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

J Infect Dis. 1991 Jul;164(1):43-52. doi: 10.1093/infdis/164.1.43.

Abstract

Twenty-four patients infected with human immunodeficiency virus type 1 (HIV-1) who had CD4+ counts of 0.2-0.5 x 10(9) cells/l received granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with zidovudine plus escalating doses of daily subcutaneous interferon-alpha. Mean neutropenia-inducing doses of interferon-alpha were 9.4 x 10(6) and 10.6 x 10(6) 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 microgram/kg/day for these two groups, respectively, although the mean minimum effective GM-CSF dose for both was only 0.30 microgram/kg/day. Serum p24 antigen declined greater than 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-alpha therapy without adversely affecting the antiviral properties of the combination.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • CD4-Positive T-Lymphocytes
  • Drug Evaluation
  • Drug Therapy, Combination
  • Erythema / chemically induced
  • Follow-Up Studies
  • Gene Products, gag / blood
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • HIV Antigens / blood
  • HIV Core Protein p24
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Injections, Subcutaneous
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Leukocyte Count
  • Male
  • Neutropenia / chemically induced
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Sarcoma, Kaposi / complications
  • Viral Core Proteins / blood
  • Zidovudine / administration & dosage
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use*

Substances

  • Gene Products, gag
  • HIV Antigens
  • HIV Core Protein p24
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Viral Core Proteins
  • Zidovudine
  • Granulocyte-Macrophage Colony-Stimulating Factor