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
作者:
Jesper Eugen-Olsen,
Astrid Iversen,
Peter Garred,
Uffe Koppelhus,
Court Pedersen,
Thomas Benfield,
Anne Sorensen,
Theresa Katzenstein,
Ebbe Dickmeiss,
Jan Gerstoft,
Peter Skinhøj,
Arne Svejgaard,
Jens Nielsen,
Bo Hofmann,
期刊:
AIDS
(OVID Available online 1997)
卷期:
Volume 11,
issue 3
页码: 305-310
ISSN:0269-9370
年代: 1997
出版商: OVID
关键词: HIV;CD4 T cells;disease progression;CKR-5;CKR-5 deletion
数据来源: OVID
摘要:
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.Design:Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed from 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-seronegative 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 none was heterozygous. The frequency of heterozygotes in long-term nonprogressors 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.Conclusion: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.
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