The potential roles of IgG glycosylation in the development of non-communicable comorbidities in people with HIV

The introduction of effective antiretroviral therapy (ART) has transformed Human Immunodeficiency Virus (HIV) infection from a once-fatal diagnosis into a manageable chronic condition, with life expectancy in people with HIV approaching that of the general population. However, this extended lifespan has unveiled a critical secondary challenge: an accelerated incidence of age-associated non-communicable comorbidities (AANCC), including cardiovascular disease, type II diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and HIV-associated cognitive impairment. Although ART effectively suppresses viral replication, it does not fully resolve the chronic immune activation and low-grade inflammation that characterise treated HIV infection. This persistent inflammatory milieu is hypothesised to drive the premature onset of comorbidities, yet the specific mechanisms underlying incident AANCC remain incompletely elucidated. IgG glycosylation is known to modulate inflammation in the general population, and concentrations of two IgG glycosylation traits, galactosylation and sialylation, are reportedly decreased in people with HIV. Whether IgG agalactosylation and asialylation contribute to inflammation and AANCC development in this population therefore warrants investigation. In this review, we examine how HIV infection may alter IgG glycosylation and the potential contribution of these changes to AANCC progression in people with and without HIV.