Disease Management and Health Outcomes

, Volume 10, Issue 2, pp 85–91 | Cite as

Clinical and Economic Implications of Non-Adherence to HAART in HIV Infection

  • Alissa Scalera
  • Ahmed M. Bayoumi
  • Paul Oh
  • Nancy Risebrough
  • Neil Shear
  • Alice Lin-in Tseng
Leading Article


Highly active antiretroviral therapy (HAART) has dramatically altered the natural history of HIV disease. Studies demonstrate that ≥95% adherence is necessary to garner the full benefits of HAART. However, appropriate adherence to treatment is difficult and challenging. This paper provides an overview of potential clinical and economic outcomes associated with poor adherence to HAART. Since there are no studies exploring the costs associated with poor adherence to HAART, we discuss potential direct and indirect costs accrued with more frequent treatment failures, selection of resistant strains, increased hospitalizations and a faster progression to AIDS associated with poor adherence to HAART. Additionally, we review studies of interventions and strategies to improve adherence to HAART. Although, single-focus interventions have enhanced the chances of achieving viral suppression by 10 to 23%, the literature has demonstrated that for long-term treatments, programs employing diverse interventions that continue over time are more effective. Under constrained healthcare budgets, government, healthcare managers and policy makers require accurate and timely information concerning the cost effectiveness of adherence intervention programs. We discuss considerations in determining the cost effectiveness of an adherence intervention program.



The authors have stated that there was no conflict of interest related to the contents of this paper and there was no funding to assist with the preparation of this study.


  1. 1.
    Panel on Clinical Practices for Treatment of HIV Infection: Department of Health and Human Services (DHHS) and the Henry J. Kaiser Family Foundation. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. HIV/AIDS Treatment Information Service 2001 Aug 13: In press.Google Scholar
  2. 2.
    Hammer SM, Katzenstein DA, Hughes MD, et al. 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(15): 1081–90.PubMedCrossRefGoogle Scholar
  3. 3.
    Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 1997; 337(11): 734–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Palella FJ, Delaney KM, Moorman A, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338(13): 853–60.PubMedCrossRefGoogle Scholar
  5. 5.
    Tseng AL-I. Compliance issues in the treatment of HIV infection. Am J Health Syst Pharm 1998; 55(17): 1817–24.PubMedGoogle Scholar
  6. 6.
    Probstfield JL. Clinical trial prerandomization compliance (adherence) screen. In: Cramer JA, Spilker B, editors. Patient compliance in medical practice and clinical trials. New York: Raven Press, 1991: 323–33.Google Scholar
  7. 7.
    Lerner BH, Gulick RM, Dubler NN. Rethinking nonadherence: historical perspectives on triple-drug therapy for HIV disease. Ann Intern Med 1998; 129(7): 573–8.PubMedGoogle Scholar
  8. 8.
    Andrews L, Friedland G. Progress in HIV therapeutics and the challenges of adherence to antiretroviral therapy. Infect Dis Clin North Am 2000; 14(4): 901–28.PubMedCrossRefGoogle Scholar
  9. 9.
    Melbourne KM, Geletko SM, Brown SL, et al. Medication adherence in patients with HIV infection: a comparison of two measurement methods. AIDS Read 1999; 9(5): 329–38.PubMedGoogle Scholar
  10. 10.
    Murri R, Ammassari A, De Luca A, et al. Definition and measurement of adherence to antiretroviral drugs in HIV-1-infected patients. Lancet 1999; 353: 1974.PubMedCrossRefGoogle Scholar
  11. 11.
    Ostrop NJ, Hallett KA, Gill MJ. Long-term patient adherence to antiretroviral therapy. Ann Pharmacother 2000; 34: 703–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Chesney MA, Ickovics JR, Chambers DB, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. AIDS Care 2000; 12(3): 255–66.PubMedCrossRefGoogle Scholar
  13. 13.
    Gifford A, Bormann JE, Shively MJ, et al. Predictors of self-reported adherence and plasma HIV concentrations in patients on multidrug antiretroviral regimens. J Acquir Immune Defic Syndr 2000; 23: 386–95.PubMedGoogle Scholar
  14. 14.
    Kleeberger CA, Phair JP, Starthdee SA, et al. Determinants of heterogenous adherence to HIV-antiretroviral therapies in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 2001; 26(1): 82–92.PubMedGoogle Scholar
  15. 15.
    Stone VE, Adelson-Mitty J, Duefield CA, et al. Adherence to protease inhibitor (PI) therapy in clinical practice: usefulness of demographics, attitudes and knowledge as predictors. In: 12th International Conference on AIDS 1998: Geneva, Switzerland; 1998 Jun 28–Jul 3.Google Scholar
  16. 16.
    Paiva V, Santos N, Ventura-Filipe EM, et al. Compliance with reverse transcriptase inhibitors or combination therapy among HIV+ women in Sao Paulo, Brazil. In: 38th International Conference on Antimicrobial Agents and Chemotherapy 1998: San Francisco, CA; 1998 Sep 24–27.Google Scholar
  17. 17.
    Tuldra A, Ferrer MJ, Rodriguez C, et al. A proposed model to predict compliance with antiretroviral therapy. In: 12th International Conference on AIDS 1998: Geneva, Switzerland; 1998 Jun 28–Jul 3.Google Scholar
  18. 18.
    Chesney MA. Factors affecting adherence to antiretroviral therapy. Clin Infect Dis 2000; 30 Suppl 2: S171–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Stein MD, Rich JD, Maksad J, et al. Adherence to antiretroviral therapy among HIV-infected methadone patients: effects of ongoing illicit drug use. Am J Drug Alcohol Abuse 2000; 26(2): 195–205.PubMedCrossRefGoogle Scholar
  20. 20.
    Vanhove GF, Schapiro JM, Winters MA, et al. Patient compliance and drug failure in protease inhibitor monotherapy. JAMA 1996; 276(24): 1955–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Hecht FM, Colfax G, Swanson M, et al. Adherence and effectiveness of protease inhibitors in clinical practice. In: 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5; Chicago, Ill; 1998.Google Scholar
  22. 22.
    Raboud JM, Rae S, Vella S, et al. Meta-analyses of two randomized controlled trials comparing combined zidovudine and didanosine therapy with combined zidovudine, didanosine, and neverapine therapy in patients with HIV. J Aquir Immune Defic Syndr 1999; 22(3): 260–6.Google Scholar
  23. 23.
    Haubrich RH, Little SJ, Currier JS, et al. The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. AIDS 1999; 13(9): 1099–107.PubMedCrossRefGoogle Scholar
  24. 24.
    Paterson PL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21–30.PubMedGoogle Scholar
  25. 25.
    Hirsch MS, Conway B, D’Aquila RT, et al. Antiretroviral drug resistance testing in adults with HIV infection. Implication for clinical management. JAMA 1998; 279(24): 1984–91.PubMedCrossRefGoogle Scholar
  26. 26.
    Kuritzkes D. Managing drug resistance. Medscape HIV/AIDS 1999: 5 (Supplement).Google Scholar
