RT-SHIV MODEL FOR RESISTANCE TO AIDS THERAPY

描述：(改编自申请者摘要)：高度活跃 抗逆转录病毒疗法(HAART)是#年艾滋病治疗的重大进展。 人类。HAART可长期抑制无法检测到的HIV-1病毒载量 在许多患者中的水平。然而，HIV-1仍处于潜伏或持续状态 在这些患者中形成，并可在停止药物治疗后重新出现。 HAART或其他治疗方法的另一个主要障碍是出现 艾滋病毒-1的耐药和多药耐药变种。的一个主要目标 该项目是在动物模型上建立类似HAART的治疗方法。我们的目标是 不是为了提供药物测试系统，而是为了进一步发展动物 可用于艾滋病治疗研究的模型系统 在感染了HIV-1的人身上很难或不可能做到的事情。在……里面 特别是，我们希望研究低水平病毒复制和 HAART期间的延迟/持久性。出于这个原因，我们将使用嵌合体 含有HIV-1逆转录酶的猿猴免疫缺陷病毒 (RT-SHIV)，这将使体外和体内研究组合成为可能 含有核苷类似物和非核苷反向抑制剂 转录酶(NNRTI)。我们还将把这个模型用于药物研究。 含有蛋白水解酶抑制剂的组合。利用长期目标 在长时间内探测病毒复制和/或持续位置的模型 HAART，并评估其他干预方法，试图根除 来自水库的病毒。

DESCRIPTION: (Adapted from the Applicant's Abstract): Highly active antiretroviral therapy (HAART) has been a major advance in treatment of AIDS in humans. HAART provides long term suppression of HIV-1 loads to undetectable levels in many patients. Nevertheless, HIV-1 remains in a latent or persistent form in these patients and can reemerge when drug therapy is discontinued. Another major barrier to HAART or other therapeutic approaches is the emergence of drug-resistant and multi-drug resistant variants of HIV-1. A major goal of this project is to establish HAART-like therapy in an animal model. Our goal is not to provide a drug testing system but rather to further develop the animal model system to the point where it can be useful for studies of AIDS therapy that are difficult or impossible to do in humans infected by HIV-1. In particular, we wish to study sites of low-level virus replication and latency/persistence during HAART. For this reason, we will use a chimera of simian immunodeficiency virus (SIV) containing the HIV-1 reverse transcriptase (RT-SHIV), which will enable in vitro and in vivo studies of combinations containing nucleoside analogs and non-nucleoside inhibitors of reverse transcriptase (NNRTI). We will also use this model for studies of drug combinations that include protease inhibitors. Long-term goals are (to) utilize the model to probe sites of virus replication and/or persistence in prolonged HAART, and to evaluate other intervention approaches in attempts to eradicate virus from reservoirs.