The New England Journal of Medicine
e-mail icon  FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |    Advanced Search
Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe
 
Original Article
PreviousPrevious
Volume 355:2283-2296 November 30, 2006 Number 22
NextNext

CD4+ Count–Guided Interruption of Antiretroviral Treatment
The Strategies for Management of Antiretroviral Therapy (SMART) Study Group

 Sign up for free e-toc
 

This Article
-Full Text
- PDF
-PDA Full Text
-PowerPoint Slide Set
-Supplementary Material

Commentary
-Editorial
by Currier, J. S.

Tools and Services
-Add to Personal Archive
-Add to Citation Manager
-Notify a Friend
-E-mail When Cited
-E-mail When Letters Appear

More Information
-PubMed Citation
ABSTRACT

Background Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV).

Methods We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease.

Results A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1).

Conclusions Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov] .)


Source Information

The members of the writing group (W.M. El-Sadr [cochair], Harlem Hospital Center and Columbia University, New York; J.D. Lundgren [cochair], Hvidovre University Hospital, Denmark; J.D. Neaton [cochair], University of Minnesota, Minneapolis; F. Gordin, Washington Veterans Affairs Medical Center, Washington, DC; D. Abrams, University of California, San Francisco; R.C. Arduino, University of Texas Medical School, Houston; A. Babiker, Medical Research Council, London; W. Burman, Denver Public Health Department; N. Clumeck, Centre Hospitalier Universitaire Saint-Pierre, Brussels; C.J. Cohen, Community Research Initiative of New England, Boston; D. Cohn, Denver Public Health Department; D. Cooper, National Centre in HIV Epidemiology and Clinical Research, Sydney; J. Darbyshire, Medical Research Council, London; S. Emery, National Centre in HIV Epidemiology and Clinical Research, Sydney; G. Fätkenheuer, University Hospital, Cologne; B. Gazzard, Medical Research Council, London; B. Grund, University of Minnesota, Minneapolis; J. Hoy, National Centre in HIV Epidemiology and Clinical Research, Melbourne; K. Klingman, National Institute of Allergy and Infectious Diseases, Bethesda, MD; M. Losso, Hospital General de Agudos J.M. Ramos Mejia, Buenos Aires; N. Markowitz, Henry Ford Hospital, Detroit; J. Neuhaus, University of Minnesota, Minneapolis; A. Phillips, Royal Free Hospital School of Medicine, London; and C. Rappoport, University of California, San Francisco) of the SMART study assume responsibility for the overall content and integrity of the article.

Address reprint requests to Dr. El-Sadr at Harlem Hospital Center, Division of Infectious Diseases, Rm. 3107, 506 Lenox Ave., New York, NY 10037, or at wme1{at}columbia.edu.

Full Text of this Article


This article has been cited by other articles:


HOME  |  SUBSCRIBE  |  SEARCH  |  CURRENT ISSUE  |  PAST ISSUES  |  COLLECTIONS  |  PRIVACY  |  TERMS OF USE  |  HELP  |  beta.nejm.org

Comments and questions? Please contact us.

The New England Journal of Medicine is owned, published, and copyrighted © 2010 Massachusetts Medical Society. All rights reserved.