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Investigation of the factors influencing on HIV mother-to-child transmission and disease progression

HIV母婴传播及疾病进展影响因素调查

基本信息

批准号：
14256005
负责人：
ICHIMURA Hiroshi
金额：
$ 12.4万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

(1)Investigation of the factors influencing on mother-to-child transmission (MTCT) of HIV-1 and disease progression : There have been few reports on the factors influencing on HIV-1 MTCT in Africa, where most cases of HIV MTCT exist, and the effect of host immune factors on clinical course left unconfirmed. In the cohort study on the prevention of MTCT using short course zidovudine (ZDV) in western Kenya, we found that CCR5-2132T/T and -2554T/T were associated with increased HIV-1 MTCT and RANTES-403 A/A was associated with decreased MTCT among infants whose mother took ZDV, and that no SNP (single nucleotide polymorphism) analyzed in the study was found to be associated with mortality rate at the age of 24 months. In addition, no ZDV-resistant associated mutation was observed in infants' HIV-1 clones, and some ZDV-resistant associated mutations were observed in a part of HIV-1 clones sampled from the mothers before and after ZDV-treatment, but they were all secondary mutations. These results suggest that the cause of MTCT of HIV-1 in spite of short-term ZDV treatment was not associated with an induction of ZDV-resistant mutants.(2)Factors influencing on the clinical courses among HIV-infected Japanese hemophiliacs : We previously reported the relationship between SNPs in the CCR5 promoter region and the clinical courses in HIV-1-infected Japanese hemophiliacs. In the current study, we further analyzed the relationship between the SNPs, such as RANTES promoter-28G/-403A, RANTESIn1.1C, SDF-1 3'A, IL-4 promoter-589T and DC-SIGNpromoter-139C/-336C, and disease progression, and found that RANTES-28G was associated with delayed AIDS progression, while DCSIGN-139C was associated with accelerated AIDS progression in HIV-1-infected Japanese hemophiliacs.

(1) HIV-1母婴传播（MTCT）及疾病进展影响因素调查：在HIV-1母婴传播病例最多的非洲地区，关于HIV-1母婴传播影响因素的报道较少，宿主免疫因素对临床病程的影响也未得到证实。在肯尼亚西部使用短疗程齐多夫定（ZDV）预防MTCT的队列研究中，我们发现在母亲服用ZDV的婴儿中，CCR5-2132T/T和-2554T/T与HIV-1 MTCT升高相关，RANTES-403 A/A与MTCT降低相关，并且研究中分析的SNP（单核苷酸多态性）未发现与24月龄死亡率相关。此外，在婴儿HIV-1克隆中未观察到zdv耐药相关突变，在zdv治疗前后从母亲身上采集的部分HIV-1克隆中观察到一些zdv耐药相关突变，但都是继发性突变。这些结果表明，尽管短期ZDV治疗，HIV-1 MTCT的原因与ZDV抗性突变的诱导无关。(2)影响hiv -1日本血友病患者临床病程的因素：我们之前报道了CCR5启动子区域snp与hiv -1日本血友病患者临床病程的关系。在本研究中，我们进一步分析了RANTES启动子- 28g /-403A、RANTESIn1.1C、SDF-1 3'A、IL-4启动子- 589t和DC-SIGNpromoter-139C/-336C等snp与疾病进展的关系，发现在hiv -1感染的日本血友病患者中，RANTES- 28g与延迟艾滋病进展相关，而DCSIGN-139C与加速艾滋病进展相关。