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AIDS-related lymphomas (ARLs) significantly contribute to mortality in HIV-infected patients. Optimal chemotherapy treatment and the use of rituximab remain controversial. The aim of the present cohort study was to analyze the outcome of HIV-infected patients diagnosed with ARL, with regard to the use of rituximab, clinical characteristics and histopathological markers.This observational uncontrolled multicenter cohort study included 163 HIV-infected patients with ARL diagnosed between January 2005 and December 2008 in Germany.Patients with CD20-positive ARL had a significantly better overall survival (OS) and progression-free survival (PFS) than patients with CD20-negative ARL [hazard ratio 0.28, 95% confidence interval (CI) 0.15–0.53 and hazard ratio 0.29, 95% CI 0.16–0.53]. In CD20-positive cases, the use of rituximab was associated with better OS and PFS (n = 128, hazard ratio 0.48, 95% CI 0.25–0.93 and hazard ratio 0.47, 95% CI 0.26–0.86), even in patients with severe immune deficiency at ARL diagnosis (CD4 T-cell count<100 cells/μl, n = 33; OS: hazard ratio 0.25, 95% CI 0.07–0.90). In multivariate analysis, CD4 T-cell counts more than 100 cells/μl and the use of rituximab were associated with better OS and PFS. In total, there were 12 polychemotherapy-associated deaths, which were not related to specific therapy regimens or to the use of rituximab.In patients with CD20-positive ARL, CD4 T-cell count at ARL diagnosis and the use of rituximab had strong impact on survival. Rituximab was beneficial in ARL even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections.