title: Hepatitis B virus resistance substitutions: long-term analysis by next-generation sequencing.
abstract: HBV phylogenetics and resistance-associated mutations (RAMs) were surveyed by next-generation sequencing of 21 longitudinal samples from seven patients entering antiviral therapy. The virus populations were dominated by a few abundant lineages that coexisted with substantial numbers of low-frequency variants. A few low-frequency RAMs were observed before treatment, but new ones emerged, and their frequencies increased during therapy. Together, these results support the idea that chronic HBV infection is dominated by a few virus lineages and that an accompanying plethora of diverse, low-frequency variants may function as a reservoir that potentially contribute to viral genetic plasticity, potentially affecting patient outcome.
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917 (C1083ACA), Buenos Aires, Argentina.|Laboratorio de Virología y Genética Molecular, Facultad de Ciencias Naturales sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Begrano S/N (9100), Trelew, Chubut, Argentina.
authors.forename: Leandro R
authors.initials: LR
authors.lastname: Jones
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917 (C1083ACA), Buenos Aires, Argentina.|Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11, C1121ABG, Buenos Aires, Argentina.
authors.forename: Mariano
authors.initials: M
authors.lastname: Sede
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917 (C1083ACA), Buenos Aires, Argentina.|Laboratorio de Virología y Genética Molecular, Facultad de Ciencias Naturales sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Begrano S/N (9100), Trelew, Chubut, Argentina.
authors.forename: Julieta M
authors.initials: JM
authors.lastname: Manrique
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917 (C1083ACA), Buenos Aires, Argentina. quarleri@fmed.uba.ar.|Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11, C1121ABG, Buenos Aires, Argentina. quarleri@fmed.uba.ar.
authors.forename: Jorge
authors.identifier: http://orcid.org/0000-0001-5110-8773
authors.initials: J
authors.lastname: Quarleri
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010802:Phylogeny
chemical_list: D000998:Antiviral Agents