Hematologic toxicity associated with interferon-based hepatitis C therapy in HIV type 1-coinfected subjects.
BACKGROUND
This study investigates whether dose modifications for adverse hematologic effects or the use of hematopoietic growth factors influenced the outcome of therapy for hepatitis C virus (HCV) infection in patients who were coinfected with HCV and human immunodeficiency virus (HIV) and who were participants in a randomized, controlled trial.


METHODS
Subjects were randomized to receive ribavirin plus interferon-alfa-2a (IFN-alfa-2a) or pegylated IFN-alfa-2a for a total of 48 weeks. Doses were modified for a number of adverse effects (including hematologic toxicity), and hematopoietic growth factors were administered at the discretion of the physician. Associations of dose modifications or initiation of hematopoietic growth factor support with treatment outcomes were determined by standard statistical methods.


RESULTS
One hundred thirty-three subjects were included in this study. Subjects treated with pegylated IFN-alfa-2a were more likely to have had dose modifications (dose reduction or discontinuation) than were those treated with IFN-alfa-2a. By multivariate analysis, treatment with pegylated IFN-alfa-2a is associated with higher sustained virologic and/or histologic response. Dose modifications for nonhematologic toxicity are independently associated with lower sustained virologic and/or histologic responses. Although hematologic toxicity was not directly associated with clinical outcome in this analysis, use of hematopoietic growth factors was associated with an increased sustained virologic and/or histologic response.


CONCLUSIONS
Dose modifications for anti-HCV therapy may adversely affect the outcome of treatment of HCV in individuals who are coinfected with HIV. The use of hematopoietic growth factor support may be associated with an improved clinical response to therapy.
Behler
Caroline M
CM
Department of Hematology and Oncology, University of California-San Francisco, San Francisco, CA 94143-1270, USA. caroline.behler@ucsf.edu
Vittinghoff
Eric
E
Lin
Feng
F
Chung
Raymond T
RT
Peters
Marion G
MG
Robbins
Gregory K
GK
Volberding
Paul A
PA
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1; D006402:Hematologic Diseases / Q000139:chemically induced; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D020714:Maximum Tolerated Dose; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a