Coppola Nicola, Martini Salvatore, Pisaturo Mariantonietta, Sagnelli Caterina, Filippini Pietro, Sagnelli Evangelista
Nicola Coppola, Salvatore Martini, Mariantonietta Pisaturo, Pietro Filippini, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy.
World J Virol. 2015 Feb 12;4(1):1-12. doi: 10.5501/wjv.v4.i1.1.
Hepatitis C virus (HCV) infection is one of the most frequent causes of comorbidity and mortality in the human immunodeficiency virus (HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals (DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa (Peg-IFN) + ribavirin (RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCV-genotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence.
丙型肝炎病毒(HCV)感染是人类免疫缺陷病毒(HIV)感染者中最常见的合并症和死亡原因之一,肝脏相关死亡率目前是HIV阳性患者的第二大死因,因此应采用适当的抗病毒疗法来对抗HCV感染。2011年开始了直接抗病毒药物(DAAs)时代,HCV NS3/4A蛋白酶抑制剂特拉匹韦和博赛匹韦被批准用于治疗HCV 1型感染,每种药物都与聚乙二醇化干扰素α(Peg-IFN)+利巴韦林(RBV)联合使用。第一代DAAs的加入,显著提高了HCV 1型患者抗病毒治疗的疗效,无论是HCV单感染患者还是HIV/HCV合并感染患者,并且增强了HCV/HIV合并感染患者对Peg-IFN + RBV治疗反应不佳的情况。这些治疗方法显示出比Peg-IFN + RBV更高的持续病毒学应答率,但由于高 pill负担以及HCV NS3/4A蛋白酶抑制剂与抗逆转录病毒药物之间的多种药代动力学相互作用,耐受性和依从性降低。然后在2013年,新一代DAAs出现了,其特点是疗效高、耐受性好、pill负担低且治疗疗程缩短。第二代和第三代DAAs还包括不含干扰素的治疗方案,在最近针对HIV阳性患者的小型试验中,这些方案在疗效、耐受性和依从性方面都显示出令人欣慰的初步结果。