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The benefits of continuing antiretroviral therapy are questionable in human immunodeficiency virus (HIV) type 1-infected patients with profound immunodeficiency and multiple treatment failure due to viral resistance.From the French Hospital Database on HIV, we selected 12,765 patients with a CD4+ cell count <200 cells/mm3 who received a combination antiretroviral therapy (cART) during 2000-2005. Three groups of patients were defined: patients who interrupted cART at least once, patients who had at least 2 consecutive detectable viral loads (VLs) while receiving cART, and patients who had undetectable VL during treatment with cART. Incidence rates and risks of new acquired immunodeficiency syndrome-defining events (ADEs) were assessed among the 3 groups of patients, overall and after CD4+ cell count stratification (<50 and 50-200 cells/mm3).The estimated incidence rates ± standard deviation of ADEs were 18.5±1.9, 14.5±0.7, and 4.9±0.5, respectively, for patients who interrupted cART, patients who had detectable VL during treatment with cART, and patients who had undetectable VL during treatment with cART. These differences were observed in both CD4+ cell count strata. Overall, after adjustment, risks of a new ADE in patients who had detectable VL and in patients who had undetectable VL while receiving cART were 22% and 62% lower, respectively, than in patients who stopped cART. Among patients with CD4+ cell count <50 cells/mm3, the risk of a new ADE was 22% lower in patients who continued to receive a failing cART regimen than in patients who stopped treatment with cART. Likewise, among patients with a CD4+ cell count of 50-200 cells/mm3, the risk was 34% lower in patients who continued to receive a failing cART regimen than in those who stopped taking cART.Even when effective virological control is no longer achievable, cART still reduces the risk of ADEs in profoundly immunodeficient HIV-infected patients.