A cost-effectiveness analysis of E/C/F/TAF vs three boosted regimens in the Italian context
DOI:
https://doi.org/10.7175/fe.v18i1.1312Keywords:
HIV, HAART, E/C/F/TAF, Cost-effectivenessAbstract
BACKGROUND: Highly Active Antiretroviral Therapy (HAART) has transformed HIV into a lifelong condition. Following the chronicity of the disease, and significant increase in lifespan – the prevalence of comorbidities increased in HIV+ subjects that are exposed both to a higher risk of developing cardiovascular disease, renal disease, osteopenia/osteoporosis and diabetes, and to the risk of developing them early. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate (E/C/F/TAF), a complete, Single-Tablet antiretroviral Regimen (STR) that combines the effectiveness and tolerability of integrase inhibitors with an innovative backbone was recently introduced in Italy. Compared to Tenofovir Disoproxil Fumarate (TDF), TAF reaches the sites of action more efficiently, reducing tenofovir plasma concentration to more than 90% and the risk of off-target effects.
OBJECTIVE: A patient-level micro-simulation model was adapted to the Italian context to evaluate E/C/F/TAF cost-effectiveness vs three boosted regimens for HIV+ patients treatment.
METHODS: A Markov micro-simulation model was adapted to the Italian context for the evaluation of the cost-effectiveness in patients with HIV. The total cost per patient accounts for drug therapies and the management of adverse events and comorbidities. The quality-adjusted life expectancy (in QALYs) is calculated by weighing the years of life lived by the utility weights. A 70-year time horizon was adopted to simulate a lifetime analysis; shorter time horizons were considered in the sensitivity analyses. 3.5% discount rate was applied both for costs and future benefits. The rate of virologic suppression at 48 weeks with E/C/F/TAF is 92.3%; for the other treatments such proportion is calculated by applying to the reference rate the relative risks, as calculated in a recent network meta-analysis (NMA). Alternative treatments considered in this analysis are three boosted regimens commonly used in Italy: tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat in STR; tenofovir disoproxil fumarate/emtricitabine + darunavir/ritonavir; tenofovir disoproxil fumarate/emtricitabine + atazanavir/ritonavir.
RESULTS: E/C/F/TAF improves survival and quality of life (20.17 LY and 14.89 QALY), with the lowest total cost (€ 280,528), thus resulting dominant over three comparators considered as starting therapy. The sensitivity analysis confirms the results of the base case: at a willingness-to-pay threshold of € 30,000 per QALY, the E/C/F/TAF strategy is the most cost-effective, with a 90% probability and it is the most cost-effective even with a threshold of € 10,000 per QALY, with a 50% probability.
CONCLUSION: E/C/F/TAF can be a sustainable alternative to currently available treatments, combining the advantage of the STR to lower risks of kidney and bone damage than observed in regimens based on TDF.
References
Ancelle-Park R, Klein JP, Stroobant A, et al. Expanded European AIDS case definition. The Lancet 1993; 341: 441; https://doi.org/10.1016/0140-6736(93)93040-8
Guaraldi G, Zona S, Menozzi M, et al. Cost of noninfectious comorbidities in patients with HIV. Clinicoecon Outcomes Res 2013; 5: 481-8; https://doi.org/10.2147/CEOR.S40607
Capeau J. Premature Aging and Premature Age-Related Comorbidities in HIV-Infected Patients: Facts and Hypotheses. Clin Infect Dis 2011; 53: 1127-9; https://doi.org/10.1093/cid/cir628
Restelli U, Croce D, Bonfanti P, et al. Applicazione dell’approccio patient based per la determinazione dei costi sanitari diretti pubblici della cura e assistenza per l’infezione da HIV. Sanità Pubblica e Privata 2011: 50-6
Wohl D, Oka S, Clumeck N, et al. A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results. J Acquir Immune Defic Syndr 2016; 72: 58-64; https://doi.org/10.1097/QAI.0000000000000940
Antinori A, Angeletti C, Ammassari A, et al. Adherence in HIV-positive patients treated with single-tablet regimens and multi-pill regimens: findings from the COMPACT study. J Int AIDS Soc 2012; 15(Suppl 4): 18098; https://doi.org/10.7448/IAS.15.6.18098
Wild L, Kiff C, Fenwick E, et al. Cost-effectiveness of E/C/F/TAF in the United Kingdom (UK): assessment through a novel individual patient simulation. 21st International AIDS Conference. Durban, South Africa; 18-22 July 2016
SIMIT – In collaborazione con Ministero della Salute. Linee guida italiane - Utilizzo dei farmaci antiretrovirali e gestione diagnostico-clinica delle persone con infezione da HIV-1. 22 Novembre 2016. Available at http://www.salute.gov.it/imgs/C_17_pubblicazioni_2545_allegato.pdf (last accessed July 2017)
Friis-Møller N, Thiébaut R, Reiss P, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: the Data collection on Adverse Effects of Anti-HIV Drugs Study. Eur J Cardiovasc Prev Rehabil 2010; 17: 491-501; https://doi.org/10.1097/HJR.0b013e328336a150
Mocroft A, Lundgren JD, Ross M, et al. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study. PLoS Med 2015; 12: e1001809; https://doi.org/10.1371/journal.pmed.1001809
Wilson PW, Meigs JB, Sullivan L, et al. Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study.. Arch Intern Med 2007; 167: 1068-74; https://doi.org/10.1001/archinte.167.10.1068
Parikh NI, Pencina MJ, Wang TL, et al. A risk score for predicting near-term incidence of hypertension: the Framingham Heart Study. Ann Intern Med 2008; 148: 102-10; https://doi.org/10.7326/0003-4819-148-2-200801150-00005
Battalora L, Buchacz K, Armon C, et al. New fracture risk and FRAX 10-year probability of fracture in HIV-infected adults. Value Health 2014; 17: A268
Capri S, Ceci A, Terranova L, et al. Guidelines for economic evaluations in Italy: recommendations from the Italian group of pharmacoeconomic studies. Drug Inf J 2001; 35: 189-201; https://doi.org/10.1177/009286150103500122
European Union. Guide to Cost-Benefit Analysis of Investment Projects. Economic appraisal tool for Cohesion Policy 2014-2020. Available at http://ec.europa.eu/regional_policy/sources/docgener/studies/pdf/cba_guide.pdf (last accessed 2017)
Italian Health Economics Association (AIES). A proposal for guidelines for the economic evaluation of health interventions in Italy. PharmacoEconomics Italian Research Articles 2009; 11: 83-93
Evans D. Social discount rate for the European Union: new estimates. In: Florio M, ed. Cost-Benefit Analysis and Incentives in Evaluation: The Structural Funds of the European Union. Edward Elgar Publishing, 2007
Iannazzo S, Pradelli L, Carsi M, et al. Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy. Value Health 2011; 14: 80-9; https://doi.org/10.1016/j.jval.2010.10.023
Bandera A, Gori A, Sabbatini F, et al. Evaluation of prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy. PLoS One 2015; 10: e0124252; https://doi.org/10.1371/journal.pone.0124252
Vescini F, Cozzi-Lepri A, Borderi M, et al. Prevalence of hypovitaminosis D and factor associated with vitamin D deficiency and morbidity among HIV-infected patients enrolled in a large Italian cohort. J Acquir Immune Defic Syndr 2011; 58: 163-72; https://doi.org/10.1097/QAI.0b013e31822e57e9
Borderi M, Calza L, Colangeli V, et al. Prevalence of sub-clinical vertebral fractures in HIV-infected patients. New Microbiologica 2014; 37: 25-32
De Socio GV, Ricci E, Maggi P, et al. Prevalence, awareness, treatment and control rate of hypertension in HIV-infected patients: the HIV-HY study. Am J Hypertens 2014; 27: 222-8; https://doi.org/10.1093/ajh/hpt182
Li Vecchi V, Soresi M, Giannitrapani L, et al. Dairy calcium intake and lifestyle risk factors for bone loss in HIV-infected and uninfected Mediterranean subjects. BMC Infect Dis 2012; 12: 192; https://doi.org/10.1186/1471-2334-12-192
Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 2015; 385: 2606-15; https://doi.org/10.1016/S0140-6736(15)60616-X
Agirrezabal I, LeReun C, Eddowes L, et al. Systematic Literature Review and Network Meta-Analysis of Tenofovir/Emtricitabine and Abacavir/Lamivudine Backbone Regimens For HIV-1. IAS Conference on HIV Pathogenesis, Treatment and Prevention Vancouver, Canada, July 19-22 2015
Sax PE. Maraviroc for treatment-naive patients with HIV-1 infection: is the glass half empty or half full? J Infect Dis 2010; 201: 797-9; https://doi.org/10.1086/650701
Williams I, Churchill D, Anderson J, et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012 (Updated November 2013. All changed text is cast in yellow highlight.). HIV Med 2014; 15 Suppl 1: 1-85; https://doi.org/10.1111/hiv.12119
Parienti JJ, Ragland K, Lucht F, et al. Average adherence to boosted protease inhibitor therapy, rather than the pattern of missed doses, as a predictor of HIV RNA replication. Clin Infect Dis 2010; 50: 1192-7; https://doi.org/10.1086/651419
Parienti JJ, Bangsberg DR, Verdon R, et al. Better adherence with once-daily antiretroviral regimens: a meta-analysis. Clin Infect Dis 2009; 48: 484-8; https://doi.org/10.1086/596482
Moneti V, Luis N, Rijo J, et al. Causes of virological failure in a population of 1895 HIV-infected patients: the experience of an infectious diseases service in Lisbon, Portugal. J Int AIDS Soc 2012; 15(Suppl 4): 18065; https://doi.org/10.7448/IAS.15.6.18065
Cambiano V, Lampe FC, Rodger AJ, et al. Use of a prescription-based measure of antiretroviral therapy adherence to predict viral rebound in HIV-infected individuals with viral suppression. HIV Med 2010; 11: 216-24; https://doi.org/10.1111/j.1468-1293.2009.00771.x
Hughes RA, Sterne JA, Walsh J, et al. Long-term trends in CD4 cell counts and impact of viral failure in individuals starting antiretroviral therapy: UK Collaborative HIV Cohort (CHIC) study. HIV Med 2011; 12: 583-93; https://doi.org/10.1111/j.1468-1293.2011.00929.x
Kuhne FC, Chancellor J, Mollon P, et al. A microsimulation of the cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals. HIV Clin Trials 2010; 11: 80-99; https://doi.org/10.1310/hct1102-80
Mocroft A, Furrer HJ, Miro JM, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/muL in the post-combination antiretroviral therapy era. Clin Infect Dis 2013; 57: 1038-47; https://doi.org/10.1093/cid/cit423
Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363: 2587-99; https://doi.org/10.1056/NEJMoa1011205
Mocroft A, Sterne JA, Egger M, et al. Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal. Clin Infect Dis 2009; 48: 1138-51; https://doi.org/10.1086/597468
ISTAT. Tavole di mortalità della popolazione italiana 2013. Available at http://demo.istat.it/index.html (last accessed 2017)
Health & Social Care Information Centre. National Diabetes Audit 2012-2013. Available at https://digital.nhs.uk/catalogue/PUB14970 (last accessed July 2017)
British Heart Foundation. Trends in coronary heart disease, 1961 - 2011. Available at https://www.bhf.org.uk/~/media/files/research/heart-statistics/bhf-trends-in-coronary-heart-disease.pdf (last accessed July 2017)
Marks A, Macleod C, McAteer A, et al. Chronic kidney disease, a useful trigger for proactive primary care? Mortality results from a large U.K. cohort. Fam Pract 2013; 30: 282-9; https://doi.org/10.1093/fampra/cms079
Hass B, Lungershausen J, Hertel N, et al. Cost-effectiveness of strong opioids focussing on the long-term effects of opioid-related fractures: a model approach. Eur J Health Econ 2009; 10: 309-21; https://doi.org/10.1007/s10198-008-0134-1
Kauf TL, Roskell N, Shearer A, et al. A predictive model of health state utilities for HIV patients in the modern era of highly active antiretroviral therapy. Value Health 2008; 11: 1144-53; https://doi.org/10.1111/j.1524-4733.2008.00326.x
Freedberg KA, Scharfstein JA, Seage GR, et al. The cost-effectiveness of preventing AIDS-related opportunistic infections. JAMA 1998; 279: 130-6; https://doi.org/10.1001/jama.279.2.130
National Institute for Health and Clinical Excellence. Mifamurtide for the treatment of osteosarcoma Technology appraisal guidance [TA235]. October 2011
National Institute for Health and Clinical Excellence. Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control. Clinical guideline [CG117]. March 2011
National Institute for Health and Clinical Excellence. Rituximab for aggressive non-Hodgkin’s lymphoma. Technology appraisal guidance [TA65]. September 2003
National Institute for Health and Clinical Excellence. Pneumonia in adults: diagnosis and management. Clinical guideline [CG191]. December 2014
Meeuwsen E, Melis R, van der Aa G, et al. Cost-effectiveness of one year dementia follow-up care by memory clinics or general practitioners: economic evaluation of a randomised controlled trial. PLoS One 2013; 8: e79797; https://doi.org/10.1371/journal.pone.0079797
Kulasingam SL, Benard S, Barnabas RV, et al. Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: A cost-effectiveness analysis. Cost Eff Resour Alloc 2008; 6: 4; https://doi.org/10.1186/1478-7547-6-4
Foglia E, Bonfanti P, Rizzardini G, et al. Cost-utility analysis of lopinavir/ritonavir versus atazanavir + ritonavir administered as first-line therapy for the treatment of HIV infection in Italy: from randomised trial to real world. PLoS One 2013; 8: e57777; https://doi.org/10.1371/journal.pone.0057777
Juday T, Correll T, Anene A, et al. Cost-effectiveness of the once-daily efavirenz/emtricitabine/tenofovir tablet compared with the once-daily elvitegravir/cobicistat/emtricitabine/tenofovir tablet as first-line antiretroviral therapy in HIV-infected adults in the US. Clinicoecon Outcomes Res 2013; 5: 437-45
Klepser DG, Bisanz SE, Klepser ME. Cost-effectiveness of pharmacist-provided treatment of adult pharyngitis. Am J Manag Care 2012; 18: e145-e54
Clarke P, Bisanz SE, Klepser ME. The impact of diabetes-related complications on healthcare costs: results from the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65). Diabet Med 2003; 20: 442-50; https://doi.org/10.1046/j.1464-5491.2003.00972.x
National Institute for Health and Clinical Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. CG 181/2, July 2014
Smith SM, Campbell JD. Cost-effectiveness of renin-guided treatment of hypertension. Am J Hypertens 2013; 26: 1303-10; https://doi.org/10.1093/ajh/hpt099
Ministero Della Salute. Decreto 18 ottobre 2012. Remunerazione prestazioni di assistenza ospedaliera per acuti, assistenza ospedaliera di riabilitazione e di lungodegenza post acuzie e di assistenza specialistica ambulatoriale. GU Serie Generale n.23 del 28-01-2013 - Suppl. Ordinario n. 8
Osservatorio ARNO diabete ─ Il profilo assistenziale della popolazione con diabete (Rapporto 2011) Volume XVII - collana “Rapporti ARNO” Cineca - Dipartimento SISS – Sanità
Osservatorio ARNO sui farmaci cardiovascolari ─ Focus sull’uso dei farmaci per il controllo del metabolismo lipidico (Rapporto 2009) Volume XII - collana “Rapporti ARNO” Cineca - Dipartimento SISS – Sanità
Piscitelli P, Brandi ML, Chitano G, et al. Epidemiology of fragility fractures in Italy. Clin Cases Miner Bone Metab 2011; 8: 29-34
Tarantino U, Piscitelli P, Brandi ML, et al. The Incidence of Hip, Forearm, Humeral, Ankle and Vertebral Fragility Fractures in Italy: Results from a 3-Years Multicentric Study. Arthritis Res Ther 2010; 12: R226
Cicchetti A, Ruggeri M, Codella, et al. The health and social costs of chronic kidney disease in Italy. Farmeconomia e percorsi terapeutici 2011; 12: 21-8; https://doi.org/10.7175/fe.v12i1.95
Marcello R. HTA: passaporto per l’innovazione e sfida alla sostenibilità. Roma, 12 Luglio 2013
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. The Publication Agreement can be downloaded here, and should be signed by the Authors and sent to the Publisher when the article has been accepted for publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).
- Authors are permitted to post their work online after publication (the article must link to publisher version, in html format)