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

Figures

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  Figure 1. Concentration of ASA in ng/ml measured in the systemic (plasma) and female genital tract (CVL) compartment measured at visit 3 (six weeks after starting daily ASA 81mg regimen). CVL cervico-vaginal lavage. p values < 0.05 were considered significant. The lower limits of quantitation (LLOQ) for CVL was 39 ng/mL indicated by the dotted line and for plasma was 78 ng/mL indicated by the dashed line.

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  Figure 2. Effect of ASA uptake on TXB2 level between baseline (Visit 1), Visit 3 (after 6 weeks on 81mg ASA drug regimen) and at follow-up (two weeks after ending ASA regimen) in the systemic compartment (plasma). Data was analyzed using Wilcoxon matched-pairs signed rank test. p values < 0.05 were considered significant, NS, non-significant. Median [IQR] values for visit 1 and visit 3 can be found in Supplementary Table S1 .

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  Figure 3. Correlation between the level of TXB2 in the plasma and immune activation at the mucosal and systemic compartment at visit 3 (six weeks after starting daily ASA 81mg regimen). (A) correlations between cytokines and chemokine and TXB2. (B) correlations between CD4+Tcell activation status and TXB2. (C) correlations between CD8+Tcell activation status and TXB2. (D) correlations between MAIT and Tc17 activation status and TXB2. Data was analyzed using Pearson correlation or Spearman’s rank test depending on normality of the data. p values<0.05 were considered significant. CVL, cervico-vaginal lavage; CMC, cervical mononuclear cells; PBMCs, peripheral blood mononuclear cells; CM, central memory cells; EM, effector memory cells; MFI, median fluorescent intensity indicates marker expression on a per cell bases.

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  Figure 4. T cell blood proportion and immune activation status measured by flow cytometry. (A) systemic CD4+T cell activation changes between Visit 1 (baseline) and Visit 3 (after 6 weeks daily uptake of 81mg ASA). (B) systemic CD8+T cell activation changes between Visit 1 and Visit 3. (C) correlation between systemic T cell activation and blood concentration of ASA (ng/mL) at Visit 3. (D) correlation between systemic T cell activation and CVL concentration of ASA (ng/mL) at Visit 3. Data for (A, B) was analyzed using Wilcoxon matched-pairs signed rank test, multivariate regression was performed to control for the effect of DMPA and age on immune activation changes. Median [IQR] values for visit 1 and visit 3 can be found in Supplementary Table S1 . Data for (C, D) was analyzed using Pearson correlation or Spearman’s rank test depending on normality of the data. p values<0.05 were considered significant. CM, central memory cells; MFI, median fluorescent intensity indicates marker expression on a per cell bases.

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  Figure 5. T cell mucosal proportion and immune activation status measured by flow cytometry on cervical mononuclear cells. (A) mucosal CD4+T cell activation changes between Visit 1 (baseline) and Visit 3 (after 6 weeks daily uptake of 81mg ASA). (B) mucosal CD8+T cell activation changes between Visit 1 and Visit 3. (C) correlation between mucosal T cell activation and blood concentration of ASA (ng/mL) at Visit 3. (C) correlation between mucosal T cell activation and CVL concentration of ASA (ng/mL) at Visit 3. Data for (A, B) was analyzed using Wilcoxon matched-pairs signed rank test, multivariate regression was performed to control for the effect of DMPA and age on immune activation changes. Median [IQR] values for visit 1 and visit 3 can be found in Supplementary Table S1 . Data for (C, D) was analyzed using Pearson correlation or Spearman’s rank test depending on normality of the data. p values<0.05 were considered significant. MFI, median fluorescent intensity indicates marker expression on a per cell bases.