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药物 高效抗逆转录病毒疗法（HAART）是治疗人类艾滋病的主要进展。HAART 提供长期抑制HIV-1载量到检测不到的水平，在许多 患者尽管如此，HIV-1在这些地区仍以潜伏或持续的形式存在。 患者，并可以重新出现时，药物治疗停止。另一个主要 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体。一个主要目标是 项目是在动物模型中建立HAART样治疗。我们的目标不是 提供一个药物测试系统， 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。特别是 申请人希望研究病毒复制水平低的位点， HAART期间的延迟/持续性。此外，他们希望评估新的 最大限度地减少耐药性和根除病毒库的战略， 逃避HAART。为此，他们将使用一种猿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 逆转录酶的非核苷抑制剂（NNRT 1）。他们还将利用 这个模型用于研究包括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位点 和/或长期HAART的持续性，并评估其他干预措施 试图从宿主中根除病毒。

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.