Protective effect of CCR5 Δ32 heterozygosity is restricted by SDF-1 genotype in children with HIV-1 infection
作者:
Shizuko Sei,
Anne Boler,
Giao Nguyen,
Sean Stewart,
Quan-en Yang,
Maureen Edgerly,
Lauren Wood,
Pim Brouwers,
David Venzon,
期刊:
AIDS
(OVID Available online 2001)
卷期:
Volume 15,
issue 11
页码: 1343-1352
ISSN:0269-9370
年代: 2001
出版商: OVID
关键词: children;HIV-1;CCR5 Δ32 heterozygosity;SDF1-3′ A polymorphism;disease progression;AIDS;genetic restrictions
数据来源: OVID
摘要:
ObjectiveTo determine the influences on pediatric AIDS of a heterozygous 32 base pair deletion in the CC-chemokine receptor 5 gene (CCR5 wt/Δ32) and a common polymorphism in the 3′ untranslated region of stromal cell-derived factor-1β gene transcript (SDF1-3′A).DesignThe rate of HIV-1 disease progression and viral burden were compared according to the CCR5 and SDF-1 genotypes in 127 (58 Caucasians, 60 African-Americans and nine Hispanics) perinatally HIV-1-infected children.ResultsRegardless of ethnic background, the CCR5 wt/Δ32 genotype was associated with a delayed onset of AIDS-defining infectious complications during the first 5 years of infection [relative hazard (RH) = 0.22; 95% confidence interval (CI), 0.012–1.02; P = 0.053]. Similarly, CCR5 wt/Δ32 conferred an early protection against severe immune suppression and HIV-1 encephalopathy, but only in those without SDF1-3′A (RH = 0; 95% CI, 0–0.70; P = 0.020, and RH = 0; 95% CI, 0–0.71; P = 0.021, respectively). When examined before 5 years of age (n = 81), the children with CCR5 wt/Δ32 had significantly lower levels of cell-associated HIV-1 DNA than wild-type homozygotes (P = 0.016, adjusted by race), while SDF1-3′A carriers had relatively higher levels (P = 0.047, adjusted by race). Although the disease-retarding effect of CCR5 wt/Δ32 subsequently disappeared, time to death was still significantly delayed in the CCR5 Δ32 heterozygotes without SDF1-3′A (RH = 0; 95% CI, 0–0.53; P = 0.008).ConclusionIn pediatric AIDS, the protective effect of CCR5 wt/Δ32 is more pronounced in early years of infection and appears to be abrogated by the SDF1-3′A genotype.
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