TVR-based Therapy Research Articles

Real-Life Experiences with Telaprevir in the Treatment of Chronic Genotype 1 Hepatitis C — The TEPS Study

As one of the first Direct Acting Antivirals (DAA), the protease inhibitor Telaprevir (TVR) was available in the European Union from 9/2011 until 9/2016 as a new treatment option for chronic Hepatitis C. Aim. To assess the implementation of therapy stopping rules or shortening of the treatment and their impact on sustained virological response (SVR), as well as the safety and efficacy of the TVR-based therapy during routine daily treatment of patients in Germany. Materials and Methods. 802 patients were assessed (272 treatment naïve, 520 pre-treated) in the noninterventional, multi-center study. Results. 56.6 % of the patients achieved SVR. SVR rate was higher in patients with relapse after previous treatment (68.0 %) than in patients with a previous null-response (31.1 %) and in previously untreated patients (58.1 %). Stopping rule conditions were fulfilled by 3.2 % of patients and it was implemented in 65.4 % of these. 34.3 % of the patients fulfilled the conditions for a therapy shortening. This rule was adhered to in 48.4 % of these, in 34.5 % it was not adhered to. Thus recommendations were not always being followed. Therapy shortening was considered more frequently in previously untreated (54.8 %) than for previously treated patients (24.2 %). Stopping rule application but not shortened treatment reduced therapy costs. Conclusion. The TVR-based therapy represented a breakthrough at that time. Further DAAs have been added as therapeutic options since, increasing the complexity of treatment choice and correct implementation. They represent both an opportunity and a challenge for all those involved. As one of the first Direct Acting Antivirals (DAA), the protease inhibitor Telaprevir (TVR) was available in the European Union from 9/2011 until 9/2016 as a new treatment option for chronic Hepatitis C.Aim. To assess the implementation of therapy stopping rules or shortening of the treatment and their impact on sustained virological response (SVR), as well as the safety and efficacy of the TVR-based therapy during routine daily treatment of patients in Germany.Materials and Methods. 802 patients were assessed (272 treatment naïve, 520 pre-treated) in the noninterventional, multi-center study.Results. 56.6 % of the patients achieved SVR. SVR rate was higher in patients with relapse after previous treatment (68.0 %) than in patients with a previous null-response (31.1 %) and in previously untreated patients (58.1 %). Stopping rule conditions were fulfilled by 3.2 % of patients and it was implemented in 65.4 % of these. 34.3 % of the patients fulfilled the conditions for a therapy shortening. This rule was adhered to in 48.4 % of these, in 34.5 % it was not adhered to. Thus recommendations were not always being followed. Therapy shortening was considered more frequently in previously untreated (54.8 %) than for previously treated patients (24.2 %). Stopping rule application but not shortened treatment reduced therapy costs.Conclusion. The TVR-based therapy represented a breakthrough at that time. Further DAAs have been added as therapeutic options since, increasing the complexity of treatment choice and correct implementation. They represent both an opportunity and a challenge for all those involved.

Ultra-deep sequencing analysis of resistance-associated variants during retreatment with simeprevir-based triple therapy after failure of telaprevir-based triple therapy in patients with genotype 1 hepatitis C virus infection.

Simeprevir (SMV)-based triple therapy is an effective retreatment option following failure of telaprevir (TVR)-based triple therapy. However, it is unclear whether the persistence of resistance-associated variants (RAVs) induced by TVR-based therapy may reduce the treatment effect of SMV-based therapy. The factors associated with the treatment effect, including RAVs in the NS3 region, were examined in 21 patients with genotype 1b HCV infection who were treated with SMV-based therapy after failure of TVR-based therapy. Ultra-deep sequencing was carried out to detect RAVs. With the exception of one patient who discontinued treatment owing to adverse events, the sustained virologic response (SVR) rate was 50% (10/20). Ultra-deep sequencing at the start of SMV-based therapy revealed that TVR-resistant variants were detected in six patients (29%), and no variants were observed at position 168. Cross-resistance between TVR and SMV with low frequency was detected in only one patient, and this patient achieved SVR. Higher SVRs for SMV-based therapy were attained in patients who discontinued treatment owing to the adverse effects of prior TVR-based therapy (discontinuation 100% vs. non-discontinuation 29%, P = 0.005), and patients who relapsed following prior pegylated interferon plus ribavirin therapy (relapse 100% vs. non-response 20%, P = 0.007). In this study, ultra-deep sequencing analysis revealed that TVR and/or SMV-resistant variants may have no influence on the effect of SMV-based therapy after failure of TVR-based therapy. Patients who discontinued treatment owing to adverse effects of TVR-based therapy and relapsers to previous pegylated interferon/ribavirin therapy would be good candidates for retreatment with SMV-based therapy.

