Effect of recombinant human granulocyte-macrophage colony-stimulating factor on HIV-related leukopenia: a randomized, controlled clinical study.

OBJECTIVE

To assess the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on white blood cell (WBC) count and on the rate of opportunistic infections in a large and selected population of leukopenic HIV-positive patients compared with non-treated controls.

DESIGN

Open-label, randomized, comparative clinical study.

SETTING

University hospitals and AIDS centres.

PATIENTS AND METHODS

One hundred and twenty-three leukopenic HIV-positive patients received recombinant human GM-CSF (300 microg subcutaneously daily for 1 week, and 150 microg subcutaneously two times weekly for 11 weeks thereafter); the control group comprised 121 non-treated leukopenic HIV-positive patients. A complete blood cell count with differential, platelet count, reticulocyte count, and CD4+ and CD8+ T-cell subset counts were performed in both patient groups at baseline and at weeks 1, 12 and 24.

RESULTS

The administration of GM-CSF resulted in a significant increase of WBC count in patients compared with non-treated controls. Total leukocyte count increased by 22% at week 1 and by 65% at week 12 compared with baseline levels; a 20% increase of total leukocyte count was still present at week 24. Increases of neutrophils, eosinophils and monocytes were responsible for the majority of the increase in WBC count. Opportunistic infections occurred in 61.7% of GM-CSF-treated patients and in 72% of the patients of the control group (relative risk, 0.86; 95% confidence interval, 0.72-1.03; P = 0.123). Mild flu-like side-effects were observed in most patients receiving GM-CSF, although they were not sufficiently severe to warrant withdrawal from the study.

CONCLUSIONS

GM-CSF was well tolerated and biologically active in leukopenic HIV-positive patients, with a significant, although time-limited, increase of WBC count compared with non-treated patients. The administration of this growth factor should be considered in ameliorating the myelosuppression observed with some cell-cycle-specific antiviral and anti-neoplastic agents.