title: Association between CCR5 genotype and the clinical course of HIV-1 infection.
abstract: BACKGROUND
  Heterozygosity for a 32-nucleotide deletion in the C-C chemokine receptor 5 gene (CCR5 delta 32) is associated with delayed disease progression in persons infected with HIV-1.
  
  
  OBJECTIVE
  To compare the predictive value of CCR5 genotype with that of established markers in the clinical course of HIV-1 infection.
  
  
  METHODS
  Retrospective longitudinal study and nested case-control study. The latter included only long-term survivors, who were individually matched with progressors.
  
  
  METHODS
  Amsterdam, the Netherlands.
  
  
  METHODS
  364 homosexual men with HIV-1 infection.
  
  
  METHODS
  Polymerase chain reaction was used for CCR5 genotyping. Univariate and multivariate Cox proportional hazard analyses were done for disease progression with CCR5 genotype, CD4+ T-lymphocyte counts, T-lymphocyte function, HIV-1 biological phenotype (syncytium-inducing or non-syncytium-inducing HIV-1), and viral RNA load in serum as covariates.
  
  
  RESULTS
  In the case-control study, 48% of long-term survivors were heterozygous for CCR5 delta 32 compared with 9% of progressors (odds ratio, 6.9 [95% CI, 1.9 to 24.8]). In the total study sample, CCR5 delta 32 heterozygotes had significantly delayed disease progression (P < 0.001; relative hazard, 0.4 [CI, 0.3 to 0.6]), a 1.5-fold slower decrease in CD4+ T-lymphocyte count (P = 0.01), and a 2.6-fold lower viral RNA load (P = 0.01) at approximately 2.3 years after seroconversion compared with CCR5 wild-type homozygotes. At the end of the study, both groups showed the same prevalence of syncytium-inducing HIV-1, but CCR5 delta 32 heterozygotes had a delayed conversion rate. The protective effect of CCR5 delta 32 heterozygosity was stronger in the presence of only non-syncytium-inducing HIV-1. The CCR5 genotype predicted disease progression independent of viral RNA load, CD4+ T-lymphocyte counts, T-lymphocyte function, and HIV-1 biological phenotype.
  
  
  CONCLUSIONS
  The addition of CCR5 genotype to currently available laboratory markers may allow better estimation of the clinical course of HIV-1 infection.
authors.affiliation: Central Laboratory of the Red Cross Blood Transfusion Service, University of Amsterdam Academic Medical Center, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: de Roda Husman
authors.forename: M
authors.initials: M
authors.lastname: Koot
authors.forename: M
authors.initials: M
authors.lastname: Cornelissen
authors.forename: I P
authors.initials: IP
authors.lastname: Keet
authors.forename: M
authors.initials: M
authors.lastname: Brouwer
authors.forename: S M
authors.initials: SM
authors.lastname: Broersen
authors.forename: M
authors.initials: M
authors.lastname: Bakker
authors.forename: M T
authors.initials: MT
authors.lastname: Roos
authors.forename: M
authors.initials: M
authors.lastname: Prins
authors.forename: F
authors.initials: F
authors.lastname: de Wolf
authors.forename: R A
authors.initials: RA
authors.lastname: Coutinho
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D018450:Disease Progression; D005838:Genotype; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015993:Life Tables; D008137:Longitudinal Studies; D008297:Male; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D019713:Receptors, CCR5 / Q000235:genetics*; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D015415:Biomarkers; D015483:HIV Antibodies; D019713:Receptors, CCR5