Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count: Results of the IDEAL study

Interferon alfa has been used to treat chronic hepatitis C virus (HCV) infection since the early 1990s and remains the backbone of many treatment regimens involving HCV protease inhibitors [1–3]. Interferon alfa, however, has many side effects, including cytopenias [1]. When patients are treated with one of the long-acting, pegylated formulations of interferon, pegylated interferon (peg-IFN) alfa-2a, or peg-IFN alfa-2b, in combination with ribavirin (RBV) for up to 48 weeks, the incidence of severe neutropenia, defined as an absolute neutrophil count (ANC) of <0.5 × 109 cells/L, ranges from 4% to 12% [4, 5]. Furthermore, more modest declines in ANC to <0.75 × 109 cells/L have been reported in up to 30% of patients [4, 5]. Due to concern for increased infection risk in the setting of neutropenia, the prescribing information for both approved peg-IFN products recommends peg-IFN dose reduction and discontinuation in patients with ANC <0.75 × 109 cells/L and <0.5 × 109 cells/L, respectively [4, 5]. These treatment modifications are not without consequence; they have been associated with a decreased likelihood of achieving sustained virologic response (SVR) [6–8]. In this context, the relationship of neutropenia and incident infection during treatment with peg-IFN-based HCV therapy has been extensively investigated. The risk of infection associated with severe neutropenia due to chemotherapy among cancer patients and recipients of hematopoietic cell transplants is well established; however, most studies have not demonstrated any increased infection risk among patients who develop neutropenia while receiving peg-IFN [6, 9–14]. Nevertheless, up to 23% of patients develop acute infections during HCV treatment [6, 10–14]. The risk factors for acute infection, particularly clinically severe infections, have not been fully established in these relatively small studies [6, 10–14]. Because of the large number of patients treated with peg-IFN (>3000) and the breadth of data collected, the Individualized Dosing Efficacy vs Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) study provides a unique opportunity to evaluate the incidence of and risk factors associated with acute infections among patients receiving HCV treatment with peg-IFN/RBV, with an emphasis on understanding the relationship between treatment-induced cytopenias and infection [15].