The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting Antiviral Therapies: What We Can Learn from the Protease Inhibitors.

Direct-acting antiviral (DAA) therapies have revolutionised the treatment of hepatitis C virus (HCV). The financial cost of DAAs however is significant, and first generation protease inhibitors (PIs) also require frequent monitoring of viral RNA levels to guide treatment. In this context, we examined the relevance of HCV antigen testing to evaluate the potential role in monitoring virological response to HCV antiviral treatment with the PI-based triple therapies, telaprevir (TVR) and boceprevir (BOC). Chronic HCV-infected individuals (n = 152) enrolled in the Irish Hepatitis C Outcomes Research Network (ICORN) study were prospectively analysed for baseline markers and the early viral kinetics associated with SVR. The sustained virological response (SVR) rates in the cohort receiving TVR and BOC were 87.3% and 73.8%, respectively. Baseline factors associated with successful outcome in TVR therapy were age (P = 0.0098), IFNL3 genotype (P = 0.0330) and viral load (P = 0.0456). RNA level at week 4 (P = 0.0068) and viral antigen negativity at week 2 (P = 0.0359) were predictive of SVR for TVR-based therapy. In BOC therapy, prior interferon treatment (P = 0.0209) and IFNL3 genotype (P = 0.0410) were baseline predictors of SVR. Evidence of viraemia based either on viral RNA or antigen at week 4 predicted SVR in these patients. Our data showed that rapid decline of HCV antigen to negative level at week 2 in TVR treatment and <0.96 log fmol/l in BOC treatment after commencement of PI triple therapy were associated with SVR. HCV antigen measurement should be considered as a potential alternative for monitoring treatment response during DAA-based regimens.

Efficacy and tolerability of telaprevir (TVR)-based triple therapy in HIV/HCV-coinfected patients.

IntroductionClinical trials (CT) on triple therapy against HCV infection in HIV-infected patients including TVR plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than with PR alone. This study was aimed to evaluate the efficacy and safety of triple therapy including TVR in HIV/HCV-coinfected patients in real-life conditions.Materials and MethodsHIV/HCV genotype 1 patients seen at four Hospitals in Madrid who received therapy including TVR plus PR for at least two weeks were included. The response was evaluated during treatment, and sustained viral response (SVR) was evaluated 12 and 24 weeks after the end of the treatment.ResultsFifty-eight patients have been included; 79% male, median age 48 y.o.; 38% were IL28B rs12979860 genotype CT or TT, 58.6% of patients presented cirrhosis and 24.1% presented fibrosis F3. Infection with genotype 1a was observed in 53.4% of patients. Median baseline HCV-RNA was 3,282,263 IU/mL (77.5% had >800,000 IU/mL). The most commonly used antiretroviral (ARV) drugs were tenofovir/emtricitabine [36 (62%) patients], etravirine [21 (36%) patients], abacavir/lamivudine [18 (31%) patients], boosted protease inhibitors [16 (27.5%) patients] and raltegravir [12 (20.6%) patients]. Of the 42 (72.4%) patients who had received previous HCV treatment, 13.7% were null responders, 25.8% were partial responders and 31% had relapsed. In an ITT approach, proportions of patients with undetectable HCV RNA were 67.8% (38/56) at TW4, 83.3% (40/48) at TW12, 80% (36/45) at TW24, 79.4% at TW36 (31/39) and 72% (26/36) at TW48. Fifteen (25.8%) patients discontinued HCV therapy [8 (13.8%) because they fulfilled stopping rules, 5 (8.6%) individuals due to adverse events and 2 (3.4%) were lost to follow-up]. Rash associated with TVR (grade 1) was observed in two cases (3.4%) and all the patients showed anaemia at some point of treatment. In an analysis by ITT in the 31 patients who had a 60 week follow-up after starting therapy, SVR-12 was observed in 21 (67.7%) patients. And in the analysis by ITT in 28 patients who had a 72 week follow-up after starting therapy, SVR-24 was observed in 17 (60.7%) patients.ConclusionsResponse to triple therapy with TVR plus PR in HIV/HCV-patients under real-life conditions, and therefore, including a high proportion of difficult to treat patients, is similar to that found in CT. The safety profile of TVR-based therapy is also comparable to that shown in CT, with only a rate of discontinuation of 8.6% of individuals related to toxicity.

