Identification of Two Distinct Subsets of Long‐Term Nonprogressors with Divergent Viral Activity by Stromal‐Derived Factor 1 Chemokine Gene Polymorphism Analysis

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Abstract
Stromal-derived factor (SDF)—1, the natural ligand for CXCR4, is present in a common polymorphic variant defined by a G→A transition in the 3′ untranslated region of the gene. In persons infected with human immunodeficiency virus type 1 (HIV-1), the homozygous genotype (SDF1-3′A/3′A) has been postulated to interfere with the appearance of T-tropic syncytium-inducing strains. The polymorphism of SDF1 was correlated with HIV-1 phenotype, plasma viremia, and unspliced and multiply spliced specific transcripts in 158 virologically characterized HIV-1—infected patients (39 recent seroconverters, 75 typical progressors, and 44 AIDS patients) and in 42 HIV-1—infected long-term nonprogressors (LTNPs). Analysis of SDF1 allele distribution revealed that SDF1-3′A/3′A status is associated with low CD4 cell count (P = .0449) but not with a specific HIV-1 phenotype. In LTNPs, SDF1-+I+ condition defined a subset of persons with lower HIV-1 replication than in heterozygous subjects. The low viral activity in SDF1-+/+ LTNPs suggests that other factors play a major role in vivo in determining the course of HIV-1 infection.

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