All-oral Regimens Research Articles

Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside Inhibitors Leading to the Discovery of MK-8876.

Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants. Ultimately, a biology and medicinal chemistry collaboration led to the discovery of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic potency profile and maintained potency against clinically relevant mutants. It demonstrated moderate bioavailability in rats and dogs, but showed low plasma clearance characteristics consistent with once-daily dosing. Herein we describe the efforts which led to the discovery of MK-8876, which advanced into Phase 1 monotherapy studies for evaluation and characterization as a component of an all-oral direct-acting drug regimen for the treatment of chronic HCV infection.

From the Editor’s desk...: July 2017

From the Editor’s desk...: July 2017

Interferon-Free Therapy in Elderly Patients With Advanced Liver Disease.

Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. Retrospective analysis of hepatitis C virus (HCV) patients aged ≥65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged ≥80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin ≤3.5 g/dl was the only independent negative predictor of response (0.25 (0.15-0.41); P<0.01). Regarding tolerability, the rate of severe adverse events increased with age category (8.8, 13, and 14%; P=0.04). In addition, the main predictors of mortality (2.3%) were age ≥75 years (2.59 (1.16-5.83); P =0.02) and albumin ≤3.5 (17 (6.3-47); P <0.01). SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56).

Phase II study of apatinib plus vinorelbine, a novel combination of all-oral regimen in heavily pretreated patients with metastatic HER2-negative breast cancer.

TPS1123 Background: Antiangiogenic therapy in combination with chemotherapy is effective in control advanced breast cancer(ABC). Apatinib is an oral, highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). Phase II clinical trials of Apatinib single agent had presented objective response and manageable toxicity in heavily pretreated, metastatic breast cancer. The median progression free survival (PFS) and median overall survival (OS) of single agent in both triple-negative and non-triple-negative breast cancer were 3.3-4.0 months and 10.3-10.6 months, respectively. The overall response rate and disease control rate (DCR) reached 16.7% and 66.7%, respectively. This all-oral phase II study aims to investigate the efficacy and safety of the oral vinorelbine-Apatinib combination in pre-treated metastatic breast cancer(MBC). Methods: This single arm prospective study enrolled patients with HER2(Human epidermal growth factor receptor-2 ) negative advanced breast cancer, pretreated with anthracycline and taxanes, and who failed in the metastatic setting at least one prior chemotherapy regimen. The estimated Enrollment was 40 patients.The primary end point of this study was PFS. Secondary end points included objective response rate (ORR), DCR, OS and safety. Patients were treated with apatinib 500/425mg daily plus oral vinorelbine 60-80 mg/m2 day1,8,15 every 3 weeks/cycle. Starting doses of Apatinib were chosen according to age, weight and patient status. Patients eligible were evaluated by CT or MRI scan at baseline and every 2 cycles (6 weeks) there after until disease progressed. Adverse events (AEs) were assessed and graded in accordance with the Common Terminology Criteria for AEs, version 4.0. Clinical trial information: NCT02768415.

Outcome of All-Oral Direct-Acting Antiviral Regimens on the Rate of Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Genotype 1-Related Chronic Liver Disease

Objectives: There is little information on the risk factors for hepatocellular carcinoma (HCC) and outcome of treatment with an all-oral combination of direct-acting antiviral regimens following eradication of hepatitis C virus (HCV) RNA. Methods: The study subjects were 1,170 patients with HCV genotype 1-related chronic liver disease treated with either NS5A inhibitor plus NS3/4A protease inhibitor (n = 707), NS5A inhibitor plus NS5B polymerase inhibitor (n = 345), or NS5A inhibitor, NS3/4A protease inhibitor plus ritonavir (n = 118), for 12-24 weeks. All patients were free of HCC before and during therapy. Results: In this retrospective study, 22 patients developed HCC during the follow-up (time from the end of antiviral therapy until the last visit: 1.3 years). At 1 and 2 years after completion of the treatment, the cumulative HCC rates for the whole group were 1.8 and 2.3%, respectively, and 1.4 and 1.8%, respectively, for 1,065 patients who showed sustained virological response (SVR). The risk factors for HCC identified by multivariate analysis were hypoalbuminemia, thrombocytopenia, a high α-fetoprotein level, and non-SVR for all patients, and hypoalbuminemia and a high α-fetoprotein level for patients with SVR. Conclusion: Eradication of HCV RNA by direct-acting antiviral regimens might reduce the risk of HCC. Albumin and α-fetoprotein levels are significant risk factors for HCC.

