Abstract Details

Title Genetic Influences on Long-term CSF and Plasma Biomarker Stability in People With HIV

Topic Infectious Disease

Presentation(s) S22 - Neuroinfectious Disease: Basic Sciences (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Objective To investigate whether host genetic variants influence 12-year stability of inflammatory, oxidative, and neurodegenerative biomarkers in PWH.

Background People with HIV (PWH) on effective antiretroviral therapy (ART) often show persistent inflammation and neurodegeneration. In the CHARTER cohort, several cerebrospinal fluid (CSF) and plasma biomarkers remained highly consistent for more than a decade, suggesting that host genetics may influence long-term biological “set points.”

Design/Methods Although 308 participants completed both baseline and 12-year visits, only those with paired biomarker samples were analyzed for each assay (n = 146–163). Biomarker stability was defined as the consistency of intra-individual levels over time, assessed by within-person correlations and residual-based models adjusted for age, sex, and ART status. Because data completeness varied, each biomarker was modeled independently using complete cases only. Separate multivariable regressions (adjusted for age, sex, ART, and baseline levels) examined associations between 19 candidate single-nucleotide polymorphisms (SNPs) and biomarker changes. Plasma markers included 8-oxo-dG, Aβ-42, CRP, D-dimer, IL-6, MCP-1, neopterin, protein carbonyls, sAPPα, sCD14, sCD40L, and sTNFR-II; CSF analyses included the same plus NFL, total tau, and pTau-181.

Results Most biomarkers showed high intra-individual stability over 12 years. The strongest correlations were seen for CSF Aβ-42 (r = 0.84), CSF sTNFR-II (r = 0.86), and plasma IL-6 (r = 0.32). Participants with higher baseline values tended to maintain rank order at follow-up, despite aging and ART changes. Distinct patterns in CSF and plasma indicated partially independent regulation. SNPs in neuroinflammatory and immune-response genes were associated with biomarker residuals after adjustment.

Conclusions Among PWH with paired biomarker data, CSF and plasma markers demonstrated remarkable long-term stability, implying intrinsic biological regulation. Genetic variation appears to modulate these enduring profiles, supporting biomarker stability as a potential endophenotype for studying genetic vulnerability to neurodegeneration in chronic HIV.

Authors/Disclosures
Daniel V. De Siqueira Lima, Jr., MD PRESENTER	Dr. De Siqueira Lima has nothing to disclose.
Mattia Trunfio, MD, PhD	Dr. Trunfio has nothing to disclose.
Jamison Burks, PhD	Dr. Burks has nothing to disclose.
Scott L. Letendre, MD (HNRC, UCSD)	The institution of Dr. Letendre has received research support from National Institutes of Health. The institution of Dr. Letendre has received research support from University at Buffalo. Dr. Letendre has received publishing royalties from a publication relating to health care.
Benjamin Smarr, PhD	Prof. Smarr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ouraring Inc. Prof. Smarr has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INTO Inc. Prof. Smarr has stock in Ouraring Inc. The institution of Prof. Smarr has received research support from DoD/MTEC. The institution of Prof. Smarr has received research support from Intel Inc.
Patricia K. Riggs, DO	Dr. Riggs has nothing to disclose.
Donald Franklin, Jr., Research Administrator	Mr. Franklin has nothing to disclose.
Ronald J. Ellis, MD, PhD, FAAN (UC San Diego)	Dr. Ellis has nothing to disclose.

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