Journal of General Internal Medicine

, Volume 14, Issue 7, pp 395–401 | Cite as

Delays in protease inhibitor use in clinical practice

  • Kathleen M. Fairfield
  • Howard Libman
  • Roger B. Davis
  • David M. Eisenberg
  • Russell S. Phillips
Original Articles


OBJECTIVE: To determine the clinical factors associated with delayed protease inhibitor initiation.

DESIGN: Chart review and telephone survey.

SETTING: General medicine practice at an academic medical center in Boston, Mass.

PATIENTS: One hundred ninety patients living with HIV and a viral load of more than 10,000 copies/ml.

MEASUREMENTS AND MAIN RESULTS: The main outcome measurement was time to first protease inhibitor prescription after first elevated HIV viral load (>10,000 copies/ml). In this cohort, 190 patients had an elevated viral load (median age 39; 87% male; 12% history of injection drug use; 63% AIDS; 53% with depression; 17% history of pneumocystis pneumonia; 54% CD4 <200). In Cox proportional hazards modeling, significant univariate correlates for delayed protease inhibitor initiation were higher CD4 cell count (hazard ratio [HR] 2.38 for CD4 200–500 compared with <200, 95% confidence interval [CI] 1.59, 3.57; and HR 8.33 for CD4 >500; 95% CI 2.63, 25.0), higher viral load (HR 0.43 for each 10-fold increase; 95% CI 0.31, 0.59), injection drug use (HR 2.08; 95% CI 1.05, 4.17), AIDS (HR 0.24; 95% CI 0.15, 0.36), and history of pneumocystis pneumonia (HR 0.32; 95% CI 0.21, 0.49). In multivariate models adjusted for secular trends in protease inhibitor use, factors significantly associated with delay of protease inhibitor initiation (p<.05) were higher CD4 cell count (for CD4 200–500, HR 2.63; 95% CI 1.61, 4.17; for CD4 >500, HR 11.11; 95% CI 3.57, 33.33), higher viral load (HR 0.66 for each 10-fold increase; 95% CI 0.45, 0.98), history of pneumocystis pneumonia (HR 0.57; 95% CI 0.37, 0.90), history of depression (HR 1.49; 95% CI 1.03, 2.13), and history of injection drug use (HR 2.70; 95% CI 1.35, 5.56).

CONCLUSIONS: HIV-infected patients with higher CD4 cell counts or a history of depression or history of injection drug use have significant and lengthy delays of protease inhibitor therapy. Although some delays may be clinically appropriate, enhancement of provider and patient education might prove beneficial. Further research should examine reasons for delays in protease inhibitor initiation and their appropriateness.

Key Words

HIV protease inhibitors depression injection drug use 


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  1. 1.
    O’Brien TR, Blattner WA, Waters D, et al. Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. JAMA. 1996;276:105–10.PubMedCrossRefGoogle Scholar
  2. 2.
    Mellors JW, Kingsley LA, Rinaldo CR, et al. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med. 1995;122:573–9.PubMedGoogle Scholar
  3. 3.
    Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD, HIV-1 dynamics in vivo: virion clearance rate, infected cell lifespan, and viral generation time. Science. 1996;271:1582–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Cohen OJ, Pantaleo G, Holodniy M, et al. Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue. Proc Natl Acad Sci USA. 1995;92:6017–21.PubMedCrossRefGoogle Scholar
  5. 5.
    Carpenter CCJ, Fischl MA, Hammer SM, et al., for the International AIDS Society. Antiretroviral Therapy for HIV infection in 1996: recommendations of an international panel. JAMA. 1996;276:146–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Carpenter CCJ, Fischl MA, Hammer SM, et al., for the International AIDS Society. Antiretroviral Therapy for HIV infection in 1997: updated recommendations of the International AIDS Society—USA Panel. JAMA. 1997;277:1962–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Deeks SG, Smith M, Holodniy M, Kahn JO. HIV-1 protease inhibitors: a review for clinicians. JAMA. 1997;277:145–53.PubMedCrossRefGoogle Scholar
  8. 8.
    Williams A, Friedland G. Adherence, compliance, and HAART. AIDS Clinical Care. 1997;9:51–4,58.PubMedGoogle Scholar
  9. 9.
    Safran C, Rury C, Rind DM, Taylor WC. A computer-based outpatient medical record for a teaching hospital. MD Comput. 1991;8:291–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Makadon HJ, Delbanco SF, Delbanco TL. Caring for people with AIDS and HIV infection in hospital-based primary care practice. J Gen Intern Med. 1990;5:446–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Fairfield KM, Eisenberg DM, Davis RB, Libman H, Phillips RS. Patterns of use, expenditures, and perceived efficacy of complementary and alternative therapies in HIV-infected patients. Arch Intern Med. 1998;158:2257–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Kleinbaum DG, Kupper LL, Muller KE. Applied Regression Analysis and Other Multivariable Methods. Belmont, Calif: Duxbury Press; 1988.Google Scholar
  13. 13.
    Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989;129:125–37.PubMedGoogle Scholar
  14. 14.
    US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. Washington, DC: US Department of Health and Human Services. 1998;47(RR-5):43–82.Google Scholar
  15. 15.
    Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. Atlanta, Ga: Centers for Disease Control and Prevention; 1997:9 (No. 1).Google Scholar
  16. 16.
    Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338:853–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Detels R, Munoz A, McFarlane G, et al. Increased survival time to AIDS and death associated with use of combined therapy in the multicenter AIDS cohort study. Presented at the 5th Conference on Retroviral Opportunistic Infection, Feb 1–5, 1998. Abstract 115.Google Scholar
  18. 18.
    McNaghten AD, Hanson DL, Jones JL, Ward JW, Dworkin MS. The effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS. Presented at the 5th Conference on Retroviral Opportunistic Infection, Feb 1–5, 1998. Abstract 81.Google Scholar
  19. 19.
    Celentano DD, Vlahov D, Cohn S, Shadle VM, Obasanjo O, Moore RD. Self-reported antiretroviral therapy in injection drug users. JAMA. 1998;280:544–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Strathdee SA, Palepu A, Cornelisse PG, et al. Barriers to use of free antiretroviral therapy in injection drug users. JAMA. 1998;280:547–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Mayne TJ, Vittinghoff E, Chesney MA, Barrett DC, Coates TJ. Depressive affect and survival among gay and bisexual men infected with HIV. Arch Intern Med. 1996;156:2233–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Singh N, Squier C, Sivek C, Wagener M, Nguyen MH, Yu VL. Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance. AIDS Care. 1996;8:261–9.PubMedCrossRefGoogle Scholar

Copyright information

© Society of General Internal Medicine 1999

Authors and Affiliations

  • Kathleen M. Fairfield
    • 1
  • Howard Libman
    • 1
  • Roger B. Davis
    • 1
  • David M. Eisenberg
    • 1
    • 2
  • Russell S. Phillips
    • 1
  1. 1.Division of General Medicine and Primary CareBeth Israel Deaconess Medical CenterBoston
  2. 2.the Center for Alternative Medicine ResearchDepartment of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical SchoolBoston

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