Economic modeling of the combined effects of HIV-disease, cholesterol and lipoatrophy based on ACTG 5142 trial data

Kit N Simpson, Birgitta Dietz, Robert W Baran, Kevin W Garren, Sharon A Riddler, Menaka Bhor, Richard H Haubrich, Kit N Simpson, Birgitta Dietz, Robert W Baran, Kevin W Garren, Sharon A Riddler, Menaka Bhor, Richard H Haubrich

Abstract

Background: This study examines the cost and consequences of initiating an ARV regimen including Lopinavir/ritonavir (LPV/r) or Efavirenz (EFV), using data from a recent clinical trial in a previously published model of HIV-disease.

Methods: We populated the Markov model of HIV-disease with data from ACTG 5142 study to estimate the economic outcomes of starting ARV therapy with a PI-containing regimen as compared to an NNRTI-containing regimen, given their virologic and immunologic efficacy and effects on cholesterol and lipoatrophy. CNS toxicities and GI tolerability were not included in the model because of their transient nature or low cost remedies, and therefore lack of economic impact. CD4+ T-cell counts and the HIV-1 RNA (viral load) values from the study were used to assign a specific health state (HS) to each patient for each quarter year. The resulting frequencies used as "raw" data directly into the model obviate the reliance on statistical tests, and allow the model to reflect actual patient behavior in the clinical trial. An HS just below the last observed HS was used to replace a missing value.

Results: The modeled estimates (undiscounted) for the LPV/r-based regimen resulted in 1.41 quality-adjusted life months (QALMs) gained over a lifetime compared to the EFV-based regimen. The LPV/r-based regimen incurred $7,458 (1.8%) greater cost over a lifetime due to differences in drug costs and survival. The incremental cost effectiveness ratio using the discounted cost and QALYs was $88,829/QALY. Most of the higher costs accrue before the 7th year of treatment and were offset by subsequent savings. The estimates are highly sensitive to the effect of lipoatrophy on Health-related Quality of Life (HRQOL), but not to the effect of cholesterol levels.

Conclusions: The cost effectiveness of ARV regimens may be strongly affected by enduring AEs, such as lipoatrophy. It is important to consider specific AE effects from all drugs in a regimen when ARVs are compared.

Trial registration: (ClinicalTrials.gov number, NCT00050895http://[ClinicalTrials.gov]).

Figures

Figure 1
Figure 1
Model Structure.
Figure 2
Figure 2
Effects of Sensitivity Analysis on the Incremental Cost Effectiveness Ratio Estimates for the Model.

