We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of <100 cells/microL, compared with patients who had CD4+ cell counts of > or =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of <100 cells/microL was associated with higher mortality.