Observational studyJournal of neuroinflammation2017
Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment.
Observational study in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Cognitive impairment and CSF proteome modification after oral bacteriotherapy in HIV patients.Journal of neurovirology · 2020Trial
- Mitochondrial control of blood-brain barrier homeostasis in neuroinflammatory psychiatric disorders.Frontiers in molecular neuroscience · 2026Review
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- Sex-Biased Associations of Circulating Ferroptosis Inhibitors with Reduced Lipid Peroxidation and Better Neurocognitive Performance in People with HIV.Antioxidants (Basel, Switzerland) · 2024Article
- Cell-free DNA-based liquid biopsies in neurology.Brain : a journal of neurology · 2023Review
- Neuroimaging and immunological features of neurocognitive function related to substance use in people with HIV.Journal of neurovirology · 2023Article
- New Perspectives on the Importance of Cell-Free DNA Biology.Diagnostics (Basel, Switzerland) · 2022Review
- Higher CSF Ferritin Heavy-Chain (Fth1) and Transferrin Predict Better Neurocognitive Performance in People with HIV.Molecular neurobiology · 2021Observational
- Utility of a Short Neuropsychological Protocol for Detecting HIV-Associated Neurocognitive Disorders in Patients with Asymptomatic HIV-1 Infection.Brain sciences · 2021Article
- Association of cell free mitochondrial DNA and caspase-1 expression with disease severity and ARTs efficacy in HIV infection.Molecular biology reports · 2021Article
- New Potential Axes of HIV Neuropathogenesis with Relevance to Biomarkers and Treatment.Current topics in behavioral neurosciences · 2021Article
- The Value of Serum Cell-Free DNA Levels in Patients With Schizophrenia.Frontiers in psychiatry · 2021Article
- Circulating levels of ATP is a biomarker of HIV cognitive impairment.EBioMedicine · 2020Article
- Priming Astrocytes With HIV-Induced Reactive Oxygen Species Enhances TheirFrontiers in microbiology · 2020Article
- Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.Scientific reports · 2019Article
- Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.Molecular neurobiology · 2019Article
- HIV infection and latency induce a unique metabolic signature in human macrophages.Scientific reports · 2019Article
- Sex-Specific Negative Association between Iron Intake and Cellular Aging Markers: Mediation Models Involving TNFOxidative medicine and cellular longevity · 2019Article
- HIV-Associated Neurocognitive Impairment in the Modern ART Era: Are We Close to Discovering Reliable Biomarkers in the Setting of Virological Suppression?Frontiers in aging neuroscience · 2019Article
- ccf-mtDNA as a Potential Link Between the Brain and Immune System in Neuro-Immunological Disorders.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 1 country.
Funding
Abstract
backgroundMitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.
methodsWe quantified cell-free mtDNA in CSF by droplet digital PCR in 332 CHARTER participants who underwent comprehensive neuropsychiatric evaluation. NC performance was assessed using the global deficit score (GDS) as either a continuous or a binary measure (GDS ≥ 0.5, impaired vs. GDS < 0.5, unimpaired). CSF, clinical, and biomarker data from the earliest available time point were analyzed. Cell-free mtDNA associations with CSF inflammation and iron-related biomarkers [CXCL10, IL-6, IL-8, TNF-a, transferrin (TF), ceruloplasmin (CP), and vascular endothelial growth factor (VEGF)], VL, and GDS were evaluated by multivariable regression.
resultsCSF cell-free mtDNA levels were significantly lower in participants with undetectable (vs. detectable) VL in either plasma (p < 0.001) or CSF (p < 0.001) and in those on antiretroviral therapy (ART; p < 0.001). Participants on ART with undetectable VL in both CSF and plasma had lower mtDNA levels than those with detectable VL in both compartments (p = 0.001). Higher mtDNA levels were observed in participants in the highest vs. lowest tertile (T3 vs. T1) of CSF CXCL10 (T3 vs. T1, p < 0.001) and TNF-a (T3 vs. T1, p < 0.05) in unadjusted analyses. MtDNA levels also correlated with CSF leukocyte count. After adjusting for CSF leukocyte count and VL, mtDNA levels were also associated with other inflammation- and iron-related biomarkers in CSF, including TF (T3 vs. T1, p < 0.05) and CP (T3 vs. T1, p < 0.05). With additional correction for ART use, mtDNA was also negatively associated with CSF VEGF (p < 0.05) and IL-6 (p = 0.05). We observed no associations of CSF mtDNA levels with age or GDS-defined NC impairment.
conclusionsCSF cell-free mtDNA levels were associated with HIV RNA and ART status, as well as with biomarkers of iron transport and VEGF, a growth factor with known effects on mitochondrial integrity and autophagy. CSF mtDNA may be a biomarker of iron dysregulation and/or neuroinflammation during HIV infection.
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Registered trials
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