Plasma proteomic signatures in HIV-infected individuals post-SARS-CoV-2 infection

Abstract The long-term immunological effects of prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in people living with Human Immunodeficiency Virus (HIV) remain poorly understood. This study aimed to characterize plasma proteomic alterations associated with previous SARS-CoV-2 infection in HIV-infected individuals and to identify potential biomarkers and affected pathways. High-throughput liquid chromatography–tandem mass spectrometry (LC–MS/MS) was performed on plasma obtained from three groups: HIV-infected individuals with documented prior SARS-CoV-2 infection, HIV-monoinfected individuals, and healthy controls. A total of 13,675 proteins were identified. Hierarchical clustering and sparse partial least squares discriminant analysis revealed distinct proteomic profiles in the prior-SARS-CoV-2 group. Ten proteins with the highest discriminatory power—PRR11, TEX14, METTL9, NMD3, PXT1, CRISP2, MELK, SPF27, GCP6, and GTPBP8—were associated with cell cycle regulation, RNA processing, apoptosis, mitochondrial function, and cytoskeletal organization. Subcellular localization indicated predominant nuclear and cytoplasmic involvement, suggesting alterations in transcriptional regulation and intracellular structural dynamics. These signatures imply that preceding SARS-CoV-2 exposure may compound HIV-associated immune dysregulation and disrupt cellular homeostasis. The findings offer novel molecular insights into the persistent biological impact of SARS-CoV-2 in the context of HIV and identify candidate proteomic biomarkers with potential utility for risk stratification and targeted intervention in immunocompromised populations.