Homozygous Δ32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient

Background: Recent research has found that entry of non-syncytium-inducing (NSI),monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that Δ32/Δ32 homozygous individuals are protected against infection. Objective: To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects. Design and methods: CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation. Results: The wild-type/Δ32 heterozygous and Δ32/Δ32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the Δ32/Δ32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype. Conclusions: Δ32/Δ32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.