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 O.2–0.5 × 109 cells/l received granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with zidovudine plus escalating doses of daily subcutaneous interferon-α. Mean neutropenia-inducing doses of interferon-α were 9.4 × 106 and 10.6 × 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 interferon-α therapy without adversely affecting the antiviral properties of the combination.