Immunodeficiency and intrinsic IFN resistance are associated with viral breakthrough to HCV therapy in HIV-coinfected patients

Veronique Nussenblatt, Mary McLaughlin, Catherine A. Rehm, Richard A. Lempicki, Terry Brann, Jun Yang, Michael Proschan, Helene C. Highbarger, Robin L. Dewar, Tom Imamichi, Chad Koratich, Avidan U. Neumann, Henry Masur, Michael A. Polis, Shyam Kottilil

Research output: Contribution to journalArticle

Abstract

Viral breakthroughs (VB), defined as having detectable HCV VL while on anti-HCV therapy after achieving maximal suppression, have not yet been characterized with the use of PEG-IFN in HIV/HCV-coinfected patients. We evaluated possible mechanisms for VB among HIV/HCV-coinfected patients receiving PEG-IFN/RBV. Thirty HIV/HCV coinfected patients were treated with PEG-IFN (1.5 μg/kg sc qwk) and RBV (1-1.2 g daily) for 48 weeks. Liver chemistry, HCV VL, genotyping, DNA microarray, and sequencing of HCV E-2 envelope were performed before and during treatment. VB had lower baseline HCV VL but higher ALT and AST than relapsers (ETR) (p < 0.05) and lower CD4+ T lymphocytes (%) than patients with sustained virological responses (SVR), but similar first and second phase HCV viral kinetics (vs. ETR and SVR; p > 0.05). HCV genotypes and envelope sequences were similar for patients with VB pretreatment and at break-through. VB had higher levels of interferon-induced gene (IFIG) expression pretreatment than patients with ETR (p < 0.01). HIV/HCV-coinfected patients have a high rate of VB on PEG-IFN/RBV therapy characterized by higher levels of IFIG expression, immunodeficiency, and hepatic inflammation. Novel strategies are required for the treatment of persons with VB.

Original languageEnglish (US)
Pages (from-to)1354-1359
Number of pages6
JournalAIDS research and human retroviruses
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2007

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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  • Cite this

    Nussenblatt, V., McLaughlin, M., Rehm, C. A., Lempicki, R. A., Brann, T., Yang, J., Proschan, M., Highbarger, H. C., Dewar, R. L., Imamichi, T., Koratich, C., Neumann, A. U., Masur, H., Polis, M. A., & Kottilil, S. (2007). Immunodeficiency and intrinsic IFN resistance are associated with viral breakthrough to HCV therapy in HIV-coinfected patients. AIDS research and human retroviruses, 23(11), 1354-1359. https://doi.org/10.1089/aid.2007.0091