Peginterferon Alfa-2b Research Articles

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

Background:Telaprevir (TVR,T) and boceprevir (BOC,B) are direct-acting antivirals (DAAs) used for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection. This analysis evaluated the cost-effectiveness of TVR combined with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin (RBV) compared with Peg-IFN alfa-2a and RBV (PR) alone or BOC plus Peg-IFN alfa-2b and RBV in treatment-experienced patients.Methods:A Markov cohort model of chronic genotype 1 HCV disease progression reflected the pathway of experienced patients retreated with DAA therapy. The population was stratified by previous response to treatment (i.e., previous relapsers, partial responders, and null responders). Sustained virologic response (SVR) rates were derived from a mixed-treatment comparison that included results from separate Phase III trials of TVR and BOC. Incremental cost per life year (LY) gained and quality-adjusted-life-year (QALY) gained were computed at lifetime, adopting the NHS perspective. Costs and health outcomes were discounted at 3.5%. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Sub-group analyses were carried out by interleukin (IL)-28B genotype.Results:Higher costs and improved outcomes were associated with T/PR relative to PR alone for all experienced patients (ICER of £6079). T/PR was cost-effective for each sub-group population with high SVR advantage in relapsers (ICER of £2658 vs £7593 and £20,875 for partial and null responders). T/PR remained cost-effective regardless of IL-28B sub-type. Compared to B/PR, T/PR prolonged QALYs by 0.57 and reduced lifetime costs by £13,960 for relapsers. For partial responders T/PR was less costly but less efficacious than B/PR, equating to an ICER of £128,117 per QALY gained.Limitations:No head-to-head trial provides direct evidence of better efficacy of T/PR vs B/PR.Conclusion:T/PR is cost-effective compared with PR alone in experienced patients regardless of treatment history and IL-28B genotype. Compared to B/PR, T/PR is always cost-saving but only more effective in relapsers.

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.

Single-Dose Infliximab in Hepatitis C Genotype 1 Treatmentnaive Patients with High Serum Levels of Tumour Necrosis Factor-Alpha Does Not Influence the Efficacy of Pegylated Interferon Alpha-2B/Ribavirin Therapy

Serum tumour necrosis factor-alpha (TNF-α) levels correlate negatively with hepatitis C virus (HCV) antiviral response. To test the hypothesis that a single infliximab induction dose would positively influence on-treatment virological response and sustained virological response (SVR). The present study was a phase IIIB, randomized, prospective, open-label pilot trial conducted at eight Canadian sites. Treatment-naive HCV genotype 1-infected patients 18 to 65 years of age with high serum TNF-α values (>300 pg⁄mL) were randomly assigned to receive a single pretreatment induction infliximab infusion (5 mg⁄kg) seven days before antiviral therapy (arm A) or no pretreatment (arm B). All patients received pegylated interferon α2b (1.5 μg⁄kg⁄week) plus weight-based ribavirin (800 mg⁄day to 1400 mg⁄day) for up to 48 weeks. Eighty-five patients (arm A [n=41], arm B [n=44]; 70% male) received pegylated interferon α2b. The mean age (48.1 years), race (81% white) and METAVIR fibrosis stage (F0-2 = 79%, F3-4 = 21%) were similar between groups. Infliximab was well tolerated without attributable severe adverse events; 56.5% completed the study (arm A [n=21], arm B [n=27]). Most discontinuations were due to virological failure at weeks 12 (n=20 [23.5%]) and 24 (n=7 [8.2%]) and did not differ according to group. Numerically lower proportions of infliximab recipients achieved rapid virological response (19.5% versus 36.4%), complete early virological response (43.9% versus 59.1%) and SVR (34.1% versus 52.3%). However, between-group differences did not reach statistical significance. No differences in adverse event profile or laboratory measures were noted. A single infliximab dose before pegylated-interferon α2b and ribavirin therapy did not result in greater viral decline during the first 12 weeks of HCV therapy or improved SVR.

