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

Sargramostim is a yeast-derived, recombinant human granulocyte-macrophage c olony-stimulating factor with therapeutic potential in human immunodeficien cy 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, inclu ding indinavir or ritonavir, received sargramostim or placebo 3 times a wee k for 8 weeks. Analysis of HIV virus load excluded any 0.5 log,. increase d ue to sargramostim (95% confidence interval, -0.68 to 0.44). Sargramostim w as well tolerated, and inflammatory cytokines and surrogate markers of dise ase progression, such as serum levels of interleukin-10 and soluble tumor n ecrosis factor receptors types I and II, remained stable in subjects receiv ing sargramostim. Sargramostim treatment was associated with a trend toward decreased HIV RNA (>0.5 log(10)) and increased CD4(+) cell count (>30%), T hese results became statistically significant only when subjects with basel ine 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.