin Bicêtre dInstitut Pasteur, Unité de régulation des infections rétrovirales, Paris eService de Microbiologie, CHU Carémeau fINSERM U1047, Centre National de Référence des Brucella (L.A.), UFR de Médecine Université Montpellier 1, Nîmes gFaculté de Médecine Paris Sud XI, Le Kremlin Bicêtre hAPHP, Laboratoire de Virologie, CHU Necker, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noel
authors.forename: Faroudy
authors.initials: F
authors.lastname: Boufassa
authors.forename: Camille
authors.initials: C
authors.lastname: Lécuroux
authors.forename: Asier
authors.initials: A
authors.lastname: Saez-Cirion
authors.forename: Christine
authors.initials: C
authors.lastname: Bourgeois
authors.forename: Catherine
authors.initials: C
authors.lastname: Dunyach-Remy
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
authors.forename: Alain
authors.initials: A
authors.lastname: Venet
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000097:blood*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D020276:HIV Long-Term Survivors; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines