Pro-inflammatory and pro-resolving lipid mediators of inflammation in HIV: effect of aspirin intervention

Background Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared to HIV-seronegative individuals (SN). Inflammation contributes to this risk but the role of lipid mediators, with central roles in inflammation, in HIV infection remain to be established; further aspirin reduces CVD risk in the general population through production of some of these anti-inflammatory lipid mediators, but they have not been studied in PWH. Methods We evaluated the relationship between plasma lipid mediators (i.e. 50 lipid mediators including classic eicosanoids and specialized pro-resolving mediators (SPMs)) and HIV status; and the impact of aspirin in PWH on regulating these autacoids. Plasma samples were obtained from 110 PWH receiving antiretroviral therapy (ART) from a randomized trial of aspirin (ACTG-A5331) and 107 matched SN samples (MACS-WIHS Combined Cohort). Findings PWH had lower levels of arachidonic acid-derived pro-inflammatory prostaglandins (PGs: PGE(2) and PGD(2)) and thromboxanes (Tx: TxB(2)), and higher levels of select pro-resolving lipid mediators (e.g. RvD4 and MaR2(n-3) (DPA)) compared to SN. At the interval tested, aspirin intervention was observed to reduced PGs and Tx, and while we did not observe an increase in aspirin triggered mediators, we observed the upregulation of other SPM in aspirin treated PWH, namely MaR2(n-3) (DPA). Interpretation Together these observations demonstrate that plasma lipid mediators profiles, some with links to systemic inflammation and CVD risk, become altered in PWH. Furthermore, aspirin intervention did not increase levels of aspirin-triggered pro-resolving lipid mediators, consistent with other reports of an impaired aspirin response in PWH. Copyright (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

People with HIV have an increased risk of cardiovascular disease compared to HIV-negative individuals. In this study, we found that HIV-positive individuals have lower levels of pro-inflammatory lipid mediators and higher levels of pro-resolving lipid mediators compared to HIV-negative individuals. We also observed that aspirin treatment in HIV-positive individuals reduced the levels of pro-inflammatory lipid mediators and upregulated certain pro-resolving lipid mediators.