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

作者：Saison J; Ferry T; Demaret J; Boulch D Maucort; Venet F; Perpoint T; Ader F; Icard V; Chidiac C; Monneret G^*

来源：Clinical and Experimental Immunology, 2014, 176(3): 401-409.

DOI：10.1111/cei.12278

• HAART
• immune activation
• immunological response
• regulatory T cells
• very low-level viraemia

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 center dot 339, P=0 center dot 001, and OR=0 center dot 803, P=0 center dot 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.

• 出版日期2014-6