Skip to main content
NCBI home page
CMAJ : Canadian Medical Association Journal logoLink to CMAJ : Canadian Medical Association Journal
. 1999 Mar 9;160(5):659–665.

Improved survival among HIV-infected patients after initiation of triple-drug antiretroviral regimens

R S Hogg, B Yip, C Kully, K J Craib, M V O'Shaughnessy, M T Schechter, J S Montaner
PMCID: PMC1230111  PMID: 10102000

Abstract

BACKGROUND: The efficacy of triple-drug antiretroviral regimens in the treatment of patients infected with HIV has been established in several randomized clinical trials. However, the effectiveness of these new regimens in patient populations outside clinical trials remain unproven. This study compared mortality and AIDS-free survival among HIV-infected patients in British Columbia who were treated with double- and triple-drug regimens. METHODS: The authors used a prospective, population-based cohort design to study a population of HIV-positive men and women 18 years or older for whom antiretroviral therapy was first prescribed between Oct. 1, 1994, and Dec. 31, 1996; all patients were from British Columbia. Rates of progression from the initiation of antiretroviral therapy to death or to diagnosis of primary AIDS were determined for patients who initially received an ERA-II regimen (2 nucleoside analogue reverse transcriptase inhibitors [NRTIs] including lamivudine or stavudine, or both) and for those who initially received an ERA-III regimen (triple-drug regimen consisting of 2 NRTIs and a protease inhibitor [indinavir, ritonavir or saquinavir] or a non-NRTI [nevirapine]). RESULTS: A total of 500 men and women (312 receiving an ERA-III regimen and 188 an ERA-III regimen) were eligible. Patients in the ERA-III group survived significantly longer than those in the ERA-II group. As of Dec. 31, 1997, 40 patients had died (35 in the ERA-II group and 5 in the ERA-III group), for a crude mortality rate of 8.0%. The cumulative mortality rates at 12 months were 7.4% (95% confidence interval [CI] 5.9% to 8.9%) for patients in the ERA-II group and 1.6% (95% CI 0.7% to 2.5%) for those in the ERA-III group (log rank p = 0.003). The likelihood of death was more than 3 times higher among patients in the ERA-II group (mortality risk ratio 3.82 [95% CI 1.48% to 9.84], p = 0.006). After adjustment for prophylaxis for Pneumocystis carinii pneumonia or Mycobacterium avium infection, AIDS diagnosis, CD4+ cell count, sex and age at initiation of therapy, the likelihood of death among patients in the ERA-II group was 3.21 times higher (95% CI 1.24 to 8.30, p = 0.016) than in the ERA-III group. Cumulative rates of progression to AIDS or death at 12 months were 9.6% (95% CI 7.7% to 11.5%) in the ERA-II group and 3.3% (95% CI 1.8% to 4.8%) in the ERA-III group (log rank p = 0.006). After adjustment for prognostic variables (prophylaxis for P. carinii pneumonia or M. avium infection, CD4+ cell count, sex and age at initiation of treatment), the likelihood of progression to AIDS or death at 12 months among patients in the ERA-II group was 2.37 times higher (95% CI 1.04 to 5.38, p = 0.040) than in the ERA-III group. INTERPRETATION: This population-based cohort study confirms that patients initially treated with a triple-drug antiretroviral regimen comprising 2 NRTIs plus protease inhibitor or a non-NRTI have a lower risk of morbidity and death than patients treated exclusively with 2 NRTIs.

Full Text

The Full Text of this article is available as a PDF (138.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cameron D. W., Heath-Chiozzi M., Danner S., Cohen C., Kravcik S., Maurath C., Sun E., Henry D., Rode R., Potthoff A. Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group. Lancet. 1998 Feb 21;351(9102):543–549. doi: 10.1016/s0140-6736(97)04161-5. [DOI] [PubMed] [Google Scholar]
  2. Carpenter C. C., Fischl M. A., Hammer S. M., Hirsch M. S., Jacobsen D. M., Katzenstein D. A., Montaner J. S., Richman D. D., Saag M. S., Schooley R. T. Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel. JAMA. 1998 Jul 1;280(1):78–86. doi: 10.1001/jama.280.1.78. [DOI] [PubMed] [Google Scholar]
  3. Collier A. C., Coombs R. W., Schoenfeld D. A., Bassett R. L., Timpone J., Baruch A., Jones M., Facey K., Whitacre C., McAuliffe V. J. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. N Engl J Med. 1996 Apr 18;334(16):1011–1017. doi: 10.1056/NEJM199604183341602. [DOI] [PubMed] [Google Scholar]
  4. Gulick R. M., Mellors J. W., Havlir D., Eron J. J., Gonzalez C., McMahon D., Richman D. D., Valentine F. T., Jonas L., Meibohm A. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med. 1997 Sep 11;337(11):734–739. doi: 10.1056/NEJM199709113371102. [DOI] [PubMed] [Google Scholar]
  5. Hammer S. M., Squires K. E., Hughes M. D., Grimes J. M., Demeter L. M., Currier J. S., Eron J. J., Jr, Feinberg J. E., Balfour H. H., Jr, Deyton L. R. 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. N Engl J Med. 1997 Sep 11;337(11):725–733. doi: 10.1056/NEJM199709113371101. [DOI] [PubMed] [Google Scholar]
  6. Hogg R. S., Heath K. V., Yip B., Craib K. J., O'Shaughnessy M. V., Schechter M. T., Montaner J. S. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA. 1998 Feb 11;279(6):450–454. doi: 10.1001/jama.279.6.450. [DOI] [PubMed] [Google Scholar]
  7. Hogg R. S., O'Shaughnessy M. V., Gataric N., Yip B., Craib K., Schechter M. T., Montaner J. S. Decline in deaths from AIDS due to new antiretrovirals. Lancet. 1997 May 3;349(9061):1294–1294. doi: 10.1016/S0140-6736(05)62505-6. [DOI] [PubMed] [Google Scholar]
  8. Hogg R. S., Rhone S. A., Yip B., Sherlock C., Conway B., Schechter M. T., O'Shaughnessy M. V., Montaner J. S. Antiviral effect of double and triple drug combinations amongst HIV-infected adults: lessons from the implementation of viral load-driven antiretroviral therapy. AIDS. 1998 Feb 12;12(3):279–284. doi: 10.1097/00002030-199803000-00005. [DOI] [PubMed] [Google Scholar]
  9. Hogg R. S., Strathdee S. A., Craib K. J., O'Shaughnessy M. V., Montaner J. S., Schechter M. T. Lower socioeconomic status and shorter survival following HIV infection. Lancet. 1994 Oct 22;344(8930):1120–1124. doi: 10.1016/s0140-6736(94)90631-9. [DOI] [PubMed] [Google Scholar]
  10. Montaner J. S., Reiss P., Cooper D., Vella S., Harris M., Conway B., Wainberg M. A., Smith D., Robinson P., Hall D. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA. 1998 Mar 25;279(12):930–937. doi: 10.1001/jama.279.12.930. [DOI] [PubMed] [Google Scholar]
  11. Palella F. J., Jr, Delaney K. M., Moorman A. C., Loveless M. O., Fuhrer J., Satten G. A., Aschman D. J., Holmberg S. D. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853–860. doi: 10.1056/NEJM199803263381301. [DOI] [PubMed] [Google Scholar]
  12. Strathdee S. A., Palepu A., Cornelisse P. G., Yip B., O'Shaughnessy M. V., Montaner J. S., Schechter M. T., Hogg R. S. Barriers to use of free antiretroviral therapy in injection drug users. JAMA. 1998 Aug 12;280(6):547–549. doi: 10.1001/jama.280.6.547. [DOI] [PubMed] [Google Scholar]

Articles from CMAJ: Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association

RESOURCES