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.
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.
Eugen-Olsen
J
J
Department of Infectious Diseases, Copenhagen University Hospitals, Hvidovre, Denmark.
Iversen
A K
AK
Garred
P
P
Koppelhus
U
U
Pedersen
C
C
Benfield
T L
TL
Sorensen
A M
AM
Katzenstein
T
T
Dickmeiss
E
E
Gerstoft
J
J
Skinhøj
P
P
Svejgaard
A
A
Nielsen
J O
JO
Hofmann
B
B
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*
D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV