A phase i/ii trial of zidovudine, interferon-α, and granulocyte-macrophage colony-stimulating factor in the treatment of human immunodeficiency virus type 1 infection

Twenty-four patients infected with human immunodeficiency virus type 1 (HIV-1) who had CD4⁺ counts of 0.2-0.5 X 10⁹ cells/l received granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with zidovudine plus escalating doses of daily subcutaneous inter- feron-a. Mean neutropenia-inducing doses of interferon-α were 9.4 X 10⁶ and 10.6 X 10⁶ IU/day for groups receiving 100 or 200 mg zidovudine every 4 h, respectively. Mean GM-CSF doses used to reverse neutropenia were 0.64 and 0.63 μg/kg/day for these two groups, respectively, although the mean minimum effective GM-CSF dose for both was only 0.30 μg/kg/day. Serum p24 antigen declined >70% in all 5 antigenemic patients. Toxicities included a dose-dependent increase in lymphokine-like side effects (100%), anorexia and weight loss (42%), fatigue (42%), and anemia (50%). While toxicities of the combination can be significant, low-dose GM-CSF readily ameliorated neutropenia associated with zidovudine and α therapy without adversely affecting the antiviral properties of the combination.