Immune Activation Biomarkers, Inflammatory Markers, and Subclinical Atherosclerosis among People Living with HIV in Kenya

Abstract

Introduction: People living with HIV (PLWH) are at a high risk of developing cardiovascular disease (CVD). Interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) have been associated with the onset of subclinical atherosclerosis. We assessed the association between immune biomarkers and carotid intima media thickness (CIMT), an indicator of subclinical atherosclerosis, among HIV-negative individuals and PLWH in Kisumu, Kenya.Methods: In a cross-sectional study among adults seeking care at Kisumu Hospital in Kenya, we measured CIMT using ultrasound and analyzed concentrations of IL-1β, IL-6, TNF-α, and hsCRP using multiplex immunoassay. CIMT and concentrations of immune markers between the two groups were compared using Kruskal-Wallis test and multivariate linear regression was used to assess the associations between CIMT and immune markers after adjusting for traditional CVD risk factors. Results: 117 HIV-negative individuals and 145 PLWH had CIMT and immune marker data available and were included in the analyses. Participants had a mean CIMT of 0.42 mm (SD: 0.12) and there was a trend for PLWH to have lower CIMT than HIV-negative participants (0.41 mm; SD: 0.11 vs 0.44 mm; SD: 0.14; p = .056). Differences in the concentrations of IL-1β, IL-6, TNF-α, and hsCRP by HIV status were not statistically significant. There was an association between IL-1β an CIMT: a 1 pg/ml increase in IL-1β was associated with a decrease in CIMT of 0.0397 mm (-0.0794, -0.0001; p = .05). IL-6, TNF-α, and hsCRP concentrations were not significantly associated with CIMT. Higher serum levels of IL-1β were associated with lower CIMT measurements among HIV-negative persons, but not among PLWH. Conclusion: We found that higher plasma levels of IL-1β, IL-6, TNF-α, and hsCRP were not associated with higher CIMT, however an increase in IL-1β was consistently associated with lesser CIMT values. There was no significant association between IL-1β and CIMT among PLWH.