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).


METHODS
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.


CONCLUSIONS
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.
Mellgren
A
A
Clinic of Infectious Diseases, Södra Alvsborgs Sjukhus, Borås, Sweden. asa_mellgren@yahoo.com
Price
R W
RW
Hagberg
L
L
Rosengren
L
L
Brew
B J
BJ
Gisslén
M
M
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D018696:Neuroprotective Agents / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D012367:RNA, Viral; C044882:neurofilament protein L