Tu186 - Episodic Viremia in Women with HIV Alters IgG Galactose, IgG3 gp120, and Inflammatory Cytokines

Abstract Text: People living with HIV (PLWH) often exhibit chronic low-level immune activation, contributing to increased susceptibility to chronic comorbidities. This process, called inflammaging, has been linked to IgG glycosylation patterns. It has been shown that a reduction in galactose modifications on IgG correlates with a pro-inflammatory state. Our study evaluates how episodic viral rebound affects IgG galactosylation and pro-inflammatory biomarkers, providing potential markers for HIV disease progression.

Repository plasma from ten women with HIV (WWH) in the MWCCS (formerly WIHS) on cART, who experienced a single viremic episode (>200 copies/mL), was analyzed. Timepoints before, during, and after viremia were assessed. Subjects were stratified by viral load (low: < 1000 copies/mL vs. high: >5000 copies/mL). Bulk IgG galactose was quantified via ECL blot, HIV gp120-specific antibodies via ELISA, and inflammatory cytokines (e.g., IFN-y, IL-17a, IL-2) via Luminex. cART levels were measured by mass spectrometry.

Six of ten WWH showed a 38% reduction in IgG galactose levels during viremia; four had a sustained reduction post-resolution (average 36% reduction). In high viral load cases, IgG3 gp120 inversely correlated with IgG galactosylation (p=0.0376), while IL-2 correlated positively (p=0.0378). IL-17a correlated with IgG3 gp120 across viral loads (p=0.0323). Eight of ten individuals had reduced or undetectable cART levels during viremia.

These findings reveal IgG galactose reductions during viremia, indicating heightened inflammation and immune dysregulation. IgG galactosylation may serve as a valuable biomarker for inflammation and comorbidity risk in PLWH, highlighting the impact of episodic viremia on immune function and disease progression.