Although HIV infection is often associated with several rheumatic diseases, the coexistence of this retroviral infection and systemic lupus erythematous is extremely uncommon. Etiopathogenetic relationship between these disorders is very complex and still problematic, so that diagnostic workout, because of their extensive clinical and serological overlap. Generally, HIV-related immunosuppression improves lupus-associated symptoms, and antiretroviral therapy may lead to an autoimmune disease flare, subsequent to the increase of circulating CD4+ cell number. A HIV-infected female patient with systemic lupus erythematosus, occurred few months after the highly active anti-retroviral therapy initiation, is described.