Skip to main content

Modelling the Cost Effectiveness of Lamivudine/Zidovudine Combination Therapy in HIV Infection

Summary

The use of combination antiretroviral therapy is supported by clinical evidence for its superiority over monotherapy. Lamivudine (3TC) has been studied in combination with zidovudine (ZDV) and is recommended for use specifically in combination therapy. With the associated increase in drug acquisition cost, the economics of combination therapy versus monotherapy warrant study. An economic evaluation was undertaken to compare 3TC/ZDV combination therapy with ZDV monotherapy, taking a UK public finance perspective.

The cost effectiveness of each of the 2 treatments was estimated using a Markov model of progression through 3 HIV-positive disease states: (i) CD4 cells >200 and <500 cells/mm3; (ii) CD4 <200 cells/mm3, non-AIDS; and (iii) AIDS to eventual death. Progression probabilities and life expectancy were derived from a cohort treated at Chelsea and Westminster Hospital in London, using data for 1987 to 1995, along with cost data for a ZDV intent-to-treat population for 1994 and 1995. The relative risk of progression for 3TC/ZDV compared with ZDV monotherapy was estimated from meta-analysis of 4 completed comparative trials. To predict the effect of 3TC/ZDV on life expectancy and lifetime costs, progression probabilities were adjusted by the relative risk statistic for the duration of treatment with 3TC/ZDV

On the basis of an estimated relative risk of progression of 0.509 (95% CI 0.365 to 0.710), treatment with 3TC/ZDV is predicted to yield an incremental cost-effectiveness ratio of £6276 (95% CI £5337 to £9075) per life year saved (discounted at 6% per year). Extensive sensitivity analyses were performed to test the effects of varying values of input parameters on the model results. Under reasonable assumptions, the predicted cost effectiveness of 3TC/ZDV combination therapy compares favourably with previously reported economic analyses of various HIV treatments.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Hammer S, Katzenstein D, Hughes M, et al., for the ACTG 175 Study Team. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. N Engl J Med 1996; 335: 1081–1090

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Delta Co-ordinating Committee. Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Lancet 1996; 348: 283–91

    Article  Google Scholar 

  3. 3.

    Montaner J, Cooper D, Katlama C, et al., for the CAESAR Coordinating Committee. The CAESAR trial: final results [abstract 367]. 4th Conference on Retroviruses and Opportunistic Infections; 1997 Jan 22–26; Washington, D.C., 132

    Google Scholar 

  4. 4.

    Saravolatz L, Collins G, Hodges J, et al. Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. N Engl J Med 1996; 335: 1099–1106

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    EPIVIR Summary of Product Characteristics. UK: Glaxo Wellcome UK Limited, 1996

  6. 6.

    Schulman KA, Lynn LA, Glick HA, et al. Cost-effectiveness of low-dose zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection. Ann Intern Med 1991; 114: 798–802

    PubMed  CAS  Google Scholar 

  7. 7.

    Simpson K, Hatziandreu EJ, Andersson F, et al. Cost effectiveness of antiviral treatment with zalcitabine plus zidovudine for AIDS patients with CD4+ counts less than 300/μl in 5 European countries. Pharmacoeconomics 1994; 6: 553–62

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Beck JR, Pauker SG. The Markov process in medical prognosis. Med Decis Making 1983; 3 (4): 419–58

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Longini IM, Clark WS, Gardner LI, et al. The dynamics of CD4+ T-lymphocyte decline in HIV-infected individuals: a Markov modeling approach. J Acquir Immune Defic Syndr 1991; 4: 1141–7

    PubMed  Google Scholar 

  10. 10.

    Oddone EZ, Cowper P, Hamilton JD, et al. Cost effectiveness analysis of early zidovudine treatment of HIV infected patients. BMJ 1993; 307: 1322–5

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Beck EJ, Kennelly J, McKevitt C, et al. Changing use of hospital services and costs at a London AIDS referral centre, 1983–89. AIDS 1994; 8: 367–77

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Petrou S, Dooley M, Whitaker L, et al. Cost and utilisation of community services for people with HIV infection in London. Health Trends 1995; 27 (2): 62–8

    PubMed  CAS  Google Scholar 

  13. 13.

