Miailhes Patrick, Gilbert Camille, Lacombe Karine, Arends Joop E, Puoti Massimo, Rockstroh Jürgen K, Sogni Philippe, Fontaine Hélène, Rosenthal Eric, Winnock Maria, Loko Marc-Arthur, Wittkop Linda, Dabis François, Salmon Dominique
Department of Infectious and Tropical Diseases, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
Centre INSERM U897-Epidemiologie-Biostatistique, INSERM, ISPED, Bordeaux, France.
Liver Int. 2015 Sep;35(9):2090-9. doi: 10.1111/liv.12799. Epub 2015 Feb 23.
BACKGROUND & AIMS: The efficacy and safety of triple therapy combining boceprevir (BOC) or telaprevir (TVR) with pegylated interferon-alfa and ribavirin (PegIFN/RBV) has rarely been investigated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) genotype 1-coinfected patients with cirrhosis.
We conducted a European (France, Italy, Germany, Netherlands) multicentre study of triple therapy in cirrhotic HIV/HCV GT1-coinfected patients.
Fifty-nine patients (47 TVR, 12 BOC) were studied. Median CD4 cell count was 457 (293-578)/mm(3), and HIV viral load was <50 copies/ml in 93% of patients. The HCV genotype was GT1a (78%) or GT1b (13%). Previous PegIFN/RBV therapy had resulted in non-response (73%) or relapse (12%), and 15% of patients were treatment-naïve. The sustained virological response rate at week 12 (SVR12) was 53% overall (57% with TVR, 36% with BOC). A baseline HCV-RNA level <800 000 IU/ml tended to be associated with SVR12 (65 vs 42%, P = 0.11). In multivariate analysis, a virological response at week 4 after BOC or TVR initiation was significantly associated with SVR12 (P = 0.040). Early discontinuation of triple therapy was frequent (n = 26, 44%), because of non-response/breakthrough (65%) or adverse events (AEs) (35%). Three patients died. Severe anaemia (<9 g/dl) occurred in 14 patients (25%), leading to RBV dose reduction (22%), erythropoietin use (56%) or blood transfusion (14%). In multivariate analysis, lack of RBV dose reduction was significantly associated with severe AEs (P = 0.006).
More than half of HIV/HCV GT1-coinfected patients with cirrhosis achieved a SVR12. To avoid unnecessary adverse effects, therapy should be discontinued if no response is obtained at week 4.
在合并感染人类免疫缺陷病毒/丙型肝炎病毒（HIV/HCV）1型的肝硬化患者中，很少研究博赛匹韦（BOC）或特拉匹韦（TVR）联合聚乙二醇化干扰素-α和利巴韦林（PegIFN/RBV）的三联疗法的疗效和安全性。
我们在欧洲（法国、意大利、德国、荷兰）开展了一项针对合并感染HIV/HCV GT1型的肝硬化患者的三联疗法多中心研究。
共研究了59例患者（47例使用TVR，12例使用BOC）。CD4细胞计数中位数为457（293 - 578）/mm³，93%的患者HIV病毒载量<50拷贝/ml。HCV基因型为GT1a（78%）或GT1b（13%）。既往PegIFN/RBV治疗导致无应答（73%）或复发（12%），15%的患者未接受过治疗。第12周时的持续病毒学应答率（SVR12）总体为53%（使用TVR的患者为57%，使用BOC的患者为36%）。基线HCV-RNA水平<800 ０００ IU/ml倾向于与SVR12相关（65%对42%，P = 0.11）。在多变量分析中，开始使用BOC或TVR后第4周出现病毒学应答与SVR12显著相关（P = 0.040）。三联疗法的早期停药很常见（n = 26，44%），原因是无应答/突破（65%）或不良事件（AE）（35%）。3例患者死亡。14例患者（25%）出现严重贫血（<9 g/dl），导致利巴韦林剂量减少（22%）、使用促红细胞生成素（56%）或输血（14%）。在多变量分析中，未减少利巴韦林剂量与严重不良事件显著相关（P = 0.006）。
超过一半的合并感染HIV/HCV GT1型的肝硬化患者实现了SVR12。为避免不必要的不良反应，如果在第4周未获得应答，应停止治疗。