The Successful Use of Telaprevir to Treat Hepatitis C Recurrence After Liver Transplantation in an HIV Co-Infected Patient

The protease inhibitors, telaprevir (TVR) and boceprevir, have revolutionized the treatment of chronic hepatitis C virus (HCV) genotype 1 infection (1). Both medications are substrates and inhibitors of the cytochrome P450 3A (CYP3A) which are important for the metabolism of many commonly used medications including those used to treat human immunodeficiency virus (HIV) infection and immunosuppressive agents (2). Therefore, these protease inhibitors are not currently approved by the Food and Drug Administration for use in orthotopic liver transplantation (OLT) recipients or HIV co-infected patients because of concerns about serious drug interactions. Limited data are available on using TVR-based triple therapy to treat HCV recurrence after OLT (3) and in HIV co-infected patients (4). Since the introduction of highly active antiretroviral therapy (HAART), chronic HCV infection has become a major cause of morbidity and mortality in the HIV-infected population, and OLT has been performed in selected HIV-HCV co-infected patients (5, 6). HCV recurrence after OLT in co-infected patients is a major issue with significant effect on transplant outcomes (7, 8). This provides rationale for treating HCV recurrence with the highly effective protease inhibitors despite concerns about interactions with both immunosuppressive and HIV medications. Here we report our experience in treating recurrent HCV after OLT in a patient with HIV co-infection with TVR-based triple therapy. A 62-year-old white man with a history of HIV infection, chronic HCV genotype 1b infection complicated by the development of cirrhosis, and hepatocellular carcinoma underwent OLT in August 2011. He developed recurrent hepatitis C with a grade 2/4 inflammation, and stage 2/4 fibrosis disease was found on his liver biopsy approximately 9 months after transplantation. HAART regimen included emtricitabine-tenofovir 200 to 300 mg daily, etravirine 200 mg twice daily, and darunavir-ritonavir 600 to 100 mg twice daily owing to failure of several previous regimens and development of significant HIV resistance. His CD4 count was 461 cells/μL and he was negative for HIV-1 RNA by polymerase chain reaction. His immunosuppression regimen consisted of tacrolimus 0.5 mg every 15 days (because he was on HIV protease inhibitors) and mycophenolate mofetil 500 mg twice daily. His transaminases were in the 150 to 300 U/L range. His baseline HCV RNA was at 4,920,000 IU/mL, and his interleukin 28B genotype was CT. Before starting TVR-based triple therapy, we stopped his darunavir-ritonavir and started raltegravir 400 mg twice daily to avoid having the patient on both HCV and HIV protease inhibitors. His tacrolimus level was increased to 0.5 mg twice daily during the transitioning period. On day 1 of TVR-based therapy, the patient was started on TVR 750 mg thrice daily, ribavirin 400 mg twice daily, and pegylated interferon α2a 180 μg weekly. In addition, he took 0.5 mg of tacrolimus, and the tacrolimus level was checked at 12 and 24 hours and every other day thereafter for 2 weeks to assess tacrolimus pharmacokinetics. No additional tacrolimus was given until the level was around 4 to 6 ng/mL. The mean area under the concentration time curve (AUC) for tacrolimus while on TVR was 348 ng·hr/mL compared to an expected AUC of 67 ng·hr/mL without TVR. The highest tacrolimus level that we encountered was 10 ng/mL (at 12-hr level after the initial dose). His maintenance dose of tacrolimus while on TVR was 0.5 mg every 5 days. His HCV RNA was detectable but not quantifiable (<43 IU/mL) at week 4 of HCV therapy and became undetectable at week 8. Laboratory tests while on HCV therapy are shown in Table 1. He completed the 12-week course of telaprevir, continued on ribavirin/pegylated interferon α2a, and switched back to his original HAART regimen. Different time points and changes to his HIV/immunosuppressive regimens are demonstrated in Figure 1. He completed a total of 48 weeks of HCV therapy and his HCV RNA was negative 12 weeks after the end of treatment, indicating that he achieved a sustained virologic response.TABLE 1: Laboratory tests and virological responsesFIGURE 1: Different treatment time points and changes to tacrolimus dose.This case demonstrates that telaprevir-based triple therapy can be used to treat HCV recurrence in HIV co-infected patients as long as they are followed up closely at centers experienced in transplanting HIV patients. Frequent adjustments to tacrolimus dosage were necessary, but this did not cause any harmful effects to the liver graft or renal function. Future studies are needed to assess the possibility of using telaprevir in combination with HIV protease inhibitors and calcineurin inhibitors in patients with OLT. Naim Alkhouri, MD 1 Gurshawn Singh, MD1 William D. Carey, MD1 John J. Fung, MD, PhD2 Nizar N. Zein, MD1 Bijan Eghtesad, MD2 Alan Taege, MD3 1Department of Gastroenterology and Hepatology, Digestive Disease Institute Cleveland Clinic Foundation Cleveland, OH 2 Department of Hepatopancreatobiliary and Transplant Surgery, Digestive Disease Institute, Cleveland Clinic Foundation Cleveland, OH 3 Department of Infectious Diseases Cleveland Clinic Foundation Cleveland, OH

