Abstract Details

Title Progressive Increase in Cerebrospinal Fluid (CSF) Neopterin and Relation to Neuropsychological Performance during Primary HIV-1 Infection Prior to Antiretroviral Therapy

Topic Infections/AIDS/Prion Disease

Presentation(s) P06 - (-)

Poster/Presentation
Number 189

Objective

Background BACKGROUND: Nervous system inflammation contributes to brain injury in HIV infection. CSF neopterin is a biomarker predominantly produced intrathecally by activated macrophages that correlates with markers of neuronal damage in HIV infection.

Design/Methods DESIGN/METHODS: Antiretroviral-naive subjects identified with PHI (<1 year since HIV transmission) in Gothenburg, Sweden and San Francisco, USA participated in phlebotomy, lumbar puncture, and 4 neuropsychological tests (summarized as NPZ4) at baseline, 6 weeks, and every 6 months thereafter. Mixed-effects models were used to analyze longitudinal CSF neopterin and NPZ4. Nonparametric tests and Shapiro-Wilk were used to compare groups and check for normality.

Results RESULTS: 81 antiretroviral-naive subjects were enrolled at median 100 days after HIV transmission, with a median follow-up of 321 days (number of visits range 1 to 13). At baseline, the median CSF neopterin concentration was 10.2 nmol/L, with 81% of subjects having levels above 5.8 nmol/L, the normal reference range. A mixed-effects model identified a baseline CSF neopterin of 21 nmol/L as a cutoff value that determined the longitudinal trajectory of CSF neopterin (p<0.001). CSF neopterin increased by 2.91% per 10 weeks in subjects with baseline CSF neopterin <21nmol/L (n=61; p<0.001), and decreased by 6.7% in subjects with baseline levels >21nmol/L (n=20; p=0.001). NPZ4 declined by .014 (n=51; p=0.021) and .231 (n=10; p=0.012) per 10 weeks in the two groups, respectively.

Conclusions CONCLUSIONS: Our results indicate that CSF neopterin levels progressively increase in the majority of antiretroviral-naive subjects during early infection, suggesting rising intrathecal inflammation. Further efforts are needed to identify and treat patients during the early stages of HIV, especially those with highly elevated CSF neopterin, as these subjects in our study showed a faster decline in NPZ4 than those with milder elevations.

Authors/Disclosures
Joome Suh, MD (Brigham and Women's Hospital) PRESENTER	Dr. Suh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Suh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Richard W. Price, MD, FAAN (San Francisco General Hospital)	No disclosure on file
	No disclosure on file
	No disclosure on file
Serena Spudich, MD (Yale University)	The institution of Dr. Spudich has received research support from NIH.
Michael D. Geschwind, MD, PhD, FAAN (UCSF)	Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Brainstorm Cell Therapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Walter Grubb. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Reata Pharmaceuticals, Inc..

��ɫ��

��ɫ��