Systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection have significant overlapping clinical features, making diagnosis challenging. We report a case of new-onset SLE initially mistreated as HIV infection due to a false-positive fourth-generation HIV antigen/antibody (Ag/Ab) test. A young female in her 30s presented with fatigue, oral thrush, and a positive HIV Ag/Ab combo test. She was started on fluconazole and highly active antiretroviral therapy (HAART), but deteriorated with recurrent fevers and worsening mental status, requiring ICU admission. Surprisingly, her HIV confirmatory tests were negative, but rheumatologic serologies were positive. The overall clinical, laboratory and biopsy results confirmed the diagnosis of SLE. She was treated with pulse steroid therapy and immunosuppressive agents with marked improvement and was subsequently discharged. Rarely do SLE patients present with false-positive HIV tests, thus masking and delaying treatment for critical SLE. Clinicians should understand the limitations of screening tests and have high suspicions and consider the diagnoses of both diseases.

Keywords: false-positive; hiv; immunocompromised; intensive care; systemic lupus erythematosus.

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