Baseline factors and very early viral response (week 1) for predicting sustained virological response in telaprevir-based triple combination therapy for Japanese genotype 1b chronic hepatitis C patients: a multicenter study

Genetic polymorphisms near Interleukin 28B (IL28B) (rs8099917) and a rapid virological response (RVR) have been reported as predictors for a sustained virological response (SVR) to telaprevir (TVR)-based triple combination therapy. However, the association between SVR and viral kinetics earlier than week 4 after initiation of therapy remains unclear. Thus, we evaluated the SVR prediction ability of baseline factors and reduced hepatitis C virus (HCV) RNA levels at week 1 after the initiation of TVR-based therapy in Japanese genotype-1b chronic hepatitis C (CHC) patients. A total of 156 Japanese CHC patients received a 24-week regimen of TVR-based therapy. Baseline factors and reduction in HCV RNA levels at weeks 1 and 4 after the initiation of therapy were analyzed for SVR prediction. Multiple logistic regression analysis for SVR in TVR-based therapy identified the IL28B TT genotype, a reduction of ≥ 4.7 log10 IU/mL in HCV RNA levels at week 1, RVR, and treatment-naïve/relapse. Whereas the SVR rate was higher than 90 % regardless of the reduction in HCV RNA levels at week 1 in patients with the TT genotype, a reduction of ≥ 4.7 log10 IU/mL in HCV RNA levels at week 1 was the strongest predictor of SVR in patients with the non-TT genotype, as determined by multiple logistic regression analysis (P = 0.0043). The IL28B TT genotype is the most important baseline factor for predicting SVR, and a ≥ 4.7 log10 IU/mL reduction in HCV RNA at week 1 is a useful very early on-treatment predictor of SVR, especially in the non-TT genotype.

Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in previously untreated chronic hepatitis C genotype 1 patients

Background:Telaprevir (T, TVR) is a direct-acting antiviral (DAA) used for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection. The sustained virological response (SVR) rates, i.e., undetectable HCV RNA levels 24 weeks after the end of treatment, is what differentiate treatments. This analysis evaluated the cost-effectiveness of TVR combined with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin (RBV), with Peg-IFN and RBV (PR) alone or with boceprevir (B, BOC) plus Peg-IFN alfa-2b and RBV, in naïve patients.Methods:A Markov cohort model of chronic HCV disease progression reflected the pathway of naïve patients initiating anti-HCV therapy. SVR rates were derived from a mixed-treatment comparison including results from Phase II and III trials of TVR and BOC, and trials comparing both PR regimens. SVR has significant impact on survival, quality-of-life, and costs. Incremental cost per life year (LY) gained and quality-adjusted-life-year (QALY) gained were computed at lifetime, adopting the (National Health Service) NHS perspective. Cost and health outcomes were discounted at 3.5%. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Sub-group analyses were also performed by interleukin (IL)-28B genotype and fibrosis stage.Results:Higher costs and improved outcomes were associated with T/PR relative to PR alone, resulting in an ICER of £12,733 per QALY gained. T/PR retained a significant SVR advantage over PR alone and was cost-effective regardless of IL-28B genotype and fibrosis stages. T/PR regimen ‘dominated’ B/PR, generating 0.2 additional QALYs and reducing lifetime cost by £2758. Sensitivity analyses consistently resulted in ICERs less than £30,000/QALY for the T/PR regimen over PR alone.Limitations:No head-to-head trial provides direct evidence of better efficacy of T/PR vs B/PR.Conclusion:The introduction of TVR-based therapy for genotype 1 HCV patients is cost-effective for naïve patients at the £30,000 willingness-to-pay threshold, regardless of IL-28B genotype or fibrosis stage.

Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial

Baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR), a marker for insulin resistance, has been associated with poor virologic response to peginterferon alpha/ribavirin (PR) in chronic hepatitis C. We evaluated the association between baseline HOMA-IR and pretreatment factors on sustained virologic response (SVR) to telaprevir (TVR) in genotype 1 patients with hepatitis C and prior peginterferon/ribavirin (PR) treatment failure. Patients were randomized to 12 weeks of TVR (750 mg q8h) plus peginterferon (180 μg/week) and ribavirin (1,000-1,200 mg/day) (with or without a 4-week lead-in) followed by PR, or PR alone (PR48), for 48 weeks. Univariate and multiple logistic regression analyses explored the prognostic significance of baseline HOMA-IR alone and adjusted for other pretreatment factors and SVR. The TVR arms were pooled for the purposes of this analysis. In all, 662 patients were randomized; 578 had baseline HOMA-IR and other prognostic data and were included in this analysis. Median baseline HOMA-IR was 2.6 (interquartile range [IQR] 1.7-4.3); 207 (36%), 206 (36%), and 165 (29%) patients had baseline HOMA-IR <2, 2 to <4, and ≥ 4, respectively. Male gender, higher body mass index, triglycerides, gamma-glutamyl transpeptidase, maximum alanine aminotransferase/aspartate aminotransferase, and fibrosis stage were associated with higher baseline HOMA-IR. Baseline HOMA-IR was associated with SVR in univariate analysis, but not after adjustment for other baseline prognostic factors (TVR: OR = 0.95, 95% confidence interval [CI]: 0.71,1.29; PR48: 0.60; 95% CI: 0.25,1.43). In patients with prior PR treatment failure, baseline HOMA-IR correlated with SVR in univariate but not multivariate analyses, suggesting other factors have a more direct causal relationship with virologic response to TVR-based therapy than HOMA-IR.

Dynamic and Rapid Changes in Viral Quasispecies by Udps in Chronic Hepatitis C Patients Receiving Telaprevir-Based Therapy

