Sex-specific associations between cerebrospinal fluid inflammatory biomarkers and cognition in antiretroviral-naïve people with HIV in rural Uganda

Julia Denniss; Rebecca T Veenhuis; Yanxun Xu; Lang Lang; Deanna Saylor; Sarah M Lofgren; David R Boulware; Noeline Nakasujja; Aggrey Anok; Steven J Reynolds; Thomas C Quinn; Gertrude Nakigozi; Leah H Rubin

doi:10.1016/j.bbi.2024.12.012

Sex-specific associations between cerebrospinal fluid inflammatory biomarkers and cognition in antiretroviral-naïve people with HIV in rural Uganda

Brain Behav Immun. 2024 Dec 10:125:1-8. doi: 10.1016/j.bbi.2024.12.012. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
² Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
³ Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, United States; Division of Biostatistics and Bioinformatics at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁴ Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, United States.
⁵ Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
⁶ Department of Psychiatry, Makerere University, Kampala, Uganda.
⁷ Rakai Health Sciences Program, Kalisizo, Uganda.
⁸ Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, United States; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address: [email protected].

PMID: 39667634
DOI: 10.1016/j.bbi.2024.12.012

Abstract

Globally, people with HIV (PWH) experience a broad spectrum of cognitive impairment that can be noted both before and after initiation of antiretroviral therapy (ART). Sex differences in immune function have been implicated in differential cognitive outcomes. Here, we report sex differences in cerebrospinal fluid (CSF) markers in relation to cognitive performance in a subset of ART-naïve PWH participating in the Rakai Neurology Cohort Study. Participants (55 % male, 45 % female, overall mean age 36.5 years, SD = 8.7) underwent a lumbar puncture and a cognitive battery prior to ART initiation. CSF was collected, and 14 inflammatory markers were analyzed. Individual cognitive test z-scores were generated based on local normative data. We used a series of least absolute shrinkage and selection operator (lasso) regressions to examine associations between CSF inflammatory markers and cognitive outcomes. CSF inflammatory levels did not differ significantly between sexes except for IL-8 being higher in men. In women with HIV, there were more significant associations between inflammatory markers and cognitive performance than men with HIV. Additionally, inflammatory markers were associated with a broader range of cognitive domains in women compared to men with HIV. Patterns of association differed by sex in this young, ART-naïve Ugandan cohort, and several associations in a particular sex persisted or shifted when compared to a post-ART timepoint. Further study into sex-specific patterns of inflammation is warranted to improve cognitive outcomes in PWH.

Keywords: Cognition; Cytokines; HIV; Immune; Sex differences.