Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival

Mari M. Kitahata(Harborview Medical Center), Stephen J. Gange(Harborview Medical Center), Alison G. Abraham(Harborview Medical Center), Barry Merriman(Harborview Medical Center), Michael S Saag(University of Alabama at Birmingham), Amy C. Justice(Harborview Medical Center), Robert S. Hogg(AIDS Vancouver), Steven G. Deeks(Harborview Medical Center), Joseph J. Eron(University of North Carolina at Chapel Hill), John T. Brooks(Harborview Medical Center), Sean B. Rourke(University of Toronto), M. John Gill(Harborview Medical Center), Ronald J. Bosch(Harvard University), Jeffrey N. Martin(University of California, San Francisco), Marina B. Klein(McGill University), Lisa P. Jacobson(Harborview Medical Center), Benigno Rodríguez(Harborview Medical Center), Timothy R. Sterling(Vanderbilt University), Gregory D. Kirk(Harborview Medical Center), Sonia Napravnik(University of North Carolina at Chapel Hill), Anita Rachlis(University of Toronto), Liviana Calzavara(Harborview Medical Center), Michael A. Horberg(Harborview Medical Center), Michael J. Silverberg(Kaiser Permanente), Kelly A. Gebo(Harborview Medical Center), James J. Goedert(National Institutes of Health), Constance A. Benson(University of California, San Diego), Ann C. Collier(Harborview Medical Center), Stephen E. Van Rompaey(Harborview Medical Center), Heidi M. Crane(Harborview Medical Center), Rosemary G. McKaig(Harborview Medical Center), Bryan Lau(Harborview Medical Center), Aimee Freeman(Johns Hopkins University), Richard D. Moore(Harborview Medical Center)
New England Journal of Medicine
April 1, 2009
10.1056/nejmoa0807252
Cited by 1,109Open Access
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Abstract

BACKGROUND: The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS: We 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). RESULTS: In 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). CONCLUSIONS: The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

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