Distinctive Inflammatory Proteomic Profile of HIV‐1 Elite Controllers: A Comparative Study in a Spanish Cohort

Elite controllers (EC) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of functional cure. Significant evidence suggests that despite viral control, EC subjects may have altered levels of systemic inflammation. We have performed a comprehensive characterization of the systemic inflammation profile in EC compared to non-controllers PLWH either with or without ART-mediated control of viral replication. 40 participants were included: 10 EC, 10 non-controllers PLWH on ART (onART), 10 non-controllers PLWH ART-naïve (offART), and 10 uninfected controls (UC) as reference. Plasmatic levels of 92 surrogate markers of inflammation were assessed using the proximity extension assay (Olink proteomics, Sweden). An additional panel of nine proteins was also assayed by comercial ELISA. Differential expression analysis, principal component analysis (PCA), and clustering analysis were carried out using the Metaboanalyst software and the R software. Pathway enrichment analysis (PEA) was carried out using the STRING platform. Compared to UC, offART group showed the highest disturbance in the inflammatory markers with 30 different proteins differentially expressed (DE) (29/30 upregulated; p