title: Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment.
abstract: BACKGROUND
  Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care.
  
  
  METHODS
  Forty-nine consecutive plasma samples for which an original Trofile(TM) assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call.
  
  
  RESULTS
  According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97%) and a higher negative predictive value (91%), but almost equal specificity and an equal positive predictive value.
  
  
  CONCLUSIONS
  In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc.
authors.affiliation: Department of General Internal Medicine, Infectious Diseases and Psychosomatic Medicine, University Hospital Ghent, Ghent, Belgium. linos.vandekerckhove@ugent.be
authors.forename: Linos
authors.initials: L
authors.lastname: Vandekerckhove
authors.forename: Chris
authors.initials: C
authors.lastname: Verhofstede
authors.forename: Els
authors.initials: E
authors.lastname: Demecheleer
authors.forename: Stephane
authors.initials: S
authors.lastname: De Wit
authors.forename: Eric
authors.initials: E
authors.lastname: Florence
authors.forename: Katrien
authors.initials: K
authors.lastname: Fransen
authors.forename: Michel
authors.initials: M
authors.lastname: Moutschen
authors.forename: Wendy
authors.initials: W
authors.lastname: Mostmans
authors.forename: Kabamba
authors.initials: K
authors.lastname: Kabeya
authors.forename: Nicola
authors.initials: N
authors.lastname: Mackie
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
authors.forename: Dolores
authors.initials: D
authors.lastname: Vaira
authors.forename: Kurt
authors.initials: K
authors.lastname: Van Baelen
authors.forename: Ina
authors.initials: I
authors.lastname: Vandenbroucke
authors.forename: Veerle
authors.initials: V
authors.lastname: Van Eygen
authors.forename: Herwig
authors.initials: H
authors.lastname: Van Marck
authors.forename: Dirk
authors.initials: D
authors.lastname: Vogelaers
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Stuyver
mesh_terms: D003510:Cyclohexanes / Q000627:therapeutic use*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D000077592:Maraviroc; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014230:Triazoles / Q000627:therapeutic use*; D056189:Viral Tropism
chemical_list: D003510:Cyclohexanes; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014230:Triazoles; D000077592:Maraviroc