Markers of extracellular matrix degradation and inflammasome activation are associated with carotid plaques in virally suppressed people with HIV in Botswana.

Abstract

HIV is associated with increased risk of cardiovascular disease. We investigated soluble markers of extracellular matrix (ECM) remodeling and inflammation in relation to presence of carotid plaques in a well-characterized adult cross-sectional study of people with HIV (PWH) and matched people without HIV in Botswana. Using enzyme immunoassays we analyzed plasma ECM remodeling mediators including Galectin-3 (GAL-3), Cystatin B (CysB) and Growth/differentiation factor 15 (GDF-15) and the inflammatory marker IL-18 in 196 without HIV and 197 PWH of which 36 were ART-naïve. We found i) PWH had higher plasma levels of the ECM markers GAL-3 and CysB and the NLRP3 inflammasome activation marker IL-18, mainly in ART naïve participants, ii) PWH on ART had markedly higher GDF-15, associated with use of first generation nucleoside analogs; iii) high levels of CysB and IL-18 correlated with presence of carotid plaques. In PWH, high levels of CysB and IL-18 were associated with the presence of carotid plaques. For IL-18 this was observed in the study population as a whole, while the association for CysB was restricted to PWH.