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Substance abuse increases the risks for infections and impairs medication adherence among HIV/AIDS patients. However, little is known about the characteristics of substance abuse and its impact on medication adherence among HIV-positive women with a history of child sexual abuse (CSA). In the present study, 148 HIV-positive women with a history of CSA completed a structured interview assessing CSA severity, psychological status, substance abuse, medication adherence, and sexual decision-making. Severity of CSA was significantly associated with substance use but not with adherence. Participants who had used hard drugs and who had lower self-esteem and adherence self-efficacy reported significantly lower levels of adherence. Additional research on how CSA experiences impact health behaviors is needed to help develop culturally congruent interventions to reduce risk behaviors and facilitate better medication adherence for this vulnerable population.