title: Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection.
abstract: BACKGROUND
  CXCR4-using virus is associated with higher viral load and accelerated human immunodeficiency virus (HIV) disease progression. Additionally, CCR5 antagonists may not reduce the HIV-1 RNA load when mixed/dual-tropic or CXCR4-using virus is present. The determination of coreceptor tropism may be required before CCR5 or CXCR4 antagonists are initiated, unless reliable predictive markers of coreceptor use are established.
  
  
  METHODS
  Samples from treatment-naive and -experienced HIV-1-positive individuals with date-matched CD4 and CD8 cell counts and HIV-1 RNA, clade, and pol sequences were assessed for coreceptor usage, by use of the ViroLogic PhenoSense assay.
  
  
  RESULTS
  Coreceptor use determination was successful in 563 of 861 samples. Non-clade B virus was present in 18.6% of samples. CXCR4 or mixed/dual-tropic CCR5/CXCR4 virus was present in 112 of samples (19.9%). Only 4 samples (0.7%) showed exclusive CXCR4 use. In a multivariate model, higher CD4 cell count, lower viral load, and higher natural killer cell counts were significantly associated with CCR5 usage. No associations with treatment experience, clade, or pol gene mutations were observed.
  
  
  CONCLUSIONS
  The prevalence of CCR5-tropic HIV-1 phenotype declines with decreasing CD4 cell count and increasing viral load. Mixed/dual tropic virus is found in all CD4 cell count and viral load strata. Coreceptor usage is not influenced by viral clade.
authors.affiliation: Chelsea and Westminster Hospital, London, United Kingdom. gm@moyleg.demon.co.uk
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Moyle
authors.forename: Adrian
authors.initials: A
authors.lastname: Wildfire
authors.forename: Sundhiya
authors.initials: S
authors.lastname: Mandalia
authors.forename: Howard
authors.initials: H
authors.lastname: Mayer
authors.forename: James
authors.initials: J
authors.lastname: Goodrich
authors.forename: Jeannette
authors.initials: J
authors.lastname: Whitcomb
authors.forename: Brian G
authors.initials: BG
authors.lastname: Gazzard
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D011933:Reagent Kits, Diagnostic; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*
chemical_list: D012367:RNA, Viral; D011933:Reagent Kits, Diagnostic; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine