The durability of HAART regimens is often limited by antiretroviral toxicity and nonadherence, which lead to virologic failure. We sought to determine sociodemographic and psychosocial patient factors predictive of short-term discontinuation of HAART regimens overall and stratified by the reason for discontinuation. A retrospective cohort study of the UAB 1917 Clinic Cohort evaluated short-term HAART regimen discontinuation (within 12 months of regimen initiation) between 1/1995 and 8/2004 classified as (1) gastrointestinal (GI) toxicity, (2) non-GI toxicity, (3) virologic failure or nonadherence (VF/NA), (4) loss to follow-up, and (5) other. Multivariable multinomial logistic regression models accounting for dependent observations were fit to assess the relationship between patient factors and type-specific regimen discontinuation. Among the 738 study participants, 1026 of 1852 HAART regimens (55%) were discontinued within 12 months of initiation. In multivariable analysis, discontinuation for GI toxicity was more common in patients lacking private health insurance and those with a history of intravenous (IV) drug use, whereas non-GI toxicity was more common in younger patients and females. African-American patients and those with a history of IV drug use were more likely to stop a regimen due to VF/NA. Loss to follow-up was more common in younger patients, individuals who were uninsured, and those with a history of IV drug use. Short-term discontinuation of HAART regimens is more common in vulnerable populations that bear a disproportionate burden of the U.S. HIV/AIDS epidemic. More vigilant monitoring of patient populations at higher risk of toxicity and virologic failure may allow for improved HAART regimen durability. © 2008 Mary Ann Liebert, Inc.