CD4+count-guided interruption of antiretroviral treatment

El-Sadr, W. M., Lundgren, J. D., Neaton, J. D., Gordin, F., Abrams, D., Arduino, R. C., Babiker, A., Burman, W., Clumeck, N., Cohen, C. J., Cohn, D., Cooper, D., Darbyshire, J., Emery, S., Faetkenheuer, G., Gazzard, B., Grund, B., Hoy, J., Klingman, K., Losso, M., Mejia, J. M. Ramos, Markowitz, N., Neuhaus, J., Phillips, A. and Rappoport, C. (2006) CD4+count-guided interruption of antiretroviral treatment. New England Journal of Medicine, 355 22: 2283-2296. doi:10.1056/NEJMoa062360

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Author El-Sadr, W. M.
Lundgren, J. D.
Neaton, J. D.
Gordin, F.
Abrams, D.
Arduino, R. C.
Babiker, A.
Burman, W.
Clumeck, N.
Cohen, C. J.
Cohn, D.
Cooper, D.
Darbyshire, J.
Emery, S.
Faetkenheuer, G.
Gazzard, B.
Grund, B.
Hoy, J.
Klingman, K.
Losso, M.
Mejia, J. M. Ramos
Markowitz, N.
Neuhaus, J.
Phillips, A.
Rappoport, C.
Title CD4+count-guided interruption of antiretroviral treatment
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
Publication date 2006-11-01
Year available 2006
Sub-type Article (original research)
DOI 10.1056/NEJMoa062360
Open Access Status File (Publisher version)
Volume 355
Issue 22
Start page 2283
End page 2296
Total pages 14
Place of publication Waltham, MA, United States
Publisher Massachusetts Medical Society
Language eng
Formatted 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. ( number, NCT00027352.)
Keyword Clinical-Trials
Combination Therapy
Aids Events
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID MC_U122886352
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Faculty of Medicine
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Citation counts: TR Web of Science Citation Count  Cited 1375 times in Thomson Reuters Web of Science Article | Citations
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