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

AIDS Research and Human Retroviruses
Veronique NussenblattShyam Kottilil

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 mug/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 t...Continue Reading

Associated Clinical Trials

Jun 28, 2001·Shyamasundaran Kottilil, M.D., Shyamasundaran Kottilil, M.D.

References

Sep 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S OkadaS Mishiro
Mar 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L RoffiF Dianzani
Oct 31, 1998·Journal of Viral Hepatitis·J M Pawlotsky
Jul 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·E J HeathcoteD G Albert
Jan 4, 2003·Gastroenterology·Marc G GhanyJay H Hoofnagle
Feb 1, 2003·Annals of Internal Medicine·Mark S Sulkowski, David L Thomas
Jul 30, 2004·The New England Journal of Medicine·Francesca J TorrianiUNKNOWN APRICOT Study Group
Jul 30, 2004·The New England Journal of Medicine·Raymond T ChungUNKNOWN AIDS Clinical Trials Group A5071 Study Team
Dec 16, 2004·JAMA : the Journal of the American Medical Association·Fabrice CarratUNKNOWN ANRS HCO2 RIBAVIC Study Team
Aug 8, 2006·Gastroenterology·Hari S ConjeevaramUNKNOWN Virahep-C Study Group

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.