RT-SHIV MODEL FOR RESISTANCE TO AIDS THERAPY

描述：（改编自申请人摘要）：高活性 抗逆转录病毒疗法（HAART）是治疗艾滋病的一项重大进展， 人类HAART可长期抑制HIV-1载量， 许多患者的水平。尽管如此，HIV-1仍然处于潜伏或持续的状态， 在这些患者中形成，并可在药物治疗停止时重新出现。 HAART或其他治疗方法的另一个主要障碍是 耐药和耐多药的HIV-1变种。的一个主要目标 该项目是在动物模型中建立HAART样疗法。我们的目标是 不是为了提供药物测试系统，而是为了进一步开发这种动物， 模型系统的点，它可以用于艾滋病治疗的研究 这在HIV-1感染者身上很难或不可能做到。在 特别是，我们希望研究低水平病毒复制的位点， HAART期间的延迟/持续性。为此，我们将使用一个嵌合体， 含有HIV-1逆转录酶的猿猴免疫缺陷病毒（SIV） （RT-SHIV），这将使体外和体内研究的组合 含有核苷类似物和非核苷的逆转录酶抑制剂 转录酶（NNRTI）。我们还将使用该模型进行药物研究， 包括蛋白酶抑制剂的组合。长期目标是利用 该模型用于探测病毒复制和/或持久性的位点 HAART，并评估其他干预方法， 病毒从水库。

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.