Monocyte correlates of neurocognitive impairment in chronic HIV infection include early, persistent changes with ART
10 affiliations
- 1Division of Microbiology, Tulane National Biomedical Research Center, Tulane University, Covington, Louisiana, USA.
- 2Biology Department, Boston College, Chestnut Hill, Massachusetts, USA.
- 3Innate Pharma, Marseille, France.
- 4Department of Medicine, Rutgers Institute of Translational Medicine and Science, Rutgers Biomedical Health and Sciences, Rutgers University, New Brunswick, New Jersey, USA.
- 5Division of Neurology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.
- 6SEARCH Foundation, Bangkok, Thailand.
- 7Department of Global Health, Amsterdam Medical Center, University of Amsterdam, Amsterdam, Netherlands.
- 8Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
- 9International Vaccine Institute, Seoul, South Korea.
- 10Department of Microbiology & Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Abstract
Persistent monocyte activation contributes to HIV-associated neurocognitive disorders (HAND), yet biomarkers that predict neurocognitive impairment before and after antiretroviral therapy (ART) remain incompletely defined. We evaluated monocyte subsets and activation markers in participants from the SEARCH007 cohort before ART initiation and at 6 and 12 months following treatment. Increased frequencies of CD14+CD16+ monocytes and elevated CD163 expression were associated with worsening neurocognitive performance and HAND severity. Plasma soluble CD163 levels increased with neurocognitive impairment and correlated with plasma HIV RNA levels, while CCR2 expression was associated with a composite neuropsychological performance Z-score (NPZglobal). Notably, CD169 expression was elevated across all monocyte subsets and demonstrated a stepwise increase with worsening neurocognitive impairment. Although ART reduced overall monocyte activation, elevated CD169 expression persisted in some individuals despite virologic suppression. Bayesian kernel machine regression and random forest analyses identified CD169 expression as one of the strongest predictors of cognitive impairment, surpassing plasma viral load, CD4+ T cell count, and several established monocyte activation markers. These findings identify monocyte CD169 expression as a biomarker of neurocognitive dysfunction before and during the first year of ART and support further investigation of its role in HAND pathogenesis.
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BibTeX
@article{nguyen2026monocyte,
title = {{Monocyte correlates of neurocognitive impairment in chronic HIV infection include early, persistent changes with ART}},
author = {Hai Duc Nguyen and Andrew K. Ding-Su and Caroline Soulas and Tricia H. Burdo and Patrick Autissier and Pasiri Sithinamsuwan and Nitiya Chomchey and Jintanat Ananworanich and Victor Valcour and Silvia Ratto-Kim and Woong-Ki Kim and Kenneth C. Williams},
journal = {JCI Insight},
year = {2026},
month = aug,
doi = {10.1172/jci.insight.194766},
url = {https://doi.org/10.1172/jci.insight.194766},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Monocyte correlates of neurocognitive impairment in chronic HIV infection include early, persistent changes with ART
AU - Hai Duc Nguyen
AU - Andrew K. Ding-Su
AU - Caroline Soulas
AU - Tricia H. Burdo
AU - Patrick Autissier
AU - Pasiri Sithinamsuwan
AU - Nitiya Chomchey
AU - Jintanat Ananworanich
AU - Victor Valcour
AU - Silvia Ratto-Kim
AU - Woong-Ki Kim
AU - Kenneth C. Williams
PY - 2026
DA - 2026/08/27
JO - JCI Insight
DO - 10.1172/jci.insight.194766
UR - https://doi.org/10.1172/jci.insight.194766
AB - Persistent monocyte activation contributes to HIV-associated neurocognitive disorders (HAND), yet biomarkers that predict neurocognitive impairment before and after antiretroviral therapy (ART) remain incompletely defined. We evaluated monocyte subsets and activation markers in participants from the SEARCH007 cohort before ART initiation and at 6 and 12 months following treatment. Increased frequencies of CD14+CD16+ monocytes and elevated CD163 expression were associated with worsening neurocognitive performance and HAND severity. Plasma soluble CD163 levels increased with neurocognitive impairment and correlated with plasma HIV RNA levels, while CCR2 expression was associated with a composite neuropsychological performance Z-score (NPZglobal). Notably, CD169 expression was elevated across all monocyte subsets and demonstrated a stepwise increase with worsening neurocognitive impairment. Although ART reduced overall monocyte activation, elevated CD169 expression persisted in some individuals despite virologic suppression. Bayesian kernel machine regression and random forest analyses identified CD169 expression as one of the strongest predictors of cognitive impairment, surpassing plasma viral load, CD4+ T cell count, and several established monocyte activation markers. These findings identify monocyte CD169 expression as a biomarker of neurocognitive dysfunction before and during the first year of ART and support further investigation of its role in HAND pathogenesis.
SN - 2379-3708
ER -