@article{32a57efcb16346dfb82a3361ccf11661,
title = "Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count: Results of the IDEAL study",
abstract = "Background. Myelosuppression due to pegylated interferon (peg-IFN) is common during treatment for hepatitis C virus. The relationship between infection risk and decreases in leukocyte lines, however, is not well established. The objective of this analysis was to determine the incidence of and risk factors for infections during peg-IFN/ribavirin (RBV) therapy. Methods. A total of 3070 treatment-naive, chronic hepatitis C genotype 1-infected patients were treated for up to 48 weeks with peg-IFN alfa-2b 1.5 μg/kg/week or 1 μg/kg/week, or peg-IFN alfa-2a 180 μg/week plus RBV. Ontreatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 109 cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 109 cells/L. Granulocyte colony-stimulating factor was prohibited. Data on infections were captured at each study visit and categorized according to MedDRA version 13.0. Results. A total of 581 (19%) patients experienced moderate, severe, or life-threatening infections as assessed by the investigator; 648 (21%) patients had at least 1 neutrophil count <0.75 × 109 cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 × 109 cells/L at any time while on treatment. Twelve patients had severe or life-threatening infection and grade 3/4 neutropenia, but only 4 had temporally related infections. In a multivariate logistic regression model, nadir lymphocyte count, history of depression, and female sex, but not nadir neutrophil count, were associated with moderate, severe, or life-threatening infection. Conclusions. Nadir lymphocyte count, not nadir neutrophil count, was independently associated with moderate, severe, or life-threatening infections in the IDEAL study. Clinicians should be aware of their patients' absolute lymphocyte counts during peg-IFN/RBV therapy; peg-IFN dose reductions may be a consideration in patients with significant lymphocytopenia (<0.5 × 109 cells/L).",
keywords = "Hepatitis C virus, Infections, Interferon, Lymphopenia, Neutropenia",
author = "Melia, {Michael T.} and Norbert Br{\"a}u and Fred Poordad and Lawitz, {Eric J.} and Shiffman, {Mitchell L.} and McHutchison, {John G.} and Muir, {Andrew J.} and Galler, {Greg W.} and Nyberg, {Lisa M.} and Lee, {William M.} and Eugene Schiff and Jianmin Long and Stephanie Noviello and Brass, {Clifford A.} and Pedicone, {Lisa D.} and Sulkowski, {Mark S.}",
note = "Funding Information: Potential conflicts of interest. M. T. M. has provided expert testimony unrelated to HCV infection. N. B. has served on the advisory board for Jans-sen; has received research funding from Bristol-Myers Squibb, Vertex, and Gilead; and is a member of the speakers{\textquoteright} bureaus for Vertex and Onyx. F. P. has received research funding from Abbvie, Achillon Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead Sciences, GlaxoSmithKline, Globe-lmmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Medarex, Medtronic, Merck, Novartis, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Vertex Pharmaceuticals, and ZymoGenetics; has served as an advisor to Abbvie, Achillon Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Globelmmune, Merck, Santaris Pharmaceuticals, Tibotec/Janssen, Theravance, and Vertex Pharmaceuticals; and is a member of the speakers{\textquoteright} bureaus for Gilead, Kad-mon, Merck, Onyx/Bayer, Salix, and Vertex. E. J. L. has received research funding from Merck; has served as consultant to Abbott Laboratories, Achil-lon Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, BioCryst, Biotica, Enanta, Globelmmune, Idenix Pharmaceuticals, Inhibitex Pharmaceuticals, Janssen, Merck, Novartis, Pharmasset, Santaris Pharmaceuticals, Tibotec, Theravance, and Vertex Pharmaceuticals; has received research funding from Abbott Laboratories, Achillon Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Globelmmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Medarex, Medtronic, Merck, Novartis, Phar-masset, Presidio, Roche, Santaris Pharmaceuticals, Schering-Plough, Scynexis Pharmaceuticals, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics; and is a member of the speakers{\textquoteright} bureaus for Gilead, Kadmon, Merck, and Vertex. M. L. S. has received research funding from Abbott, Achillion, Bristol-Myers Squibb, Gilead, Merck, and the Virginia Commonwealth University Medical Center; has served as consultant to Bristol-Myers Squibb, Gilead, Janssen, Merck, and Vertex; and is a member of the speakers{\textquoteright} bureaus for Genentech, Gilead, Merck, and Vertex. J. G. M. is an employee of and owns stock or stock options in Gilead Sciences. A. J. M. has received research funding from Abbott, Achillon Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Globelmmune, Medtronic, Merck, Pfizer, Roche, Scynexis Pharmaceuticals, and Vertex Pharmaceuticals, and has served as a consultant for Achillon Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Merck, Profectus BioSciences, Salix, Scynexis Pharmaceuticals, and Vertex Pharmaceuticals. G. W. G. has received research funding from Schering-Plough. L. M. N. has received research support from Abbvie, Bristol-Myers Squibb, Gilead, Pharmasset, Roche/Genentech, and Schering-Plough/Merck; has served as a consultant to Schering-Plough/Merck; and is a member of the speakers{\textquoteright} bureau for Schering-Plough/Merck. W. M. L. has received research support from Anadys Pharmaceuticals, Boehringer-Ingelheim, Bristol-Myers Squibb, Cumberland, Gilead, GlaxoSmithKline, Merck, Roche, and Siemens, and has served as a consultant to Lilly and Novartis. E. S. has served as a consultant for Gilead and Merck, and has received research funding from Abbott, Anadys Pharmaceuticals, Beckman Coulter, Bristol-Myers Squibb, Discovery Life Sciences, Gilead, Medtronics, Merck, Novelos Therapeutics, Orsure Technologies, Roche Molecular, and Vertex Pharmaceuticals. J. L. is an employee of Merck. S. N. has served as a consultant to Schering-Plough, is a former employee of Schering-Plough, is a current employee of Bristol-Myers Squibb, and owns stock or stock options in Schering-Plough/Merck and Bristol-Myers Squibb. C. A. B. is a former employee of Merck/Schering-Plough; is a current employee of Novartis, owns stock and stock options in Merck; and owns stock in Novartis. L. D. P. is a former employee of Schering-Plough and owns stock or stock options in Schering-Plough. M. S. S. has received research funding from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, and Vertex Pharmaceuticals, and has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, and Vertex Pharmaceuticals. Funding Information: This work was supported by grants from Schering-Plough Research Institute, now Merck Research Laboratories. Funding Information: Financial support. This work was supported by grants from Schering-Plough Research Institute, now Merck Research Laboratories. Publisher Copyright: {\textcopyright} The Author 2014. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2014",
doi = "10.1093/cid/ciu009",
language = "English (US)",
volume = "58",
pages = "960--969",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "7",
}