Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) has similar cure rates for patients coinfected with HCV and human immunodeficiency virus (HIV), relative to patients infected with HCV only. Researchers examined the potential of host plasma metabolites to predict treatment response in baseline patients with HIV-HCV and found that increased baseline levels of N-acetylspermidine and 2-acetolactate levels were associated with HCV treatment failure in patients with HIV-HCV.

The study, published in Frontiers in Molecular Biosciences, provided sofosbuvir and daclatasvir to 43 total non-cirrhotic patients with HIV-HCV over a 12-week period. Researchers measured pre- and post-treatment plasma metabolite profiles in 20 of the patients, among which 10 patients achieved sustained viral response (SVR) and 10 did not respond to treatment.

The lead author, Gaurav Tripathi, and colleagues identified 563 features using metabolomic and spectral databases. Pre-therapy, 39 metabolites (20 upregulated and 19 downregulated) were differentiated between responders and non-responders (foldchange [FC] ± 1.5; p < 0.05) and associated with tryptophan metabolism, nicotinamide metabolism, and others. After therapy, 62 plasma metabolites (12 upregulated and 50 downregulated; FC ± 1.5; p < 0.05) were differentiated between responders and non-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 non-responders.”

Finally, the researchers used random forest and multivariate linear regression analysis to identify that baseline levels of N-acetylspermidine (FC >2; area under curve [AUC] = 0.940; Bfactor = –0.267) and 2-acetolactate (FC >2; AUC = 0.880; Bfactor = –0.713) differed significantly between responders and non-responders and “was able to predict the failure of treatment response.”

Source: Frontiers in Molecular Biosciences