Although HIV infection is often associated with several rheumatic diseases, the coexistence of this retroviral infection and systemic lupus erythematosus (SLE) is extremely uncommon. Generally, HIV-related immunosuppression improves SLE symptoms, and antiretroviral therapy may lead to an autoimmune disease flare subsequent to the increase of circulating CD4+ cell number. Two HIV-infected female patients with SLE and discoid lupus erythematosus (DLE) diagnosed a few months after the highly active antiretroviral therapy initiation, are described. To our knowledge, this is the second case of DLE and the twenty-seventh case of SLE reported to date in association with HIV infection.