Positive Human Immunodeficiency Virus (HIV) Test Following Influenza Vaccination: A Case Report

False-positive human immunodeficiency virus (HIV) test results following influenza vaccination are rare today. However, with evolving vaccine formulations, unexpected cross-reactivity remains a potential concern. This case highlights the importance of recognizing this phenomenon to prevent misdiagnosis and patient anxiety. After obtaining her annual flu shot, an 82-year-old woman on hemodialysis (HD) was repeatedly discovered to have positive HIV enzyme-linked immunosorbent assay (ELISA) test results without having risk factors, and previously, the test was negative. As described in the literature, subsequent testing during the anticipated reversion period demonstrated a return to negativity, confirming a false-positive result. Cross-reactivity between HIV ELISA tests and influenza vaccines has been reported infrequently due to potential immunologic interactions. This case shows the necessity of interpreting positive HIV results with caution, especially in recently vaccinated individuals and populations undergoing frequent serological testing, such as HD patients. Clinicians should be aware of the cross-reactivity between the HIV ELISA test and the flu vaccination to recognize false-positive results, even with current influenza vaccine formulations. Awareness of this can prevent unnecessary patient distress, misdiagnosis, and unwarranted interventions.