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. Neutropenia often leads to dose-reduction or discontinuation of important myelosuppressive 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-comparative, multicentre study in 200 HIV-positive patients with neutropenia [absolute neutrophil count (ANC) <1.0 x 10⁹/l]. Filgrastim was started at 1 μg/kg/day subcutaneously for 28 days. This initial treatment phase was followed by a maintenance phase, using 300 μg on 1-7 days/week. In both phases the dose of filgrastim was adjusted to achieve an ANC of 2-5 x 10⁹/l. Results: Filgrastim reversed neutropena in 98% of patients (ANC ≤ 2 x 10⁹/l), with a median time to reversal of 2 days (range 1-16) and a median dose of 1 μg/kg/day (range 0.5-10). Most patients (96%) achieved reversal of neutropenia with a filgrastim dose of ≤ 300 μg/day (≤ 1 vial/day). Normal ANCs were then maintained with a median of 1 μg/kg/day (range 0.22-10.6) during the treatment phase and 3 x 300 μg vials/week (range 1-7) during the maintenance phase. 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 allowed > 80% of patients to increase or maintain dose-levels of these four medications or add them to their therapy. The number of these four medications received per patient increased by > 20% during filgrastim therapy. Filgrastim was well tolerated. CD4, CD8 and total lymphocyte counts all increased slightly, and there was no difference in HIV-1 p24 antigen levels. Conclusion: Filgrastim rapidly reverses neutropenia and maintains normal ANC in patients with HIV infection. This allows greater use of myelosuppressive medications without the potentially life-threatening complications of neutropenia.