FILGRASTIM TO TREAT NEUTROPENIA AND SUPPORT MYELOSUPPRESSIVE MEDICATION DOSING IN HIV-INFECTION

Background: Patients with HIV infection frequently experience disease or treatment-related myelosuppression leading to neutropenia. Neutrope nia often leads to dose-reduction or discontinuation of important myel osuppressive therapy. Objective: To examine the efficacy and safety of filgrastim for reversing neutropenia and determine the effect of this on use of myelosuppressive medications. Design: Open-label, non-compa rative, multicentre study in 200 HIV-positive patients with neutropeni a [absolute neutrophil count (ANC) < 1.0 x 10(9)/l]. Filgrastim was st arted at 1 mu g/kg/day subcutaneously for 28 days. This initial treatm ent phase was followed by a maintenance phase, using 300 mu g on 1-7 d ays/week. In both phases the dose of filgrastim was adjusted to achiev e an ANC of 2-5 x 10(9)/l. Results: Filgrastim reversed neutropenia in 98% of patients (ANC greater than or equal to 2 x 10(9)/l), with a me dian time to reversal of 2 days (range 1-16) and a median dose of 1 mu g/kg/day (range 0.5-10). Most patients (96%) achieved reversal of neu tropenia with a filgrastim dose of less than or equal to 300 mu g/day (less than or equal to 1 vial/day). Normal ANCs were then maintained w ith a median of 1 mu g/kg/day (range 0.22-10.6) during the treatment p hase and 3 x 300 pg vials/week (range 1-7) during the maintenance phas e. Ganciclovir, zidovudine, co-trimoxazole and pyrimethamine were the drugs most frequently considered to be causing neutropenia, and 83% of patients received one or more of these in the study. Filgrastim allow ed > 80% of patients to increase or maintain dose-levels of these four medications or add them to their therapy. The number of these four me dications received per patient increased by > 20% during filgrastim th erapy. Filgrastim was well tolerated. CD4, CD8 and total lymphocyte co unts all increased slightly, and there was no difference in HIV-1 p24 antigen levels. Conclusion: Filgrastim rapidly reverses neutropenia an d maintains normal ANC in patients with HIV infection. This allows gre ater use of myelosuppressive medications without the potentially life- threatening complications of neutropenia.