Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Morawetz RA; Rizzardi GP; Glauser D; Rutschmann O; Hirschel B; Perrin L; Opravil M; Flepp M; von Overbeck J; Glauser MP; Ghezzi S; Vicenzi E; Poli G; Lazzarin A; Pantaleo G

doi:10.1002/eji.1830271220

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Journal article

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Morawetz RA Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Rizzardi GP
Glauser D
Rutschmann O
Hirschel B
Perrin L
Opravil M
Flepp M
von Overbeck J
Glauser MP
Ghezzi S
Vicenzi E
Poli G
Lazzarin A
Pantaleo G

1998-02-17

Published in:

European journal of immunology. - 1997

English Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-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/delta ccr5 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/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, 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/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

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