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Among HIV-infected persons, high-level adherence to antiretroviral medications (>90%–95%) is associated with improved immunologic, virologic, and clinical outcomes, and is necessary to prevent the emergence of viral resistance. This study examines whether lifetime traumatic events including physical and sexual abuse, are associated with antiretroviral nonadherence. We present a cross-sectional analysis of the Coping with HIV/AIDS in the Southeast (CHASE) Study, analyzing data from the enrollment interview and medical records of study subjects. The CHASE Study is a prospective cohort study of consecutively sampled HIV-infected subjects from infectious diseases clinics in five southern states; Alabama, Georgia, Louisiana, North Carolina, and South Carolina. Four hundred seventy-four (78%) of the 611 CHASE study subjects reported being treated with antiretroviral medications at enrollment and are included in this analysis. Nonadherence was defined as the patient's self-report of missing any doses of their antiretroviral medications over the previous 7 days. Among study subjects, 54% reported a history of physical and/or sexual abuse, 91% reported at least one lifetime traumatic event, and 24% reported nonadherence with their antiretrovirals. In multivariable logistic regression analysis, the number of categories of lifetime traumatic events (p = 0.03), the Addiction Severity Index (ASI) alcohol score (p = 0.02), and being uninsured (p = 0.04) were associated with antiretroviral nonadherence. The finding that lifetime traumatic events are associated with antiretroviral nonadherence, particularly among those who have been traumatized in multiple ways, highlights the complex and often persisting manifestations of such trauma and calls for further investigation.