Urgency to treat patients with chronic hepatitis C in Asia.

Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over 50% of HCV patients worldwide live in the region, where HCV genotypes 1b, 2, 3, and 6 are the most prevalent. Treatment outcomes for chronic hepatitis C vary by ethnicity, and Asian patients achieve higher sustained virologic response rates following interferon (IFN)-based therapy than non-Asians. However, low efficacy, poor safety profile, and subcutaneous administration limit the use of IFN-based therapies. Superior virologic outcomes have been observed with different classes of direct-acting antivirals (DAAs) alone or in combination, and several all-oral DAA regimens are available in Asia. These regimens have shown excellent efficacy and favorable tolerability in clinical trials, yet there is a need for further studies of DAAs in a real world context, particularly in Asia. Furthermore, IFN-free treatment may not be accessible for many patients in the region, and IFN-based regimens remain an option in some countries. There is a need to improve current clinical practices for HCV management in Asia, including effective screening, disease awareness, and prevention programs, and to further understand the cost-effectiveness of IFN-free regimens. The evolution of potent treatments makes HCV eradication a possibility that should be available to all patients. However, access to these therapies in Asian countries has been slow, primarily because of economic barriers that continue to present a hurdle to optimal treatment.

Estimating cost-effectiveness associated with all-oral regimen for chronic hepatitis C in China.

BackgroundAll-oral regimens are associated with higher effectiveness and shorter treatment duration for chronic hepatitis C. Given its superior effect and enormous patients in China, clinicians or patients may be compelled to consider delaying treatment for all-oral regimen.ObjectiveTo estimate cost-effectiveness of delaying treatment for all-oral regimen in the subsequent years under different assumptions about their price and efficacy compared with standard of care in China.MethodsA state-transition Markov model was developed to estimate lifetime costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB) were calculated. And sensitivity analyses were also performed to assess the impact of uncertainty.ResultsFor treatment naive patients with Genotype 1, immediate treatment with all-oral regimen under assumed cost and efficacy at present was cost-effective compared with peginterferon α-2a (PegIFN) regimen at present with an ICER of $12536 per QALY gained and a positive NB of $6832 at a willingness-to-pay threshold of $21209. And it was more than 95% likely to be cost-effective if weekly drug cost was less than $1000. Moreover, patients delaying treatment for all-oral regimen in the 1st year were associated with increase in QALYs of 0.62 and increase in cost of $10114 compared with initiating PegIFN regimen at present, which resulted in a positive NB of $3115.ConclusionFrom a payer perspective, all-oral regimen is associated with good long-term health and economic benefit for treatment-naive patients infected with HCV genotype 1. Particularly, if all-oral regimen would become available at lower price in the future, delaying treatment for all-oral regimen may be a good choice for patients in China.

Exposure-Safety Response Relationship for Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Ribavirin in Patients with Chronic Hepatitis C Virus Genotype 1 Infection: Analysis of Data from Five Phase II and Six Phase III Studies.

All-oral direct-acting antiviral regimens that include combinations of ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin were evaluated in hepatitis C virus-infected patients in phase II/III clinical studies. The objective of these analyses was to quantify the relationship between exposures of the components of the regimen and laboratory values and to determine covariates that could influence the relationship. Exposure-safety response relationships between individual components of the direct-acting antiviral regimens and clinically important laboratory values were explored using data from 2998 patients from 11 phase II/III clinical studies. Multivariate logistic regression analyses were used to identify significant relationships between predictor variables and response variables. No statistically significant associations were observed between ombitasvir, dasabuvir, or ritonavir exposures and maximum post-baseline alanine aminotransferase (ALT) or total bilirubin grade or minimum hemoglobin grade. A two-fold increase in paritaprevir exposure from therapeutic exposure was predicted to increase the probability of experiencing a grade 3 or higher increase in ALT by 0.5% and bilirubin by 1.1%. In the phase II/III clinical studies, ALT and bilirubin increases were reversible with continued dosing or after treatment cessation. Other correlates with adverse events of clinical importance included concomitant ribavirin treatment, sex, race, and presence of cirrhosis, consistent with previous observations. Exposure-response analyses from phase II/III studies with the combination direct-acting antiviral regimen indicated no statistically significant relationships with ombitasvir, dasabuvir, or ritonavir exposure, but a statistically significant association was observed between paritaprevir exposure and the probability of experiencing a grade 3 or higher increase in ALT or bilirubin.

