title: Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection.
abstract: BACKGROUND
  Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)-naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven.
  
  
  METHODS
  MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters.
  
  
  RESULTS
  Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1-infected patients (8.2% vs 2.5%; P = .004).
  
  
  CONCLUSIONS
  Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin-transmission vs sporadic appearance-of these variants determines their impact on ART needs to be further explored.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. karin.metzner@usz.ch
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Metzner
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Preiswerk
authors.forename: Beda
authors.initials: B
authors.lastname: Joos
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Christine
authors.initials: C
authors.lastname: Leemann
authors.forename: Philip
authors.initials: P
authors.lastname: Rieder
authors.forename: Dominique
authors.initials: D
authors.lastname: Braun
authors.forename: Christina
authors.initials: C
authors.lastname: Grube
authors.forename: Herbert
authors.initials: H
authors.lastname: Kuster
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Vincent
authors.initials: V
authors.lastname: Aubert
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Vernazza
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016000:Cluster Analysis; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013557:Switzerland; D055815:Young Adult
keywords: HIV-1; allele-specific real-time PCR; drug resistance; drug-resistant HIV-1 minority variants; prevalence; primary HIV-1 infection; transmission