Lack of in vivo effect of granulocyte-macrophage colony-stimulating factor on human immunodeficiency virus type 1.
Neutropenia complicates HIV disease or its treatment in a large proportion of patients. Hematopoietic growth factor support has been tested in a number of clinical settings in HIV disease and has been demonstrated to be of benefit for specific parameters. One consideration regarding the use of hematopoietic growth factors in HIV disease is their potential effect on HIV viral burden, since alterations in HIV expression have been documented with certain cytokines in vitro. It has also been reported that some cytokines, notably GM-CSF, potentiate the antiviral properties of thymidine analogs such as zidovudine (AZT) in vitro. We tested these observations in vivo. Twelve HIV-positive patients with a CD4 cell count < or = 200/mm3 or HIV plasma viremia who were receiving a stable dose of zidovudine were enrolled into three dose cohorts of yeast-derived GM-CSF at 50, 125, or 250 micrograms/m2 daily by subcutaneous self-injection for 28 days. Measurements of HIV activity included serum acid-dissociated HIV p24 antigen levels, plasma and peripheral blood mononuclear cell (PBMC) limiting dilution HIV culture, and plasma HIV quantitative competitive polymerase chain reaction (PCR). Serum and intracellular zidovudine levels were measured as well as hematologic, immunologic, and toxicity parameters. Virologic measures showed neither significant upregulation nor downregulation of serum acid-dissociated HIV p24 antigen, plasma and PBMC HIV culture, or PCR in association with GM-CSF administration. A trend toward increased intracellular AZT levels was noted, but this did not achieve statistical significance (p = 0.073). CD4 and CD8 lymphocytes were essentially unaffected while absolute neutrophil counts increased with GM-CSF administration as expected. These data suggest that administration of GM-CSF does not perturb HIV activity or immunologic parameters in patients receiving AZT for advanced HIV disease. No potentiation of AZT antiviral effect was demonstrated.
Scadden
D T
DT
Division of Hematology/Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Pickus
O
O
Hammer
S M
SM
Stretcher
B
B
Bresnahan
J
J
Gere
J
J
McGrath
J
J
Agosti
J M
JM
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001772:Blood Cell Count / Q000187:drug effects; D015331:Cohort Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015215:Zidovudine / Q000627:therapeutic use*
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D016179:Granulocyte Colony-Stimulating Factor; D015215:Zidovudine