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NEUROLOGY 2007;69:1536-1541
© 2007 American Academy of Neurology

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

Å Mellgren, MD, PhD, R. W. Price, MD, L. Hagberg, MD, PhD, L. Rosengren, MD, PhD, B. J. Brew, MBBS, MD, FRACP and M. Gisslén, MD, PhD

From the Clinic of Infectious Diseases, Södra Älvsborgs Sjukhus, Borås, Sweden (Å.M.); Departments of Infectious Diseases (Å.M., L.H., M.G.) and Neurology (L.R.), The Sahlgrenska Academy at Göteborg University, Sweden; Department of Neurology, University of California–San Francisco, San Francisco General Hospital, CA (R.W.P.); and Departments of Neurology and HIV Medicine, St Vincent's Hospital, University of New South Wales, Sydney, Australia (B.J.B.).

Address correspondence and reprint requests to Dr. Mellgren, Clinic of Infectious Diseases, Södra Älvsborgs Sjukhus, Borås, Sweden S-501 82 asa_mellgren{at}yahoo.com.

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.

Abbreviations: ADC = AIDS dementia complex; HAART = highly active antiretroviral treatment; IQR = intraquartile range; IRIS = immune reconstitution inflammatory syndrome; LP = lumbar puncture; MAC = mycobacterium avium complex; NFL = neurofilament protein; OI = opportunistic infection; PCP = pneumocystis jiroveci pneumonia; WBC = white blood cell.

Supplemental data at www.neurology.org

This study was supported by grants from the NIH (R01 NS043103, R01 NS37660, R01 MH62701, and MO1-RR00083), the Medical Faculty of Göteborg University (ALFGBG-2874), the Research Foundation of Swedish Physicians against AIDS, FoU-enheten Södra Älvsborg, and from Stiftelsen Fokus Föreningsparbanken.

Disclosures: The authors report no conflicts of interest.

Received October 20, 2006. Accepted in final form April 30, 2007.




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