Lower Sustained Virological Response Rates Research Articles

Treatment of HCV genotype 2 with sofosbuvir and ribavirin results in lower sustained virological response rates in real life than expected from clinical trials.

Hepatitis C virus (HCV) infections with genotype 2 (GT2) are generally considered as easy to treat. The current standard therapy is 12weeks of sofosbuvir and ribavirin. However, sustained virological response (SVR) rates varied substantially in distinct subgroups. Therefore, re-assessing the efficacy of interferon-free therapy in cohorts with larger patient numbers is warranted. The German Hepatitis C registry is a national multicenter cohort. Patients are treated at the discretion of the physician. Data are collected by a web-based data system and confirmed by plausibility checks and on-site monitoring. A total of 265 (4.3%) of 6034 patients enrolled in the registry were infected with GT2, and 236 had initiated treatment (60% males, 98% Caucasian, median age 54years). Treatment with sofosbuvir and ribavirin for 12weeks achieved SVR at week 12 post-treatment (SVR12) in 136/164 (83%) patients. SVR12 rates for this regimen were 80% (35/44) in treatment-experienced patients, 74% (20/27) in cirrhotics and 75% (21/28) in patients with HCV-RNA ≥6 million IU/mL. The overall SVR rate in patients treated with sofosbuvir/ribavirin 12weeks per protocol (PP), excluding therapy discontinuation or lost to follow-up, was 135/151 (89%). PP SVR12 rates were 91% for treatment naïve, 83% for cirrhotic and 80% for treatment-experienced patients respectively. In this large GT2 cohort, sofosbuvir and ribavirin for 12weeks achieved lower SVR rates compared to treatment outcomes expected from phase 3 trials. These findings highlight the need for establishing alternative treatment strategies for GT2 patients, especially in patients with unfavourable outcome factors.

Challenges in Special Populations: HIV/HCV Coinfection, Liver Transplantation and Patients with End-Stage Renal Disease

Until recently, the combination of PEG-interferon and ribavirin (RBV) was the main treatment for all genotypes of chronic hepatitis C virus (HCV) infection. Sustained virological response (SVR) rates varied significantly across patient subgroups and the concept of ‘special populations' emerged. Now, in the era of direct acting antivirals, with a better safety profile and higher efficacy rates, those patients with comorbidities or conditions that limited IFN-based antiviral treatment but with unmet medical needs have been considered for therapy again. With the currently approved all-oral antivirals, patients coinfected with human immunodeficiency virus and HCV have SVR rates similar to patients with HCV monoinfection. However, drug-drug interactions (DDIs) with antiretroviral drugs are still challenging. In the setting of liver transplantation, with an accelerated course of hepatitis C, previous IFN-RBV treatments were poorly tolerated and attained low SVR rates. Today, all-oral therapies have proven to be efficacious and safe in this population. Nevertheless, questions such as the optimal treatment duration or the need for RBV still remain opened. In this population as well, DDIs are an issue, as some regimens require adjustments and monitoring of immunosuppressive drugs during therapy. Finally, preliminary data show promising results in terms of efficacy and safety in patients with end-stage renal disease. However, there is clear need for more clinical studies since treatment options are still very limited.

The prevalence and impact of thrombocytopenia, anaemia and leucopenia on sustained virological response in patients receiving hepatitis C therapy: evidence from a large 'real world' cohort.

