title: Detection of minor populations of drug-resistant HIV-1 in acute seroconverters.
abstract: OBJECTIVE
  The transmission of drug-resistant HIV-1 is a major health concern. To date, most clinical studies have relied on sequencing techniques for genotypic analyses which do not allow quantification of minority viral populations below 25%. As minor populations of drug-resistant HIV-1 could impact the efficiency of antiretroviral therapy, this study was performed to determine the prevalence of minor populations of drug-resistant HIV-1 in acute seroconverters.
  
  
  METHODS
  Forty-nine acute seroconverters from two clinical centers in Germany were included in the study. Individuals were identified between June 1999 and March 2003, and none had received antiretroviral therapy prior to sampling. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction using allele-discriminating oligonucleotides for three key resistance mutations: L90M (protease), K103N and M184V (reverse transcriptase). The approximate discriminative power was between 0.01 and 0.2%.
  
  
  RESULTS
  Drug-resistant variants were detected in 10 of 49 patients (20.4%). The L90M mutation was found in one of 49 (2%), the K103N mutation in five of 49 (10.2%) and the M184V mutation in six of 49 (12.2%) patients, respectively. In five of the 10 individuals with detectable drug-resistant virus (50%), the detected population represented a minor viral quasi-species (< 25% of viruses) and was not detected by direct sequencing.
  
  
  CONCLUSIONS
  The prevalence of minor populations of drug-resistant HIV-1 in acute seroconverters can be frequently detected and may impact the success of antiretroviral therapy.
authors.affiliation: University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Germany. karin.metzner@viro.med.uni-erlangen.de
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Metzner
authors.forename: Pia
authors.initials: P
authors.lastname: Rauch
authors.forename: Hauke
authors.initials: H
authors.lastname: Walter
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zöllner
authors.forename: Heiko
authors.initials: H
authors.lastname: Jessen
authors.forename: Knud
authors.initials: K
authors.lastname: Schewe
authors.forename: Stefan
authors.initials: S
authors.lastname: Fenske
authors.forename: Holger
authors.initials: H
authors.lastname: Gellermann
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stellbrink
mesh_terms: D000208:Acute Disease; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D006679:HIV Seropositivity / Q000175:diagnosis* / Q000188:drug therapy; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction