Don’t Drop the B: Risk of Hepatitis B Virus Infection and Reactivation in the Era of Tenofovir-Sparing Regimens for Treatment and Prevention of HIV

Tenofovir-sparing antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) are increasingly used. However, these regimens may increase the risk of new hepatitis B virus (HBV) infection or reactivation due to lack of full activity against HBV. The magnitude and mechanism of risk can vary by baseline HBV serologic profile and need to be discussed with the patient before switching regimens. Importantly, these risks can be mitigated through HBV screening, vaccination, and post-switch monitoring. Here, we synthesize the evidence across different clinical scenarios and propose a practical workflow to reduce the potential but preventable risk during transitions to tenofovir-sparing regimens. Finally, we highlight knowledge gaps and outline future research priorities. The decision to switch to tenofovir-sparing ART or PrEP should not be made solely through the lens of HIV efficacy and convenience and must incorporate HBV prevention and reactivation risk.