The recently launched nucleotide polymerase inhibitor sofosbuvir represents a significant turn in the treatment paradigm of chronic hepatitis C. While effective, sofosbuvir is also associated with a considerable cost.
The objective of this study was to evaluate the cost effectiveness of sofosbuvir-containing regimens in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 5 (HCV-G5) mono-infection in South Africa (SA).
We constructed a lifetime horizon decision-analytic Markov model of the natural history of HCV infection to evaluate the cost effectiveness of sofosbuvir–ledipasvir (SOF/LDV) monotherapy against sofosbuvir triple therapy (SOF-TT) (sofosbuvir + pegylated interferon and ribavirin [peg-INF/RBV]) and the current standard of care (SOC) (peg-INF/RBV) for patients with chronic HCV-G5 in the South African context. The model was populated with data from published literature, expert opinion and South African private sector cost data. The price modelled for sofosbuvir was the predicted South African private sector price of 82,129.32 South African rand (R) (US$7000) for 12 weeks. The analysis was conducted from a third-party payer perspective.
The outcome measures were discounted and undiscounted costs (in 2015 South African rand and US dollars) and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).
Outcomes from the cost-effectiveness model show that SOF/LDV yields the most favourable future health economic outcomes compared with SOF-TT and the current SOC in SA. Findings relating to the lifetime incremental cost per QALY gained for patients infected with HCV-G5 indicate that SOF/LDV dominated both SOF-TT and SOC, i.e. SOF/LDV is less costly and more effective.
Outcomes from this analysis suggest that at a price of R123,190 ($US10,500) for 12 weeks of SOF/LDV might be cost effective for South African patients infected with HCV-G5.
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US$1 = R11.73276 .
The METAVIR scoring system is a scoring method used for measuring the degree of liver inflammation and staging of fibrosis in patients with hepatitis C. It uses a grading and a staging system where the grade indicates the amount of inflammation and the stage represents the amount of fibrosis or scarring. The grade is usually scored from 0 to 4 (0 = no activity and 3 or 4 = severe activity). The fibrosis score is also assigned a number from 0 to 4 (0 = no scarring; 1 = minimal scarring; 2 = scarring extending outside the areas in the liver that contains blood vessels; 3 = bridging fibrosis, spreading and connecting to other areas that contain fibrosis; and 4 = cirrhosis or advanced scarring of the liver) .
In SA, medicine prices are regulated (Medicines and Related Substances Act, SA, 2014) and consist of a regulated SEP, VAT and a professional fee charged by the dispensing pharmacist, which makes discounting of any sort illegal .
SA does not have a WTP threshold. We thus assumed an ICER of three times the gross domestic product (GDP)/capita as cost effective .
Utility value for SOF/LDV for 24 weeks = 0.741 .
WHO (World Health Organization). Hepatitis C fact sheet N°164. 2013. http://www.who.int/mediacentre/factsheets/fs164/en/. Accessed 9 Dec 2013.
Abuelhasssan W. Review: hepatitis C virus infection in 2012 and beyond. South Afr J Epidemiol Infect. 2012;27(3):93–7.
Karoney MJ, Siika AM. Hepatitis C virus (HCV) infection in Africa: a review. Pan Afr Med J. 2013;14:44.
Prabdial-Sing N, Puren A, Schoub B. The status of hepatitis C—the silent “volcano” in South Africa. Commun Dis Surveill Bull. 2013;11(1):22–5.
Tucker TJ, Voight M, Bird A, Robson S, Gibbs B, Kannemeyer J, et al. Hepatitis C virus infection rate in volunteer blood donors from the Western Cape — comparison of screening tests and PCR. S Afr Med J. 1997;87(5):603–5.
Vardas E, Ross MH, Sharp G, McAnerney J, Sim J. Viral hepatitis in South African healthcare workers at increased risk of occupational exposure to blood-borne viruses. J Hosp Infect. 2002;50(1):6–12.
Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011;17(2):107–15.
Massard J, Ratziu V, Thabut D, Moussalli J, Lebray P, Benhamou Y, et al. Natural history and predictors of disease severity in chronic hepatitis C. J Hepatology. 2007;44:S19–24.
