title: X4 Tropic Virus Prediction Is Associated with a Nadir CD4 T-Cell Count below 100 Cells/mm.
abstract: OBJECTIVE
  The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients.
  
  
  METHODS
  Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed.
  
  
  RESULTS
  According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01).
  
  
  CONCLUSIONS
  We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm(3) that must be taken into account when considering a CCR5 antagonist therapy switch.
authors.affiliation: EA4294 Unité de Virologie Clinique et Fondamentale, UPJV et Centre Hospitalo-Universitaire, Amiens, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sechet
authors.forename: Catherine
authors.initials: C
authors.lastname: Roussel
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Schmit
authors.forename: Carlo
authors.initials: C
authors.lastname: Saroufim
authors.forename: Kamel
authors.initials: K
authors.lastname: Ghomari
authors.forename: Dominique
authors.initials: D
authors.lastname: Merrien
authors.forename: François
authors.initials: F
authors.lastname: Cordier
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Pik
authors.forename: Nathalie
authors.initials: N
authors.lastname: Landgraf
authors.forename: Youcef
authors.initials: Y
authors.lastname: Douadi
authors.forename: Dominique
authors.initials: D
authors.lastname: Liné
authors.forename: Gilles
authors.initials: G
authors.lastname: Duverlie
authors.forename: Sandrine
authors.initials: S
authors.lastname: Castelain
mesh_terms: D000328:Adult; D000465:Algorithms; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D005260:Female; D005602:France; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D019713:Receptors, CCR5 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology*; D056189:Viral Tropism
chemical_list: C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4