title: Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA.
abstract: OBJECTIVE
  The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT).
  
  
  METHODS
  GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut-off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples.
  
  
  RESULTS
  In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances were observed at an FPR of 10%, and six RNA-R5/DNA-X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA-X4/DNA-R5 and seven RNA-R5/DNA-X4 discordances were seen at an FPR of 10%, and 10 RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs).
  
  
  CONCLUSIONS
  GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia.
authors.affiliation: AIDS Reference Laboratory and AIDS Reference Centre, Ghent University and Ghent University Hospital, Ghent, Belgium. Chris.verhofstede@ugent.be
authors.forename: C
authors.initials: C
authors.lastname: Verhofstede
authors.forename: D
authors.initials: D
authors.lastname: Brudney
authors.forename: J
authors.initials: J
authors.lastname: Reynaerts
authors.forename: D
authors.initials: D
authors.lastname: Vaira
authors.forename: K
authors.initials: K
authors.lastname: Fransen
authors.forename: A
authors.initials: A
authors.lastname: De Bel
authors.forename: C
authors.initials: C
authors.lastname: Seguin-Devaux
authors.forename: S
authors.initials: S
authors.lastname: De Wit
authors.forename: L
authors.initials: L
authors.lastname: Vandekerckhove
authors.forename: A-M
authors.initials: AM
authors.lastname: Geretti
mesh_terms: D000465:Algorithms; D004279:DNA, Viral / Q000097:blood*; D005784:Gene Amplification; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load / Q000235:genetics*; D056189:Viral Tropism / Q000235:genetics*; D014766:Viremia / Q000821:virology
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral