Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Abstract

Background: Severe complications of chronic hepatitis C -i.e. cirrhosis and hepatocellular carcinoma -are important causes of morbidity and mortality worldwide. Despite the overwhelming rates of sustained virologic response achieved after therapy with different combinations of direct-acting antiviral drugs (DAAs), treatment failure is still recorded, and is due to the mutations harboured by hepatitis C virus (HCV) resistance associated variants (RAVs) selected during therapy. Baseline RAVs testing was found significant for guiding treatment in the cases of treatment failure and, sometimes, in naïve patients.Methods: Romanian chronic hepatitis C patients unexposed to DAAs and infected with subtype 1b HCV were studied. Serum samples were used for Sanger population sequencing of a fragment containing NS3 viral protease, known to harbour resistance mutation against protease inhibitors (PIs).Results: Catalytic triad and zinc-binding site in the studied sequences were conserved. Low-intermediate resistance mutations to first generation PIs were detected either alone or in conjunction with resistance substitutions associated with second generation PIs. Cross-resistance and reduced susceptibility to certain DAAs were observed.Discussion: This study focused on HCV patients infected with subtype 1b strains, the most prevalent in Romania. The rate of RAVs found in this work is consistent with the results reported by similar studies from other countries. Noticeably, numerous polymorphisms of unknown significance to DAAs resistance, but reflecting the

Extended panel of biomarkers for long term monitoring of effectiveness of 3 direct antiviral regimen in HCV genotype 1b infection: results from a Romanian infectious disease hospital

“…No data regarding the patients' compliance could be collected. The number of the patients with long-term follow-up is small; no antiviral resistance profile could be evaluated in patients who failed the treatment, even if several studies show that treatment failure is due to the mutations harbored by HCV resistance associated variants (RAVs) selected during therapy [25].…”