Analysis of Site Performance in Academic-based and Community-based Centers in the IDEAL Study

To evaluate differences in metrics of quality and site performance in academic and community sites participating in a multicenter study. In the Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy study, the participation of 76 academic-based and 42 community-based US centers provided an opportunity to evaluate various metrics of quality and site performance. A secondary data analysis of the Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy study was performed. There were 3070 treatment-naive, hepatitis C virus genotype 1 infected patients were included. We retrospectively evaluated rates of screen failure, completion, and discontinuation of treatment and follow-up, treatment adherence, and virologic response by site type. Of the patients screened, 63% and 37% were in academic and community centers, respectively. Screen failure rates were similar (30% to 32%). End-of-treatment response, relapse, and sustained virologic response (SVR) rates in academic and community centers did not differ. SVR was achieved in 40% of patients at academic sites and 39% at community sites. Adherence to ≥80% of peginterferon-α and ribavirin dosing for ≥80% assigned duration was also similar (46% in academic and 47% in community centers). In both academic and community centers, 54% of patients completed treatment; there were similar discontinuation rates for treatment failure and adverse events. There were no significant differences in adherence, adverse events, rates of discontinuation, on-treatment virologic response, and SVR when comparing academic and community sites. The performance of academic-based and experienced community-based sites in clinical trials is largely similar for the treatment of chronic hepatitis C.

Pharmacoeconomic analysis of the treatment of chronic hepatitis C with peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin in Spain

BackgroundAn independent meta-analysis of randomized comparative trials of peginterferons alfa-2a and alfa-2b, both combined with ribavirin, analyzed the probability of achieving a sustained virological response (SVR). ObjectiveTo estimate the long-term cost-effectiveness of treatment of patients with chronic hepatitis C with peginterferon alfa-2a (180μg/week) plus ribavirin (800–1200mg/day) vs. alfa-2b (1.5μg/kg/week) plus ribavirin (800–1400mg/day), from the perspective of the Spanish National Health System. MethodsA Markov model was developed with 7 health states to simulate lifetime disease progression. SVR was calculated from the meta-analysis data. Transition probabilities and health state utilities were obtained from published literature. Direct healthcare costs were obtained from the drug catalog, while costs of disease-related complications were obtained from published studies and healthcare cost database. Costs were expressed in 2010€. The annual discount rate applied was 3.5% for both costs and benefits. ResultsSVR rate for treatment with alfa-2a was higher than with alfa-2b; the differences were 6.0%, 7.6% and 8.7% for all genotypes, genotypes 1/4 and genotypes 2/3, respectively. Each patient would gain 0.469, 0.600 and 0.685 life-years and 0.155, 0.198 and 0.227 quality-adjusted life-years with alfa-2a vs. alfa-2b, for the respective genotypes. The cost saving per patient treated with alfa-2a would be €705, €672 and €1900, for all genotypes and for genotypes 1/4 and 2/3, respectively, alfa-2a being dominant. ConclusionsAccording to the present model, treatment of patients with chronic hepatitis C with peginterferon alfa-2a is cost-effective compared with peginterferon alfa-2b, both combined with ribavirin.

Predicting Early and Sustained Virological Responses in Prior Nonresponders to Pegylated Interferon alpha-2b Plus Ribavirin Retreated With Peginterferon alpha-2a Plus Ribavirin and the Benefit-Risk Ratio of Retreatment

