title: Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy.
abstract: BACKGROUND
  Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression.
  
  
  METHODS
  CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison.
  
  
  RESULTS
  Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels.
  
  
  CONCLUSIONS
  After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.
authors.affiliation: Department of Infectious Diseases, University of Gothenburg, Journalvagen 10, Gothenburg, 416 50, Sweden. aylin.yilmaz@gu.se
authors.forename: Aylin
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Kathryn
authors.initials: K
authors.lastname: Crozier
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.forename: Serena
authors.initials: S
authors.lastname: Spudich
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén
mesh_terms: D000328:Adult; D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000134:cerebrospinal fluid*; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D019798:Neopterin