Botha JF, Kassianides C, Schneider HR, Song E, Spearman W, van der Merwe SW. South African hepatitis C management guidelines 2010. South Afr Gastroenterol. 2010;8(1). http://www.sages.co.za/content/images/SouthAfricanHepatitisCGuidelines.pdf. Accessed 12 Dec 2014.
Pearlman BL, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis. 2011;52(7):889–900.
OANDA currency converter. Average exchange rate for the first quarter of 2015. 2015. http://www.oanda.com/currency/converter/. Accessed 3 May 2015.
Ford N, Singh K, Cooke GS, Mills EJ, Von Schoen-Angerer T, Kamarulzaman A, et al. Expanding access to treatment for hepatitis C in resource-limited settings: lessons From HIV/AIDS. Clin Inf Dis. 2012;54(10):1465–72.
Dillon J. Management of hepatitis C. Prim Health Care. 2007;17(5):25–9.
Gravitz L. A smouldering public-health crisis. Nature. 2011;474:S2–4.
Gilead Sciences, Inc. Sovaldi®. Highlights of prescribing information. 2015. http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf. Accessed 10 Apr 2015.
Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;368(1):33–44.
Gilead Sciences. Sofosbuvir with Peginterferonalfa 2a and ribavirin for 12 weeks in treatment-naive subjects with chronic genotype 1, 4, 5, or 6 HCV infection (NEUTRINO) [ClincalTrials.gov identifier NCT01641640]. US National Institutes of Health, ClinicalTrials.gov. 2013. https://clinicaltrials.gov/ct2/show/NCT01641640. Accessed 24 Feb 2014.
Leof A, Gerrity M, Thielke A, King V. Sofosbuvir for the treatment of hepatitis C and evaluation of the 2014 American Association for the Study of Liver Diseases treatment guidelines. Portland: Center for Evidence-based Policy, Oregon Health & Science University; 2014.
FDA (US Food and Drug Administration). FDA approves first combination pill to treat hepatitis C. 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418365.htm. Accessed 13 Nov 2014.
Abergel A, Loustaud-Ratti V, Metivier S, Jiang D, Kersey K, Knox SJ, et al. Ledipasvir/sofosbuvir for the treatment of patients with chronic genotype 4 or 5 HCV infection [conference report]. The International Liver Congress 2015: 50th annual meeting of the European Association for the Study of the Liver (EASL); 22–26 Apr 2015; Vienna. http://natap.org/2015/EASL/EASL_80.htm. Accessed 21 Aug 2015.
European Association for the Study of the Liver (EASL). EASL recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;63:199–236.
American Association for the Study of Liver Diseases (AASLD). Summary of recommendations for patients who are initiating therapy for HCV infection by HCV genotype. 2015. http://www.hcvguidelines.org/printpdf/full-report/initial-treatment-box-summary-recommendations-patients-who-are-initiating-therapy-hcv. Accessed 28 Aug 2015.
Jack A. Indian health activists move to prevent Gilead’s drug patent. 2013. Financial Times 2013 Nov 24. http://www.ft.com/intl/cms/s/0/7dd38ee4-551a-11e3-86bc-00144feabdc0.html?siteedition=intl#axzz2ldUq9CwB. Accessed 25 Nov 2014.
Africa South. Medicines and Related Substances Act (Act no. 101 of 1965): regulations relating to a transparent pricing system for medicines and schedules substances (Government notice no. R68). Government. Gazette. 2013;36118:1.
Sonderup MW, Abuelhassan W, Spearman W. IL28B polymorphisms are not predictive in hepatitis C genotype 5 infected South African patients [abstract]. In: 63rd annual meeting of the American Association for the Study of Liver Diseases; 9–13 Nov 2012; Boston. Hepatology 2012;56(4 Suppl. S1). http://onlinelibrary.wiley.com/doi/10.1002/hep.26040/epdf. Accessed 17 Feb 2015.
Alberti A, Chemello L, Benvegnhù L. Natural history of hepatitis C. J Hepatol. 1999;31(Suppl. 1):11–24.
Alawazi W, Cunningham M, Dearden J, Foster GR. Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection. Aliment Pharmacol Ther. 2013;32:344–55.
Sweeting M, De Angelis D, Neal KR, Ramsay ME, Irving W, Wright M, et al. Estimated progression rates in three United Kingdom hepatitis C cohorts differed according to method of recruitment. J Clin Epidemiol. 2006;59:144–52.
Saab S, Hunt D, Stone M, McClune A, Tong M. Timing of hepatitis C antiviral therapy in patients with advanced liver disease: a decision analysis model. Liver Transplant. 2010;16:748–59.
Hutchinson S, Bird S, Goldberg D. Modeling the current and future disease burden of hepatitis C among injection drug users in Scotland. Hepatology. 2005;42:711–23.
Actuarial Society of South Africa. Actuarial Society of South Africa HIV demographic model 2008 version. 2008. http://www.actuarialsociety.org.za/login.aspx?ReturnUrl=%2fLinkClick.aspx%3ffileticket%3d28pixMrSjsM%253d%26portalid%3d2. Accessed 1 Feb 2015.
D’Heygere F, George C, Van Vlierberghe H, Decaestecker J, Nakad A, Adler M, et al. Efficacy of interferon-based antiviral therapy in patients with chronic hepatitis C infected with genotype 5: a meta-analysis of two large prospective clinical trials. J Med Virol. 2011;83:815–9.
Thein HH, Krahn M, Kaldor JM, Dore GJ. Estimation of utilities for chronic hepatitis C from SF-36 scores. Am J Gastroenterol. 2005;100(3):643–51.
Chong CA, Gulamhussein A, Heathcote EJ, Lilly L, Sherman M, Naglie G, et al. Health-state utilities and quality of life in hepatitis C patients. Am J Gastroenterol. 2003;98(3):630–8.
Kerr C, Lloyd A, Ali S, Goreb C, Tyas DA. Impact of treatment attributes of peginterferon for hepatitis C on quality of life and treatment preference. Health Outcomes Res Med. 2012;3(3):e153–67.
Stepanova M, Nader F, Cure S, Bourhis F, Hunt, Younossi M. Patients’ preferences and health utility assessment with SF-6D and EQ-5D in patients with chronic hepatitis C treated with sofosbuvir regimens. Alim. Pharmacol Ther. 2014;40:676–85.
Younossi ZM, Stepanova M, Marcellin P, Afdhal N, Kowdley KV, Zeuzem S, et al. Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the ION-1, -2, and -3 clinical trials. Hepatology. 2015;61(6):1798–808.
McLernon DJ, Dillon J, Donnan PT. Health-state utilities in liver disease: a systematic review. Med Decis Making. 2008;28:582–92.
Hsu PC, Krajden M, Yoshida EM, Anderson FH, Tomlinson GA, Krahn MD. Does cirrhosis affect quality of life in hepatitis C virus-infected patients? Liver Int. 2009;29(3):449–58.
Longworth L, Bryan S. An empirical comparison of EQ-5D and SF-6D in liver transplant patients. Health Econ. 2003;12(12):1061–7.
Franciscus A. HCV diagnostic tools: grading and staging a liver biopsy. http://hcvadvocate.org/hepatitis/factsheets_pdf/biopsy.pdf. Accessed 2 Mar 2015.
Sonderup, M. Treating hepatitis B and C (in South Africa). World Hepatitis Day Presentation. 2013. http://hcvadvocate.org/hepatitis/factsheets_pdf/grade_stage.pdf. Accessed 17 Feb 2015.
Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–74.
Ferenci P, Lafer H, Scherzer TM, Maieron A, Hofer H, Stauber R, Austrian Hepatitis Study Group, et al. Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 patients with slow virologic response. Gastroenterol. 2010;138(2):503–12.
Council for Medical Schemes. Reference Price List (RPL). National reference price list for services by medical practitioners, effective from 1 January 2009. 2009. http://wcawca.co.za/files/bhf_2009_medical_practitioners.pdf. Accessed 10 Oct 2014.
Statistics South Africa (STATS SA). Statistical Release P0141: Consumer Price Index (CPI). 2015. http://www.statssa.gov.za. Accessed 20 Mar 2015.
The Official Pharmaceutical Bluebook. 2015. http://www.pbb.co.za/. Accessed 3 Feb 2015.
South Africa. Medicines and Related Substances Act (Act no. 101 of 1965): regulations relating to a transparent pricing system for medicines and schedules substances (Government notice no. R264). Government Gazette, 37527, 2014 Apr 3.
Pollack A. FDA Approves pill to treat hepatitis C. NY Times 2013 Dec 7. http://www.nytimes.com/2013/12/07/business/fda-approves-pill-to-treat-hepatitis-c.html?ref=health. Accessed 9 Dec 2013.
Gilead Sciences, Inc. Gilead announces generic licensing agreements to increase access to hepatitis C treatments in developing countries. 2014. http://www.gilead.com/news/press-releases/2014/9/gilead-announces-generic-licensing-agreements-to-increase-access-to-hepatitis-c-treatments-in-developing-countries. Accessed 25 May 2015.
Gilead Sciences, Inc. Chronic hepatitis C treatment expansion: generic manufacturing for developing countries. 2014. http://www.gilead.com/~/media/Files/pdfs/other/HCVGenericAgreementFactSheet.pdf. Accessed 6 Nov 2014.
NATCO Pharma Ltd. NATCO receives generic sofosbuvir (Sovaldi®) approval for India. News and announcements: 11 March 2015. http://natcopharma.co.in/about/news/#news1. Accessed 20 Aug 2015.
FEROZSONS Laboratories Ltd. 2014. Ferozsons Lab, Gilead Sciences sign agreement. News center. 2014. http://www.ferozsons-labs.com/index.php?option=com_news&view=news&news_id=78#. Accessed 20 Aug 2015.
GTPI (The Working Group on Intellectual Property of the Brazilian Network for the Integration of Peoples). Brazil is excluded from license authorizing production of generic medicine for hepatitis C. 2014. http://www.deolhonaspatentes.org.br/media/file/GTPI_statement_Gilead_license_sofosbuvir.pdf. Accessed 20 Aug 2015.
Fick M, Hirschler B. 2014. Gilead offers Egypt new hepatitis C drug at 99 percent discount. Reuters. 2014. http://www.reuters.com/article/2014/03/21/us-hepatitis-egypt-gilead-sciences-idUSBREA2K1VF20140321. Accessed 20 Aug 2015.
Government of South Africa. BRICS (Brazil, Russia, India, China, South Africa). 2015. http://www.gov.za/about-government/brics-brazil-russia-india-china-south-africa. Accessed 4 Jul 2015.
WHO (World Health Organization). Cost effectiveness and strategic planning: cost-effectiveness thresholds. 2015. http://www.who.int/choice/costs/CER_thresholds/en/. Accessed 19 May 2015.
De Groote K, Michielsen P, Delwaide J. Cost-effectiveness model for sofosbuvir in chronic hepatitis C [abstract]. 17th Annual European ISPOR Congress; 8–12 Nov 2014; Amsterdam. http://orbi.ulg.ac.be/bitstream/2268/174731/1/ISPOR%20poster_BE_FINALversie(b)%20(voorkeur).pdf. Accessed 20 Aug 2015.
Chhatwal J, Kanwal F, Roberts MS, Dunn MA. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med. 2015;162(6):397–406.
Younossi ZM, Park H, Saab S, Ahmed A, Dieterich D, Gordon SC. Cost-effectiveness of all-oral sofosbuvir/ledipasvir regimens in patients with chronic hepatitis C genotype 1 infection. Aliment Pharmacol Ther. 2015;41(6):544–63.
Leleu H, Blachier M, Rosa I. Cost-effectiveness of sofosbuvir in the treatment of patients with hepatitis C. J Viral Hep. 2015;22:376–83.
Deuffic-Burban S, Schwarzinger M, Obach D, Mallet V, Pol S, Pageaux GP, et al. Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141). J Hepatol. 2014;61(1):7–14.
Petta S, Cabibbo G, Enea M, Macaluso FS, Plaia A, Bruno R, et al. Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C. Hepatology. 2014;59:1692–705.
