Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection

Objective: Increased levels of the light-chain neurofilament protein ( NFL) in CSF provide a marker of CNS injury in several neurodegenerative disorders and have been reported in the AIDS dementia complex ( ADC). We examined the effects of highly active antiretroviral treatment ( HAART) on CSF NFL in HIV-1-infected subjects with and without ADC who underwent repeated lumbar punctures ( LPs). Method: NFL was measured by ELISA ( normal reference value < 250 ng/ L) in archived CSF samples from 53 patients who had undergone LPs before and after initiation of HAART. Results: Twenty-one of the subjects had increased CSF NFL at baseline, with a median level of 780 ng/ L and an intraquartile range ( IQR) of 480 to 7300. After 3 months of treatment, NFL concentrations had fallen to normal in 48% ( 10/21), and the median decreased to 340 ng/ L ( IQR < 250 to 4070) ( p < 0.001), whereas at 1 year, only 4 of 16 of the 21 subjects observed for this length still had elevated NFL levels. Thirty-two subjects had normal NFL at baseline, and all but one remained normal at follow-up. These effects on CSF NFL were seen in association with clinical improvement in ADC patients, decreases in plasma and CSF HIV-1 RNA and CSF neopterin, and increases in blood CD4 T cell counts. Conclusion: HAART seems to halt the neurodegenerative process(es) caused by HIV-1, as shown by the significant decrease in CSF NFL after treatment initiation. CSF NFL may serve as a useful marker in monitoring CNS injury in HIV-1 infection and in evaluating CNS efficacy of antiretroviral therapy.