Adverse Reactions (AR) to maraviroc.

ObjectivesMaraviroc may reduce hepatic inflammation in people with HIV and non-alcoholic fatty liver disease (HIV-NAFLD) through CCR5-receptor antagonism, which warrants further exploration.MethodsWe performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characteristics for maraviroc. The primary outcomes were safety, recruitment and retention rates, adherence and data completeness. Secondary outcomes included the change in Fibroscan-assessed liver stiffness measurements (LSM), controlled attenuation parameter (CAP) and Enhanced Liver Fibrosis (ELF) scores.ResultsFifty-three participants (53/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP & ELF scores were 6.2 (IQR 4.6–7.8) kPa, 325 (IQR 279–351) dB/m and 9.1 (IQR 8.6–9.6) respectively. Primary outcomes: all individuals eligible after screening were randomised; there was 92% (SD 6.6%) adherence to maraviroc [target >90%]; 83% (95%CI 70%-92%) participant retention [target >65%]; 5.5% of data were missing [target ConclusionsThis feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis.Trial registrationClinical trial registry: ISCRTN, registration number 31461655.**研究目的** 马拉维若（maraviroc）可通过CCR5受体拮抗作用，减轻人类免疫缺陷病毒（HIV）合并非酒精性脂肪性肝病（HIV-NAFLD）患者的肝脏炎症，该效应有待进一步探索。 **研究方法** 本研究针对病毒学抑制的HIV-1感染者合并无肝硬化的NAFLD患者，开展一项开放标签、96周、1:1随机对照可行性试验，比较马拉维若联合优化背景治疗（optimised background therapy, OBT）与单纯OBT的干预效果。给药方案遵循马拉维若药品特性概要中针对HIV治疗的推荐剂量。本研究的主要结局指标包括安全性、招募与留存率、治疗依从性及数据完整性；次要结局指标包括瞬时弹性成像（Fibroscan）评估的肝脏硬度测量值（liver stiffness measurements, LSM）、受控衰减参数（controlled attenuation parameter, CAP）及肝纤维化增强评分（Enhanced Liver Fibrosis, ELF）的变化情况。 **研究结果** 本研究共招募53名受试者（完成目标招募量的88%，目标招募60人），其中23人接受马拉维若联合OBT治疗；受试者中89%为男性，19%合并2型糖尿病。受试者基线时的LSM、CAP及ELF评分中位数分别为6.2（四分位距4.6~7.8）kPa、325（四分位距279~351）dB/m及9.1（四分位距8.6~9.6）。主要结局指标方面：所有经筛查符合入组条件的受试者均完成随机分组；马拉维若治疗依从率为92%（标准差6.6%），预设目标为＞90%；受试者留存率为83%（95%置信区间70%~92%），预设目标为＞65%；数据缺失率为5.5%（预设目标 **研究结论** 本可行性研究为HIV-NAFLD患者使用马拉维若的安全性提供了初步证据，同时证明该研究的招募、留存及依从性均符合预期。上述数据支持开展确证性随机对照试验，以评估马拉维若对肝脏脂肪变性及纤维化的影响。 **试验注册** 临床试验注册平台：ISCRTN，注册编号31461655。