Plasma NfL and sCD14 Are Associated with Polypharmacy and Recurrent Falls in Virally Suppressed Older People with HIV

People with HIV (PWH) are living longer due to effective antiretroviral therapy (ART) but face accelerated aging, accumulating comorbidities, and high rates of polypharmacy. Whether neuroinflammatory biomarkers are associated with polypharmacy and adverse clinical outcomes such as falls in this population is unknown.

We performed a cross-sectional analysis of baseline data from 600 virally suppressed PWH ≥40 years enrolled in the ACTG A5322 HAILO cohort. Plasma neurofilament light chain (NfL), neopterin, and soluble CD14 (sCD14) were measured. Multivariable logistic regression examined associations between each biomarker and polypharmacy (five or more non-ART medications), recurrent falls (two or more falls/6 months), and slow gait speed less than one m/s), adjusting for age, sex, and comorbidity burden.

The median age was 54 years, 78% of participants were male, and 232 participants (39%) had polypharmacy. Elevated NfL was independently associated with polypharmacy in multivariable analysis (aOR 1.16 [95% CI 1.07-1.26]). In the total population, elevated NfL (OR 1.24 [1.05-1.46]) and sCD14 (OR 1.12 [1.01-1.23]) were each associated with recurrent falls. Among participants with polypharmacy, only elevated sCD14 remained associated with recurrent falls on stratified multivariable analysis (OR 1.15 [1.02-1.30]). No biomarker was significantly associated with slow gait speed.

In older virally suppressed PWH, plasma NfL and sCD14 are associated with distinct adverse clinical phenotypes-medication burden and fall risk, respectively, and may serve as complementary biomarkers of distinct biological pathways relevant to aging in HIV.