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Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression

✍ Scribed by Renate A. Morawetz; G. Paolo Rizzardi; Didier Glauser; Olivier Rutschmann; Bernard Hirschel; Luc Perrin; Milos Opravil; Markus Flepp; Jan von Overbeck; Michel P. Glauser; Silvia Ghezzi; Elisa Vicenzi; Guido Poli; Adriano Lazzarin


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
489 KB
Volume
27
Category
Article
ISSN
0014-2980

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✦ Synopsis


Abstract

Homozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β‐chemokine receptor 5 (CCR5) gene, which encodes for the major co‐receptor for macrophage‐tropic HIV‐1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/Δccr5 genotype was found more frequently in long‐term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan‐Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4^+^ T cell counts >500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4^+^ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild‐type (69 % of LTNP) and the heterozygous (31.0 %) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.