CCR5 promoter polymorphisms, CCR5 59029A and CCR5 59353C, are under represented in HIV-1-infected long-term non-progressors

Objective: To determine the influence of CCR5 promoter polymorphisms on HIV -1 progression to AIDS and to evaluate the interaction between CCR5 structu ral polymorphisms and those occurring in the regulatory region of the same gene. Participants: Seventy-one HIV-1-infected long-term non-progressors with a C D4+ T cell count of > 500 x 10(6)/l more than 8 years after infection were compared with 75 HIV-1-infected individuals who had progressed to AIDS and/ or death within 8 years and with a further 119 HIV-1-positive patients who had CD4+ T cell counts of 200-500 x 10(6)/l. An additional 92 HIV-negative individuals were also studied. Methods: CCR5 Delta 32 genotype was determined by PCR with primers spanning the 32 base pair deletion. CCR2-64I, CCR5 59029A/G and CCR5 59353C/T genot ypes were determined by PCR followed by restriction fragment length polymor phism analysis. Results: Strong linkage disequilibrium between the CCR5 59029A/G and CCR5 5 9353C polymorphic variants was identified. CCR5 59029A and CCR5 59353C homo zygotes were found to be significantly under-represented in the long-term n on-progressor group as compared with the other HIV-1-positive groups, with the effect being more marked in the absence of the CCR5 Delta 32 and CCR2 6 41 mutations. Conclusions: This study provides the first evidence for an association betw een CCR5 promoter polymorphisms and long-term asymptomatic HIV-1 infection, with individuals lacking the CCR5 59029A/CCR5 59353C homozygous genotype l ikely to progress more slowly towards AIDS and/or death. (C) 2000 Lippincot t Williams & Wilkins.