Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: a randomized controlled trial.
2000
ContextWhile interleukin 2 (IL-2) is capable of inducing a marked expansion
of the CD4 T-lymphocyte pool, limited data exist on whether IL-2 treatment
can add significantly to the immunologic and virologic effects of potent antiretroviral
therapy (ART).ObjectiveTo determine the rate and magnitude of CD4 cell recovery and viral suppression
when using a combination therapy of IL-2 and ART compared with ART alone.Design and SettingRandomized, controlled multicenter trial conducted from April 1996 through
April 1998 at 8 clinical sites in the United States.PatientsEighty-two adult outpatients who were infected with human immunodeficiency
virus (HIV) and had baseline CD4 cell counts of 200 × 106/L
to 500 × 106/L and baseline RNA levels of fewer than 10,000
copies/mL were randomized; 78 completed the study.InterventionsThirty-nine patients were randomly assigned to receive a combination
therapy of subcutaneous IL-2 (administered in 5-day courses every 8 weeks
at a starting dosage of 7.5 mIU twice per day) and ART; 43 were to receive
ART therapy alone.Main Outcome MeasuresInterleukin 2 safety and differential effects on CD4 cell counts, CD4
cell percentages, and plasma HIV RNA levels.ResultsThe mean (SD) percentage increase in CD4 cell counts at 1 year for patients
who received IL-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 IL-2 recipients and control patients, respectively (P=.03). Twenty (67%) of 30 evaluable patients receiving IL-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 IL-2 and were managed with antipyretics, hydration,
rest, and dosage reduction as needed.ConclusionsIntermittent therapy with IL-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 IL-2
therapy will translate into improved clinical outcomes.
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