Immunoaging at Early Ages Could Drive a Higher Comorbidity Burden in People with HIV on Antiretroviral Therapy Compared with the Uninfected Population

Abstract

This is an observational, cross-sectional, comparative case-control, pilot study aimed at assessing the impact of HIV infection and age on immunological markers in people with HIV (PWH) on antiretroviral therapy (ART). The study included 40 PWH on ART, divided into two age groups (40-45 years vs. ≥60 years), and 30 HIV-uninfected controls matched by sex and age. The results show that older PWH on ART had more comorbidities and a higher frequency of CD8 T cells compared to older controls, with a significant decrease in CD8 naïve T cells with age. Additionally, younger PWH on ART exhibited higher frequencies of activated CD8 T cells and elevated levels of inflammatory markers (sCD14, IL-6) compared to age-matched controls, with values similar to those of older PWH on ART. These findings suggest that younger PWH on ART may experience accelerated immunoaging, highlighting the need for early interventions in this population.

Keywords: HIV; aging; inflammaging.

Figure 1

Comorbidities in the study groups. (A) Number of comorbidities according to age and HIV status. (B) A heat map representing the relative frequency of each comorbidity in each group.

Figure 2

Total and CD4 and CD8 T-cell subsets. The frequency of total (A) and CD4 T-cell subsets (B) are plotted for the 4 groups under study. The frequency of total (C) and CD8 T-cell subsets (D) are shown for the 4 groups under study. For all panels, individual and median values are indicated for the 4 groups under study: younger uninfected (inverted triangles), younger PWH on ART (squares), older uninfected (triangles), and older PWH on ART (diamonds). p-values from Kruskal–Wallis tests are indicated for the comparison between the 4 groups under study, and only significant p-values from Dunn’s multiple comparison tests between groups are shown. For (B,D), Kruskal–Wallis tests were performed for each individual T-cell subset.

Figure 3

Immune senescence, activation, and exhaustion of CD4 and CD8 T cells. The frequency of senescent (CD57+) CD4 (A) and CD8 T cells (B) are plotted for the 4 groups under study. A comparison of the levels of immune activation, measured by the frequency of HLA-DR+CD38+ cells, is shown for CD4 (C) and CD8 T cells (D). Finally, the frequency of exhausted (PD-1+) CD4 (E) and CD8 T cells (F) is plotted. For all panels, individual and median values are indicated for the 4 groups under study: younger uninfected (inverted triangles), younger PWH on ART (squares), older uninfected (triangles), and older PWH on ART (diamonds). p-values from Kruskal–Wallis tests are indicated for the comparison among the 4 groups under study, and only significant p-values from Dunn’s multiples comparison tests between groups are shown.

Figure 4

Soluble proinflammatory markers. The levels of soluble CD14 (sCD14, (A)), IL-6 (B), C-reactive protein (CRP; (C)), and D-Dimer (D) are plotted for the 4 groups under study. For all panels, individual and median values are indicated for the 4 groups under study: younger uninfected (inverted triangles), younger PWH on ART (squares), older uninfected (triangles), and older PWH on ART (diamonds). p-values from Kruskal–Wallis tests are indicated for the comparison among the 4 groups under study, and only significant p-values from Dunn’s multiples comparison tests between groups are shown.