The aim of the study was to explore the extent of thrombocytopenia (TCP), anaemia and leucopenia in patients with hepatitis C and evaluate how they impact the management of antiviral therapy, the attainment of sustained virological response (SVR), and some therapy-related adverse events. The Scottish Hepatitis C Clinical Database was used in this retrospective study. The prevalence of TCP, anaemia and leucopenia was evaluated. The impact of the three deficiencies on antiviral therapy management, serious adverse events and SVR attainment was assessed in patients who received therapy. The prevalence of TCP, anaemia and leucopenia was 18.5, 0.9 and 0.2% among 4907 treated patients at baseline, increasing to 72, 25.8 and 5.4% during treatment, respectively. Dose reduction occurred in 29.3% of the patients without TCP; this percentage was higher in those with baseline TCP (53%) and in those who acquired it during treatment (35%). Similar results were found for anaemia and leucopenia. Baseline TCP (odds ratio=0.67, P<0.001) and baseline anaemia (odds ratio=0.43, P=0.03) were identified as risk factors associated with lower SVR rate; acquired TCP and anaemia were not associated with reduced SVR. Baseline TCP or anaemia increased the risk of dose cessation. Patients who acquired TCP, anaemia or leucopenia during treatment did not exhibit compromised SVR rates, whereas patients with TCP or anaemia at baseline did. The potential benefit of growth factors in maintaining SVR rate is likely to be confined to those with baseline TCP or anaemia rather than to those who acquire it during therapy, where dose reduction does not appear to reduce the chance of SVR.

SAT-193 - Low Sustained Virologic Response (SVR) Rates in Genotype (GT) 2 and 3 Patients with Quantifiable Hepatitis C Virus (HCV) at Week 4 of Treatment with Sofosbuvir (SOF) Containing Regimens

SAT-193 - Low Sustained Virologic Response (SVR) Rates in Genotype (GT) 2 and 3 Patients with Quantifiable Hepatitis C Virus (HCV) at Week 4 of Treatment with Sofosbuvir (SOF) Containing Regimens

Current guidelines and prioritizing treatment of hepatitis C virus in HIV-infected patients.

Coinfection with hepatitis C virus (HCV) and HIV is a significant public health problem worldwide. The broad spectrum antivirals interferon-alpha (IFN) and ribavirin (RBV) have lower sustained virologic response rates in HIV-HCV coinfection compared with HCV monoinfection, with significant associated toxicities and prolonged treatment courses. The recent availability of direct acting antivirals (DAA) has transformed the treatment of HCV, with the opportunity of cure available for most patients with much more tolerable regimens. These regimens are now being studied in HIV-HCV coinfection. DAA-based regimens for HIV-HCV coinfection have shown excellent efficacy, with cure rates similar to HCV monoinfection. Either in combination with IFN and RBV, or in 'IFN-free' regimens, cure rates of over 90% are the goal for all HIV-HCV-infected individuals. Data are excellent in genotype 1 infection, but further data on genotype 2-6 are required. These regimens have been shown to be cost-effective in HCV monoinfection, and are likely to be cost-effective in HIV-HCV coinfection. Nonetheless they remain expensive. Recent guidelines have identified coinfected patients as a group for prioritization for treatment, regardless of fibrosis stage. Earlier treatment of those likely to transmit HCV is also recommended. With the use of DAA, HCV infection in HIV should be curable for most patients, and HIV-infected patients should be prioritized for treatment. The optimal treatment regimens for some genotypes have yet to be determined. The significant cost of DAA-containing regimens is likely to significantly impair their widespread use for the short to medium term, even in well resourced settings, and those with more advanced liver disease are likely to access them first.

Factors Associated with Failure to Achieve SVR in Hepatitis C Genotype 3 Patients Within an Integrated Care Delivery System.

Achievement of sustained virologic response (SVR) and factors associated with treatment failure in hepatitis C virus (HCV) genotype 3 have been described in tertiary and referral care settings, with rates of SVR reported to range between 72% and 89%. Fewer data exist on SVR outside of these settings. To describe rates of SVR and characterize factors associated with achievement of SVR within an integrated health care delivery system. A retrospective cohort study of genotype 3 HCV patients treated with dual therapy (pegylated interferon-alpha plus ribavirin) was conducted at Kaiser Permanente Southern California. Adult patients diagnosed with HCV and testing positive for HCV-RNA genotype 3 were identified from electronic medical records. Data were collected on patient demographics, baseline health status, and comorbid conditions. A multivariate logistic regression model was used to determine the association between baseline patient factors and SVR. A total of 484 HCV genotype 3 patients met the eligibility criteria. The median age was 49 years, and 65.7% were male. Overall, 252 (52.1%) achieved SVR. Aged ≥ 45 years and male gender were associated with lower rates of SVR; cirrhosis and chronic diseases (diabetes and chronic obstructive pulmonary disease) were also associated with lower rates of SVR. SVR was lower in patients within an integrated care delivery system than in those in tertiary and referral centers. Males and older patients had lower rates of SVR, as well as patients with cirrhosis, diabetes, and chronic obstructive pulmonary disease.