Sa1510 - The Impact of Hepatitis B Virus Infection on Sustained Virologic Response and HBV Reactivation in Patients with Chronic Hepatitis C who Treated by all-Oral Direct-Acting Antivirals Regimens

Sa1510 - The Impact of Hepatitis B Virus Infection on Sustained Virologic Response and HBV Reactivation in Patients with Chronic Hepatitis C who Treated by all-Oral Direct-Acting Antivirals Regimens

Sa1518 - Sofosbuvir-Based all-Oral Regimens for Patients with Chronic Hepatitis C Genotype 2 Infection: Integrated Analysis of Eleven Clinical Studies

Sa1518 - Sofosbuvir-Based all-Oral Regimens for Patients with Chronic Hepatitis C Genotype 2 Infection: Integrated Analysis of Eleven Clinical Studies

HCV core antigen as an alternate test to HCV RNA for assessment of virologic responses to all-oral, interferon-free treatment in HCV genotype 1 infected patients

In light of the advances in HCV therapy, simplification of diagnosis confirmation, pre- treatment diagnostic workup and treatment monitoring is required to ensure broad access to interferon-free therapies. HCV core antigen (HCV cAg) testing is rapid, giving results in approximately 60min, and less expensive than HCV RNA methods. While extensive data on the analytical performance of HCV cAg relative to RNA or comparisons in longitudinal studies of patients on interferon based (response guided) therapy there is very limited data on the relative performance of HCV cAg in diagnosis and monitoring patients receiving all-oral interferon free regimens. Furthermore, there is no data in the literature that describes the specificity of HCV cAg in patients with resolved HCV infection i.e. anti-HCV positive/HCV RNA negative. In this study a total of 1201 plasma samples from the 411 HCV genotype 1 subjects with a HCV RNA viral load >50,000IU/ml who enrolled in a clinical trial with ombitasvir, ritonavir-boosted paritaprevir and dasabuvir, with or without ribavirin were retrospectively tested in a blinded fashion with HCV cAg test and results were compared to HCV RNA levels. The specificity of the HCV cAg test was also evaluated in anti-HCV positive but HCV RNA negative samples. Overall concordance between HCV cAg and HCV RNA was 98.6% while concordance in pre-treatment samples was 99.5% (409/411; n=2 HCV RNA pos. with viral loads>3 Mill IU/ml but HCV cAg neg.) and 99.24% in post treatment week 12 samples (391/394; n=2 HCV RNA pos.<25IU/ml and n=1 HCV RNA pos. 2180IU/ml). Specificity in anti-HCV positive HCV RNA negative samples tested was 100%.

Phase I Trial of Everolimus and Capecitabine in Metastatic HER2− Breast Cancer

BackgroundThe mammalian target of rapamycin (mTOR) pathway is a driver of breast tumorigenesis. The mTOR inhibitor everolimus reverses antihormonal therapy resistance and is an approved therapy for metastatic breast cancer. A synergistic effect with fluoropyrimidine has been suggested. The present study evaluated the safety and tolerability of an all-oral combination of everolimus and capecitabine for metastatic breast cancer (MBC). Patients and MethodsMBC patients naive to capecitabine and mTOR inhibitors who had received ≤ 3 previous chemotherapy regimens in the metastatic setting were eligible for the present study. The patients were scheduled to receive capecitabine 825 mg/m2 twice daily for 14 days in a 21-day cycle, combined with everolimus in 5 separate dose cohorts: 2.5 mg every other day, 2.5 mg daily, 5 mg daily, 7.5 mg daily, and 10 mg daily. A 3+3 design was used. The maximum tolerated dose was based on the dose-limiting toxicity of everolimus plus capecitabine. ResultsA total of 18 patients were enrolled in the present trial. The median age was 58 years. Most had received previous anthracycline (83%) and taxane (94%) therapy. The maximum tolerated dose was everolimus 7.5 mg daily and capecitabine 825 mg/m2. The incidence of grade 3 events was low and mainly hematologic in nature. One incident each of grade 4 neutropenia, thrombocytopenia, hyperglycemia, and mucositis occurred. No grade 5 events occurred. The clinical benefit rate was 50%. The median progression-free survival was 196 days, and the median overall survival was 569 days. ConclusionThe all-oral regimen of everolimus with capecitabine is active and well tolerated, with encouraging results for progression-free survival, overall survival, and clinical benefit rate in patients with MBC.

Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis

Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 y; 53.6% women) were recruited from hospitals in Paris, France, from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n= 32) or 24 weeks (n= 9), and were evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks of therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56 ± 0.18 at baseline to 0.21 ± 0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low-memory B cells, CD4+CXCR5+ interleukin 21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 mo), no patients had a serious adverse event or relapse of vasculitis.

Efficacy and safety of direct-acting antiviral regimens in HIV/HCV-co-infected patients – French ANRS CO13 HEPAVIH cohort

There is little data available on the use of new oral direct-acting antiviral (DAA) regimens to treat human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients in real-life settings. Here, the efficacy and safety of all-oral DAA-based regimens in HIV/HCV-co-infected patients enrolled in the French nationwide ANRS CO13 HEPAVIH observational cohort are reported. HIV/HCV-co-infected patients enrolled in the ANRS CO13 HEPAVIH observational cohort were included if they began an all-oral DAA-based regimen before 1st May 2015 (12-week regimens) or 1st February 2015 (24-week regimens). Treatment success (SVR12) was defined by undetectable HCV-RNA 12weeks after treatment cessation. Exact logistic regression analysis was used to identify factors associated with SVR12. A total of 323 patients (74% men) with a median age of 53years were included, 99% of whom were on combination antiretroviral therapy (cART). HIV RNA load was <50 copies/ml in 88% of patients; median CD4 cell count was 540/mm3; 60% of patients were cirrhotic; 68% had previously received unsuccessful anti-HCV treatment. cART was protease inhibitor (PI)-based in 23%, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in 15%, and integrase inhibitor (II)-based in 38%, while 24% of patients received other regimens. The SVR12 rate was 93.5% overall (95% confidence interval [CI]: 90.2-95.9), 93.3% (88.8-96.4) in patients with cirrhosis and 93.8% (88.1-97.3) in patients without cirrhosis. The SVR12 rates were 93.1% (84.5-97.7), 91.8% (80.4-97.7) and 95.8% (90.5-98.6) respectively, in patients receiving PI-based, NNRTI-based and II-based cART. In adjusted analysis, SVR12 was not associated with HIV RNA load, the cART regimen, cirrhosis, prior anti-HCV treatment, the duration of anti-HCV therapy, or ribavirin use. The most common adverse effects were fatigue and digestive disorders. New all-oral DAA regimens were well-tolerated and yielded high SVR12 rates in HIV/HCV-co-infected patients. We evaluated efficacy and safety of all-oral DAA regimens in a large French nationwide observational cohort study of HIV/HCV co-infected patients. Sustained virological response 12weeks after treatment cessation was 93.5% overall. The all-oral DAA regimens were well-tolerated and most common adverse effects were fatigue and digestive disorders.

Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1–Coinfected Patients Treated in Routine Practice

Large cohorts are needed to assess human immunodeficiency virus (HIV)/hepatitis C virus (HCV) real-world treatment outcomes. We examined the effectiveness of ledipasvir/sofosbuvir with or without ribavirin (LDV/SOF ± RBV) and ombitasvir/ paritaprevir/ritonavir plus dasabuvir (OPrD) ± RBV in HIV/HCV genotype 1 (GT1)-coinfected patients initiating HCV therapy in clinical practice. Observational intent-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry to identify HIV/HCV GT1-coinfected veterans initiating 12 weeks of LDV/SOF ± RBV or OPrD ± RBV. Multivariate models of sustained virologic response (SVR) included age, race, cirrhosis, proton pump inhibitor (PPI) prescription, prior HCV treatment, body mass index, genotype subtype, and HCV treatment regimen. Nine hundred ninety-six HIV/HCV GT1-coinfected veterans initiated therapy: 757 LDV/SOF, 138 LDV/SOF + RBV, 28 OPrD, and 73 OPrD + RBV. Overall SVR was 90.9% (823/905); LDV/SOF 92.1% (631/685), LDV/SOF + RBV 86.3% (113/131), OPrD 88.9% (24/27), and OPrD + RBV 88.7% (55/62). SVR was 85.9% (176/205) and 92.4% (647/700) in those with and without cirrhosis (P = .006). SVR was similar between African Americans (90.5% [546/603]) and all others (91.7% [277/302]). PPI use with LDV/SOF ± RBV did not affect SVR (89.7% [131/146] with PPI and 91.5% [613/670] without PPI). Cirrhosis was predictive of reduced SVR (0.51 [95% confidence interval {CI}, .31-.87]; P = .01). Median creatinine change did not differ among patients receiving LDV/SOF and tenofovir disoproxil fumarate (TDF) without a protease inhibitor (PI) (0.18 [interquartile range {IQR}, 0.08-0.30]; n = 372), LDV/SOF and TDF/PI (0.17 [IQR, 0.04-0.30]; n = 100), and LDV/SOF without TDF (0.15 [IQR, 0.00-0.30]; n = 423). SVR rates in HIV/HCV GT1-coinfected patients were high. African American race or PPI use with LDV/SOF ± RBV was not associated with lower SVR rates, but cirrhosis was. Renal function did not worsen on LDV/SOF regimens with TDF.

