title: The safety and efficacy of granulocyte-macrophage colony-stimulating factor (Sargramostim) added to indinavir- or ritonavir-based antiretroviral therapy: a randomized double-blind, placebo-controlled trial.
abstract: Sargramostim is a yeast-derived, recombinant human granulocyte-macrophage colony-stimulating factor with therapeutic potential in human immunodeficiency virus (HIV) infection. Its safety and activity when used in combination with protease inhibitors were evaluated in a randomized, double-blind trial in which 20 HIV-infected subjects on stable antiretroviral regimens, including indinavir or ritonavir, received sargramostim or placebo 3 times a week for 8 weeks. Analysis of HIV virus load excluded any 0. 5 log10 increase due to sargramostim (95% confidence interval, -0.68 to 0.44). Sargramostim was well tolerated, and inflammatory cytokines and surrogate markers of disease progression, such as serum levels of interleukin-10 and soluble tumor necrosis factor receptors types Iota and IotaIota, remained stable in subjects receiving sargramostim. Sargramostim treatment was associated with a trend toward decreased HIV RNA (>0.5 log10) and increased CD4+ cell count (>30%). These results became statistically significant only when subjects with baseline virus loads within the limits of detection or baseline CD4 cell count >50 were analyzed. No difference in indinavir pharmacokinetics was observed before or after sargramostim therapy.
authors.affiliation: Division of Infectious Diseases, Roger Williams Medical Center, Providence, RI 02908, USA. Gail_Skowron@brown.edu
authors.forename: G
authors.initials: G
authors.lastname: Skowron
authors.forename: D
authors.initials: D
authors.lastname: Stein
authors.forename: G
authors.initials: G
authors.lastname: Drusano
authors.forename: K
authors.initials: K
authors.lastname: Melbourne
authors.forename: J
authors.initials: J
authors.lastname: Bilello
authors.forename: D
authors.initials: D
authors.lastname: Mikolich
authors.forename: K
authors.initials: K
authors.lastname: Rana
authors.forename: J M
authors.initials: JM
authors.lastname: Agosti
authors.forename: A
authors.initials: A
authors.lastname: Mongillo
authors.forename: J
authors.initials: J
authors.lastname: Whitmore
authors.forename: M J
authors.initials: MJ
authors.lastname: Gilbert
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers; D016001:Confidence Intervals; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012367:RNA, Viral / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D015415:Biomarkers; D017320:HIV Protease Inhibitors; D010919:Placebos; D012367:RNA, Viral; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D016753:Interleukin-10; C081222:sargramostim; D019469:Indinavir; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019438:Ritonavir