HIV 2-LTR Dynamics and Cryptic Viremia

描述（由申请人提供）：我们开发了一种在向明显抑制性抗病毒方案中加入整合酶抑制剂（如雷特格韦）后形成2-LTR HIV DNA附加体的简单模型。当最近的雷特格韦强化实验的2-LTR浓度数据适合我们的模型时，结果强烈表明-LTR游离体形成于抗病毒药物无法包含HIV复制的隔室中。本项目的主要研究目标是开发特定的可检验假设，以指导未来的临床验证实验，以证实这些发现。了解艾滋病毒复制的机制可能会继续在患者的血液中检测不到病毒是至关重要的努力治疗和/或治愈艾滋病毒感染。如果 如果隐性病毒血症持续存在，HIV阳性患者最终会产生耐药病毒， 被迫改变治疗方案。在拟议的研究中开发的数学模型可能提供一个微创的实验方法来检测和量化隐性病毒血症。这是能够在艾滋病毒医学中研究和消除这种现象的关键的第一步。我们将使用贝叶斯统计来验证我们的模型对一个新的数据集，开发模型扩展，使我们能够计划其他测量，并制定采样时间表，优化信息，同时最大限度地减少成本和实验的侵入性。

DESCRIPTION (provided by applicant): We have developed a simple model of the formation of 2-LTR HIV DNA episomes following the addition of integrase inhibitor such as raltegravir to an apparently suppressive antiviral regimen. When 2-LTR concentration data from recent raltegravir intensification experiments is fit to our model, the results strongly suggest that the -LTR episomes are being formed in a compartment where the antiviral drugs are unable to contain HIV replication. The primary research objective of this project is to develop specific testable hypotheses to guide a future clinical validation experiment to confirm these findings. Understanding the mechanisms by which HIV replication may continue in patients with no virus detectable in their blood is critically important to efforts to treat and/or cure HIV infection. If cryptic viremia persists, the HIV-positive patient will eventually develop drug-resistant virus and be forced to switch treatment regimens. The mathematical models developed in the proposed research may provide a minimally invasive experimental method to detect and quantify cryptic viremia. This is a critical first step in being able to study and eliminate this phenomenon in HIV medicine. We will use Bayesian statistics to validate our model against a new dataset, develop model extensions that allow us to plan for other measurements, and develop sampling schedules that optimize the information while minimizing the cost and invasiveness of the experiment.