Brighton and Sussex University Hospitals NHS Trust, Brighton
Brighton and Sussex University Hospitals NHS Trust, Brighton.
BMJ Open. 2020 Jul 6;10(7):e035596. doi: 10.1136/bmjopen-2019-035596.
At least 30% of people living with HIV (PLWH) infection have non-alcoholic fatty liver disease (NAFLD), which has now become a leading cause of hepatic fibrosis and cirrhosis. Management is based largely on lifestyle modifications, which are difficult to achieve, and therapeutic options are urgently needed. Maraviroc (MVC), through antagonism of CCR5 receptors, may reduce hepatic fibrosis progression and could be an effective treatment for NAFLD. However, dosing is usually two times per day, unlike most currently recommended antiretroviral therapies. This study will investigate the feasibility and acceptability of addition of MVC to combination antiretroviral therapy in PLWH and NAFLD as a treatment for NAFLD.
This is a phase IV, randomised, open-label, non-invasive feasibility study. Sixty individuals with well-controlled HIV-1 and NAFLD will be recruited from UK HIV clinics and randomised 1:1 to receive either optimised background therapy (OBT) plus MVC or OBT alone. Follow-up will be every 24 weeks for 96 weeks. The primary outcome measures will include recruitment and retention rates, adverse events and adherence. Secondary outcomes will include changes in markers of hepatic fibrosis, including the Enhanced Liver Fibrosis score, median liver stiffness measurement and controlled attenuation parameter scores on Fibroscan, and quality of life assessments. Analyses will be performed according to intention-to-treat principles. For secondary outcomes, estimated differences and 95% CIs between the groups using a t-method will be presented for continuous variables and as exact 95% binomial CIs for categorical variables.
Ethical approval was obtained through the London Dulwich UK Research Ethics Committee (reference 17/LO/2093). Results will be disseminated both through community groups and peer-reviewed scientific literature. SRCTN31461655. EudraCT number 2017-004141-24; Pre-results.
至少 30%的人类免疫缺陷病毒（HIV）感染者患有非酒精性脂肪性肝病（NAFLD），这已成为肝纤维化和肝硬化的主要原因。治疗主要基于生活方式的改变，但这些改变很难实现，因此急需治疗选择。马拉维若（MVC）通过拮抗 CCR5 受体，可能会减缓肝纤维化的进展，因此可能是治疗 NAFLD 的有效方法。然而，MVC 的剂量通常为每天两次，与大多数目前推荐的抗逆转录病毒疗法不同。本研究将调查将 MVC 添加到 HIV 感染者和 NAFLD 的联合抗逆转录病毒治疗中作为 NAFLD 治疗的可行性和可接受性。
这是一项四期、随机、开放标签、非侵入性可行性研究。将从英国 HIV 诊所招募 60 名 HIV-1 控制良好且患有 NAFLD 的个体，并将其随机分为 1:1 组，分别接受优化背景治疗（OBT）加 MVC 或 OBT 单独治疗。随访时间为 96 周，每 24 周一次。主要观察指标将包括招募和保留率、不良事件和依从性。次要结局将包括肝纤维化标志物的变化，包括增强型肝脏纤维化评分、肝硬度中位数测量值和 Fibroscan 的受控衰减参数评分，以及生活质量评估。分析将根据意向治疗原则进行。对于次要结局，将使用 t 检验法在两组间呈现连续变量的估计差值和 95%置信区间（CI），并以确切的 95%二项式 CI 呈现分类变量。
伦敦 Dulwich 英国伦理委员会获得了伦理批准（参考号 17/LO/2093）。结果将通过社区团体和同行评议的科学文献进行传播。SRCTN31461655。EudraCT 编号 2017-004141-24；预结果。
