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 d isease progression, respectively. The CCR5/Delta ccr5 genotype was fou nd more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6% p < 0.0001), in agreement with previous studies. Ka plan-Meier survival analyses showed that a slower progression of disea se, 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, w hen 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%) geno types. Therefore, there are other factors which play a major role in d etermining the status of nonprogression in the majority of LTNP. Furth ermore, there was no evidence that the CCR5/Delta ccr5 genotype was as sociated with different rates of disease progression in the group of p rogressors. Taken together, these results indicate that the CCR5/Delta ccr5 genotype is neither essential nor sufficient for protection agai nst the progression of HIV disease.