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Whole Genome Sequencing / RNA, Viral · Journal article
Diagnostic Microbiology and Infectious Disease · August 9, 2026
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This is a prospective characterization of HCV genotypes and resistance-associated substitutions in a small Indian cohort undergoing DAA therapy, with first-reported identification of subtype 6xa. The observation of NS5A resistance mutations in one patient who relapsed raises concerns about DAA susceptibility in specific subtypes, but the single-case relapse finding and small sample preclude generalizable treatment recommendations.
Prospective hospital-based observational study. Patients with confirmed active HCV infection receiving direct-acting antiviral therapy in a hospital-based setting in India.. Intervention: Direct-acting antiviral therapy (specific agents and regimens not detailed in source). n = 70. India (single centre implied by 'hospital-based study').
Genotype 3 predominated at 64.3% (n=45), followed by genotype 6 at 21.4% (n=15) and genotype 1 at 14.2% (n=10) Unusual HCV subtype 6xa detected in 2 patients with no NS5A resistance mutations identified One genotype 3b patient relapsed at 24 weeks post-DAA completion carrying NS5A resistance-associated substitutions 30 K and 31 M at both baseline and relapse, conferring high-level resistance to NS5A inhibitors
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Clinicians should be aware that HCV subtype 6xa exists in the Indian population and that genotype 3b patients may harbour baseline NS5A resistance mutations conferring potential treatment failure; however, the single relapse case does not provide sufficient evidence to change current DAA prescribing practice, and surveillance in larger cohorts is needed.
First descriptive report of HCV genome sequencing and resistance patterns in an Indian cohort; uncontrolled, hospital-based study with small sample and no comparator arm, useful for surveillance but insufficient to guide treatment decisions.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should be aware that HCV subtype 6xa exists in the Indian population and that genotype 3b patients may harbour baseline NS5A resistance mutations conferring potential treatment failure; however, the single relapse case does not provide sufficient evidence to change current DAA prescribing practice, and surveillance in larger cohorts is needed.
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Introduction and objectives. Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment.Patients and methods. In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis.Results. Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors.Conclusion. This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.
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