    Holmberg SD, Buchbinder SP, Conley LJ, et al. The spectrum of medical conditions and symptoms before acquired immunodeficiency syndrome in homosexual and bisexual men infected with the human immunodeficiency virus. Am J Epidemiol 1995; 141 (5): 395–406

    PubMed  CAS  Google Scholar 

  14. 14.

    Gable CB, Tierce JC, Simison D, et al. Costs of HIV+/AIDS at CD4+ counts disease stages based on treatment protocols. J Acquir Immune Defic Syndr 1996; 12: 413–20

    Article  CAS  Google Scholar 

  15. 15.

    Phillips AN, Lee CA, Elford J, et al. The cumulative risk of AIDS as the CD4 lymphocyte count declines. J Acquir Immune Defic Syndr 1992; 5: 148–52

    PubMed  CAS  Google Scholar 

  16. 16.

    Eron JJ, Benoit SL, Jemsek JJ, et al. Treatment with lamivudine, zidovudine or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. N Engl J Med 1995; 333: 1662–9

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Katlama C, Ingrand D, Loveday C, et al. Safety and efficacy of lamivudine (3TC)/zidovudine (ZDV) combination in anti-retroviral-naive (<4 weeks prior ZDV therapy) HIV-1 infected patients: a comparison with zidovudine monotherapy. JAMA 1996; 276: 118–25

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Bartlett J, Benoit SL, Johnson V, et al. The safety and efficacy of lamivudine plus zidovudine compared with zalcitabine plus zidovudine in the treatment of zidovudine-experienced HIV-infected patients. Ann Intern Med 1996; 125: 161–172

    PubMed  CAS  Google Scholar 

  19. 19.

    Eron JJ, Bartlett JA, Johnson J, et al. Prolonged immunologic and virologic effects of 3TC and zidovudine in subjects who remained on blinded combination therapy beyond 52 weeks in two North American clinical trials [abstract OP7.6]. In: 3rd International Congress on Drug Therapy in HIV Infection; 1996 Nov 3–7; Birmingham. AIDS 1996 Nov; 10 (Suppl. 2): S16

    Google Scholar 

  20. 20.

    Staszewski S, Hill AM, Bartlett JA, et al. Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: a meta-analysis of controlled trials. AIDS 1997; 11: 477–83

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Staszewski S, Loveday C, Picazo JJ, et al. Safety and efficacy of lamivudine (3TC)/zidovudine (ZDV) combination in zidovudine experienced HIV-1 infected patients: a comparison with zidovudine monotherapy. JAMA 1996; 276: 111–7

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Petrou S, Dooley M, Whitaker L, et al. The economic costs of caring for people with HIV infection and AIDS in England and Wales. Pharmacoeconomics 1996; 9 (4): 332–40

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Simpson KN, LaVallee RL. Antiviral drug cost offsets in seven developed countries: saquinavir, zalcitabine and zidovudine [abstract OP6.6]. In: 3rd International Congress on Drug Therapy in HIV Infection; 1996 Nov 3–7; Birmingham. AIDS 1996 Nov; 10 (Suppl. 2): S15

    Google Scholar 

  24. 24.

    Moore RD, Hidalgo J, Bareta JC, et al. Zidovudine therapy and health resource utilization in AIDS. J Acquir Immune Defic Syndr 1994; 7: 349–54

    PubMed  CAS  Google Scholar 

  25. 25.

    Phillips AN, Davey Smith G, Johnson M. Will we ever know when to treat HIV infection? BMJ 1996; 313: 608–10

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Drummond MF, Stoddart GL, Torrance GW. Methods for the evaluation of health care programmes. Oxford: Oxford University Press, 1987

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jeremy V. Chancellor.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chancellor, J.V., Hill, A.M., Sabin, C.A. et al. Modelling the Cost Effectiveness of Lamivudine/Zidovudine Combination Therapy in HIV Infection. Pharmacoeconomics 12, 54–66 (1997). https://doi.org/10.2165/00019053-199712010-00006

Download citation

Keywords

  • Human Immunodeficiency Virus
  • Discount Rate
  • Human Immunodeficiency Virus Infection
  • Lamivudine
  • Zidovudine