HIV Drug Resistance Database

HIV耐药数据库

• 批准号: 10699882
• 负责人: ROBERT William SHAFER
• 金额: $ 71.45万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699882
• 关键词: 2019-nCoV; Acquired Immunodeficiency Syndrome; Address; Anti-Retroviral Agents; Antiviral Agents; Antiviral Therapy; Biological; COVID-19 treatment; Capsid; Clinical; Clinical Data; Clinical Management; Clinical Trials; Cohort Studies; Computer software; Conduct Clinical Trials; Data; Data Collection; Data Set; Databases; Development; Drug resistance; Ensure; Epidemiologist; Epidemiology; Failure; Fostering; Foundations; Funding; Genbank; Genotype; Geographic Locations; Goals; Grant; HIV; HIV drug resistance; HIV therapy; In Vitro; Individual; Integrase; Knowledge; Laboratories; Laboratory Research; Literature; Logic; Meta-Analysis; Metadata; Modernization; Molecular Target; Monitor; Mutation; Outcome; Patients; Peptide Hydrolases; Persons; Pharmaceutical Preparations; Play; Positioning Attribute; Predisposition; Prevalence; Prevention; Public Health; Publishing; R24; RNA-Directed DNA Polymerase; Recording of previous events; Regimen; Research; Research Personnel; Resistance; Resources; Role; Scientist; Sequence Analysis; Sorting; Testing; Therapy Clinical Trials; Update; Virus; Work; antiretroviral therapy; combat; data sharing; database query; design; drug development; drug resistant virus; experience; fighting; high risk; improved; knowledge base; molecular sequence database; novel; novel strategies; open source; pandemic disease; pathogenic virus; population based; predicting response; programs; public database; public repository; recruit; resistance mutation; response; success; systematic review; targeted treatment; transmission process

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.

项目概要 HIV 耐药性 (HIVDR) 是抗逆转录病毒 (ARV) 治疗 (ART) 成功的一个威胁，也是一个主要的 艾滋病毒感染者出现病毒学衰竭，是消除艾滋病这一公共卫生问题的障碍。 （VF）在 ART 期间处于发展 HIVDR 并将耐药病毒传播给他人的高风险中 主要感染耐药病毒的人发生 VF 的风险很高，并且进一步增加 全面、准确且公开的 HIVDR 数据对于基于人群的研究至关重要。 监测获得性和传播的 HIVDR、管理 HIV 感染者以及 确定整体药物开发需求的公共数据库，用于整理、注释、综合和分析。 传播 HIVDR 研究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，并将加快相关研究 HIVDR 的机制以及对最新 ARV 治疗方案反应的预测因素。 斯坦福大学艾滋病毒耐药性数据库 (HIVDB) 提供了一个独特的概念框架 解决有关艾滋病毒治疗主要分子靶点的数据密集型问题：逆转录酶， 蛋白酶、整合酶和衣壳也已集成到 HIVDB 的序列分析程序中。 世界各地许多研究实验室的工作流程将有助于实现该提案的目标。 研究人员通过使他们能够参与 HIVDR 监测、ART 临床试验和 ARV 开发 找出已发表文献中的差距，将 HIVDB 的贡献纳入新颖的分析中，以及 发现新知识。 我们的第一个目标是扩大 HIVDB 作为一种资源，为临床治疗提供科学基础。 HIVDR 突变的流行病学意义，并解决 HIVDR 知识的空白，包括 对最近批准的抗逆转录病毒药物、用于新适应症的既定抗逆转录病毒药物的耐药性的相关性，以及 我们将实施增加用于预防和治疗的长效抗逆转录病毒药物的策略。 数据共享有助于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 基因型耐药测试解释程序的逻辑 预测抗逆转录病毒药物组合和常见抗逆转录病毒治疗方案的病毒学反应。 并推广使用我们的序列分析软件来分析其他致病病毒 可以进行抗病毒治疗。 我们的第三个目标是将 HIVDB 转变为一个完全开源且可转让的项目。 这一目标将支持研究人员使用 HIVDB 来推进他们的研究，使他们能够无缝地 将 HIVDR 数据纳入他们的研究中也将促进长期可持续性。 HIVDB 项目。

项目成果

Amino Acid Prevalence of HIV-1 pol Mutations by Direct Polymerase Chain Reaction and Single Genome Sequencing.

通过直接聚合酶链反应和单基因组测序分析 HIV-1 pol 突变的氨基酸流行率。

• 发表时间: 2019
• 影响因子: 1.5
• 作者: Tzou, Philip L;Rhee, Soo;Shafer, Robert W
• 通讯作者: Shafer, Robert W

Adherence to contemporary antiretroviral treatment regimens and impact on immunological and virologic outcomes in a US healthcare system.

遵守当代抗逆转录病毒治疗方案及其对美国医疗保健系统免疫学和病毒学结果的影响。

• 发表时间: 2022
• 影响因子: 3.7
• 作者: T Tchakoute, Christophe;Rhee, Soo;Hare, C Bradley;Shafer, Robert W;Sainani, Kristin
• 通讯作者: Sainani, Kristin

Highly Ambiguous HIV-1 Pol Positions Encoding Multiple Amino Acids Usually Result from Antiviral or Immune Selection Pressure.

编码多个氨基酸的高度模糊的 HIV-1 Pol 位点通常是由抗病毒或免疫选择压力造成的。

• 发表时间: 2023-03
• 影响因子: 1.5
• 作者: Tao, Kaiming;Rhee, Soo;Tzou, Philip L;Holmes, Susan P;Shafer, Robert W
• 通讯作者: Shafer, Robert W

Coronavirus Antiviral Research Database (CoV- 2 RDB): An Online Database Designed to Facilitate 3 Comparisons Between Candidate Anti-Coronavirus 4 Compounds 5

冠状病毒抗病毒研究数据库 (CoV-2 RDB)：一个在线数据库，旨在促进 3 候选抗冠状病毒 4 化合物之间的比较 5

• DOI: 10.5812/pedinfect.104225
• 发表时间: 2024-09-14
• 期刊: Archives of Pediatric Infectious Diseases
• 影响因子: 0.7
• 作者: P. Tzou;Kaiming Tao;J. Nouhin;Soo;Benjamin D Hu;Shruti R Pai;Neil Parkin;Robert W Shafer
• 通讯作者: Robert W Shafer

Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria.

尼日利亚大型预防和治疗项目中艾滋病毒/艾滋病成人和青少年一线抗逆转录病毒治疗失败的预测因素。

• 发表时间: 2020
• 作者: Ndembi, Nicaise;Murtala;Tola, Monday;Jumare, Jibreel;Aliyu, Ahmad;Alabi, Peter;Mensah, Charles;Abimiku, Alash'le;Quiñones;Crowell, Trevor A;Rhee, Soo;Shafer, Robert W;Gupta, Ravindra;Blattner, William;Charur
• 通讯作者: Charur