Grupo de Virología Clínica, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain.
Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Complexo Hospitalario Universitario de Ferrol (CHUF), Sergas, Ferrol, Spain.
J Med Virol. 2018 Jun;90(6):1094-1098. doi: 10.1002/jmv.25048. Epub 2018 Mar 12.
The presence of resistance-associated substitutions (RASs) at NS5A region might compromise the efficacy of Direct Acting Antiviral agents (DAAs). HCV resistance at NS5A region is mainly focused on patients with hepatitis C virus (HCV) genotypes 1a (G1a) and 3 (G3) with other factors of poor treatment response (ie cirrhosis, prior treatment-exposure, or HCV-RNA >800 000 IU/mL). Herein, we evaluated in a cohort of HCV G1a and G3 infected patients the prevalence of RASs at domain I NS5A using population-based sequencing and the impact of RASs on the optimization of current therapeutic strategies. The RASs considered as clinically relevant were: M28A/G/T, Q30D/E/H/G/K/L/R, L31M/V/F, H58D, and Y93C/H/N/S for G1a and Y93H for G3. A total of 232 patients naïve to NS5A inhibitors were included (166 G1a, 66 G3). The overall prevalence of NS5A RASs for G1a and G3 patients was low (5.5%) or null, respectively. A high proportion of patients harbored, at least, one factor of poor response (78.9% for G1a, and 75.8% for G3). Overall, the rates of patients harboring NS5A RASs in combination with any of the other factors were low and the vast majority of patients (G1a> 94% and G3 100%) could be treated with standard treatments of 12 weeks without ribavirin. In conclusion, testing NS5A RASs in specific HCV-infected populations (ie G1a & G3, cirrhosis, prior treatment experienced, HCV-RNA >800 000 IU/mL) might be useful to optimize current NS5A-based therapies avoiding ribavirin-related toxicities, and shortening treatment duration in the majority of patients.
NS5A 区域存在耐药相关替换（RAS）可能会影响直接作用抗病毒药物（DAA）的疗效。NS5A 区域的 HCV 耐药主要集中在丙型肝炎病毒（HCV）基因型 1a（G1a）和 3（G3）的患者中，这些患者存在其他治疗反应不良的因素（即肝硬化、既往治疗暴露或 HCV-RNA >800000IU/mL）。在此，我们通过基于人群的测序评估了 HCV G1a 和 G3 感染患者中 I 型 NS5A 区域 RAS 的流行情况，并研究了 RAS 对优化现有治疗策略的影响。被认为具有临床相关性的 RAS 包括：G1a 中的 M28A/G/T、Q30D/E/H/G/K/L/R、L31M/V/F、H58D 和 Y93C/H/N/S，以及 G3 中的 Y93H。共纳入 232 例对 NS5A 抑制剂初治的患者（166 例 G1a，66 例 G3）。G1a 和 G3 患者的 NS5A RAS 总体流行率较低（分别为 5.5%和零）。很大一部分患者至少存在一种治疗反应不良的因素（G1a 为 78.9%，G3 为 75.8%）。总体而言，携带 NS5A RASs 并伴有其他任何因素的患者比例较低，绝大多数患者（G1a>94%，G3 为 100%）可采用无利巴韦林的 12 周标准治疗方案进行治疗。总之，在特定 HCV 感染人群（即 G1a 和 G3、肝硬化、既往治疗史、HCV-RNA >800000IU/mL）中检测 NS5A RAS 可能有助于优化基于 NS5A 的现有治疗方案，避免利巴韦林相关的毒性，并缩短大多数患者的治疗时间。
