Background <p>Previous studies have indicated a strong association between CD169 and HIV-1 infection, showing significant elevation of CD169 during infection and viral replication. This study aimed to investigate whether CD169 could serve as a biomarker for the early diagnosis of HIV-1 infection.</p> Methods <p>We recruited patients with acute people with HIV(PWH), ART-treated PWH and HIV-1 negative volunteers. Clinical data and peripheral blood samples were collected. CD169 expression on CD14⁺ monocytes was detected by flow cytometry, and soluble CD169 in plasma was assayed to investigate its relationship with HIV-1 infection and disease progression.</p> Results <p>Our study detected a high proportion of CD169⁺CD14⁺ monocytes in individuals with acute PWH. Furthermore, we observed that CD169 expression levels were elevated in PWH who had stopped taking their medication.</p> Conclusion <p>The discovery of CD169 expression in CD14⁺ monocytes as a biomarker for early HIV-1 infection or AIDS diagnosis offers new possibilities for early intervention and treatment, potentially improving clinical outcomes for PWH.</p> Clinical Trial <p>Not applicable.</p>