Developing Botswana Laboratory Capacity in HIV Genomics and HIV Cure

项目摘要 博茨瓦纳一直是受HIV-1影响最严重的国家之一，一直位居前三 按过去20年的艾滋病毒-1流行率分列的国家。这个国家以提供免费服务作为回应 2002年针对HIV-1感染者(PLWH)的抗逆转录病毒治疗(ART)和积极的 预防策略。这导致了艾滋病毒-1发病率和相关死亡率的下降，该国 是全球第三个达到联合国艾滋病规划署95-95-95艾滋病毒-1诊断、治疗和病毒目标的国家 压制。博茨瓦纳哈佛艾滋病研究所伙伴关系自1996年成立以来， 以实验室为基础，进行研究人员发起的临床试验、观察性和流行病学研究 研究和实施科学研究。必和必拓实验室还进行了分子病毒学研究 这项研究有助于确定HIV-1 C亚型的分子特征， 在博茨瓦纳和南部非洲占主导地位。我们借鉴了经验的深度和广度 经过20多年由研究人员发起的研究、培训和能力建设， 获得艾滋病毒-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性NEXT- 世代测序在SARS-CoV-2 Omicron变种的第一次测序中至关重要 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 帮助婴幼儿和青少年了解HIV-1储存库。 因此，我们的目标是通过这一应用加强必和必拓在HIV-1基因组学和分子病毒学方面的研究 博茨瓦纳的能力和增加撒哈拉以南非洲地区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，因此将是 帮助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)发展和推进必和必拓作为HIV-1基因组学区域 卓越中心。我们将利用过去20年发展起来的病原体基因组学专业知识。 通过举办艾滋病毒-1测序、生物信息学分析和测序课程，促进能力建设 数据解释。在我们与博茨瓦纳大学合作的基础上，哈佛大学陈同海学院 公共卫生(HSPH)以及麻省理工学院、麻省理工学院和哈佛大学的拉贡研究所，我们将针对学生和教职员工 来自当地和地区机构的培训。我们将促进艾滋病毒基因组学的发展，使 可供当地大学和该区域其他国家使用，以及2)建立HIV-1水库 为必和必拓正在进行的和计划中的HIV-1治愈研究提供支持的化验。我们计划建立检测方法来检测 对博茨瓦纳PLWH中HIV-1病毒宿主的评估。实验室科学家将接受一些关于以下方面的培训 这些化验在波士顿的合作者实验室(麻省理工学院拉贡研究所、麻省理工学院和哈佛大学)进行。我们会 还培训和建立了艾滋病毒-1病毒感染者特征的生物信息学分析能力。 1

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