BACKGROUND: Older people with HIV (PWH) experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps due to residual inflammation despite suppressive antiretroviral therapy. Cell-free mitochondrial DNA (cfmtDNA) released during necrosis-mediated cell death potentially acts as both mediator and marker of inflammatory dysregulation. Thus, we evaluated plasma cfmtDNA as a potential biomarker of geriatric syndromes.

METHODS: Participants underwent the Montreal Cognitive Assessment (MoCA), frailty testing, and measurement of plasma cfmtDNA by qPCR and inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNFα) in this cross-sectional study.

RESULTS: Across 155 participants, the median age was 60 years (Q1, Q3: 56, 64), one third were female and 92% had HIV-1 viral load <200 copies/ml. Median MoCA score was 24 (21, 27). Plasma cfmtDNA level was higher in those with cognitive impairment (MoCA <23) (p=0.02 by t-test) and remained significantly associated with cognitive impairment in a multivariable logistic regression model controlling for age, sex, race, CD4 T-cell nadir, HIV-1 viremia and depression. Two-thirds of participants met criteria for a pre-frail or frail state; higher plasma cfmtDNA was associated with slow walk and exhaustion but not overall frailty state. Cognitive dysfunction was not associated with CRP, IL-6, IFNγ, or TNFα, and frailty state was only associated with IL-6.

CONCLUSIONS: Plasma cfmtDNA may have a role as a novel biomarker of cognitive dysfunction and key components of frailty. Longitudinal investigation of cfmtDNA is warranted to assess its utility as a biomarker of geriatric syndromes in older PWH.