IMMUNOLOGY AND EARLY DIAGNOSIS OF HIV-1 INFECTION IN THE NEONATE

目前可用于治疗HIV-1的化合物 疾病主要由链终止剂如齐多夫定（ZDV）控制， 已被证明是易感的新生感染的有效抑制剂， 细胞，但对慢性 被感染的细胞因此，为了最大限度地提高这些药物的治疗效果， 治疗后应尽快开始， 感染和之前建立一个大水库的感染 细胞由于大多数群体都有感染HIV-1的风险，这是不切实际的。 然而，HIV-1血清阳性母亲所生的婴儿呈现出独特的 自暴露时间起，有机会进行早期治疗干预 定义明确（即在子宫内或出生时）。然而，新生儿也 由于血清学评估， 真正的抗体状态是复杂的母亲的存在， 抗体的因此，旨在早期诊断HIV-1的替代策略 新生儿的感染必须发展。这个项目的总体目标是 项目是将联合收割机目前可用的免疫学和病毒学 技术纳入评估小组，将提供明确的 在尽可能早的时间点发现HIV-1感染的证据。病毒学 通过新鲜淋巴细胞的病毒培养来评估测定， 直接捕获血浆或血清中的p24抗原，并检测病毒DNA 通过聚合酶链反应。血清学评价将包括HIV-1 IgM蛋白质印迹和肽特异性抗体应答。HIV-1特异性 细胞反应性，淋巴细胞亚群的变化， 将评估对各种刺激的胚变反应。的影响 HIV-1感染后也会产生各种细胞因子 评估。

The current armamentarium of compounds available for the treatment of HIV-1 disease is dominated by chain terminators like zidovudine (ZDV) which have been shown to be potent inhibitors of de novo infection of susceptible cells in vitro, but with no demonstrable activity against chronically infected cells. Therefore, to maximize the therapeutic efficacy of these compounds, treatment should be initiated as soon as possible after infection and before the establishment of a large reservoir of infected cells. With most groups at risk for HIV-1 infection, this is not practical. However, infants born to HIV-1 seropositive mothers present a unique opportunity for early therapeutic intervention since their time of exposure is well defined (ie in utero or during birth). However, newborns also present a formidable obstacle to early diagnosis since serologic assessment of true antibody status is complicated by the presence of maternal antibody. Therefore, alternate strategies aimed at early diagnosis of HIV-1 infection in the newborn must be developed. The overall goal of this project is to combine currently available immunologic and virologic technologies into an assessment panel which will provide definitive evidence of HIV-1 infection at the earliest possible timepoints. Virologic determinations will be assessed by viral culture of fresh lymphocytes, direct p24 antigen capture of 'plasma or serum, and detection of viral DNA by the polymerase chain reaction. Serologic evaluations will include HIV-1 IgM Western blot and peptide specific antibody responses. HIV-1 specific cellular reactivity, changes in the lymphocyte subpopulations and blastogenic responses to various stimuli will be evaluated. The effects of HIV-1 infection on the production of various cytokines will also be assessed.