  27. 27.
    Kempf DJ, Rode RA, Xu Y, et al. The duration of viral suppression during protease inhibitor therapy for HIV-1 infection is predicted by plasma HIV-1 RNA at the nadir. AIDS 1998; 12(5): F9–14.PubMedCrossRefGoogle Scholar
  28. 28.
    Hodinka RL. What clinicians need to know about antietroviral drugs and viral resistance. Infect Dis Clin North Am 1997; 11(4): 945–67.PubMedCrossRefGoogle Scholar
  29. 29.
    Yerly S, Kaiser L, Perneger TV, et al. Time of initiation of antiretroviral therapy: impact on HIV-1 viraemia. AIDS 2000; 14(3): 243–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Boden D, Hurley A, Zhang L, et al. HIV-1 drug resistance in newly infected individuals. JAMA 1999; 282(12): 1135–41.PubMedCrossRefGoogle Scholar
  31. 31.
    Bangsberg DR, Perry S, Charlebois ED, et al. Adherence to HAART predicts progression to AIDS. In: 8th Conference on Retroviruses and Opportunistic Infections 2001: Chicago, Ill; 2001 Feb 4–8.Google Scholar
  32. 32.
    Mannheimer S, Friedland G, Matts J, et al. Antiretroviral adherence correlates with quality of life. In: 8th Conference on Retroviruses and Opportunistic Infections 2001: Chicago, Ill; 2001 Feb 4–8.Google Scholar
  33. 33.
    Rudd P. In search of the gold standard for compliance measurement. Arch Intern Med 1979; 139(6): 627–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Cramer JA. Overview of methods to measure and enhance patient compliance. In: Spiker B, editor. Patient compliance in medical practice and clinical trials. New York: Raven Press, 1991: 3–10.Google Scholar
  35. 35.
    Bond WS, Hussar DA. Detection methods and strategies for improving medication compliance. Am J Hosp Pharm 1991; 48(9): 1978–88.PubMedGoogle Scholar
  36. 36.
    Stansell J, Barrett J, DeGuzman C, et al. Incremental costs of HIV suppression in HIV therapeutic failure. In: 7th Conference on Retroviruses and Opportunistic Infections 2000: San Francisco, CA; 2000 Jan 30–Feb 2.Google Scholar
  37. 37.
    Rodriguez-Rosado R, Jimenez-Nacher I, Soriano V, et al. Virological failure and adherence to antiretroviral therapy in HIV-infected patients. AIDS 1998; 12(9): 1112–3.PubMedGoogle Scholar
  38. 38.
    Haynes RB, Taylor W, Sackett DL, et al. Can simple clinical measurements detect patient noncompliance? Hypertension 1980; 2(6): 757–64.PubMedCrossRefGoogle Scholar
  39. 39.
    Mullins CD, Whitelaw G, Cooke JL, et al. Indirectcost of HIV infection in England. Clin Ther 2000; 22(11): 1333–45.PubMedCrossRefGoogle Scholar
  40. 40.
    Tuldra A, Fumaz CR, Ferrer MJ, et al. Prospective randomized two-arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000; 25(3): 221–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Knobel H, Carmona A, Lopez JL, et al. Adherence to highly active antiretroviral treatment: impact of individualized assessment [in Spanish]. Enferm Infec Microbiol Clin 1999; 17: 78–81.Google Scholar
  42. 42.
    Haddad M, Inch C, Glazier RH, et al. Patient support and education for adherence to highly active antiretroviral therapy in people living with HIV/AIDS (Cochrane Review). Available in The Cochrane Library. Oxford: Updated Software, 2001.Google Scholar
  43. 43.
    Mannheimer S, Hirsch Y, El-Sadr W. The impact of the ALR alarm device on antiretroviral (AR) adherence among HIV-infected outpatients in Harlem. In: 12th International Conference on AIDS 1998: 1998 Jun 28–Jul 3.Google Scholar
  44. 44.
    Stenzel M, McKenzie M, Flanigan T, et al. A pilot program of modified directly observed therapy (MDOT) to enhance adherence to highly active antiretroviral therapy (HAART): 6-month follow-up. In: 38th International Conference on Antimicrobial Agents and Chemotherapy 1999: San Francisco, California; 1998 Sep 24–27.Google Scholar
  45. 45.
    Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient compliance. A meta-analysis. Med Care 1998; 36(8): 1138–61.Google Scholar
  46. 46.
    Detsky AS, Naglie IG. Aclinician’s guide to cost-effectiveness analysis. Ann Intern Med 1990; 113(2): 147–53.PubMedGoogle Scholar
  47. 47.
    Drummond MF, O’Brien B, Stoddart GL, et al. Methods for economic evaluation of health care programmes. 2nd ed. New York: Oxford University Press, 1998.Google Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Alissa Scalera
    • 1
    • 2
    • 3
    • 9
  • Ahmed M. Bayoumi
    • 3
    • 4
    • 5
  • Paul Oh
    • 6
  • Nancy Risebrough
    • 6
  • Neil Shear
    • 2
  • Alice Lin-in Tseng
    • 7
    • 8
  1. 1.Neurobehavioral Research, Mental Health ServiceSt Michael’s HospitalTorontoCanada
  2. 2.Department of Pharmacology, Faculty of MedicineUniversity of TorontoTorontoCanada
  3. 3.Inner City Health Research UnitSt. Michael’s HospitalTorontoCanada
  4. 4.Department of Medicine, Faculty of MedicineUniversity of TorontoTorontoCanada
  5. 5.Ontario HIV Treatment NetworkTorontoCanada
  6. 6.HOPE Research CentreSunnybrook and Women’s College Health Science CenterTorontoCanada
  7. 7.Immunodeficiency ClinicToronto General HospitalTorontoCanada
  8. 8.Faculty of PharmacyUniversity of TorontoTorontoCanada
  9. 9.Department of PharmacologyUniversity of TorontoCanada

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