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Low frequency of activated T cells in people living with HIV, aviremic under treatment, and presenting neurocognitive disorders

Title
Low frequency of activated T cells in people living with HIV, aviremic under treatment, and presenting neurocognitive disorders
Presenter
Lucy Kundura
Authors
L. Kundura * (1), R. Cezar (2), M. Pastore (3), L.-A. Gutierrez (4), C. Berr (4), C. Reynes (3), J. Reynes (5,6), A. Makinson (5,6), P. Corbeau (1,6)
Institutions
(1) Institute of Human Genetics - CNRS, Homing, immune activation and infection, Montpellier, France, (2) Nîmes University Hospital, Immunology Department, Nîmes, France, (3) Institute of Functional Genomics - CNRS, Montpellier, France, (4) Institute for Neurosciences of Montpellier - CNRS, Montpellier, France, (5) Montpellier University Hospital, Infectious and Tropical Diseases Department, Montpellier, France, (6) Montpellier University, Montpellier, France

BACKGROUND: Prevalence of HIV-associated neurocognitive disorders (HAND), either asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND), or HIV-associated dementia in people living with HIV (PLWH) under efficient combined antiretroviral therapy is high. Here, we looked for links between immune activation and HAND in an HIV-population over 55 years age with controlled HIV-disease.
METHODS: This study is an ancillary study of the French national ANRS EP58 HAND 55-70 project (Clinical trial registration NCT02592174). We recruited 71 PLWH with a mean (±SD) age of 62±2.4 years; CD4 count, 553±249 cells/µL; CD4:CD8 ratio, 1.03±0.58; duration of infection, 20.0±7.7 years under efficient treatment during at least two years (<50 copies/mL and less than 2 viremic blips). We used the Frascati criteria to classify neurocognitive performances. We analyzed 31 peripheral blood soluble and cell surface markers of T cell, NK cell, monocyte, endothelial cell activation and inflammation by ELISA and flow cytometry. We performed two hierarchical clustering analyses, one at a participants' level, and the other one at a markers' level.
RESULTS: We found that 53% of PLWH were classified as HAND (ANI, n=21; MND n= 12). The proportion of CD8+ (44.3±10.3 vs. 52.6±10.4 %, p = 0.002), activated (HLA-DR-positive) CD4+ (19.6±10.3 vs. 28.9±14 %, p = 0.002) and activated (HLA-DR-positive) CD8+ (19.6±10.3 vs. 28.9±14.0 %, p = 0.025) T cells were lower in participants with ANI or MND than in participants without HAND. The double hierarchical clustering identified six different immune activation profiles in participants. Participants with one of these profiles, also characterized by a low frequency of circulating activated CD4+ T cells, presented more frequently ANI and MND (odds ratio 8.8 [95% CI 1.0-77.0], p = 0.041) than the participants with other profiles.
CONCLUSIONS: We did not find a positive correlation between HAND and circulating markers of immune activation in ageing PLWH. Our observation of a low percentage of activated T cells in peripheral blood raises the interesting hypothesis of a recruitment of these lymphocytes into the central nervous system.

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