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.
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.
Critical Care Medicine Department, National Institutes of Health, Bethesda, MD 20892.
R T
RT
Davey
V J
VJ
Davey
J A
JA
Metcalf
J J
JJ
Zurlo
J A
JA
Kovacs
J
J
Falloon
M A
MA
Polis
K M
KM
Zunich
H
H
Masur
H C
HC
Lane
D000284:Administration, Oral; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D004890:Erythema / Q000139:chemically induced; D005500:Follow-Up Studies; D015683:Gene Products, gag / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015488:HIV Antigens / Q000097:blood; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012514:Sarcoma, Kaposi / Q000150:complications; D014758:Viral Core Proteins / Q000097:blood; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor