BACKGROUND: Prevalence of neurocognitive impairment in HIV-1 infected patients 
is reported to be high. Whether this is a result of active HIV-related 
neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by 
measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, 
sensitive method.
METHODS: With a cross-sectional design, CSF concentrations of neurofilament 
protein light (NFL) (marker of neuronal injury), neopterin (intrathecal 
immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) 
were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated 
neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on 
combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 
204). 46 HIV-infected patients were included in both treated and untreated 
groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic 
patients were analyzed before and after treatment initiation.
RESULTS: While HAD patients had the highest NFL concentrations, elevated CSF NFL 
was also found in 33% of untreated neuroasymptomatic patients, mainly in those 
with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the 
untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 
and 3.9 years older, respectively. Neopterin correlated with NFL levels in 
untreated groups while the albumin ratio correlated with NFL in both untreated 
and treated groups.
CONCLUSIONS: Increased CSF NFL indicates ongoing axonal injury in many 
neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain 
higher levels than controls, indicating either continued virus-related injury or 
an aging-like effect of HIV infection. NFL correlates with neopterin and albumin 
ratio, suggesting an association between axonal injury, neuroinflammation and 
blood-brain barrier permeability. NFL appears to be a sensitive biomarker of 
subclinical and clinical brain injury in HIV and warrants further assessment for 
broader clinical use.