Use of filgrastim as adjuvant therapy in patients with AIDS-related cytomegalovirus retinitis

Background: Neutropenia in AIDS predisposes to bacterial infection. Granulocyte colony-stimulating factor (filgrastim) can reverse neutropenia. Objective: To determine the effects of filgrastim on bacterial infections, hospitalization, and mortality in patients with cytomegalovirus retinitis and AIDS. Methods: Using a person-time analysis, a retrospective cohort study of filgrastim adjuvant therapy in three multicenter clinical trials of anti-cytomegalovirus therapy during the period 1990-1997 measured filgrastim use, bacterial infections, and mortality. Results: Of 719 patients, 379 patients used filgrastim for 31% of the follow-up time. There was an inverse relationship between the 389 confirmed bacterial infections, including 186 bacteremias, and absolute neutrophil counts. Before adjustment for CD4 T-cells counts and antibiotic/antiretroviral therapy, filgrastim was associated with reduced risk of catheter-related bacteremia [relative risk (RR), 0.52; P = 0.02] and repeat bacterial infection (RR, 0.41; P = < 0.01). After adjustment, the RR of catheter-related bacteremia with filgrastim use was decreased (RR_adj, 0.69; P = 0.16) and the RR of repeat bacterial infection with filgrastim use was of marginal significance (RR_adj, 0.57; P = 0.07), possibly due to the confounding effect of trimethoprim-sulfamethoxazole on all bacteremia (RR_adj, 0.55; P= < 0.01). Unrelated to bacteremia, filgrastim use was associated with a 56% reduction in mortality (P < 0.01). Conclusions: There was a large survival benefit associated with filgrastim use in this study but the reasons for this benefit are unclear. Although a reduction in crude risk of some bacterial infections with filgrastim use was detected, after adjustment for potentially confounding factors these risks were smaller and no longer statistically significant.