RT-SHIV MODEL FOR RESISTANCE TO AIDS THERAPY

描述：（改编自申请人的摘要）高活性抗逆转录病毒药物 治疗（HAART）是人类治疗艾滋病的重大进步。高效抗逆转录病毒疗法 在许多情况下可长期抑制 HIV-1 负荷至检测不到的水平 患者。然而，HIV-1 在这些疾病中仍然处于潜伏或持续的状态。 患者可能会在药物治疗停止后再次出现。另一个专业 HAART 或其他治疗方法的障碍是药物的出现 HIV-1 的耐药性和多重耐药性变体。此次活动的一个主要目标 该项目的目的是在动物模型中建立类似HAART的疗法。目标不是 提供药物测试系统而是进一步开发动物模型 系统已达到可用于艾滋病治疗研究的程度 在感染 HIV-1 的人类中很难或不可能做到这一点。特别是， 申请人希望研究低水平病毒复制的位点 HAART 期间的潜伏期/持续性。此外，他们希望评估新的 最大限度地减少耐药性并根除病毒库的策略 逃避HAART。为此，他们将使用猿猴免疫缺陷病毒的嵌合体 (SIV) 含有 HIV-1 逆转录酶 (RT-SHIV)，这将使 含有核苷类似物的组合的体外和体内研究 逆转录酶非核苷抑制剂（NNRT1）。他们还将使用 该模型用于研究包含蛋白酶抑制剂的药物组合。 长期目标是利用该模型来探测病毒复制位点 和/或长期坚持HAART，并评估其他干预措施 尝试从储存库中根除病毒的方法。

DESCRIPTION: (Adapted from 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. The 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, the applicants wish to study sites of low level virus replication and latency/persistence during HAART. In addition, they wish to evaluate new strategies to minimize resistance and to eradicate the pool of virus that evades HAART. For this they 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 (NNRT1). They will also use this model for studies of drug combinations that include protease inhibitors. Long-term goals are 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.