An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection

Jeffrey J. Sevigny*, Steven M. Albert, Michael P. McDermott, Giovanni Schifitto, Justin C. McArthur, Ned Sacktor, Katherine Conant, Ola A. Selnes, Yaakov Stern, Daniel R. McClernon, Donna Palumbo, Karl Kieburtz, Garrett Riggs, Bruce Cohen, Karen Marder, Leon G. Epstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Background: Several markers of immuneactivation 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 α (TNF-α), 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. Design: Cohort study. Setting: Enrollees in the Northeast AIDS Dementia Study. Participants: Three hundred twenty-nine subjects who were positive for HIV-1 and had a CD4 cell count of less than 200/μL (or <300/μL 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-α, MCP-1, MMP-2, and M-CSF levels. Main Outcome Measures: Cox proportional hazards regression models were used to examine the associations between the variables of interest (using timedependent 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. Conclusion: In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death.

Original languageEnglish (US)
Pages (from-to)97-102
Number of pages6
JournalArchives of Neurology
Issue number1
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)


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