G-CSF association with prolonged survival in HIV-infected patients with disseminated Mycobacterium avium complex...

Clarithromycin can ameliorate symptoms and improve survival in disseminated Mycobacterium avium complex (DMAC) infection. Optimal combinations of this drug with other agents remain unknown. Granulocyte colony stimulating factor (G-CSF) is a cytokine that can improve phagocytosis of M. avium complex in vitro. We aim to determine if G-CSF administration is associated with improved survival in patients with DMAC in a retrospective, cohort study. Case records from 1991 to 1995 of 91 patients with DMAC at Parkland Memorial Hospital were reviewed for date of initial DMAC diagnosis, baseline CD4 count, race, sex, antiretroviral use, G-CSF use, therapy for DMAC (clarithromycin, ethambutol, ciprofloxacin and rifabutin) and date of death. Of 91 cases identified, 25 were treated with G-CSF and 66 never received this drug. Baseline characteristics were similar in each group including CD4 count (40 cells/mm3 vs 33 cells/mm3, P=0.68), clarithromycin use (18 patients vs 52 patients, P=0.90), and antiretroviral use (20 patients vs 42 patients, P=0.21). Subjects treated with G-CSF lived longer than those who did not receive this drug (355 days vs 211 days, P<0.01). In the subgroup treated with clarithromycin, G-CSF was also associated with increased survival (377 days vs 252 days, P<0.01). Cox proportional hazards model showed a decreased risk of death in patients treated with G-CSF (RH=0.22, P<0.01), clarithromycin (RH=0.13, P<0.01) and ethambutol (RH=0.51, P=0.02). Ciprofloxacin and rifabutin use did not influence survival. These data support the use of clarithromycin and ethambutol in the treatment of DMAC. Addition of G-CSF to a regimen of clarithromycin and ethambutol may increase survival in DMAC and should be studied prospectively.