HIV Drug Resistance Database

项目总结 艾滋病毒耐药性(HIVDR)是对抗逆转录病毒(ARV)治疗(ARV)成功的威胁，也是 阻碍消除艾滋病这一公共卫生问题。出现病毒学故障的艾滋病毒携带者 (VF)在抗逆转录病毒治疗期间感染HIVDR并将抗药性病毒传播给他人的风险很高，而 主要感染抗药性病毒的人发生室颤的风险很高，并进一步增加 在HIVDR。全面、准确和公开的HIVDR数据对于以人口为基础的 监测获得性和传播性艾滋病毒/艾滋病、艾滋病毒感染患者的管理和 确定总体药物开发需求。一个公共数据库，用于管理、注释、合成和 传播来自HIVDR研究的数据将使识别和表征HIVDR突变成为可能 与监测、临床管理和药物开发最相关，并将加快研究 HIVDR的机制和对最新ARV方案应答的预测因素。 斯坦福艾滋病毒耐药性数据库(HIVDB)为 解决有关艾滋病毒治疗的主要分子靶点的数据密集型问题：逆转录酶， 蛋白水解酶、整合酶和衣壳。HIVDB的序列分析程序也已整合到 全球许多研究实验室的工作流程。实现这项建议的目标将有助于 从事HIVDR监测、ART临床试验和ARV开发的研究人员使他们能够 找出已出版文献中的差距，将HIVDB的贡献纳入新的分析，以及 发现新知识。 我们的首要目标将包括将HIVDB扩展为一种资源，为临床提供科学基础 和HIVDR突变的流行病学意义，并解决HIVDR知识中的空白，包括 对新近批准的抗逆转录病毒药物、用于新适应症的已建立的抗逆转录病毒药物以及 将用于预防和治疗的长效抗逆转录病毒药物。我们将实施战略，增加 数据共享，以帮助确保该项目的长期可持续性。 我们的第二个目标将涉及扩展HIVDB基因耐药测试解释程序的逻辑 预测抗逆转录病毒联合疗法和普通抗逆转录病毒疗法的病毒学应答。我们将演示 并推广使用我们的序列分析软件分析其他致病病毒 抗病毒治疗是可用的。 我们的第三个目标将涉及将HIVDB转变为一个完全开放源码和可移植的项目。完成 这一目标将支持使用HIVDB的研究人员通过使他们能够无缝地 将HIVDR数据整合到他们的研究中。实现这一目标也将促进长期可持续性。 HIVDB项目的一部分。

PROJECT SUMMARY HIV drug resistance (HIVDR) is a threat to the success of antiretroviral (ARV) therapy (ART) and a major barrier to the elimination of AIDS as a public health problem. Persons with HIV who develop virological failure (VF) during ART are at high risk of developing HIVDR and transmitting a drug-resistant virus to others while persons primarily infected with a drug-resistant virus are at high risk of developing VF and a further increase in HIVDR. Comprehensive, accurate, and publicly available HIVDR data are essential for population-based monitoring of acquired and transmitted HIVDR, for the management of HIV-infected patients, and for identifying overall drug-development needs. A public database that curates, annotates, synthesizes, and disseminates data from HIVDR studies will make it possible to identify and characterize the HIVDR mutations most relevant to surveillance, clinical management, and drug development, and will expedite research into the mechanisms of HIVDR and the predictors of response to the newest ARV regimens. The Stanford HIV Drug Resistance Database (HIVDB) provides a unique conceptual framework for addressing data-intensive questions about the main molecular targets of HIV therapy: reverse transcriptase, protease, integrase, and capsid. HIVDB’s sequence analysis programs have also become integrated into the workflows of many research laboratories worldwide. Accomplishing the Aims of this proposal will assist researchers engaged in HIVDR surveillance, ART clinical trials, and ARV development by enabling them to identify gaps in the published literature, incorporate contributions from HIVDB into novel analyses, and discover new knowledge. Our first Aim will involve expanding HIVDB as a resource that provides the scientific foundations of the clinical and epidemiological significance of HIVDR mutations and that address gaps in HIVDR knowledge including the correlates of resistance to recently approved ARVs, established ARVs used for new indications, and the long-acting ARVs that will be used for prevention and treatment. We will implement strategies to increase data sharing to help ensure the long-term sustainability of this project. Our second Aim will involve extending the logic of HIVDB’s genotypic resistance test interpretation program to predict the virological response to ARV combinations and common ART regimens. We will demonstrate and promote the use of our sequence analysis software for the analysis of other pathogenic viruses for which antiviral therapy is available. Our third Aim will involve converting HIVDB into a fully open source and transferable project. Accomplishing this aim will support researchers using HIVDB to advance their research by enabling them to seamlessly integrate HIVDR data into their research. Accomplishing this aim will also foster the long-term sustainability of the HIVDB project.