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CD4+ Lymphocytes Are an Incomplete Surrogate Marker for Clinical Progression in Persons with Asymptomatic HIV Infection Taking Zidovudine
- Sungsub Choi, PhD;
- Stephen W. Lagakos, PhD;
- Robert T. Schooley, MD; and
- Paul A. Volberding, MD
- From McGill University, Montreal, Quebec, Canada; the Harvard School of Public Health, Boston, Massachusetts; the University of Colorado Health Science Center, Denver, Colorado; the University of California, San Francisco, California. A partial list of the institutions participating in the AIDS Clinical Trials Group appears in the Appendix. Requests for Reprints: Sungsub Choi, PhD, Department of Epidemiology and Biostatistics, McGill University, Purvis Hall, 1020 Pine Avenue West, Montreal, Quebec H3A 1A2, Canada. Acknowledgments: This research is an activity of the AIDS Clinical Trials Group. The authors thank Song-Heng Liou for preparing the data, Donna Jacobsen for editorial assistance, and Daniel S. Stein, MD, for helpful comments. Grant Support: By the Statistical and Data Analysis Center of the AIDS Clinical Trials Group, under NIAID Contract No. NO1-AI-95030. The Burroughs Wellcome Company partly funded editorial and word processing support.
Abstract
Objective: To determine the extent to which lymphocytes, particularly those with the CD4 surface antigen, are a surrogate marker for the development of the acquired immunodeficiency syndrome (AIDS) in persons with asymptomatic human immunodeficiency virus (HIV) infection.
Design: Analysis of data from the AIDS Clinical Trials Group Protocol 019, a placebo-controlled, double-blind, randomized trial.
Setting: University-based referral centers.
Patients: Asymptomatic HIV-infected patients with 500 or fewer CD4+ cells/mm3 at baseline who were given placebo (350 patients) or one of two daily doses of zidovudine (725 patients).
Measurements: Baseline and interim measurements of CD4+ and other leukocytes were assessed. Patients were followed for progression to AIDS.
Results: Patients' lymphocyte levels were correlated with progression to AIDS (P < 0.001; relative risk for each depletion of 50 CD4+ cells/mm3, 1.75; 95% CI, 1.53 to 2.01); however, only a small portion (0% to 37%) of the effect of zidovudine on this progression was statistically explained by its effect on CD4+ lymphocyte levels. A substantial portion of zidovudine's effect on delaying progression to AIDS that was independent of the levels of these markers occurred within the first 16 weeks of therapy. In patients who had not progressed to AIDS by week 16, most of the subsequent zidovudine effect in reducing the risk for progression could be explained by its effect on net CD4+ percent (percentage of CD4+ lymphocytes among all leukocytes) for the first 16 weeks of therapy.
Conclusion: Levels of CD4+ lymphocytes are an incomplete surrogate marker for progression to AIDS, and the association is especially weak during the first 16 weeks of zidovudine therapy.
- Copyright 2004 by the American College of Physicians
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