Unmasking Hepatitis B Risks in Long-Acting ART: Laurence Brunet, PhD, and Gerald Pierone, MD

Success in HIV management often comes down to the details, and as clinicians increasingly embrace long-acting injectables, one detail is proving critical: hepatitis B virus (HBV) status. At the Conference on Retroviruses and Opportunistic Infections 2026, the conversation shifted to a growing safety concern—the potential for HBV reactivation in patients transitioning away from tenofovir-based oral antiretroviral therapy (ART). Laurence Brunet, PhD, of Epividian, and Gerald Pierone, MD, chief medical officer of Whole Family Health Center, sat down to parse new findings that reveal how often baseline HBV screening is missed in clinical practice, creating a preventable risk for patients making the switch.

Brunet, a clinical epidemiologist with expertise in HIV comorbidities, explained that while long-acting cabotegravir-rilpivirine is highly effective for maintaining HIV viral suppression, it does not have activity against HBV. That distinction becomes critical when patients with unrecognized chronic HBV infection—or prior exposure—are switched off tenofovir-containing regimens that previously provided dual HIV/HBV coverage. In their data set, a subset of patients had evidence of chronic infection, including those who were hepatitis B surface antigen–positive or had detectable HBV DNA, placing them at risk for reactivation after the switch.

Pierone noted that this risk was not unexpected from a biological standpoint. However, what stood out was how often comprehensive HBV serologic testing and DNA monitoring were incomplete in real-world practice. Without consistent baseline screening—surface antigen, core antibody, and surface antibody—clinicians may inadvertently transition patients to long-acting therapy without recognizing the need for continued HBV-active treatment. Both experts emphasized that this is not a reason to avoid long-acting therapy but rather a call to strengthen routine screening and monitoring protocols.

The conversation returned to practical steps for clinicians. Before switching to long-acting cabotegravir-rilpivirine, patients should undergo full HBV serologic testing to identify chronic infection and determine immunity status. Those who are not immune should be vaccinated. For patients with chronic HBV, HBV-active agents such as tenofovir or entecavir should be continued alongside long-acting HIV therapy to prevent reactivation. Ongoing monitoring, including HBV DNA and liver function tests, remains essential, particularly in the early months after transition.

Brunet also highlighted a key limitation of the current analysis: Missing HBV serology and DNA data made it difficult to fully ascertain the true incidence of reactivation. This gap underscores the need for more systematic surveillance and prospective studies to evaluate vaccination effectiveness and define optimal monitoring intervals for individuals with prior HBV exposure.

As long-acting antiretroviral options become more widely adopted, both Brunet and Pierone stressed that clinicians must keep hepatitis B top of mind. With appropriate screening, vaccination, and continued HBV-active treatment when indicated, long-acting therapy can be used confidently while minimizing preventable complications from HBV reactivation.

Reference

Dieterich DT, Brunet L, Hasu RK, et al. HIV-HBV coinfection and long-acting cabotegravir + rilpivirine in the US: HBV and HIV outcomes. Presented at: Conference on Retroviruses and Opportunistic Infections; February 22-25, 2026; Denver, CO. Poster 593.