Comorbidities Associated With Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein Levels Among People Living With HIV
Elena Beideck1, Petra Bachanova2, Linzy Rosen3, Hemi Park4, Pia Kivisakk Webb4, Felicia Chow7, Kunling Wu8, Leah Rubin10, Katherine Tassiopoulos9, Robert Parker5, Emily Hyle6, Shibani Mukerji4
1Division of Infectious Diseases, Beth Israel Deaconess Medical Center, 2Vaccine and Immunotherapy Center, 3Medical Practice Evaluation Center, 4Department of Neurology, 5Biostatistics Center, 6Division of Infectious Diseases, Massachusetts General Hospital, 7Zuckerberg San Francisco General Hospital, 8Center for Biostatistics in AIDS Research, 9Department of Epidemiology, Harvard T.H. Chan School of Public Health, 10Department of Neurology, Johns Hopkins University School of Medicine
Objective:

To examine associations between comorbidities and plasma levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in people living with HIV (PLWH) on antiretroviral therapy (ART) without cognitive impairment.

Background:

NfL and GFAP are increasingly studied as biomarkers in neurologic conditions. Their use among PLWH has been proposed, but examination of levels among cognitively unimpaired PLWH on ART and associations with comorbidities are needed to optimize interpretation.

Design/Methods:

The study population included cognitively unimpaired PLWH from the ACTG HAILO study: age ≥45 years, on ART, with HIV RNA <200 copies/mL, and eGFR≥30 mL/min/1.73m2. Cognitively unimpaired status was based on composite results of four neuropsychological tests. Plasma NfL and GFAP were quantified by the Simoa assay. Multivariable linear regression models for log-transformed NfL and GFAP were fitted to examine cross-sectional relationships between biomarker levels and ASCVD risk, eGFR, neuropathy, demographics, and HIV-related variables.

Results:

Among 371 subjects, mean (SD) age was 53.2 (6.3) years, 67 (18.1%) were female, and 209 (56.3%) were non-Hispanic White. Mean (SD) BMI was 28.5 (5.8) kg/mm3, 31 (8.4%) had eGFR <60, and 207 (57.8%) had ASCVD risk ≥5%. In linear regression, age (β= 0.090, p<0.001) and self-identified White race (β=0.085, p<0.001) were positively associated with NfL. GFR (β= -0.065, p<0.001), BMI (β= -0.011, p<0.001), and CD4 nadir (β= -0.007, p=0.032) were negatively associated with NfL. Age (β= 0.107, p<0.001) was positively associated with GFAP. GFR (β= -0.084, p<0.001), BMI (β= -0.004, p=0.040), ASCVD risk (β= -0.018, p=0.024), and male sex at birth (β= -0.100, p=0.001) were negatively associated with GFAP. HIV-related factors did not show clinically impactful associations with either biomarker.

Conclusions:

In this cross-sectional analysis of cognitively unimpaired PLWH, age, lower eGFR and BMI were associated with higher NFL and GFAP. ASCVD risk and race showed variable associations. HIV-related factors did not show clinically impactful associations.

10.1212/WNL.0000000000217226
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