Journal of General Internal Medicine

, Volume 17, Issue 10, pp 756–765 | Cite as

A prospective study of predictors of adherence to combination antiretroviral medication

  • Carol E. Golin
  • Honghu Liu
  • Ron D. Hays
  • Loren G. Miller
  • C. Keith Beck
  • Jeanette Ickovics
  • Andrew H. Kaplan
  • Neil S. Wenger
Original Articles

Abstract

OBJECTIVE: Adherence to complex antiretroviral therapy (ART) is critical for HIV treatment but difficult to achieve. The development of interventions to improve adherence requires detailed information regarding barriers to adherence. However, short follow-up and inadequate adherence measures have hampered such determinations. We sought to assess predictors of long-term (up to 1 year) adherence to newly initiated combination ART using an accurate, objective adherence measure.

DESIGN: A prospective cohort study of 140 HIV-infected patients at a county hospital HIV clinic during the year following initiation of a new highly active ART regimen.

MEASURES AND MAIN RESULTS: We measured adherence every 4 weeks, computing a composite score from electronic medication bottle caps, pill count and self-report. We evaluated patient demographic, biomedical, and psychosocial characteristics, features of the regimen, and relationship with one’s HIV provider as predictors of adherence over 48 weeks. On average, subjects took 71% of prescribed doses with over 95% of patients achieving suboptimal (<95%) adherence. In multivariate analyses, African-American ethnicity, lower income and education, alcohol use, higher dose frequency, and fewer adherence aids (e.g., pillboxes, timers) were independently associated with worse adherence. After adjusting for demographic and clinical factors, those actively using drugs took 59% of doses versus 72% for nonusers, and those drinking alcohol took 66% of doses versus 74% for nondrinkers. Patients with more antiretroviral doses per day adhered less well. Participants using no adherence aids took 68% of doses versus 76% for those in the upper quartile of number of adherence aids used.

CONCLUSIONS: Nearly all patients’ adherence levels were suboptimal, demonstrating the critical need for programs to assist patients with medication taking. Interventions that assess and treat substance abuse and incorporate adherence aids may be particularly helpful and warrant further study.

Key words

adherence antiretroviral medication compliance HIV 

References

  1. 1.
    Markowitz M, Saag M, Powderly WG, et al. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med. 1995;333:1534–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Danner SA, Carr A, Leonard JM, et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group. N Engl J Med. 1995;333:1528–33.PubMedCrossRefGoogle Scholar
  3. 3.
    Collier AC, Coombs RW, Schoenfeld DA, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine and zalcitabine. N Engl J Med. 1996;334:1011–7.PubMedCrossRefGoogle Scholar
  4. 4.
    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;337:734–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Mathez D, Truchis P, Gorin I, et al. Ritonavir, AZT, DDC, as a triple combination in AIDS patients. Presented at the Third Conference on Retroviruses and Opportunistic Infection, Washington, DC, February 1, 1996.Google Scholar
  6. 6.
    Gulick RM, Mellors JW, Havlir D, et al. Simultaneous vs.sequential initiation of therapy with indinavir, zidovudine, and lamivudine for HIV-1 infection: 100-week follow-up. JAMA. 1998;280:35–41.PubMedCrossRefGoogle Scholar
  7. 7.
    Paterson L, 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
  8. 8.
    Bangsberg DR, Hecht FM, Charlebois ED, et al. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS. 2000;14:357–66.PubMedCrossRefGoogle Scholar
  9. 9.
    Bangsberg DR, Perry S, Charlebois E, Clark R, Robertson M, Moss AR. Adherence to HAART predicts progression to AIDS. AIDS. 2001;15:1181–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Montessori V, Heath B, Yip R, et al. Predictors of adherence with triple combination antiretroviral therapy. Presented at the Seventh Conference on Retroviruses and Opportunistic Infection, January 30–February 2, 2000.Google Scholar
  11. 11.
    Carpenter CJ, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society—USA Panel. JAMA. 1998;280:78–86.PubMedCrossRefGoogle Scholar
  12. 12.
    Reichman LB. Compliance with zidovudine therapy. Ann Intern Med. 1990;113:332–3.PubMedGoogle Scholar
  13. 13.
    Chow R, Chin T, Fong IW, Bendayan R. Medication use patterns in HIV-positive patients. Can J Hosp Pharm. 1993;46:171–5.PubMedGoogle Scholar
  14. 14.
    Nobel H, Carmona A, Grau S, Pedro-Botet J, Diez A. Adherence and effectiveness of highly active antiretroviral therapy. Arch Intern Med. 1998;158:1953.CrossRefGoogle Scholar
  15. 15.
    Condra JH, Schleif WA, Blahy OM, et al. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature. 1995;374:569–71.PubMedCrossRefGoogle Scholar
  16. 16.
    el-Farrash MA, Kuroda MJ, Kitazaki T, et al. Generation and characterization of a human immunodeficiency virus type 1 (HIV-1) mutant resistant to an HIV-1 protease inhibitor. J Virol. 1994;68:233–9.PubMedGoogle Scholar
  17. 17.
    Ho DD, Toyoshima T, Mo H, et al. Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor. J Virol. 1994;68:2016–20.PubMedGoogle Scholar
  18. 18.
    Jacobsen H, Yasargil K, Winslow DL, et al. Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959. Virology. 1995;206:527–34.PubMedCrossRefGoogle Scholar
  19. 19.
    Kaplan AH, Michael SF, Wehbie RS, et al. Selection of multiple HIV-1 variants with decreased sensitivity to an inhibitor of the viral protease. Proc Natl Acad Sci USA. 1994;91:5597–601.PubMedCrossRefGoogle Scholar
  20. 20.
    Lin Y, Lin X, Hong L, et al. Effect of point mutations on the kinetics and the inhibition of human immunodeficiency virus type 1 protease: relationship to drug resistance. Biochemistry. 1995;34:1143–52.PubMedCrossRefGoogle Scholar
  21. 21.
    Liu HH, Golin CG, Miller L, et al. A comparison study of multiple measures of adherence to HIV protease inhibitors. Ann Intern Med. 2001;134:968–77.PubMedGoogle Scholar
  22. 22.
    Eldred LJ, Wu AW, Chaisson RE, Moore RD. Adherence to antiretroviral and pneumocystis prophylaxis in HIV disease. J Acquir Immune Defic Syndr. 1998;18:117–25.Google Scholar
  23. 23.
