SARS-CoV-2 viral shedding in people living with HIV: prolonged duration despite antiviral therapy

Abstract Background People living with HIV (PLWH) may exhibit delayed SARS-CoV-2 clearance, but whether this occurs after standardized anti-SARS-CoV-2 therapy remains unclear, and the underlying immunological mechanisms are poorly understood. Methods We conducted an observational cohort study of 149 hospitalized patients with confirmed SARS-CoV-2 infection (32 PLWH, 117 HIV-negative controls) who received anti-SARS-CoV-2 treatment between December 2022 and June 2023. Viral shedding duration and early clearance (day 5) were compared between groups. Multivariate logistic regression and Cox proportional hazards models identified predictors of viral clearance. In a subset of participants from the same cohort, plasma cytokines were quantified by Luminex multiplex assay in 100 individuals. Results PLWH had significantly longer median viral shedding duration (22 vs. 14 days, P < 0.001) and lower early clearance rates (15.6% vs. 60.7%, P < 0.001). HIV infection was the strongest independent predictor of impaired clearance (adjusted OR for early clearance = 0.026, 95% CI: 0.004–0.159; HR for viral clearance = 0.351, 95% CI: 0.197–0.626). Higher lymphocyte count correlated with faster clearance (HR = 1.999, 95% CI: 1.372–2.914). Cytokine profiling revealed that HIV+/SARS-CoV-2 + co-infection was associated with elevated levels of immunosuppressive molecules IL-10 and PD-L1 alongside type I interferon activation. Conclusions PLWH experience substantially prolonged SARS-CoV-2 shedding despite antiviral therapy. This delay is associated with an immune signature of functional exhaustion characterized by elevated IL-10 and PD-L1. Early antiviral intervention and extended monitoring should be prioritized for this vulnerable population.