Inhibiting Glycan Degradation Prevents HIV-Induced Inflammaging and Cognitive Impairment

The mechanisms underlying this decline remain poorly understood. Here, we identify pro-inflammatory glycan degradation, characterized by loss of sialic acid and galactose, alterations that are hallmarks of premature aging, as key contributors to HIV-associated cognitive impairment (HIV-CI).

In two independent cohorts of people living with HIV, these degradative changes were enriched in individuals with cognitive impairment, particularly women, and correlated with worse neurocognitive performance. In both a humanized mouse model of HIV and Eco-HIV, a complementary model that allows behavioral testing, pharmacological inhibition of glycan degradation with sialidase inhibitors prevented virally induced inflammation, immune activation, accelerated aging, and memory deficits.