References

    1. Palella FJ Jr, Delaney KM, Moorman AC. et al.Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853–60. doi: 10.1056/NEJM199803263381301.
    1. Hogg RS, Yip B, Kully C. et al.Improved survival among HIV-infected patients after initiation of triple-drug antiretroviral regimens. CMAJ. 1999;160:659–65.
    1. Arici C, Ripamonti D, Ravasio V. et al.Long-term clinical benefit after highly active antiretroviral therapy in advanced HIV-1 infection, even in patients without immune reconstitution. Int J STD AIDS. 2001;12:573–81. doi: 10.1258/0956462011923741.
    1. Carpenter CC, Fischl MA, Hammer SM. et al.Antiretroviral therapy for HIV infection in 1996. Recommendations of an international panel. International AIDS Society-USA. JAMA. 1996;276:146–54. doi: 10.1001/jama.276.2.146.
    1. Carpenter CC, Cooper DA, Fischl MA. et al.Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2000;283:381–90. doi: 10.1001/jama.283.3.381.
    1. Hammer SM, Saag MS, Schechter M. et al.Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA Panel. JAMA. 2006;296:827–43. doi: 10.1001/jama.296.7.827.
    1. Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2009. 12-26-09.
    1. Yeni PG, Hammer SM, Hirsch MS. et al.Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel. JAMA. 2004;292:251–265. doi: 10.1001/jama.292.2.251.
    1. Gulick RM, Ribaudo HJ, Shikuma CM. et al.Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA. 2006;296(7):769–81. doi: 10.1001/jama.296.7.769.
    1. Gallant JE, Staszewski S, Pozniak AL. et al.Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naïve patients: a 3-year randomized trial. JAMA. 2004;292(2):191–201. doi: 10.1001/jama.292.2.191.
    1. Staszewski S, Morales-Ramirez J, Tashima KT. et al.Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med. 1999;341(25):1865–73. doi: 10.1056/NEJM199912163412501.
    1. Riddler SA, Haubrich R, DiRienzo AG, Peeples L, Powderly WG, Klingman KL, Garren KW, George T, Rooney JF, Brizz B, Lalloo UG, Murphy RL, Swindells S, Havlir D, Mellors JW. AIDS Clinical Trials Group Study A5142 Team. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008;358(20):2095–106. doi: 10.1056/NEJMoa074609.
    1. Squires K, Lazzarin A, Gatell JM. et al.Comparison of Once-Daily Atazanavir With Efavirenz, Each in Combination With Fixed- Dose Zidovudine and Lamivudine, As Initial Therapy for Patients Infected With HIV. J Acquir Immune Defic Syndr. 2004;36(5):1011–9. doi: 10.1097/00126334-200408150-00003.
    1. Walmsley S, Bernstein B, King M. et al.Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med. 2002;346:2039–46. doi: 10.1056/NEJMoa012354.
    1. Nachman SA, Stanley K, Yogev R. et al.Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team. JAMA. 2000;283:492–8. doi: 10.1001/jama.283.4.492.
    1. Eron J Jr, Yeni P, Gathe J Jr. et al.The KLEAN study of fosamprenavirritonavir versus lopinavir-ritonavir, each in combination with abacavirlamivudine for initial treatment of HIV infection over 48 weeks: a randomized non-inferiority trial. Lancet. 2006;368:476–82. doi: 10.1016/S0140-6736(06)69155-1.
    1. Wood E, Hogg RS, Yip B, Moore D, Harrigan PR, Montaner JS. Superior virological response to boosted protease inhibitor-based highly active antiretroviral therapy in an observational treatment programme. HIV Med. 2007;8:80–5. doi: 10.1111/j.1468-1293.2007.00430.x.
    1. Lima VD, Hogg RS, Harrigan PR. et al.Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS. 2007;21:685–92. doi: 10.1097/QAD.0b013e32802ef30c.
    1. Barreiro P, Soriano V, Casas E, Gonzalez-Lahoz J. Different degree of immune recovery using antirretroviral regimens with protease inhibitors or non-nucleosides. AIDS. 2002;16:245–249. doi: 10.1097/00002030-200201250-00014.
    1. Yasdanpanah Y, Sissoko D, Egger M. et al.Clinical efficacy of antiretroviral combination therapy based on protease inhibitors or non-nucleoside analogue reverse transcriptase inhibitors: indirect comparison of controlled trials. BMJ. 2004;328:249–256. doi: 10.1136/bmj.37995.435787.A6.
    1. Simpson KN, Jones WJ, Rajagopalan R, Dietz B. Cost-effectiveness of lopinavir/ritonavir compared to atazanavir plus ritonavir in antiretroviral-experienced patients in the U.S.: Modeling the combined effects of HIV and Heart Disease. Clin Drug Invest. 2007;27(7):443–452. doi: 10.2165/00044011-200727070-00001.
    1. Haubrich R, Riddler S, DiRienzo G, AIDS. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles; 2007. Metabolic outcomes of ACTG 5142: A prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection. in press Abstract 38.
    1. Simpson KN, Roberts G, Hicks CB, Finnern HW. Cost-effectiveness of Tipranavir in Treatment Experienced HIV Patients in the US. HIV Clinical Trials. 2008;9(4):225–37. doi: 10.1310/hct0904-225.
    1. Simpson KN, Luo MP, Chumney ECG, Sun E, Brun S, Ashraf T. Cost effectiveness of using lopinavir vs. nelfinavir as the first highly active antiretroviral therapy regimen for HIV infection. HIV Clinical Trials. 2004;5(5):294–304. doi: 10.1310/WT81-MEM4-5C4L-CHPK.
    1. Simpson KN, Strassburger A, Jones WJ, Dietz B, Rajagopalan R. Comparison of Markov Model and Discrete Event Simulation (DES) Techniques for HIV Disease. PharmacoEconomics. 2009;27(2):159–165. doi: 10.2165/00019053-200927020-00006.
    1. Dolan P. Modeling valuations for EuroQoL health states. Med Care. 1998;35:1095–108.
    1. Mrus JM, Yi MS, Freedberg KA. et al.Utilities derived from visual analog scores in patients with HIV/AIDS. Med Decision Making. 2003;23(5):414–421. doi: 10.1177/0272989X03256884.
    1. Hornberger J, Shewade A, Loutfy MR, Rajagopalan R. Cost consequences of HIV-associated lipoatrophy. AIDS Care.
    1. Simpson KN. Unpublished Medicaid costs data for South Carolina, USA. 2002.
    1. Castiel D, Herve C, Gaillard M. et al.Cost-utility analysis of early thrombolytic therapy. PharmacoEconomics. 1992;1(6):438–42. doi: 10.2165/00019053-199201060-00004.
    1. Fleming T. Red Book: Pharmacy's Fundamental reference. Montvale, PDR Network; 2007.
    1. Swindells S, Jiang H, Mukherjee L, 16th Conference on Retroviruses and Opportunistic Infections (CROI) Montreal, Canada; 2009. AIDS Clinical Trials Group. Virologic Drug Resistance Is Not Associated with AIDS-defining Events or Mortality: An ACTG Longitudindal Linked Randomized Trials Analysis. abstract 659.
    1. WHO. Cost-effectiveness thresholds. 2008.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi