Cento Valeria, Di Paolo Daniele, Di Carlo Domenico, Micheli Valeria, Tontodonati Monica, De Leonardis Francesco, Aragri Marianna, Antonucci Francesco Paolo, Di Maio Velia Chiara, Mancon Alessandro, Lenci Ilaria, Manunta Alessandra, Taliani Gloria, Di Biagio Antonio, Nicolini Laura Ambra, Nosotti Lorenzo, Sarrecchia Cesare, Siciliano Massimo, Landonio Simona, Pellicelli Adriano, Gasbarrini Adriano, Vecchiet Jacopo, Magni Carlo Federico, Babudieri Sergio, Mura Maria Stella, Andreoni Massimo, Parruti Giustino, Rizzardini Giuliano, Angelico Mario, Perno Carlo Federico, Ceccherini-Silberstein Francesca
Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
Hepatology Unit, University Hospital of Rome "Tor Vergata", Rome, Italy.
Dig Liver Dis. 2015 Feb;47(2):157-63. doi: 10.1016/j.dld.2014.11.010. Epub 2014 Nov 24.
Triple therapy with telaprevir/boceprevir + pegylated-interferon+ribavirin can achieve excellent antiviral efficacy, but it can be burdened with resistance development at failure.
To evaluate kinetics of hepatitis C virus (HCV) RNA decay and early resistance development, in order to promptly identify patients at highest risk of failure to first generation protease inhibitors.
HCV-RNA was prospectively quantified in 158 patients receiving pegylated-interferon+ribavirin+telaprevir (N = 114) or+boceprevir (N = 44), at early time-points and during per protocol follow-up. Drug resistance was contextually evaluated by population sequencing.
HCV-RNA at week-2 was significantly higher in patients experiencing virological failure to triple-therapy than in patients with sustained viral response (2.3 [1.9-2.8] versus 1.2 [0.3-1.7]log IU/mL, p < 0.001). A 100 IU/mL cut-off value for week-2 HCV-RNA had the highest sensitivity (86%) in predicting virological success. Indeed, 23/23 (100%) patients with undetectable HCV-RNA reached success, versus 26/34 (76.5%) patients with HCV-RNA<100 IU/mL, and only 11/31 (35.5%) with HCV-RNA > 100 IU/mL (p < 0.001). Furthermore, differently from failing patients, none of the patient with undetectable HCV-RNA at week-2 had baseline/early resistance.
With triple therapy based on first generation protease inhibitors, suboptimal HCV-RNA decay at week-2 combined with early detection of resistance can help identifying patients with higher risk of virological failure, thus requiring a closer monitoring during therapy.
特拉匹韦/博赛匹韦+聚乙二醇干扰素+利巴韦林三联疗法可实现出色的抗病毒疗效，但治疗失败时可能会出现耐药性。
评估丙型肝炎病毒（HCV）RNA衰减动力学和早期耐药性发展情况，以便及时识别第一代蛋白酶抑制剂治疗失败风险最高的患者。
前瞻性地对158例接受聚乙二醇干扰素+利巴韦林+特拉匹韦（n = 114）或+博赛匹韦（n = 44）治疗的患者在早期时间点及按方案随访期间进行HCV-RNA定量检测。通过群体测序对耐药性进行同步评估。
三联疗法病毒学失败患者第2周时的HCV-RNA显著高于持续病毒学应答患者（2.3[1.9 - 2.8]对1.2[0.3 - 1.7]log IU/mL，p < 0.001）。第2周HCV-RNA的100 IU/mL临界值在预测病毒学成功方面具有最高敏感性（86%）。实际上，HCV-RNA检测不到的23/23（100%）例患者获得成功，而HCV-RNA<100 IU/mL的患者为26/34（76.5%），HCV-RNA>100 IU/mL的患者仅11/31（35.5%）（p < 0.001）。此外，与治疗失败患者不同，第2周HCV-RNA检测不到的患者均无基线/早期耐药性。
对于基于第一代蛋白酶抑制剂的三联疗法，第2周时HCV-RNA衰减欠佳并伴有早期耐药性检测有助于识别病毒学失败风险较高的患者，因此在治疗期间需要更密切的监测。
