Title

Frequencies of CD4⁺ and CD8⁺ T cells immune activation are reduced in PLWH after 5 years of antiretroviral therapy

Presenter

Luca Maddaloni

Authors

L. Maddaloni¹, L. Santinelli¹, G. Bugani¹, A. Lazzaro¹, C.M. Lofaro¹, S. Caiazzo¹, L. Sorrentino², A. D'Auria², C. Scagnolari², G. Ceccarelli¹, C.M. Mastroianni¹, G. d'Ettorre¹

Institutions

¹Sapienza University of Rome, Public Health and Infectious Diseases, Rome, Italy, ²Sapienza University of Rome, Virology Laboratory, Department of Molecular Medicine, Rome, Italy

BACKGROUND: Chronic immune activation represents one of the main determinants of a senescent immune phenotype in people living with HIV-1 (PLWH). To address the effectiveness of antiretroviral therapy (ART) in reducing chronic CD4⁺ and CD8⁺T cells immune activation, an observational study comparing peripheral blood immune activation status between ART-naïve, less than 5 years and more than 5 years ART-treated PLWH was conducted.
METHODS: Peripheral blood mononuclear cells (PBMC) were collected from ART-naïve (n=14), less than 5 years (n=13) and more than 5 years (n=26) ART-treated PLWH recruited at the Department of Public Health and Infectious Diseases of “Sapienza” University of Rome (Italy) and Immunophenotype and activation levels were evaluated by multiparameter flow cytometry on CD4⁺ and CD8⁺ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)] by the following anti-human monoclonal antibodies: CD3-PerCP, CD4-APC-Vio770, CD8-FITC, CD45RO-PE-Vio770, CD27-VioBlue, CD38-APC, and HLA-DR-PE. Statistical analyses were performed using Prism and p<0.05 were statistically significant.
RESULTS: Frequencies of CD4⁺ naïve and CD8⁺ naïve T cells expressing CD38, HLA-DR or both markers were similar between the three groups. PLWH treated for more than 5 years exhibited lower frequencies of CD38⁺ (p = 0.0074 and 0.0021) and CD38⁺ HLA-DR⁺ CD4⁺ TCM and TEM cells (p = 0.0152 and p = 0.0002, respectively), CD38⁺ CD8⁺ TCM cells (p = 0.0358), CD38⁺ HLA-DR⁺ CD8⁺ TCM and TEM cells (p = 0.0068 and p = 0.0026, respectively) as compared to ART-naïve PLWH. Moreover, PLWH ART-treated for less than 5 years had increased levels of CD38⁺ (p = 0.0058) and CD38⁺ HLA-DR⁺ CD4⁺ TEM cells (p = 0.0018) compared to PLWH treated for more than 5 years. By contrast, no differences in the percentages of the other T cell subsets (HLA-DR⁺ CD4⁺TCM and TEM cells, CD38⁺ HLA-DR⁺ and HLA-DR⁺ CD8⁺ TCM cells, HLA-DR⁺ CD8⁺ TEM cells) were recorded among the three groups.
CONCLUSIONS: These findings suggest the efficacy of ART in reducing the immune activation levels of distinct CD4⁺ and CD8⁺ T cell subsets in PLWH after 5 years of ART.

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