title: An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection.
abstract: BACKGROUND
  Several markers of immune activation have been identified as potential prognostic markers for human immunodeficiency virus (HIV)-associated morbidity and mortality, but the results from studies are conflicting.
  
  
  OBJECTIVE
  To evaluate whether neurocognitive status and baseline levels of plasma and cerebrospinal fluid tumor necrosis factor alpha (TNF-alpha), macrophage chemoattractant protein 1 (MCP-1), matrix metalloproteinase 2 (MMP-2), or macrophage colony-stimulating factor (M-CSF) are associated with time to death in a cohort with advanced HIV infection.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Enrollees in the Northeast AIDS Dementia Study.
  
  
  METHODS
  Three hundred twenty-nine subjects who were positive for HIV-1 and had a CD4 cell count of less than 200/microL (or <300/microL but with cognitive impairment at baseline) were assessed for CD4 cell count, neurocognitive status, pertinent demographic and clinical variables, and plasma and cerebrospinal fluid HIV RNA, TNF-alpha, MCP-1, MMP-2, and M-CSF levels.
  
  
  METHODS
  Cox proportional hazards regression models were used to examine the associations between the variables of interest (using time-dependent covariates, where applicable) and time to death, adjusting for possible confounders.
  
  
  RESULTS
  There were 50 deaths in the cohort after a median of 25.2 months of follow-up. The cumulative incidences of death were 7% at 1 year and 16% at 2 years. In Cox proportional hazards regression analyses adjusting for demographic, clinical, and immunological variables, HIV-associated dementia (hazard rate, 6.10; P = .001) was significantly associated with time to death; (log) plasma MCP-1 level (hazard rate, 3.38; P = .08) trended toward significance.
  
  
  CONCLUSIONS
  In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death.
authors.affiliation: Department of Neurology and Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. jsevigny@chpnet.org
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Sevigny
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albert
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.forename: Katherine
authors.initials: K
authors.lastname: Conant
authors.forename: Ola A
authors.initials: OA
authors.lastname: Selnes
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
authors.forename: Daniel R
authors.initials: DR
authors.lastname: McClernon
authors.forename: Donna
authors.initials: D
authors.lastname: Palumbo
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
authors.forename: Garrett
authors.initials: G
authors.lastname: Riggs
authors.forename: Bruce
authors.initials: B
authors.lastname: Cohen
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
authors.forename: Leon G
authors.initials: LG
authors.lastname: Epstein
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003952:Diagnostic Imaging; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009017:Morbidity; D016016:Proportional Hazards Models; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2