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

Background: The efficacy of triple-drug antiretroviral regimens in the trea tment of patients infected with HIV has been established in several randomi zed clinical trials. However, the effectiveness of these new regimens in pa tient populations outside clinical trials remains unproven. This study comp ares mortality and AIDS-free survival among HIV-infected patients in Britis h 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 fr om the initiation of antiretroviral therapy to death or to diagnosis of pri mary AIDS were determined for patients who initially received an ERA-II reg imen (2 nucleoside analogue reverse transcriptase inhibitors [NRTIs] includ ing lamivudine or stavudine, or both) and for those who initially received an ERA-III regimen (triple-drug regimen consisting of 2 NRTIs and a proteas e inhibitor [indinavir, ritonavir or saquinavir] or a non-NRTI [nevirapine] ). Results: A total of 500 men and women (312 receiving an ERA-II regimen and 188 an ERA-III regimen) were eligible. Patients in the ERA-III group surviv ed 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 m onths 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 g roup (log rank p = 0.003). The likelihood of death was more than 3 times hi gher 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 Pneumocysti s carinii pneumonia or Mycobacterium avium infection, AIDS diagnosis, CD4cell count, sex and age at initiation of therapy, the likelihood of death a mong patients in the ERA-II group was 3.21 times higher (95% CI 1.24 to 8.3 0, 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% Cl 1.8% to 4.8%) in the ERA-III group (log rank p = 0.0 06). 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 i nitially treated with a triple-drug antiretroviral regimen comprising 2 NRT Is plus a protease inhibitor or a non-NRTI have a lower risk of morbidity a nd death than patients treated exclusively with 2 NRTIs.