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NLM AIDSLINE
Protection against parenteral HIV-1 infection by homozygous deletion in the C-C chemokine receptor 5 gene.
Kupfer B; Kaiser R; Brackmann HH; Effenberger W; Rockstroh JK; Matz B;
November 30, 1999
AIDS. 1999 Jun 18;13(9):1025-8. Unique Identifier : AIDSLINE

OBJECTIVES: To investigate the role of the CC chemokine receptor 5 (CCR5) for parenteral transmission of HIV-1. DESIGN: The prevalence of the delta32 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 delta32 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 delta32/delta32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous delta32 deletion. CONCLUSIONS: The delta32/delta32 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.

JOURNAL ARTICLE Base Sequence Cohort Studies CD4 Lymphocyte Count DNA/ANALYSIS Genotype Hemophilia A/*COMPLICATIONS/GENETICS Human HIV Infections/COMPLICATIONS/*IMMUNOLOGY/*TRANSMISSION HIV-1/*PHYSIOLOGY Receptors, CCR5/*GENETICS RNA, Viral/BLOOD Sequence Deletion

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