Munteanu Daniela I, Rockstroh Jürgen K
Department of Medicine I, Bonn University Hospital, Bonn, Germany and Adults III Department, Matei Bals National Institute of Infectious Diseases, Bucharest, Romania.
Department of Medicine I, Bonn University Hospital, Sigmund-Freud-Str. 25, Bonn 53105, Germany.
Ther Adv Infect Dis. 2013 Apr;1(2):71-80. doi: 10.1177/2049936113479591.
Pilot trials evaluating the efficacy and safety of the first licensed hepatitis C virus (HCV) protease inhibitors (PIs), boceprevir (BOC) and telaprevir (TVR), for the treatment of genotype 1 infection in HCV/HIV co-infected patients revealed similar results as in HCV mono-infected patients. HCV liver disease progresses more rapidly in co-infected patients, particularly with advanced immunodeficiency. Therefore, HCV treatment in HIV is of great importance. However, dual therapy with pegylated interferon (PegIFN) and ribavirin (RBV) has been associated with lower cure rates and increased toxicities in co-infected subjects, thereby limiting overall HCV therapy uptake. The availability of HCV PIs opens new perspectives for HCV cure in co-infected patients, with a 70% sustained virologic response (SVR) rate in HCV treatment-naïve patients. Despite these impressive advances, the use of the new treatment options has been low, reflecting the complex issues with modern triple HCV therapy. Indeed pill burden, adverse events (AEs), drug-drug interactions (DDIs) and high costs complicate HCV therapy in HIV. So far, studies have shown no tolerability differences in mono- and co-infected patients with the early stages of liver fibrosis. Regarding DDIs between HVC PIs and antiretroviral drugs, TVR can be safely administered with efavirenz (with dose adjustment of TVR), etravirine (ETR), rilpivirine, boosted atazanavir (ATV/r) and raltegravir (RAL), while BOC can be safely administered with ETR, RAL and potentially ATV/r for treatment-naïve patients under careful monitoring. Currently, the great number of HCV molecules under development is promising substantially improved treatment paradigms with shorter treatment durations, fewer AEs, less DDIs, once-daily administration and even interferon-free regimens. The decision to treat now with the available HCV PIs or defer therapy until the second generation of HCV direct acting antivirals become available should be based on liver fibrosis staging and fibrosis progression during follow up. More data are urgently needed regarding the efficacy of triple therapy in HIV/HCV co-infected patients who previously failed PegIFN/RBV therapy as well as in patients with more advanced fibrosis stages.
评估首批获批的丙型肝炎病毒（HCV）蛋白酶抑制剂（PIs）博赛匹韦（BOC）和特拉匹韦（TVR）治疗HCV/HIV合并感染患者基因1型感染的疗效和安全性的初步试验结果显示，与HCV单感染患者相似。HCV合并感染患者的肝脏疾病进展更快，尤其是在晚期免疫缺陷患者中。因此，HIV患者的HCV治疗非常重要。然而，聚乙二醇干扰素（PegIFN）和利巴韦林（RBV）的联合治疗在合并感染患者中与较低的治愈率和更高的毒性相关，从而限制了整体HCV治疗的应用。HCV PIs的出现为合并感染患者的HCV治愈开辟了新的前景，初治HCV患者的持续病毒学应答（SVR）率达70%。尽管取得了这些令人瞩目的进展，但新治疗方案的使用并不广泛，这反映出现代三联HCV治疗存在的复杂问题。确实，药片负担、不良事件（AE）、药物相互作用（DDI）和高成本使HIV患者的HCV治疗变得复杂。到目前为止，研究表明肝纤维化早期的单感染和合并感染患者在耐受性方面没有差异。关于HVC PIs与抗逆转录病毒药物之间的DDI，TVR可与依非韦伦（需调整TVR剂量）、依曲韦林（ETR）、rilpivirine、增强型阿扎那韦（ATV/r）和拉替拉韦（RAL）安全联用，而BOC可与ETR、RAL以及在密切监测下可能与ATV/r安全联用，用于初治患者。目前，大量正在研发的HCV分子有望带来显著改善的治疗模式，治疗疗程更短、AE更少、DDI更少、每日一次给药甚至无需干扰素治疗方案。现在决定使用现有的HCV PIs进行治疗还是推迟治疗直至第二代HCV直接作用抗病毒药物上市，应基于肝纤维化分期以及随访期间的纤维化进展情况。对于先前PegIFN/RBV治疗失败的HIV/HCV合并感染患者以及纤维化程度更严重阶段的患者，三联疗法的疗效迫切需要更多数据。