The Role of Direct-acting Antivirals in the Treatment of Children with Chronic Hepatitis C.

In the United States, chronic infection with the hepatitis C virus (HCV) affects an estimated 0.1–2% of the pediatric population, who are consequently at risk for major complications, including cirrhosis, hepatocellular carcinoma, and death. The current standard of treatment for chronic hepatitis C (CHC) in children is pegylated-interferon-alpha (PEG-IFN) in combination with ribavirin. PEG-IFN/ribavirin therapy is approved for children ages 3 and older; however, it is often held from use until adulthood because of its extensive list of potential side effects and high likelihood of causing adverse symptoms. While CHC is usually indolent in children and adolescents, immediately treating and curbing the spread of HCV before adulthood is important, as there can be transmission to other individuals via sexual activity and infected females can later vertically transmit the infection during pregnancy, the latter representing the most common means of transmission for children in the United States. The recent development of direct-acting antivirals has shown promising results in clinical trials for use in children and has dramatically increased the rates of sustained virological response in adults while improving side effect profiles as compared to interferon-based treatments. Given the usually indolent course of CHC in children, significant side effects of the currently-approved PEG-IFN/ribavirin therapy, and likely availability of all-oral interferon-free regimens for children within a few years, deferring treatment in clinically-stable children with CHC in anticipation of upcoming superior treatment modalities may be justified.

Engagement in the Hepatitis C Care Cascade Among Homeless Veterans, 2015.

The Veterans Health Administration (VHA) is the largest provider of hepatitis C virus (HCV) care nationally and provides health care to >200 000 homeless veterans each year. We used the VHA's Corporate Data Warehouse and HCV Clinical Case Registry to evaluate engagement in the HCV care cascade among homeless and nonhomeless veterans in VHA care in 2015. We estimated that, among 242 740 homeless veterans in care and 5 424 712 nonhomeless veterans in care, 144 964 (13.4%) and 188 156 (3.5%), respectively, had chronic HCV infection. Compared with nonhomeless veterans, homeless veterans were more likely to be diagnosed with chronic HCV infection and linked to HCV care but less likely to have received antiviral therapy despite comparable sustained virologic response rates. Homelessness should not necessarily preclude HCV treatment eligibility with available all-oral antiviral regimens.

Analysis of Adherence to AllOral HCV Therapy in a Cohort of People who Inject Drugs (PWID)

The majority of prevalent and incident cases of HCV infection in Canada occur among people who inject drugs (PWID). The benefits of more effective and better tolerated all-oral regimens will only be achieved with proper strategies to ensure adherence in this population. We hypothesize that the provision of treatment within a multidisciplinary centre attending to all health care needs will maximize the likelihood of achieving this goal. Within a cohort of 87 patients receiving all oral HCV therapy over a median of 12 weeks, 1135/1150 (98.7%) scheduled weekly appointments were attended, with pill counts reflecting over 90% adherence to therapy. In this model of care, adherence to HCV therapy among PWID met or exceeded the standard established in clinical trials. These data directly address one of the major concerns about increasing availability of HCV treatment among PWID and lend further support to the expansion of such programs in clinical practice.

SAT-274 - Sofosbuvir-based all-oral regimens for patients with chronic hepatitis C genotype 2 infection: integrated analysis of eleven clinical studies

SAT-274 - Sofosbuvir-based all-oral regimens for patients with chronic hepatitis C genotype 2 infection: integrated analysis of eleven clinical studies