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 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. 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.
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 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. 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.
Authors: A Garzino-Demo; R B Moss; J B Margolick; F Cleghorn; A Sill; W A Blattner; F Cocchi; D J Carlo; A L DeVico; R C Gallo Journal: Proc Natl Acad Sci U S A Date: 1999-10-12 Impact factor: 11.205
Authors: R Zamarchi; P Allavena; A Borsetti; L Stievano; V Tosello; N Marcato; G Esposito; V Roni; C Paganin; G Bianchi; F Titti; P Verani; G Gerosa; A Amadori Journal: Clin Exp Immunol Date: 2002-02 Impact factor: 4.330
Authors: F Cocchi; A L DeVico; R Yarchoan; R Redfield; F Cleghorn; W A Blattner; A Garzino-Demo; S Colombini-Hatch; D Margolis; R C Gallo Journal: Proc Natl Acad Sci U S A Date: 2000-12-05 Impact factor: 11.205
Authors: Paul R Gorry; Rebecca L Dunfee; Megan E Mefford; Kevin Kunstman; Tom Morgan; John P Moore; John R Mascola; Kristin Agopian; Geoffrey H Holm; Andrew Mehle; Joann Taylor; Michael Farzan; Hui Wang; Philip Ellery; Samantha J Willey; Paul R Clapham; Steven M Wolinsky; Suzanne M Crowe; Dana Gabuzda Journal: Virology Date: 2007-01-18 Impact factor: 3.616
Authors: N L Michael; J A Nelson; V N KewalRamani; G Chang; S J O'Brien; J R Mascola; B Volsky; M Louder; G C White; D R Littman; R Swanstrom; T R O'Brien Journal: J Virol Date: 1998-07 Impact factor: 5.103
Authors: O J Cohen; S Paolucci; S M Bende; M Daucher; H Moriuchi; M Moriuchi; C Cicala; R T Davey; B Baird; A S Fauci Journal: J Virol Date: 1998-07 Impact factor: 5.103