Rockstroh Juergen K, Soriano Vicente, Plonski Frank, Bansal Meena, Fätkenheuer Gerd, Small Catherine B, Asmuth David M, Pialoux Gilles, Mukwaya Geoffrey, Jagannatha Shyla, Heera Jayvant, Pineda Juan A
HIV Clin Trials. 2015 Mar-Apr;16(2):72-80. doi: 10.1179/1528433614Z.0000000011.
One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxicity has been observed with prolonged use of antiretroviral agents.
To evaluate the hepatic safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with HCV and/or HBV.
In this 148-week randomized, double-blind, placebo-controlled, multicentre study (NCT01327547), subjects received maraviroc twice daily (n = 70) or placebo (n = 67) in combination with other antiretroviral agents.
the percentage at week 48 of subjects with Grade 3 and Grade 4 ALT abnormalities, defined as >5 × upper limit of normal (ULN) if baseline ALT ≤ ULN or >3.5 × baseline if baseline ALT>ULN in the maraviroc versus the placebo arm.
At week 48, one subject in each group had met the primary endpoint definition. No subjects met protocol-defined liver stopping criteria and there were no cases of Hy's law or treatment-related hepatobiliary serious adverse events. No significant difference in change from baseline in enhanced liver fibrosis or hepatic elastography was observed between groups. Treatment-related hepatobiliary adverse events were reported in one and two subjects receiving maraviroc and placebo, respectively; discontinuations due to treatment-related AEs occurred in four and two subjects receiving maraviroc and placebo, respectively; two deaths were reported in the placebo group.
The use of maraviroc does not increase hepatotoxicity in HIV-1-infected subjects co-infected with HCV and/or HBV through 48 weeks of treatment.
在感染人类免疫缺陷病毒（HIV）的患者中，临床上较为相关的合并症之一是由乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）导致的进行性肝病。此外，长期使用抗逆转录病毒药物会出现肝毒性。
评估马拉维若与其他抗逆转录病毒药物联合使用时，对合并感染HCV和/或HBV的HIV-1感染者的肝脏安全性。
在这项为期148周的随机、双盲、安慰剂对照、多中心研究（NCT01327547）中，受试者每日两次接受马拉维若（n = 70）或安慰剂（n = 67），并联合使用其他抗逆转录病毒药物。
在第48周时，马拉维若组与安慰剂组中，谷丙转氨酶（ALT）出现3级和4级异常的受试者百分比，若基线ALT≤正常上限（ULN），则定义为>5×ULN；若基线ALT>ULN，则定义为>3.5×基线值。
在第48周时，每组各有1名受试者达到主要终点定义。没有受试者达到方案定义的肝脏停药标准，也没有出现Hy法则或与治疗相关的肝胆严重不良事件。两组之间在增强肝纤维化或肝脏弹性成像方面，与基线相比没有显著差异。分别有1名和2名接受马拉维若和安慰剂的受试者报告了与治疗相关的肝胆不良事件；因治疗相关不良事件停药的受试者，接受马拉维若和安慰剂的分别有4名和2名；安慰剂组报告了2例死亡。
在合并感染HCV和/或HBV的HIV-1感染者中，使用马拉维若进行48周治疗不会增加肝毒性。
