(P23) Systemic inflammation in people living with HIV on successful therapy: higher risk of neurological diseases and inflamm-aging

Författare/Medförfattare

Ujjwal Neogi [1]

Affiliates

Department of Laboratory Medicine, ANA Futura, Karolinska Institute, Flemingsberg Campus, Stockholm Sweden [1]

Abstract

Background: Long-term HIV infection, even with successful combination antiretroviral therapy (cART), is associated with an enhanced and accentuated onset of premature-aging or age-related diseases in people living with HIV (PLHIV). The present study aimed to evaluate the levels of systemic inflammation and predict the risk of age-associated diseases by machine learning approach in PLHIV on long-term suppressive ART using a large number of biomarkers of the inflammation and immune activation and untargeted metabolomics profile.
Method: Blood samples were obtained from therapy naïve PLHIV (Pre-ART, n=43), PLHIV on ART for >5 years (ART, n=53), and HIV-negative healthy controls (HIVNC, n=41) after screening 258 individuals. Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, and telomere length. In a subset of samples, untargeted metabolite profiling was carried out using Ultra-High-Performance Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (UHPLC/MS/MS).
Results: Despite a median duration of eight years of successful ART, sCD14, sCD163, 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL, and TRANCE levels continued to be significantly elevated in the ART group as compared to HC. Metabolic abnormalities in amino acid levels, energetics, phospholipids, and complex lipids, were observed, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS). Ingenuity Pathway Analysis of metabolites indicated a higher risk of inflammatory and neurological diseases in PLHIV (Figure 1), which was further supported by the plasma proteomics.
Conclusions: Put together, these data suggest that HIV-1 infected individuals, even those on long term successful ART, may be at higher risk of developing inflammatory diseases leading to inflamm-aging. Metabolic abnormalities were observed in amino acid levels, energetics and phospholipids and complex lipids, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS).