Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
PharmacoEconomics
Erschienen in: PharmacoEconomics 5/2013

01.05.2013 | Original Research Article

Lopinavir/Ritonavir Versus Darunavir Plus Ritonavir for HIV Infection: A Cost-Effectiveness Analysis for the United States

verfasst von: Kit N. Simpson, Pamela P. Pei, Jörgen Möller, Robert W. Baran, Birgitta Dietz, William Woodward, Kristen Migliaccio-Walle, J. Jaime Caro

Erschienen in: PharmacoEconomics | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

The ARTEMIS trial compared first-line antiretroviral therapy (ART) with lopinavir/ritonavir (LPV/r) to darunavir plus ritonavir (DRV + RTV) for HIV-1-infected subjects. In order to fully assess the implications of this study, economic modelling extrapolating over a longer term is required.

Objective

The aim of this study was to simulate the course of HIV and its management, including the multiple factors known to be of importance in ART.

Methods

A comprehensive discrete event simulation was created to represent, as realistically as possible, ART management and HIV outcomes. The model was focused on patients for whom clinicians believed that LPV/r or DRV + RTV were good options as a first regimen. Prognosis was determined by the impact of initial treatment on baseline CD4+ T-cell count and viral load, adherence, virological suppression/failure/rebound, acquired resistance mutations, and ensuing treatment changes. Inputs were taken from trial data (ARTEMIS), literature and, where necessary, stated assumptions. Clinical measures included AIDS events, side effects, time on sequential therapies, cardiovascular events, and expected life-years lost as a result of HIV infection. The model underwent face, technical and partial predictive validation. Treatment-naive individuals similar to those in the ARTEMIS trial were modelled over a lifetime, and outcomes with first-line DRV + RTV were compared with those with LPV/r, both paired with tenofovir and emtricitabine. Up to three regimen changes were permitted. Drug prices were based on wholesale acquisition cost. Outcomes were lifetime healthcare costs (in 2011 US dollars) from the US healthcare system perspective and quality-adjusted life-years (QALYs) (discounted at 3 % per annum).

Results

Choice of LPV/r over DRV + RTV as initial ART resulted in nearly identical clinical outcomes, but distinctly different economic consequences. Starting with an LPV/r regimen potentially results in approximately US$25,000 discounted lifetime savings. Accumulated QALYs for LPV/r and DRV + RTV were 12.130 and 12.083, respectively (a 19-day difference). In sensitivity analyses, net monetary benefit ranged from US$12,000 to US$31,000, favouring LPV/r (base case US$27,762).

Conclusions

A comprehensive simulation of lifetime course of HIV in the USA indicated that using LPV/r as first-line therapy compared with DRV + RTV may result in cost savings, with similar clinical outcomes.
Literatur
1.
Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337(11):725–33.PubMedCrossRef
2.
Montaner JS, Reiss P, Cooper D, Vella S, Harris M, Conway B, et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA. 1998;279(12):930–7.PubMedCrossRef
3.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338(13):853–60.PubMedCrossRef
4.
Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis. 2006;194(1):11–9.PubMedCrossRef
5.
Braithwaite RS, Justice AC, Chang C-CH, Fusco JS, Raffanti SR, Wong JB, et al. Estimating the proportion of patients infected with HIV who will die of comorbid diseases. Am J Med. 2005;118(8):890–8.PubMedCrossRef
6.
7.
8.
Ortiz R, Dejesus E, Khanlou H, Voronin E, van Lunzen J, Andrade-Villanueva J, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS. 2008;22(12):1389–97.PubMedCrossRef
9.
Mills AM, Nelson M, Jayaweera D, Ruxrungtham K, Cassetti I, Girard P-M, et al. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009;23(13):1679–88.PubMedCrossRef
10.
11.
Hutchinson AB, Farnham PG, Dean HD, Ekwueme DU, del Rio C, Kamimoto L, et al. The economic burden of HIV in the United States in the era of highly active antiretroviral therapy: evidence of continuing racial and ethnic differences. J Acquir Immune Defic Syndr. 2006;43(4):451–7.PubMedCrossRef
12.
Schackman BR, Gebo KA, Walensky RP, Losina E, Muccio T, Sax PE, et al. The lifetime cost of current human immunodeficiency virus care in the United States. Med Care. 2006;44(11):990–7.PubMedCrossRef
13.
Simpson KN, Rajagopalan R, Dietz B. Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir + ritonavir regimens in the CASTLE study. Adv Ther. 2009;26(2):185–93.PubMedCrossRef
14.
15.
Caro JJ, Moller J, Getsios D. Discrete event simulation: the preferred technique for health economic evaluations? Value Health. 2010;13(8):1056–60.PubMedCrossRef
16.
Karnon J, Stahl J, Alan B, et al. Modeling using discrete event simulation: a report of the ISPOR-SMDM modeling good research practices task force working group 4. Value Health. 2012;15(6):821–7.PubMedCrossRef
17.
Antiretroviral Cohort Collaboration (ART-CC). Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression. JAIDS. 2009;52:357–63.
18.
Molina J-M, Podsadecki TJ, Johnson MA, Wilkin A, Domingo P, Myers R, et al. A lopinavir/ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks. AIDS Res Hum Retrovir. 2007;23(12):1505–14.PubMedCrossRef
19.
Murphy RL, da Silva BA, Hicks CB, Eron JJ, Gulick RM, Thompson MA, et al. Seven-year efficacy of a lopinavir/ritonavir-based regimen in antiretroviral-naive HIV-1-infected patients. HIV Clin Trials. 2008;9(1):1–10.PubMedCrossRef
20.
Gathe J, daSilva B, Loutfy M, et al. Study M05-730 primary efficacy results at week 48: phase 3, randomized, open-label study of lopinavir–ritonavir (LPV/r) tablets once-daily (OD) vs. twice-daily (BID), co-administered with tenofovir (TDF) plus emtricitabine (FTC) in antiretroviral naïve (ARV) HIV-1-infected subjects. In: 15th Conference on retroviruses and opportunistic infections (CROI), Boston, MA; 3–6 Feb 2008.
21.
22.
Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, D’Arminio Monforte A, et al. Cardiovascular disease risk factors in HIV patients—association with antiretroviral therapy. Results from the DAD study. AIDS. 2003;17(8):1179–93.PubMedCrossRef
23.
Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, Squier C, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133(1):21–30.PubMedCrossRef
24.
King MS, Brun SC, Kempf DJ. Relationship between adherence and the development of resistance in antiretroviral-naive, HIV-1-infected patients receiving lopinavir/ritonavir or nelfinavir. J Infect Dis. 2002;191(12):2046–52.CrossRef
25.
Mannheimer S, Friedland G, Matts J, Child C, Chesney M. The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis. 2002;34(8):1115–21.PubMedCrossRef
26.
Deeks SG, Barbour JD, Grant RM, Martin JN. Duration and predictors of CD4 T-cell gains in patients who continue combination therapy despite detectable plasma viremia. AIDS. 2002;16(2):201–7.PubMedCrossRef
27.
Gonzalez de Requena D, Bonora S, Garazzino S, Sciandra M, D’Avolio A, Raiteri R, et al. Nevirapine plasma exposure affects both durability of viral suppression and selection of nevirapine primary resistance mutations in a clinical setting. Antimicrob Agents Chemother. 2005;49(9):3966–9.PubMedCrossRef
28.
Nelson M, Girard PM, DeMasi R, et al. Adherence to darunavir/ritonavir and lopinavir/ritonavir in treatment-naïve, HIV-infected patients in ARTEMIS: 96 week data. In: 15th Annual conference of the British HIV Association, London; 8–9 Oct 2009.
29.
30.
Ghani AC, de Wolf F, Ferguson NM, Donnelly CA, Coutinho R, Miedema F, et al. Surrogate markers for disease progression in treated HIV infection. J Acquir Immune Defic Syndr. 2001;28(3):226–31.PubMed
31.
Ghani AC, Henley WE, Donnelly CA, Mayer S, Anderson RM. Comparison of the effectiveness of non-nucleoside reverse transcriptase inhibitor-containing and protease inhibitor-containing regimens using observational databases. AIDS. 2001;15(9):1133–42.PubMedCrossRef
32.
Gebo KA, Gallant JE, Keruly JC, Moore RD. Absolute CD4 vs. CD4 percentage for predicting the risk of opportunistic illness in HIV infection. J Acquir Immune Defic Syndr. 2004;36(5):1028–33.PubMedCrossRef
33.
Rahim S, Fredrick LM, da Silva BA, Bernstein B, King MS. Geographic and temporal trends of transmitted HIV-1 drug resistance among antiretroviral-naive subjects screening for two clinical trials in North America and Western Europe. HIV Clin Trials. 2009;10(2):94–103.PubMedCrossRef
34.
Hill A, Pulido F, Arribas J, Moecklinghoff C. Prevalence of IAS-USA PI mutations during episodes of viremia in the MONET trial of darunavir/ritonavir, with or without nucleoside analogues. In: 8th European HIV drug resistance workshop, 2010, Sorrento; 17–19 Mar 2010.
35.
Cahn P, Fourie J, Grinsztejn B, Hodder S, Molina J-M, Ruxrungtham K, et al. Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients. AIDS. 2011;25(7):929–39.PubMedCrossRef
36.
Ghosn J, Flandre P, Cohen-Codar I, Girard PM, Chaix ML, Raffi F, et al. Long-term (96-week) follow-up of antiretroviral-naive HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial. HIV Med. 2010;11(2):137–42.PubMedCrossRef
37.
Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991;121(1 Part 2):293–8.PubMedCrossRef
38.
39.
Andrulis DP, Weslowski VB, Hintz E, Spolarich AW. Comparisons of hospital care for patients with AIDS and other HIV-related conditions. JAMA. 1992;267(18):2482–6.PubMedCrossRef
40.
Caro JJ, Stillman IO, Danel A, Getsios D, McEwan P. Cost effectiveness of rimonabant use in patients at increased cardiometabolic risk: estimates from a Markov model. J Med Econ. 2007;10:239–54.CrossRef
41.
Huang JS, Becerra K, Fernandez S, Lee D, Mathews WC. The impact of HIV-associated lipodystrophy on healthcare utilization and costs. AIDS Res Ther. 2008;5:14.PubMedCrossRef
42.
US Bureau of Labor Statistics. Consumer price index, medical care. Washington, DC: US Bureau of Labor Statistics. Series Id: CUUR0000SAM2 Not Seasonally Adjusted. Area: U.S. city average. Item: Medical care services. Base Period: 1982-84=100. http://​data.​bls.​gov/​. Accessed 8 May 2011.
43.
44.
Moore RD, Chaisson RE. Cost-utility analysis of prophylactic treatment with oral ganciclovir for cytomegalovirus retinitis. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16(1):15–21.PubMedCrossRef
45.
Simpson KN, Dietz B, Baran RW, Garren KW, Riddler SA, Bhor M, et al. Economic modeling of the combined effects of HIV-disease, cholesterol and lipoatrophy based on ACTG 5142 trial data. Cost Eff Resour Alloc. 2011;9:5.PubMedCrossRef
46.
Bayoumi AM, Redelmeier DA. Preventing Mycobacterium avium complex in patients who are using protease inhibitors: a cost-effectiveness analysis. AIDS. 1998;12(12):1503–12.PubMedCrossRef
47.
Eddy DM, Hollingworth W, Caro JJ, et al. Model transparency and validation: a report of the ISPOR-SMDM modeling good research practices task force working group 7. Value Health. 2012;15:845–50.CrossRef
48.
Kaplan SS, Hicks CB. Safety and antiviral activity of lopinavir/ritonavir-based therapy in human immunodeficiency virus type 1 (HIV-1) infection. J Antimicrob Chemother. 2005;56(2):273–6.PubMedCrossRef
49.
Hicks C, King MS, Gulick RM, White AC, Eron JJ, Kessler HA, et al. Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 year follow-up study. AIDS. 2004;18(5):775–9.PubMedCrossRef
50.
Grosse SD. Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold. Expert Rev Pharmacoecon Outcomes Res. 2008;8(2):165–78.PubMedCrossRef
51.
Weinstein MC. How much are Americans willing to pay for a quality-adjusted life year? Med Care. 2008;46(4):343–5.PubMedCrossRef
52.
Briggs A, Weinstein M, Fenwick E, et al. Model parameter estimation and uncertainty: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-6. Value Health. 2012;32(5):722–32.
53.
Glick HA. Sampling uncertainty: what we are doing right and where we are going wrong. In: ISPOR western pharmacoeconomics conference, 2009, Pasadena, CA; 18–20 Mar 2009.
54.
Caro J, Briggs A, Siebert U, et al. Modeling good research practices—overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-1. Value Health. 2012;15(6):796–803.PubMedCrossRef
55.
Mocroft A, Lundgren JD. Starting highly active antiretroviral therapy: why, when and response to HAART. J Antimicrob Chemother. 2004;54(1):10–3.PubMedCrossRef
56.
Brogan AJ, Mrus J, Hill A, Sawyer AW, Smets E. Comparative cost-efficacy analysis of darunavir/ritonavir and other ritonavir-boosted protease inhibitors for first-line treatment of HIV-1 infection in the United States. HIV Clin Trials. 2010;11(3):133–44.PubMedCrossRef
57.
Mauskopf J, Brogan A, Martin S, Smets E. Cost effectiveness of darunavir/ritonavir in highly treatment-experienced, HIV-1-infected adults in the USA. Pharmacoeconomics. 2010;28(Suppl 1):83–105.PubMedCrossRef
58.
Moeremans K, Annemans L, Lothgren M, Allegri G, Wyffels V, Hemmet L, et al. Cost effectiveness of darunavir/ritonavir 600/100 mg bid in protease inhibitor-experienced, HIV-1-infected adults in Belgium, Italy, Sweden and the UK. Pharmacoeconomics. 2010;28(Suppl 1):107–28.PubMedCrossRef
59.
Moeremans K, Hemmett L, Hjelmgren J, Allegri G, Smets E. Cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment-experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults in Belgium, Italy, Sweden and the UK. Pharmacoeconomics. 2010;28(Suppl 1):147–67.PubMedCrossRef
60.
Siebert U, Alagoz O, Bayoumi AM, et al. State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-3. Value Health. 2012;15(6):812–20.PubMedCrossRef
61.
Roberts M, Russel L, Paltiel AD, et al. Conceptualizing a model: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-2. Value Health. 2012;15(6):804–11.PubMedCrossRef
62.
63.
Barros ZM, de Alencar Ximenes RA, Miranda-Filho DB, de Albuquerque MdFPM, Melo HRL, Carvalho EH, et al. Comparison between the Framingham and prospective cardiovascular of Munster scores for risk assessment of coronary heart disease in human immunodeficiency virus-positive patients in Pernambuco, Brazil. Metab Syndr Relat Disord. 2010;8(6):489–97.PubMedCrossRef
64.
Falcone EL, Mangili A, Skinner S, Alam A, Polak JF, Wanke CA. Framingham risk score and early markers of atherosclerosis in a cohort of adults infected with HIV. Antivir Ther. 2011;16(1):1–8.PubMedCrossRef
65.
Friis-Moller N, Thiebaut R, Reiss P, Weber R, Monforte ADA, De Wit S, 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(5):491–501.PubMedCrossRef
66.
Johnson M, Grinsztejn B, Rodriguez C, Coco J, DeJesus E, Lazzarin A, et al. 96-week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures. AIDS. 2006;20(5):711–8.PubMedCrossRef
67.
Madruga JV, Berger D, McMurchie M, Suter F, Banhegyi D, Ruxrungtham K, et al. Efficacy and safety of darunavir–ritonavir compared with that of lopinavir–ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet. 2007;370(9581):49–58.PubMedCrossRef
68.
Dragsted UB, et al. A phase IV randomised, open-label, multicentre trial to evaluate safety and efficacy of indinavir/ritonavir (800/100 mg BID) vs. saquinavir/ritonavir (1000/100 mg BID) in adult HIV-1 infection: the MaxCmin 1 trial. In: 8th ECCATH, Athens; 29–31 Oct 2001.
69.
Madruga JV, Cahn P, Grinsztejn B, Haubrich R, Lalezari J, Mills A, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007;370(9581):29–38.PubMedCrossRef
70.
Steigbigel RT, Cooper DA, Teppler H, Eron JJ, Gatell JM, Kumar PN, et al. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin Infect Dis. 2010;50(4):605–12.PubMedCrossRef
71.
72.
Hicks CB, Cahn P, Cooper DA, Walmsley SL, Katlama C, Clotet B, et al. Durable efficacy of tipranavir–ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet. 2006;368(9534):466–75.PubMedCrossRef
73.
Lalezari JP, Henry K, O’Hearn M, Montaner JSG, Piliero PJ, Trottier B, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348(22):2175–85.PubMedCrossRef
74.
Trotta MP, Cozzi-Lepri A, Ammassari A, Vecchiet J, Cassola G, Caramello P, et al. Rate of CD4+ cell count increase over periods of viral load suppression: relationship with the number of previous virological failures. Clin Infect Dis. 2010;51(4):456–64.PubMedCrossRef
75.
Simpson KN, Luo MP, Chumney E, Sun E, Brun S, Ashraf T. Cost-effectiveness of lopinavir/ritonavir versus nelfinavir as the first-line highly active antiretroviral therapy regimen for HIV infection. HIV Clin Trials. 2004;5(5):294–304.PubMedCrossRef
76.
Simpson K. Event data for South Carolina Medicaid patients from 2002 and 2003. Columbia: S.C. Budget and Control Board, Office of Research & Statistics; 2005.
77.
78.
Metadaten
Titel
Lopinavir/Ritonavir Versus Darunavir Plus Ritonavir for HIV Infection: A Cost-Effectiveness Analysis for the United States
verfasst von
Kit N. Simpson
Pamela P. Pei
Jörgen Möller
Robert W. Baran
Birgitta Dietz
William Woodward
Kristen Migliaccio-Walle
J. Jaime Caro
Publikationsdatum
01.05.2013
Verlag
Springer International Publishing AG
Erschienen in
PharmacoEconomics / Ausgabe 5/2013
Print ISSN: 1170-7690
Elektronische ISSN: 1179-2027
DOI
https://doi.org/10.1007/s40273-013-0048-3

Weitere Artikel der Ausgabe 5/2013

PharmacoEconomics 5/2013 Zur Ausgabe

Review Article

Optimal Global Value of Information Trials: Better Aligning Manufacturer and Decision Maker Interests and Enabling Feasible Risk Sharing

Editorial

How Much Should the NHS Pay for a QALY?

Commentary

Pharmacoeconomic Guidelines Should Prescribe Inclusion of Indirect Medical Costs! A Response to Grima et al.

Review Article

Rituximab for the First-Line Maintenance Treatment of Follicular Non-Hodgkin’s Lymphoma

Original Research Article

The Determinants of Cost-Effectiveness Potential: An Historical Perspective on Lipid-Lowering Therapies

Review Article

Golimumab for the Treatment of Ankylosing Spondylitis: A NICE Single Technology Appraisal