Abstract
Cerebrospinal fluid (CSF) neurofilament light protein (NfL) is a marker of central nervous system neuro-axonal injury. A novel, ultra-sensitive assay can determine plasma NfL. In untreated people-with-HIV (PWH), CSF and plasma NfL are strongly correlated. We aimed to assess this correlation in PWH on suppressive antiretroviral treatment (ART) and lifestyle-similar HIV-negative individuals enrolled into the COmorBidity in Relation to AIDS (COBRA) study. Differences in paired CSF (sandwich ELISA, UmanDiagnostics) and plasma (Simoa digital immunoassay, Quanterix™) NfL between PWH and HIV-negative participants were tested using Wilcoxon’s test; associations were assessed using Pearson’s correlation. CSF and plasma NfL, standardised to Z-scores, were included as dependent variables in linear regression models to identify factors independently associated with values in PWH and HIV-negative participants. Overall, 132 PWH (all with plasma HIV RNA < 50 copies/mL) and 79 HIV-negative participants were included. Neither CSF (median 570 vs 568 pg/mL, p = 0.37) nor plasma (median 10.7 vs 9.9 pg/mL, p = 0.15) NfL differed significantly between PWH and HIV-negative participants, respectively. CSF and plasma NfL correlated moderately, with no significant difference by HIV status (PWH: rho = 0.52; HIV-negative participants: rho = 0.47, p (interaction) = 0.63). In multivariable regression analysis, higher CSF NfL Z-score was statistically significantly associated with older age and higher CSF protein, and higher plasma NfL Z-score with older age, higher serum creatinine and lower bodyweight. In conclusion, in PWH on ART, the correlation between CSF and plasma NfL is moderate and similar to that observed in lifestyle-similar HIV-negative individuals. Consideration of renal function and bodyweight may be required when utilising plasma NfL.
Highlights
Cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) is well-established as a sensitive biomarker of active central nervous system (CNS) neuro-axonal injury (Gaetani et al 2019; Khalil et al 2018; Olsson et al 2019)
We observed that the correlation between CSF and plasma NfL in people with HIV (PWH) is moderate and similar to that observed in a cohort of lifestyle-similar HIV-negative controls
The previous report suggesting a strong correlation in a cohort of mainly untreated PWH (Gisslén et al 2015) is likely a consequence of the much higher concentrations of CSF and plasma NfL seen in that cohort, where the median CSF and plasma NfL concentrations in
Summary
Cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) is well-established as a sensitive biomarker of active central nervous system (CNS) neuro-axonal injury (Gaetani et al 2019; Khalil et al 2018; Olsson et al 2019). Injured axons leak neurofilament protein into the CSF, proportional to the severity of the injury(Gaetani et al 2019). Elevated CSF NfL concentrations are well-documented in many neurological. Elevated CSF NfL concentrations can be detected in neuroasymptomatic people with HIV (PWH) not on ART, especially in those with low CD4+ counts (Krut et al 2014; Peterson et al 2014)
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