Chemokine receptor polymorphisms and human immunodeficiency virus disease progression

The role of polymorphisms in genes encoding chemokines and their receptors (CCR2B, SDF-1, and the promoter region of CCR5) in human immunodeficiency v irus (HIV) disease progression was studied in 132 white HIV type 1 (HIV-1)- infected participants from a United Kingdom cohort study. Genotyping was do ne by use of amplification refractory mutation system-polymerase chain reac tion with sequence-specific primers, and Cox proportional hazards models we re used to examine the impact of polymorphisms on time to a CD4 cell count <200 x 10(6)/L and to CDC stage IV disease, The results confirm a significa nt association Of the CCR2B-64I mutant genotype with slower progression to a CD4 count <200 (hazards ratio [HR], 0.39; 95% confidence interval [CI], 0 .17-0.91) but not with the SDF-1 alpha 3'UTR homozygous mutation. The effec ts of the CCR5 and CCR2 mutations were genetically independent and similar in the magnitude of their protective effect on progression to a CD4 count < 200 cells. A novel finding was an association of borderline significance be tween homozygosity for C at nucleotide position 59353 in the CCR5 promoter region and a slower rate of CD4 cell decline to <200 X 10(6)/L (HR, 0.58; 9 5% CI, 0.34-0.996).