title: Similar predictions of etravirine sensitivity regardless of genotypic testing method used: comparison of available scoring systems.
abstract: BACKGROUND
  The aims of this study were to compare various genotypic scoring systems commonly used to predict virological outcome to etravirine, and examine their concordance with etravirine phenotypic susceptibility.
  
  
  METHODS
  Six etravirine genotypic scoring systems were assessed: Tibotec 2010 (based on 20 mutations; TBT 20), Monogram, Stanford HIVdb, ANRS, Rega (based on 37, 30, 27 and 49 mutations, respectively) and virco(®)TYPE HIV-1 (predicted fold change based on genotype). Samples from treatment-experienced patients who participated in the DUET trials and with both genotypic and phenotypic data (n=403) were assessed using each scoring system. Results were retrospectively correlated with virological response in DUET. κ coefficients were calculated to estimate the degree of correlation between the different scoring systems.
  
  
  RESULTS
  Correlation between the five scoring systems and the TBT 20 system was approximately 90%. Virological response by etravirine susceptibility was comparable regardless of which scoring system was utilized, with 70-74% of DUET patients determined as susceptible to etravirine by the different scoring systems achieving plasma viral load <50 HIV-1 RNA copies/ml. In samples classed as phenotypically susceptible to etravirine (fold change in 50% effective concentration ≤3), correlations with genotypic score were consistently high across scoring systems (≥70%).
  
  
  CONCLUSIONS
  In general, the etravirine genotypic scoring systems produced similar results, and genotype-phenotype concordance was high. As such, phenotypic interpretations, and in their absence all genotypic scoring systems investigated, may be used to reliably predict the activity of etravirine.
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. jvingerh@its.jnj.com
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: Steven
authors.initials: S
authors.lastname: Nijs
authors.forename: Lotke
authors.initials: L
authors.lastname: Tambuyzer
authors.forename: Annemie
authors.initials: A
authors.lastname: Hoogstoel
authors.forename: David
authors.initials: D
authors.lastname: Anderson
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D060005:Genotyping Techniques; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009570:Nitriles; D010641:Phenotype; D011379:Prognosis; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine