Relationship between discordant response to HAART, Tregs, immune activation and low-level viraemia
- PMID: 25397422
- PMCID: PMC4225367
- DOI: 10.7448/IAS.17.4.19672
Relationship between discordant response to HAART, Tregs, immune activation and low-level viraemia
Abstract
Introduction: 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.
Similar articles
-
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.Clin Exp Immunol. 2014 Jun;176(3):401-9. doi: 10.1111/cei.12278. Clin Exp Immunol. 2014. PMID: 24460818 Free PMC article.
-
Severe immune dysregulation affects CD4⁺CD25(hi)FoxP3⁺ regulatory T cells in HIV-infected patients with low-level CD4 T-cell repopulation despite suppressive highly active antiretroviral therapy.J Infect Dis. 2012 May 15;205(10):1501-9. doi: 10.1093/infdis/jis230. Epub 2012 Mar 28. J Infect Dis. 2012. PMID: 22457273
-
Thymic function in HIV-infection.Dan Med J. 2013 Apr;60(4):B4622. Dan Med J. 2013. PMID: 23651726 Review.
-
Residual viraemia in HIV-1-infected patients with plasma viral load <or=20 copies/ml is associated with increased blood levels of soluble immune activation markers.Scand J Immunol. 2008 Dec;68(6):652-60. doi: 10.1111/j.1365-3083.2008.02184.x. Scand J Immunol. 2008. PMID: 19055701
-
Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.J Antimicrob Chemother. 2013 Nov;68(11):2616-25. doi: 10.1093/jac/dkt245. Epub 2013 Jul 5. J Antimicrob Chemother. 2013. PMID: 23833186
Cited by
-
Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV.BMC Infect Dis. 2021 Jun 12;21(1):557. doi: 10.1186/s12879-021-06260-y. BMC Infect Dis. 2021. PMID: 34116650 Free PMC article.
-
Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study.PLoS One. 2016 Jul 20;11(7):e0159446. doi: 10.1371/journal.pone.0159446. eCollection 2016. PLoS One. 2016. PMID: 27438000 Free PMC article.
-
The predictive role of CD4+ cell count and CD4/CD8 ratio in immune reconstitution outcome among HIV/AIDS patients receiving antiretroviral therapy: an eight-year observation in China.BMC Immunol. 2019 Aug 28;20(1):31. doi: 10.1186/s12865-019-0311-2. BMC Immunol. 2019. PMID: 31455209 Free PMC article.
-
The Prognosis for Delayed Immune Recovery in HIV-Infected Children might be Associated with Pre-cART CD4 + T cell Count Irrespective of Co-Infection with Tuberculosis.Res Sq [Preprint]. 2024 Apr 19:rs.3.rs-4243586. doi: 10.21203/rs.3.rs-4243586/v1. Res Sq. 2024. Update in: BMC Res Notes. 2025 Jan 7;18(1):6. doi: 10.1186/s13104-024-07032-y PMID: 38699317 Free PMC article. Updated. Preprint.
References
-
- Rodger AJ, Lodwick R, Schechter M, Deeks S, Amin J, Gilson R, et al. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS. 2013;27:973–9. - PubMed
-
- Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10:490–500. - PubMed
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous