We examined factors associated with virological failure in 310 HIV-infected patients receiving atazanavir (ATV). Independent links were identified with virological failure under ATV: virological failure previous history (P = 0.006) and ATV underdosing (P = 0.04). A maintenance therapy was protective (P = 0.01). The optimal therapeutic ranges of ATV concentration were found to be from 300 ng/ml (or 180 for patients treated with maintenance therapy) to 650 ng/ml for C24 and from 1000 ng/ml (or 500 for patients treated with maintenance therapy) to 2000 ng/ml for C12.