Discussion
inflammation, PWH
CVD, INFLAMMATION
In this study, we assessed the relationship between circulating lipid mediators of inflammation and resolution with HIV status, monocyte activation and aspirin treatment. When compared with SN, PWH on suppressive ART had lower levels of Tx and various PGs, and higher MaRIn our comparison between PWH on ART and SN, we observed lower levels of AA-derived PG and Tx in PWH, with TxBOur findings related to sCD14 and lipid mediators showed relationships among PWH on suppressive ART. sCD14 had positive associations with various PGs and TxBAfter aspirin intervention, we observed expected large reductions in levels of PGs and Tx with both doses of aspirin. Aspirin binds and acetylates the cyclooxygenase (COX)-2 enzyme active site, leading to blocking of PG and Tx production.The limitations of our study are related to assessment of lipid mediators only at the beginning and end of treatment, merging samples from multiple studies (i.e. ACTG, MACS/WIHS) and limited data on gut integrity markers. The mechanisms behind the observed changes in lipid mediators of inflammation in PWH are not clear and future studies will need to address this. Despite these limitations, our study has multiple strengths. These include well-characterized and well-matched study populations, measurement of a comprehensive panel of pro- and anti-inflammatory lipid mediators along with paired soluble protein marker data, and a randomized controlled design to study the effect of aspirin treatment on lipid mediators.In conclusion, we observed distinct lipid mediator profiles among PWH compared to SN individuals. There were also relationships observed between lipid and markers of monocyte activation important in CVD. n−3 DPA-derived RvD5, linked with improved intestinal integrity, were inversely associated with sCD14 in PWH, suggesting intervention potential for this SPMs to improve intestinal integrity and reduce monocyte activation. We also noted that aspirin did not increase levels of aspirin-triggered SPMs in PWH, in line with other findings showing a defective aspirin response in PWH, and could help partly explain why aspirin was unable to reduce monocyte activation and systemic inflammation in PWH.