Open AccessRelationship between discordant response to HAART, Tregs, immune activation and low‐level viraemia
Author(s) -
Saison Julien,
Ferry Tristan,
Demaret Julie,
MaucortBoulch Delphine,
Venet Fabienne,
Perpoint Thomas,
Ader Florence,
Icard Vinca,
Chidiac Christian,
Monneret Guillaume
Publication year - 2014
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.17.4.19672
Subject(s) - cd38 , medicine , immunology , foxp3 , immune system , il 2 receptor , cd8 , effector , t cell , biology , genetics , stem cell , cd34
The incomplete immune recovery upon effective long‐term highly active antiretroviral therapy (HAART) has been associated with increased morbidity and mortality in HIV infected patients [1]. Immune cellular activation, Tregs or very low‐level viraemia has been alternatively suspected, but never investigated simultaneously [2]. Materials and Methods We performed a cross‐sectional study in 87 aviraemic patients (men=62, mean CD4+T cells=570/mm 3 , mean duration of HAART=12 years). Patients with at least 500 CD4+ T cells /mm 3 were classified as complete immunological responders (cIR), whereas remaining patients were classified as inadequate immunological responder (iIR). Tregs were characterized based on CD4+CD25highFoxP3+phenotype using a one‐step intracellular staining. Effector Tregs and terminal effectors Tregs were respectively defined as CD4+CD25+FoxP3+CD45RA‐, and CD4+CD25+FoxP3+CD45RA‐HLADR+phenotypes as recently described [3]. Activated T cells were identified using (i) elevated HLA‐DR expression for CD4+T cells, and (ii) increased expressions of HLA‐DR, or CD38, or both (HLADR+CD38+cells) for CD8+T cells. Very low‐level viraemia was defined as detectable viraemia between 1 and 39 cp/mL. Univariate and multivariate analyses were performed to identify determinants of iIR. Results Thirty‐nine patients were classified as iIR, and 48 as cIR. Patients from the iIR group were significantly older (55 vs 50 years, p=0.027), and had percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs significantly higher (5.3 vs 4%, p=0.014; 9 vs 7.5%, p=0,022; 8 vs 6.3%, p=0.01 and 1.8 vs 1.3%, p=0,033 among CD4+T cells, respectively). Neither the percentage of activated CD8+T cell nor very low‐level viraemia 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 independently associated with iIR (OR=2.339, p=0.001, and OR=0.803, p=0.041, respectively). Conclusions We present here the largest study investigating simultaneously immune response to long‐term HAART, immune activation of CD4+ and CD8+ T cells, Tregs percentages and very low‐level viraemia. Our results highlight the importance of Tregs in CD4 homeostasis. This aspect should now be prospectively explored in a large cohort of patients.