Therapy for hepatitis C genotype 3: moving forward.

Until recently, the standard of care for hepatitis C virus genotype 3 infection was response-guided therapy with pegylated interferon plus ribavirin for 16 to 48 or 72 weeks. The introduction of sofosbuvir plus ribavirin has revolutionized hepatitis C virus therapy. Nowadays, the recommend treatment regimen is a combination of sofosbuvir and a weight-based ribavirin dose for 24 weeks. For easy to treat patients (e.g. naïve or previously treated patients without cirrhosis), this combination achieves high sustained virologic response rates and is well tolerated. However, in treatment-experienced patients with cirrhosis, sustained virologic response is lower due to unknown reasons. The combination of two direct-acting antiviral agents, sofosbuvir and daclatasvir, for 12 weeks is also associated with low sustained virologic response rates in this special population, for whom new drugs and different strategies are now under evaluation. Currently, the high cost of all these drugs limits access to treatment in many countries.

Cost-effectiveness of sofosbuvir plus ribavirin with or without pegylated interferon for the treatment of chronic hepatitis C in Italy

Objective:Across Italy up to 7.3% of the population is infected with hepatitis C virus (HCV), with long-term complications resulting in high medical costs and significant morbidity and mortality. Current treatment options have limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological response (SVR) rates, especially for the most severe patients). Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir, administered with ribavirin (RBV) and with or without pegylated interferon (PEG-INF), resulted in >90% SVR across treatment-naïve (TN) genotype (GT) 1–6 patients. It is also the first treatment option for patients that are unsuitable for interferon (UI). This analysis evaluates the cost – effectiveness of sofosbuvir for GTs 1–6 in Italy.Research design and methods:A Markov model followed a cohort of 10,000 patients until they reached 80 years old. Approximately 20% of naïve and 30% of experienced patients initiated treatment at the cirrhosis stage. Comparators included PEG-INF + RBV for all GTs and plus telaprevir or boceprevir for GT1, or no treatment. Costs and outcomes were discounted at 3% and the cost perspective was that of the National Health Service in Italy.Results:Sofosbuvir was cost-effective with incremental cost-effectiveness ratios (ICERs) below €40,000/QALY in all patient populations, particularly in cirrhotic patients. The exception was for a mixed cohort of GT2 TN patients where the ICER was €68,500/QALY and for a cirrhotic cohort of GT4/5/6 where the ICER was €68,434/QALY. Nevertheless, the prevalence of HCV in this patient population is expected to be low. Results were robust to sensitivity analysis.Conclusions:Sofosbuvir-based regimens are cost-effective in Italy, particular for the most severe patients. The interferon-free regimens are a real treatment option for UI patients. The high cure rates of this breakthrough treatment are expected to substantially reduce the burden of HCV in Italy.

Modelling the interaction between danoprevir and mericitabine in the treatment of chronic HCV infection.

Modelling HCV RNA decline kinetics under therapy has proven useful for characterizing treatment effectiveness. Here we model HCV viral kinetics (VK) in 72 patients given a combination of danoprevir, a protease inhibitor, and mericitabine, a nucleoside polymerase inhibitor, for 14 days in the INFORM-1 trial. A biphasic VK model with time-varying danoprevir and mericitabine effectiveness and Bliss independence for characterizing the interaction between both drugs provided the best fit to the VK data. The average final antiviral effectiveness of the drug combination varied between 0.998 for 100 mg three times daily of danoprevir and 500 mg twice daily of mericitabine and 0.9998 for 600 mg twice daily of danoprevir and 1,000 mg twice daily of mericitabine. Using the individual parameters estimated from the VK data collected over 2 weeks, we were not able to reproduce the low sustained virological response rates obtained in a more recent study where patients were treated with a combination of mericitabine and ritonavir-boosted danoprevir for 24 weeks. This suggests that drug-resistant viruses emerge after 2 weeks of treatment and that longer studies are necessary to provide accurate predictions of longer treatment outcomes.

