Reduced prevalence of the CCR5 Δ32 heterozygous genotype in human immunodeficiency virus-infected individuals with AIDS dementia complex

Heterozygosity for a 32-bp deletion in the CCR5 gene (CCR5 Delta 32), which encodes the coreceptor for macrophage-tropic non-syncytium-inducing (NSI) human immunodeficiency virus type 1 (HIV-1) variants, results in a lower CCR5 expression and reduced NSI HIV-1 replication, Because infection of macrophages and microglial cells by NSI HIV-1 is considered to be instrumental for the development of AIDS dementia complex (ADC), we studied whether the CCR5 Delta 32 heterozygous genotype correlated with a reduced frequency of ADC, Two (4.1%) of 49 patients with ADC versus 27 (14.5%) of 186 AIDS patients without ADC were heterozygous for CCR5 Delta 32 (P = .05). In contrast, a point mutation in the first transmembrane domain of CCR2 (CCR2 64I) did not show this protective effect (P = .57), The reduced prevalence of the CCR5 Delta 32 allele among patients with ADC may indicate a reduced or absent reservoir of macrophage-tropic NSI HIV-1 in the brain of CCR5 Delta 32 heterozygotes.