COMBINATION OF GANCICLOVIR AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN THE TREATMENT OF CYTOMEGALOVIRUS RETINITIS IN AIDS PATIENTS

The efficacy and safety of a combination of ganciclovir plus GM-CSF wa s 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 mu g/kg daily subcutaneously) to maintain absolute neu trophil counts between 2500 and 5000 cells/mu l. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving gan ciclovir plus GMCSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving g anciclovir plus zidovudine who became neutropenic In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrop hil counts than ganciclovir-alone patients (p = 0.0001). Overall, 12.5 % of patients treated with GM-CSF developed neutropenia (absolute neu trophil counts < 500/mu l phase A and < 750/mu l phase B) compared wit h 45 % of patients treated without GM-CSE GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 misse d doses of a possible 6584 in the ganciclovir-alone group (p = 0.011). There was a trend, although not statistically significant, for patien ts in the GM-CSF group to experience delayed progression of their reti nitis. There was no consistent evidence that GM-CSF stimulated the pro liferation of cytomegalovirus or human immunodeficiency virus in the G M-CSF group compared with patients receiving ganciclovir alone. The ad dition of GM-CSF to standard ganciclovir therapy for the treatment of cytomegalovirus retinitis reduced the haematological toxicity of the a ntiviral drug and allowed closer adherence to the dosage schedule. In addition, patients were able to receive concomittant zidovudine therap y.