Assessment of Plasma Neurofilament Light as a Biomarker of Neuronal Injury in Young Adults with Perinatal HIV Infection

Abstract

Background: Higher plasma concentration of neurofilament light (pNfL) is associated with neurodegeneration. However, to our knowledge, up to now, there are no data in HIV patients with infection due to vertical transmission. This is the first study to report pNfL in a cohort of HIV perinatally infected (PHIV) young adults compared with non-HIV (HIV-) controls.Methods: Thirty-three PHIV patients and 25 age-matched HIV- were recruited to this cross-sectional study. Plasma NfL concentrations were compared between both groups. In a subgroup of 48 participants (25 PHIV patients and 23 HIV-), brain volumes through magnetic resonance imaging (MRI) and neuropsychological testing (NT), were also conducted and compared with pNfL values.Plasma NfL concentration was measured using Single Molecule Array (Simoa) immunoassay.NT included fluid intelligence and processing speed through the WAIS-IV Coding subtest, and the Stroop Test.ResultsFifty-eight participants were included, median age 20.7 years [IQR 17.8-23.4]. 100% of the patients were under antiretroviral treatment (cART) and 85% had viral load <50 copies/ml.Although no statistically significant differences were found between patients and controls regarding pNfL concentration, there was a trend towards higher levels in patients with viral load >50 copies/ml.With regard to brain volumes and NT, in the PHIV group, lower white matter volumes and lower score in the coding subtest were associated with higher pNfL values. ConclusionsMost PHIV adolescents under cART have similar levels of pNfL than HIV-. As reported in adults, those with HIV-RNA >50 copies/ml showed higher values and lower white matter volumes that may imply an ongoing CNS injury. Plasma NfL could be a feasible biomarker of CNS injury in PHIV patients with unsuppressed viral load.

Relationships between plasma neurofilament light chain protein, cognition, and brain aging in people with HIV

“…Previously, higher CSF NfL demonstrated significant relationships with reduced metabolites in the brain using magnetic resonance spectroscopy (MRS) in ART-naive PWH [16] but did not show an association with brain volumes or fractional anisotropy in PWH on ART [17]. Plasma NfL has previously been associated with smaller white matter volumes in a cohort of 58 people with perinatally acquired HIV on ART [18].…”