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1.
Hepatology ; 78(2): 607-620, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36999537

RESUMEN

BACKGROUND AND AIMS: Suboptimal rates of sustained virological response have been reported in patients infected with an "unusual," non-1a/1b HCV genotype 1 subtype. The objectives of this study were to assess the proportion of non-1a/1b genotype 1 subtypes in a population of HCV-infected patients who failed to achieve sustained virological response after first-line direct-acting antiviral treatment, to virologically characterize their failures and to assess their outcomes on retreatment. APPROACH AND RESULTS: Samples addressed between January 2015 and December 2021 to the French National Reference Center for Viral Hepatitis B, C, and D were prospectively analyzed by means of Sanger and deep sequencing. Among 640 failures, 47 (7.3%) occurred in patients infected with an "unusual" genotype 1 subtype. Samples were available in 43 of them; 92.5% of these patients were born in Africa. Our results show the presence at baseline and at treatment failure of NS3 protease and/or NS5A polymorphisms conferring inherent reduced susceptibility to direct-acting antivirals in these patients, together with the presence at failure of additional resistance-associated substitutions not naturally present as dominant species, but jointly selected by first-line therapy. CONCLUSIONS: Patients infected with "unusual" HCV genotype 1 subtypes are over-represented among direct-acting antiviral treatment failures. Most of them were born and likely infected in sub-Saharan Africa. "Unusual" HCV genotype 1 subtypes naturally carry polymorphisms that confer reduced susceptibility to the drugs currently used to cure hepatitis C, in particular the NS5A inhibitors. Retreatment with sofosbuvir plus an NS3 protease and an NS5A inhibitor is generally efficacious.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Humanos , Antivirales , Hepatitis C Crónica/tratamiento farmacológico , Genotipo , Quimioterapia Combinada , Farmacorresistencia Viral/genética , Proteínas no Estructurales Virales/genética , Hepacivirus/genética , Insuficiencia del Tratamiento , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Retratamiento , Péptido Hidrolasas/genética , Péptido Hidrolasas/uso terapéutico
2.
Emerg Infect Dis ; 26(6): 1287-1290, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32441621

RESUMEN

We report the discovery of a new orthobunyavirus, Cristoli virus, by means of shotgun metagenomics. The virus was identified in an immunodepressed patient with fatal encephalitis. Full-length genome sequencing revealed high-level expression of a virulence factor, possibly explaining the severity of the infection. The patient's recent history suggests circulation in France.


Asunto(s)
Encefalitis , Orthobunyavirus , Virus , Francia/epidemiología , Humanos , Metagenómica , Orthobunyavirus/genética
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