Viral Diversity an Innovative Biomarker for Refining Estimates of HIV Incidence

病毒多样性是改进艾滋病毒发病率估计的创新生物标志物

• 批准号: 10538707
• 负责人: Sikhulile Moyo
• 金额: $ 13.65万
• 依托单位: BOTSWANA-HARVARD AIDS INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10538707
• 关键词: 2019-nCoV; AIDS prevention; Adopted; Advisory Committees; African; Algorithms; Area; Bioinformatics; Biological Assay; Biological Markers; Biometry; Country; Cross-Sectional Studies; Data; Development; Development Plans; Epidemic; Epidemiology; Evaluation; Exclusion; Genetic Recombination; Genome; Genomics; Genotype; HIV; HIV Genome; HIV Infections; HIV-1; Incidence; Individual; Infection; Institution; Intervention; Laboratories; Lead; Leadership; Length; Longitudinal Studies; Measurement; Measures; Mentors; Mentorship; Methodology; Methods; Modeling; Molecular; Molecular Epidemiology; Monitor; Outcome; Patients; Persons; Phylogenetic Analysis; Policy Maker; Population; Prevention Research; Process; Public Health; RNA; Research; Research Personnel; Research Project Grants; Resource-limited setting; Role; Sampling; Sensitivity and Specificity; Serology; Specificity; Specimen; Students; Supervision; Surveys; Testing; Time; Training; Training Activity; Uncertainty; Viral; Viral Genome; Virus; Virus Replication; antiretroviral therapy; bioinformatics pipeline; career; career development; cost; cost effective; experience; genome sequencing; improved; innovation; longitudinal analysis; low income country; next generation sequencing; potential biomarker; practical application; pre-exposure prophylaxis; programs; prospective; public health emergency; research study; response; scale up; screening; seroconversion; skills; tool; transmission process; trend

Project Summary Candidate: Dr Sikhulile Moyo is unwaveringly committed to an overarching career focused on contributing to ending the HIV epidemic and related public health emergencies. He committed to a career focused on finding cost-effective tools for estimating the impact of interventions and towards HIV cure research. He envisions himself as a leader globally, in research aimed towards tracking and eliminating new HIV infections & towards developing an HIV cure, working with researchers, program implementers and policy makers for rapid and cost-effective evaluation of interventions. Dr Moyo’s 5-year career development plan is focused on three key areas: phylogenetics, epidemiology and biostatistics; cross-sectional Incidence and Implementation; and HIV cure & characterization of early founder viruses, and SARS-COV-2 genomics. In order to achieve his short- and medium-term career objectives he seeks to: a) develop advanced methodologic and analytic skills in molecular epidemiology, phylogenetic analysis and bioinformatics; b) expand laboratory expertise in real-time high-throughput next generation sequencing and accurate and reliable quantification of proviral reservoirs for advancing HIV cure studies, and c) strengthen leadership abilities particularly in managing large scientific projects, population-level surveys, and diverse research teams with expertise in different fields, organizational leadership and student research supervision. Training activities will encompass formal training and coursework, practical application through the proposed research project, and direct mentorship from my highly experienced mentorship and advisory team. These activities will draw on the strengths of the mentorship team and leading research institutions with strong collaborative ties and have a record of mentoring young investigators to R01 and independence. Research: The study aims to introduce an innovative approach to estimating HIV incidence, which is very important for national HIV programs / public health, and also for HIV prevention research, but can be expensive and challenging to do. The specific aims are: 1) To assess adjusted viral diversity as a potential biomarker of HIV incidence. 2) To refine results of serological screening in subsets of true- and false-recent cases, and patients with established infection (ART-naïve and on ART), by adjusted viral diversity. We will test whether viral diversity within the most informative regions across the HIV-1C genome adjusted for multiplicity of transmission, recombination, and level of viral replication could be used to refine the results of serological screening and improve specificity and sensitivity. We expect that the adjusted viral diversity within the most informative regions will increase specificity and sensitivity in estimation of HIV incidence within the 4 subsets of individuals targeted in this Aim to ≥95%. Establishing a cost-effective algorithm to estimate incidence is of critical public health importance in low resource settings.

项目概要 候选人：Sikhulile Moyo 博士坚定不移地致力于致力于为以下领域做出贡献的总体职业生涯 结束艾滋病毒流行和相关的突发公共卫生事件。他致力于致力于寻找 用于评估干预措施的影响和艾滋病毒治疗研究的具有成本效益的工具。他设想 他本人作为全球领导者，致力于追踪和消除新的艾滋病毒感染以及 与研究人员、项目实施者和政策制定者合作，开发艾滋病毒治疗方法，以实现快速、有效的治疗 干预措施的成本效益评估。 Moyo 博士的 5 年职业发展计划重点关注三个关键 领域：系统发育学、流行病学和生物统计学；横截面发生率和实施；和艾滋病毒 早期创始人病毒的治愈和表征以及 SARS-COV-2 基因组学。为了实现他的短 他寻求的中期职业目标是： a) 发展以下方面的先进方法和分析技能 分子流行病学、系统发育分析和生物信息学； b) 实时扩展实验室专业知识 高通量下一代测序以及原病毒库的准确可靠的定量 推进艾滋病毒治疗研究，以及 c) 加强领导能力，特别是在管理大型科学方面 项目、人群调查以及具有不同领域专业知识的多元化研究团队、组织 领导和学生研究监督。培训活动将包括正式培训和 课程作业、拟议研究项目的实际应用以及我的高度直接指导 经验丰富的导师和顾问团队。这些活动将利用导师团队的优势 与领先的研究机构有着密切的合作关系，并拥有指导年轻人的记录 调查员对R01和独立性。 研究：该研究旨在引入一种创新方法来估计艾滋病毒发病率，该方法非常有效 对于国家艾滋病毒计划/公共卫生以及艾滋病毒预防研究很重要，但可以 昂贵且具有挑战性。具体目标是： 1）评估调整后的病毒多样性作为潜在的 HIV发病率的生物标志物。 2) 细化真实和假近期子集的血清学筛查结果 病例和已确诊感染的患者（未接受过 ART 的和正在接受 ART 的患者），通过调整病毒多样性。我们将测试 HIV-1C 基因组中信息最丰富的区域内的病毒多样性是否会根据多样性进行调整 传播、重组和病毒复制水平的研究可用于完善血清学结果 筛选并提高特异性和敏感性。我们预计调整后的病毒多样性将在最 信息区域将提高估计 4 个子集内的 HIV 发病率的特异性和敏感性 此目标的目标人群达到 ≥95%。建立一种具有成本效益的算法来估计发病率的关键是 在资源匮乏的环境中至关重要的公共卫生重要性。