Urine Cell-Free Mitochondrial DNA as a Marker of Weight Loss and Body Composition in Older Adults With HIV

Background: Older adults with HIV (OAH) experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps because of chronic inflammation. Cell-free mitochondrial DNA (cfmtDNA) released from cells undergoing necrosis-mediated cell death potentially acts as both a mediator and marker of inflammatory dysregulation. We hypothesized that urinary cfmtDNA would be associated with frailty, body composition, and fall history in OAH. Methods: OAH completed frailty testing, a psychosocial survey, body composition assessment, and measurement of urine cfmtDNA and urine albumin:creatinine in this cross-sectional study. Urine cfmtDNA was measured by quantative polymerase chain reaction and normalized to urinary creatinine. Results: Across 150 participants, the mean age was 61 years (SD 6 years), half identified as Black, one-third were women, and 93% had HIV-1 viral load <200 copies/mL. Two-thirds met criteria for a prefrail or frail state. Those with unintentional weight loss had higher urine cfmtDNA concentrations (P = 0.03). Higher urine cfmtDNA was inversely associated with the skeletal muscle index (beta = -0.19, P < 0.01) and fat mass index (beta = -0.08, P = 0.02) in separate multiple linear regression models adjusted for age, sex, and presence of moderate-severe albuminuria. Conclusions: In this cross-sectional study of OAH, higher levels of urine cfmtDNA were more common in subjects with less robust physical condition, including unintentional weight loss and less height-scaled body mass of fat and muscle. These findings suggest urine cfmtDNA may reflect pathophysiologic aging processes in OAH, predisposing them to geriatric syndromes. Longitudinal investigation of urine cfmtDNA as a biomarker of geriatric syndromes is warranted.