Cytokine Concentrations in Seminal Plasma and Blood in HIV Infection: Differential Modulation by Antiretroviral Therapy and Association with HIV RNA Levels and CD4+T Cell Count

Background and Objectives: The complex cytokine network in seminal fluid during human immunodeficiency virus (HIV) infection remains incompletely understood. This study aimed to investigate inflammatory cytokine levels in the semen of individuals with chronic HIV infection and assess the effects of antiretroviral therapy ART on cytokine networks. Materials and Methods: A total of 26 HIV infected individuals were recruited, including 16 treatment-naïve (TN) patients, 10 patients receiving ART for over 2 years with plasma HIV viral loads of < 20 copies/mL (CR group), and 4 healthy controls (HC). Differences in inflammatory cytokine levels were analyzed using the Olink assay in paired seminal plasma and blood samples, along with correlations between cytokine levels and indicators of disease progression. Moreover, differences in cytokine networks between seminal plasma and blood plasma were analyzed, and the effects of ART on these networks were evaluated. Results: HIV infection and ART altered cytokine networks in seminal plasma compared with those in HC. The levels of semen cluster 1 (interferon-γ, IL-12B, MCP-2, MCP-4, and Flt3L) in the TN group were significantly higher than those in the HC group. HIV infection was associated with increased rigidity of the seminal cytokine network, and significant differences were observed between the cytokine networks of seminal and blood plasma, both with and without ART. Additionally, seminal plasma levels of Flt3L, MCP-4, IL-1alpha, OSM, TWEAK, VEGFA, transforming growth factor-alpha, HGF, NT-3, IL-4, IL-17C, beta-NGF, FGF-19, and TRAIL were significantly correlated with baseline HIV RNA levels and CD4 + T cell counts. Conclusion: ART had a greater effect on cytokine levels in blood plasma than in seminal plasma. Seminal plasma also exhibited higher concentrations of cytokines associated with indicators of HIV disease progression than blood plasma. Keywords: cytokine, human immunodeficiency virus, plasma, seminal