To evaluate the predictive value of complete early virological response (cEVR) on sustained virological response (SVR) following retreatment with peginterferon alpha-2a (40 kDa) plus ribavirin in previous nonresponders to peginterferon alpha-2b (12 kDa). In the randomized multinational retreatment with Pegasys in patients not responding to PegIntron therapy study, a 72-week regimen of peginterferon alpha-2a (40 kDa) plus ribavirin improved SVR rates over a standard 48-week regimen in previous nonresponders to peginterferon alpha-2b (12 kDa). cEVR, defined as hepatitis C virus RNA <50 IU/mL at treatment week 12, was an important predictor of SVR. We conducted an exploratory analysis of the retreatment with Pegasys in patients not responding to PegIntron therapy study data to better define the predictive value of cEVR for SVR in this patient population. In total, 157 of the 942 patients achieved a cEVR (16.7%). SVR rates were higher with 72 versus 48 weeks of retreatment in patients with a cEVR (57% vs. 35%), whereas SVR rates were <5% in patients without cEVR in both groups. The relative adverse event (AE) burden was lower with 72 weeks of treatment (8.1 vs. 10.1 AEs/y of treatment) as was the estimated number of AEs per SVR achieved (55 vs. 100). Cumulative treatment duration required to achieve 1 SVR was lower with 72 weeks of treatment (6.7 vs. 10.0 y/SVR) and lower still assuming that treatment was stopped at week 12 for non-cEVR patients (3.6 vs. 7.1 y/SVR). cEVR is a reliable predictor of SVR in patients retreated with peginterferon alpha-2a (40 kDa) plus ribavirin. Seventy-two-week retreatment has a more favorable benefit-risk ratio than 48 weeks, especially when cEVR is used to identify patients most likely to be cured.

Treatment of chronic hepatitis C with peginterferon alfa-2b, plus ribavirin in end stage renal disease patients treated by hemodialysis: single Saudi center experience

Introduction: Hepatitis C virus (HCV) infection is a global health problem, common worldwide, leading to acute and chronic hepatitis and its consequences of hepatic cirrhosis and hepatocellular carcinoma. Antiviral therapy of HCV+ in dialysis patients with interferon-α (INF-α) gives slightly better results than in the general population, but is poorly tolerated and associated with side effects. Although, Ribavirin in not recommended for dialysis patients, the addition of small doses of this medication to pegylated INF is discussed. Purpose: The aim of this study is to assess the efficacy and safety of peginterferon alfa-2b (12 kDa) plus Ribavirin in hemodialysis chronic HCV patients. Methods: Fourteen end-stage renal disease patients (ESRD) on regular hemodialysis (HD) in Prince Salman Center for Kidney Diseases (PSCKD), ten males (71.4%) and four females (28.6) were enrolled in a prospective study. All the patients have Hepatitis C Virus infection; were treated by pegylated interferon alpha-2b (peginterferon alfa-2b) 1 mcg/kg/week subcutaneously with Ribavirin 200 mg three times weekly; for 48 weeks. Two patients were non responsive to previous course of 24 weeks peginterferon alfa-2a. HCV –RNA PCR qualitative and quantitative were tested before, 12, 48 weeks of treatment and 24 weeks after for sustained virologic response (SVR) results. α-fetoprotein level was measured in all the 14 patients before starting treatment to exclude any evidence of hepatocellular carcinoma. Results: One patient (7.1%) refused to complete the treatment because he could not tolerate the side effects and treatment was stopped after the third dose. After 12 weeks, three of 14 patients (21.4%) were still HCV-RNA PCR positive and there were not two log decrees in quantitative PCR, so treatment was stopped in this group of patients. One patient of the remaining had more than two log decrees in quantitative PCR, while nine were seroconverted to HCV–RNA PCR negative, so the treatment was completed for 48 weeks in 10 patients. After 48 weeks of treatment, qualitative and quantitative HCV–RNA PCR were done for 10 patients and the results were still negative (71.4%). Results of qualitative and quantitative HCV–RNA PCR done 24 weeks later showed that 10 patients still negative and SVR was (64%). Their mean ALT and AST dropped from 54.36 ± 36.79 IU/dL and 31.52 ± 17.02 IU/dL before starting therapy to 37.26 ± 36.53 IU/dL and 25.37 ± 23.72 IU/dL, respectively, after termination. Their mean hemoglobin (Hb) level dropped from 11.31 ± 0.86 to 10.06 ± 1.06 g/dL; (p < 0.001), and white blood cell count (WBC) dropped from 6.14 ± 0.65 × 103/mm3 to 4.51 ± 0.95 × 103/mm3; (p < 0.001). Platelet count fell from 130.11 ± 48.06 × 103/mm3 to 63.03 ± 23.19 × 103/mm3; (p < 0.001), also erythropoietin dose increased from 182.14 ± 39.30 IU/kg/w to 253.93 ± 83.07 IU/kg/w, (p = 0.776). Conclusion: Peginterferon alfa-2b (12 kDa) plus Ribavirin therapy in hemodialysis chronic HCV patients is safe, well tolerated and effective with accepted rates of sustained virological response up to 64%.

Risk factors for hepatocellular carcinoma in hepatitis C patients with normal alanine aminotransferase treated with pegylated interferon and ribavirin

Pegylated interferon (Peg-IFN) plus ribavirin combination therapy is effective in patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase levels (NALT). However, it remains unclear whether the risk of hepatocellular carcinoma (HCC) incidence is actually reduced in virological responders. In this study, HCC incidence was examined for 809 patients with NALT (ALT≤40IU/mL) treated with Peg-IFN alpha-2b and ribavirin for a mean observation period of 36.2 ± 16.5months. The risk factors for HCC incidence were analysed by Kaplan-Meier method and Cox proportional hazards model. On multivariate analysis among NALT patients, the risk of HCC incidence was significantly reduced in patients with sustained virological response (SVR) or relapse compared with those showing nonresponse (NR) (SVR vs NR, hazard ratio (HR): 0.16, P=0.009, relapse vs NR, HR: 0.11, P=0.037). Other risk factors were older age (≥65years vs <60years, HR: 6.0, P=0.032, 60-64 vs <60years, HR: 3.2, P=0.212) and male gender (HR: 3.9, P=0.031). Among 176 patients with PNALT (ALT≤30IU/mL), only one patient developed HCC and no significant risk factors associated with HCC development were found. In conclusion, antiviral therapy for NALT patients with HCV infection can lower the HCC incidence in responders, particularly for aged and male patients. The indication of antiviral therapy for PNALT (ALT≤30IU/mL) patients should be carefully determined.

Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C

The aim of this study was to characterize the population pharmacokinetics of peginterferon (PEG-IFN) alfa-2b in pediatric patients with chronic hepatitis C and to identify covariates influencing PEG-IFN alfa-2b disposition. Pharmacokinetic data from a multicenter open-label study of subcutaneously administered peginterferon alfa-2b (60 μg/m(2)/wk) plus oral ribavirin (15 mg/kg/day) in patients with chronic hepatitis C aged 3-17 years old was used to develop a population pharmacokinetic nonlinear mixed-effects model. The final population pharmacokinetic analysis was conducted with the pooled data from 107 pediatric patients. A one-compartment model with first-order absorption, first-order elimination, exponential inter-individual variability on clearance, and a combination additive and proportional residual error model adequately described the PEG-IFN alfa-2b pharmacokinetic profile. Age (apparent clearance and apparent volume of distribution) and sex (apparent clearance) were significant covariates. The mean body surface area normalized apparent clearance of PEG-IFN alfa-2b was 0.56 L/h/m(2), and was similar when evaluated across the pediatric age groups. The final population model suggests age-dependent increases in clearance and volume of distribution of PEG-IFN alfa-2b in pediatric patients with chronic hepatitis C. The apparent clearance normalized to body surface area was similar across pediatric age groups, supporting the use of body size-adjusted dosing in pediatric subjects.

Treatment of chronic hepatitis C by Pegylated Interferon Alfa-2b (Peg2b) and Ribavirin (RBV): Age-and gender dependent frequency of hematological alterations in a German real-life cohort

Treatment of chronic hepatitis C by Pegylated Interferon Alfa-2b (Peg2b) and Ribavirin (RBV): Age-and gender dependent frequency of hematological alterations in a German real-life cohort

Thyroid dysfunction induced by peginterferon alfa-2b (Peg-2b)/Ribavirin (Rbv) is associated with higher SVR rates in patients with HCV Genotype 1 (G1) infection due to improved early virologic response at week 4 and week 12

