CD4+ lymphocytes are an incomplete surrogate marker for clinical progression in persons with asymptomatic HIV infection taking zidovudine

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.