We evaluated whether plasma biomarkers of neuroinflammation and immune activation are associated with motor impairment in middle-aged and older people with HIV (PWH).

Despite effective antiretroviral therapy (ART), motor impairment remains a common comorbidity among aging PWH. Prior work has linked individual cytokines (soluble CD14 [sCD14], TNF-α) with complex motor task deficits, but the cumulative effect of multiple biomarkers is unknown.

This prospective, cross-sectional study included 56 PWH attending the University of North Carolina-Chapel Hill Infectious Diseases clinic, aged ≥50 years, on stable ART for ≥1 year, with undetectable plasma HIV RNA for ≥6 months. Participants completed neuropsychological testing, including Grooved Pegboard dominant and non-dominant hands, for motor performance, and Patient Health Questionnaire-9 for depressive symptoms. Plasma was assayed for TNF-α, TGF-β, sCD27, sCD14, CXCL10, sCD163, and CCL2, neuroinflammation or immune activation biomarkers in HIV. Motor impairment was defined as motor T-score <40. Pearson correlations were used across cognitive domains. Principal component analysis reduced biomarker measures to two components (PC1: TNF-α, CXCL10; PC2: TGF-β, sCD27, sCD163). Multivariable regression, adjusting for sex, evaluated associations between PCs and motor T-scores.

Participants’ mean (standard deviation [SD]) age was 60.7 (6.2) years, 32.1% female, 13.9 (2.7) educational years. Over half (51.8%) self-identified as African American/Black. Median HIV duration was 26 (interquartile range [IQR] 15–32) years; current CD4 725 (453–849), nadir CD4 445 (252–650). Sixteen percent had moderate-to-severe depressive symptoms, and 23.2% had motor impairment. Motor T-scores did not correlate with executive function, memory or processing speed domains. PC2 was significantly inversely associated with motor performance (t= –3.33, p=0.002), whereas PC1 was not (p=0.874).

In aging PWH, higher cumulative immune activation from TGF-β, sCD27, sCD163 is associated with worse motor performance despite stable ART and viral suppression. These findings highlight the need to target chronic neuroimmune activation in aging PWH.