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

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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: PGE2 and PGD2) and thromboxanes (Tx: TxB2), and higher levels of select pro-resolving lipid mediators (e.g. RvD4 and MaR2n-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 MaR2n-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.

Funding: NIH.

Dalli J, Kitch D, O'Brien MP, Hunt PW, Funderburg N, Moisi D, Gupta A, Brown TT, Tien PC, Aberg JA, Shivakoti R. Pro-inflammatory and pro-resolving lipid mediators of inflammation in HIV: effect of aspirin intervention. EBioMedicine. 2023 Mar;89:104468. doi: 10.1016/j.ebiom.2023.104468. Epub 2023 Feb 13. PMID: 36791659; PMCID: PMC10025757.