LP55 : Response guided therapy is not dead: Low Sustained Virologic Response (SVR) rates in patients who have detectable Hepatitis C Virus (HCV) at week 4 of treatment with SOFOSBUVIR (SOF) containing regimens

LP55 : Response guided therapy is not dead: Low Sustained Virologic Response (SVR) rates in patients who have detectable Hepatitis C Virus (HCV) at week 4 of treatment with SOFOSBUVIR (SOF) containing regimens

Su1393 Prevalence and Self-Recognition of Chronic Constipation: An Internet Survey in Japan

BODY: Background: Newly approved interferon-free regimens for chronic genotype 1 hepatitis C virus (HCV) infection are associated with remarkable improvements in safety and efficacy compared with prior interferon-based regimens. Pivotal phase 3 registration trials for sofosbuvir-based regimens confirm high efficacy with sustained virologic response (SVR) rates >90% across key patient populations. However, studies evaluating realworld efficacy outside restricted clinical trial settings suggest lower SVR rates. We evaluated eligibility of a real-world population for pivotal phase 3 sofosbuvir-based trials. Method: We queried the electronic health database of a large academic medical center to identify

Su1391 Psychological State of Subjects With Irritable Bowel Syndrome and Headache: Annual Health Check-up Survey Results

BODY: Background: Newly approved interferon-free regimens for chronic genotype 1 hepatitis C virus (HCV) infection are associated with remarkable improvements in safety and efficacy compared with prior interferon-based regimens. Pivotal phase 3 registration trials for sofosbuvir-based regimens confirm high efficacy with sustained virologic response (SVR) rates >90% across key patient populations. However, studies evaluating realworld efficacy outside restricted clinical trial settings suggest lower SVR rates. We evaluated eligibility of a real-world population for pivotal phase 3 sofosbuvir-based trials. Method: We queried the electronic health database of a large academic medical center to identify

Optimal Duration of Pegylated Interferon Plus Ribavirin Therapy for Chronic Hepatitis C Genotype 3 Patients who do not Achieve Rapid Virological Response

Chronic hepatitis C (CHC) genotype-3 (G-3) patients treated with standard 24-week pegylated interferon plus ribavirin(PEG-RBV) therapy achieve sustained virological response(SVR) rate of 69-82%. Patients who do not achieve rapid virological response(RVR) have lower SVR rate. Data regarding optimal management of this subgroup is scarce. We aimed to determine the most appropriate treatment duration in CHC G-3 patients who do not achieve RVR. Treatment naïve CHC G-3 patients treated with PEG-RBV therapy were included in this retrospective analysis. Patients with cirrhosis were excluded. RVR was assessed in all patients beyond the year 2007. RVR non-achievers were advised extended treatment beyond 24 weeks. Of the total 685 patients started on treatment, 646 completed treatment (mean age 39.1±12 years, 68.3% males). In the pre-'RVR assessment' period (2004-2006), SVR with standard 24 week therapy was 72.3% (112/155). In post-'RVR assessment' period (2007-2013), 75.8% (402/530) patients achieved RVR; and 91.5% (368/402) of these achieved SVR with standard 24 weeks therapy. Among RVR non-achievers (n=128), 51 patients opted for extended 36 week therapy, 12 for 48 week therapy, while 65 stopped therapy at 24 weeks. Choice of treatment duration was dependent entirely on the affordability of the patient. SVR with extended therapy (36/48 weeks) was significantly higher than standard 24 week therapy in RVR non-achievers (82.5% vs. 52.3%; P=0.003). However, SVR rate in 36 week group was not significantly different from 48 week group (84.3% vs. 75%; P=0.425]. On multivariate analysis, duration of treatment (36/48 week vs. 24 week; P<0.001) was significantly associated with SVR. SVR rates in CHC G-3 patients treated with PEG-RBV in northern India were comparable to western data. Standard 24 week therapy is adequate for RVR-achievers. However, in RVR non-achievers, extended 36 week therapy significantly improves SVR, while further extension to 48 week does not provide any additional advantage.

Peg-IFN and ribavirin treatment for recurrence of genotype 2 and 3 hepatitis C after liver transplantation

Background: Relapse of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. Tolerance for treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV) is suboptimal and withdrawals due to adverse events frequent. We sought to improve tolerance for treatment to improve outcome. Methods: We used concentration-guided RBV dosing to achieve an intended 10 μmol/L concentration with darbepoetin support in combination with peg-IFN alfa-2a, 180 μg for genotype 1 and 135 μg for genotype 2/3 to improve tolerance. Results: A total of 51/54 patients (94%) completed a full treatment course. In the per-protocol analysis 43% of patients (22/51) achieved sustained virological response (SVR), 82% with HCV genotype 2/3 and 22% with genotype 1, p = 0.0001. Patients with IL28B CC achieved SVR in 73% (8/11) and patients with non-CC in 33% (14/43), p = 0.016. Patients with mild fibrosis (fibrosis stage 1–2) achieved SVR in 56% (15/27), and patients with advanced fibrosis (fibrosis stage 3–4) in only 26% (7/27), p = 0.0267. Conclusions: Concentration-guided RBV dosing with darbepoetin support substantially improves tolerance and offers high adherence to a full peg-IFN and RBV treatment course in patients with post-transplant HCV relapse. With this approach genotype 2 and 3 infections can be treated cost-effectively post-transplant. Genotype 1, IL28B non-CC genotype, and advanced fibrosis predicted a low SVR rate.

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3.

To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV). We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence. A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4). In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes.

Anti-C1q Antibody as a Predictor of Chronic HCV Genotype 4 Response to Treatment in Egyptian Children

Background: Hepatitis C virus (HCV) infection has been reported to be the most common blood born pathogen all over the world. The prevalence of HCV in children in developed countries ranges between 0.1 and 0.4 %, and is generally lower than in adults. Combinedpegylated interferon and ribavirin is still the only standard of care treatment in spite of its side effects, high costs and low sustained virological response (SVR) rates. Hence, this provides a compelling reason for the identification of biomarker predictors of disease response to treatment. Objective: To evaluate anti-C1q antibody as a predictor of chronic HCV response to treatment with combined pegylated interferon alpha-2b and ribavirin in Egyptian children. Methodology: This study was conducted on forty-four chronic HCV-infected children (Male/Female: 30/14; aged 12.02±3.1 years) from the outpatient clinic, Pediatric Hepatology Department, National Liver Institute, Menoufiya University. They were given combined pegylated interferon alpha-2b (Peg-IFN-α-2b) and ribavirin (RBV) for 48 weeks and a quantitative polymerase chain reaction (PCR) for hepatitis C virus Ribonucleic acid was performed at 12, 24, 48 weeks during treatment and after another 24 weeks post-treatment. Anti-HCV antibody and Real-time PCR for HCV-RNA was performed (the detection limit was 15 IU/mL). Anti-C1q antibodies were performed by enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of Anti-C1q antibodies were significantly higher (P = 0.001) in the Non-responders group (mean = 14.61± 6.749ng/ml) compared to the SVR one (mean = 2.27 ± 3.77ng/ml). No statistically significant difference (P > 0.05) had been found between SVR and Non-responders regarding the age, ALT, viral load, or hepatic necroinflammatory activity and liver fibrosis. Anti-C1q at a cutoff value of9.05ng/ml, had sensitivity and specificity of 84.6% and 75% respectively and 92% positive predictive value. No significant correlation between the serum level of anti-C1q antibodies and the age, sex or HCV viral load, liver enzymes, and the degree of fibrosis and necroinflammatory activity was found (P> 0.05) for all parameters. Conclusion: Anti-C1q could be a good predictor for HCV treatment and should be included in pretreatment laboratory assessment for proper choice of chronic HCV children patients who will benefit from combination therapy.

Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies

Simeprevir is an oral hepatitis C virus (HCV) NS3/4A protease inhibitor approved for treatment of chronic HCV infection. Baseline NS3 polymorphisms in all patients and emerging mutations in patients who failed to achieve sustained virologic response (SVR) with simeprevir plus peginterferon/ribavirin (PR) in Phase IIb/III studies are described. Baseline sequencing data were available for 2007 genotype 1 (GT1)-infected patients. Post-baseline data were available for 197/245 simeprevir-treated patients who did not achieve SVR. In vitro simeprevir susceptibility was assessed in a transient replicon assay as site-directed mutants or in chimeric replicons with patient-derived NS3 protease sequences. Baseline NS3 polymorphisms at positions associated with reduced in vitro susceptibility to simeprevir (43, 80, 122, 155, 156, and/or 168; EC50 fold change >2.0) were uncommon (1.3% [26/2007]), with the exception of Q80K, which confers ∼10-fold reduction in simeprevir activity in vitro (13.7% [274/2007]; GT1a 29.5% [269/911], GT1b 0.5% [5/1096]). Baseline Q80K had minor effect on initial response to simeprevir/PR, but resulted in lower SVR rates. Overall, 91.4% of simeprevir-treated patients [180/197] without SVR had emerging mutations at NS3 positions 80, 122, 155, and/or 168 at failure (mainly R155K in GT1a with and without Q80K, and D168V in GT1b), conferring high-level resistance in vitro (EC50 fold change >50). Emerging mutations were no longer detectable by population sequencing at study end in 50% [90/180] of patients (median follow-up 28.4weeks). Simeprevir treatment failure was usually associated with emerging high-level resistance mutations, which became undetectable over time in half of the patients.

Core amino acid variation at position 110 is associated with sustained virological response in Caucasian patients with chronic hepatitis C virus 1b infection.

The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 [86-118] mg/dL vs. 76 [54-88] mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.

Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response.

In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and posttreatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR.

Citalopram for the Prevention of Depression and Its Consequences in HIV-Hepatitis C Coinfected Individuals Initiating Pegylated Interferon/Ribavirin Therapy: A Multicenter Randomized Double-Blind Placebo-Controlled Trial

Background: Depression related to interferon-alpha (IFN-α) is common, may reduce adherence, and can be treatment limiting. HIV-HCV coinfected persons experience lower sustained virologic response rates and commonly have psychiatric comorbidities, thus they may benefit from prevention of depression. Objective: The aim of the study was to determine whether prophylactic citalopram can increase HCV treatment adherence and reduce the incidence of moderate depression in HIV-HCV coinfected patients initiating PEG-IFN-α/ribavirin therapy. Methods:This was an investigator-initiated Canadian multicenter randomized, double-blind placebo-controlled trial. HIV-HCV coinfected patients were randomized in a 1:1 ratio to receive citalopram or placebo 3 weeks prior to starting PEG-IFN-α2b/ribavirin, stratified by study center and HCV genotype. The protocol design permitted the comparison of prophylaxis with the treatment of emergent depression. The primary outcomes were adherence (assessed through questionnaire and returned medication) and time to moderate depression measured by Beck Depression Inventory-II (BDI-II) score greater than 15, confirmed 2 weeks apart. Results: Seventy-six patients (36 citalopram/40 placebo) were randomized. Overall adherence was high, ranging from 95% (week 12) to 91% (week 48). There was no difference between arms with respect to mean or median adherence at any study time point. Cumulative incidence of moderate depression did not differ significantly by group (log rank P = .32). The hazard ratio for moderate depression was 0.81 (95% CI, 0.26 to 2.54) for citalopram compared with placebo when adjusted for baseline BDI-II score. Conclusions: A strategy of prophylactic citalopram compared to treatment of emergent depression was not associated with higher adherence or a reduction in treatment-limiting depression nor did it significantly reduce depressive symptoms among HIV-HCV coinfected persons during treatment for HCV.