CCR5-Δ32和CCR2-64I等位基因对围产期感染HIV-1儿童疾病进展的影响：一项国际荟萃分析。

Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis.

作者信息

Ioannidis John P A, Contopoulos-Ioannidis Despina G, Rosenberg Philip S, Goedert James J, De Rossi Anita, Espanol Teresa, Frenkel Lisa, Mayaux Marie-Jeanne, Newell Marie-Louise, Pahwa Savita G, Rousseau Christine, Scarlatti Gabriella, Sei Shizuko, Sen Luisa, O'Brien Thomas R

机构信息

Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

出版信息

AIDS. 2003 Jul 25;17(11):1631-8. doi: 10.1097/01.aids.0000060411.18106.0f.

DOI:10.1097/01.aids.0000060411.18106.0f

PMID:12853745

Abstract

OBJECTIVE

Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-delta32 and CCR2-64I in an international meta-analysis.

METHODS

Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated.

RESULTS

There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-delta32 and CCR2-64I showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (CI) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P=0.01 for the time-dependent model). For CCR2-64I, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P<0.01 for the time-dependent model). CCR5-delta32 and CCR2-64I offered no clear protection after clinical AIDS had developed.

CONCLUSION

The CCR5-delta32 and CCR2-64I alleles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

摘要

目的

在围产期感染儿童中，CCR5和CCR2基因的某些等位基因对疾病进展速度的影响尚不清楚。我们通过一项国际荟萃分析研究了CCR5-Δ32和CCR2-64I的影响。

方法

基因型数据来自10项研究，共1317名感染HIV-1的儿童（随访7263人年）。按研究和种族分组进行事件发生时间分析。终点包括进展至临床艾滋病、死亡以及临床艾滋病诊断后的死亡。特别研究了基因效应的时间依赖性。

结果

不同队列中观察到的疾病进展率存在很大异质性。对于进展至临床艾滋病，CCR5-Δ32和CCR2-64I总体上均显示出不显著的保护趋势[风险比分别为0.84，95%置信区间（CI）0.58 - 1.23；以及0.87，95%CI 0.67 - 1.14]。然而，生存分析显示出统计学上显著的时间依赖性。CCR5-Δ32携带者在生命的前3年没有死亡，而在随后几年没有保护作用（风险比0.95；95%CI 0.43 - 2.10）（时间依赖性模型P = 0.01）。对于CCR2-64I，生命前6年的死亡风险比为0.69（95%CI 0.39 - 1.21），随后几年为2.56（95%CI 1.26 - 5.20）（时间依赖性模型P<0.01）。临床艾滋病发生后，CCR5-Δ32和CCR2-64I没有提供明确的保护作用。