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Antiretroviral therapy, interferon sensitivity, and virologic setpoint in human immunodeficiency virus/hepatitis C virus coinfected patients
Author(s) -
Balagopal Ashwin,
Kandathil Abraham J.,
Higgins Yvonne H.,
Wood Jonathan,
Richer Justin,
Quinn Jeffrey,
Eldred Lois,
Li Zhiping,
Ray Stuart C.,
Sulkowski Mark S.,
Thomas David L.
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.27158
Subject(s) - hepatitis c virus , interquartile range , medicine , viral load , coinfection , immunology , virology , hepatitis c , interferon , hepacivirus , virus , alpha interferon , gastroenterology
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 (ΔHCV IFN ) 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 ΔHCV IFN at 72 hours (ΔHCV IFN,72 ) increased in 15/19 (78.9%) participants by a median (interquartile range [IQR]) of 0.11 log 10 IU/mL (0.00‐0.40; P < 0.05). Increases in ΔHCV IFN,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 ΔHCV IFN,72 of 0.78 log 10 IU/mL (95% confidence interval [CI] 0.36,1.20). Pre‐ and post‐ART ΔHCV IFN,72 were closely associated ( r = 0.87; P < 0.001). HCV virologic setpoint also changed after ART (ΔHCV ART ): transient median increases of 0.28 log 10 IU/mL were followed by eventual median decreases from baseline of 0.21 log 10 IU/mL ( P = 0.002). A bivariate model of HIV RNA control ( P < 0.05) and increased expression of a nine‐gene ISG signature ( P < 0.001) predicted the eventual decreased ΔHCV ART . 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. (H epatology 2014;60:477–486)