RT-SHIV MODEL FOR RESISTANCE TO AIDS THERAPY

描述：(改编自申请者摘要)高效抗逆转录病毒 治疗(HAART)是人类艾滋病治疗的重大进展。HAART 长期将HIV-1病毒载量抑制到无法检测到的水平 病人。然而，HIV-1仍然以潜伏或持久的形式存在于这些 患者并可能在停止药物治疗后重新出现。另一大专业 HAART或其他治疗方法的障碍是药物的出现 HIV-1的耐药和多药耐药变种。这样做的一个主要目标是 该项目是在动物模型上建立类似HAART的疗法。我们的目标不是 为了提供药物测试系统，而是为了进一步发展动物模型 系统，以使其可用于艾滋病治疗的研究，这些研究 在感染HIV-1的人身上很难或不可能做到这一点。尤其是， 申请者希望研究低水平病毒复制和 HAART期间的延迟/持久性。此外，他们还希望评估新的 将耐药性降至最低并根除 避开HAART。为此，他们将使用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 含有核苷类似物和核苷类似物的化合物的体外和体内研究 非核苷类逆转录酶抑制剂(NNRT1)。他们还将使用 这一模型用于研究含有蛋白酶抑制剂的药物组合。 长期目标是利用该模型探测病毒复制的位置 和/或延长HAART的持续性，并评估其他干预措施 试图从水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.