Plasma galectin-9 as a predictor of adverse non-AIDS events in persons with chronic HIV during suppressive antiretroviral therapy

Thomas A. Premeaux, Carlee B. Moser, Ashley McKhann, Martin Hoenigl, Elizabeth I. Laws, Draven L. Aquino, Michael M. Lederman, Alan L. Landay, Sara Gianella, Lishomwa C. Ndhlovu

Research output: Contribution to journalArticlepeer-review


Background:People with HIV (PWH) on antiretroviral therapy (ART) still experience an increased risk of morbidity and mortality, presumably driven by chronic inflammation, yet predictors of discrete or combinatorial outcomes remain unclear. Galectin-9 (Gal-9), a driver of both inflammatory and immunosuppressive responses, has been associated with HIV disease progression and multimorbidity.Objective:To determine whether plasma Gal-9 levels are associated with the occurrence of specific non-AIDS events (NAEs) in PWH initiating ART.Design:We performed a nested case-control study of PWH enrolled from 2001 to 2009 and evaluated pre-ART (66 cases, 97 controls), a year post-ART (112 cases, 211 controls), and immediately preceding an event (89 cases, 162 controls). Events included myocardial infarction/stroke, malignancy, serious bacterial infection, or death.Methods:Plasma Gal-9 levels were assessed by ELISA. Conditional logistic regression assessed associations with NAEs and Spearman's correlations compared Gal-9 with other previously assessed biomarkers.Results:NAEs occurred at a median of 2.8years (1.7-4.6) after ART initiation. Higher Gal-9 levels were associated with increased risk of NAEs at year 1 and preevent [odds ratio (OR) per 1 interquartile range=1.4-1.6; all P<0.05], specifically myocardial infarction/stroke at year 1 (OR=1.9; P=0.029). Gal-9 also correlated with multiple inflammatory and immune activation predictors of NAEs (all timepoints).Conclusion:Elevated Gal-9 levels are predictive of deleterious NAEs, particularly cardiovascular complications. Whether the Gal-9 pathway, potentially binding to its putative ligands, is active in the pathogenesis of these outcomes warrants further investigation to determine if targeting Gal-9 may slow or reverse the risk of NAEs.

Original languageEnglish (US)
Pages (from-to)2489-2495
Number of pages7
Issue number15
StatePublished - Dec 1 2021
Externally publishedYes


  • antiretroviral therapy
  • biomarkers
  • galectins
  • HIV
  • morbidity
  • viral suppression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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