title: Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure.
abstract: Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters. Double 148R+N155H mutants were also detected in 1.7% of viruses at virological failure in association with E138K and/or G163R. Our findings illustrate the ability of HIV-1 to escape from suboptimal antiretroviral drug pressure through selection of pre-existing drug-resistant mutants, underscoring the importance of using fully active antiretroviral regimens to treat all HIV-1-infected subjects.
authors.affiliation: HIVACAT, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Codoñer
authors.forename: Christian
authors.initials: C
authors.lastname: Pou
authors.forename: Alexander
authors.initials: A
authors.lastname: Thielen
authors.forename: Federico
authors.initials: F
authors.lastname: García
authors.forename: Rafael
authors.initials: R
authors.lastname: Delgado
authors.forename: David
authors.initials: D
authors.lastname: Dalmau
authors.forename: José Ramon
authors.initials: JR
authors.lastname: Santos
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Buzón
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Picado
authors.forename: Miguel
authors.initials: M
authors.lastname: Alvarez-Tejado
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Lidia
authors.initials: L
authors.lastname: Ruiz
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000187:drug effects / Q000235:genetics; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D012641:Selection, Genetic / Q000187:drug effects; D017211:Treatment Failure
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase