title: CCR5Delta32 and promoter polymorphisms are not correlated with initial virological or immunological treatment response.
abstract: OBJECTIVE
  Natural genetic polymorphisms within the CCR5 gene and promoter have been linked to patterns of HIV-1 clinical disease progression in untreated individuals. The objective of this retrospective study was to assess the influence of the CCR5Delta32 mutation and promoter polymorphisms on virological and immunological treatment outcome in 436 antiretroviral-naive individuals initiating their first therapy, over a mean follow-up time of 22 months.
  
  
  METHODS
  Genotypes for the CCR5Delta32 and promoter were determined by polymerase chain reaction amplification of human DNA from plasma, followed by gel electrophoresis for CCR5Delta32 or DNA sequencing for the promoter polymorphisms. Time to virological failure [defined as the second plasma viral load > or = 400 copies HIV-1 RNA/ml) and immunological failure (defined as time to achieve two successive CD4 cell counts below baseline) were analyzed by Kaplan-Meier methods.
  
  
  RESULTS
  The five most common CCR5 promoter polymorphisms were observed at positions 208(G/T), 303(A/G), 627(C/T), 676(A/G), and 927(C/T). Allele frequencies were 0.24(208T), 0.38(303G), 0.44(627T), 0.35(676G) and 0.18(927T). The CCR5Delta32 allele frequency was 0.08. The promoter polymorphisms existed in strong linkage disequilibrium with each other and the Delta32. No significant effect of the individual CCR5Delta32 or promoter polymorphisms could be demonstrated with respect to time to treatment failure as defined by virological or immunological parameters (P > or = 0.07). Similarly, when combined CCR5Delta32 and promoter genotypes were analyzed in order to account for linkage disequilibrium, no significant effect was observed on time to virological or immunological failure (P > 0.6).
  
  
  CONCLUSIONS
  CCR5Delta32 and promoter genotypes may not be of clinical relevance in predicting initial virological or immunological response to antiretroviral therapy.
authors.affiliation: British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, 603-1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: K J
authors.initials: KJ
authors.lastname: Chan
authors.forename: W
authors.initials: W
authors.lastname: Dong
authors.forename: R
authors.initials: R
authors.lastname: Hogg
authors.forename: M V
authors.initials: MV
authors.lastname: O'Shaughnessy
authors.forename: J S
authors.initials: JS
authors.lastname: Montaner
authors.forename: P R
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D015331:Cohort Studies; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D015810:Linkage Disequilibrium; D010349:Patient Compliance; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D019713:Receptors, CCR5 / Q000145:classification / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019713:Receptors, CCR5