Persistent inflammatory activation in people living with HIV. Involvement in atherosclerosis.

Francisco Illanes-Álvarez¹Denisse Márquez-Ruiz¹Sara Cuesta-Sancho²Irene Campaña Gómez³Andrés Martín-Aspas³Ismael Tinoco-Racero¹Mercedes Márquez-Coello⁴José Antonio Girón-González^1*

• ¹Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación de Cádiz (INIBICA), Cádiz, Spain
• ²Hospital Universitario Puerta del Mar, Instituto para la Investigación e Innovación Biomédica de Cádiz (INIBICA). Institute of Biomedicine and Molecular Genetics (University of Valladolid), Cádiz, Spain
• ³Hospital Universitario PUerta del Mar. Instituto para la Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
• ⁴Facultad de Medicina. Universidad de Cádiz. Instituto para la Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain

Background. An increased prevalence of atherosclerosis has been observed in people living with HIV (PLWH). This study aimed to analyze levels of inflammatory, immune, endothelial, platelet, and coagulation parameters, as well as their relationship with subclinical atherosclerosis. Methods. A total of 120 PLWH with chronic infection and undetectable HIV load, along with 30 age- and sex-matched controls (HIV-uninfected individuals), were selected. Serum levels of proinflammatory molecules, including interleukin 6 (IL-6), soluble CD163, and high-sensitivity C-reactive protein, were measured. Additionally, neutrophil extracellular traps (NET)-derived parameters (anti-nucleosome antibody titers and myeloperoxidase concentrations), activated T lymphocytes, endothelial (E-selectin, vascular cell adhesion molecule 1), platelet (P-selectin, Platelet factor 4) and coagulation (D-dimer) markers were assessed. Cardiovascular risk factors were evaluated using the REGICOR and ASCVD risk estimators. In a subset of 61 individuals (18 controls and 43 PLWH), subclinical atherosclerosis was assessed by carotid Doppler ultrasound. Results. Levels of IL-6, sCD163, anti-nucleosome antibodies, and activated T lymphocytes were elevated in PLWH compared to controls. Likewise, serum levels of platelet factor 4 and D-dimer were higher in PLWH. Those PLWH with carotid atherosclerotic lesions exhibited higher REGICOR and ASCVD scores, as well as elevated IL-6 concentrations, compared to those PLWH without carotid atherosclerotic lesions. Multivariable analysis identified the REGICOR score and IL-6 serum levels as independent factors associated with atherosclerosis. Conclusions. PLWH with long-term viral load control exhibit increased levels of inflammatory, immune, platelet and coagulation markers. Subclinical atherosclerosis in this population is independently influenced by both classic cardiovascular risk factors and inflammatory activation.