Developing Botswana Laboratory Capacity in HIV Genomics and HIV Cure

发展博茨瓦纳艾滋病毒基因组学和艾滋病毒治疗实验室能力

• 批准号: 10688320
• 负责人: Simani Gaseitsiwe
• 金额: $ 10万
• 依托单位: BOTSWANA-HARVARD AIDS INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688320
• 关键词: Acquired Immunodeficiency Syndrome; Adolescent; Affect; Africa South of the Sahara; African; Anti-Retroviral Agents; Area; Bioinformatics; Biological Assay; Boston; Botswana; Certification; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Core Facility; Country; DNA; Data; Data Analyses; Development; Diagnosis; Drug resistance; Educational workshop; Evolution; Faculty; Flow Cytometry; Funding; Future; Generations; Genomic Segment; Genomics; Genotype; Grant; HIV; HIV-1; HIV-1 vaccine; Health Personnel; Human; Incidence; Infant; Institution; Investigator-Initiated Research; Investments; Knowledge; Laboratories; Laboratory Scientists; Molecular; Molecular Virology; Mother-to-child HIV transmission; Observational Study; Output; Patients; Persons; Pharmaceutical Preparations; Prevalence; Prevention strategy; Public Health; Public Health Schools; Research; Research Personnel; Rest; SARS-CoV-2 B.1.1.529; Scientist; Southern Africa; Students; Training; Training Activity; United States National Institutes of Health; Universities; Vaccine Design; Viral; Work; World Health Organization; antiretroviral therapy; cohort; emerging pathogen; epidemiology study; experience; graduate student; implementation science; improved; interest; laboratory experience; member; mortality; next generation sequencing; pathogen; pathogen genomics; pressure; professional students; programs; resistance mutation; skills; success; treatment program; university student; variants of concern; virtual

Project Summary Botswana has been one of the countries most affected by HIV-1 and has always been in the top 3 countries by HIV-1 prevalence for the past 20 years. The country has responded gallantly by providing free antiretroviral therapy (ART) to persons living with HIV-1 (PLWH) in 2002 and an aggressive combination of prevention strategies. This has resulted in reduced HIV-1 incidence and associated mortality and the country was the third globally to reach the UNAIDS 95-95-95 targets of HIV-1 diagnosis, treatment, and viral suppression. Since its inception in 1996, the Botswana Harvard AIDS Institute Partnership (BHP) has conducted investigator-initiated clinical trials, observational and epidemiologic studies, laboratory-based studies, and implementation science research. BHP laboratory also carries out molecular virology research on HIV and this research has been instrumental in molecular characterizing HIV-1 subtype C, which predominates in Botswana and Southern Africa. We draw upon the depth and breadth of the experience gained over more than 2 decades of investigator-initiated research, training, and capacity building to increase access to HIV-1 genomics training. Since 2017, we have invested in implementing pathogen agnostic next- generation sequencing which was critical in the first sequencing of the SARS-CoV-2 Omicron variant of concern in Botswana. Working with our collaborators we have also established cohorts of very early treated infants and adolescents for understanding HIV-1 reservoirs. We, therefore, aim through this application to strengthen BHP in HIV-1 genomics and molecular virology capacity in Botswana and increase access to pathogen genomics in the sub-Saharan Africa region as a center of excellence. The capacity developed here will be crosscutting for virologic studies and will thus be instrumental in BHP lab’s continued diversification into research on other emerging pathogens of global public health interest. To achieve this, we aim to 1) develop and advance BHP as an HIV-1 genomics regional center of excellence. We will leverage the expertise in pathogen genomics developed over the past 20 years to facilitate capacity building by hosting courses in HIV-1 sequencing, bioinformatic analysis, and sequence data interpretation. Building on our collaboration with the University of Botswana, Harvard T.H. Chan School of Public Health (HSPH), and the Ragon Institute of MGH, MIT & Harvard, we will target students and faculty from local and regional Institutions for the training. We will facilitate the development of HIV genomics, make them accessible to local universities and other countries in the region, and 2) To establish HIV-1 Reservoir assays in support of the ongoing and planned HIV-1 cure studies at BHP. We plan to set up assays for the assessment of HIV-1 reservoirs in PLWH in Botswana. Laboratory scientists will be trained on a number of these assays at the collaborator’s laboratory in Boston (Ragon Institute of MGH, MIT & Harvard). We will also train and establish capacity for the bioinformatic analysis for HIV-1 reservoir characterization. 1

项目摘要 博茨瓦纳一直是受HIV-1影响最大的国家之一，一直处于前三名 过去20年来，HIV-1的流行率国家。该国通过提供免费的回应 2002年对患有HIV-1（PLWH）的人的抗逆转录病毒疗法（ART），并具有积极的组合 预防策略。这导致HIV-1发病率和相关死亡率降低了 是全球第三次达到UNAID的HIV-1诊断，治疗和病毒的目标95-95-95 抑制。自1996年成立以来，博茨瓦纳哈佛大学研究所合作伙伴关系（bhp）已有 进行了研究者发起的临床试验，观察性和流行病学研究，基于实验室 研究和实施科学研究。必和必拓实验室还进行分子病毒学研究 关于艾滋病毒和这项研究在表征HIV-1亚型C的分子中发挥了作用， 在博茨瓦纳和南部非洲占主导地位。我们利用体验的深度和广度 在研究人员发起的研究，培训和能力建设中，获得了超过20年的增加 获得HIV-1基因组学培训。自2017年以来，我们已经投资于实施病原体不可知论的下一步 生成测序在SARS-COV-2 OMICRON变体的第一次测序中至关重要 博茨瓦纳的关注。与我们的合作者合作，我们还建立了非常早期治疗的人群 婴儿和青少年了解HIV-1水库。 因此，我们旨在通过这种应用来增强基因组学和分子病毒学中的基本生涯 博茨瓦纳的能力并增加了撒哈拉以南非洲地区的病原体基因组学作为一个 卓越中心。这里开发的能力将是病毒学研究的横切，因此将是 BHP实验室的持续多样化为全球公众的其他新兴病原体的研究发挥了作用 健康利益。为了实现这一目标，我们的目标是1）发展和推进必和必然根基因组作为HIV-1基因组学区域 卓越中心。我们将利用过去20年发展的病原体基因组学专业知识 通过在HIV-1测序，生物信息学分析和顺序中托管课程来促进能力建设 数据解释。建立在我们与博茨瓦纳大学哈佛大学T.H.合作的基础上陈学校 公共卫生（HSPH）和MGH，麻省理工学院和哈佛大学的Ragon研究所，我们将针对学生和教职员工 来自地方和地区机构的培训。我们将支持艾滋病毒基因组学的发展，使 它们可供当地大学和该地区其他国家 /地区访问，2）建立HIV-1水库 支持有必要的正在进行的HIV-1治疗研究的测定。我们计划为 在博茨瓦纳PLWH中对HIV-1储层的评估。实验室科学家将接受许多培训 这些测定在波士顿的合作者实验室（MGH，麻省理工学院和哈佛大学）。我们将 还可以训练并建立用于HIV-1储层表征的生物信息学分析的能力。 1