Saab S, Gordon SC, Park H, Sulkowski M, Ahmed A, Younossi Z. Cost-effectiveness analysis of sofosbuvir plus peginterferon/ribavirin in the treatment of chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther. 2014;40(6):657–75.
Pfeil AM, Reich O, Guerra IM, Cure S, Negro F, Müllhaupt B, et al. Cost-effectiveness analysis of sofosbuvir compared to current standard treatment in Swiss patients with chronic hepatitis C. PLOS One. 2015;10(5):e0126984. doi:10.1371/journal.pone.0126984.
Zarski J, Hutchison JM, Bronowicki J, Sturm N, Garcia-Kennedy R, Hodaj E, et al. Rate of natural disease progression in patients with chronic hepatitis C. J Hepatol. 2003;38:307–14.
El-Kamary SS, Jhaveri R, Shardell MD. All-cause, liver-related, and non-liver-related mortality among HCV-infected individuals in the general US population. Clin Infect Dis. 2011;53:150–7.
Shisana O, Rehle T, Simbayi LC, Zuma K, Jooste S, Zungu N, et al. South African National HIV Prevalence, Incidence and Behaviour Survey, 2012. Cape Town: HSRC Press; 2014. http://www.hsrc.ac.za/uploads/pageContent/4565/SABSSM%20IV%20LEO%20final.pdf. Accessed 15 Jun 2015.
Parboosing R. Clinical and epidemiological aspects of HIV and hepatitis C virus co-infection in KwaZulu-Natal Province of South Africa [thesis—MMed]. Durban: UKZN; 2008.
Molina JM, Orkin C, Iser DM, Zamora FX, Nelson M, Stephan C, et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet. 2015;385(9973):1098–106.
Gilead Sciences. Efficacy and safety of sofosbuvir plus ribavirin in chronic genotype 1, 2 and 3 hepatitis C Virus (HCV) and human immunodeficiency virus (HIV) co-infected adults. 2014 [ClinicalTrials.gov identifier NCT01667731]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/show/NCT01667731. Accessed 24 Aug 2015.
Gilead Sciences. Ledipasvir/sofosbuvir fixed-dose combination with ribavirin or GS-9669 in subjects with chronic genotype 1 HCV infection. 2015 [ClinicalTrials.gov identifier NCT01984294]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01984294. Accessed 7 Jun 2015.
Gilead Sciences, Inc. Gilead announces phase 2 data for investigational all-oral regimen of sofosbuvir plus GS-5816 for the treatment of chronic hepatitis C. 2014. http://www.gilead.com/news/press-releases/2014/11/gilead-announces-phase-2-data-for-investigational-alloral-regimen-of-sofosbuvir-plus-gs5816-for-the-treatment-of-chronic-hepatitis-c. Accessed 15 Feb 2015.
Ilanca Fraser and Tienie Stander conceived the design of the study. Ilanca Fraser was responsible for model construction, data collection, data analysis and interpretation of results. Johanita Burger supervised the study concept and writing of the manuscript. Mark Sonderup and Tienie Stander co-supervised the study concept, evaluated the model for clinical/technical accuracy and assisted with data collection. Johanita Burger, Martie Lubbe and George Dranitsaris reviewed the manuscript carefully for final approval.
This study was financially supported by the North-West University, under number 20098871 and Gilead Sciences Inc., under number PO # 801097865.
Conflict of interest
Ilanca Fraser does not report competing interests. Johanita Burger does not report competing interests. Martie Lubbe does not report competing interests. George Dranitsaris does not report competing interests. As a potential competing interest, Mark Sonderup reports that he has consulted to Gilead Sciences Inc. in the past five years. As a potential competing interest, TS reports that, as an employer of HEXOR (Pty) Ltd., he has consulted to Gilead Sciences, Inc. in the past five years.
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Fraser, I., Burger, J., Lubbe, M. et al. Cost-Effectiveness Modelling of Sofosbuvir-Containing Regimens for Chronic Genotype 5 Hepatitis C Virus Infection in South Africa. PharmacoEconomics 34, 403–417 (2016). https://doi.org/10.1007/s40273-015-0356-x
- Sustained Virologic Response
- Sustained Virologic Response Rate
- Early Virologic Response
- Annual Transition Probability