Nucleic acid oxidation is associated with biomarkers of neurodegeneration in CSF in people with HIV

OBJECTIVE: To determine whether oxidative stress in virologically suppressed people with HIV (PWH) may contribute to or result from neurodegeneration, we measured 7,8-dihydro-8-oxoguanine (8-oxo-dG), a marker of DNA damage due to oxidative stress, and markers of age-related neurodegeneration, specifically, reduced levels of CSF Aβ-42, and elevated CSF total tau and neurofilament light (NFL). METHODS: This cross-sectional study prospectively enrolled participants at 6 US centers in the CNS HIV Antiretroviral Effects Research study. Inclusion criteria included HIV+ with a plasma level of HIV RNA ≤50 copies/mL. Exclusions included significant CNS confounding conditions. Measurements of total tau and Aβ-42 were performed by bead suspension array. NFL and 8-oxo-dG were measured using ELISA. RESULTS: Participants were 53 PWH, mean age 55 (±9.3) years, 19% women, and 48% non-Hispanic White. Higher 8-oxo-dG correlated with markers of AD-related neurodegeneration including lower CSF Aβ-42 (r = −0.34; p = 0.012) and higher CSF NFL (r = 0.39; p = 0.0091) and total tau (r = 0.6696; p < 0.0001). Relationships remained after adjusting for demographic variables. Levels of protein carbonyls, a marker of protein oxidation, were not related to neurodegeneration markers. CONCLUSIONS: Among virologically suppressed PWH, nucleic acid oxidation was associated with standard CSF biomarkers of neurodegeneration. Potential sources of oxidative stress in PWH include low-level HIV replication, inflammation, mitochondrial dysfunction, and specific antiretroviral drugs. Results suggest that the higher levels of oxidative stress among PWH may play a role in neurodegeneration. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among virologically suppressed PWH, nucleic acid oxidation is associated with standard CSF biomarkers of neurodegeneration.