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

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/mu l (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 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/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.