Plasma Glycomic Markers of Accelerated Biological Aging During Chronic HIV Infection

People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1216 women and men, living with virally-suppressed HIV or without HIV. Our glycan-based machine learning models indicate that chronic HIV infection accelerates the accumulation of pro-aging-associated glycomic alterations by an average of 3 years in women and 3.5 years in men. Consistently, PWH exhibit heightened expression of senescence-associated glycan-degrading enzymes compared to their controls. HIV/ART-mediated glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, may precede the development of such comorbidities, and are linked to compromised anti-viral IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic-based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.