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

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. 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/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. 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.

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