Plasma Cell-Free Mitochondrial DNA as a Marker of Geriatric Syndromes in Older Adults With HIV.

Background: Older people with HIV 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, interleukin-6 (IL-6), interferon gamma, and tumor necrosis factor alpha 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. The median MoCA score was 24 (21, 27). The plasma cfmtDNA level was higher in those with cognitive impairment (MoCA <23) ( P = 0.02 by the 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 the criteria for a prefrail or frail state; higher plasma cfmtDNA was associated with slow walk and exhaustion but not overall frailty state. Cognitive dysfunction was not associated with C-reactive protein, IL-6, interferon gamma, or tumor necrosis factor alpha, 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 people with HIV.
Competing Interests: E.L.S., M.C.R., and Y.-S.Z. have no conflicts of interest. C.D.J is a consultant for TheraTechnologies. K.C.H. receives consulting fees from Faeth Therapeutics, Inc.; is on the review board for PESI, Inc.; and receives personal fees for reviewing professional nutrition education programing for PESI, Inc. The spouse of H.M.D.-V. holds employment at Elanco. The spouse of M.E.C. is a cofounder and shareholder and serves on the Scientific Advisory Board of Proterris, Inc. M.J.G. reports research support to the institution (Weill Cornell) from Gilead Sciences and Regeneron; is a consultant for Enzychem, Regeneron, ReAlta Life Sciences, and Sobi and receives royalties from Springer and UpToDate.
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