Context. While interleukin 2 (lL-2) is capable of inducing a marked expansion of the CD4 T-lymphocyte pool, limited data exist on whether lL-2 treatment can add significantly to the immunologic and virologic effects of potent antiretroviral therapy (ART). Objective. To determine the rate and magnitude of CD4 cell recovery and viral suppression when using a combination therapy of lL-2 and ART compared with ART alone. Design and Setting. Randomized, controlled multicenter trial conducted from April 1996 through April 1998 at 8 clinical sites in the United States. Patients. Eighty-two adult outpatients who were infected with human immunodeficiency virus (HIV) and had baseline CD4 cell counts of 200 x 106/L to 500 x 106/L and baseline RNA levels of fewer than 10000 copies/mL were randomized; 78 completed the study. Interventions. Thirty-nine patients were randomly assigned to receive a combination therapy of subcutaneous lL-2 (administered in 5-day courses every 8 weeks at a starting dosage of 7.5 mlU twice per day) and ART; 43 were to receive ART therapy alone. Main Outcome Measures. Interleukin 2 safety and differential effects on CD4 cell counts, CD4 cell percentages, and plasma HIV RNA levels. Results. The mean (SD) percentage increase in CD4 cell counts at 1 year for patients who received lL-2 was 112% (113%) compared with 18% (35%) in recipients of ART alone (P<.001). Both groups had mean (SD) increases in CD4 cell percentage: from 20.4% (6.3%) to 32.3% (12.4%) for the combination therapy group compared with 20.4% (5.1%) to 23.0% (7.2%) for recipients of ART alone (P<.001). Using a sensitive viral RNA assay, mean viral load changes were -0.28 and 0.09 log10 copies for lL-2 recipients and control patients, respectively (P=.03). Twenty (67%) of 30 evaluable patients receiving lL-2 achieved final viral loads of fewer than 50 copies/mL compared with 13 (36%) of 36 control patients (P=.02). Toxic effects were common among patients who received lL-2 and were managed with antipyretics, hydration, rest, and dosage reduction as needed. Conclusions. Intermittent therapy with lL-2 and ART produced a substantially greater increase in CD4 cells and was associated with a larger decrease in viral load than ART alone. Clinical end- point trials will be necessary to determine whether the enhanced viral suppression and CD4 cell increases associated with lL-2 therapy will translate into improved clinical outcomes.
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