Direct Antiviral Treatment Research Articles

The effect of direct antiviral treatment on the depression, anxiety, fatigue and quality-of-life in chronic hepatitis C patients.

In this study, we aimed to investigate the effects of direct antiviral treatment on depression, anxiety, fatigue and quality of life in patients with chronic hepatitis C. Subjects included in study were treatment experienced and treatment naive chronic hepatitis C patients admitted to the hepatology outpatient clinic between December 2016 and June 2017. Before and after the treatment, Beck depression, Beck anxiety, liver-specific quality of life and fatigue severity-impact scales were administered. Descriptive statistical methods, Kolmogorov-Smirnov distribution test Wilcoxon sign and kappa coefficient tests were used to evaluate the study data. Forty-four patients were included in the study; however, it was completed with 35 patients only, as some of the patients were excluded for various reasons. There was no significant difference between depression and anxiety scores of the patients before and after the treatment, but depression and anxiety were found to be recovered in 28.5% (4/14) and 23.5% (4/17) of the subjects, respectively. At the end of the treatment, fatigue severity-impact scales and liver-specific quality of life were not significantly different from those before the treatment. In this study, we found that direct antivirals did not lead to depression, anxiety or fatigue and did not decrease liver-specific quality of life. In some cases, depression and anxiety decreased after the treatment.

A Case of Pulmonary Arterial Hypertension Secondary to Hepatitis C Direct Antiviral Treatment with Harvoni® (Ledipasvir/Sofosbuvir Fixed-Dose Combination)

Introduction: Direct-acting antivirals (DAA) have revolutionised the treatment of hepatitis C virus (HCV), replacing interferon regimes which have higher adverse events and lower success rates (80% vs >90%). However, the adverse profile of DAAs has yet to be determined. Objectives/Aims: To explore the possible adverse outcome of pulmonary arterial hypertension (PAH) as a result of Sofosbuvir treatment. Methods: Case Report. Results: We report a new case of recently diagnosed PAH following successful treatment HCV with Ledipasvir/Sofosbuvir fixed-dose combination. This study adds to growing evidence – at least 5 cases so far – suggesting a causal relationship between Sofosbuvir and PAH or exacerbating previously mild PAH. Unlike previous reports, this case did not identify as having the previously associated risk factors of HIV co-infection of portal hypertension, presenting a stronger case for causality of PAH. Conclusion: With more cases arising, further exploration as to the suitability of patients receiving DAA treatment for HCV may be necessary as part of the screening process. A prospective study would be required, as the data is often confounded by lack of preliminary right heart studies, and other clinical factors that act as confounders of the PAH.

Transitioning from interferon-based to direct antiviral treatment options: A potential shift in barriers and facilitators of treatment initiation among people who use drugs?

BackgroundMultiple barriers for accessing hepatitis C virus (HCV) treatment were identified during the interferon-based (IFN) treatment era for people who inject drugs (PWID). Whether these barriers persist since the introduction of IFN-free direct-acting antiviral (DAA) agents in Canada remains to be documented. This study examined temporal trends in HCV treatment initiation and associated factors during the transition from INF-based to all-oral DAA regimens. MethodsThe study population was drawn from a prospective cohort of PWID in Montreal, Canada. At three-month/one-year intervals between 2011 and 2017, participants with chronic HCV infection completed an interviewer-administered questionnaire on socio-demographic characteristics, drug use and health service utilisation, including HCV treatment. Time-updated Cox multivariate regression models, stratified by DAA + INF (2011-2013) and all-oral DAA (2014–2017) availability periods, were conducted to examine associations between time to HCV treatment initiation and associated barriers and facilitators. ResultsOf 308 participants (85% male, median age 42 [IQR: 33, 50]), 80 (26%) initiated HCV treatment during 915 person-years (PY). Incidence rates increased from 1.6 /100 PY (95%CI:0.9–2.6) in 2011 to 12.7 (10.6–15.1) in 2017 (p-trend = 0.0012). In multivariate analyses, visiting a primary care physician (2011–2013: aHR = 3.63[1.21–10.9]; 2014–2017: 2.52[1.10–5.77]) and frequent injection (0.23[0.05–0.99] and 0.49[0.24–0.99]) were consistently associated with treatment initiation. Participants aged >40 (2.27[1.24–4.13]), receiving opioid agonist therapy (OAT) (2.17[1.19–3.94]), and reporting prior HCV treatment (3.00[1.75–5.15]) were more likely to initiate treatment in the all-oral DAA period. ConclusionTreatment initiation increased between 2011 and 2017, but still remains low among PWID. Primary care visiting was a key facilitator regardless of the period, while engagement in OAT and health services, indicated by prior HCV treatment, increased the likelihood of treatment initiation in the DAA era. These findings suggest that access to health services is essential but not enough to scale up treatment in this population.

SAT-250-Effects of sustained virological response on the endothelial dysfunction and the cardiovascular risk in hepatitis C after direct antiviral angets treatment: HEPCAR study

SAT-250-Effects of sustained virological response on the endothelial dysfunction and the cardiovascular risk in hepatitis C after direct antiviral angets treatment: HEPCAR study

Comparative Study of Hematological Disorders of Antiviral Treatments in Algerian Chronic Hepatitis C Patients

Viral hepatitis C (HCV) is a major health problem that affects important number of people around the world, the emergence of new direct antiviral treatments is a real therapeutic revolution to days it allows the cure hepatitis C in the majority of patients, but these treatments is accompanied by numerous side effects. Sofosbuvir, Pegylated interferon and Ribavirin are the standard care for the treatment of chronic hepatitis C in Algeria. In this study, we are interesting to investigate hematological toxicity of Antiviral treatment in Algerian patients with chronic hepatitis C. We carried out a comparative study, which involved 300 men and women Algerian at different ages. The determination of the various Epidemiological, Hematological, biochemical (AST, ALT, Glycemia) and virological (Viral load) parameters was performed. The analysis of 300 data shows that the infection with hepatitis C affects the age group between (46 - 65 years) with a percentage of 67% with a female predominance 82% and a clear predominance of genotype 1b with a percentage (89%), Dual therapy (Sofosbuvir + Ribavirin) and triple therapy (Sofosbuvir + Ribavirin + Pegylated interferon) induce a high hematological toxicity - Hemolytic anemia ( revealed by a decrease of the number of Red blood cell and Hemoglobin level, as well as the percentage of hematocrit and the increase of mean corpuscular volume that induced the increase of red blood cell masse and the expansion) - Thrombocytopenia (revealed by the decrease in the number of platelets ) and leukopenia (translated by the decrease in the number of White blood cells and lymphocytes as well as monocytes, and a very significant increase in granulocytes) whereas in monotherapy (Sofosbuvir) a low toxicity was noticed, the Patients how receiving triple therapy (Sofosbuvir + Ribavirin + Pegylated interferon) can be developing diabetes mellitus. Antiviral treatments were significantly induced hemolytic anemia, leucopenia and thrombopenia in Algerian patients with chronic hepatitis C.

2222. Impact of Sustained Virologic Response Achieved Through Newer Direct Acting Antivirals in Hepatitis C Infection on Diabetes Mellitus

BackgroundHepatitis C virus (HCV) infection is one of the leading causes of mortality and morbidity in the United States with an incidence of about 0.7 cases per 100,000 population and a prevalence of ~2.7 to 3.9 million people. To our knowledge only one study was performed so far to assess the relation between treating hepatitis C virus using direct acting antiviral drugs (DAA) and reduction in the severity of type 2 diabetes mellitus (DM). Our study aims to assess the effect of SVR in hepatitis C virus on type 2 DM. The effect of the management with newer agents leading to sustained virologic response (SVR) on type 2 DM was analyzed in hepatitis C virus infection.MethodsWe performed a retrospective chart review in our hepatitis clinic located in Shreveport, Louisiana. Patients with age greater than 18 years old, who has both uncontrolled hepatitis C and type 2 DM, seen in our clinic from November 1, 2014 to December 31, 2017 were included. Hospital electronic health records were screened for diagnosis of hepatitis C and uncontrolled type 2 DM by ICD codes. We performed paired sample t-test between pre- and 6-month post-treatment-values of fasting blood sugar and Body Mass Index (BMI).ResultsThere was a statistically significant improvement in fasting blood sugar levels following hepatitis C therapy from 184.2 ± 74.8 to 133.06 ± 48.2 (P < 0.01), with an improvement of 51.2 ± 77.6 respectively (N = 49).There was a statistically significant improvement in HbA1c levels following hepatitis C therapy from 8.062 ± 1.8 to 7.019 ± 0.96 (P < 0.05), with an improvement of 1.042 ± 2.03 respectively (N = 21).There was no statistically significant improvement in BMI levels following hepatitis C therapy from 29.91 ± 6.6 to 29.79 ± 6.7 (P > 0.05), with slight improvement of 0.11 ± 2.08 respectively (N = 49).ConclusionWe conclude that there was statistical significant reduction in fasting blood sugar and hemoglobin A1C levels after achieving sustained virological response with new direct antiviral treatment for hepatitis C. A pre- and posttreatment change in body mass index was statistically not significant implies that change in blood sugar level was not due to weight loss. There was no change in diabetic medication during the period of the study or there were no dose adjustments occurred.Disclosures All authors: No reported disclosures.

All-oral direct antiviral treatment for hepatitis C chronic infection in a real-life cohort: The role of cirrhosis and comorbidities in treatment response.

BackgroundHepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA).Patients and methodsAll patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis.ResultsFive hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively.ConclusionTreatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death.

P-G5 Differential immune response to HCV peptides as cancer-progression biomarkers of HCV-infections

HCV infections are the main cause of chronic liver disease and in part of lymphoproliferative disorders. Most HCV infections (&gt;90%) determine chronic hepatitis, 30% of which progress to liver cirrhosis and 3% annually to Hepatocellular Carcinoma (HCC). The progression rate is mainly articulated in low (&gt;40 years) and high (&lt;10 years) speed progressors, with the latter being associated to male gender, &lt;40 years of age, &gt;150mL daily alcohol consumption. Current progression markers are mainly based on biochemical evaluation of liver damage (elevation of alanine and aspartate transaminases) and inflammation (elevation of alpha-fetoprotein). Such markers are not specific and elevated also for other infections (ie, HBV and HCMV) or metabolic disorders (ie, steatosis). Specific HCV-related markers would be relevant to identify HCV co-factors and to select high priority people for direct anti-viral treatment. To identify HCC progression markers, samples from HCV+ patients at different infection stage have been analyzed on the HCV-peptide platform newly developed by JPT Peptide Technologies GmbH (Germany). It covers the complete HCV-protein arrays with &gt;3000 overlapping 15-amino-acid-long peptides from all structural and non structural HCV proteins. The currently available data (from 7 HCV+ asymptomatic, 5 HCV+ with cryoglobulinemia, 9 HCV cirrhosis/HCC and 5 HCV− patients) demonstrates that in asymptomatic patients the level of anti-HCV is in general very low (including anti-capsid/core proteins), while high levels of immunoresponse anti-non-structural proteins is present in patients with liver cancer. Confirmation of such data would support the anti-non structural response as biomarker of cancer progression in HCV+ patients.

Excellent outcome of direct antiviral treatment for chronic hepatitis C in Switzerland.

The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete. We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC. We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis. Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92-96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94-98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87-100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87-97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76-94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan® in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naïve and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations. In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients.

Implications of HCV RNA level at week 4 of direct antiviral treatments for hepatitis C.

We aimed to determine whether the HCV viral load after four weeks of treatment (W4VL) with direct-acting antiviral agents (DAAs) predicts sustained virologic response (SVR) in a real-world clinical setting. We identified 21095 patients who initiated DAA-based antiviral treatment in the national Veterans Affairs (VA) healthcare system from 01/01/2014 to 06/30/2015. Week 4 viral load was categorized as undetectable, detectable below quantification (DBQ), detectable above quantification (DAQ) with viral load ≤42IU/mL and DAQ with viral load >42IU/mL. Week 4 viral load was undetectable in 36.1%, detectable below quantification in 45.6%, DAQ ≤42 in 9.3%, DAQ >42 in 9.1%. Detectable above quantification was much more common and undetectable week 4 viral load much less common when tested with the Abbott RealTime HCV assay vs the Roche COBAS AmpliPrep/COBAS TaqMan Version 2 assay. Compared to patients with undetectable week 4 viral load (SVR=93.5%), those with detectable below quantification (SVR=91.8%, adjusted odds ratio [AOR] 0.79, P-value=.001), DAQ ≤42 (SVR=90.0%, AOR 0.63, P-value<.001) and DAQ >42 (SVR=86.2%, AOR 0.52, P-value<.001) had progressively lower likelihood of achieving SVR after adjusting for baseline characteristics and treatment duration. Among genotype 1-infected patients who were potentially eligible for 8-week sofosbuvir/ledipasvir monotherapy, we did not find evidence that treatment for 12weeks instead of 8weeks was associated with higher SVR, even among those with detectable above quantification. In summary, DBQ and DAQ W4VL are very common in real-world practice, contrary to what was reported in clinical trials, and strongly predict reduced SVR across genotypes and clinically relevant patient subgroups. Whether and how week 4 viral load results should influence treatment decisions requires further study.

