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

Arch Neurol. 2007;64(1):97-102.

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 (TNF-), 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-, 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 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.

Conclusion  In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death.

Author Affiliations: Department of Neurology and Gertrude H. Sergievsky Center (Drs Sevigny, Albert, Stern, and Marder), Taub Institute for Research on Alzheimer's Disease (Drs Albert and Marder), and Department of Psychiatry (Dr Marder), College of Physicians and Surgeons, Columbia University, New York, and Department of Neurology, University of Rochester, Rochester (Drs McDermott, Schifitto, Palumbo, Kieburtz, and Riggs), NY; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Md (Drs McArthur, Sacktor, Conant, and Selnes); GlaxoSmithKline, Inc, Research Triangle Park, NC (Mr McClernon); and Department of Neurology (Dr Cohen) and Department of Pediatrics and Children's Memorial Research Center (Dr Epstein), Feinberg School of Medicine, Northwestern University, Chicago, Ill. Dr Sevigny is now with the Department of Neurology, Beth Israel Medical Center, New York, NY.

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