title: A randomized, placebo-controlled trial of granulocyte-macrophage colony-stimulating factor and nucleoside analogue therapy in AIDS.
abstract: Preliminary preclinical and clinical data suggest that granulocyte-macrophage colony-stimulating factor (GM-CSF) may decrease viral replication. Therefore, 105 individuals with AIDS who were receiving nucleoside analogue therapy were enrolled in a placebo-controlled, double-blind study and were randomized to receive either 125 microgram/m(2) of yeast-derived, GM-CSF (sargramostim) or placebo subcutaneously twice weekly for 6 months. Subjects were evaluated for toxicity and disease progression. A significant decrease in mean virus load (VL) was observed for the GM-CSF treatment group at 6 months (-0.07 log(10) vs. -0.60 log(10); P=.02). More subjects achieved human immunodeficiency virus (HIV)-RNA levels <500 copies/mL at >/=2 evaluations (2% on placebo vs. 11% on GM-CSF; P=.04). Genotypic analysis of 46 subjects demonstrated a lower frequency of zidovudine-resistant mutations among those receiving GM-CSF (80% vs. 50%; P=.04). No difference was observed in the incidence of opportunistic infections (OIs) through 6 months or survival, despite a higher risk for OI among GM-CSF recipients. GM-CSF reduced VL and limited the evolution of zidovudine-resistant genotypes, potentially providing adjunctive therapy in HIV disease.
authors.affiliation: Universidade Federal da Bahia and 2Hospital Sao Rafael, Salvador, Bahia, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Brites
authors.forename: M J
authors.initials: MJ
authors.lastname: Gilbert
authors.forename: D
authors.initials: D
authors.lastname: Pedral-Sampaio
authors.forename: F
authors.initials: F
authors.lastname: Bahia
authors.forename: C
authors.initials: C
authors.lastname: Pedroso
authors.forename: A P
authors.initials: AP
authors.lastname: Alcantara
authors.forename: M D
authors.initials: MD
authors.lastname: Sasaki
authors.forename: J
authors.initials: J
authors.lastname: Matos
authors.forename: B
authors.initials: B
authors.lastname: Renjifo
authors.forename: M
authors.initials: M
authors.lastname: Essex
authors.forename: J B
authors.initials: JB
authors.lastname: Whitmore
authors.forename: J M
authors.initials: JM
authors.lastname: Agosti
authors.forename: R
authors.initials: R
authors.lastname: Badaro
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor