Triple therapy with first-generation protease inhibitors may be a milestone for chronic hepatitis C infection (HCV) treatment, but it also substantially increases rates of infection, especially in patients with advanced liver disease. Researchers from Medical University of Graz, Austria, citing reports that link boceprevir and telaprevir to impaired neutrophil elastase activity in vitro, conducted a study to determine whether protease inhibitors were at the root of the infections.
The study compared 152 chronic HCV patients treated with peginterferon and ribavirin, either with or without boceprevir and telaprevir, against 33 control patients. In both retrospective and prospective cohorts, clinically relevant infections were significantly more common during protease inhibitor therapy. Thirteen percent of retrospective patients developed infections on peginterferon and ribavirin vs 31% on protease inhibitors; 18% of the prospective patients on telaprevir and 33% of the boceprevir group developed clinically relevant infections. None of the patients receiving peginterferon and ribavirin developed infections, and they less often required hospitalization or treatment discontinuation.
The researchers also found neutrophil phagocytosis in patients dropped to 40% of baseline when protease inhibitors were added to peginterferon and ribavirin but returned to normal 6 months after treatment ended.
The researchers advise selecting patients for triple therapy carefully by focusing on other risk factors for infection and monitoring them closely during treatment.
Spindelboeck W, Horvath A, Tawdrous M, et al. PLoS ONE. 2016;11(3): e0150299. doi:10.1371/journal.pone.0150299