T cell activation predicts carotid artery stiffness among HIV-infected women

Abstract

Objectives: HIV disease is associated with increased arterial stiffness, which may be related to inflammation provoked by HIV-related immune perturbation. We assessed the association of T cell markers of immune activation and immunosenescence with carotid artery stiffness among HIV-infected women.

Methods: Among 114 HIV-infected and 43 HIV-uninfected women, we measured CD4+ and CD8+ T cell populations expressing activation (CD38+HLA-DR+) and senescence (CD28-CD57+) markers. We then related these measures of immune status with parameters of carotid artery stiffness, including decreased distensibility, and increased Young's elastic modulus, as assessed by B-mode ultrasound.

Results: HIV infection was associated with increased CD4+ T cell activation, CD8+ T cell activation and CD8+ T cell senescence. Among HIV-infected women, adjusted for age, HIV medications, and vascular risk factors, higher CD4+CD38+HLA-DR+ T cell frequency was associated with decreased carotid artery distensibility (β=-2.00, 95% confidence interval [CI]=-3.86, -0.14, P=0.04) and increased Young's modulus (β=1.00, 95% CI=0.03, 1.97, P=0.04). These associations were affected little by further adjustment for CD4+ T cell count and viral load. Among HIV-infected women, higher frequencies of immunosenescent T cells, including CD4+CD28-CD57+ and CD8+CD28-CD57+ T cells, were also associated with decreased arterial distensibility. Among HIV-uninfected women, frequencies of activated or senescent T cells were not significantly associated with measures of carotid stiffness.

Discussion: T cell activation and senescence are associated with arterial stiffness, suggesting that pro-inflammatory populations of T cells may produce functional or structural vascular changes in HIV-infected women.

Figure 1. Scatterplot of carotid artery distensibility and Young’s elastic modulus

Left panel, HIV-uninfected women. Right panel, HIV-infected women. Pearson correlations between carotid artery distensibility and Young’s elastic modulus were r = −0.79 (95% confidence interval = −0.88 to −0.65, p < 0.0001) among HIV-uninfected women and r = −0.76 (95% confidence interval = −0.83 to −0.67, p < 0.0001) among HIV-infected women.

Figure 2. Among HIV-infected women, correlation of % CD4+CD38+HLA-DR+ with carotid artery distensibility (left panel) and Young’s elastic modulus (right panel)

Linear regression was used to estimate intercepts and slopes as follows: distensibility = 23.0 – 5.9 log(% CD4+CD38+HLA-DR+), with 95% confidence intervals for the slope = −9.8 to −2.1. Young’s elastic modulus = 4.5 + 2.4 × log(% CD4+CD38+HLA-DR+), with 95% confidence intervals for the slope = 0.6 to 4.3.