IMMUNOLOGY AND EARLY DIAGNOSIS OF HIV 1 INFECTION IN THE NEONATE

目前可用于治疗HIV-1的化合物的工具箱 疾病由齐多夫定(ZDV)等链终止物主导，它们具有 已被证明是易感人群新生感染的有效抑制物 体外培养的细胞，但没有明显的抗慢性病活性 被感染的细胞。因此，为了最大限度地发挥这些药物的治疗效果 化合物，应尽快开始治疗后， 感染和之前建立的大型感染水库 细胞。由于大多数人群面临感染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一种独特的 因为他们暴露的时间，有机会进行早期治疗干预 是明确的(即在子宫内或在分娩期间)。然而，新生儿也 自血清学评估以来，对早期诊断构成了巨大的障碍 真正的抗体状态因母体的存在而变得复杂 抗体。因此，旨在早期诊断艾滋病毒-1的替代战略 新生儿的感染必须发展起来。这个项目的总体目标是 项目是将目前可用的免疫学和病毒学相结合 技术纳入评估小组，该小组将提供最终的 在尽可能早的时间点发现艾滋病毒感染的证据。病毒学 检测结果将通过新鲜淋巴细胞的病毒培养进行评估， 直接捕获血浆或血清中的p24抗原，并检测病毒DNA 通过聚合酶链式反应。血清学评估将包括HIV-1 免疫球蛋白印迹和多肽特异性抗体反应。HIV-1特异性 细胞反应性、淋巴细胞亚群的变化和 将评估对不同刺激的胚性反应。的影响 HIV-1感染对各种细胞因子的产生也会 评估过了。

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.