Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Authors

  • J. Saison,

    1. Immunology Laboratory, E. Herriot Hospital, Lyon, France
    2. Infectious and Tropical Disease Unit, Croix Rousse Hospital, Lyon, France
    3. Lyon-1 University, Lyon, France
    4. CIRI (Centre International de Recherche en Infectiologie), Lyon, France
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  • T. Ferry,

    1. Infectious and Tropical Disease Unit, Croix Rousse Hospital, Lyon, France
    2. Lyon-1 University, Lyon, France
    3. CIRI (Centre International de Recherche en Infectiologie), Lyon, France
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  • J. Demaret,

    1. Immunology Laboratory, E. Herriot Hospital, Lyon, France
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  • D Maucort Boulch,

    1. Service de Biostatistique, Hospices Civils de Lyon, Lyon, France
    2. Lyon-1 University, Lyon, France
    3. Equipe Biostatistique Santé, Villeurbanne, France
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  • F. Venet,

    1. Immunology Laboratory, E. Herriot Hospital, Lyon, France
    2. Lyon-1 University, Lyon, France
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  • T. Perpoint,

    1. Infectious and Tropical Disease Unit, Croix Rousse Hospital, Lyon, France
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  • F. Ader,

    1. Infectious and Tropical Disease Unit, Croix Rousse Hospital, Lyon, France
    2. Lyon-1 University, Lyon, France
    3. CIRI (Centre International de Recherche en Infectiologie), Lyon, France
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  • V. Icard,

    1. Virology Laboratory, Croix Rousse Hospital, Lyon, France
    2. CIRI (Centre International de Recherche en Infectiologie), Lyon, France
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  • C. Chidiac,

    1. Infectious and Tropical Disease Unit, Croix Rousse Hospital, Lyon, France
    2. Lyon-1 University, Lyon, France
    3. CIRI (Centre International de Recherche en Infectiologie), Lyon, France
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  • G. Monneret,

    Corresponding author
    1. Immunology Laboratory, E. Herriot Hospital, Lyon, France
    2. Lyon-1 University, Lyon, France
    • Correspondence: G. Monneret, Immunology Laboratory, Hopital E. Herriot, Hospices Civils de Lyon, 5 place d'Arsonval, 69437 Lyon Cedex 03, France.

      E-mail: guillaume.monneret@chu-lyon.fr

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  • and on behalf of the Lyon HIV Cohort Study


Summary

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4+ T cell count (> or < 500/mm3). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4+ lymphocytes, including Treg subsets, and CD8+ T cells was performed. Percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4+ T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4+ and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4+ T cells should now be explored prospectively in a large patients cohort.

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