Select Committee on Health Minutes of Evidence


Memorandum by Alec Miners, Brunel University (SH 100)

  This is an "edited" and "updated" version of the discussion that accompanied an economic evaluation comparing treatment with highly active antiretroviral therapy with two nucleoside analogues (NA) [1].

  Since 1997, the mainstay of antiretroviral therapy for individuals in the UK infected with the human immunodeficiency virus (HIV) has been treatment with highly active antiretroviral therapy (HAART) which includes the addition of at least one protease inhibitor (PI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a third nucleoside analogue (NA) in combination with two NAs. This is based on evidence that HAART is more efficacious in reducing disease progression and mortality compared with two NAs alone [2-6]. However, ever increasing pressures on health care budgets has made it important for health care technologies not only to demonstrate their safety and efficacy but also to show that they are cost-effective.

  In this economic evaluation of HAART, cost-effectiveness was assessed using modelling techniques to combine information on treatment costs and disease progression for adults from observational data from English treatment centres. Assuming that the clinical effect of HAART lasts for five years, produced ICERs of £14,602 per life-year saved and £17,698 per QALY saved. Moreover, although the sensitivity analysis showed that the baseline ICER was particularly sensitive to variables such as the discount rate, by assuming continuous costs of HAART for the whole 20-year period despite but on average five-year treatment effects, a conservative estimate of the cost-effectiveness of HAART was produced. Using the Wessex Institute of Public Health Decision Matrix [7] which takes into account the size of the ICER and the quality of the information used in its construction to interpret these results, the use of HAART for adults compared with dual NA therapy is "recommended" on economic grounds.

  The ICER of £14,602 per life-year saved is higher than the ICERs produced by Cook et al. [8] of US$13,229 (approximately £8,500) per life-year saved and Reisbrough et al. [9] CAN$13,900 (approximately £8,200). Apart from the fact that these studies are set in different health care systems, in our study the costs of HAART were assumed to be continuous and independent of clinical effect. The study by Risebrough et al. also included estimates of the costs of salvage therapy and the indirect costs associated with HIV infection. If indirect costs were included in our analysis, cost-effectiveness is likely to increase because many individuals infected with HIV are likely to be of working age and treatment may help to reduce these indirect costs. Sendi et al. [10] estimated the incremental cost-effectiveness of HAART with at least one PI from a Swiss health services perspective to be 33,000 CHF (approximately £10,000) per life-year saved. However, for this Swiss study, the comparative treatment programme was "no treatment" which is unrealistic in an English setting. A more recent US economic evaluation by Freedberg et al. [11] reported the cost-effectiveness of HAART to be US$23,000 (approximately £15,000) per QALY gained. However, this study also compared the use of HAART with "no treatment".

  In conclusion, the results from this analysis suggest that HAART is, at the very least, a moderately cost-effective method of treating individuals infected with HIV compared with two NAs alone. However, reductions in the cost of HAART would dramatically increase cost-effectiveness and longer-term data on the relative effectiveness of HAART are required to fully substantiate these findings. Finally, whether treatment with an NNRTI as a third drug is more cost-effective than treatment with a PI and when treatment should be started, remains to be determined.

REFERENCES:

  1.  Miners AH, Sabin CA, Trueman P, Youle M, Mocroft A, Johnson M, and Beck EJ: Assessing the cost-effectiveness of HAART for adults with human immunodeficiency virus in England. HIV Medicine 2001, 2:52-58.

  2.  Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D, Richman DD, Valentine FT, Jonas L, Meibohm A, Emini EA, Chodakewitz, and JA: Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. New England Journal of Medicine 1997, 337:734-739.

  3.  Palella FJJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten, GA, Aschman DJ, and Holmberg SD: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. New England Journal of Medicine 1998, 338:853-860.

  4.  The AVANTI study group: AVANTI 2. Randomized, double-blind trial to evaluate the efficacy and safety of zidovudine plus lamivudine versus zidovudine plus lamivudine plus indinavir in HIV-infected antiretroviral-naive patients. AIDS 2000, 14:367-374.

  5.  Hirsch M, Steigbigel R, Staszewski S, Mellors J, Scerpella E, Hirschel B, Lange J, Squires K, Rawlins S, Meibohm A, and Leavitt R: A randomized, controlled trial of indinavir, zidovudine, and lamivudine in adults with advanced human immunodeficiency virus type 1 infection and prior antiretroviral therapy. Journal of Infectious Diseases 1999, 180:659-665.

  6.  Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJJ, Feinberg JE, Balfour HHJ, Deyton LR, Chodakewitz JA, and Fischl MA: 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. New England Journal of Medicine 1997, 337:725-733.

  7.  Stevens A, Colin-Jones D, and Gabbay J: "Quick and clean": authoritative health technology assessment for local health care contracting. Health Trends 1995, 27:37-42.

  8.  Cook J, Dasbach E, Coplan P, Markson L, Yin D, Meibohm A, Nguyen BY, Chodakewitz J, and Mellors J: Modeling the long-term outcomes and costs of HIV antiretroviral therapy using HIV RNA levels: application to a clinical trial. AIDS Research & Human Retroviruses 1999, 15:499-508.

  9.   Reisbrough, N., Oh, P., Rachlis, R., McMurchy, D., Bast, M., and Doswell, M. Economic evaluation of triple ART with indinavir or abacavir and ZDV+3TC compared to dual therapy ZDV+3TC. 6th Conference on Retroviruses and Opportunistic Infections, Chicago (Abstract 103); 1999.

  10.  Sendi PP, Bucher C, Harr T, Craig BA, Schweitert M, Pfluger D, Gafni A, Battegay M, and for the Swiss HIV Cohort Study: Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. AIDS 1999, 13:1115-1122.

  11.  Freedberg KA, Losina E, Weinstein MC, Paltiel AD, Cohen CJ, Seage GR, Craven DE, Zhang H, Kimmel AD, and Goldie SJ: The cost-effectiveness of combination antiretroviral therapy for HIV disease. New England Journal of Medicine 2001, 344:824-831.


 
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Prepared 2 September 2002