CCR5 promoter polymorphisms, CCR5 59029A and CCR5 59353C, are under represented in HIV-1-infected long-term non-progressors. The Australian Long-Term Non-Progressor Study Group.
OBJECTIVE
To determine the influence of CCR5 promoter polymorphisms on HIV-1 progression to AIDS and to evaluate the interaction between CCR5 structural polymorphisms and those occurring in the regulatory region of the same gene.


METHODS
Seventy-one HIV-1-infected long-term non-progressors with a CD4+ T cell count of > 500 x 10(6)/I 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 delta32 genotype was determined by PCR with primers spanning the 32 base pair deletion. CCR2-64I, CCR5 59029A/G and CCR5 59353C/T genotypes were determined by PCR followed by restriction fragment length polymorphism analysis.


RESULTS
Strong linkage disequilibrium between the CCR5 59029A and CCR5 59353C polymorphic variants was identified. CCR5 59029A and CCR5 59353C homozygotes were found to be significantly under-represented in the long-term non-progressor group as compared with the other HIV-1-positive groups, with the effect being more marked in the absence of the CCR5 delta32 and CCR2 64I mutations.


CONCLUSIONS
This study provides the first evidence for an association between CCR5 promoter polymorphisms and long-term asymptomatic HIV-1 infection, with individuals lacking the CCR5 59029A/CCR5 59353C homozygous genotype likely to progress more slowly towards AIDS and/or death.
Clegg
A O
AO
Department of Immunology, Westmead Hospital, University of Sydney, Australia.
Ashton
L J
LJ
Biti
R A
RA
Badhwar
P
P
Williamson
P
P
Kaldor
J M
JM
Stewart
G J
GJ
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D005838:Genotype; D020276:HIV Long-Term Survivors; D015497:HIV-1; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine