Transient hepatitis B surface antigen positivity after hepatitis B vaccination in an HIV pre-exposure prophylaxis user

Abstract

Transient detection of hepatitis B surface antigen (HBsAg) following hepatitis B vaccination is a rare but recognized phenomenon that may be misinterpreted as acute hepatitis B virus (HBV) infection. We report a case illustrating this diagnostic challenge in an HIV pre-exposure prophylaxis (PrEP) user. A 36-year-old man presented in October 2025 for PrEP initiation. He reported condomless sex with multiple male partners and occasional on-demand use of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) obtained from a partner. Screening for sexually transmitted infections in August 2025 showed negative viral hepatitis serologies. Two days prior to the PrEP consultation, he received a combined hepatitis A/B vaccine in preparation for travel to Thailand.Routine baseline testing revealed isolated HBsAg positivity. The patient was asymptomatic and recalled for further evaluation. Repeat testing eight days later showed HBsAg negativity, newly positive anti-HBs antibodies, undetectable HBV DNA, negative hepatitis D serology, and normal liver enzymes. Follow-up serology fourteen days later confirmed sustained HBsAg negativity with isolated anti-HBs positivity. The rapid resolution of HBsAg in close temporal proximity to vaccination, together with the absence of hepatitis B core antibodies and undetectable HBV DNA, supported transient post-vaccination antigenemia rather than acute HBV infection.Transient HBsAg positivity after vaccination has previously been described, particularly among hemodialysis patients. Retrospective studies indicate that circulating recombinant HBsAg may be detected shortly after immunization, most commonly within five days but occasionally up to twenty days. To our knowledge, this is the first reported case of transient HBsAg positivity in a PrEP user. This is clinically relevant given the anti-HBV activity of TDF and evidence suggesting that TDF-based PrEP reduces HBV acquisition. As incident HBV infection during PrEP use is uncommon, isolated HBsAg positivity shortly after vaccination may create diagnostic uncertainty. Awareness of this phenomenon is essential to avoid misdiagnosis, unnecessary anxiety, and inappropriate interruption of PrEP.