Effect of early versus deferred antiretroviral therapy for HIV on survival.

TitleEffect of early versus deferred antiretroviral therapy for HIV on survival.
Publication TypeJournal Article
Year of Publication2009
AuthorsKitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, Hogg RS, Deeks SG, Eron JJ, Brooks JT, Rourke SB, M Gill J, Bosch RJ, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Goedert JJ, Benson CA, Collier AC, Van Rompaey SE, Crane HM, McKaig RG, Lau B, Freeman AM, Moore RD
Corporate AuthorsNA-ACCORD Investigators
JournalN Engl J Med
Volume360
Issue18
Pagination1815-26
Date Published2009 Apr 30
ISSN1533-4406
KeywordsAdult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Confounding Factors (Epidemiology), Drug Administration Schedule, Female, HIV, HIV Infections, Humans, Male, Middle Aged, Proportional Hazards Models, Risk, RNA, Viral, Survival Analysis
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.

DOI10.1056/NEJMoa0807252
Alternate JournalN. Engl. J. Med.
PubMed ID19339714
PubMed Central IDPMC2854555
Grant ListK01 AI071725 / AI / NIAID NIH HHS / United States
K01 AI071725-01A1 / AI / NIAID NIH HHS / United States
K01 AI071754 / AI / NIAID NIH HHS / United States
K01 AI071754-01A1 / AI / NIAID NIH HHS / United States
K23 AI060464 / AI / NIAID NIH HHS / United States
K23 AI060464-05 / AI / NIAID NIH HHS / United States
K24 DA000432 / DA / NIDA NIH HHS / United States
K24 DA000432-09 / DA / NIDA NIH HHS / United States
K24 DA000432-10 / DA / NIDA NIH HHS / United States
M01 RR000052 / RR / NCRR NIH HHS / United States
M01 RR000052-46 / RR / NCRR NIH HHS / United States
P30 AI027757 / AI / NIAID NIH HHS / United States
P30 AI027757-229020 / AI / NIAID NIH HHS / United States
P30 AI027767 / AI / NIAID NIH HHS / United States
P30 AI027767-17 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 AI050410-099002 / AI / NIAID NIH HHS / United States
P30 AI054999 / AI / NIAID NIH HHS / United States
P30 AI054999-07 / AI / NIAID NIH HHS / United States
R01 AA016893 / AA / NIAAA NIH HHS / United States
R01 AA016893-01A2 / AA / NIAAA NIH HHS / United States
R01 AG026250 / AG / NIA NIH HHS / United States
R01 AG026250-01A2 / AG / NIA NIH HHS / United States
R01 DA004334 / DA / NIDA NIH HHS / United States
R01 DA004334-21A2 / DA / NIDA NIH HHS / United States
R01 DA011602 / DA / NIDA NIH HHS / United States
R01 DA011602-02 / DA / NIDA NIH HHS / United States
R01 DA011602-11A2 / DA / NIDA NIH HHS / United States
R01 DA012568 / DA / NIDA NIH HHS / United States
R01 DA012568-01 / DA / NIDA NIH HHS / United States
R01 MH054907 / MH / NIMH NIH HHS / United States
R01 MH054907-15 / MH / NIMH NIH HHS / United States
R21 AA015032 / AA / NIAAA NIH HHS / United States
R21 AA015032-02 / AA / NIAAA NIH HHS / United States
R24 AI067039 / AI / NIAID NIH HHS / United States
R24 AI067039-01A1 / AI / NIAID NIH HHS / United States
R56 DA004334 / DA / NIDA NIH HHS / United States
U01 AA013566 / AA / NIAAA NIH HHS / United States
U01 AA013566-02 / AA / NIAAA NIH HHS / United States
U01 AI031834 / AI / NIAID NIH HHS / United States
U01 AI031834-07 / AI / NIAID NIH HHS / United States
U01 AI034989 / AI / NIAID NIH HHS / United States
U01 AI034989-16 / AI / NIAID NIH HHS / United States
U01 AI034993 / AI / NIAID NIH HHS / United States
U01 AI034993-06 / AI / NIAID NIH HHS / United States
U01 AI034994 / AI / NIAID NIH HHS / United States
U01 AI034994-06 / AI / NIAID NIH HHS / United States
U01 AI035004 / AI / NIAID NIH HHS / United States
U01 AI035004-08S1 / AI / NIAID NIH HHS / United States
U01 AI035039 / AI / NIAID NIH HHS / United States
U01 AI035039-07 / AI / NIAID NIH HHS / United States
U01 AI035040 / AI / NIAID NIH HHS / United States
U01 AI035040-07 / AI / NIAID NIH HHS / United States
U01 AI035041 / AI / NIAID NIH HHS / United States
U01 AI035041-07 / AI / NIAID NIH HHS / United States
U01 AI035042 / AI / NIAID NIH HHS / United States
U01 AI035042-07 / AI / NIAID NIH HHS / United States
U01 AI035043 / AI / NIAID NIH HHS / United States
U01 AI035043-12 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI038855-04 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI038858-07 / AI / NIAID NIH HHS / United States
U01 AI042590 / AI / NIAID NIH HHS / United States
U01 AI042590-07 / AI / NIAID NIH HHS / United States
U01 AI042590-12 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068634-01 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-01 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
U01 AI069432-01 / AI / NIAID NIH HHS / United States
U01 AI069434 / AI / NIAID NIH HHS / United States
U01 AI069434-01 / AI / NIAID NIH HHS / United States
U01 AI069918 / AI / NIAID NIH HHS / United States
U01 AI069918-01 / AI / NIAID NIH HHS / United States
U01 AI069918-04S1 / AI / NIAID NIH HHS / United States
U01 HD032632-16 / HD / NICHD NIH HHS / United States
UL1 RR024131 / RR / NCRR NIH HHS / United States
UL1 RR024131-047355 / RR / NCRR NIH HHS / United States
UL1 RR025747-02 / RR / NCRR NIH HHS / United States
Z01 CP010176-07 / / Intramural NIH HHS / United States