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Elevated IP10 levels are associated with immune activation and low CD4+ T-cell counts in HIV controller patients

Noel, Nicolasa,b; Boufassa, Faroudyc; Lécuroux, Camillea; Saez-Cirion, Asierd; Bourgeois, Christinea; Dunyach-Remy, Catherinee,f; Goujard, Cécileb,c,g; Rouzioux, Christineh; Meyer, Laurencec; Pancino, Gianfrancod; Venet, Alaina; Lambotte, Oliviera,b,g; the ANRS C021 CODEX Study Group

doi: 10.1097/QAD.0000000000000174
Basic Science

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.

Design: 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.

Conclusion: HICs display a number of inflammatory features associated with persistent T-cell immune activation.

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.

Correspondence to Professor Olivier Lambotte, MD, PhD, Service de Médecine Interne, CHU Bicêtre, 78 rue du Général Leclerc, F-94275 Le Kremlin Bicêtre Cedex, France. Tel: +33 145 212 783; fax: +33 145 212 733; e-mail: olivier.lambotte@bct.aphp.fr

Received 16 August, 2013

Revised 3 December, 2013

Accepted 3 December, 2013

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