Baseline Plasma Metabotype Correlates With Direct-Acting Antiviral Therapy Nonresponse for HCV in HIV-HCV Coinfected Patients

Gaurav Tripathi; Sheetalnath Rooge; Manisha Yadav; Babu Mathew; Nupur Sharma; Vasundhra Bindal; Hamed Hemati; Jaswinder Singh Maras; Ekta Gupta

doi:10.3389/fmolb.2021.748014

Baseline Plasma Metabotype Correlates With Direct-Acting Antiviral Therapy Nonresponse for HCV in HIV-HCV Coinfected Patients

Front Mol Biosci. 2022 Jan 10:8:748014. doi: 10.3389/fmolb.2021.748014. eCollection 2021.

Authors

Gaurav Tripathi¹, Sheetalnath Rooge², Manisha Yadav¹, Babu Mathew¹, Nupur Sharma¹, Vasundhra Bindal¹, Hamed Hemati¹, Jaswinder Singh Maras¹, Ekta Gupta²

Affiliations

¹ Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
² Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India.

Abstract

Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV-HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV-HCV patients. Methods: Non-cirrhotic HIV-HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders). Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = -0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = -0.713) significantly differentiated between nonresponders from responders in HIV-HCV coinfected patients and was able to predict the failure of treatment response. Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV-HCV coinfected patients.

Keywords: HCV (hepatitis C); HIV - human immunodeficiency virus; coinfection (HIV infection); direct-acting antiviral drugs; metabolomic analyses.