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影响最严重的国家之一， 过去20年来，艾滋病毒1型流行率在各国的分布情况。这个国家勇敢地做出了回应， 2002年对艾滋病毒1型感染者进行抗逆转录病毒疗法， 预防战略。这导致艾滋病毒-1发病率和相关死亡率下降， 是全球第三个达到联合国艾滋病规划署95-95-95目标的艾滋病毒-1诊断，治疗和病毒 镇压自1996年成立以来，博茨瓦纳哈佛艾滋病研究所伙伴关系（BHP） 进行了药物启动的临床试验，观察性和流行病学研究，基于实验室的 研究和实施科学研究。必和必拓实验室还开展分子病毒学研究 这项研究有助于对HIV-1亚型C进行分子表征， 主要分布在博茨瓦纳和南部非洲。我们利用经验的深度和广度 获得了超过20年的研究，培训和能力建设，以增加 获得HIV-1基因组学培训。自2017年以来，我们已投资实施病原体不可知论next- 第二代测序在SARS-CoV-2 Omicron变异体的首次测序中至关重要， 博茨瓦纳的担忧。与我们的合作者合作，我们还建立了非常早期治疗的队列。 婴儿和青少年了解艾滋病毒-1水库。 因此，我们的目的是通过这种应用程序，以加强BHP在HIV-1基因组学和分子病毒学 提高博茨瓦纳的能力，并增加撒哈拉以南非洲地区获得病原体基因组学的机会， 卓越中心这里发展的能力将是病毒学研究的交叉领域，因此， 有助于必和必拓实验室继续多样化研究全球公众的其他新兴病原体 健康兴趣。为了实现这一目标，我们的目标是1）发展和推进BHP作为HIV-1基因组学区域 卓越中心我们将利用过去20年来在病原体基因组学方面的专业知识 通过举办HIV-1测序、生物信息学分析和测序课程， 数据解释在我们与博茨瓦纳大学、哈佛T. H.阐教 公共卫生（HSPH）和MGH，麻省理工学院和哈佛的Ragon研究所，我们将针对学生和教师 从当地和区域机构的培训。我们将促进艾滋病毒基因组学的发展， 2）建立HIV-1储存库 这些检测支持必和必拓正在进行和计划进行的HIV-1治愈研究。我们计划建立检测方法， 评估博茨瓦纳艾滋病毒携带者中的HIV-1宿主。实验室科学家将接受一些培训， 在波士顿的合作者实验室（麻省理工学院和哈佛的Ragon研究所）进行这些测定。我们将 还培训和建立对HIV-1储存库特征进行生物信息学分析的能力。 1