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Despite the high prevalence of both mental disorders and HIV infection in much of sub-Saharan Africa, little is known about the occurrence of mental health disorders among HIV-infected individuals. We conducted a cross-sectional study among individuals enrolled into HIV care and treatment services near Cape Town, South Africa. Psychiatric diagnoses were measured using the Mini-International Neuropsychiatric Interview (MINI) administered by trained research nurses. In addition, all participants were administered brief rating scales for depression (the Center for Epidemiological Studies Depression Scale [CES-D]), posttraumatic stress disorder (PTSD), the Harvard Trauma Questionnaire (HTQ), and alcohol dependence/abuse (the Alcohol Use Disorders Identification Test [AUDIT]). The median age among the 465 participants was 33 years and 75% were female; 48% were receiving antiretroviral therapy. Overall, the prevalence of depression, PTSD and alcohol dependence/abuse was 14% (n = 62), 5% (n = 24), and 7% (n = 35), respectively. In multivariate analysis, the prevalence of all disorders was significantly higher among individuals who spoke Afrikaans compared to Xhosa. While the AUDIT showed excellent sensitivity and specificity in detecting MINI-defined dependence/abuse (area under the receiver-operating characteristic curve, 0.96), the HTQ and CES-D had lower performance characteristics in detecting PTSD (0.74) and depression (0.76), respectively. These data demonstrate high levels of depression, PTSD and alcohol dependence/abuse among HIV-infected individuals in this setting. Additional research is required to refine these rating scales for maximum applicability in cross-cultural populations. More generally, HIV care and treatment services represent an important venue to identify and manage individuals with common mental disorders in resource-limited settings.