Antiretroviral therapy, interferon sensitivity, and virologic setpoint in human immunodeficiency virus/hepatitis C virus coinfected patients

Ashwin Balagopal, Abraham Kandathil, Yvonne H. Higgins, Jonathan Wood, Justin Richer, Jeffrey Quinn, Lois Eldred, Zhiping Li, Stuart Campbell Ray, Mark Sulkowski, David L Thomas

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause substantial mortality, especially in persons chronically infected with both viruses. HIV infection raises plasma HCV RNA levels and diminishes the response to exogenous alpha interferon (IFN). The degree to which antiretroviral therapy (ART) control of infection overcomes these HIV effects is unknown. Participants with HIV-HCV coinfection were enrolled in a trial to measure HCV viral kinetics after IFN administration (ΔHCVIFN) twice: initially before (pre-ART) and then after (post-ART) HIV RNA suppression. Liver tissue was obtained 2-4 hours before each IFN injection to measure interferon stimulated genes (ISGs). Following ART, the ΔHCVIFN at 72 hours (ΔHCVIFN,72) increased in 15/19 (78.9%) participants by a median (interquartile range [IQR]) of 0.11 log10 IU/mL (0.00-0.40; PIFN,72 post-ART were associated with decreased hepatic expression of several ISGs (r=-0.68; P=0.001); a 2-fold reduction in a four-gene ISG signature predicted an increase in ΔHCVIFN,72 of 0.78 log10 IU/mL (95% confidence interval [CI] 0.36,1.20). Pre- and post-ART ΔHCVIFN,72 were closely associated (r=0.87; PART): transient median increases of 0.28 log10 IU/mL were followed by eventual median decreases from baseline of 0.21 log10 IU/mL (P=0.002). A bivariate model of HIV RNA control (PART. Conclusion: ART is associated with lower post-IFN HCV RNA levels and that change is linked to reduced hepatic ISG expression. These data support recommendations to provide ART prior to IFN-based treatment of HCV and may provide insights into the pathogenesis of HIV-HCV coinfection. (Hepatology 2014;60:477-486)

Original languageEnglish (US)
Pages (from-to)477-486
Number of pages10
JournalHepatology
Volume60
Issue number2
DOIs
StatePublished - 2014

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Hepacivirus
Interferons
HIV
RNA
Therapeutics
Coinfection
Genes
Liver
Gastroenterology
Virus Diseases
Infection Control
Interferon-alpha
Confidence Intervals
Viruses
Gene Expression
Injections
Mortality

ASJC Scopus subject areas

  • Hepatology

Cite this

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title = "Antiretroviral therapy, interferon sensitivity, and virologic setpoint in human immunodeficiency virus/hepatitis C virus coinfected patients",
abstract = "Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause substantial mortality, especially in persons chronically infected with both viruses. HIV infection raises plasma HCV RNA levels and diminishes the response to exogenous alpha interferon (IFN). The degree to which antiretroviral therapy (ART) control of infection overcomes these HIV effects is unknown. Participants with HIV-HCV coinfection were enrolled in a trial to measure HCV viral kinetics after IFN administration (ΔHCVIFN) twice: initially before (pre-ART) and then after (post-ART) HIV RNA suppression. Liver tissue was obtained 2-4 hours before each IFN injection to measure interferon stimulated genes (ISGs). Following ART, the ΔHCVIFN at 72 hours (ΔHCVIFN,72) increased in 15/19 (78.9{\%}) participants by a median (interquartile range [IQR]) of 0.11 log10 IU/mL (0.00-0.40; PIFN,72 post-ART were associated with decreased hepatic expression of several ISGs (r=-0.68; P=0.001); a 2-fold reduction in a four-gene ISG signature predicted an increase in ΔHCVIFN,72 of 0.78 log10 IU/mL (95{\%} confidence interval [CI] 0.36,1.20). Pre- and post-ART ΔHCVIFN,72 were closely associated (r=0.87; PART): transient median increases of 0.28 log10 IU/mL were followed by eventual median decreases from baseline of 0.21 log10 IU/mL (P=0.002). A bivariate model of HIV RNA control (PART. Conclusion: ART is associated with lower post-IFN HCV RNA levels and that change is linked to reduced hepatic ISG expression. These data support recommendations to provide ART prior to IFN-based treatment of HCV and may provide insights into the pathogenesis of HIV-HCV coinfection. (Hepatology 2014;60:477-486)",
author = "Ashwin Balagopal and Abraham Kandathil and Higgins, {Yvonne H.} and Jonathan Wood and Justin Richer and Jeffrey Quinn and Lois Eldred and Zhiping Li and Ray, {Stuart Campbell} and Mark Sulkowski and Thomas, {David L}",
year = "2014",
doi = "10.1002/hep.27158",
language = "English (US)",
volume = "60",
pages = "477--486",
journal = "Hepatology",
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TY - JOUR

