title: Correlation between genotypic predictions based on V3 sequences and phenotypic determination of HIV-1 tropism.
abstract: OBJECTIVE
  Replacing phenotypic assays with simple genotypic predictions of HIV-1 coreceptor usage would make the clinical use of CCR5 antagonists easier.
  
  
  METHODS
  Paired genotypic and phenotypic determination of HIV-1 coreceptor usage was performed to assess several genotypic approaches for detecting CXCR4-using and CCR5-using viruses in a clinical setting.
  
  
  METHODS
  HIV-1 coreceptor usage was prospectively assessed using plasma samples from 103 patients who were candidates for treatment with a CCR5 antagonist. Direct sequencing of the V3 region and a sensitive recombinant virus phenotypic entry assay were performed in parallel for each patient from the same bulk env PCR product.
  
  
  RESULTS
  The 103 patients had a median CD4+ T lymphocyte count of 268 x 10(6)cells/l and nadirs of 98 x 10(6)cells/l. Paired genotypic and phenotypic data were obtained for 98 of the 103 patients. For detecting CXCR4-using viruses, the genotypic rule based on amino-acid residues at positions 11/25 and the overall net charge of V3 was 77% sensitive and 96% specific. The Geno2pheno bioinformatic tool was 88% sensitive and 87% specific. The WebPSSM tool prediction with the SI/NSI matrix was 77% sensitive and 94% specific. The global concordance between genotypic and phenotypic data was 91% with the rule combining the amino-acid residues at positions 11/25 and V3 net charge.
  
  
  CONCLUSIONS
  Genotypic predictions performed well in paired genotypic and phenotypic assessment of HIV-1 coreceptor usage. Multicenter studies analyzing the correlations between the genotypic determination of HIV-1 tropism and clinical response to CCR5 antagonists are needed to validate this approach in clinical practice.
authors.affiliation: INSERM, U563, Université Toulouse III Paul-Sabatier, Faculté de Médecine Toulouse-Purpan, CHU de Toulouse, Hôpital Purpan, Laboratoire de Virologie, Toulouse, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Raymond
authors.forename: Pierre
authors.initials: P
authors.lastname: Delobel
authors.forename: Maud
authors.initials: M
authors.lastname: Mavigner
authors.forename: Michelle
authors.initials: M
authors.lastname: Cazabat
authors.forename: Corinne
authors.initials: C
authors.lastname: Souyris
authors.forename: Karine
authors.initials: K
authors.lastname: Sandres-Sauné
authors.forename: Lise
authors.initials: L
authors.lastname: Cuzin
authors.forename: Bruno
authors.initials: B
authors.lastname: Marchou
authors.forename: Patrice
authors.initials: P
authors.lastname: Massip
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet