We have retrospectively studied the influence of highly active antiretroviral therapy (HAART) on the outcome of AIDS-related lymphomas (ARL) as well as the possible influence of the virological response to HAART on complete response (CR) rate and survival in our series of ARL treated with CHOP. Two groups of patients were studied: (1) 44 patients who did not take HAART when the lymphoma was diagnosed, and (2) 26 patients treated with HAART concomitantly and after chemotherapy. There were 4 (9%) women in group 1 versus 11 (42%) in group 2 (P = 0.01), and serum lactate dehydrogenase (LDH) level was lower in group 2. The response rate to CHOP was higher in group 2 patients (15 out of 23, 65%) than in those of group 1 (16 out of 44, 36%) (P = 0.025). The factors associated with improvement of CR in the multivariate analysis were the administration of HAART (P = 0.004) and International Prognostic Index (IPI) score < or = 2 (P = 0.006). Among group 2 patients, those with a virological response to HAART and with IPI score < or = 2 had better response rate to chemotherapy (odds ratios 9.3 and 11.8, respectively). The median (95% CI) overall survival (OS) for group 1 patients was 7 (3-11) months, whereas it has not been reached for group 2 (P = 0.002). The only parameters influencing OS in the multivariate analysis were HAART (0.003), as a protective factor and IPI score > 2 (P = 0.015) with negative influence. Among patients treated with HAART, those with virological response had higher OS probability (P = 0.004), whereas those with IPI score > 2 had an unfavorable prognosis (P = 0.014). The only variable with statistical significance for disease free survival (DFS) in the univariate and multivariate analyses was HAART (P = 0.0168 and P = 0.028, respectively). We conclude that HAART is an independent prognostic factor for CR attainment, OS and DFS in patients with ARL treated with CHOP. Those patients with virological response to HAART had a better survival.