Abstract
INTRODUCTION: HIV/hepatitis B virus (HBV) coinfection elevates the risk of liver-related complications compared to HIV or HBV mono-infections. While some antiretroviral therapy (ART) regimens slow liver disease progression, the long-term effects of tenofovir-based and non-tenofovir-based ART on advanced liver disease events in people with HIV/HBV remain unclear. METHODS: People with HIV/HBV and aged ≥ 18 years or older who initiated ART between April 2016 and January 2024 were included from the US HealthVerity claims database. Advanced liver disease events (cirrhosis, liver decompensation, hepatocellular carcinoma [HCC], and liver transplant) were evaluated overall and individually among people who received tenofovir alafenamide (TAF)-based, tenofovir disoproxil fumarate (TDF)-based, or non-tenofovir-based ART; people with events prior to ART initiation were excluded. The time to advanced liver disease events were estimated with Kaplan-Meier methods. Adjusted hazard ratios and 95% CIs were calculated using Cox proportional hazards models. To evaluate liver function over time, alanine aminotransferase and aspartate aminotransferase levels before and after ART initiation were assessed for up to 1 year using adjusted mixed-effect models. RESULTS: Among 3095 people included, 76% initiated TAF-based, 13% initiated TDF-based, and 11% initiated non-tenofovir-based ART. TAF-based and TDF-based ART had significantly longer times to any advanced liver disease event compared to non-tenofovir-based ART (log-rank P < 0.01). After adjustment, both TAF-based and TDF-based ART retained significantly reduced the risk of any advanced liver disease event and TAF-based ART had a lower risk of cirrhosis and risk of HCC compared with non-tenofovir-based ART (P < 0.05). Tenofovir-based ART was associated with stable liver enzyme levels over time. CONCLUSIONS: Tenofovir-based ART was associated with a reduced risk of severe liver-related complications overall. TAF-based ART was associated with progression to cirrhosis and HCC, relative to non-tenofovir-based ART in people with HIV/HBV. These findings highlight the importance of tenofovir-based ART regimens in improving outcomes for people with HIV/HBV.