Although HIV infection can mimic the manifestations of various autoimmune disorders, the coexistence of HIV and systemic lupus erythematosus (SLE) has been rarely reported. The exact impact of HIV on SLE and vice versa is unclear. We report an HIV-seropositive female on highly active antiretroviral therapy presenting with features of SLE. Herein, an attempt has been made to discuss the various complex clinical and therapeutic implications along with the influence on disease course and prognosis.