Reactions 1704, p43 - 2 Jun 2018 Viral resistance and treatment failure secondary to acquired gene mutation: 23 case reports In a study, 23 patients [ages and sexes not stated] developed viral resistance and treatment failure secondary to acquired gene mutation following direct acting antiviral (DAA) therapy with asunaprevir, beclabuvir, daclatasvir, ledipasvir, peginterferon, ribavirin, simeprevir or sofosbuvir for chronic genotype 1b hepatitis-C virus (HCV) infection [routes, dosages and durations of treatments to reactions onsets not stated]. The patients, who had chronic genotype 1b hepatitis-C virus (HCV) infection, and who had failed to respond to prior DAA treatment were enrolled in a study. Of these, 16 patients had received prior DAA treatment with daclatasvir plus asunaprevir, two patients had received simeprevir plus peg- interferon and ribavirin, which was later switched to daclatasvir plus asunaprevir, one patient had received daclatasvir plus asunaprevir, which was later switched to ledipasvir plus sofosbuvir and that was again switched to daclatasvir, asunaprevir plus beclabuvir, one patient had received daclatasvir plus asunaprevir, which was later switched to daclatasvir, asunaprevir plus beclabuvir, one patient had received ledipasvir plus sofosbuvir, which was later switched to daclatasvir, asunaprevir plus beclabuvir, one patient had received ledipasvir plus sofosbuvir, which was later switched to ledipasvir plus sofosbuvir, and the remaining one patient had received simeprevir plus peg-interferon and ribavirin, which was later switched to daclatasvir plus asunaprevir, that was again changed to ledipasvir plus sofosbuvir, and that was again switched to daclatasvir, asunaprevir plus beclabuvir. Subsequently, 16 patients developed relapse of HCV infections after the cessation of the DAA treatment, and remaining seven patients developed breakthrough HCV infections during the DAA treatment. The DAA therapy was eventually stopped in the seven patients, who developed breakthrough HCV infections during the therapy. After 1–38 months of end of the DAA therapy (at the current presentation), a gene analysis was performed, which revealed presence of treatment-emergent drug resistance-associated variants (RAVs). It was determined that this acquired gene mutation had caused resistance to the DAA treatment resulting in treatment failure. Author comment: "A substantial number of patients who have failed prior DAA treatments acquire RAVs. Treatment- emergent NS5A-RAVs, in particular, are known to persist for a long time, suggesting that they do not impose a high fitness trade off." "According to our findings and previous reports, RAVs present after failure of DAA treatment may reflect complex patterns and remain refractory to DAA re-treatment." Teraoka Y, et al. Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice. Biochemical and Biophysical Research Communications 500: 152-157, No. 2, 2 Jun 2018. Available from: URL: https:// doi.org/10.1016/j.bbrc.2018.04.005 - Japan 803323778 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704
Reactions Weekly – Springer Journals
Published: Jun 2, 2018
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