    Kastrissios H, Suarez JR, Hammer S, Katzenstein D, Blaschke TF. The extent of non-adherence in a large AIDS clinical trial using plasma dideoxynucleoside concentrations as a marker. AIDS. 1998;12:2305–11.PubMedCrossRefGoogle Scholar
  24. 24.
    Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med. 1999;131:81–7.PubMedGoogle Scholar
  25. 25.
    Deeks SG, Hecht FM, Swanson M, et al. HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. AIDS. 1999;13:F35–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Haynes RB, Taylor DW, Sackett DL. Compliance in Health Care. Baltimore, Md: Johns Hopkins University Press; 1979.Google Scholar
  27. 27.
    Cramer J, Mattson RH, Prevey ML, Scheer RD, Ouellette V. How often is medication taken as prescribed? A novel assessment technique. JAMA. 1989;261:3272–7.CrossRefGoogle Scholar
  28. 28.
    Golin CE, DiMatteo MR, Gelberg L. The role of patient participation in the doctor visit. Implications for adherence to diabetes care. Diabetes Care. 1996;19:1153–64.PubMedCrossRefGoogle Scholar
  29. 29.
    Glasgow RE, Strycker LA, Toobert DJ, Eakin E. A social-ecologic approach to assessing support for disease self-management: the Chronic Illness Resources Survey. J Behav Med. 2000;23:559–83.PubMedCrossRefGoogle Scholar
  30. 30.
    Golin CE, DiMatteo MR, Meisler AW. Adherence in AIDS clinical trials: a framework for clinical research and clinical care. J Clin Epidemiol. 1997;50:385–91.CrossRefGoogle Scholar
  31. 31.
    Samet JH, Libman H, Steger KA, et al. Compliance with zidovudine therapy in patients infected with human immunodeficiency virus, type 1: a cross-sectional study in a municipal hospital clinic. Am J Med. 1992;92:495–502.PubMedCrossRefGoogle Scholar
  32. 32.
    Samuels JE, Hendrix J, Hilton M, Marantz PR, Sloan V, Small CB. Zidovudine therapy in an inner city population. J Acquir Immune Defic Syndr. 1990;3:877–83.PubMedGoogle Scholar
  33. 33.
    Broers B, Morabia A, Hirschel B. A cohort study of drug users’ compliance with zidovudine treatment. Arch Intern Med. 1994;154:1121–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Muma RD, Ross MW, Parcel GS, Pollard RB. Zidovudine adherence among individuals with HIV infection. AIDS Care. 1995;7:439–47.PubMedCrossRefGoogle Scholar
  35. 35.
    Weidle PJ, Ganera CE, Irwin KL, et al. Adherence to antiretroviral medications in an inner-city population. J Acquir Immune Defic Syndr. 1999;22:498–502.PubMedGoogle Scholar
  36. 36.
    Holzemer W, Henry S, Portillo CJ, Miramontes H. The Client Adherence Profiling-Intervention Tailoring (CAP-IT) intervention for enhancing adherence to HIV/AIDS medications: a pilot study. J Assoc Nurses AIDS Care. 2000;11:36–44.PubMedCrossRefGoogle Scholar
  37. 37.
    Murphy D, Roberts K, Marelich W, Hoffman D. Barriers to antiretroviral adherence among HIV-Infected adults. AIDS Patient Care. 2000;14:47–58.CrossRefGoogle Scholar
  38. 38.
    Chesney M, Ickovics J, Chambers D, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. AIDS Care. 2000;12:255–66.PubMedCrossRefGoogle Scholar
  39. 39.
    Murri R, Ammassari A, Gallicano K, et al. Patient-reported nonadherence to HAART is related to protease inhibitor levels. J Acquir Immune Defic Syndr. 2000;24:123–8.PubMedGoogle Scholar
  40. 40.
    Catz S, Kelly J, Bogart L, Benotsch E, McAuliffe T. Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease. Health Psychol. 2000;19:124–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Holzemer WL, Corless IB, Nokes KM, et al. Predictors of self-reported adherence in persons living with HIV disease. Aids Patient Care STDS. 1999;13:185–97.PubMedGoogle Scholar
  42. 42.
    Kalichman SC, Ramachandran B, Catz S. Adherence to combination antiretroviral therapies in HIV patients of low health literacy. J Gen Intern Med. 1999;14:267–73.PubMedCrossRefGoogle Scholar
  43. 43.
    Tuldra A, Fumaz C, 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;25:221–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Gifford A, Bormann J, Shively M, Wright B, Richman D, Bozzette S. Predictors of self-reported adherence and plasma HIV concentration in patients on multidrug antiretroviral regimens. J Acquir Immune Defic Syndr. 2000;23:386–95.PubMedGoogle Scholar
  45. 45.
    Roberts KJ. Barriers to and facilitators of HIV-positive patients’ adherence to antiretroviral treatment regimens. Aids Patient Care STDS. 2000;14:155–68.PubMedCrossRefGoogle Scholar
  46. 46.
    Gordillo V, del Amo J, Soriano V, Gonzalez-Lahoz J. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS. 1999;13:1763–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Proctor VE, Tesfa A, Tompkins DC. Barriers to adherence to highly active antiretroviral therapy as expressed by people living with HIV/AIDS. Aids Patient Care STDS. 1999;13:535–44.PubMedCrossRefGoogle Scholar
  48. 48.
    Meystre-Agustoni G, Dubois-Arber F, Cochand P, Telenti A. Antiretroviral therapies from the patient’s perspective. AIDS Care. 2000;12:717–21.PubMedCrossRefGoogle Scholar
  49. 49.
    Turner B, Newschaffer C, Zhang D, Cosler L, Hauck W. Antiretroviral use and pharmacy-based measurement of adherence in postpartum HIV infected women. Med Care. 2000;38:911–25.PubMedCrossRefGoogle Scholar
  50. 50.
    Laine C, Newschaffer CJ, Zhang D, Cosler L, Hauck WW, Turner BJ. Adherence to antiretroviral therapy by pregnant women infected with human immunodeficiency virus: a pharmacy claims-based analysis. Obstet Gynecol. 2000;95:167–73.PubMedCrossRefGoogle Scholar
  51. 51.
    Moatti JP, Carrieri MP, Spire B, Gastaut JA, Cassuto JP, Moreau J. Adherence to HAART in French HIV-infected injecting drug users: the contribution of buprenorphine drug maintenance treatment. The Manif 2000 study group. AIDS. 2000;14:151–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Ostrop N, Hallett K, Gill J. Long-term patient adherence to antiretroviral therapy. Ann Pharmacother. 2000;34:703–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Leider JM, Kalkut G. Understanding adherence to HIV medication. [letter]. Ann Intern Med. 2000;132:418.PubMedGoogle Scholar
  54. 54.
    Sherbourne C, Hays RD, Ordway L, DiMatteo R, Kravitz RL. Antecendents of adherence to medical recommendations: results from the medical outcomes study. J Behav Med. 1992;15:447–67.PubMedCrossRefGoogle Scholar
  55. 55.
    Glasgow RE. Social-environmental factors in diabetes. Barriers to diabetes self-care. In: Bradlely C, ed. Handbook of Psychology and Diabetes Research and Practice. Berkshire, UK: Hardwood Academic; 1994;335–49.Google Scholar
  56. 56.
    Golin CE, Isasi F, Breny Bontempi J, Eng G. Secret pills: HIV-positive patients’ experiences taking antiretroviral therapy. AIDS Educ and Prev. 2002;14:317–28.Google Scholar
  57. 57.
    Anderson L. Health care communication and selected psychological adherence in diabetes management. Diabetes Care. 1990;13:66–7.Google Scholar
  58. 58.
    Rost K. The influence of patient participation on satisfaction and compliance. Diabetes Educ. 1989;15:134–8.CrossRefGoogle Scholar
  59. 59.
    Street R, Piziak V, Carpentier W, et al. Provider-patient communication and metabolic control. Diabetes Care. 1993;16:714–21.PubMedCrossRefGoogle Scholar
  60. 60.
    Kaplan SM, Greenfield S, Ware J. Assessing the effects of physician-patient interaction on the outcomes of chronic disease. Med Care. 1989;27:110–27.CrossRefGoogle Scholar
  61. 61.
    Stewart M. What is a successful doctor-patient interview. A study of interactions and outcomes. Soc Sci Med. 1984;19:167–75.PubMedCrossRefGoogle Scholar
  62. 62.
    Rost K, Carter WI. Introduction of information during the initial medical visit: consequences for patient follow-through with physician recommendations for medication. Soc Sci Med. 1989;28:315–21.PubMedCrossRefGoogle Scholar
  63. 63.
    Greenfield S, Kaplan SH, Ware JE Jr, Yano EM, Frank HJ. Patients’ participation in medical care: effects on blood sugar control and quality of life in diabetes. J Gen Intern Med. 1988;3:448–57.PubMedCrossRefGoogle Scholar
  64. 64.
    Korsch B, Gozzi E, Francis V. Gaps in doctor-patient communication. Doctor-patient interaction and patient satisfaction. Pediatrics. 1968;42:855–71.PubMedGoogle Scholar
  65. 65.
    Roter D, Hall J. Doctors Talking with Patients/Patients Talking with Doctors. Westport, Conn: Auburn House; 1993.Google Scholar
