Faculty Bibliography

BACKGROUND: New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. AIM: The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. DESIGN: A decision-analytic Markov model. DATA SOURCE: Published literature and clinical trial data. TIME HORIZON: Life Time. PERSPECTIVE: Third-party payer. INTERVENTION: This study compared four approved regimens in treatment-naive genotype 1 chronic hepatitis C patients, including pegylated interferon and ribavirin (PR), first generation triple therapy (boceprevir + PR and telaprevir + PR), second generation triple therapy (sofosbuvir + PR and simeprevir + PR) and all-oral DAA regimens (ledipasvir/sofosbuvir and ombitasvir + paritaprevir/ritonavir + dasabuvir +/- ribavirin). OUTCOME MEASURE: Quality-adjusted cost of care (QACC). QACC was defined as the increase in treatment cost minus the increase in the patient's quality-adjusted life years (QALYs) when valued at $50,000 per QALY. RESULTS: All-oral therapy improved the average sustained virologic response (SVR) rate to 96%, thereby offsetting the high drug acquisition cost of $85,714, which resulted in the highest benefit based on the efficiency frontier. Furthermore, while oral therapies increased HCV drug costs by $48,350, associated QALY gains decreased quality-adjusted cost of care by $14,120 compared to dual therapy. When the value of a QALY was varied from $100,000 to $300,000, the quality adjusted cost of care compared to dual therapy ranged from - $21,234 to - $107,861, - $89,007 to - $293,130, - $176,280 to - $500,599 for first generation triple, second generation triple, and all-oral therapies, respectively. Primary efficacy and safety measurements for drug regimens were sourced from clinical trials data rather than a real-world setting. Factors such as individual demographic characteristics, comorbidities and alcohol consumption of the individual patients treated may alter disease progression but were not captured in this analysis. CONCLUSION: New DAA treatments provide short-term and long-term clinical and economic value to society. PRIMARY FUNDING SOURCE: Gilead Sciences, Inc.

The increased life expectancy of persons infected with human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) has resulted in renewed attention to non-HIV-related diseases exacerbated by HIV infection. Coinfection with hepatitis C virus (HCV) is a particular area of concern, as the global prevalence has been estimated at 2.5-5 million people. In this article, we discuss the epidemiology of HCV infection and reinfection, HCV-related liver disease progression in the era of effective ART, and the efficacy of emerging HCV treatment strategies in persons with HIV/HCV coinfection. New data regarding treatment of persons with HIV/HCV coinfection suggest that HCV treatment should be a priority in those with HIV. Results from recent studies using all-oral HCV regimens have shown high rates of sustained virologic response in both clinical trials and real-world settings. A multidisciplinary approach to HCV treatment in those with HIV is recommended for optimal patient management. Following HCV cure, practitioners also need to be mindful of the risks for HCV reinfection and educate patients on protective measures.

BACKGROUND: Patients with hepatitis C virus (HCV) monoinfection achieve high sustained virological response (SVR) rates on sofosbuvir (SOF)-containing regimens. Real world data on patients coinfected with HCV and the human immunodeficiency virus (HIV) treated with SOF-based regimens are lacking. METHODS: This observational cohort study included HIV/HCV coinfected adults with genotype 1 HCV initiating treatment with a SOF-containing regimen between April, 2014, and December, 2014, (n= 89) at the Mount Sinai Hospital or the Brooklyn Hospital Center. The primary outcome was sustained virological response (SVR) at 12 weeks after the end of treatment. The secondary outcomes were risk factors for treatment failure, serious adverse events and side effects. A post-hoc per protocol analysis of SVR was performed on patients who completed treatment and follow-up. RESULTS: In an intention-to-treat analysis, SVR rates were 76% (31/41) for simeprevir (SMV)/SOF, 94% (16/17) for SMV/SOF/ribavirin (RBV), and 52% (16/31) for SOF/RBV. The SVR rates of SMV/SOF/RBV and SMV/SOF did not differ significantly in this small study (p=0.15); however the SVR rate of SMV/SOF/RBV was higher than that of SOF/RBV (p<0.01). In a per-protocol analysis, SMV/SOF/RBV had a higher SVR rate than SOF/RBV: 100% (16/16) versus 57% (16/28) (p <0.01). The most commonly reported adverse effects were rash, pruritus, fatigue and insomnia. One patient, who had decompensated cirrhosis prior to treatment initiation, died while receiving SMV/SOF. CONCLUSIONS: SMV/SOF+/-RBV is an effective and safe option with minimal adverse effects for most HIV positive patients with genotype 1 HCV. SMV should be avoided in patients with decompensated cirrhosis.

Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved.