Protection against parenteral HIV-1 infection by homozygous deletion in the C-C chemokine receptor 5 gene

Objectives: To investigate the role of the CC chemokine receptor 5 (CCR5) for parenteral transmission of HIV-1. Design: The prevalence of the D32 deletion within the CCR5 gene was determined in a cohort of 207 patients, who had received documented amounts of non-antibody-tested and non-inactivated clotting factor concentrate. Methods: Chromosomal DNA of haemophiliacs was isolated from whole blood. A portion of the CCR5 gene spanning the D32 deletion was amplified by PCR. The resulting DNA fragments were analysed by agarose gel electrophoresis. Results: The rate of HIV-1 infection was correlated strongly with increasing amounts of inoculated clotting factor concentrate. None of the HIV-positive patients (n=129) had the D32/D32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous D32 deletion. Conclusions: The D32/D32 genotype was highly protective against HIV-1 infection, even in patients who had received millions of non-inactivated clotting factor units. As it is likely that in the early 1980s plasma pools were contaminated not only with monocyte-tropic HIV-1 strains, CCR5 appears to be the major mediator of HIV-1 infection. Furthermore, we conclude that there must be other protective mechanisms in multiply exposed non-infected haemophiliacs who have wild-type CCR5.