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. (June 2014)

• Record Type: Journal Article
• Authors: Saison, J.; Ferry, T.; Demaret, J.; Maucort Boulch, D; Venet, F.; Perpoint, T.; Ader, F.; Icard, V.; Chidiac, C.; Monneret, G.
• Is Part Of: Clinical and experimental immunology. Volume 176:Number 3(2014:Jun.)
• Page Start: 401
• Page End: 409
• Publication Date: 2014-06
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12278
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>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 (T<sub>regs</sub>) 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, <italic>n</italic> = 48) and inadequate immunological responders (iIR, <italic>n</italic> = 39), depending on the CD4<sup>+</sup> T cell count (> or < 500/mm<sup>3</sup>). Clinical and virological data (including very low‐level viraemia) were collected. In parallel, immunophenotyping of CD4<sup>+</sup> lymphocytes, including T<sub>reg</sub> subsets, and CD8<sup>+</sup> T cells was performed. Percentages of activated CD4<sup>+</sup> T cells, T<sub>regs</sub>, effector T<sub>regs</sub> and terminal effector T<sub>regs</sub> were found to be significantly elevated in iIR. Neither the percentage of activated CD8<sup>+</sup> T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4<sup>+</sup> T cell count and percentage of T<sub>regs</sub> were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, <italic>P</italic> = 0·001, and OR = 0·803, <italic>P</italic> = 0·041]. We present here the largest study investigating simultaneously the immune response to long‐term HAART, activation of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, T<sub>reg</sub> percentages and very low‐level viraemia. Causative interactions between T<sub>regs</sub> and CD4<sup>+</sup> T cells should now be explored prospectively in a large patients cohort.</p> </abstract>