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) f or parenteral transmission of HIV-1. Design: The prevalence of the Delta 32 deletion within the CCR5 gene was de termined in a cohort of 207 patients, who had received documented amounts o f 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 Delta 32 deletion was amplified by PC R. The resulting DNA fragments were analysed by agarose gel electrophoresis . Results: The rate of HIV-1 infection was correlated strongly with increasin g amounts of inoculated clotting factor concentrate. None of the HIV-positi ve patients (n = 129) had the Delta 32/Delta 32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous Delta 32 deletion. Conclusions: The Delta 32/Delta 32 genotype was highly protective against H IV-1 infection, even in patients who had received millions of non-inactivat ed clotting factor units. As it is likely that in the early 1980s plasma po ols were contaminated not only with monocyte-tropic HIV-1 strains, CCR5 app ears to be the major mediator of HIV-1 infection. Furthermore, we conclude that there must be other protective mechanisms in multiply exposed non-infe cted haemophiliacs who have wild-type CCR5. (C) 1999 Lippincott Williams & Wilkins.