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The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is being increasingly reported and, because of the immunological disturbances demonstrated in HIV-infected patients, diagnostic and therapeutic difficulties may arise when the 2 conditions coexist. Antiphospholipid antibodies are demonstrable in patients with both conditions, but clinical manifestations of the antiphospholipid syndrome (APS) in HIV-infected patients, although reported, are uncommon.We describe a patient with HIV infection and SLE who manifested 4 episodes of deep vein thrombosis (DVT) complicated by pulmonary embolism. Enzyme-linked immunosorbant assay was used to test for the presence of antiphospholipid antibodies, including anticardiolipin antibodies, anti—β2-glycoprotein 1 antibodies, and antiprothrombin antibodies (anti-PT). Additionally, we performed a computer-assisted search of the literature (via the Medline database) to identify all reported cases of HIV infection plus SLE.We document the case of 35-year-old African woman with HIV infection and SLE who developed recurrent episodes of DVT and pulmonary embolism in the presence of anti-PT and discuss in depth the pathogenic role of these antibodies and the clinical challenges posed to clinicians by the coexistence of HIV and SLE in the same patient.Immunological reconstitution in HIV-infected patients contributes to the appearance of multiple autoimmune conditions, including SLE and APS. The recognition of the coexistence of these autoimmune disorders in HIV-infected patients has important implications in the treatment of and prognosis for these individuals.