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      Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India

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          Abstract

          Background & aims

          Availability of directly-acting antivirals (DAAs) has changed the treatment landscape of hepatitis C virus (HCV) infection. The high price of DAAs has restricted their use in several countries. However, in some countries such as India, generic DAAs are available at much cheaper price. This study examined whether generic DAAs could be cost-saving and how long it would take for the treatment to become cost-saving/effective.

          Methods

          A previously-validated, mathematical model was adapted to the HCV-infected population in India to compare the outcomes of no treatment versus treatment with DAAs. Model parameters were estimated from published studies. Cost-effectiveness of HCV treatment using available DAAs was calculated, using a payer’s perspective. We estimated quality-adjusted life years (QALYs), disability-adjusted life years (DALYs), total costs, and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and probabilistic sensitivity analyses were conducted.

          Results

          Compared with no treatment, the use of generic DAAs in Indian HCV patients would increase the life expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV-infected persons could prevent 3400–3850 decompensated cirrhosis, 1800–2500 HCC, and 4000–4550 liver-related deaths. The results were sensitive to the costs of DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and quality of life after sustained virologic response.

          Conclusions

          Treatment with generic DAAs available in India will improve patient outcomes, provide a good value for money within 2 years, and be ultimately cost-saving. Therefore, in this and similar settings, HCV treatment should be a priority from a public health as well an economic perspective.

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          Most cited references24

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          Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients.

          Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C. A cohort of 384 European cirrhotic patients was enrolled at seven tertiary referral hospitals and followed up for a mean period of 5 years. Inclusion criteria were biopsy-proven cirrhosis, abnormal serum aminotransferase levels, absence of complications of cirrhosis, and exclusion of hepatitis A and B viruses and of metabolic, toxic, or autoimmune liver diseases. Antibodies against hepatitis C virus were positive in 98% of 361 patients tested. The 5-year risk of hepatocellular carcinoma was 7% and that of decompensation was 18%. Death occurred in 51 patients (13%), with 70% dying of liver disease. Survival probability was 91% and 79% at 5 and 10 years, respectively. Two hundred five patients (53%) were treated with interferon alfa. After adjustment for clinical and serological differences at baseline between patients treated or not treated with interferon, the 5-year estimated survival probability was 96% and 95% for treated and untreated patients, respectively. In this cohort of patients, life expectancy is relatively long, in agreement with the morbidity data showing a slowly progressive disease.
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            All-Oral 12-Week Treatment With Daclatasvir Plus Sofosbuvir in Patients With Hepatitis C Virus Genotype 3 Infection: ALLY-3 Phase III Study

            Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection are limited, with the currently approved all-oral regimens requiring 24-week treatment and the addition of ribavirin (RBV). This phase III study (ALLY-3; http://ClinicalTrials.gov: NCT02032901) evaluated the 12-week regimen of daclatasvir (DCV; pangenotypic nonstructural protein [NS]5A inhibitor) plus sofosbuvir (SOF; pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were either treatment naïve (n = 101) or treatment experienced (n = 51) and received DCV 60 mg plus SOF 400 mg once-daily for 12 weeks. Coprimary endpoints were the proportions of treatment-naïve and treatment-experienced patients achieving a sustained virological response (SVR) at post-treatment week 12 (SVR12). SVR12 rates were 90% (91 of 101) and 86% (44 of 51) in treatment-naïve and treatment-experienced patients, respectively; no virological breakthrough was observed, and ≥99% of patients had a virological response (VR) at the end of treatment. SVR12 rates were higher in patients without cirrhosis (96%; 105 of 109) than in those with cirrhosis (63%; 20 of 32). Five of seven patients who previously failed treatment with an SOF-containing regimen and 2 of 2 who previously failed treatment with an alisporivir-containing regimen achieved SVR12. Baseline characteristics, including gender, age, HCV-RNA levels, and interleukin-28B genotype, did not impact virological outcome. DCV plus SOF was well tolerated; there were no adverse events (AEs) leading to discontinuation and only 1 serious AE on-treatment, which was unrelated to study medications. The few treatment-emergent grade 3/4 laboratory abnormalities that were observed were transient. Conclusion: A 12-week regimen of DCV plus SOF achieved SVR12 in 96% of patients with genotype 3 infection without cirrhosis and was well tolerated. Additional evaluation to optimize efficacy in genotype 3–infected patients with cirrhosis is underway. (Hepatology 2015;61:1127–1135)
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              Chronic Hepatitis C Virus (HCV) Disease Burden and Cost in the United States

              Hepatitis C virus (HCV) infection is a leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. A better understanding of HCV disease progression and the associated cost can help the medical community manage HCV and develop treatment strategies in light of the emergence of several potent anti-HCV therapies. A system dynamic model with 36 cohorts was used to provide maximum flexibility and improved forecasting. New infections incidence of 16,020 (95% confidence interval, 13,510-19,510) was estimated in 2010. HCV viremic prevalence peaked in 1994 at 3.3 (2.8-4.0) million, but it is expected to decline by two-thirds by 2030. The prevalence of more advanced liver disease, however, is expected to increase, as well as the total cost associated with chronic HCV infection. Today, the total cost is estimated at $6.5 ($4.3-$8.4) billion and it will peak in 2024 at $9.1 ($6.4-$13.3) billion. The lifetime cost of an individual infected with HCV in 2011 was estimated at $64,490. However, this cost is significantly higher among individuals with a longer life expectancy. Conclusion This analysis demonstrates that US HCV prevalence is in decline due to a lower incidence of infections. However, the prevalence of advanced liver disease will continue to increase as well as the corresponding healthcare costs. Lifetime healthcare costs for an HCV-infected person are significantly higher than for noninfected persons. In addition, it is possible to substantially reduce HCV infection through active management.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                17 May 2017
                2017
                : 12
                : 5
                : e0176503
                Affiliations
                [1 ]Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
                [2 ]Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts, United States of America
                [3 ]Harvard Medical School, Boston, Massachusetts, United States of America
                [4 ]World Health Organization India Country Office, New Delhi, India
                [5 ]World Health Organization Regional Office for the South-East Asia, Communicable Diseases Department, New Delhi, India
                [6 ]H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America
                University of North Carolina at Chapel Hill School of Dentistry, UNITED STATES
                Author notes

                Competing Interests: Chhatwal has received a research grant from Gilead and an advisory fee from Merck and Gilead. Other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                • Conceptualization: RA QC AG NS JC.

                • Data curation: JC QC.

                • Formal analysis: QC.

                • Methodology: RA QC AG NS RP TA JC.

                • Project administration: JC.

                • Software: QC.

                • Supervision: RA QC.

                • Validation: RA QC JC.

                • Visualization: RA QC JC.

                • Writing – original draft: RA JC.

                • Writing – review & editing: RA QC AG NS RP TA JC.

                Author information
                http://orcid.org/0000-0001-8741-4430
                Article
                PONE-D-17-05355
                10.1371/journal.pone.0176503
                5435174
                28520728
                ee490ba8-bff0-4a4c-b5aa-3f2246d8b96e
                © 2017 Aggarwal et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 February 2017
                : 11 April 2017
                Page count
                Figures: 5, Tables: 4, Pages: 15
                Funding
                The author(s) received no specific funding for this work.
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