Thyroid dysfunction induced by peginterferon alfa-2b (Peg-2b)/Ribavirin (Rbv) is associated with higher SVR rates in patients with HCV Genotype 1 (G1) infection due to improved early virologic response at week 4 and week 12

Leukocytes decline &gt; 2500/µl during Peginterferon Alfa-2B (PEG-2B)/Ribavirin (RBV) treatment predicts favorable SVR rates in difficult-to-treat patients with HCV Genotype 1 (G1) infection in real-life

Background and aims: Leukocyte decline during antiviral treatment of chronic HCV infection may reflect pharmacodynamic effects of pegylated interferons. We therefore investigated the possible association between leukocyte decline and SVR in difficult-to-treat patients (pts) undergoing Peg2b/RBV therapy for HCV G1 infection in real-life.

Cutaneous side effects of combined therapy with sorafenib and pegylated interferon alpha‐2b in metastatic melanoma (phase II DeCOG trial)

During a clinical study with combined therapy of sorafenib and pegylated interferon alpha-2b (SoraPeg study) of the German Dermatologic Oncology Group (ADO/DeCOG), multiple and severe cutaneous side effects were observed. This study sought to analyze these cutaneous side effects, particularly because future studies with combinations of interferon alpha and targeted therapies are planned. In a multicenter phase-II-DeCOG study (NCT00623402) in 10 dermato-oncology centers, 55 patients with metastatic melanoma received a combination of sorafenib (2 x 400 mg/day orally) and pegylated interferon alpha-2b (3 μg/kg body weight 1 x/week subcutaneously). All cutaneous side effects were documented. Forty-one patients (74.5 %) developed cutaneous side effects, particularly exanthems (51.2 %), hand-foot syndrome (36.5 %), alopecia (36.5 %) and pruritus (24.4 %). Due to the cutaneous side effects, dose reductions were required in 10 patients, interruption of therapy in 10 cases and permanent discontinuation of therapy and in one patient with extensive follicular-cystic lesions. Exanthems were seen more frequently in women (76.2 %) than in men (23.8 %). The occurrence of cutaneous side effects was not correlated with clinical outcome or prognosis. The combination of sorafenib/pegylated interferon alpha-2b caused more cutaneous side effects than have been reported for single agents. Despite intensive dermatologic management of the cutaneous side effects 24 % of patients required a dose modification.

A Randomized Trial of Daclatasvir with Peginterferon Alfa-2B and Ribavirin for HCV Genotype 1 Infection

Daclatasvir-containing regimens have the potential to address limitations of current regimens combining peginterferon alfa and ribavirin with first-generation protease inhibitors for treatment of chronic HCV genotype 1 infection. In this randomized, double-blind study, 27 Japanese treatment-naive patients received once-daily daclatasvir 10 mg or 60 mg or placebo, each combined with peginterferon alfa-2b/ribavirin; 18 prior null (n=9) or partial (n=9) responders received the same daclatasvir-containing regimens without a placebo arm. Daclatasvir recipients with protocol-defined response (HCV RNA<15 IU/ml at week 4, undetectable at week 12) were treated for 24 weeks; those without protocol-defined response and placebo recipients continued treatment to week 48. Sustained virological response 24 weeks post-treatment (SVR24) was achieved by 66.7%, 90.0% and 62.5% of treatment-naive patients in the daclatasvir 10 mg, 60 mg and placebo groups, respectively. Prior non-responders had more frequent virological failure; 22.2% and 33.3% of daclatasvir 10 mg and 60 mg recipients, respectively, achieved SVR24. Adverse events were similar across groups and were typical of peginterferon alfa-2b/ribavirin. Pyrexia, headache, alopecia, decreased appetite and malaise were the most common adverse events; two daclatasvir recipients discontinued due to adverse events. Daclatasvir 60 mg combined with peginterferon alfa-2b and ribavirin achieved a high rate of SVR24 in treatment-naive patients with HCV genotype 1 infection, with tolerability similar to that of peginterferon alfa-2b/ribavirin alone. However, regimens with greater antiviral potency are needed for prior non-responders.

Co-infection: new battlegrounds in HIV/AIDS

Co-infection: new battlegrounds in HIV/AIDS

Virological Escape in HCV Genotype-1-Infected Patients Receiving Daclatasvir plus Ribavirin and Peginterferon Alfa-2A or Alfa-2B

Daclatasvir (DCV; BMS-790052) is a picomolar inhibitor of HCV non-structural protein 5A (NS5A) and has demonstrated efficacy in patients chronically infected with HCV. In the double-blind, randomized studies AI444021 and AI444022, 71 Japanese patients chronically infected with HCV genotype 1 (predominantly genotype 1b) received DCV (10 mg or 60 mg) plus peginterferon alfa-2b or alfa-2a and ribavirin. Virological failure occurred in 14% (5/36) of treatment-naive patients and 54% (19/35) of prior alfa/ribavirin non-responders. Resistance testing was performed on baseline samples and samples with HCV RNA≥1,000 IU/ml at week 1 through post-treatment week 24. Baseline NS5A resistance-associated polymorphisms had less impact on virological response rates than IL28B genotype. All patients with virological failure had NS5A DCV-resistant variants at the time of failure. The predominant NS5A variants were L31V/M/I plus Y93H; this combination was detected in 100% (5/5) of treatment-naive patients and 74% (14/19) of non-responders with failure. Emergent resistance variants in prior non-responders (four viral breakthroughs, one relapse) were more varied with novel combinations such as L31F-ΔP32 and L28M-R30Q-A92K detected. Significant loss in DCV antiviral activity was generally only seen with ≥ two resistance-associated NS5A substitutions. All DCV-resistant variants were still detected at end of study. Virological failure in HCV genotype 1b treatment-naive Japanese patients receiving DCV plus alfa-2a/ribavirin or alfa-2b/ribavirin was associated with enrichment of NS5A resistance variants L31V/M-Y93H. In prior non-responders, emergent variants associated with failure also included NS5A-A92K or NS5A-ΔP32. As with L31-Y93 variants, these variants persisted.

Interferon-based therapy reduces risk of stroke in chronic hepatitis C patients: a population-based cohort study in Taiwan

Hepatitis C virus (HCV) infection has been linked to an increased risk of insulin resistance and carotid atherosclerosis. To investigate the association between HCV infection and stroke, and the effect of interferon-based therapy (IBT) on stroke risk in chronic hepatitis C (CHC) patients. We conducted a retrospective cohort study that followed up 3113 subjects with a newly detected HCV infection and 12 452 age- and gender-matched subjects without HCV infection selected from a random sample of 10(6) beneficiaries from the Taiwan National Health Insurance Program up to 5 years. Use of IBT was defined as treatment with interferon alpha, pegylated interferon alpha-2a or pegylated interferon alpha-2b for at least 3 months. The hazard ratio (HR) for newly detected stroke was calculated for subjects with HCV compared to those without HCV, and for IBT-treated HCV patients compared to non-IBT-treated HCV patients while adjusting for possible confounding factors. The overall person-years of follow-up were 8624.11 in patients with HCV, 54,533.69 in patients without HCV, 666.65 in IBT-treated patients, and 7886.49 in nontreated patients. The multivariable-adjusted hazard ratio (HR) for newly detected stroke was 1.23 for subjects with HCV compared to the age- and sex-matched subjects without HCV (adjusted HR = 1.23, 95% CI = 1.06-1.42, P = 0.008). Moreover, use of IBT significantly reduced the risk of stroke in HCV patients (adjusted HR = 0.39, 95% CI = 0.16-0.95, P = 0.039) after adjusting for known prognostic factors. Interferon-based therapy may reduce the long-term risk of stroke in patients with chronic HCV infection.

Improvement of Neurocognitive Function in Responders to an Antiviral Therapy for Chronic Hepatitis C

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders. Successful eradication of HCV leads to a significant improvement of relevant aspects of attentional and neurocognitive performance, indicating that the neurocognitive impairment caused by chronic HCV infection is potentially reversible. This therefore suggests an added therapeutic benefit of antiviral treatment in HCV infection. Improvement of neurocognitive function may be an additional treatment indication in patients with HCV. (HEPATOLOGY 2013;58:497-504).

Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial

Rates of sustained virological response (SVR) to peginterferon-ribavirin are low in patients with hepatitis C virus (HCV) genotype 1 and HIV. We aimed to assess efficacy and safety of triple therapy with boceprevir plus pegylated interferon alfa-2b (peginterferon) and ribavirin, which increases rates of SVR in patients with HCV alone. In our double-blind, randomised controlled phase 2 trial, we enrolled adults (18-65 years) with untreated HCV genotype 1 infection and controlled HIV (HIV RNA <50 copies per mL) at 30 academic and non-academic study sites. We randomly allocated patients (1:2) according to a computer generated sequence, stratified by Metavir score and baseline HCV RNA level, to receive peginterferon 1·5 μg/kg per week with weight-based ribavirin (600-1400 mg per day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg boceprevir three times per day (boceprevir group) for 44 weeks. Non-nucleoside reverse-transcriptase inhibitors, zidovudine, and didanosine were not permitted. The primary efficacy endpoint was SVR (defined as undetectable plasma HCV RNA) at follow-up week 24 after end of treatment. We assessed efficacy and safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00959699. From Jan 15, 2010, to Dec 29, 2010, we enrolled 99 patients, 98 of whom received at least one treatment dose. 40 (63%) of 64 patients in the boceprevir group had an SVR at follow-up week 24, compared with ten (29%) of 34 control patients (difference 33·1%, 95% CI 13·7-52·5; p=0·0008). Adverse events were more common in patients who received boceprevir than in control patients: 26 (41%) versus nine (26%) had anaemia, 23 (36%) versus seven (21%) pyrexia, 22 (34%) versus six (18%) decreased appetite, 18 (28%) versus five (15%) dysgeusia, 18 (28%) versus five (15%) vomiting, and 12 (19%) versus two (6%) neutropenia. Three patients who received boceprevir plus peginterferon-ribavirin and four controls had HIV virological breakthrough. Boceprevir in combination with peginterferon-ribavirin could be an important therapeutic option for patients with HCV and HIV. Merck.

Boceprevir for HCV in patients with HIV: where next?

Hepatitis C virus (HCV) is a major burden on public health worldwide, and liver disease has become a leading cause of death in patients co-infected with HIV. 1 Hanafiah KM Groeger J Flaxman AD Wiersman ST Global epidemiology of hepatitis c virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013; 57: 1333-1342 Crossref PubMed Scopus (1941) Google Scholar , 2 Weber R Sabin C Friis-Møller N et al. Liver-related deaths in persons infected with the HIV: the D:A:D study. Arch Intern Med. 2006; 166: 1632-1641 Crossref PubMed Scopus (931) Google Scholar In view of poor responses to pegylated interferon-alfa (peginterferon) in combination with ribavirin and the striking decreases in liver-related morbidity and mortality related to achievement of a sustained virological response (SVR), safer and more effective therapies are urgently needed for these patients. 3 Chung RT Anderson J Volberding P et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. New Engl J Med. 2004; 351: 451-459 Crossref PubMed Scopus (838) Google Scholar , 4 Torriani FJ Rodriguez-Torres M Rockstroh JK et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. New Engl J Med. 2004; 351: 438-450 Crossref PubMed Scopus (1186) Google Scholar , 5 Limketkai NK Mehta SH Sutcliffe CG et al. Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV. JAMA. 2012; 308: 370-378 Crossref PubMed Scopus (168) Google Scholar , 6 van der Meer AJ Veldt BJ Feld JJ et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012; 308: 2584-2593 Crossref PubMed Scopus (1179) Google Scholar Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trialBoceprevir in combination with peginterferon–ribavirin could be an important therapeutic option for patients with HCV and HIV. Full-Text PDF