Low-Dose Acetylsalicylic Acid Reduces T Cell Immune Activation: Potential Implications for HIV Prevention

Abstract

IntroductionAcetylsalicylic acid (ASA) is a well-known and safe anti-inflammatory. At low-dose, it is prescribed to prevent secondary cardiovascular events in those with pre-existing conditions and to prevent preeclampsia. Little is known about how low-dose ASA affects the immune response. In this study, we followed women to assess how ASA use modifies T cells immune phenotypes in the blood and at the genital tract.MethodsHIV uninfected women from Kenya were enrolled in this study and followed for one month to assess baseline responses including systemic/mucosal baseline immune activation. Participants then received 81mg of ASA daily for 6 weeks to assess changes to T cell immune activation (systemic and mucosal) relative to baseline levels.ResultsThe concentration of ASA measured in the blood was 58% higher than the level measured at the female genital tract. In the blood, the level of ASA was inversely correlated with the following: the proportion of Th17 expressing HLA-DR (p=0.04), the proportion of effector CD4+ T cells expressing CCR5 (p=0.03) and the proportion of CD8+Tc17 expressing CCR5 (p=0.04). At the genital tract, ASA use correlated with a decreased of activated CD4+T cells [CD4+CCR5+CD161+ (p=0.02) and CD4+CCR5+CD95+ (p=0.001)].ConclusionThis study shows that ASA use impacts the immune response in both the systemic and genital tract compartments. This could have major implications for the prevention of infectious diseases such as HIV, in which the virus targets activated T cells to establish an infection. This could inform guidelines on ASA use in women.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02079077.

Kinetics of Circulating Extracellular Vesicles Over the 24‐Hour Dosing Interval After Low‐Dose Aspirin Administration in Patients at Cardiovascular Risk

“…Leukocyte‐derived EV concentrations may reflect the fact that aspirin at low doses is able to inhibit innate immune‐mediated responses, by reducing the frequency of activated CD4+ T cells 47 . It is also well known that low doses of aspirin ameliorate endothelial function, improving vasodilation, reducing thrombosis, and inhibiting atherosclerosis 48,49 .…”

“…38,46 Leukocyte-derived EV concentrations may reflect the fact that aspirin at low doses is able to inhibit innate immune-mediated responses, by reducing the frequency of activated CD4+ T cells. 47 It is also well known that low doses of aspirin ameliorate endothelial function, improving vasodilation, reducing thrombosis, and inhibiting atherosclerosis. 48,49 Since the concentrations of endothelial-derived EVs exposing PS were significantly lower at T10 vs. T24, suggesting lower endothelial cell apoptosis, it is intriguing to speculate that low doses of aspirin shift such a balance toward the antiapoptotic side for the endothelial compartment, also influencing the release of EVs.…”

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

“… 24 We recently found that this mechanism is linked with the immune-directed activities of aspirin in experimental chronic inflammation. 25 Although aspirin has been shown to reduce aspects of systemic inflammation and immune activation in healthy volunteers, 26 , 27 aspirin did not reduce biomarkers of HIV-related immune activation in PWH receiving ART in a placebo-controlled trial. 28 Furthermore, in PWH on ART, the effects of aspirin on the inhibition of platelet activation are impaired.…”