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The median duration of highly active antiretroviral therapy (HAART) regimens was reported to be 11.8 months in one US study, but that study included both treatment-experienced and treatment-naive patients. The duration of initial HAART regimens for treatment-naive patients alone has not been reported. We selected 405 antiretroviral-naive patients who were seen at the University of Alabama at Birmingham HIV Outpatient Clinic from 1 January 1996 through 9 October 2001, and we assessed the duration of initial and successive HAART regimens in this group. Any antiretroviral medication change, excluding dosage changes, that lasted ≥14 days was considered to indicate the start of a new regimen. The median duration of regimens was determined by Kaplan-Meier analysis, and proportional hazards regression was used to identify factors associated with shorter duration of initial regimen. The median duration of initial regimens was 1.6 years, and medication toxicity-associated events were the cause of one-half of discontinuations. Only a history of opportunistic infection and injection drug use were significantly associated with shorter regimen duration.