Time to viral suppression is not related to achievement of SVR12 in HCV GT1‐infected patients treated with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin

Abstract

Abbreviations: 3D, 3 direct-acting antiviral; DSV, dasabuvir; LLOD, lower limit of detection; LLOQ, lower limit of quantification; OBV, ombitasvir; PTV/r, paritparevir codosed with ritonavir; SVR, sustained virologic response. Summary High rates of sustained virologic response at post-treatment week 12 (SVR12) were achieved in six phase 3 trials of ombitasvir (OBV, an NS5A inhibitor), paritaprevir (an NS3/4A protease inhibitor) co-dosed with ritonavir (PTV/r) + dasabuvir (DSV, an NS5B RNA polymerase inhibitor) (ie, 3D regimen) with or without ribavirin (RBV) in adults with chronic genotype (GT) 1 hepatitis C virus (HCV) infection. We assessed whether time to first HCV RNA value below the lower limit of quantification in patients with and without cirrhosis was associated with achievement of SVR12. Data were analysed from GT1-infected patients enrolled in six phase 3 studies of 3D ± RBV. Patients who experienced non-virologic failure were excluded from analysis. HCV RNA was determined using the Roche COBAS TaqMan RT-PCR assay (lower limit of quantification, LLOQ =25 IU/mL). SVR12 was analysed by week of first HCV RNA suppression, defined as HCV RNA <LLOQ. The analysis included a total of 2027 patients. Cumulative proportions of subjects with initial HCV RNA suppression <LLOQ at weeks 1, 2, 4 and 6 were 31%, 81%, 99% and 100%, respectively. SVR12 was achieved by 98%, 97%, 98% and 92% of patients with initial suppression at Weeks 1, 2, 4 and 6, respectively (P=.42, trend test). Across six phase 3 trials of 3D ± RBV, most patients achieved viral suppression by week 2. Time to viral suppression was not associated with subsequent achievement of SVR12, suggesting that on-treatment virologic monitoring may not be necessary with this regimen. K E Y W O R D S direct-acting antiviral, interferon-free therapy, sustained virologic response 1 | INTRODUCTION In the era of interferon (IFN)-based therapies for hepatitis C virus (HCV) infection, several factors have been associated with failure to achieve sustained virologic response (SVR), including but not limited to slower viral suppression kinetics, interleukin 28B (IL28B) CT or TT polymorphisms, African-American race, male gender, insulin resistance, older age and, most importantly, advanced fibrosis 1,2. | 281 ALQAHTANI eT AL. While the development of first-generation protease inhibitors such as boceprevir and telaprevir in combination with pegylated IFN (pegIFN) and ribavirin (RBV) increased SVR rates relative to standalone treatment with pegIFN/RBV, negative predictors of SVR including cirrhosis and prior treatment experience with pegIFN/RBV remained relevant 3,4. Historically, an integral goal of patient management and an important on-treatment predictor of SVR has been the achievement of a rapid virologic response (RVR; defined as undetectable HCV RNA at treatment week 4) 5. While the addition of boceprevir to pegIFN/ RBV increased overall SVR rates, early viral kinetics remained a predictor of response 6. Indeed, a Response Guided Therapy (RGT) study of pegIFN/RBV plus ...

Safety and Efficacy of Ombitasvir, Paritaprevir With Ritonavir ± Dasabuvir With or Without Ribavirin in Patients With Human Immunodeficiency Virus-1 and Hepatitis C Virus Genotype 1 or Genotype 4 Coinfection: TURQUOISE-I Part 2

“…Although cross-study comparisons should be interpreted with caution, it is encouraging that of the 22 black patients enrolled in TURQUOISE-I Part 2, 1 patient experienced relapse, and this was the only relapse in the study; although conclusions cannot be made with statistical accuracy, this observation is confirmed by the results of TURQUOISE-I, Part 1b, wherein 41% (9 of 22) of patients were black, and all achieved SVR12 [ 16 ]. Together, these results support previous results indicating that black race is not a predictor of relapse with the OBV/PTV/r plus DSV regimen [ 21 ]. The recent C-EDGE CO-INFECTION study conducted in treatment-naive patients with HCV genotype 1, 4, or 6 and HIV coinfection demonstrated that 96% (210 of 218) of patients achieved SVR12 after 12 weeks of treatment with elbasvir/grazoprevir, with 5 patients (2%) experiencing relapse [ 22 ].…”

Real‐world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for patients with chronic hepatitis C virus genotype 1b infection in Taiwan

“…In lines with the trial reports, we confirmed that the SVR 12 rates were comparable in our patients receiving PrOD‐based treatment, regardless of sex, age, prior treatment experience, HBsAg status, RBV usage, baseline HCV RNA levels, eGFR or stage of hepatic fibrosis . In addition, we also found that the viral decline at week 2 of treatment did not affect the SVR 12 rates . Among cirrhotic patients, our data were also in line with TURQUOISE‐II and TURQUOISE‐III studies that the SVR 12 rates were comparable for those with or without RBV …”

Real‐world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis

“…Until recently, therapy regimen included a first‐generation protease inhibitor, interferon and ribavirin, but nowadays the strategy includes interferon‐free regimens . The treatment lasts between 12 and 24 weeks, depending on patient's characteristics and the SVR rate in cirrhotic HCV genotype 1‐infected patients is more than 90% . In Romania too, hepatitis C is a major health problem .…”