Pilot study of low-dose interleukin-2, pegylated interferon-alpha 2b, and ribavirin for the treatment of hepatitis C virus infection in patients with HIV infection.
BACKGROUND
Patients infected with hepatitis C virus (HCV) and human immunodeficiency virus have a diminished HCV virologic response to standard interferon (IFN)-based therapies. We explored the strategy of initial immunostimulatory therapy with interleukin (IL)-2, followed by the addition of specific anti-HCV therapy, as a possible synergistic approach to treatment.


METHODS
Coinfected subjects (n=23) with CD4 cell counts >300 cells/ micro L received low-dose IL-2 daily for 12 weeks, followed by pegylated IFN- alpha 2b and ribavirin for an additional 48 weeks. The primary end point was permanent discontinuation of treatment before week 24 due to toxicity or intolerance.


RESULTS
Six subjects (26.1%) discontinued treatment before week 24, and 11 (47.8%) discontinued treatment before week 60. Overall, 4 subjects discontinued because of adverse events. Four of 23 (17%; 95% confidence interval [CI], 5%-39%) had sustained virologic responses. Of 17 subjects with increased levels of alanine aminotransferase at baseline, 13 had follow-up measurements at week 60, of which 6 (46%) were normal.


CONCLUSIONS
Low-dose IL-2 plus PEG-IFN and ribavirin was associated with a high discontinuation rate. Although the study was not powered for efficacy, CIs surrounding the treatment response rate suggest that this strategy should not be pursued in larger trials.
Glesby
Marshall J
MJ
Weill Medical College of Cornell University, New York, NY 10021, USA. mag2005@med.cornell.edu
Bassett
Roland
R
Alston-Smith
Beverly
B
Fichtenbaum
Carl
C
Jacobson
Elizabeth L
EL
Brass
Clifford
C
Owens
Susan
S
Sulkowski
Mark
M
Race
Elizabeth M
EM
Sherman
Kenneth E
KE
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b