title: Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals.
abstract: OBJECTIVE
  Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course of the disease.
  
  
  METHODS
  Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed form 1985 to 1996 and 37 blood donors were analysed for their CKR-5 genotype by polymerase chain reaction.
  
  
  RESULTS
  Two (6%) of the 35 HIV-seropositive subjects at high-risk of infection were homozygous and seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV-seropositive subjects were heterozygous and none was homozygous. Two subgroups of patients who had an opposite course of the HIV disease were identified. Of nine long-term non-progressors, six (66%) were heterozygous for the deletion. This frequency is significantly higher than in nine rapid progressors of whom non was heterozygous. The frequency of heterozygotes in long-term non-progressors was also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly better prognosis within the first 7 years of follow-up for those who were heterozygous for the deletion. Heterozygous individuals also had a significantly slower decrease in CD4 T-cell count per year.
  
  
  CONCLUSIONS
  Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospitals, Hvidovre, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Eugen-Olsen
authors.forename: A K
authors.initials: AK
authors.lastname: Iversen
authors.forename: P
authors.initials: P
authors.lastname: Garred
authors.forename: U
authors.initials: U
authors.lastname: Koppelhus
authors.forename: C
authors.initials: C
authors.lastname: Pedersen
authors.forename: T L
authors.initials: TL
authors.lastname: Benfield
authors.forename: A M
authors.initials: AM
authors.lastname: Sorensen
authors.forename: T
authors.initials: T
authors.lastname: Katzenstein
authors.forename: E
authors.initials: E
authors.lastname: Dickmeiss
authors.forename: J
authors.initials: J
authors.lastname: Gerstoft
authors.forename: P
authors.initials: P
authors.lastname: Skinhøj
authors.forename: A
authors.initials: A
authors.lastname: Svejgaard
authors.forename: J O
authors.initials: JO
authors.lastname: Nielsen
authors.forename: B
authors.initials: B
authors.lastname: Hofmann
mesh_terms: D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018572:Disease-Free Survival; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*
chemical_list: D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV