BACKGROUND: Case series of patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) have reported different frequencies of human immunodeficiency virus (HIV) infection; some series suggest that HIV infection may cause TTP. METHODS: We systematically reviewed all reports of HIV infection in case series of patients with TTP. We analyzed data from the Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry, an inception cohort of 362 consecutive patients, for 1989-2007. RESULTS: Nineteen case series reported the occurrence of HIV infection at the time of diagnosis of TTP in 0%-83% of patients; individual patient data were rarely described. The Oklahoma TTP-HUS Registry determined the HIV status at the time of diagnosis of TTP in 351 (97%) of 362 patients. HIV infection was documented in 6 (1.84%; 95% CI, 0.68%-4.01%) of 326 adult patients (age, 26-51 years); follow-up data were complete for all 6 patients. The period prevalence of HIV infection among all adults in the Oklahoma TTP-HUS Registry region for 1989-2007 was 0.30%. One patient had typical features of TTP with 5 relapses. Five patients had single episodes; in 4, the clinical features that had initially suggested the diagnosis of TTP were subsequently attributed to malignant hypertension (in 3 patients) and disseminated Kaposi sarcoma (in 1 patient). CONCLUSIONS: HIV infection, similar to other inflammatory conditions, may trigger acute episodes of TTP in susceptible patients. More commonly, acquired immunodeficiency syndrome-related disorders may mimic the clinical features of TTP. If the diagnosis of TTP is suggested in a patient with HIV infection, there should be careful evaluation for alternative diagnoses and cautious consideration of plasma exchange, the required treatment for TTP.