Telaprevir (TVR) is a protease inhibitor (PI) used in chronic hepatitis C treatment with pegylated interferon plus ribavirin. We analysed the prevalence and kinetic development of TVR resistance upon treatment. A total of 24 cirrhotic patients (genotype 1a, n=8; genotype 1b, n=16) previously non-responders to standard therapy were treated with TVR-based therapy. The distribution of TVR-resistant variants was assessed at every HCV-RNA-positive time point by 454 ultra-deep pyrosequencing (UDPS) during a mean follow-up period of 9.4 months. A median of 6,837 reads/specimen was studied. Based on control UDPS, we considered mutations as real when present >0.4%. TVR-resistant variants were found at baseline in 8/24 patients (33.3%). Four of the 24 patients (16.7%), all genotype 1a, did not achieve HCV RNA<100 IU/ml between week (W)2 and W12 and stopped treatment. No statistical significant difference was observed in the prevalence of resistant mutants between responders and non-responders (25% [5/20] and 75% [3/4], respectively). The proportion of genotype 1a patients with R155K/T/Q at baseline was higher in non-responders than in responders (50% versus 0%). During treatment failure, significant enrichment in V36A/M and R155K/T/Q was observed but their frequency reverted back to baseline after TVR discontinuation. TVR-resistant variants are widely present at baseline. The presence of TVR-resistant mutants at baseline, even in high abundance (>20%), did not always preclude TVR treatment success. The detection of R155K/T/Q at baseline may predict failure in genotype 1a patients. At failure, which occurred in genotype 1a patients, a significant enrichment in V36A/M and R155K/T/Q was observed.

Effect of Telaprevir on the Pharmacokinetics of Tacrolimus in the Treatment of Hepatitis C After Liver Transplantation Presidential Poster

Purpose: Limited data are available on using telaprevir (TVR)-based triple therapy to treat HCV recurrence post-liver transplantation (LTx). A study in healthy volunteers shows that TVR leads to major increase in tacrolimus (TAC) blood concentration. We report our preliminary experience on the effects of TVR on TAC pharmacokinetics (PK) and the safety of TVR-based therapy in the post-LTx setting. Methods: Patients with HCV genotype 1 recurrence post-LTx on stable dose of TAC for at least 6 months prior to starting the antiviral regimen were included in this study. TVR-based triple therapy was started with TVR 750 mg TID, ribavirin 600 mg daily, and peg-interferon α2a 180 mcg weekly. On day 1 of treatment, TAC at half the pre-treatment daily dose was given and levels were checked at 12 and 24 hours and every other day thereafter for 2 weeks to assess TAC PK. No additional TAC was given until the level was around 4-6 ng/mL. Once the maintenance dose of TAC was established, levels were assessed weekly. Results: Four patients (1F, 3M), mean age 56.3 years, mean time from LTx 3.25 years, and mean fibrosis stage of 2.5 were treated. Two were HCV treatment naïve and two were prior null-responders post-LTx. The mean duration of treatment was 10.75 weeks (range 8-16 weeks). The pre-treatment TAC dose ranged from 1-3 mg twice daily. The TAC dose required to maintain therapeutic levels was found to be approximately ¼- ½ the pre-treatment daily dose at a frequency of once weekly. The mean area under the concentration time curve (AUC) for TAC while on TVR was 1353.46 ng.hr/mL (range 685.25-2040.05) compared to an expected AUC of 67 ng.hr/mL without TVR. The highest TAC level that we encountered in our study was 16.2 ng/mL (at 12-hour level after the initial dose). Clinically significant anemia (Hb <10 g/dL) developed in 2, requiring a decrease of the ribavirin dose to 400 mg daily and starting epoietin. No significant neurologic toxicity was encountered. The mean creatinine increased from 1.12 to 1.35 mg/dL. We did not encounter any infections or episodes of acute rejection. Conclusion: 1. TVR had a profound effect on TAC metabolism; 2. Dose reduction of TAC based on blood levels is associated with normal TAC blood levels; 3. TVR therapy for HCV recurrence post-OLT in patients on TAC-based immunosuppression appears feasible; 4. The effect on renal function requires additional study. Longer follow-up is needed to demonstrate efficacy in achieving control of HCV. Disclosure: Naim Alkhouri, MD - Speaker's Bureau and Advisory Board Member of Vertex (makers of telaprevir). Nizar N Zein - Speaker's Bureau and Advisory Board Member of Vertex (makers of telaprevir).

Interim Results Presented at EASL From PROVE 1 Clinical Trial of Investigational Drug Telaprevir in Patients with Genotype 1 Hepatitis C

In a late-breaking presentation at the 42nd Annual Meeting of the European Association for the Study of the Liver (EASL) on April 14, researchers presented data from a planned interim analysis of the PROVE 1 clinical trial (Table 1). This is the first trial to evaluate short-duration therapy with the investigational hepatitis C protease inhibitor telaprevir (TVR; Vertex Pharmaceuticals, Cambridge, MA; VX-950) in combination with pegylated interferon alfa 2a (peg-IFN) and ribavirin (RBV) in treatment-naïve, genotype 1-infected hepatitis C patients.Table 1Interim HCV RNA Results for Patients Enrolled in the PROVE 1 TrialTreatment assignmentPatients with HCV RNA <30 IU/mL at end of 4 weeks of dosingPatients with HCV RNA <10 IU/mL at end of 4 weeks of dosingPatients with HCV RNA <10 IU/mL at end of 12 weeks of dosing, DC = FaIntent-to-treat, discontinuation = failure analysis. Patients who had HCV RNA <10IU/mL at the time of discontinuation are counted as failures; however, these patients will be followed postdiscontinuation to determine if the achieve a sustained virologic response (SVR).Patients with HCV RNA <10 IU/mL at end of 12 weeks of dosing (last on-treatment value carried forward)TVR = peg-IFN + RBV (arms B, C, and D)153/175 (88%)138/175 (79%)123/175 (70%)149/175 (85%)Placebo + peg-IFN = RBV (arm A)12/75 (16%)8/75 (11%)29/75 (39%)32/75 (43%)HCV, hepatitis C virus; IFN, interferon; RBV, ribavirin; TVR, telaprevir.a Intent-to-treat, discontinuation = failure analysis. Patients who had HCV RNA <10IU/mL at the time of discontinuation are counted as failures; however, these patients will be followed postdiscontinuation to determine if the achieve a sustained virologic response (SVR). Open table in a new tab HCV, hepatitis C virus; IFN, interferon; RBV, ribavirin; TVR, telaprevir. The data from PROVE 1 demonstrated a high rate of rapid viral response (RVR) in the TVR groups and a low rate of on-treatment viral breakthrough, and suggested that 12 weeks of TVR-based therapy enabled some patients to clear the virus. “The high rates of RVR observed in the TVR groups in and the fact that some patients have remained persistently viral negative 20 weeks after stopping the 12 weeks of TVR-based therapy, suggest that we may be able to shorten the treatment duration in genotype 1 [hepatitis C virus] HCV patients,” said Dr John McHutchison, Principal Investigator for the PROVE 1 study and Director of Gastroenterology and Hepatology Research at Duke Clinical Research Institute. At 4 weeks, 88% and 79% of patients receiving TVR achieved a RVR as measured by plasma HCV RNA <30 IU/mL and <10 IU/mL, respectively. Six of 9 patients in 1 treatment arm who completed 12 weeks of treatment and who had achieved an RVR as defined by the study protocol (<10 IU/mL) continued to have undetectable HCV RNA 20 weeks after stopping all treatment. The treatment discontinuation rate due to adverse events through 12 weeks was 11% in TVR arms and 3% in the control arm. Rash, gastrointestinal events, and anemia were the most common events leading to discontinuation in the TVR arms. A total of 250 patients were enrolled in PROVE 1 and received ≥1 dose of TVR or placebo in addition to peg-IFN + ribavirin (RBV) in the study. A total of 175 patients received ≥1 dose of TVR in 1 of 3 arms (treatment arms; B, C, and D) and 75 patients received ≥1 dose of placebo (arm A). Treatment with TVR resulted in a high proportion of patients achieving a RVR at 4 weeks. At the time of the interim analysis, all patients had either completed 12 weeks or discontinued from the study before week 12. “These interim results are encouraging and suggest that high sustained viral response (SVR) rates may be achieved with regimens that are 24 weeks in total duration. We look forward to 24 week follow-up data from the initial group of patients who stopped treatment at 12 weeks, and follow-up data from patients in the study who received 24 weeks of treatment,” McHutchison said.