Table 1.
Drugs with anti-inflammatory properties to reduce atherosclerosis in HIV disease.
| Mechanism of action | Drug examples | References | Notes |
|---|---|---|---|
| COAGULATION | |||
| COX-1 pathway inhibition | Aspirin | (69, 92) | No differences in soluble markers (sCD14, IL-6, sCD163, D-dimer) or T-cell or monocyte activation. |
| Adenosine reuptake inhibitor | Dipyramidole | (93) | Decreased CD4+ T-cell activation in pooled analysis. No changes in soluble markers (sCD14, IL-6, sCD163, CRP, IL-10, sCD27, D-dimer) |
| Factor Xa inhibitor | Edoxaban | (94) | No differences in inflammation (IL-6, TNF-RI, IL-1β, sCD163, sCD14, or monocyte activation markers. Lowered D-dimer and thrombin antithrombin (TAT). |
| Coagulation inhibition Factor IIa inhibitor |
Dabigatran | (95, 96) | Attenuated atherosclerotic plaque formation, decreased collagen content and ROS production, observed improved endothelial function |
| METABOLISM | |||
| Inhibits dihydrofolate reductase enzyme Inhibits binding of IL1β to its surface receptor | Methotrexate | (97, 98) | No significant effect on endothelial function or inflammatory biomarkers (hs-CRP, IL-6, IP-10, sCD163, sCD14, D-dimer, fibrinogen, VCAM) associated with decreased CD8+ T-cells, saw more safety events (Hsue) LDMTX with some effect on brachial artery US that correlated with decreased D-dimer |
| HMGCoA enzyme inhibition | Statins | (99, 100) | Decreased sCD14 and IP-10 levels, decreased activated T-cells (Funderberg); Reduction in non-calcified plaque volume and high-risk coronary plaques (Lo); Reducing ASCVD risk, ongoing REPRIEVE trial |
| Inhibition of ATP-citrate lyase and activation of AMP activated protein kinase in the liver | Bempedoic acid | (101–103) | Prevention of atherosclerotic plaque development and associated inflammation; lowers LDL, total cholesterol, apolipoprotein B, hs-CRP- unclear clinical effect |
| CYTOKINE SIGNALING | |||
| mAB blocking IL-1β | Canakinumab | (104, 105) | Lower rates of recurrent CVD independent of lipid lowering, higher incidence of fatal infection, expensive therapy Decreased rates of hs-CRP, IL-6 and sCD163, no impact on T cell activation or monocyte subsets Decreased arterial inflammation on FDG-PET |
| mAB binding IL-6 | Tocilizumab | (106) | Expensive therapy, effective for treatment of Castleman disease; reduced levels of secretory phospholipase A2-IIA, lipoprotein (a), fibrinogen, D-dimers, elevated paraoxonase; increased LDL and triglyceride levels |
| Jak-inhibitors | Ruxolitinib/tofacitinib/baricitinib | (107) | Ruxolitinib with no decrease IL-6 levels, decrease in sCD14, increase in circulating T- cells |
| IL-1R | Anakinra | (108) | Improved myocardial deformation; decreased hs-CRP at time of NSTE-ACS |
| TNF-alpha inhibitors | Infliximab—Etanercept—Adalimumab | (109) | Increased total cholesterol and HDL levels in RA patients; no change in CRP levels, potentiated response to acetylcholine |
| COINFECTIONS | |||
| Competitive inhibitor of deoxyguanosine triphosphate inhibiting viral DNA polymerases | Valgancyclovir | (110) | Reduced CD8 activation, no significant difference in CRP |
| GUT MICROBIOME | |||
| Alteration of microbiome | Probiotics | (111, 112) | Increase in Th17 cell subsets; Lipopolyscharide binding protein and hs-CRP decrease with probiotics in PWH, not sCD14 and D-dimer; Increase in serum serotonin, decreased tryptophan in plasma, reduction in CD38 and HLA-DR expression on PBMCs |
| Antibiotic | rifaximin | (113) | No effect on LPS (lipopolysaccharide) and sCD14 at 2 weeks, decrease LPS in cirrhotic patients |