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00925njm 22002777a 4500 dc Lara-Aguilar, Violeta author Crespo-Bermejo, Celia author Llamas-Adán, Manuel author Grande-García, Sergio author Cortijo-Alfonso, María Engracia author Martín-Carbonero, Luz author Domínguez, Lourdes author Ryan, Pablo author de Los Santos, Ignacio author Bartolomé-Sánchez, Sofía author Valle-Millares, Daniel author Jimenez-Sousa, Maria Angeles author Briz, Veronica author Fernandez-Rodriguez, Amanda author Multidisciplinary HIV/Hepatitis Viral Coinfection Group (COVIHEP) author 2023-07 Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence-Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27-2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP-associated factors [granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-β, interleukin (IL)-1β, IL-2, IL-8, IL-13, tumor necrosis factor (TNF)-α, IL-1α, IL-1RA, IL-7, IL-15, C-X-C motif chemokine ligand 10 (IP-10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL-1α, IP-10, and placental growth factor 1 (PIGF-1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral-induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence. J Med Virol. 2023 Jul;95(7):e28955. 10.1002/jmv.28955 1096-9071 Journal of medical virology 37465865 http://hdl.handle.net/20.500.12105/16335 HCV/HIV SASP Oxidative stress Senescence Spontaneous clearance Telomere HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART