Understanding HIV's impact on RR/MDR-TB development and transmission through genomics

通过基因组学了解 HIV 对 RR/MDR-TB 发展和传播的影响

• 批准号: 10889587
• 负责人: Tara Catherine Bouton
• 金额: $ 7.56万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-02 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10889587
• 关键词: Address; Affect; African; Area; Automobile Driving; Award; Biometry; Caring; Cause of Death; Clinical; Clinical Data; Collection; Communicable Diseases; Communities; Compensation; Competence; Containment; Country; Data; Development; Disease; Drug resistance; Drug resistance in tuberculosis; Drug resistant Mycobacteria Tuberculosis; Environment; Epidemic; Evolution; Extramural Activities; Funding; Genetic Epistasis; Genomics; Genus Mycobacterium; Goals; Grant; Growth; HIV; HIV resistance; HIV/TB; In Vitro; Incidence; Individual; Infection; International; Intervention; Isoniazid resistance; K-Series Research Career Programs; Knowledge; Laboratories; Low Prevalence; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Minority; Modeling; Molecular Epidemiology; Monitor; Multidrug-Resistant Tuberculosis; Mutation; Outcome; Patients; Persons; Pharmaceutical Preparations; Physicians; Population; Positioning Attribute; Predisposition; Preparation; Prevalence; Province; Public Health; Publishing; Regimen; Research; Research Personnel; Research Project Grants; Resistance; Resources; Retrospective cohort; Rifampicin resistance; Risk; Risk Factors; Robin bird; Role; Sampling; Scientist; Site; South Africa; South African; Specimen; Sputum; Techniques; Therapeutic; Time; Training; Translating; Tuberculosis; Tuberculosis diagnosis; United States National Institutes of Health; Variant; Work; absorption; analysis pipeline; antiretroviral therapy; biobank; career; case finding; clinical epidemiology; co-infection; cohort; cost; cost effective; deep sequencing; drug quality; epidemiologic data; experience; fitness; genomic data; high risk; improved; isoniazid; multidisciplinary; mycobacterial; next generation sequencing; pressure; prospective; recruit; resistance mutation; resistant strain; skills; transmission process; tuberculosis treatment; whole genome

PROJECT SUMMARY Through this K23 award, the candidate, an infectious disease physician with advanced training in tuberculosis (TB) and global TB/HIV research, will become an independent physician-scientist bridging clinical and molecular epidemiology and drug-resistance genomics. The candidate’s long-term goal is to improve our understanding of the relationship between HIV, drug-resistant TB mutations, TB transmission and clinical outcomes in order to better target interventions and guide treatment. To meet these goals, the candidate requires: 1) Skills in the analysis of large clinical cohorts; 2) Fluency with existing molecular epidemiology analysis and modelling; 3) Working knowledge of next generation sequencing techniques and analysis pipelines; 4) Experience in the recruitment and management of prospective clinical cohorts; 5) Professional development and preparation for extramural funding. This K23 outlines a 5-year plan of coursework, hands on training, and assembles a multidisciplinary mentorship team to address these competencies. Dr. Karen Jacobson (primary mentor) has over 10 years’ experience conducting international tuberculosis studies and a successful NIH-funded grant portfolio. Prof. Robin Warren and Dr. David Engelthaler (co-mentors) are experts in Mycobacterium tuberculosis drug resistance and next generation sequencing techniques, respectively. Drs. C. Robert Horsburgh and Laura White (advisors), together with Prof. Helen Cox (advisor) will provide clinical and molecular epidemiology expertise along with biostatistical modelling support. This K23 will address our lack of understanding of the association between HIV and rifampin-resistant/multidrug-resistant TB (RR/MDR- TB). The candidate will leverage a bank of RR/MDR-TB specimens from the Western Cape Province, South Africa, to examine how transmitted and acquired TB drug resistance varies over a twelve-year period among people living with and without HIV (aim 1). Next, the role of TB drug-resistance compensating mutations in RR/MDR-TB transmission at the community-level will be examined in a retrospective cohort in Worcester, South Africa, including the impact of HIV and other risk factors (aim 2). Finally, in a prospective pilot cohort, whole genome and next generation sequencing techniques will be used to examine whether TB drug resistance evolves differently during TB treatment in people with and without HIV, and in those presenting on and off antiretroviral therapy in Worcester, South Africa (aim 3). Knowledge gained from this study will translate into interventions to decrease the risk of RR/MDR-TB infection and improve long-term outcomes for people with HIV. By building upon her prior research experience and training, utilizing the biobank of RR/MDR-TB specimens and a well-established research site, along with methodologic training and expert mentorship, the candidate is well positioned to accomplish the proposed training and research aims and to then apply for an R01 award focused on exploring evolution of TB drug resistance in high burden TB/HIV coinfection settings.

项目总结

项目成果

Directly Observed Therapy to Measure Adherence to Tuberculosis Medication in Observational Research: Protocol for a Prospective Cohort Study.

• DOI: 10.2196/24510
• 发表时间: 2021-06-16
• 期刊: JMIR research protocols
• 影响因子: 1.7
• 作者: Ragan EJ;Gill CJ;Banos M;Bouton TC;Rooney J;Horsburgh CR;Warren RM;Myers B;Jacobson KR
• 通讯作者: Jacobson KR

Smoked drug use in patients with TB is associated with higher bacterial burden.

• DOI: 10.5588/ijtld.22.0650
• 发表时间: 2023-06-01
• 期刊: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
• 作者: Myers B;Carney T;Rooney J;Malatesta S;Ragan EJ;White LF;Natcheva H;Bouton TC;Weber SE;Farhat M;McIlleron H;Theron D;Parry CDH;Horsburgh CR;Warren RM;Jacobson KR
• 通讯作者: Jacobson KR