Fierer Daniel S, Wyles David L
Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, USA.
Open Forum Infect Dis. 2020 Mar 16;7(4):ofaa095. doi: 10.1093/ofid/ofaa095. eCollection 2020 Apr.
Direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) result in initial cure rates of 95% to 99% and re-treatment cure rates of 95%. Nevertheless, given the sheer magnitude of infected persons, some will ultimately fail multiple DAA therapies, and re-treatment of these persons has not been adequately studied.
We evaluated treated an HIV-infected man with cirrhosis from genotype 1b HCV who had failed 3 DAA regimens.
We treated and cured our "particularly difficult-to-cure" patient with sofosbuvir plus glecaprevir/pibrentasvir plus ribavirin for 24 weeks. We discuss the literature on potential biological factors behind his treatment failures such as lack of HCV seroconversion during his infection course, and multiple failures of hepatitis B seroconversion after vaccination, and the rationale for choosing his curative salvage regimen.
There are no clinical trials-proven re-treatment regimens for "particularly difficult-to-cure" patients. Multiple patient- and virus-related factors that do not affect cure rates in treatment-naive patients may need to be considered in choosing a re-treatment regimen for these patients. These regimens may need to include combinations drugs that are not available in single-tablet form, addition of ribavirin, and longer durations of treatment than standard.
丙型肝炎病毒（HCV）的直接抗病毒（DAA）疗法初始治愈率为95%至99%，再次治疗的治愈率为95%。然而，鉴于感染者数量众多，一些人最终会多次DAA治疗失败，而对这些人的再次治疗尚未得到充分研究。
我们评估并治疗了一名感染HIV且患有1b型HCV肝硬化的男性，他已3次DAA治疗方案失败。
我们使用索磷布韦加格卡瑞韦/哌仑他韦加利巴韦林对我们这位“特别难以治愈”的患者进行了24周的治疗并治愈。我们讨论了关于其治疗失败背后潜在生物学因素的文献，如感染过程中缺乏HCV血清转化，以及接种疫苗后多次乙肝血清转化失败，以及选择其挽救性治愈方案的理由。
对于“特别难以治愈”的患者，尚无经临床试验验证的再次治疗方案。在为这些患者选择再次治疗方案时，可能需要考虑多个不影响初治患者治愈率的患者和病毒相关因素。这些方案可能需要包括非单片制剂形式的联合药物、添加利巴韦林以及比标准疗程更长的治疗时间。
