Antiretroviral therapy, interferon sensitivity, and virologic setpoint in human immunodeficiency virus/hepatitis C virus coinfected patients
Year: 2014
Type: article
Abstract: UNLABELLED: 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; P < 0.05). Increases in ΔHCVIFN,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; P < 0.001). HCV virologic setpoint also changed after ART (ΔHCVART ): 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 (P < 0.05) and increased expression of a nine-gene ISG signature (P < 0.001) predicted the eventual decreased ΔHCVART . 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.
Source: Hepatology
DOI: 10.1002/hep.27158
Institution: Johns Hopkins University
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Gilead Sciences, Johns Hopkins University, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute on Drug Abuse, NIH Office of the Director, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G1489286228, G1872012040, G270093248, HIV HCV Coinfection Antiviral Therapy and Fibrosis, The Progression of Hepatitis C Among IDUs with HIV, G4245178508, Institute for Clinical and Translational Research, Institute for Clinical and Translational Research, G9000038098, The Johns Hopkins Center for AIDS Research (JHU CFAR)
OpenAlex ID: W2155356028