title: Naturally occurring hepatitis B virus (HBV) variants with primary resistance to antiviral therapy and S-mutants with potential primary resistance to adefovir in Argentina.
abstract: Hepatitis B virus (HBV) variants may either emerge in patients with chronic hepatitis B (CHB) as a result of positive selection pressure exerted by their own immune response, or during therapy with nucleos(t)ide analogues (NAs). Naturally occurring HBV variants with primary antiviral resistance are rarely observed. The aim of this study was to retrospectively analyze the (eventual) circulation of HBV variants with natural resistance to NAs currently used as therapy for CHB in Argentina. This study reports 13 cases of CHB-infected patients with natural antiviral resistance to at least one NA. Five of them were also carriers of S-variants that might escape the humoral immune system recognition with potential resistance to adefovir. In addition to the already reported A2 HBV subgenotype association to NAs natural resistance, E and F genotypes association to such resistance is described for the first time. These findings suggest that sequence analysis of the HBV reverse transcriptase might be an essential tool before starting antiviral therapy, in order to choose the proper NAs for optimizing the therapeutic management of chronically infected patients. Moreover, the circulation and transmission of S-mutants with resistance to such antiviral drugs should be of public health concern as they may represent an additional risk for the community.
authors.affiliation: Centro para el Estudio de Hepatitis Virales, Depto. de Microbiología, Universidad de Buenos Aires, Argentina.
authors.forename: María L
authors.initials: ML
authors.lastname: Cuestas
authors.forename: Cintia W
authors.initials: CW
authors.lastname: Rivero
authors.forename: María L
authors.initials: ML
authors.lastname: Minassian
authors.forename: Amalia I
authors.initials: AI
authors.lastname: Castillo
authors.forename: Emiliano A
authors.initials: EA
authors.lastname: Gentile
authors.forename: Julieta
authors.initials: J
authors.lastname: Trinks
authors.forename: Liliana
authors.initials: L
authors.lastname: León
authors.forename: Graciela
authors.initials: G
authors.lastname: Daleoso
authors.forename: Bernardo
authors.initials: B
authors.lastname: Frider
authors.forename: Carol
authors.initials: C
authors.lastname: Lezama
authors.forename: Marcela
authors.initials: M
authors.lastname: Galoppo
authors.forename: Gisela
authors.initials: G
authors.lastname: Giacove
authors.forename: Verónica L
authors.initials: VL
authors.lastname: Mathet
authors.forename: José R
authors.initials: JR
authors.lastname: Oubiña
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D001118:Argentina; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D063065:Organophosphonates / Q000494:pharmacology*; D012189:Retrospective Studies
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine