Chuo Ching-Yi, Zachry Woodie, de Boer Melanie, Telep Laura, Tao Li
Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
Infect Dis Ther. 2025 Jul 15. doi: 10.1007/s40121-025-01192-5.
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.
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.
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.
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.
与单纯感染人类免疫缺陷病毒（HIV）或乙型肝炎病毒（HBV）相比，HIV/HBV合并感染会增加肝脏相关并发症的风险。虽然一些抗逆转录病毒疗法（ART）方案可减缓肝病进展，但基于替诺福韦和非基于替诺福韦的ART对HIV/HBV感染者晚期肝病事件的长期影响仍不明确。
从美国HealthVerity索赔数据库中纳入2016年4月至2024年1月开始接受ART治疗的年龄≥18岁的HIV/HBV感染者。对接受基于丙酚替诺福韦（TAF）、富马酸替诺福韦二吡呋酯（TDF）或非替诺福韦的ART治疗的患者总体及个体评估晚期肝病事件（肝硬化、肝失代偿、肝细胞癌[HCC]和肝移植）；排除ART治疗开始前出现这些事件的患者。采用Kaplan-Meier方法估计晚期肝病事件的发生时间。使用Cox比例风险模型计算调整后的风险比和95%置信区间。为评估随时间变化的肝功能，使用调整后的混合效应模型评估ART治疗开始前后长达1年的丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平。
在纳入的3095名患者中，76%开始接受基于TAF的ART治疗，13%开始接受基于TDF的ART治疗，11%开始接受非替诺福韦的ART治疗。与非替诺福韦的ART治疗相比，基于TAF和基于TDF的ART治疗出现任何晚期肝病事件的时间显著更长（对数秩检验P<0.01）。调整后，基于TAF和基于TDF的ART治疗均显著降低了任何晚期肝病事件的风险，且与非替诺福韦的ART治疗相比，基于TAF的ART治疗发生肝硬化和HCC的风险更低（P<0.05）。基于替诺福韦的ART治疗与肝酶水平随时间稳定相关。
总体而言，基于替诺福韦的ART治疗与严重肝脏相关并发症风险降低相关。在HIV/HBV感染者中，相对于非替诺福韦的ART治疗，基于TAF的ART治疗与进展为肝硬化和HCC相关。这些发现凸显了基于替诺福韦的ART方案对改善HIV/HBV感染者预后的重要性。
