Title : When acute EBV mimics HIV: A case of false positive p24 antigen and low-level HIV antibody reactivity
Abstract:
False positive HIV screening results, while uncommon, carry significant clinical and psychological consequences due to the anxiety and diagnostic uncertainty they generate. One recognised but rare cause is acute Epstein-Barr virus (EBV) infection, which may cross-react with fourth-generation HIV assays, particularly the p24 antigen and low-level HIV antibody reactivity.
We describe the case of a 57-year-old man with a background of hypothyroidism and atrial fibrillation who presented with sore throat, diffuse rash, dark urine, fatigue, and tender cervical and occipital lymphadenopathy. Laboratory findings showed lymphocytosis and markedly elevated liver enzymes. Fourth-generation HIV tests were repeatedly reactive, demonstrating p24 antigen and low-level HIV-1/2 antibody reactivity. However, HIV-1 and HIV-2 RNA viral loads were consistently undetectable. EBV serology confirmed acute infection, with VCA IgM positivity and transient EBV DNA detection. Other viral and syphilis serologies were negative, and an initial weakly positive monkeypox PCR was not reproducible. The patient’s wife, who was pregnant, tested negative for HIV. Clinical recovery was achieved with supportive management, liver function normalised, and subsequent HIV serology remained negative, confirming a false positive HIV result due to acute EBV infection.
This case highlights an important diagnostic pitfall: EBV infection can mimic acute HIV seroconversion. The consequences of a false HIV diagnosis are significant, extending beyond clinical mismanagement to serious psychosocial implications, particularly in the context of a pregnant partner. The discrepancy between reactive screening tests and undetectable HIV RNA levels underscores the necessity of confirmatory testing and careful clinical correlation.
Clinicians should remain vigilant for this rare phenomenon, as recognising EBV-associated false positives can prevent misdiagnosis, alleviate unnecessary psychological distress, and reinforce the importance of cautious interpretation of discordant HIV results.
