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Multicenter Study Comparative Study
Effect of early versus deferred antiretroviral therapy for HIV on survival.
- Mari M Kitahata, Stephen J Gange, Alison G Abraham, Barry Merriman, Michael S Saag, Amy C Justice, Robert S Hogg, Steven G Deeks, Joseph J Eron, John T Brooks, Sean B Rourke, M John Gill, Ronald J Bosch, Jeffrey N Martin, Marina B Klein, Lisa P Jacobson, Benigno Rodriguez, Timothy R Sterling, Gregory D Kirk, Sonia Napravnik, Anita R Rachlis, Liviana M Calzavara, Michael A Horberg, Michael J Silverberg, Kelly A Gebo, James J Goedert, Constance A Benson, Ann C Collier, Stephen E Van Rompaey, Heidi M Crane, Rosemary G McKaig, Bryan Lau, Aimee M Freeman, Richard D Moore, and NA-ACCORD Investigators.
- University of Washington, Harborview Medical Center, 325 Ninth Ave., Box 359931, Seattle, WA 98104, USA. kitahata@u.washington.edu
- N. Engl. J. Med. 2009 Apr 30; 360 (18): 181518261815-26.
BackgroundThe optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.MethodsWe conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group).ResultsIn the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001).ConclusionsThe early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.2009 Massachusetts Medical Society
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