A randomized, placebo-controlled trial of granulocyte-macrophage colony-stimulating factor and nucleoside analogue therapy in AIDS

Preliminary preclinical and clinical data suggest that granulocyte-macropha ge colony-stimulating factor (GM-CSF) may decrease viral replication. There fore, 105 individuals with AIDS who were receiving nucleoside analogue ther apy were enrolled in a placebo-controlled, double-blind study and were rand omized to receive either 125 mug/m(2) of yeast-derived, GM-CSF (sargramosti m) or placebo subcutaneously twice weekly for 6 months. Subjects were evalu ated for toxicity and disease progression. A significant decrease in mean v irus load (VL) was observed for the GM-CSF treatment group at 6 months (-0, 07 log,, vs. -0.60 log(10); P = .02), More subjects achieved human immunode ficiency virus (HIV)-RNA levels <500 copies/mt at <greater than or equal to >2 evaluations (2% on placebo vs. 11% on GM-CSF; P = .04), Genotypic analys is of 46 subjects demonstrated a lower frequency of zidovudine-resistant mu tations among those receiving GM-CSF (80% vs. 50%; P = .04), No difference was observed in the incidence of opportunistic infections (OIs) through 6 m onths or survival, despite a higher risk for OI among GM-CSF recipients. GM -CSF reduced VL and limited the evolution of zidovudine-resistant genotypes , potentially providing adjunctive therapy in HIV disease.