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 language | English (US) |
|---|---|
| Pages (from-to) | 1354-1359 |
| Number of pages | 6 |
| Journal | AIDS Research and Human Retroviruses |
| Volume | 23 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Virology
- Infectious Diseases
Cite this
Immunodeficiency and intrinsic IFN resistance are associated with viral breakthrough to HCV therapy in HIV-coinfected patients. / Nussenblatt, Veronique; McLaughlin, Mary; Rehm, Catherine A.; Lempicki, Richard A.; Brann, Terry; Yang, Jun; Proschan, Michael; Highbarger, Helene C.; Dewar, Robin L.; Imamichi, Tom; Koratich, Chad; Neumann, Avidan U.; Masur, Henry; Polis, Michael A.; Kottilil, Shyam.
In: AIDS Research and Human Retroviruses, Vol. 23, No. 11, 01.11.2007, p. 1354-1359.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunodeficiency and intrinsic IFN resistance are associated with viral breakthrough to HCV therapy in HIV-coinfected patients
AU - Nussenblatt, Veronique
AU - McLaughlin, Mary
AU - Rehm, Catherine A.
AU - Lempicki, Richard A.
AU - Brann, Terry
AU - Yang, Jun
AU - Proschan, Michael
AU - Highbarger, Helene C.
AU - Dewar, Robin L.
AU - Imamichi, Tom
AU - Koratich, Chad
AU - Neumann, Avidan U.
AU - Masur, Henry
AU - Polis, Michael A.
AU - Kottilil, Shyam
PY - 2007/11/1
Y1 - 2007/11/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=38449092863&partnerID=8YFLogxK
U2 - 10.1089/aid.2007.0091
DO - 10.1089/aid.2007.0091
M3 - Article
C2 - 18184077
AN - SCOPUS:38449092863
VL - 23
SP - 1354
EP - 1359
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 11
ER -