QUANTITATIVE IN SITU HYBRIDIZATION--HIV1 RNA CLEARANCE FROM LYMPHOID TISSUE

人类免疫缺陷病毒(HIV)治疗的新进展 感染增加了我们对临床病程和 改善了感染艾滋病毒患者的预后。介绍了 蛋白水解酶抑制剂(PI)与核苷类似物逆转 高效抗逆转录病毒治疗的转录酶抑制物(NRTI) 人类抗逆转录病毒疗法(HAART)的临床应用减少了艾滋病毒的治疗。这个 HAART后HIV在血浆中的衰变特征 经过仔细的描述。然而，在治疗中断时或在 一旦出现耐药病毒株，病毒载量迅速 在血浆中爬行。这表明，病毒的动力学在 作为HIV储藏室的隔间有不同的腐烂 外周血中相同细胞类型的特征。因此， 现在人们的注意力已经转向了血浆以外的隔间，特别是 淋巴组织，以更全面地了解病毒周转的动力学 在对HAART做出全面回应后。 外周病毒载量的下降几乎一致地伴随着 CD4+淋巴细胞的增加和临床的显著改善 减少机会性感染的发生率，延长生存时间。这个 这种明显的免疫部分恢复的机制是 人们对此知之甚少。 该项目的目标是描述艾滋病毒的衰变特征 HAART治疗患者的淋巴组织内分布及其关系 参与HIV免疫致病机制的关键细胞因子 疾病。患者在开始手术前的淋巴活检 HAART和第一年治疗期间的两个后续时间点 将被分成三份立即保存。血清 外周血单个核细胞(PBMC)将在 同样的时间。多种检测HIV和细胞因子IL-2的方法， IL-4、IL-6、IL-12、IFY和TNFpha将按照 方法部分。希望从这些研究中获得的结果 将对艾滋病毒的病毒动力学和 加强免疫恢复的潜在途径以及帮助 确定新的治疗策略。

Recent advances in therapy for human immunodeficiency virus (HIV) infection have increased our understanding of the clinical course and improved the prognosis of patients infected with HIV. The introduction of protease inhibitors (PI) in combination with nucleoside-analogue reverse transcriptase inhibitors (NRTI) as highly active anti-retroviral therapy (HAART) into clinical care has allowed reduction of HIV therapy. The decay characteristics of HIV in the plasma following HAART have been carefully described. However, upon interruption of therapy or in the event of the emergence of resistant strains of virus, viral load rapidly climbs in the plasma. This suggests that the viral dynamics in the compartments which serve as reservoirs for HIV have different decay characteristics from the same cell types in the peripheral blood. Thus, attention has now turned to compartments other than plasma, especially lymph tissue, to more fully understand the dynamics of viral turnover following a complete response to HAART. The fall in peripheral viral load is almost uniformly accompanied by an increase in CD4+ lymphocytes and a dramatic clinical improvement with a reduced incidence of opportunistic infections and prolonged survival. The mechanisms responisible for this apparent partial immune restitution are poorly understood. The goal of this project is characterize the decay characteristics of HIV within the lymph nodes of patients treated with HAART and its relationship to critical cytokines that are involved in the immunopathogenesis of HIV disease. Excisional lymph node biopsies from patients prior to initiating HAART and on two subsequent time points during the first year of therapy will be obtained and divided into three for immediate preservation. Serum and peripheral blood mononuclear cells (PBMC's) will be preserved at the same time. Multiple approaches of measuring HIV and the cytokines IL-2, IL-4, IL-6, IL-12, IFy, and TNFalpha will be performed as outlined in the methods section. It is hoped that the results obtained from these studies will provide additional insight into the viral dynamics of HIV and potential avenues for augmenting immune restitution as well as to help identify novel therapeutic strategies.