SAT-132 - Failure to First-Line Direct Antiviral (DAA) Treatment of HCV Infection in an Italian Real-Life Urban Setting

SAT-132 - Failure to First-Line Direct Antiviral (DAA) Treatment of HCV Infection in an Italian Real-Life Urban Setting

P0863 : “Real-life”-experience with second generation direct acting antiviral (DAA) treatment in HCV patients (n = 149)

P0863 : “Real-life”-experience with second generation direct acting antiviral (DAA) treatment in HCV patients (n = 149)

Evolution of hepatitis C virus quasispecies during repeated treatment with the NS3/4A protease inhibitor telaprevir.

In treating hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, the rapid reselection of resistance-associated variants (RAVs) is well known in patients with repeated exposure to the same class of antiviral agents. For chronic hepatitis C patients who have experienced virologic failure with direct-acting antiviral drugs, the potential for the reselection of persistent RAVs is unknown. Nine patients who received 14 days of telaprevir monotherapy were retreated with telaprevir-based triple therapy 4.3 to 5.7 years later. In four patients with virologic failure with both telaprevir-containing regimens, population-based and deep sequencing (454 GS-FLX) of the NS3 protease gene were performed before and at treatment failure (median coverage, 4,651 reads). Using deep sequencing, with a threshold of 1.0% for variant calling, no isolates were found harboring RAVs at the baseline time points. While population-based sequencing uncovered similar resistance patterns (V36M plus R155K for subtype 1a and V36A for subtype 1b) in all four patients after the first and second telaprevir treatments, deep sequencing analysis revealed a median of 7 (range, 4 to 23) nucleotide substitutions on the NS3 backbone of the resistant strains, together with large phylogenetic differences between viral quasispecies, making the survival of resistant isolates highly unlikely. In contrast, in a comparison of the two baseline time points, the median number of nucleotide exchanges in the wild-type isolates was only 3 (range, 2 to 8), reflecting the natural evolution of the NS3 gene. In patients with repeated direct antiviral treatment, a continuous evolution of HCV quasispecies was observed, with no clear evidence of persistence and reselection but strong signs of independent de novo generation of resistance. Antiviral therapy for chronic viral infections, like HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV), faces several challenges. These viruses have evolved survival strategies and proliferate by escaping the host's immune system. The development of direct-acting antiviral agents is an important achievement in fighting these infections. Viral variants conferring resistance to direct antiviral drugs lead to treatment failure. For HIV/HBV, it is well known that viral variants associated with treatment failure will be archived and reselected rapidly during retreatment with the same drug/class of drugs. We explored the mechanisms and rules of how resistant variants are selected and potentially reselected during repeated direct antiviral therapies in chronically HCV-infected patients. Interestingly, in contrast to HIV and HBV, we could not prove long-term persistence and reselection of resistant variants in HCV patients who failed protease inhibitor-based therapy. This may have important implications for the potential to reuse direct-acting antivirals in patients who failed the initial direct antiviral treatment. (The phase IIIb study described in this paper is registered at ClinicalTrials.gov under registration number NCT01054573.).

Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection

Ribavirin (RBV) is an important component of interferon (IFN)-based and direct antiviral treatment regimens for hepatitis C virus (HCV) infection. Immunomodulation, in particular improvement of the host IFN response, has been proposed as RBV's mechanism of action. Natural killer (NK) cells are sensitive biomarkers for IFN-α/β receptor signaling, as NK cell cytotoxicity and IFN-γ production are regulated by signal transducer and activator of transcription (STAT)1- and STAT4-phosphorylation, respectively. Specifically, pSTAT1-dependent NK cell cytotoxicity increases and pSTAT4-dependent IFN-γ production decreases in response to endogenous, virus-induced IFN-α and during IFN-α-based therapy. To assess whether RBV has a direct effect on NK cells and/or improves the IFN-γ response of NK cells in the presence of IFN-α, we prospectively studied 22 HCV patients with and 32 patients without 4 weeks of RBV pretreatment, who all received subsequent pegylated (Peg)IFN/ribavirin combination therapy. During RBV pretreatment, both the frequency of CD56(dim) NK cells with cytotoxic effector functions and the frequency of CD56(bright) NK cells with the capacity to produce IFN-γ decreased (P = 0.049 and P = 0.001, respectively). In vitro or in vivo exposure of NK cells to RBV improved the pSTAT4 (P < 0.01) but not pSTAT1 response of NK cells to subsequent stimulation with IFN-α. This was associated with an increase in IFN-γ production but not cytotoxicity of NK cells during subsequent IFN-α-based therapy. The frequency of IFN-γ-producing NK cells was greater in fast second-phase virological responders than in slow responders. RBV enhances the pSTAT4 and IFN-γ response of NK cells to IFN-α-stimulation.

Ribavirin Pretreatment Improves the IFN-γ Response of Natural Killer Cells to IFN-based Therapy of Hepatitis C Virus Infection

Ribavirin is an important component of interferon-based and direct antiviral treatment regimens of hepatitis C virus (HCV) infection. Immunomodulation, in particular improvement of the host interferon response, has been proposed as a mechanism of action. Natural killer (NK) cells are sensitive biomarkers for IFN-α/β receptor signaling, as NK cell cytotoxicity and IFN-γ production are regulated by STAT1- and STAT4-phosphorylation, respectively. Upon continued exposure to IFN-α, an increase in STAT1 levels limits STAT4 access at the IFN-α/β receptor and results in decreased IFN-γ production. Accordingly, NK cell IFN-γ production decreases during IFN-α-based therapy. To assess whether ribavirin improves the IFN-γ response of NK cells in the presence of IFN-α, NK cells were studied prospectively in 22 HCV patients with and 32 patients without 4 weeks of ribavirin monotherapy, and during subsequent PegIFN/ribavirin therapy. During ribavirin monotherapy, the frequency of IFN-γ producing NK cells decreased (p = 0.001) in correlation with a decrease in their ex vivo pSTAT4 levels ((Rho = 0.58, p = 0.019). However, in vitro or in vivo exposure of NK cells to ribavirin improved their pSTAT4 response to subsequent stimulation with IFN-α (P < 0.01). Furthermore, HCV patients who had received ribavirin-pretreatment showed a greater frequency of IFN-γ-producing NK cells during subsequent PegIFN/ribavirin therapy than those who had not been pretreated (P < 0.05). Finally, the frequency of IFN-γ-producing NK cells was greater in fast second-phase virological responders than in slow responders. Conclusions: Ribavirin improved the pSTAT4 and IFN-γ response of NK cells to IFN-α-treatment, which may contribute to an improved second-phase virological response.

Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C

Background and aimSevere adverse events (AEs) compromise the outcome of direct antiviral agent-based treatment in patients with advanced liver fibrosis due to HCV infection. HEP3002 is an ongoing multinational programme...

Development of boceprevir: a first‐in‐class direct antiviral treatment for chronic hepatitis C infection

The identification of hepatitis C virus (HCV) as the causative agent of non-A and non-B hepatitis, over 20 years ago, fueled an intensive effort to develop direct-acting antivirals targeting the viral polymerase and protease, two key proteins critical for HCV replication. However, it took more than two decades for these efforts to be realized with boceprevir, one of the two HCV protease inhibitors approved for treatment of HCV infection in 2011. The development of boceprevir is a major advancement in the ability to treat HCV infection and a significant step toward the long-term goal of eradicating chronic HCV infection. Both as a first-in-class agent and an entirely new modality for treating HCV infection, many challenges were encountered during the discovery and development of this compound. The lessons learned in overcoming these obstacles offer insights and pave the way for the newly emerging field of HCV antiviral therapeutics. This paper will describe the discovery and development of a first-in-class direct antiviral treatment for chronic hepatitis C infection, boceprevir, marketed around the world as Victrelis™.