  66. 66.
    Hays RD, Cunningham WE, Sherbourne CD, et al. Health-related quality of life in patients with Human Immunodeficiency Virus Infection in the United States: Results from the HIV Cost and Services Utilization Study. Am J Med. 2000;108:714–22.PubMedCrossRefGoogle Scholar
  67. 67.
    Ware JE, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34:220–33.PubMedCrossRefGoogle Scholar
  68. 68.
    Fleishman JA, Sherbourne CD, Crystal S, et al. Coping, conflictual social interactions, social support and mood among HIV-infected persons. Am J Community Psychol. 2000;28:421–53.PubMedCrossRefGoogle Scholar
  69. 69.
    Parker RM, Baker DW, Williams MV, Nurss JR. The test of functional health literacy in adults: a new instrument for measuring patients’ literacy skills. J Gen Intern Med. 1995;10:537–41.PubMedGoogle Scholar
  70. 70.
    Marin G, Sabogal F, Marin B, et al. Development of a short acculturation scale for Hispanics. Hisp J Behav Sci. 1987;9:183–205.CrossRefGoogle Scholar
  71. 71.
    DiMatteo MR, Hays RD, Gritz E. et al. Factors affecting patient adherence to cancer control regimens: development and validation of a multivariate assessment instrument. Psychol Assess. 1993;5:102–12.CrossRefGoogle Scholar
  72. 72.
    Hays RD, Shaul JA, Williams VSL, et al. Psychometric properties of the CAHPSTM 1.0 Survey measures. Consumer Assessment of Health Plans Study. Med Care. 1999;37:MS22–31.PubMedCrossRefGoogle Scholar
  73. 73.
    Kao AC, Green DC, Davis NA, Koplan JP, Cleary PD. Patients’ trust in their physicians: effects of choice, continuity, and payment method. J Gen Intern Med. 1998;13:681–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Kao AC, Green DC, Zaslavsky AM, Koplan JP, Cleary PD. The relationship between method of physician payment and patient trust. JAMA. 1998;280:1708–14.PubMedCrossRefGoogle Scholar
  75. 75.
    Cunningham WE, Markson LE, Andersen RM, et al. Prevalence and predictors of highly active antiretroviral therapy use in patients with HIV infection in the united states. HCSUS Consortium. HIV Cost and Services Utilization. J Acquir Immune Defic Syndr. 2000;25:115–23.PubMedCrossRefGoogle Scholar
  76. 76.
    Sherbourne CD, Stewart AL. The MOS social support survey. Soc Sci Med. 1991;32:705–14.PubMedCrossRefGoogle Scholar
  77. 77.
    Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24:385–96.PubMedCrossRefGoogle Scholar
  78. 78.
    Liu HH, Weiss RE, Jennrich RI, Wenger NS. PRESS model selection in repeated measures data. Computational Statistics and Data Analysis. 1999;30:169–84.CrossRefGoogle Scholar
  79. 79.
    Rigsby MO, Rosen MI, Beauvais JE, et al. Cue-dose training with monetary reinforcement: pilot study of an antiretroviral adherence intervention. J Gen Intern Med. 2000;15:841–7.PubMedCrossRefGoogle Scholar
  80. 80.
    Safren S, Boswell S, Johnson W, Salomon L, Mayer K. Initial outcome of an online paging system (MEDIMom) to increase adherence to antiretroviral therapy. Presented at the Eighth Conference on Retroviruses and Opportunistic Infection, Chicago, February 2001.Google Scholar

Copyright information

© Society of General Internal Medicine 2002

Authors and Affiliations

  • Carol E. Golin
    • 1
  • Honghu Liu
    • 2
    • 6
  • Ron D. Hays
    • 2
    • 6
  • Loren G. Miller
    • 3
    • 6
  • C. Keith Beck
    • 3
  • Jeanette Ickovics
    • 4
  • Andrew H. Kaplan
    • 5
  • Neil S. Wenger
    • 2
    • 6
  1. 1.Received from the Department of Health Behavior and Health EducationUniversity of North Carolina at Chapel Hill, Sheps Center for Health Services ResearchChapel Hill
  2. 2.the Department of MedicineUniversity of California-Los AngelesLos Angeles
  3. 3.the Divisions of Infectious Diseases and HIV ServicesHarbor-UCLA Medical CenterTorrance
  4. 4.Yale University School of Public HealthNew Haven
  5. 5.the Departments of Medicine, and Microbiology and Immunology, and Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel Hill
  6. 6.the UCLA Center for AIDS Research and AIDS InstituteLos Angeles

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