Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients

Abstract

The efficacy and safety of a combination of ganciclovir plus GM-CSF was evaluated in AIDS patients with cytomegalovirus retinitis. In phase A, patients were randomized to receive ganciclovir, 5 mg/kg every 12 h for 14 days followed by 5 mg/kg daily, with (n=24) or without (n=29) GM-CSF (1-8 μg/kg daily subcutaneously) to maintain absolute neutrophil counts between 2500 and 5000 cells/μl. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving ganciclovir plus GM-CSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving ganciclovir plus zidovudine who became neutropenic. In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrophil counts than ganciclovir-alone patients (p=0.0001). Overall, 12.5 % of patients treated with GM-CSF developed neutropenia (absolute neutrophil counts<500/μl phase A and<750/μl phase B) compared with 45 % of patients treated without GM-CSF. GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 missed doses of a possible 6584 in the ganciclovir-alone group (p=0.011). There was a trend, although not statistically significant, for patients in the GM-CSF group to experience delayed progression of their retinitis. There was no consistent evidence that GM-CSF stimulated the proliferation of cytomegalovirus or human immunodeficiency virus in the GM-CSF group compared with patients receiving ganciclovir alone. The addition of GM-CSF to standard ganciclovir therapy for the treatment of cytomegalovirus retinitis reduced the haematological toxicity of the antiviral drug and allowed closer adherence to the dosage schedule. In addition, patients were able to receive concomittant zidovudine therapy. © 1994 Friedr. Vieweg & Sohn Verlagsgesellschaft mbH.