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. 2024 Aug 1;38(10):1460-1467.
doi: 10.1097/QAD.0000000000003907. Epub 2024 Apr 26.

Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV

Preeti Moar  1 , Kyaw Linn  2 , Thomas A Premeaux  1 , Scott Bowler  1 , Urvinder Kaur Sardarni  3 , Bindu Parachalil Gopalan  4   5 , Ei E Shwe  6 , Thidar San  6 , Haymar Han  2 , Danielle Clements  7 , Chaw S Hlaing  2 , Ei H Kyu  2 , Cho Thair  2 , Yi Y Mar  2 , Nway Nway  2 , Julie Mannarino  8 , Jacob Bolzenius  8 , Soe Mar  9 , Aye Mya M Aye  2 , Ravi Tandon  10 , Robert Paul  8 , Lishomwa C Ndhlovu  1
Affiliations

Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV

Preeti Moar et al. AIDS. .

Abstract

Objective: Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored.

Design: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART ( n = 15), ART-naive ( n = 15), and adolescents without HIV (AWOH; n = 10)] and Myanmar [AWH on ART ( n = 54) and AWOH ( n = 22)] were studied. Adolescents from Myanmar underwent standardized cognitive tests.

Methods: Plasma Gal-9 and soluble mediators were measured by immunoassays and cellular immune markers by flow cytometry. We used Mann-Whitney U tests to determine group-wise differences, Spearman's correlation for associations and machine learning to identify a classifier of cognitive status (impaired vs. unimpaired) built from clinical (age, sex, HIV status) and immunological markers.

Results: Gal-9 levels were elevated in ART-treated AWH compared with AWOH in both cohorts (all P < 0.05). Higher Gal-9 in AWH correlated with increased levels of inflammatory mediators (sCD14, TNFα, MCP-1, IP-10, IL-10) and activated CD8 + T cells (all P < 0.05). Irrespective of HIV status, higher Gal-9 levels correlated with lower cognitive test scores in multiple domains [verbal learning, visuospatial learning, memory, motor skills (all P < 0.05)]. ML classification identified Gal-9, CTLA-4, HVEM, and TIM-3 as significant predictors of cognitive deficits in adolescents [mean area under the curve (AUC) = 0.837].

Conclusion: Our results highlight a potential role of Gal-9 as a biomarker of inflammation and cognitive health among adolescents with perinatally acquired HIV.

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Conflict of interest statement

L.C.N. reports grants from the NIH and has received consulting fees from work as a scientific advisor for AbbVie, ViiV Healthcare, and Cytodyn where he also serves on the Board of Directors for work outside of the submitted work. L.C.N. interests were reviewed and are managed by Weill Cornell Medicine in accordance with their conflict-of-interest policies. All other authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Circulating galectin-9 levels in adolescents with perinatally acquired HIV and markers of inflammation and immune activation.
Fig. 2
Fig. 2
Plasma levels of galectin-9 correlate with neurocognitive impairment and classifies cognitive status in adolescents, independent of HIV status.
See this image and copyright information in PMC

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