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/mu L (or < 300/mu L 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.