Interruption of Antiretroviral Treatment in HIV‐Infected Patients with Preserved Immune Function Is Associated with a Low Rate of Clinical Progression: A Prospective Study by AIDS Clinical Trials Group 5170
1Baystate Medical Center, Springfield, and 2Harvard School of Public Health, Boston, Massachusetts; 3University of California, San Francisco, and 4Stanford University Medical Center, Stanford, California; 5University of North Carolina, Chapel Hill; 6University of Washington, Seattle; 7University of Texas Southwestern Medical Center, Dallas; 8Social & Scientific Systems, Inc., Silver Spring, Maryland; 9University of Pittsburgh, Pittsburgh, Pennsylvania
Background.
We sought to determine the safety of treatment interruption (TI) and to identify parameters that would define patients with human immunodeficiency virus (HIV) for whom TI is safer.
Methods.AIDS Clinical Trials Group 5170 was a multicenter, 96‐week‐long, prospective study of HIV‐infected patients receiving antiretroviral therapy (ART) who had CD4+ cell counts >350 cells/mm3 and who underwent TI.
Results.A total of 167 patients were enrolled. The median nadir in CD4+ cell count was 436 cells/mm3. The initial decrease (i.e., during the first 8 weeks) in CD4+ cell count after ART interruption was 20 cells/mm3/week; the subsequent decrease was 2.0 cells/mm3/week until week 96. Both the CD4+ cell count before enrollment and the increase in CD4+ cell count during ART predicted early decrease; later decrease was predicted by the level of interleukin‐7 at enrollment. A Centers for Disease Control and Prevention (CDC) diagnosis of a category B or C event was made for 2 and 2 patients, respectively (all had CD4+ cell counts >350 cells/mm3). At week 96, 17 patients had CD4+ cell counts 
250 cells/mm3, and 46 patients had resumed ART; 5 patients died (unrelated to HIV or acquired immunodeficiency syndrome). In a multivariate analysis, a higher nadir in CD4+ cell count (>400 cells/mm3), a lower HIV load (<50 copies/mL) at the time of TI, and an HIV load 22,000 copies/mL before ART predicted a longer time to the primary end point (CDC category B or C event, death, CD4+ cell count 250 cells/mm3, or resumption of ART).
Conclusion.Disease progression after TI was low in this cohort. A higher nadir in CD4+ cell count, a lower HIV load before ART, and an HIV load 50 copies/mL at the time of TI predicted a longer time to the primary end point.
Received 1 September 2006; accepted 20 November 2006; electronically published 6 April 2007.
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Potential conflicts of interest: D.J.S. has received honoraria from or has been a consultant to Bristol Myers Squibb, Gilead Sciences, GlaxoSmithKline, and Abbott Pharmaceuticals and has received research grants from GlaxoSmithKline and Bristol Myers Squibb. D.M. has received honoraria from or been a consultant to Merck and Tibotec, Inc.; D.M.M. has received grants, research materials, honoraria, or has been a consultant to Gilead Sciences, Monogram Biosciences, Merck, Abbott, Bristol Myers Squibb, GlaxoSmithKline, Boehringer‐Ingelheim, Biotron Ltd., Roche, and Trimeris.
Presented in part: 13th Conference on Retroviruses and Opportunistic Infections, Denver, Colorado, 5–8 February 2006 (oral abstract 101).
Financial support: AIDS Clinical Trials Group (National Institute of Allergy and Infectious Diseases grant AI38858 and Statistical Data Analysis Center grant AI38855; General Clinical Research Center units (National Center for Research Resources grant).
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Members of AIDS Clinical Trials Group 5170 are listed after the text.