Ontology highlight
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.
SUBMITTER: Moar P
PROVIDER: S-EPMC11239096 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
Moar Preeti P Linn Kyaw K Premeaux Thomas A TA Bowler Scott S Sardarni Urvinder Kaur UK Gopalan Bindu Parachalil BP Shwe Ei E EE San Thidar T Han Haymar H Clements Danielle D Hlaing Chaw S CS Kyu Ei H EH Thair Cho C Mar Yi Y YY Nway Nway N Mannarino Julie J Bolzenius Jacob J Mar Soe S Aye Aye Mya M AMM Tandon Ravi R Paul Robert R Ndhlovu Lishomwa C LC
AIDS (London, England) 20240426 10
<h4>Objective</h4>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.<h4>Design</h4>A cross-sectional study of two independent age-matched cohorts from India [AWH on AR ...[more]