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

Background: 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.

Methods: 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 interleukin (IL)-18 in 196 without HIV and 197 PWH of which 36 were ART-naïve.

Results: 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.

Conclusion: 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, whereas the association for CysB was restricted to PWH.