title: Design and validation of new genotypic tools for easy and reliable estimation of HIV tropism before using CCR5 antagonists.
abstract: BACKGROUND
  Genotypic tools may allow easier and less expensive estimation of HIV tropism before prescription of CCR5 antagonists compared with the Trofile assay (Monogram Biosciences, South San Francisco, CA, USA).
  
  
  METHODS
  Paired genotypic and Trofile results were compared in plasma samples derived from the maraviroc expanded access programme (EAP) in Europe. A new genotypic approach was built to improve the sensitivity to detect X4 variants based on an optimization of the webPSSM algorithm. Then, the new tool was validated in specimens from patients included in the ALLEGRO trial, a multicentre study conducted in Spain to assess the prevalence of R5 variants in treatment-experienced HIV patients.
  
  
  RESULTS
  A total of 266 specimens from the maraviroc EAP were tested. Overall geno/pheno concordance was above 72%. A high specificity was generally seen for the detection of X4 variants using genotypic tools (ranging from 58% to 95%), while sensitivity was low (ranging from 31% to 76%). The PSSM score was then optimized to enhance the sensitivity to detect X4 variants changing the original threshold for R5 categorization. The new PSSM algorithms, PSSM(X4R5-8) and PSSM(SINSI-6.4), considered as X4 all V3 scoring values above -8 or -6.4, respectively, increasing the sensitivity to detect X4 variants up to 80%. The new algorithms were then validated in 148 specimens derived from patients included in the ALLEGRO trial. The sensitivity/specificity to detect X4 variants was 93%/69% for PSSM(X4R5-8) and 93%/70% for PSSM(SINSI-6.4).
  
  
  CONCLUSIONS
  PSSM(X4R5-8) and PSSM(SINSI-6.4) may confidently assist therapeutic decisions for using CCR5 antagonists in HIV patients, providing an easier and rapid estimation of tropism in clinical samples.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. evapoveda@hotmail.com
authors.forename: Eva
authors.initials: E
authors.lastname: Poveda
authors.forename: Eduardo
authors.initials: E
authors.lastname: Seclén
authors.forename: María del Mar
authors.initials: Mdel M
authors.lastname: González
authors.forename: Federico
authors.initials: F
authors.lastname: García
authors.forename: Natalia
authors.initials: N
authors.lastname: Chueca
authors.forename: Antonio
authors.initials: A
authors.lastname: Aguilera
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Rodríguez
authors.forename: Juan
authors.initials: J
authors.lastname: González-Lahoz
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000465:Algorithms; D005838:Genotype; D006678:HIV / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D015728:Receptors, HIV / Q000032:analysis*; D012680:Sensitivity and Specificity; D013030:Spain; D014773:Virology / Q000379:methods*
chemical_list: D015728:Receptors, HIV