T1 - Antiretroviral therapy, interferon sensitivity, and virologic setpoint in human immunodeficiency virus/hepatitis C virus coinfected patients

AU - Balagopal, Ashwin

AU - Kandathil, Abraham

AU - Higgins, Yvonne H.

AU - Wood, Jonathan

AU - Richer, Justin

AU - Quinn, Jeffrey

AU - Eldred, Lois

AU - Li, Zhiping

AU - Ray, Stuart Campbell

AU - Sulkowski, Mark

AU - Thomas, David L

PY - 2014

Y1 - 2014

N2 - Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause substantial mortality, especially in persons chronically infected with both viruses. HIV infection raises plasma HCV RNA levels and diminishes the response to exogenous alpha interferon (IFN). The degree to which antiretroviral therapy (ART) control of infection overcomes these HIV effects is unknown. Participants with HIV-HCV coinfection were enrolled in a trial to measure HCV viral kinetics after IFN administration (ΔHCVIFN) twice: initially before (pre-ART) and then after (post-ART) HIV RNA suppression. Liver tissue was obtained 2-4 hours before each IFN injection to measure interferon stimulated genes (ISGs). Following ART, the ΔHCVIFN at 72 hours (ΔHCVIFN,72) increased in 15/19 (78.9%) participants by a median (interquartile range [IQR]) of 0.11 log10 IU/mL (0.00-0.40; PIFN,72 post-ART were associated with decreased hepatic expression of several ISGs (r=-0.68; P=0.001); a 2-fold reduction in a four-gene ISG signature predicted an increase in ΔHCVIFN,72 of 0.78 log10 IU/mL (95% confidence interval [CI] 0.36,1.20). Pre- and post-ART ΔHCVIFN,72 were closely associated (r=0.87; PART): transient median increases of 0.28 log10 IU/mL were followed by eventual median decreases from baseline of 0.21 log10 IU/mL (P=0.002). A bivariate model of HIV RNA control (PART. Conclusion: ART is associated with lower post-IFN HCV RNA levels and that change is linked to reduced hepatic ISG expression. These data support recommendations to provide ART prior to IFN-based treatment of HCV and may provide insights into the pathogenesis of HIV-HCV coinfection. (Hepatology 2014;60:477-486)

AB - Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause substantial mortality, especially in persons chronically infected with both viruses. HIV infection raises plasma HCV RNA levels and diminishes the response to exogenous alpha interferon (IFN). The degree to which antiretroviral therapy (ART) control of infection overcomes these HIV effects is unknown. Participants with HIV-HCV coinfection were enrolled in a trial to measure HCV viral kinetics after IFN administration (ΔHCVIFN) twice: initially before (pre-ART) and then after (post-ART) HIV RNA suppression. Liver tissue was obtained 2-4 hours before each IFN injection to measure interferon stimulated genes (ISGs). Following ART, the ΔHCVIFN at 72 hours (ΔHCVIFN,72) increased in 15/19 (78.9%) participants by a median (interquartile range [IQR]) of 0.11 log10 IU/mL (0.00-0.40; PIFN,72 post-ART were associated with decreased hepatic expression of several ISGs (r=-0.68; P=0.001); a 2-fold reduction in a four-gene ISG signature predicted an increase in ΔHCVIFN,72 of 0.78 log10 IU/mL (95% confidence interval [CI] 0.36,1.20). Pre- and post-ART ΔHCVIFN,72 were closely associated (r=0.87; PART): transient median increases of 0.28 log10 IU/mL were followed by eventual median decreases from baseline of 0.21 log10 IU/mL (P=0.002). A bivariate model of HIV RNA control (PART. Conclusion: ART is associated with lower post-IFN HCV RNA levels and that change is linked to reduced hepatic ISG expression. These data support recommendations to provide ART prior to IFN-based treatment of HCV and may provide insights into the pathogenesis of HIV-HCV coinfection. (Hepatology 2014;60:477-486)

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