Hepatitis B Outcomes After Switching to Long-Acting Cabotegravir/Rilpivirine in People With HIV: Reactivation, Incident Infection, and Liver Safety Across Diverse Serological Profiles

BACKGROUND: Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) therapy for HIV, lacks activity against hepatitis B virus (HBV). We evaluate HBV serological profiles and risk of HBV reactivation (HBVr) or incident infection (HBVi) in people with HIV (PWH) switching to LA-CAB/RPV. METHODS: Prospective cohort study of PWH initiating LA-CAB/RPV at Hospital Clínic Barcelona between February/2023 and February/2025. HBV serology, vaccination status, and liver function tests (LFTs) were assessed at baseline. Follow-up LFTs were performed routinely (weeks 12, 28, and every 6 months), and HBV serology/DNA assessed if abnormal LFTs, acute hepatitis or clinical suspicion of reactivation. HBVr was defined as conversion from HBsAg negative to positive or detectable HBV DNA in anti-HBc-positive/HBsAg-negative individuals, or as HBV DNA ≥1 log increase or ≥100 IU/mL in chronic HBV (HBsAg-positive) participants. HBVi was defined as HBsAg seroconversion in HBV unexposed individuals. RESULTS: Among 741 participants-92% cis-gender male, median age 43 (IQR 35-52)-454 (61%) had vaccine-induced immunity and 25% had prior HBV exposure (anti-HBc-positive), with 3% showing isolated anti-HBc. Median follow-up was 54 weeks (IQR 28-77). No HBVr or HBVi were observed in people without chronic hepatitis at baseline. Four individuals (0.5%) with unnoticed chronic HBV infection (HBsAg-positive) started LA-CAB/RPV; two developed clinical HBVr and two remained stable after regimen switch, all four switched back to tenofovir-containing therapy. Transaminase elevations during follow-up occurred in 17% of the cohort, regardless of HBV serostatus. CONCLUSIONS: LA-CAB/RPV appears safe in individuals with prior HBV exposure, including isolated anti-HBc. Comprehensive HBV screening, vaccination, and liver monitoring are essential.