title: Increased frequency of CCR-5 delta 32 heterozygotes among long-term non-progressors with HIV-1 infection. The Australian Long-Term Non-Progressor Study Group.
abstract: BACKGROUND
  The beta-chemokine receptor CCR-5 is used as a coreceptor by macrophage-tropic strains of HIV-1 to gain entry into CD4+ cells.
  
  
  OBJECTIVE
  To determine the effect of a common 32 base-pair deletion mutation in the CCR-5 gene (CCR-5 delta 32) on progression of HIV infection to AIDS, and to assess the level of heterozygosity for this mutation in a well-defined group of long-term non-progressors (LTNP).
  
  
  METHODS
  Sixty-four HIV-1-infected LTNP (CD4+ T lymphocyte count > 500 x 10(6)/l after 8 years) were compared with 95 individuals infected within a similar period (1983-1986) but who had rapidly progressed to AIDS and death, and with a further 120 HIV-positive individuals with CD4+ counts < 500 x 10(6)/l.
  
  
  METHODS
  The presence of the CCR-5 delta 32 mutation was assessed using polymerase chain reaction with primers spanning the 32 base-pair deletion. CD4+ and CD8+ counts, plasma HIV-1 RNA, p24 antigen and beta 2-microglobulin levels in LTNP carrying the CCR-5 delta 32 mutation were compared with LTNP lacking the mutation.
  
  
  RESULTS
  A marked increase in the frequency of CCR-5 delta 32 heterozygosity was found among LTNP (35.9%) compared with rapid progressors (12.6%; P = 0.0005) and patients selected on the basis of a CD4+ T-cell count < 500 x 10(6)/l (12.5%; P = 0.0004). LTNP heterozygous for CCR-5 delta 32 had a significantly higher CD8+ T-cell count than those without the mutation (1218 versus 972 x 10(6)/l; P = 0.044). No significant correlation was observed between heterozygosity and CD4 count, viral load, p24 antigen or beta 2-microglobulin within the LTNP group.
  
  
  CONCLUSIONS
  This study provides the strongest evidence to date for the importance of a single copy of the CCR-5 delta 32 mutation in long-term non-progression of HIV infection, which may involve, in part, CD8+ T lymphocytes.
authors.affiliation: Department of Immunology, Westmead Hospital, Sydney, Australia.
authors.forename: G J
authors.initials: GJ
authors.lastname: Stewart
authors.forename: L J
authors.initials: LJ
authors.lastname: Ashton
authors.forename: R A
authors.initials: RA
authors.lastname: Biti
authors.forename: R A
authors.initials: RA
authors.lastname: Ffrench
authors.forename: B H
authors.initials: BH
authors.lastname: Bennetts
authors.forename: N R
authors.initials: NR
authors.lastname: Newcombe
authors.forename: E M
authors.initials: EM
authors.lastname: Benson
authors.forename: A
authors.initials: A
authors.lastname: Carr
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
authors.forename: J M
authors.initials: JM
authors.lastname: Kaldor
mesh_terms: D018450:Disease Progression; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D019713:Receptors, CCR5 / Q000235:genetics*; D017741:Survivors; D013997:Time Factors
chemical_list: D019713:Receptors, CCR5